Growth Hormone Supplementation in the Luteal Phase Before Microdose GnRH Agonist Flare Protocol for In Vitro Fertilization.

PubMed

Dunne, Caitlin; Seethram, Ken; Roberts, Jeffrey

2015-09-01

Growth hormone (GH) acts in both early and late follicular development to stimulate the proliferation and differentiation of granulosa cells and to increase the production of estradiol in animal and human ovaries. Investigators have therefore explored GH supplementation to improve outcomes in women undergoing in vitro fertilization, with the greatest interest in women with diminished ovarian reserve. Recent meta-analyses indicate that GH supplementation can be beneficial for poor responders undergoing IVF. In most studies, GH has been given concomitantly with gonadotropins during the follicular phase; this may not be optimal, since follicular recruitment begins during the preceding luteal phase. We therefore wished to examine the effect of GH supplementation in the luteal phase before controlled ovarian stimulation (COH) with a microdose GnRH agonist flare (MDF) protocol in women undergoing in vitro fertilization. We performed a retrospective matched case-control study of patients undergoing treatment at a private IVF facility between June 2012 and July 2013. Patients identified as poor responders to COH were offered adjuvant GH treatment as part of their ovarian stimulation regimen. The patients in the experimental group chose to take GH, 3.33 mg daily by subcutaneous injection for 14 days, before starting COH. All patients had an MDF stimulation protocol using 450 IU of follicle stimulating hormone (FSH) daily. A total of 42 women were included in the study. There were 14 women in the experimental group (GH) and 28 controls (C) matched for age, BMI, and day 3 FSH level. There was no difference between the groups in clinical pregnancy rate (GH = 29%, C = 32%, P = 0.99), number of mature oocytes retrieved (GH = 2.5, C = 5.0, P = 0.13), cycle cancellation rate (GH = 21%, C = 14%, P = 0.88), duration of COH (GH = 10.1, C = 10.1, P = 0.93), or mean peak estradiol level (GH = 4174 pmol/L, C = 5105 pmol/L, P = 0.44). The administration of growth hormone during the luteal phase before a microdose GnRH agonist flare protocol for in vitro fertilization did not improve outcomes in "poor responder" patients.

Ovarian sensitivity index is strongly related to circulating AMH and may be used to predict ovarian response to exogenous gonadotropins in IVF

PubMed Central

2011-01-01

Background Serum anti-Mullerian hormone (AMH) is currently considered the best marker of ovarian reserve and of ovarian responsiveness to gonadotropins in in-vitro fertilization (IVF). AMH assay, however, is not available in all IVF Units and is quite expensive, a reason that limits its use in developing countries. The aim of this study is to assess whether the "ovarian sensitivity index" precisely reflects AMH so that this index may be used as a surrogate for AMH in prediction of ovarian response during an IVF cycle. Methods AMH serum levels were measured in 61 patients undergoing IVF with a "long" stimulation protocol including the GnRH agonist buserelin and recombinant follicle-stimulating hormone (rFSH). Patients were divided into four subgroups according to the percentile of serum AMH and their ovarian stimulation was prospectively followed. Ovarian sensitivity index (OSI) was calculated dividing the total administered FSH dose by the number of retrieved oocytes. Results AMH and OSI show a highly significant negative correlation (r = -0.67; p = 0.0001) that is stronger than the one between AMH and the total number of retrieved oocytes and than the one between AMH and the total FSH dose. Conclusions OSI reflects quite satisfactory the AMH level and may be proposed as a surrogate of AMH assay in predicting ovarian responsiveness to FSH in IVF. Being very easy to calculate and costless, its use could be proposed where AMH measurement is not available or in developing countries where limiting costs is of primary importance. PMID:21824441

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial.

PubMed

van Tilborg, Theodora C; Eijkemans, Marinus J C; Laven, Joop S E; Koks, Carolien A M; de Bruin, Jan Peter; Scheffer, Gabrielle J; van Golde, Ron J T; Fleischer, Kathrin; Hoek, Annemieke; Nap, Annemiek W; Kuchenbecker, Walter K H; Manger, Petra A; Brinkhuis, Egbert A; van Heusden, Arne M; Sluijmer, Alexander V; Verhoeff, Arie; van Hooff, Marcel H A; Friederich, Jaap; Smeenk, Jesper M J; Kwee, Janet; Verhoeve, Harold R; Lambalk, Cornelis B; Helmerhorst, Frans M; van der Veen, Fulco; Mol, Ben Willem J; Torrance, Helen L; Broekmans, Frank J M

2012-09-18

Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT. The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines. NTR2657.

Occurrence of ovarian follicular dominance during stimulation for IVM impacts usable blastocyst yield.

PubMed

Romero, Sergio; Pella, Ricardo; Escudero, Francisco; Pérez, Ygor; García, Mario; Orihuela, Patricia

2018-03-01

To evaluate the influence of ovarian follicular dominance on the outcome of oocyte in-vitro maturation. This retrospective cohort study included 21 patients with polycystic ovaries or polycystic ovary syndrome (Rotterdam criteria, 2004) subjected to 24 invitro maturation (IVM) cycles between October 2015 and January 2017. Patients undergoing IVM received minimal gonadotropin stimulation starting on day 2 or 3 of the cycle; ovum pick-up typically occurred on days 6 to 8. No hCG-trigger shot was given. Following 30h of IVM, mature oocytes were inseminated by ICSI and the resulting embryos cultured up to the blastocyst stage. Ovarian follicular dominance was observed in nine of the 24 IVM cycles. Oocyte IVM yielded an overall maturation rate of 69.3±23.8%, and no difference was observed when the groups with or without a dominant follicle were assessed independently. The rates of fertilization and usable blastocysts per fertilized oocyte, mature oocyte (Metaphase II) or cumulus-oocyte-complex were nearly three times higher (28.7±22.5%) in the group without ovarian follicular dominance. No differences were found in the clinical pregnancy rates attained by the individuals with or without a dominant follicle after 21 vitrified-warmed blastocyst transfer cycles. Occurrence of ovarian follicular dominance during hormonal stimulation for in-vitro maturation negatively impacted embryological outcomes. Strategies devised to limit the appearance of ovarian follicular dominance must be further explored.

Inositol Treatment and ART Outcomes in Women with PCOS.

PubMed

Garg, Deepika; Tal, Reshef

2016-01-01

Polycystic ovary syndrome (PCOS) affects 5-10% of women in reproductive age and is characterized by oligo/amenorrhea, androgen excess, insulin resistance, and typical polycystic ovarian morphology. It is the most common cause of infertility secondary to ovulatory dysfunction. The underlying etiology is still unknown but is believed to be multifactorial. Insulin-sensitizing compounds such as inositol, a B-complex vitamin, and its stereoisomers (myo-inositol and D-chiro-inositol) have been studied as an effective treatment of PCOS. Administration of inositol in PCOS has been shown to improve not only the metabolic and hormonal parameters but also ovarian function and the response to assisted-reproductive technology (ART). Accumulating evidence suggests that it is also capable of improving folliculogenesis and embryo quality and increasing the mature oocyte yield following ovarian stimulation for ART in women with PCOS. In the current review, we collate the evidence and summarize our current knowledge on ovarian stimulation and ART outcomes following inositol treatment in women with PCOS undergoing in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI).

Clomiphene citrate is associated with favorable cycle characteristics but impaired outcomes of obese women with polycystic ovarian syndrome undergoing ovarian stimulation for in vitro fertilization

PubMed Central

Jiang, Shutian; Kuang, Yanping

2017-01-01

Abstract The aim of this study was to explore the effect of clomiphene citrate (CC) on the cycle characteristics and outcomes of obese women with polycystic ovarian syndrome (PCOS) undergoing ovarian stimulation for in vitro fertilization (IVF). This is a retrospective cohort study, and it was conducted at the tertiary-care academic medical center. This study included 174 obese PCOS patients undergoing IVF. In the study group (n = 90), CC and human menopausal gonadotropin (HMG) were administered simultaneously beginning on cycle day 3, while in control group (n = 84) HMG was used only. Both of the 2 groups used medroxyprogesterone acetate (MPA) for preventing premature luteinizing hormone (LH) surges. Ovulation was cotriggered by a GnRH agonist and hCG when dominant follicles matured. The primary outcome measure was the number of oocytes retrieved. Secondary outcomes included the number of top-quality embryos, maturation rate, fertilization rate, cleavage rate, incidence of premature LH surge, and OHSS. The study group received obviously lower total HMG dose [1650 (975–4800) vs 2025 (1350–3300) IU, P = 2.038E–4] but similar HMG duration. While the antral follicle count (AFC) is higher in study group, the number of oocytes retrieved and top-quality embryos are remarkably less [5 (0–30) vs 13 (0–42), P = 6.333E–5; 2 (0–14) vs 3.5 (0–15), P = .003; respectively]. The mature oocyte rate is higher in study group (P = .036). No significant differences were detected in fertilization rate and cleavage rate between 2 groups. CC has a positive influence on cycle characteristics, but might be correlated with the impaired IVF outcomes (less oocytes retrieved and top quality embryos, lower oocyte retrieval rate) in obese PCOS patients undergoing IVF, when HMG and MPA are used simultaneously. PMID:28796038

Responses to fertility treatment among patients with cancer: a retrospective cohort study.

PubMed

Dolinko, A V; Farland, L V; Missmer, S A; Srouji, S S; Racowsky, C; Ginsburg, E S

2018-01-01

Cancer treatments have significant negative impacts on female fertility, but the impact of cancer itself on fertility remains to be clarified. While some studies have shown that compared with healthy women, those with cancer require higher doses of gonadotropins resulting in decreased oocyte yields, others have shown comparable oocyte yields between the two groups. The purpose of this study is to evaluate whether there is an association between any cancer and/or type of cancer, and response to ovarian stimulation for egg and embryo banking. In this retrospective cohort study, ovarian stimulation cycles performed from June 2007 through October 2014 at a single academic medical center were reviewed to identify those undertaken for women with cancer undergoing fertility preservation ( n  = 147) or women with no cancer undergoing their first cycle due to male factor infertility ( n  = 664). Of the 147 women undergoing fertility preservation, 105 had local cancer (Stage I-III solid malignancies) and 42 had systemic cancer (hematologic or Stage IV solid malignancies). Response to ovarian stimulation was compared among these two groups and women with no cancer. Adjusting for age and BMI, women with systemic cancer had lower baseline antral follicle counts (AFC) than women with no cancer or local cancer. Women with systemic cancer required higher doses of FSH than women with no cancer or local cancer, and they had higher oocyte to AFC ratios than women with no cancer or local cancer, but greater odds of cycle cancellation as compared to women with no cancer or local cancer. No significant differences were observed among the three groups for duration of stimulation, number of oocytes and mature oocytes retrieved, or number of embryos created. Women with cancer achieve similar oocyte and embryo yields as women with no cancer, although those with systemic cancer require higher FSH doses and are at greater risk of cycle cancellation.

Occurrence of ovarian follicular dominance during stimulation for IVM impacts usable blastocyst yield

PubMed Central

Romero, Sergio; Pella, Ricardo; Escudero, Francisco; Pérez, Ygor; García, Mario; Orihuela, Patricia

2018-01-01

Objective To evaluate the influence of ovarian follicular dominance on the outcome of oocyte in-vitro maturation. Methods This retrospective cohort study included 21 patients with polycystic ovaries or polycystic ovary syndrome (Rotterdam criteria, 2004) subjected to 24 in-vitro maturation (IVM) cycles between October 2015 and January 2017. Patients undergoing IVM received minimal gonadotropin stimulation starting on day 2 or 3 of the cycle; ovum pick-up typically occurred on days 6 to 8. No hCG-trigger shot was given. Following 30h of IVM, mature oocytes were inseminated by ICSI and the resulting embryos cultured up to the blastocyst stage. Results Ovarian follicular dominance was observed in nine of the 24 IVM cycles. Oocyte IVM yielded an overall maturation rate of 69.3±23.8%, and no difference was observed when the groups with or without a dominant follicle were assessed independently. The rates of fertilization and usable blastocysts per fertilized oocyte, mature oocyte (Metaphase II) or cumulus-oocyte-complex were nearly three times higher (28.7±22.5%) in the group without ovarian follicular dominance. No differences were found in the clinical pregnancy rates attained by the individuals with or without a dominant follicle after 21 vitrified-warmed blastocyst transfer cycles. Conclusion Occurrence of ovarian follicular dominance during hormonal stimulation for in-vitro maturation negatively impacted embryological outcomes. Strategies devised to limit the appearance of ovarian follicular dominance must be further explored. PMID:29338139

Association of blood groups with ovarian reserve and outcome of in vitro fertilization treatment.

PubMed

Awartani, Khalid; Al Ghabshi, Rahma; Al Shankiti, Hanan; Al Dossari, Mohamed; Coskun, Serdar

2016-01-01

The association between ABO blood groups and ovarian reserve in infertile patients has been a point of controversy. The aim of this study was to assess the correlation of certain blood groups with ovarian reserve and response to treatment in patients undergoing infertility treatment. Retrospective medical record review. Infertility clinic in the assisted reproductive technology (ART) unit at King Faisal Specialist Hospital and Research Center, Riyadh Saudi Arabia. All patients under 40 years of age who attended the infertility clinic at a tertiary care centre in 2010 and underwent in vitro fertilization (IVF) treatment in 2010 and 2011 were divided into groups according to blood type, and clinical parameters were compared. The association between blood groups and ovarian reserve using day 3 luteinzing hormone (LH) and follicular stimulating hormone (FSH) levels, and antral follical count (AFC). In 424 patients who underwent 566 IVF cycles, age, LH, FSH and AFC were similar among the different blood groups (P=.9, .1, .5, respectively). with controlled ovarian stimulation, no difference was observed among the four groups in menopausal gonadotrophin (hMG) dose or the duration of stimulation. The number of oocytes retrieved, fertilization rate, cleavage rate, and number of embryos transferred were similar. There was no difference in the cancellation rate or pregnancy rate among the groups. There was no significant association between blood type and ovarian reserve or response during IVF treatment in our population. Anti-Mullerian hormone levels are best correlated with ovarian reserve testing. Unavailability of AMH levels. Retrospective design.

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial

PubMed Central

2012-01-01

Background Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. Methods/Design Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT. Discussion The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines. Trial registration NTR2657 PMID:22989359

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI).

PubMed

Kwan, I; Bhattacharya, S; McNeil, A; van Rumste, M M E

2008-04-16

Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation (IVF) treatment has included ultrasonography plus serum estradiol concentration to ensure safe practice by reducing the incidence and severity of ovarian hyperstimulation syndrome (OHSS). The need for intensive monitoring during ovarian stimulation in IVF is controversial. It has been suggested that close monitoring is time consuming, expensive and inconvenient for the woman and simplification of IVF therapy by using ultrasound only should be considered. This systematic review assessed the effects of ovarian monitoring by ultrasound only versus ultrasound plus serum estradiol measurement on IVF outcomes and the occurrence of OHSS in women undergoing stimulated cycles in IVF and intra-cytoplasmic sperm injection (ICSI) treatment. To quantify the effect of monitoring controlled ovarian stimulation in IVF and ICSI cycles with ultrasound plus serum estradiol concentration versus ultrasound only in terms of live birth rates, pregnancy rates and the incidence of OHSS. We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL) on the latest issue of The Cochrane Library, MEDLINE (1966 to May 2007), EMBASE (1980 to May 2007), CINAHL (1982 to May 2007), the National Research Register, and web-based trial databases such as Current Controlled Trials. There was no language restriction. Additionally all references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data. Only randomised controlled trials that compared monitoring with ultrasound plus serum estradiol concentration versus ultrasound only in women undergoing ovarian hyperstimulation for IVF and ICSI treatment were included. Two review authors independently examined the electronic search results for relevant trials, extracted data and assessed trial quality. They resolved disagreements by discussion with two other authors. Outcomes data were pooled when appropriate and summary statistics presented when limited data did not allow meta-analysis. Our search strategy identified 1119 potentially eligible reports, of which two met our inclusion criteria. These involved 411 women who underwent controlled ovarian stimulation monitoring. Our primary outcome of live birth rate was not reported in either study. One trial reported clinical pregnancy rate per woman (33% versus 31%; RR 1.07, 95% CI 0.77 to 1.49), the second trial reported clinical pregnancy rate per oocyte retrieval (22% versus 25%). There was no significant difference between the ultrasound plus estradiol group and the ultrasound alone group in the mean number of oocytes retrieved (WMD -0.55, 95% CI -1.79 to 0.69) and the incidence of ovarian hyperstimulation (RR 0.73, 95% CI 0.30 to 1.78) for the two studies. There is no evidence from randomised trials to support cycle monitoring by ultrasound plus serum estradiol as more efficacious than cycle monitoring by ultrasound only on outcomes of live birth and pregnancy rates. A large well-designed randomised controlled trial is needed that reports on live birth rates and pregnancy, with economic evaluation of the costs involved and the views of the women undergoing cycle monitoring. A randomised trial with sufficiently large sample size to test the effects of different monitoring protocols on OHSS, a rare outcome, will pose a great challenge. Until such a trial is considered feasible, cycle monitoring by transvaginal ultrasound plus serum estradiol may need to be retained as a precautionary good practice point.

Concurrent ganirelix and follitropin beta therapy is an effective and safe regimen for ovulation induction in women with polycystic ovary syndrome.

PubMed

Elkind-Hirsch, Karen E; Webster, Bobby W; Brown, Crystal P; Vernon, Michael W

2003-03-01

To evaluate controlled ovarian stimulation cycles using the GnRH antagonist ganirelix in combination with the recombinant FSH, follitropin-beta, in women with polycystic ovary syndrome (PCOS). Prospective, nonrandomized clinical study. Hospital-based infertility practice. Twenty women with PCOS planning to undergo ovarian stimulation. Fasting glucose and insulin levels were used to calculate insulin resistance ratios (FG/I). After pretreatment with oral contraceptives, serum LH levels were determined, and 250 microg ganirelix was administered on cycle day 2. Upon suppression of LH, concurrent ganirelix and follitropin-beta therapy (morning ganirelix and evening follitropin-beta) was started and continued until the day of hCG. Days of stimulation, dose of follitropin-beta, pregnancy, and ongoing pregnancy were compared based on FG/I ratios. One dose of ganirelix effectively suppressed LH levels in all patients. All patients ovulated as documented by a rise in progesterone. Significant differences were observed between the insulin-resistant and non-insulin-resistant groups for both days of stimulation and dose of follitropin-beta. The overall clinical pregnancy rate was 44.4%, with an ongoing pregnancy rate of 27.8%. In this preliminary study, we demonstrate the effectiveness of a concurrent ganirelix and follitropin-beta therapy for ovarian stimulation in women with PCOS.

Reproductive potential of mature oocytes after conventional ovarian hyperstimulation for in vitro fertilization.

PubMed

Zhang, John J; Yang, Mingxue; Merhi, Zaher

2016-05-01

To compare cumulative live birth rate according to the rate of use of metaphase II (MII) oocytes in conventional ovarian stimulation protocols for in vitro fertilization (IVF) or intracytoplasmic sperm injection. In a cohort study, patients aged 18-38 years undergoing their first IVF treatment at one US center were enrolled between February 1, 2009, and August 31, 2013. Ovarian response was categorized by the yield of MII oocytes (low: 1-2; intermediate: 3-6; high: ≥7). The main outcome measure was cumulative live birth rate over a 6-month period. Among 250 participants, 3240 oocytes (mean±SEM 12.96±0.50) were retrieved and there were 152 (60.8%) live births. Overall, 172 (68.8%) participants had a high oocyte yield, 61 (24.4%) an intermediate yield, and 17 (6.8%) a low yield. The cumulative live birth rate was 58.8% (10/17) in the low-yield group, 55.7% (34/61) in the intermediate-yield group, and 62.8% (108/172) in the high-yield group (P=0.35). In conventional ovarian stimulation, live birth rate is not affected by the ovarian response. Whether oocytes produced from a low ovarian response are biologically more effective than oocytes obtained from a high ovarian response remains to be determined. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Methylprednisolone for prevention of ovarian hyperstimulation syndrome in patients with polycystic ovarian syndrome undergoing in-vitro fertilisation: a randomised controlled trial.

PubMed

Mohammadi Yeganeh, Ladan; Moini, Ashraf; Shiva, Marzieh; Mirghavam, Naimeh; Bagheri Lankarani, Narges

2018-02-01

This study aimed to evaluate the effect of methylprednisolone on prevention of ovarian hyperstimulation syndrome (OHSS) in polycystic ovarian syndrome (PCOS) patients undergoing in-vitro fertilisation (IVF). This randomised controlled trial was carried out between November 2009 and December 2013. A total of 219 eligible patients were randomly allocated for treatment (n = 108) or control groups (n = 111). The treatment group received oral methylprednisolone starting from the first day of stimulation. These patients also received an intravenous dose of methylprednisolone on the days of egg collection and embryo transfer. The control group received no glucocorticoid treatment to prevent OHSS. Nineteen percent of patients (18/93) who received methylprednisolone developed OHSS compared with 16.5% (15/91) in the control group and no significant difference was found (p = .61). There were no significant differences between treatment and control groups in the rates of implantation (10% versus 11%, p = .77) and clinical pregnancy (23.2% versus 17.7%, p = .46). Methylprednisolone did not reduce the incidence and severity of OHSS in PCOS patients undergoing IVF and no improvement in clinical outcomes was observed. Impact statement No significant differences were found in OHSS incidence and clinical outcomes between women who received methylprednisolone and control group. There seems to be no benefit for the routine use of glucocorticoids in IVF/ICSI treatments.

Efficacy and safety of Ding-Kun-Dan for female infertility patients with predicted poor ovarian response undergoing in vitro fertilization/intracytoplasmic sperm injection: study protocol for a randomized controlled trial.

PubMed

Ma, Saihua; Ma, Ruihong; Xia, Tian; Afnan, Masoud; Song, Xueru; Xu, Fengqin; Hao, Guimin; Zhu, Fangfang; Han, Jingpei; Zhao, Zhimei

2018-02-20

Women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) who have a predicted poor ovarian response (POR) present a challenge for reproductive medicine specialists. Traditional Chinese medicine (TCM) is commonly used in China for such patients, in the belief that it will improve the ovarian response and ultimately increase pregnancy rates. However, there is a lack of high-quality evidence about the effect of TCM on improving ovarian response in such patients. The purpose of this study is to evaluate ongoing viable pregnancy rate at 12 weeks' gestation and related indicators of ovarian response in fertile women who have a predicted poor ovarian response having immediate versus delayed IVF/ICSI after 3 months of Ding-Kun-Dan (DKD) pre-treatment. This study is a multicenter, randomized controlled, parallel-group, phase III, superiority clinical trial. Two hundred and seventy-eight eligible female infertility patients with POR will be included in the study and randomly allocated into an immediate treatment group and a DKD group in a 1:1 ratio. Both groups will receive IVF or ICSI as a standard treatment while in the DKD group, a commercially available Chinese medicine, DKD, will be administrated for 3 months before the IVF/ICSI cycle starts. The primary outcome of the study is the ongoing pregnancy rate at 12 weeks' gestation. The secondary outcomes include total gonadotropin dosage, duration of stimulation, estradiol (E 2 ) and progesterone (P) levels on human chorionic gonadotropin (hCG) trigger day, cycle cancellation rate, number of oocytes retrieved, high-quality embryo rate, biochemical pregnancy rate, the change of serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and E 2 levels and all side effects, safety outcomes, and any adverse events. The protocol was approved by the Ethics Committee of the First Teaching Hospital of Tianjin university of TCM (approval no. TYLL2017[K] 004). IVF/ICSI is increasingly used to treat couples desiring a baby. Many of these women will have poor ovarian function. In China, DKD is commonly used for these patients prior to undergoing IVF/ICSI. There is no effective treatment for poor ovarian response in Western medicine currently. It is important, therefore, to undertake this randomized control trial to determine whether DKD is effective or not. Chinese Clinical Trial Registry, ID: ChiCTR-IOR-17011697 . Registered on 19 June 2017.

Outcomes of in vitro fertilization cycles among patients with polycystic ovary syndrome following ovarian puncture for in vitro maturation.

PubMed

Lin, Jia; Wang, Peiyu; Zhao, Junzhao; Xiao, Shiquan; Yu, Rong; Jin, Congcong; Zhu, Ruru

2016-12-01

To investigate the effects of ovarian puncture for in vitro maturation (IVM) on subsequent in vitro fertilization (IVF) embryo transfer cycles in patients with polycystic ovary syndrome (PCOS). A retrospective study included data from patients admitted to the First Affiliated Hospital of Wenzhou Medical University, China, between January 1, 2008 and December 31, 2014. Patients with PCOS undergoing IVF cycles after having been treated with IVM unsuccessfully were included as the study group and an IVF-procedure data-matched control group of patients undergoing their first IVF cycles was included in a 1:4 ratio. Patients with reproductive anomalies were excluded. Endocrine-hormone levels and antral follicle counts were measured and fertilization-related outcomes were evaluated. There were 49 patients included in the study group and 196 included in the control group. Within the study group, basal luteal-hormone, testosterone, and antral follicle count levels were significantly lower following IVM treatment. The total gonadotropin dose was lower (P<0.001) and the duration of stimulation was shorter (P<0.001) in the study group compared with the control group. The clinical-pregnancy rate was higher in the study group (P=0.018) and no difference was observed between the groups in ovarian hyper-stimulation syndrome (P=0.633). Previous IVM resulted in improved endocrine profiles and increased clinical-pregnancy rates among patients with PCOS undergoing IVF cycles. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Ethnicity as a determinant of ovarian reserve: differences in ovarian aging between Spanish and Indian women.

PubMed

Iglesias, Carlos; Banker, Manish; Mahajan, Nalini; Herrero, Leyre; Meseguer, Marcos; Garcia-Velasco, Juan A

2014-07-01

To investigate differences in ovarian reserve markers (antimüllerian hormone [AMH] and antral follicle count [AFC]) in Indian and Spanish women. Cross-sectional study. In vitro fertilization (IVF) clinics. Infertile Spanish (n=229) and Indian (n=236) women who underwent controlled ovarian stimulation for IVF from January to October 2012. None. Data on ovarian reserve markers and results after ovarian stimulation were collected. The mean age of women undergoing their first or second IVF cycle was significantly higher in Spanish than in Indian women (37.5±3.3 years vs. 31.5±3.8 years). Despite this 6-year age gap, AFCs were similar (9.5±4.7 vs. 9.9±4.6), as were day 3 FSH levels (7.5±4.5 IU/L vs. 6.9±2.3 IU/L). AMH levels were slightly lower in Spanish women (1.6±1.7 ng/mL vs. 2.5±1.6 ng/mL). Multivariate regression analysis showed that being Indian decreased AFC by 2.3, such that AFC in Indian women was similar to that in Spanish women 6.3 years older (95% confidence interval 3.39-1.10). Similar ovarian reserve markers and ovarian response were observed in women with a 6-year age difference in favor of the Spanish, suggesting ethnic differences in ovarian aging. Further research is needed to understand whether these differences are genetically induced or are caused by other variables, such as nutrition. Our results may help clinicians to counsel infertile women when discussing assisted reproductive technology outcomes according to age and ethnic background. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Supplementation with a recombinant human chorionic gonadotropin microdose leads to similar outcomes in ovarian stimulation with recombinant follicle-stimulating hormone using either a gonadotropin-releasing hormone agonist or antagonist for pituitary suppression.

PubMed

Cavagna, Mario; Maldonado, Luiz Guilherme Louzada; de Souza Bonetti, Tatiana Carvalho; de Almeida Ferreira Braga, Daniela Paes; Iaconelli, Assumpto; Borges, Edson

2010-06-01

To compare the outcomes of protocols for ovarian stimulation with recombinant hCG microdose, with GnRH agonists and antagonists for pituitary suppression. Prospective nonrandomized clinical trial. A private assisted reproduction center. We studied 182 patients undergoing intracytoplasmic sperm injection (ICSI) cycles, allocated into two groups: GnRH agonist group, in which patients received a GnRH agonist (n = 73), and a GnRH antagonist group, in which patients were administered a GnRH antagonist for pituitary suppression (n = 109). Pituitary suppression with GnRH agonist or GnRH antagonist. Ovarian stimulation carried out with recombinant FSH and supplemented with recombinant hCG microdose. Total dose of recombinant FSH and recombinant hCG administered; E(2) concentrations and endometrial width on the day of hCG trigger; number of follicles aspirated, oocytes and mature oocytes retrieved; fertilization, pregnancy (PR), implantation, and miscarriage rates. The total dose of recombinant FSH and recombinant hCG administered were similar between groups, as were the E(2) concentrations and endometrial width. The number of follicles aspirated, oocytes, and metaphase II oocytes collected were also comparable. There were no statistically significant differences in fertilization, PR, implantation, and miscarriage rates in the GnRH agonist and GnRH antagonist groups. When using recombinant hCG microdose supplementation for controlled ovarian stimulation (COS), there are no differences in laboratory or clinical outcomes with the use of either GnRH antagonist or agonist for pituitary suppression. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Random Start Ovarian Stimulation for Oocyte or Embryo Cryopreservation in Women Desiring Fertility Preservation Prior to Gonadotoxic Cancer Therapy.

PubMed

Danis, Rachel B; Pereira, Nigel; Elias, Rony T

2017-11-10

Women of reproductive age diagnosed with cancer are often interested in preserving gametes or reproductive tissue that would allow for future genetic parenthood. Preservation of fertility is often accomplished in young cancer patients via ovarian stimulation followed by oocyte or embryo cryopreservation. Conventional stimulation protocols, however, require 2-4 weeks to complete ovarian stimulation, oocyte retrieval and possible fertilization. Such a strategy may not be feasible in patients requiring urgent cancer treatment. Recent studies have highlighted that random start ovarian stimulation can be initiated irrespective of the phase of the menstrual cycle and is an attractive alternative to conventional ovarian stimulation. The primary aim of the current review is to discuss the feasibility and success of random start ovarian stimulation for oocyte or embryo cryopreservation in women desiring fertility preservation prior to gonadotoxic cancer therapy. We performed a systematic review of medical literature published between January 2000 to June 2017 reporting the utility of random start ovarian stimulation for fertility preservation. Search terms included "fertility preservation," "cancer," "ovarian stimulation," "random-start ovarian stimulation," "embryo cryopreservation, and" "oocyte cryopreservation." Publications were included in this review only if patients underwent random start ovarian stimulation prior to cancer therapy. Nineteen publications were identified and perused by the authors. Most publications described the utility of random start ovarian stimulation in the setting of breast cancer. Radom-start stimulation was associated with a reduced time interval between ovarian stimulation initiation and oocyte or embryo cryopreservation. The yield of mature oocytes and their developmental potential into embryos was comparable between conventional and random-start protocols, albeit with higher gonadotropin doses in the latter. The current review suggests that random start ovarian stimulation can shorten the interval between ovarian stimulation and oocyte retrieval, with the yield of oocytes and embryos being comparable to conventional stimulation protocols. Thus, random start ovarian stimulation may serve as a better option for fertility preservation in patients requiring urgent cancer treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of thermal stimulation, applied to the hindpaw via a hot water bath, upon ovarian blood flow in anesthetized nonpregnant rats.

PubMed

Uchida, Sae; Hotta, Harumi; Hanada, Tomoko; Okuno, Yuka; Aikawa, Yoshihiro

2007-08-01

The effects of thermal stimulation, applied to the hindpaw via a hot bath set to either 40 degrees C (non-noxious) or 49 degrees C (noxious), upon ovarian blood flow were examined in nonpregnant anesthetized rats. Ovarian blood flow was measured using a laser Doppler flowmeter. Blood pressure was markedly increased following 49 degrees C stimulation. Ovarian blood flow, however, showed no obvious change during stimulation, although a small increase was observed after stimulation. Ovarian blood flow and blood pressure responses to 49 degrees C stimulation were abolished after hindlimb somatic nerves proximal to the stimuli were cut. Heat stimulation (49 degrees C) resulted in remarkable increases in both ovarian blood flow and blood pressure in rats in which the sympathetic nerves supplying the ovary were cut but the hindlimb somatic nerves remained intact. The efferent activity of the ovarian plexus nerve was increased during stimulation at 49 degrees C. Stimulation at 40 degrees C had no effect upon ovarian blood flow, blood pressure or ovarian plexus nerve activity. Electrical stimulation of the distal part of the severed ovarian plexus nerve resulted in a decrease in both the diameter of ovarian arterioles, observed using a digital video microscope, and ovarian blood flow.The present results demonstrate that noxious heat, but not non-noxious warm, stimulation of the hindpaw skin in anesthetized rats influences ovarian blood flow in a manner that is attributed to reflex responses in ovarian sympathetic nerve activity and blood pressure.

A comparison between r-LH and urinary supplements containing LH activity in patients undergoing the microdose GnRH agonist flare protocol for in-vitro fertilization: a pilot study.

PubMed

Shavit, Tal; Agdi, Mohammed; Son, Weon Y; Hasson, Josseph; Dahan, Michael H

2016-08-01

The aim of this study was to compare pregnancy rates and stimulation parameters in patients with diminished ovarian reserve, who were treated with recombinant human luteinizing hormone (r-LH) or menopausal gonadotropins (hMG), as part of a microdose flare protocol. A retrospective cohort study was performed. Comparisons between the group that was stimulated with r-LH plus follicle stimulating hormone (FSH) to those treated with hMG and FSH, were performed. Measurements included: medication doses, number of oocyte collected, number of embryos obtained, pregnancy and clinical pregnancy rates. Patients in the r-LH group (N.=40) had significant higher clinical pregnancy rates (33% vs. 14%; P=0.04) and used lower dose of LH (1938 IU vs. 2807 IU; P=0.02) compared to patients that were stimulated with hMG (N.=39). r-LH may offer advantages for the treatment of diminished ovarian reserve when performing a microdose flare protocol when compared to hMG. Both larger and prospective studies should be carried out to confirm these findings.

Lysyl oxidase interacts with AGE signalling to modulate collagen synthesis in polycystic ovarian tissue

PubMed Central

Papachroni, Katerina K; Piperi, Christina; Levidou, Georgia; Korkolopoulou, Penelope; Pawelczyk, Leszek; Diamanti-Kandarakis, Evanthia; Papavassiliou, Athanasios G

2010-01-01

Abstract Connective tissue components – collagen types I, III and IV – surrounding the ovarian follicles undergo drastic changes during ovulation. Abnormal collagen synthesis and increased volume and density of ovarian stroma characterize the polycystic ovary syndrome (PCOS). During the ovulatory process, collagen synthesis is regulated by prolyl hydroxylase and lysyl oxidase (LOX) activity in ovarian follicles. LOX catalyzes collagen and elastin cross-linking and plays essential role in coordinating the control of ovarian extracellular matrix (ECM) during follicular development. We have recently shown accumulation of advanced glycation end products (AGEs), molecules that stimulate ECM production and abnormal collagen cross-linking, in ovarian tissue. However, the possible link between LOX and AGEs-induced signalling in collagen production and stroma formation in ovarian tissue from PCOS remains elusive. The present study investigates the hypothesis of AGE signalling pathway interaction with LOX gene activity in polycystic ovarian (PCO) tissue. We show an increased distribution and co-localization of LOX, collagen type IV and AGE molecules in the PCO tissue compared to control, as well as augmented expression of AGE signalling mediators/effectors, phospho(p)-ERK, phospho(p)-c-Jun and nuclear factor κB (NF-κB) in pathological tissue. Moreover, we demonstrate binding of AGE-induced transcription factors, NF-κB and activator protein-1 (AP-1) on LOX promoter, indicating a possible involvement of AGEs in LOX gene regulation, which may account for the documented increase in LOX mRNA and protein levels compared to control. These findings suggest that deposition of excess collagen in PCO tissue that induces cystogenesis may, in part, be due to AGE-mediated stimulation of LOX activity. PMID:19583806

Efficacy of corifollitropin alfa followed by recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist protocol for Korean women undergoing assisted reproduction.

PubMed

Park, Hyo Young; Lee, Min Young; Jeong, Hyo Young; Rho, Yong Sook; Song, Sang Jin; Choi, Bum-Chae

2015-06-01

To evaluate the effect of a gonadotropin-releasing hormone (GnRH) antagonist protocol using corifollitropin alfa in women undergoing assisted reproduction. Six hundred and eighty-six in vitro fertilization-embryo transfer (IVF)/intracytoplasmic sperm injection (ICSI) cycles were analyzed. In 113 cycles, folliculogenesis was induced with corifollitropin alfa and recombinant follicle stimulating hormone (rFSH), and premature luteinizing hormone (LH) surges were prevented with a GnRH antagonist. In the control group (573 cycles), premature LH surges were prevented with GnRH agonist injection from the midluteal phase of the preceding cycle, and ovarian stimulation was started with rFSH. The treatment duration, quality of oocytes and embryos, number of embryo transfer (ET) cancelled cycles, risk of ovarian hyperstimulation syndrome (OHSS), and the chemical pregnancy rate were evaluated in the two ovarian stimulation protocols. There were no significant differences in age and infertility factors between treatment groups. The treatment duration was shorter in the corifollitropin alfa group than in the control group. Although not statistically significant, the mean numbers of matured (86.8% vs. 85.1%) and fertilized oocytes (84.2% vs. 83.1%), good embryos (62.4% vs. 60.3%), and chemical pregnancy rates (47.2% vs. 46.8%) were slightly higher in the corifollitropin alfa group than in the control group. In contrast, rates of ET cancelled cycles and the OHSS risk were slightly lower in the corifollitropin alfa group (6.2% and 2.7%) than in the control group (8.2% and 3.5%), although these differences were also not statistically significant. Although no significant differences were observed, the use of corifollitropin alfa seems to offer some advantages to patients because of its short treatment duration, safety, lower ET cancellation rate and reduced risk of OHSS.

Practices and Attitudes Regarding Women Undergoing Fertility Preservation: A Survey of the National Physicians Cooperative.

PubMed

Bortoletto, Pietro; Confino, Rafael; Smith, Brigid M; Woodruff, Teresa K; Pavone, Mary Ellen

2017-09-01

To describe physician attitudes and variations in oncofertility treatment strategies. An exploratory online survey administered between December 1, 2014 and January 27, 2015 to 185 members of the National Physicians Cooperative (NPC). Twenty-eight percent (52 of 185) of NPC members responded to the online survey. Fifty percent of respondents were obstetrician-gynecologists working largely in academic medical centers. Thirty-eight percent stated that 14 was the youngest age they felt comfortable performing oocyte retrievals with 35% stating that any age was acceptable as long as they were postpubertal. Short stimulation protocols, utilizing a gonadotropin-releasing hormone (GnRH) antagonist (86%), were more common than long stimulation or microdose Lupron flare protocols (23% and 18%), respectively, which utilize a GnRH agonist. Random start protocols were used by 77% and over 90% perform luteal phase starts. When using random start protocols, 64% use gonadotropins only and 32% start GnRH antagonists alone for several days before starting gonadotropins. Fifty-five percent of physicians were comfortable stimulating ovarian cancer patients only after clearance from an oncologist. Aromatase inhibitors (77%) were significantly more common than tamoxifen (24%) for stimulation in breast cancer patients (p = 0.0006). When considering ovarian stimulation after chemotherapy, 24% expressed comfort only if blood counts are normal, 38% tend to wait 3 months. Regarding experimental treatment, 83% report discussing the use of GnRH agonists alone and 64% of clinics offer ovarian tissue cryopreservation. This study underlines the wide variation that exists in stimulation and phase start techniques, patient selection, comfort levels, and cancer type-specific decision making.

GnRH agonist versus GnRH antagonist in ovarian stimulation: is the emperor naked?

PubMed

Orvieto, R; Rabinson, J; Meltzer, S; Homburg, R; Anteby, E; Zohav, E

2006-01-01

The aim of the study was to evaluate the influence of type of GnRH-analog used during controlled ovarian hyperstimulation (COH) on the outcome of in vitro fertilization (IVF) cycles. All consecutive women aged < or = 35 years admitted to our IVF unit from January 2001 to December 2004 were enrolled in the study. Only patients undergoing up to their third IVF cycle attempt were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryos transferred, and clinical pregnancy rate were compared between women given GnRH-agonist or GnRH-antagonist during COH. Four hundred and eighty-seven consecutive IVF cycles were evaluated, 226 in the agonist group and 261 in the antagonist group. A clinical pregnancy was achieved in 93 patients in the agonist group (pregnancy rate 41.2% per cycle) and 66 patients in the antagonist grup (pregnancy rate 25.3%); this difference was statistically significant (p < 0.01). The agonist group also used significantly more gonadotropin ampoules, required longer stimulation, and had higher estradiol levels on the day of human chorionic gonadotropin administration. The midluteal long GhRH-agonist suppressive protocol should be the protocol of choice in young patients in their first three IVF cycle attempts.

GnRH antagonist, cetrorelix, for pituitary suppression in modern, patient-friendly assisted reproductive technology.

PubMed

Tur-Kaspa, Ilan; Ezcurra, Diego

2009-10-01

Gonadotropin-releasing hormone (GnRH) analogues are used routinely to prevent a premature luteinizing hormone (LH) surge in women undergoing assisted reproductive technology (ART) treatments. In contrast to GnRH agonists, antagonists produce rapid and reversible suppression of LH with no initial flare effect. To review the role of cetrorelix, the first GnRH antagonist approved for the prevention of premature LH surges during controlled ovarian stimulation in modern ART. A review of published literature on cetrorelix. Both multiple- and single-dose cetrorelix protocols were shown to be at least as effective as long GnRH agonist regimens for pituitary suppression in Phase II/III clinical trials. Furthermore, cetrorelix co-treatment resulted in similar live birth rates but a shorter duration of gonadotropin stimulation, a lower total gonadotropin dose requirement and lower incidence of ovarian hyperstimulation syndrome compared with long agonist regimens. A single-dose cetrorelix protocol further decreased the number of injections required. Preliminary studies have also produced promising data on the use of cetrorelix in modified ART protocols, such as frozen embryo transfer and donor oocyte recipient cycles. Cetrorelix offers a potential therapeutic alternative to GnRH agonists during controlled ovarian stimulation and has become an integral part of modern, patient-friendly reproductive medicine.

Long-Term Safety of Letrozole and Gonadotropin Stimulation for Fertility Preservation in Women With Breast Cancer

PubMed Central

Kim, Jayeon; Turan, Volkan

2016-01-01

Context and Objective: There has been increased attention to the issue of fertility preservation (FP). We aimed to investigate the long-term safety of FP via controlled ovarian stimulation with letrozole supplementation (COSTLES) prior to breast cancer treatment. Design, Setting, and Participants: This is a prospective, nonrandomized, controlled study conducted between the years 2002 and 2014. A total of 337 women diagnosed with stage 3 or less invasive breast cancer were enrolled during a FP consultation before chemotherapy. Of those, 120 elected to undergo COSTLES for FP prior to chemotherapy (FP group). The remaining 217 patients did not undergo any FP procedure and served as the controls. Main Outcome Measure: The primary end point was cancer recurrence defined as the detection of locoregional tumor (chest wall, regional nodal disease), distant metastases, or contralateral invasive breast cancer. Results: The baseline characteristics at enrollment were similar between the FP and control groups except for the less frequent lymph node involvement (P = .02) in the former. The mean follow-up after diagnosis was 5.0 years in the FP group and 6.9 years in the control group. In the FP group, the hazard ratio for recurrence after ovarian stimulation was 0.77 (95% confidence interval 0.28–2.13), and the survival was not compromised compared with controls (P = .61). Neither BRCA gene mutation status (P = .57) nor undergoing FP before or after breast surgery (P = .44) affected survival outcomes in the FP group. Likewise, none of the tumor characteristics including the estrogen receptor status affected the survival rates after the COSTLES. Conclusion: COSTLES is unlikely to cause a substantially increased recurrence risk in breast cancer during the 5 years after diagnosis. PMID:26751194

How to personalize ovarian stimulation in clinical practice.

PubMed

Sighinolfi, Giovanna; Grisendi, Valentina; La Marca, Antonio

2017-09-01

Controlled ovarian stimulation (COS) in in vitro fertilization (IVF) cycles is the starting point from which couple's prognosis depends. Individualization in follicle-stimulating hormone (FSH) starting dose and protocol used is based on ovarian response prediction, which depends on ovarian reserve. Anti-Müllerian hormone levels and the antral follicle count are considered the most accurate and reliable markers of ovarian reserve. A literature search was performed for studies that addressed the ability of ovarian reserve markers to predict poor and high ovarian response in assisted reproductive technology cycles. According to the predicted response to ovarian stimulation (poor- normal- or high- response), it is possible to counsel couples before treatment about the prognosis, and also to individualize ovarian stimulation protocols, choosing among GnRH-agonists or antagonists for endogenous FSH suppression, and the FSH starting dose in order to decrease the risk of cycle cancellation and ovarian hyperstimulation syndrome. In this review we discuss how to choose the best COS therapy, based on ovarian reserve markers, in order to enhance chances in IVF.

Biomarkers of ovarian reserve as predictors of reproductive potential.

PubMed

Steiner, Anne Z

2013-11-01

The size of the oocyte pool, the ovarian reserve, can determine a woman's reproductive stage. Chronologic age, anti-Müllerian hormone (AMH) levels, early follicular phase follicle-stimulating hormone levels, and early follicular phase inhibin B levels are correlated with ovarian reserve. Therefore, these biomarkers of ovarian reserve should serve as predictors of reproductive potential. Clinical and epidemiologic studies suggest that historical and laboratory biomarkers of ovarian reserve are associated with natural and treatment-related fertility. However, controversy remains as to their ability to predict reproductive potential. For infertile women undergoing assisted reproductive technology treatment, these biomarkers tend to be highly specific but not sensitive for cycle failure (nonpregnancy). While these biomarkers are being used as "fertility tests" in the general population, their value as predictors of unassisted fertility is still uncertain. Among laboratory biomarkers, AMH appears to have the most promise; however, further studies are needed to refine cutoff values and to determine test characteristics in the prediction of natural fertility or infertility in the general population. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The assesment of follicular fluid presepsin levels in poor ovarian responder womenandits relationship with the reproductive outcomes

PubMed Central

Ovayolu, Ali; Özdamar, Özkan; Gün, İsmet; Arslanbuğa, Cansev Y; Kutlu, Tayfun; Tunalı, Gülden; Uluhan, Ramazan

2015-01-01

A considerable proportion of all women undergoing IVFrespond poorly to gonadotropin stimulation. These women are reported to be associated with increased cancellation rates and lower pregnancy rates. It has been hypothesized that poor response to ovarian stimulation is a first sign of ovarian ageing or premature ovarian failure, which might be related to altered inflammatory response in the body. We aimed to compare follicular fluid presepsin levels between poor- and normo-responder patients to ovarian stimulation, to assess its relationship with reproductive outcomes. This study included infertility patients who underwent ovulation induction with either long GnRH agonist or GnRH antagonist protocols and who subsequently underwent IVF/ICSI. Included patients were assigned to two groups according to the Bologna criteria for poor ovarian response. Group 1 and 2 consisted of normo- and poor-responder patients, respectively.The 2 groups were compared in terms of FF presepsin levels. Also, any relationship between the FF presepsin levels and fertility outcomes was assessed within the groups. The groups were compared by using student’s t-test, Mann-Whitney U test and X2 test, where appropriate. Pregnancy rates were not significantly different between the groups (22.6% and 17.6%; P=0.650, respectively). FF presepsin levels were higher in Group 1, however, the difference was not statistically significant (298.0±797.4 and 149.2±422.3; P=0.190, respectively). FF presepsin levels did not significantly differ between pregnancy positive and the pregnancy negative patients in both Group 1 (243.6±531.1 and 314.3±866.5; P=0.055, respectively) and Group 2 (112.2±79.8 and 157.1±464.3; P=0.394, respectively). Consequently, FF presepsin seems not to be a reliable marker in predicting pregnancy in both normo-responder and poor-responder infertility groups. PMID:26309683

Effects of female increased body mass index on in vitro fertilization cycles outcome.

PubMed

Caillon, Hélène; Fréour, Thomas; Bach-Ngohou, Kalyane; Colombel, Agnès; Denis, Marc G; Barrière, Paul; Masson, Damien

2015-01-01

As being overweight can impair female spontaneous fertility or after assisted reproductive technology (ART) cycles, the aim of this study was to compare in vitro fertilization (IVF) outcome according to women's body mass index (BMI). Retrospective study conducted from 2006 to 2009 in the IVF unit of Nantes University Hospital, France. 582 patients undergoing standard infertility workup and controlled ovarian stimulation were categorized according to BMI into two groups: group 1: normal weight (20-24.9 kg/m(2); n=409) and group 2: overweight and obese (≥25 kg/m(2); n=149). Basal hormonal status, smoking habitus, infertility duration, IVF cycle parameters and outcome were recorded. Basal LH, FSH and estradiol levels were higher in group 1 than group 2, but ovarian reserve markers were comparable across the two BMI groups. Higher doses of gonadotropins were required in group 2 to obtain equivalent ovarian response than in group 1. No difference was observed on ovarian response and embryonic parameters. Cycle outcome were not significantly different between both groups, but we found a strong trend towards increasing transfer cancellation and miscarriage rates in group 2. Although overweight and obesity do not compromise ovarian stimulation results whenever adaptation of recombinant FSH doses is made, our data suggest an increased risk of cancellation transfer and miscarriage rate, leading to poorer IVF outcome. Copyright © 2015 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Concomitant use of FSH and low-dose recombinant hCG during the late follicular phase versus conventional controlled ovarian stimulation for intracytoplasmic sperm injection cycles.

PubMed

Iaconelli, Carla Andrade Rebello; Setti, Amanda Souza; Braga, Daniela Paes Almeida Ferreira; Maldonado, Luiz Guilherme Louzada; Iaconelli, Assumpto; Borges, Edson; Aoki, Tsutomu

2017-12-01

The objective of this study was to investigate the effects of low-dose hCG supplementation on ICSI outcomes and controlled ovarian stimulation (COS) cost. Three hundred and thirty patients undergoing ICSI were split into groups according to the COS protocol: (i) control group (n = 178), including patients undergoing conventional COS treatment; and (ii) low-dose hCG group (n = 152), including patients undergoing COS with low-dose hCG supplementation. Lower mean total doses of FSH administered and higher mean oestradiol level and mature oocyte rates were observed in the low-dose hCG group. A significantly higher fertilization rate, high-quality embryo rate and blastocyst formation rate were observed in the low-dose hCG group as compared to the control group. The miscarriage rate was significantly higher in the control group compared to the low-dose hCG group. A significantly lower incidence of OHSS was observed in the low-dose hCG group. There was also a significantly lower gonadotropin cost in the low-dose hCG group as compared to the control group ($1235.0 ± 239.0×$1763.0 ± 405.3, p < 0.001). The concomitant use of low-dose hCG and FSH results in a lower abortion rate and increased number of mature oocytes retrieved, as well as improved oocyte quality, embryo quality and blastocyst formation and reduced FSH requirements.

The role of aromatase inhibitors in ameliorating deleterious effects of ovarian stimulation on outcome of infertility treatment

PubMed Central

Mitwally, Mohamed FM; Casper, Robert F; Diamond, Michael P

2005-01-01

Clinical utilization of ovulation stimulation to facilitate the ability of a couple to conceive has not only provided a valuable therapeutic approach, but has also yielded extensive information on the physiology of ovarian follicular recruitment, endometrial receptivity and early embryo competency. One of the consequences of the use of fertility enhancing agents for ovarian stimulation has been the creation of a hyperestrogenic state, which may influence each of these parameters. Use of aromatase inhibitors reduces hyperestrogenism inevitably attained during ovarian stimulation. In addition, the adjunct use of aromatase inhibitors during ovarian stimulation reduces amount of gonadotropins required for optimum stimulation. The unique approach of reducing hyperestrogenism, as well as lowering amount of gonadotropins without affecting the number of mature ovarian follicles is an exciting strategy that could result in improvement in the treatment outcome by ameliorating the deleterious effects of the ovarian stimulation on follicular development, endometrial receptivity, as well as oocyte and embryo quality. PMID:16202169

[New possibilities resulting from oocyte banking].

PubMed

Revel, Ariel; Revel, Michel; Laufer, Neri; Kasher, Asa

2011-06-01

Oocyte cryopreservation solves the legal and ethical problems associated with the cryopreservation of embryos in patients undergoing in vitro fertilization procedures. Furthermore, it may also offer the possibility of extending the reproductive capability of young women with malignant diseases in cases where the treatment may compromise the ovarian reserve. Moreover, it may also offer alternatives for infertile patients who are subject to ovarian hyper-stimulation syndrome or premature ovarian faiLure or who require oocyte donation. The creation of banks for cryopreserved oocytes avoids the need for cycle synchronization or the formation of an over-supply of embryos destined for cryopreservation. If a Large number of oocytes is obtained it could possibly enable women and couples the opportunity to postpone childbirth according to their wishes. This paper reviews the revolution obtained by oocyte vitrification, reports on ethical issues and discusses the pros and cons of oocyte banking and its potential effects on society.

Serum AMH Level to Predict the Hyper Response in Women with PCOS and Non-PCOS Undergoing Controlled Ovarian Stimulation in ART.

PubMed

Vembu, Radha; Reddy, Nellepalli Sanjeeva

2017-01-01

It is essential to determine the cut-off value of serum anti-Mullerian hormone (AMH) to predict the hyper response in assisted reproductive technology (ART). There are few studies mentioning the cut-off value for the hyper response in infertile women but not specifically for polycystic ovary syndrome (PCOS) and non-PCOS groups. With this in background, this study was conducted. To determine the cut-off value of serum AMH to predict the hyper response in women with PCOS and non-PCOS undergoing a controlled ovarian stimulation (COS) in ART. To compare the outcome of stimulation in PCOS and non-PCOS groups. All 246 women enrolled for Intra Cytoplasmic Sperm Injection (ICSI) fulfilling the selection criteria were recruited. On the day 3 of the cycle, the serum AMH, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), estradiol and antral follicle count (AFC) were measured. They underwent COS as per the unit protocol. They were divided into PCOS and non-PCOS groups as per the Rotterdam's criteria. The mean age, duration of infertility, Body Mass Index (BMI), Ovarian reserve markers and outcome of stimulation were compared. Using the Statistical Package for the Social Sciences version 16.0 software, the significant difference was measured by multivariate analysis, as well as a one-way analysis of variance with Tukey's post-hoc test was used. Among 246 women, 31.3% were in PCOS group, and 68.7% were in non-PCOS group. Comparison of PCOS and non-PCOS groups showed a significant difference in the age with the mean age being 29.2 and 31.5 years, respectively. The mean AMH and AFC were 2-fold higher in PCOS group. The mean number of follicles, oocytes retrieved, MII and oocytes fertilised were significantly higher in PCOS group. The pregnancy rate was 52.6% in PCOS and 30.9% in non-PCOS group. In the PCOS group, 22.1% had ovarian hyper stimulation syndrome (OHSS), and only 4.7% had OHSS in non-PCOS group ( P = 0.0005). Receiving Operator Curve (ROC) curve was plotted to predict the hyper response, which showed a cut-off value of 6.85 ng/ml with a sensitivity of 66.7% and a specificity of 68.7% for PCOS group and 4.85 ng/ml with a sensitivity of 85.7% and a specificity of 89.7% in non-PCOS group. The cut-off value of serum AMH to predict the hyper response in PCOS group is 6.85 ng/ml and in non-PCOS group is 4.85 ng/ml.

Individualization of controlled ovarian stimulation in vitro fertilization using ovarian reserve markers.

PubMed

Grisendi, Valentina; La Marca, Antonio

2017-06-01

In assisted reproduction technologies (ART) the controlled ovarian stimulation (COS) therapy is the starting point from which a good oocytes retrieval depends. Treatment individualization is based on ovarian response prediction, which largely depends on a woman's ovarian reserve. Anti-Müllerian hormone (AMH) and antral follicle count (AFC) are considered the most accurate and reliable markers of ovarian reserve. A literature search was carried out for studies that addressed the ability of AMH and AFC to predict poor and/or excessive ovarian response in IVF cycles. According to the predicted response to ovarian stimulation (poor- normal- or high-response) is today possible not only to personalize pre-treatment counseling with the couple, but also to individualize the ovarian stimulation protocol, choosing among GnRH-agonists or antagonists for endogenous follicle-stimulating hormone (FSH) suppression and formulating the FSH starting dose most adequate for the single patients. In this review we discuss how to choose the best COS therapy for the single patient, on the basis of the markers-guided ovarian response prediction.

Corifollitropin alfa compared with follitropin beta in poor responders undergoing ICSI: a randomized controlled trial.

PubMed

Kolibianakis, E M; Venetis, C A; Bosdou, J K; Zepiridis, L; Chatzimeletiou, K; Makedos, A; Masouridou, S; Triantafillidis, S; Mitsoli, A; Tarlatzis, B C

2015-02-01

Does substituting 150 µg corifollitropin alfa for 450 IU follitropin beta during the first 7 days of ovarian stimulation in proven poor responders, result in retrieval of a non-inferior number (<1.5 fewer) of cumulus oocyte complexes (COCs)? A single s.c. dose of 150 µg corifollitropin alfa on the first day of ovarian stimulation, followed if necessary, from Day 8 onwards, with 450 IU of follitropin beta/day, is not inferior to daily doses of 450 IU follitropin beta. The 95% CI of the difference between medians in the number of oocytes retrieved was -1 to +1 within the safety margin of 1.5. Recent data from retrospective studies suggest that the use of corifollitropin alfa in poor responders is promising since it could simplify ovarian stimulation without compromising its outcome. Seventy-nine women with previous poor ovarian response undergoing ICSI treatment were enrolled in this open label, non-inferiority, randomized clinical trial (RCT). Inclusion criteria were: previous poor response to ovarian stimulation (≤4 COCs) after maximal stimulation, age <45 years, regular spontaneous menstrual cycle, body mass index: 18-32 kg/m(2) and basal follicle stimulating hormone ≤20 IU/l. On Day 2 of the menstrual cycle, patients were administered either a single s.c dose of 150 µg corifollitropin alfa (n = 40) or a fixed daily dose of 450 IU of follitropin beta (n = 39). In the corifollitropin alfa group, 450 IU of follitropin beta were administered from Day 8 of stimulation until the day of human chorionic gonadotrophin (hCG) administration, if necessary. To inhibit premature luteinizing hormone surge, the gonadotrophin releasing hormone antagonist ganirelix was used. Triggering of final oocyte maturation was performed using 250 µg of recombinant hCG, when at least two follicles reached 17 mm in mean diameter. The number of COCs retrieved was not statistically different between the corifollitropin alfa and the follitropin beta groups [Median 3 versus 2, 95% CI 2-4, 2-3, respectively, P = 0.26]. The 95% CI of the difference between medians in the number of oocytes retrieved was -1 to +1. A multivariable analysis adjusting for all the potential baseline differences confirmed this finding. No significant difference was observed regarding the probability of live birth between the corifollitropin alfa and the follitropin beta group (live birth per patient reaching oocyte retrieval: 7.9 versus 2.6%, respectively, difference +5.3%, 95% CI: -6.8 to +18.3). The present study was not powered to test a smaller difference (e.g. 1 COC) in terms of COCs retrieved as well as to show potential differences in the probability of pregnancy. Moreover, it would be interesting to assess whether the continuation of stimulation in the long acting FSH arm, where necessary, with 200 IU instead of 450 IU of follitropin beta would have altered the direction or the magnitude of the effect of the type of FSH, observed on the number of COCs retrieved. Corifollitropin alfa simplifies IVF treatment because it is administered in a GnRH antagonist protocol and replaces seven daily FSH injections with a single one of a long acting FSH without compromising the outcome. It could greatly reduce the burden of treatment for poor responders and this deserves further investigation. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Kisspeptin as a promising oocyte maturation trigger for in vitro fertilisation in humans.

PubMed

Kasum, Miro; Franulić, Daniela; Čehić, Ermin; Orešković, Slavko; Lila, Albert; Ejubović, Emina

2017-08-01

The aim of this review is to analyse the effectiveness of exogenous kisspeptin administration as a novel alternative of triggering oocyte maturation, instead of currently used triggers such as human chorionic gonadotropin (hCG) or gonadotropin releasing hormone (GnRH) agonist, in women undergoing in vitro fertilisation (IVF) treatment. Kisspeptin has been considered a master regulator of two modes of GnRH and hence gonadotropin secretion, pulses and surges. Administration of kisspeptin-10 and kisspeptin-54 induces the luteinising hormone (LH) surge required for egg maturation and ovulation in animal investigations and LH release during the preovulatory phase of the menstrual cycle and hypothalamic amenorrhoea in humans. Exogenous kisspeptin-54 has been successfully administered as a promising method of triggering oocyte maturation, following ovarian stimulation with gonadotropins and GnRH antagonists in women undergoing IVF, due to its efficacy considering achieved pregnancy rates compared to hCG and GnRH agonists. Also, its safety in patients at high risk of developing ovarian hyperstimulation syndrome is noteworthy. Nevertheless, further studies would be desirable to establish the optimal trigger of egg maturation and to improve the reproductive outcome for women undergoing IVF treatment.

Effect of letrozole on moderate and severe early-onset ovarian hyperstimulation syndrome in high-risk women: a prospective randomized trial.

PubMed

Mai, Qingyun; Hu, Xiaokun; Yang, Gang; Luo, Yingyi; Huang, Kejun; Yuan, Yuan; Zhou, Canquan

2017-01-01

Ovarian hyperstimulation syndrome is an iatrogenic complication of controlled ovarian stimulation. Early ovarian hyperstimulation syndrome occurs during luteal phase of controlled ovarian stimulation within 9 days after human chorionic gonadotropin trigger and reflects an acute consequence of this hormone on the ovaries. Late ovarian hyperstimulation syndrome occurs 10 or more days after human chorionic gonadotropin trigger and reflects increased endogenous human chorionic gonadotropin levels following pregnancy. Human chorionic gonadotropin stimulates granulosa-lutein cells to produce vascular endothelial growth factor messenger RNAs, which in turn raises serum vascular endothelial growth factor concentration and increases vascular permeability in women with ovarian hyperstimulation syndrome. Efforts to reduce the incidence and severity of ovarian hyperstimulation syndrome after oocyte retrieval, and in particular primary prevention efforts, are vital to prevent thrombogenesis and other serious complications. The objective of the study was to compare the efficacy of letrozole, an aromatase inhibitor, with aspirin in primary prevention of early ovarian hyperstimulation syndrome and to compare vascular endothelial growth factor levels between groups. Participants in this prospective randomized trial included 238 participants undergoing cryopreservation of the whole embryos after oocyte retrieval with at least 1 of the following high-risk factors for ovarian hyperstimulation syndrome: oocyte retrieval ≥25; estradiol level ≥5000 pg/mL on the day of human chorionic gonadotropin administration; and clinical or ultrasonographic evidence of ovarian hyperstimulation syndrome on the day of oocyte retrieval, such as ultrasonographic evidence of ascites. After human chorionic gonadotropin triggering, experimental (119 cases) and control (119 cases) groups received letrozole and aspirin, respectively, for 5 days. The 5 categories of ovarian hyperstimulation syndrome include no, yes-mild, yes-moderate, yes-severe, and yes-critical. The primary outcome was the incidence and severity of early ovarian hyperstimulation syndrome. The secondary outcome included vascular endothelial growth factor level both on the second and seventh day after the human chorionic gonadotropin trigger, and clinical and laboratory features of ovarian hyperstimulation syndrome symptoms. The incidence of ovarian hyperstimulation syndrome was significantly higher in women receiving aspirin, compared with letrozole (90.2% vs 80.4%, P = .044). Moderate and severe ovarian hyperstimulation syndrome was also higher in the aspirin group, 45.1%, compared with the letrozole group, 25.0% (P = .002). Moreover, the duration of luteal phase was shortened in letrozole group compared with aspirin group (8.1 ± 1.1 days vs 10.5 ± 1.9 days, P < .001). The vascular endothelial growth factor level was significantly higher in the letrozole-treated group than aspirin-treated group (0.49 ± 0.26 vs 0.42 ± 0.22, P = .029). Letrozole was more effective than aspirin in decreasing the incidence of moderate and severe early-onset ovarian hyperstimulation syndrome. Our results indicate that ovarian hyperstimulation syndrome might be caused through a luteolytic effect rather than through modulation of vascular endothelial growth factor, racing by a decline in estradiol and termination of early-onset ovarian hyperstimulation syndrome in advance in high-risk women with cryopreservation of the whole embryos. Copyright © 2016 Elsevier Inc. All rights reserved.

Melatonin levels in follicular fluid as markers for IVF outcomes and predicting ovarian reserve.

PubMed

Tong, Jing; Sheng, Shile; Sun, Yun; Li, Huihui; Li, Wei-Ping; Zhang, Cong; Chen, Zi-Jiang

2017-04-01

Good-quality oocytes are critical for the success of in vitro fertilization (IVF), but, to date, there is no marker of ovarian reserve available that can accurately predict oocyte quality. Melatonin exerts its antioxidant actions as a strong radical scavenger that might affect oocyte quality directly as it is the most potent antioxidant in follicular fluid. To investigate the precise role of endogenous melatonin in IVF outcomes, we recruited 61 women undergoing treatment cycles of IVF or intracytoplasmic sperm injection (ICSI) procedures and classified them into three groups according to their response to ovarian stimulation. Follicular fluid was collected to assess melatonin levels using a direct RIA method. We found good correlations between melatonin levels in follicular fluid with age, anti-Müllerian hormone (AMH) and baseline follicle-stimulating hormone (bFSH), all of which have been used to predict ovarian reserve. Furthermore, as melatonin levels correlated to IVF outcomes, higher numbers of oocytes were collected from patients with higher melatonin levels and consequently the number of oocytes fertilized, zygotes cleaved, top quality embryos on D3, blastocysts obtained and embryos suitable for transplantation was higher. The blastocyst rate increased in concert with the melatonin levels across the gradient between the poor response group and the high response group. These results demonstrated that the melatonin levels in follicular fluid is associated with both the quantity and quality of oocytes and can predict IVF outcomes as well making them highly relevant biochemical markers of ovarian reserve. © 2017 Society for Reproduction and Fertility.

IVF with planned single-embryo transfer versus IUI with ovarian stimulation in couples with unexplained subfertility: an economic analysis.

PubMed

van Rumste, Minouche M E; Custers, Inge M; van Wely, Madelon; Koks, Carolien A; van Weering, Hans G I; Beckers, Nicole G M; Scheffer, Gabrielle J; Broekmans, Frank J M; Hompes, Peter G A; Mochtar, Monique H; van der Veen, Fulco; Mol, Ben W J

2014-03-01

Couples with unexplained subfertility are often treated with intrauterine insemination (IUI) with ovarian stimulation, which carries the risk of multiple pregnancies. An explorative randomized controlled trial was performed comparing one cycle of IVF with elective single-embryo transfer (eSET) versus three cycles of IUI-ovarian stimulation in couples with unexplained subfertility and a poor prognosis for natural conception, to assess the economic burden of the treatment modalities. The main outcome measures were ongoing pregnancy rates and costs. This study randomly assigned 58 couples to IVF-eSET and 58 couples to IUI-ovarian stimulation. The ongoing pregnancy rates were 24% in with IVF-eSET versus 21% with IUI-ovarian stimulation, with two and three multiple pregnancies, respectively. The mean cost per included couple was significantly different: €2781 with IVF-eSET and €1876 with IUI-ovarian stimulation (P<0.01). The additional costs per ongoing pregnancy were €2456 for IVF-eSET. In couples with unexplained subfertility, one cycle of IVF-eSET cost an additional €900 per couple compared with three cycles of IUI-ovarian stimulation, for no increase in ongoing pregnancy rates or decrease in multiple pregnancies. When IVF-eSET results in higher ongoing pregnancy rates, IVF would be the preferred treatment. Couples that have been trying to conceive unsuccessfully are often treated with intrauterine insemination (IUI) and medication to improve egg production (ovarian stimulation). This treatment carries the risk of multiple pregnancies like twins. We performed an explorative study among those couples that had a poor prognosis for natural conception. One cycle of IVF with transfer of one selected embryo (elective single-embryo transfer, eSET) was compared with three cycles of IUI-ovarian stimulation. The aim of this study was to assess the economic burden of both treatments. The Main outcome measures were number of good pregnancies above 12weeks and costs. We randomly assigned 58 couples to IVF-eSET and 58 couples to IUI-ovarian stimulation. The ongoing pregnancy rates were comparable: 24% with IVF-eSET versus 21% with IUI-ovarian stimulation. There were two multiple pregnancies with IVF-eSET and three multiple pregnancies with IUI-ovarian stimulation. The mean cost per included couple was significantly different, €2781 with IVF-eSET and €1876 with IUI-ovarian stimulation. The additional costs per ongoing pregnancy were €2456 for IVF-eSET. In couples with unexplained subfertility, one cycle of IVF-eSET costed an additional €900 per couple compared to three cycles of IUI-ovarian stimulation, for no increase in ongoing pregnancy rates or decrease in multiple pregnancies. We conclude that IUI-ovarian stimulation is the preferred treatment to start with. When IVF-eSET results in a higher ongoing pregnancy rate (>38%), IVF would be the preferred treatment. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Cyclic AMP-dependent modification of gonad-selective TAF(II)105 in a human ovarian granulosa cell line.

PubMed

Wu, Yimin; Lu, Yunzhe; Hu, Yanfen; Li, Rong

2005-11-01

In response to gonadotropins, the elevated level of intracellular-cyclic AMP (cAMP) in ovarian granulosa cells triggers an ordered activation of multiple ovarian genes, which in turn promotes various ovarian functions including folliculogenesis and steroidogenesis. Identification and characterization of transcription factors that control ovarian gene expression are pivotal to the understanding of the molecular basis of the tissue-specific gene regulation programs. The recent discovery of the mouse TATA binding protein (TBP)-associated factor 105 (TAF(II)105) as a gonad-selective transcriptional co-activator strongly suggests that general transcription factors such as TFIID may play a key role in regulating tissue-specific gene expression. Here we show that the human TAF(II)105 protein is preferentially expressed in ovarian granulosa cells. We also identified a novel TAF(II)105 mRNA isoform that results from alternative exon inclusion and is predicted to encode a dominant negative mutant of TAF(II)105. Following stimulation by the adenylyl cyclase activator forskolin, TAF(II)105 in granulosa cells undergoes rapid and transient phosphorylation that is dependent upon protein kinase A (PKA). Thus, our work suggests that pre-mRNA processing and post-translational modification represent two important regulatory steps for the gonad-specific functions of human TAF(II)105. Copyright 2005 Wiley-Liss, Inc.

Comparison of ovulation induction and pregnacy outcomes in IVF patients with normal ovarian reserve who underwent long protocol with recombinant-FSH and highly purified-hMG.

PubMed

Celik, Cem; Sofuoğlu, Kenan; Selçuk, Selçuk; Asoğlu, Mehmet Reşit; Abalı, Remzi; Cetingöz, Elçin; Baykal, Bahar; Uludoğan, Mehmet

2011-01-01

Gonadotropins used in controlled ovarian stimulation have been increasing in number. Beside the recombinant preparations such as rec-FSH, rec-LH and h-hMG human-derived preparations have entered the market. We decided to compare the effects of rec-FSH and HP-hMG with GnRHa on embryo quality and pregnancy outcome in women undergoing an IVF cycle. In this study, data of 87 patients who had applied to our center from 2007 to 2008 and who had met all inclusion criteria, were analyzed. The patients underwent controlled ovarian hyperstimulation with HP-hMG, rec-FSH following down-regulation with a GnRHa in a long protocol, selected according to determined criteria and acquired embryo via IVF transfer. Of the 87 patients, 44 were stimulated with rec-FSH and 43 with HP-hMG. Distribution of infertility causes was similar between the groups. Duration of gonadotropin administration (p=0.677, Student's t-test) and the total dose of gonadotropin received (p=0.392, Student's t-test) were similar between the two groups. The fertilization rate of the rec-FSH group was significantly higher than the HP-hMG group (p=0.001, Mann-Whitney U test). No significant differences were observed between the study groups in biochemical, clinical and ongoing pregnancy parameters. The higher oocyte yield with rec-FSH does not result in higher quality embryos. LH activity in combination with FSH activity positively affected the oocyte and embryo maturation. Therefore, when we consider the clinical and ongoing pregnancy rates there is no inferiority of HP-hMG in controlled ovarian stimulation.

Comparison of ovulation induction and pregnacy outcomes in IVF patients with normal ovarian reserve who underwent long protocol with recombinant-FSH and highly purified-hMG

PubMed Central

Çelik, Cem; Sofuoğlu, Kenan; Selçuk, Selçuk; Asoğlu, Mehmet Reşit; Abalı, Remzi; Çetingöz, Elçin; Baykal, Bahar; Uludoğan, Mehmet

2011-01-01

Objective Gonadotropins used in controlled ovarian stimulation have been increasing in number. Beside the recombinant preparations such as rec-FSH, rec-LH and h-hMG human-derived preparations have entered the market. We decided to compare the effects of rec-FSH and HP-hMG with GnRHa on embryo quality and pregnancy outcome in women undergoing an IVF cycle. Material and Methods In this study, data of 87 patients who had applied to our center from 2007 to 2008 and who had met all inclusion criteria, were analyzed. The patients underwent controlled ovarian hyperstimulation with HP-hMG, rec-FSH following down-regulation with a GnRHa in a long protocol, selected according to determined criteria and acquired embryo via IVF transfer. Results Of the 87 patients, 44 were stimulated with rec-FSH and 43 with HP-hMG. Distribution of infertility causes was similar between the groups. Duration of gonadotropin administration (p=0.677, Student’s t-test) and the total dose of gonadotropin received (p=0.392, Student’s t-test) were similar between the two groups. The fertilization rate of the rec-FSH group was significantly higher than the HP-hMG group (p=0.001, Mann-Whitney U test). No significant differences were observed between the study groups in biochemical, clinical and ongoing pregnancy parameters. Conclusion The higher oocyte yield with rec-FSH does not result in higher quality embryos. LH activity in combination with FSH activity positively affected the oocyte and embryo maturation. Therefore, when we consider the clinical and ongoing pregnancy rates there is no inferiority of HP-hMG in controlled ovarian stimulation. PMID:24591951

The Effect of Supraphysiological Estradiol on Pregnancy Outcomes Differs between Women with PCOS and Ovulatory Women.

PubMed

Wei, Daimin; Yu, Yunhai; Sun, Mei; Shi, Yuhua; Sun, Yun; Deng, Xiaohui; Li, Jing; Wang, Ze; Zhao, Shigang; Zhang, Heping; Legro, Richard S; Chen, Zi-Jiang

2018-04-27

Supra-physiological estradiol exposure after ovarian stimulation may disrupt embryo implantation after fresh embryo transfer, compared with physiological estradiol exposure during frozen embryo transfer(FET). Women with polycystic ovary syndrome (PCOS) who usually over-respond to ovarian stimulation have a better live birth rate after elective FET than fresh embryo transfer; however ovulatory women don't. To evaluate whether the discrepancy in live birth rate after fresh versus FET between women with PCOS and ovulatory women was due to the variation in ovarian response, i.e. peak estradiol level or oocyte number. This was a secondary analysis of data from two multicenter randomized trials with similar study designs. A total of 1508 women with PCOS in the first trial and 2157 ovulatory women in the second trial were randomized to undergo either fresh or frozen embryo transfer. The primary outcome was live birth. Compared with fresh embryo transfer, FET resulted in a higher live birth rate(51.9% vs. 40.7%, OR: 1.57, 95%CI: 1.22-2.03) in PCOS women with peak estradiol level >3000pg/ml but not in those with estradiol level ≤3000pg/ml. In PCOS women with oocyte number ≥16, FET yielded a higher live birth rate(54.8% vs. 42.1%, OR: 1.67, 95%CI: 1.20-2.31), but not in those with oocyte number <16. However, in ovulatory women, the pregnancy outcomes were comparable after fresh and FET in all subgroups. Supra-physiological level of estradiol after ovarian stimulation may adversely affect pregnancy outcomes in women with PCOS; but not in ovulatory women.

Cumulative live-birth rate in women with polycystic ovary syndrome or isolated polycystic ovaries undergoing in-vitro fertilisation treatment.

PubMed

Li, Hang Wun Raymond; Lee, Vivian Chi Yan; Lau, Estella Yee Lan; Yeung, William Shu Biu; Ho, Pak Chung; Ng, Ernest Hung Yu

2014-02-01

This retrospective cohort study evaluated the cumulative live birth rate in women with polycystic ovary syndrome (PCOS) and isolated polycystic ovaries (PCO) undergoing in-vitro fertilisation (IVF) treatment. We studied 104 women with PCOS, 184 with PCO and 576 age-matched controls undergoing the first IVF treatment cycle between 2002 and 2009. The main outcome measure was cumulative live birth in the fresh plus all the frozen embryo transfers combined after the same stimulation cycle. Women in both the PCOS (n = 104) and isolated PCO groups (n = 184) had higher ovarian response parameters compared to age-matched controls (n = 576), and higher rates of withholding fresh embryo transfer for risk of ovarian hyperstimulation syndrome (OHSS). The actual incidence of moderate to severe OHSS was significantly higher in the PCOS (11.5 %) but not the isolated PCO group (8.2%) compared to controls (4.9%). The live birth rates in the fresh cycle were comparable among the 3 groups, but the PCOS group had a significantly higher miscarriage rate compared to the other 2 groups. Cumulative live birth rate was significantly higher in the isolated PCO group (60.3%), but not the PCOS group (50.0%), compared to controls (47.5%). Women in the isolated PCO group, but not the PCOS group, had a significantly higher cumulative live birth rate compared to controls. This could be explained by the quantitative effect of the higher number of transferable embryos obtained per stimulation cycle, which is uncompromised by the unfavourable embryo competence otherwise observed in PCOS.

The prevention of ovarian hyperstimulation syndrome.

PubMed

Corbett, Shannon; Shmorgun, Doron; Claman, Paul

2014-11-01

To review the clinical aspects of ovarian hyperstimulation syndrome and provide recommendations on its prevention. Preventative measures, early recognition, and prompt systematic supportive care will help avoid poor outcomes. Establish guidelines to assist in the prevention of ovarian hyperstimulation syndrome, early recognition of the condition when it occurs, and provision of appropriate supportive measures in the correct setting. Published literature was retrieved through searches of Medline, Embase, and the Cochrane Library from 2011 to 2013 using appropriate controlled vocabulary ([OHSS] ovarian hyperstimulation syndrome and: agonist IVF, antagonist IVF, metformin, HCG, gonadotropin, coasting, freeze all, agonist trigger, progesterone) and key words (ovarian hyperstimulation syndrome, ovarian stimulation, gonadotropin, human chorionic gonadotropin, prevention). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English. There were no date restrictions. Searches were updated on a regular basis and incorporated in the guideline to February 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Summary Statements 1. The particular follicle-stimulating hormone formulation used for ovarian stimulation does not affect the incidence of ovarian hyperstimulation syndrome. (I) 2. Coasting may reduce the incidence of severe ovarian hyperstimulation syndrome. (III) 3. Coasting for longer than 3 days reduces in vitro fertilization pregnancy rates. (II-2) 4. The use of either luteinizing hormone or human chorionic gonadotropin for final oocyte maturation does not influence the incidence of ovarian hyperstimulation syndrome. (I) 5. There is no clear published evidence that lowering the human chorionic gonadotropin dose will result in a decrease in the rate of ovarian hyperstimulation syndrome. (III) 6. Cabergoline starting from the day of human chorionic gonadotropin reduces the incidence of ovarian hyperstimulation syndrome in patients at higher risk and does not appear to lower in vitro fertilization pregnancy rates. (II-2) 7. Avoiding pregnancy by freezing all embryos will prevent severe prolonged ovarian hyperstimulation syndrome in patients at high risk. (II-2) 8. Pregnancy rates are not affected when using gonadotropin-releasing hormone (GnRH) agonists in GnRH antagonist protocols for final egg maturation when embryos are frozen by vitrification for later transfer. (II-2) Recommendations 1. The addition of metformin should be considered in patients with polycystic ovarian syndrome who are undergoing in vitro fertilization because it may reduce the incidence of ovarian hyperstimulation syndrome. (I-A) 2. Gonadotropin dosing should be carefully individualized, taking into account the patient's age, body mass, antral follicle count, and previous response to gonadotropins. (II-3B) 3. Cycle cancellation before administration of human chorionic gonadatropin is an effective strategy for the prevention of ovarian hyperstimulation syndrome, but the emotional and financial burden it imposes on patients should be considered before the cycle is cancelled. (III-C) 4. Gonadotropin-releasing hormone (GnRH) antagonist stimulation protocols are recommended in patients at high risk for ovarian hyperstimulation syndrome (OHSS). The risk of severe OHSS in patients on GnRH antagonist protocols who have a very robust ovarian stimulation response can be reduced by using a GnRH agonist as a substitute for human chorionic gonadotropin to trigger final oocyte maturation. (I-B) 5. A gonadotropin-releasing hormone (GnRH) antagonist protocol with a GnRH agonist trigger for final oocyte maturation is recommended for donor oocyte and fertility preservation cycles. (III-C) 6. Albumin or other plasma expanders at the time of egg retrieval are not recommended for the prevention of ovarian hyperstimulation syndrome. (I-E) 7. Elective single embryo transfer is recommended in patients at high risk for ovarian hyperstimulation syndrome. (III-C) 8. Progesterone, rather than human chorionic gonadotropin, should be used for luteal phase support. (I-A) 9. Outpatient culdocentesis should be considered for the prevention of disease progression in severe ovarian hyperstimulation syndrome. (II-2B).

Luteal Phase Support in the Intrauterine Insemination (IUI) Cycles: A Randomized Double Blind, Placebo Controlled Study

PubMed Central

Hossein Rashidi, Batool; Davari Tanha, Fatemeh; Rahmanpour, Haleh; Ghazizadeh, Mahya

2014-01-01

Objective: To evaluate the impact of luteal phase support with vaginal progesterone on pregnancy rates in the intrauterine insemination (IUI) cycles, stimulated with clomiphene citrate and human menopausal gonadotropin (hMG), in sub fertile couples. Materials and methods: This prospective, randomized, double blind study was performed in a tertiary infertility center from March 2011 to January 2012. It consisted of 253 sub fertile couples undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with clomiphene citrate (100 mg) and hMG (75 IU) in preparation for the IUI cycle. Study group (n = 127) received luteal phase support in the form of vaginal progesterone (400 mg twice a day), and control group (n = 126) received placebo. Clinical pregnancy and abortion rates were assessed and compared between the two groups. Results: The clinical pregnancy rate was not significantly higher for supported cycles than that for the unsupported ones (15.75% vs. 12.69%, p = 0.3). The abortion rate in the patients with progesterone luteal support compared to placebo group was not statistically different (10% vs. 18.75%, p = 0.45). Conclusion: It seems that luteal phase support with vaginal progesterone was not enhanced the success of IUI cycles outcomes, when clomiphene citrate and hMG were used for ovulation stimulation. PMID:25530766

Association between response to ovarian stimulation and miscarriage following IVF: an analysis of 124 351 IVF pregnancies.

PubMed

Sunkara, Sesh Kamal; Khalaf, Yacoub; Maheshwari, Abha; Seed, Paul; Coomarasamy, Arri

2014-06-01

Is there a relationship between ovarian reserve, quantified as ovarian response to stimulation, and miscarriage rate following IVF treatment? There is a strong association between the number of oocytes retrieved and miscarriage rate following IVF treatment, with the miscarriage rate decreasing with an increasing number of oocytes and then levelling off: poor responders have a higher miscarriage rate across all age groups. Poor ovarian response is a manifestation of a decline in the quantity of the primordial follicle pool. Whether poor ovarian response is associated with a decline in oocyte quality contributing to miscarriage is however debated. Anonymous data were obtained from the Human Fertilization and Embryology Authority (HFEA), the statutory regulator of assisted reproduction treatment (ART) in the UK. The HFEA has collected data on all ART performed in the UK since 1991. Data from 1991 to June 2008 involving 402 185 stimulated fresh IVF cycles and 124 351 pregnancy outcomes were analysed. Data on all women undergoing a stimulated fresh IVF treatment cycle with at least one oocyte retrieved during the period from 1991 to June 2008 were analysed for their early pregnancy outcomes. There was a strong association between the number of oocytes retrieved and the clinical miscarriage rate. The miscarriage rate fell from 20 to 13% with an increasing number of oocytes before levelling off. Stepwise logistic regression identified three cut-off points (4, 10 and 15 oocytes) at or beyond which the probability of clinical miscarriage fell. There was no increase in miscarriage rate with very high oocyte numbers (>20 oocytes). The lowest risk of miscarriage (9.9%) was for women under 38 years of age, with primary infertility without a female cause and producing more than three oocytes. Although the analysis was performed only on stimulated IVF cycles (excluding unstimulated cycles), the data had the limitation that there was no information on the total gonadotrophin consumption. The model was adjusted for age and type of infertility, but the dataset contained no information on other confounders such as body mass index (BMI) of the women to allow adjustment. Analysis of this extensive dataset suggests that poor responders have a higher risk of clinical miscarriage, indicating that poor ovarian response is associated with a parallel decline in both oocyte quantity and quality. The miscarriage rate is also higher with advanced age, secondary infertility and a female cause of infertility compared with a younger age, male factor infertility and unexplained cause.

Basal serum progesterone and history of elevated progesterone on the day of hCG administration are significant predictors of late follicular progesterone elevation in GnRH antagonist IVF cycles.

PubMed

Venetis, Christos A; Kolibianakis, Efstratios M; Bosdou, Julia K; Lainas, George T; Sfontouris, Ioannis A; Tarlatzis, Basil C; Lainas, Tryfon G

2016-08-01

Are there any baseline predictors of progesterone elevation (PE) on the day of human chorionic gonadotrophin (hCG) which are not associated with the intensity of ovarian stimulation in women undergoing in vitro fertilization (IVF) using follicle stimulating hormone (FSH) and gonadotrophin-releasing hormone (GnRH) antagonists? Basal (Day 2 of the menstrual cycle) serum progesterone concentration and history of PE are baseline variables that can predict the occurrence of PE on the day of hCG independently of the intensity of ovarian stimulation. PE on the day of hCG is associated with the magnitude of the ovarian response to stimulation. For this reason, it has been hypothesized that milder ovarian stimulation might reduce the probability of PE. However, given the fact that the number of oocytes retrieved is associated with the probability of live birth, such a strategy should be considered only in patients that are at high risk of PE on the day of hCG. This is a retrospective analysis of a cohort of fresh IVF/ICSI cycles (n = 1702) performed in a single IVF centre during the period 2001-2015. Patients in whom ovarian stimulation was performed with FSH and GnRH antagonists and with basal FSH <14.0 mIU/ml, progesterone (P) ≤1.6 ng/ml and estradiol (E2) ≤80 pg/ml on the same day (prior to the initiation of stimulation) were considered eligible. PE was defined as serum progesterone concentration >1.5 ng/ml. Pre-stimulation characteristics of patients and basal hormonal profile were assessed for their ability to predict the occurrence of PE after ovarian stimulation through generalized estimating equation univariable and multivariable regression analyses, controlling for the effect of ovarian stimulation. Furthermore, a secondary analysis in a subset of patients with multiple IVF cycles explored whether the occurrence of PE in one of the previous cycles included in this study is associated with a significantly higher occurrence of PE elevation in subsequent cycles. Univariable regression analyses showed that female age (OR: 0.97; 95% CI: 0.94-0.99), basal FSH (OR: 0.85; 95% CI: 0.79-0.92) and basal P (OR: 4.20; 95% CI: 2.47-7.12) were baseline variables that could significantly predict PE on the day of hCG. When these variables were entered in the same model as covariates, only basal FSH (OR: 0.86; 95% CI: 0.80-0.94) and basal P (OR: 3.83; 95% CI: 2.24-6.56) could still predict the occurrence of PE. Basal P (OR: 6.30; 95% CI: 3.35-11.82) was the only variable that could significantly predict the occurrence of PE on the day of hCG after adjusting for the intensity of ovarian stimulation. The secondary analysis revealed that history of PE on the day of hCG in a previous cycle was also strongly associated with an increased risk of PE in a subsequent cycle. This is a retrospective analysis and although the effect of the most important confounders was controlled for in the multivariable analysis, the presence of residual bias cannot be excluded. The findings of this study might help clinicians identify patients at high risk for late follicular PE and alter the management of their cycle. None. Not applicable. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Clomiphene Citrate versus Letrozole for Ovarian Stimulation in Therapeutic Donor Sperm Insemination.

PubMed

El Hachem, Hady; Antaki, Roland; Sylvestre, Camille; Kadoch, Isaac-Jacques; Lapensée, Louise; Bouet, Pierre Emmanuel

2017-01-01

To compare clomiphene citrate (CC) and letrozole for ovarian stimulation (OS) in therapeutic donor sperm insemination (TDI) cycles. Retrospective cohort study between January 2011 and June 2014 at a University-affiliated private IVF clinic in Montreal, Canada. 257 normo-ovulatory women ≤40 years of age with no history of infertility undergoing 590 TDI cycles in the absence of a male partner (single women and same-sex couples) or azoospermia were included. Patients received 100 mg CC daily (145 women, 321 cycles) or letrozole 5 mg daily (112 women, 269 cycles), from days 3 to 7. Only the first 3 cycles were included per patient. Our main outcome measure was cumulative live birth rates (LBR). Baseline characteristics were comparable between the 2 groups. There were no differences in LBR per cycle (16.5% (53/321) vs. 11.5% (31/269), p = 0.08) and cumulative LBR (36.6% (53/145) vs. 27.7% (31/112), p = 0.13), between CC and letrozole, respectively. Multiple pregnancy rate (11.6% (8/69) vs. 8.7% (4/46), p = 0.6) and miscarriage rate (21.7 vs. 21.7%, p = 1) were also comparable between CC and letrozole, respectively. In normo-ovulatory women undergoing TDI, OS with CC or letrozole resulted in similar live birth and twin pregnancy rates. © 2016 S. Karger AG, Basel.

Adverse eff ects of polymeric nanoparticle poly(ethylene glycol)- block-polylactide methyl ether (PEG-b-PLA) on steroid hormone secretion by porcine granulosa cells.

PubMed

Scsukova, Sona; Bujnakova, Mlynarcikova A; Kiss, A; Rollerova, E

2017-04-25

Development of nanoparticles (NPs) for biomedical applications, including medical imaging and drug delivery, is currently undergoing a dramatic expansion. Diverse effects of different type NPs relating to mammalian reproductive tissues have been demonstrated. Th e objective of this study was to explore the in vitro effects of polymeric nanoparticle poly(ethylene glycol)-blockpolylactide methyl ether (PEG-b-PLA NPs) on functional state and viability of ovarian granulosa cells (GCs), which play an important role in maintaining ovarian function and female fertility. The GCs isolated from porcine ovarian follicles were incubated with the different concentrations of PEG-b-PLA NPs (PEG average Mn=350 g/mol and PLA average Mn=1000 g/mol; 0.2-100 μg/ml) or poly(ethylene glycol) with an average molecular weight of 300 (PEG-300; 0.2- 40 mg/ml) in the presence or absence of stimulators, follicle-stimulating hormone (FSH; 1 μg/ml), androstenedione (100 nM), forskolin (10 μM) or 8Br-cAMP (100 μM), for different time periods (24, 48, 72 h). At the end of the incubation, progesterone and estradiol levels produced by GCs were measured in the culture media by radioimmunoassay. Th e viability of GCs was determined by the method using a colorimetric assay with MTT. Treatment of GCs with PEG-b-PLA NPs induced a significant decrease in basal as well as FSH-stimulated progesterone secretion above the concentration of 20 and 4 μg/ml, respectively. Moreover, PEG-b-PLA NPs reduced forskolin-stimulated, but not cAMP-stimulated progesterone production by GCs. A dose-dependent inhibition of androstenedione-stimulated estradiol release by GCs was found by the action of PEG-b-PLA NPs. Incubation of GCs with PEG-300 significantly inhibited basal as well as FSH-stimulated progesterone secretion above the concentration of 40 mg/ml. PEG-b-PLA NPs and PEG-300 significantly reduced the viability of GCs at the highest tested concentrations (100 μg/ml and 40 mg/ml, respectively). The obtained results indicate that polymeric NPs PEG-b-PLA might induce alterations in steroid hormone production by ovarian GCs and thereby could modify reproductive functions.

Vitamin D deficiency and pregnancy rates in women undergoing single embryo, blastocyst stage, transfer (SET) for IVF/ICSI.

PubMed

Polyzos, Nikolaos P; Anckaert, Ellen; Guzman, Luis; Schiettecatte, Johan; Van Landuyt, Lisbet; Camus, Michel; Smitz, Johan; Tournaye, Herman

2014-09-01

What is the influence of vitamin D deficiency on pregnancy rates among women undergoing IVF/ICSI and Day 5 (blastocyst stage) single embryo transfer (SET)? Vitamin D deficiency results in significantly lower pregnancy rates in women undergoing single blastocyst transfer. Preliminary experiments have identified the presence of vitamin D receptors in the female reproductive system. However, results regarding the effect of vitamin D deficiency on clinical outcomes are conflicting. None of the previous studies adopted a SET strategy. Serum vitamin D concentration was measured retrospectively in patients who underwent SET on Day 5. Overall 368 consecutive infertile women treated within a period of 15 months were included in the study. All patients underwent ovarian stimulation for IVF/ICSI and Day 5 SET. Serum samples were obtained 7 days prior to embryo transfer and stored frozen at -20°C. Samples were collectively analyzed for their 25-OH vitamin D content. Vitamin D deficiency was defined as serum 25-OH vitamin D levels <20 ng/ml in accordance with the Institute of Medicine and the Endocrine Society clinical practice guidelines. Clinical pregnancy rates were significantly lower in women with vitamin D deficiency compared with those with higher vitamin D values (41 versus 54%, P = 0.015).Logistic regression analysis was performed to identify whether vitamin D deficiency is independently associated with clinical pregnancy rates after controlling for 16 potential confounding factors. According to our results vitamin D deficiency was independently associated with lower clinical pregnancy rates, odds ratios [ORs (95% confidence interval (CI) 0.61 (0.39-0.95)] for vitamin D deficiency (deficient versus non-deficient women), P = 0.030. Finally, even when restricting our analysis to women undergoing elective SET (274 patients), vitamin D deficiency was again independently associated with pregnancy rates [OR (95% CI) 0.56 (0.33-0.93), P = 0.024]. Our results refer only to patients undergoing Day 5 SET. Although vitamin D deficiency appears to compromise pregnancy rates in this population, no guidance can be provided regarding a potential relationship between vitamin D deficiency and ovarian reserve or response to ovarian stimulation. Vitamin D deficiency impairs pregnancy rates in women undergoing single blastocyst transfer. Future prospective confirmatory studies are needed to validate our results and examine the exact underlying mechanism by which vitamin D levels may impair pregnancy rates in infertile women undergoing IVF/ICSI. None declared. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Total renin after gonadotropin stimulation in polycystic ovarian disease.

PubMed

Matinlauri, I; Anttila, L; Jaatinen, T A; Koskinen, P; Aalto, M; Irjala, K; Nikkanen, V

1995-02-01

To examine the influence of polycystic ovarian disease (PCOD) on the levels of total renin in plasma and follicular fluid (FF) after stimulation with hMG. Comparative study of the plasma and FF concentrations of total renin in women with and without PCOD after stimulation with hMG. In vitro fertilization-embryo transfer program at the Department of Obstetrics and Gynecology, the University Central Hospital of Turku, Finland. Thirty-six women undergoing IVF-ET for infertility with (n = 10) or without (n = 26) ultrasonographically diagnosed PCOD. Of the latter group, 15 women had tubal infertility, and the rest suffered from an anovulatory infertility and reacted with PCO-like ovarian response to stimulation. The concentrations of total renin in plasma and FF, serum E2, and protein in FF. The concentrations of plasma total renin after the gonadotropin stimulation were significantly higher in the PCOD and PCO-like groups when compared with the tubal group. The concentration of total renin in FF and the ratio of total renin per protein in FF were higher in the PCOD and PCO-like groups than in the tubal group, but the differences did not reach statistical significance. Positive correlations were found between the plasma total renin and serum E2 concentrations in the PCO-like and in the tubal group and between plasma total renin concentrations and the number of mature follicles in all groups. Follicular fluid total renin did not correlate with FF protein in any group. All findings were independent of the total hMG dosage used and the body mass index of the patients. In the present study the concentrations of total renin in plasma were enhanced markedly after gonadotropin stimulation in women with PCOD compared with women having tubal infertility. The pattern of the hormonal secretions revealed a group of infertile patients reacting biochemically like women with PCOD.

Individualized controlled ovarian stimulation in expected poor-responders: an update.

PubMed

Haahr, Thor; Esteves, Sandro C; Humaidan, Peter

2018-03-09

Controlled ovarian stimulation with subsequent multi-follicular development continues to be a keystone in ART. Evidence supports an individualized approach to ovarian stimulation, usually involving combinations of ovarian reserve tests, body mass index and age to tailor the exogenous gonadotropin dose, and potentially adjuvant treatment aiming for high safety and a shortening of time to live birth. While stimulation and trigger concepts have been developed successfully in normo- and hyperresponder patients, the poor responder patient remains difficult to manage. However, recent advances in definition and classification of the expected poor ovarian responder patient might enable a more accurate and clinically useful interpretation of new treatment concepts in a more homogenous study population. In the present review, we discuss the classification of the expected poor ovarian responder patient as well as clinically useful measurements of efficacy for controlled ovarian stimulation, and finally, we discuss the evidence for clinical management of patients with expected poor ovarian response, including adjuvant treatments such as growth hormone, androgens, and LH activity.In conclusion, the best available evidence supports that the treatment of the expected poor ovarian response patient should be individualized in all steps of ART, including the choice of GnRH analogue, the gonadotropin type and dose, ovulation trigger, and the possible use of adjuvant therapies.

Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy

ClinicalTrials.gov

2014-12-29

Fatigue; Malignant Ovarian Mixed Epithelial Tumor; Neuropathy; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Pain; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

"Anti-Mullerian Hormone: Marker for Ovarian Response in Controlled Ovarian Stimulation for IVF Patients": A First Pilot Study in the Indian Population.

PubMed

Singh, Neeta; Malik, Ekta; Banerjee, Ayan; Chosdol, Kunzang; Sreenivas, V; Mittal, Suneeta

2013-08-01

To measure the levels of early follicular phase Anti-Mullerian hormone (AMH) in Indian patients of IVF and to evaluate the AMH as a predictive marker of ovarian response in assisted reproductive technology outcome. Sixty women (age 25-40 years) selected for in vitro fertilization treatment were included in this study. Analysis of day-2 serum samples was done for the AMH, FSH, Inhibin B, and LH by ELISA kit methods. USG was done for the antral follicle count (AFC) and oocytes' retrieval. Hormone parameters were compared and correlated with the oocytes' retrieval count and the AFC. The discriminant analysis was done to compare relevance of different parameters for predicting ovarian response. The Anti-Mullerian hormone showed a significant correlation with the oocytes' retrieval after ovulation induction for IVF (r = 0.648, p < 0.0001) and no correlation was seen with serum FSH, LH, and Inhibin. Serum AMH levels show 80 % sensitivity and 80 % specificity in predicting poor ovarian response. There is a significant correlation between day-2 serum AMH levels and the oocytes' retrieval count in women undergoing ovulation induction for IVF, and the AMH is a good marker as the negative predictive values for the success of ART. There is no correlation found between other hormonal ovarian reserve markers and the oocytes' retrieval count.

Overt leptin response to controlled ovarian hyperstimulation negatively correlates with pregnancy outcome in in vitro fertilization--embryo transfer cycle.

PubMed

Chakrabarti, Jana; Chatterjee, Ratna; Goswami, Sourendrakanta; Chakravarty, Baidyanath; Kabir, Syed Nazrul

2012-05-01

A critical body mass of adipose tissue is essential for the normal development of female reproductive functions. Leptin, an adipocyte-derived hormone encoded by the 'Ob' gene has been proposed as a peripheral signal indicating the adequacy of nutritional status for reproductive functions. It is reported as a direct regulator of gametogenic and steroidogenic potential of ovary. Though leptin is widely present in reproductive tissues, its relationship to reproductive hormones is still poorly understood. Present investigation attempts to explore ovarian response to secretory profile of leptin and its impact on pregnancy outcome in women undergoing controlled ovarian hyperstimulation for in vitro fertilization and embryo transfer (IVF-ET). Patients enrolled for IVF-ET underwent pituitary-ovarian suppression by 'Long Protocol' GnRH-agonist downregulation followed by ovarian stimulation. Sera were procured at different phases of IVF-ET for the assay of estradiol, progesterone, human chorionic gonadotropin, and for leptin. Ovarian follicular fluids were also assayed for leptin. Luteinized granulosa cells were cultured in vitro to evaluate their steroidogenic potential. Statistical analyses were done by student's t-test, ANOVA, and Chi-square tests as applicable. All results were expressed as Mean ± SE. P values < 0.05 were considered significant. Positive correlation was observed between serum and ovarian follicular fluid leptin. A negative correlation was noted between the serum leptin levels and endometrial thickness. Elevated leptin response may exert adverse impacts on pregnancy success during IVF-ET possibly by modulating uterine receptivity.

Pretreatment with myo-inositol in non polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: a pilot study.

PubMed

Lisi, Franco; Carfagna, Piero; Oliva, Mario Montanino; Rago, Rocco; Lisi, Rosella; Poverini, Roberta; Manna, Claudio; Vaquero, Elena; Caserta, Donatella; Raparelli, Valeria; Marci, Roberto; Moscarini, Massimo

2012-07-23

Aim of this pilot study is to examine the effects of myo-inositol administration on ovarian response and oocytes and embryos quality in non PolyCystic Ovary Syndrome (PCOS) patients undergoing multiple follicular stimulation and in vitro insemination by conventional in vitro fertilization or by intracytoplasmic sperm injection. One hundred non-PCOS women aged <40 years and with basal FSH <10 mUI/ml were down-regulated with triptorelin acetate from the mid-luteal phase for 2 weeks, before starting the stimulation protocol for oocytes recovery. All patients received rFSH, at a starting dose of 150 IU for 6 days. The dose was subsequently adjusted according to individual response. Group B (n=50) received myo-inositol and folic acid for 3 months before the stimulation period and then during the stimulation itself. Group A (n-50) received only folic acid as additional treatment in the 3 months before and through treatment. Total length of the stimulation was similar between the two groups. Nevertheless, total amount of gonadotropins used to reach follicular maturation was found significantly lower in group B. In addition, the number of oocytes retrieved was significantly reduced in the group pretreated with myo-inositol. Clinical pregnancy and implantation rate were not significantly different in the two groups. Our findings suggest that the addition of myo-inositol to folic acid in non PCOS-patients undergoing multiple follicular stimulation for in-vitro fertilization may reduce the numbers of mature oocytes and the dosage of rFSH whilst maintaining clinical pregnancy rate. Further, a trend in favor of increased incidence of implantation in the group pretreated with myo-inositol was apparent in this study. Further investigations are warranted to clarify this pharmacological approach, and the benefit it may hold for patients.

Post-operative ovarian adhesion formation after ovarian drilling: a randomized study comparing conventional laparoscopy and transvaginal hydrolaparoscopy.

PubMed

Giampaolino, Pierluigi; Morra, Ilaria; Tommaselli, Giovanni Antonio; Di Carlo, Costantino; Nappi, Carmine; Bifulco, Giuseppe

2016-10-01

To compare conventional laparoscopic ovarian drilling (LOD) with transvaginal hydrolaparoscopy (THL) ovarian drilling in terms of ovarian adhesion formation, evaluated using office THL during follow-up in CC-resistant anovulatory patients affected by PCOS. Prospective randomized study on 246 CC-resistant women with PCOS. The patients enrolled were divided into two groups, 123 were scheduled to undergo LOD and 123 to undergo THL ovarian drilling. Six months after the procedure all patients were offered office transvaginal hydrolaparoscopy (THL) follow-up, under local anesthesia to evaluate adhesion formation. Duration of the procedure was significantly shorter in the THL group in comparison with LOD group (p < 0.0001). No intra- or post-operative complication was observed in any of the patients in both groups. Post-operative THL follow-up after 6 months showed that 15 (15.5 %) patients in the THL group and 73 (70.2 %) in the LOD group showed the presence of ovarian adhesion. This difference was highly significant with a p value <0.0001 and a relative risk of 0.22 [95 % IC 0.133-0.350]. This study seems to indicate that THL ovarian drilling may reduce the risk of ovarian adhesion formation and could be used as a safe and effective option to reduce ovarian adhesion formation in patients undergoing ovarian drilling.

Gonadotropin-releasing hormone agonist trigger increases the number of oocytes and embryos available for cryopreservation in cancer patients undergoing ovarian stimulation for fertility preservation.

PubMed

Pereira, Nigel; Kelly, Amelia G; Stone, Logan D; Witzke, Justine D; Lekovich, Jovana P; Elias, Rony T; Schattman, Glenn L; Rosenwaks, Zev

2017-09-01

To compare the oocyte and embryo yield associated with GnRH-agonist triggers vs. hCG triggers in cancer patients undergoing controlled ovarian stimulation (COS) for fertilization preservation. Retrospective cohort study. Academic center. Cancer patients undergoing COS with letrozole and gonadotropins or gonadotropin-only protocols for oocyte or embryo cryopreservation. Gonadotropin-releasing hormone agonist or hCG trigger. Number of metaphase II (MII) oocytes or two-pronuclei (2PN) embryos available for cryopreservation were primary outcomes. Separate multivariate linear regression models were used to assess the effect of trigger type on the primary outcomes, after controlling for confounders of interest. A total of 341 patients were included, 99 (29.0%) in the GnRH-agonist group and 242 (71%) in the hCG group. There was no difference in the baseline demographics of patients receiving GnRH-agonist or hCG triggers. Within the letrozole and gonadotropins group (n = 269), the number (mean ± SD, 11.8 ± 5.8 vs. 9.9 ± 6.0) and percentage of MII oocytes (89.6% vs. 73.0%) available for cryopreservation was higher with GnRH-agonist triggers compared with hCG triggers. Similar results were noted with GnRH-agonist triggers in the gonadotropin-only group (n = 72) (i.e., a higher number [13.3 ± 7.9 vs. 9.3 ± 6.0] and percentage of MII oocytes [85.7% vs. 72.8%] available for cryopreservation). Multivariate linear regression demonstrated approximately three more MII oocytes and 2PN embryos available for cryopreservation in the GnRH-agonist trigger group, irrespective of cancer and COS protocol type. Utilization of a GnRH-agonist trigger increases the number of MII oocytes and 2PN embryos available for cryopreservation in cancer patients undergoing COS for fertility preservation. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Best practices for controlled ovarian stimulation in IVF

PubMed Central

Jungheim, Emily S.; Meyer, Melissa; Broughton, Darcy E.

2015-01-01

As applications for IVF have expanded over the years, so too have approaches to controlled ovarian stimulation (COS) for IVF. With this expansion and improved knowledge of basic reproductive biology, there is increasing interest in how COS practice influences IVF outcomes, and whether or not specific treatment scenarios call for personalized approaches to COS. For the majority of women undergoing COS and their treating physicians, the goal is to achieve a healthy live birth through IVF in a fresh cycle. Opinions on how COS strategy best leads to this common goal varies among centers as many clinicians base COS strategy not on evidence obtained through prospective randomized trials, but rather through observational studies and experience. Overall, when it comes to COS most clinicians recognize the approach should not be “one size fits all”, but rather a patient-centered approach that takes the existing evidence into consideration. The pages that follow outline the existing evidence for best practices in COS for IVF highlighting how these practices may be incorporated into a patient-centered approach. PMID:25734345

Gonadotropin-releasing hormone antagonist use in controlled ovarian stimulation and intrauterine insemination cycles in women with polycystic ovary syndrome.

PubMed

Ertunc, Devrim; Tok, Ekrem C; Savas, Aysun; Ozturk, Ilay; Dilek, Saffet

2010-03-01

To observe the effects of ganirelix on controlled ovarian stimulation and intrauterine insemination (COS/IUI) cycles in women with polycystic ovary syndrome (PCOS). Prospective, randomized, controlled clinical study. An academic clinical research center. Women with PCOS and anovulatory infertility undergoing COS/IUI. Recombinant FSH therapy was started on day 3. In women assigned to the control group (n = 47), treatment was continued up to the day of hCG administration. In patients assigned to receive GnRH antagonist (n = 42), ganirelix was added when the leading follicle was > or =14 mm. Pregnancy rates, serum E(2), P, and LH levels, and follicle numbers at hCG day, prevalence of premature luteinization, and cost of stimulation. Serum E(2), P, and LH levels were significantly lower in the ganirelix group. Although premature luteinization and cycle cancellation was encountered less in the ganirelix group, the pregnancy rates per cycle were similar (15.4% vs. 10.7%). Patients would pay 6,153 dollars more for each pregnancy when using ganirelix. Gonadotropin-releasing hormone antagonist resulted in more monofollicular development, less premature luteinization, and less cycle cancellation in IUI cycles of patients with PCOS; however, the cost of stimulation increased without an improvement in pregnancy rates. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Oocyte mitochondrial deletions and heteroplasmy in a bovine model of ageing and ovarian stimulation.

PubMed

Hammond, Elizabeth R; Green, Mark P; Shelling, Andrew N; Berg, Martin C; Peek, John C; Cree, Lynsey M

2016-04-01

Maternal ageing and ovarian stimulation result in the accumulation of mitochondrial DNA (mtDNA) deletions and heteroplasmy in individual oocytes from a novel bovine model for human assisted reproductive technology (ART). The levels of mtDNA deletions detected in oocytes increased with ovarian ageing. Low levels of mtDNA heteroplasmy were apparent across oocytes and no relationship was identified with respect to ovarian ageing or ovarian stimulation. Oocyte quality decreases with ovarian ageing and it is postulated that the mtDNA may have a role in this decline. The impact of ovarian stimulation on oocyte quality is poorly understood. Human studies investigating these effects are often limited by the use of low quality oocytes and embryos, variation in age and ovarian stimulation regimens within the patients studied, as well as genetic and environmental variability. Further, no study has investigated mtDNA heteroplasmy in individual oocytes using next-generation sequencing (NGS), and little is known about whether the oocyte accumulates heteroplasmic mtDNA mutations following ageing or ovarian stimulation. A novel bovine model for the effect of stimulation and age in human ART was undertaken using cows generated by somatic cell nuclear transfer (SCNT) from one founder, to produce a homogeneous population with reduced genetic and environmental variability. Oocytes and somatic tissues were collected from young (3 years of age; n = 4 females) and old (10 years of age; n = 5 females) cow clones following multiple natural ovarian cycles, as well as oocytes following multiple mild (FSH only) and standard (based on human a long GnRH agonist protocol) ovarian stimulation cycles. In addition, oocytes were recovered in a natural cycle from naturally conceived cows aged 4-13.5 years (n = 10) to provide a heterogeneous cohort for mtDNA deletion studies. The presence or absence of mtDNA deletions were investigated using long-range PCR in individual oocytes (n = 62). To determine the detection threshold for mtDNA heteroplasmy levels in individual oocytes, a novel NGS methodology was validated; artificial mixtures of the Bos taurus and Bos indicus mitochondrial genome were generated at 1, 2, 5, 15 and 50% ratios to experimentally mimic different levels of heteroplasmy. This NGS methodology was then employed to determine mtDNA heteroplasmy levels in single oocytes (n = 24). Oocyte mtDNA deletion and heteroplasmy data were analysed by binary logistic regression with respect to the effects of ovarian ageing and ovarian stimulation regimens. Ovarian ageing, but not ovarian stimulation, increased the number of oocytes exhibiting mtDNA deletions (P = 0.04). A minimum mtDNA heteroplasmy level of 2% was validated as a sensitive (97-100%) threshold for variant detection in individual oocytes using NGS. Few mtDNA heteroplasmies were detected across the individual oocytes, with only 15 oocyte-specific variants confined to two of the 24 oocytes studied. There was no relationship (P > 0.05) evident between ovarian ageing or ovarian stimulation and the presence of mtDNA heteroplasmies. The low number of oocytes collected from the natural ovarian cycles limited the analysis. Fertilization and developmental potential of the oocytes was not assessed as the oocytes were destroyed for mtDNA deletion and heteroplasmy analysis. If the findings of this model apply to the human, this study suggests that the incidence of mtDNA deletions increases with age, but not with degree of ovarian stimulation, while the frequency of mtDNA heteroplasmies may be low regardless of ovarian ageing or level of ovarian stimulation. Funding was provided by Fertility Associates, the Nurture Foundation for Reproductive Research, the Fertility Society of Australia, and the Auckland Medical Research Foundation. J.C.P. is a shareholder of Fertility Associates and M.P.G. received a fellowship from Fertility Associates. The other authors of this manuscript declare no conflict of interest that could be perceived as prejudicing the impartiality of the reported research. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The effect of human chorionic gonadotrophin contained in human menopausal gonadotropin on the clinical outcomes during progestin-primed ovarian stimulation

PubMed Central

Fu, Yonglun; Ai, Ai; Cai, Renfei; Wang, Yun; Hong, Qingging; Hui, Tian; Lyu, Qifeng; Chen, Qiuju; Kuang, Yanping

2017-01-01

Progestin-primed ovarian stimulation (PPOS) protocol has recently been demonstrated to be an novel regimen for preventing premature LH surges during controlled ovarian hyperstimulation (COH) in combination with frozen-thawed embryo transfer (FET). Our prospective controlled study was to explore the effect of human chorionic gonadotropin (hCG) contained in human menopausal gonadotropin (hMG) on the clinical outcomes in normalovulatory women undergoing COH with PPOS. A total of 180 patients were allocated into three groups according to the gonadotropin (Gn) used: group A (human menopausal gonadotropin, hMG-A), group B (hMG-B) or group C (follicle stimulating hormone, FSH). The primary outcome measured was the number of oocytes retrieved. The number of oocytes retrieved in group A B C was 10.72±5.78 11.33±5.19and13.38±8.97, respectively, with no statistic significance (p>0.05). Other embryological indicators were also similar (p>0.05). The concentration of serum and urinary β-hCG on the trigger day in group A and B were not associated with embryo results (p>0.05). There was no significant differences in the clinical pregnancy rate (41.67% vs. 51.56% vs. 39.51%, p>0.05) and implantation rate (31.58%vs. 34.75%vs.25.33%) after FET among the three groups. Thus the clinical characteristics were not affected by the hCG contained in hMG in normalovulatory women treated with PPOS. PMID:29152085

The ISMAAR proposal on terminology for ovarian stimulation for IVF.

PubMed

Nargund, G; Fauser, B C J M; Macklon, N S; Ombelet, W; Nygren, K; Frydman, R

2007-11-01

IVF is performed with oocytes collected in natural and stimulated cycles. Different approaches to ovarian stimulation have been employed worldwide. Following the introduction of GnRH antagonists and strategies to reduce multiple births such as single embryo transfer, there is a genuine scientific interest in the revival of natural cycle and mild approaches to ovarian stimulation in IVF. Recent evidence suggests that application of natural and mild IVF is patient-centred, aimed at reducing the cost of treatment, patient discomfort and multiple pregnancies. However, there seems to be no consistency in the terminology used for definitions and protocols for ovarian stimulation in IVF cycles. Following the recent International Society for Mild Approaches in Assisted Reproduction (ISMAAR) meeting and communication with interested international experts, this article has recommended revised definitions and terminology for natural cycle IVF and different protocols used in ovarian stimulation for IVF. It is proposed that these terms are adopted internationally in order to achieve a consistency in clinical practice, research publications and communication with patients.

Suppression of LH during ovarian stimulation: analysing threshold values and effects on ovarian response and the outcome of assisted reproduction in down-regulated women stimulated with recombinant FSH.

PubMed

Balasch, J; Vidal, E; Peñarrubia, J; Casamitjana, R; Carmona, F; Creus, M; Fábregues, F; Vanrell, J A

2001-08-01

It has been recently suggested that gonadotrophin-releasing hormone agonist down-regulation in some normogonadotrophic women may result in profound suppression of LH concentrations, impairing adequate oestradiol synthesis and IVF and pregnancy outcome. The aims of this study, where receiver-operating characteristic (ROC) analysis was used, were: (i) to assess the usefulness of serum LH measurement on stimulation day 7 (S7) as a predictor of ovarian response, IVF outcome, implantation, and the outcome of pregnancy in patients treated with recombinant FSH under pituitary suppression; and (ii) to define the best threshold value, if any, to discriminate between women with 'low' or 'normal' LH concentrations. A total of 144 infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment were included. Seventy-two consecutive patients having a positive pregnancy test (including 58 ongoing pregnancies and 14 early pregnancy losses) were initially selected. As a control non-pregnant group, the next non-conception IVF/ICSI cycle after each conceptual cycle in our assisted reproduction programme was used. The median and range of LH values in non-conception cycles, conception cycles, ongoing pregnancies, and early pregnancy losses, clearly overlapped. ROC analysis showed that serum LH concentration on S7 was unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.52; 95% CI: 0.44 to 0.61) or ongoing pregnancy versus early pregnancy loss groups (AUC(ROC) = 0.59; 95% CI: 0.46 to 0.70). To assess further the potential impact of suppressed concentrations of circulating LH during ovarian stimulation on the outcome of IVF/ICSI treatment, the three threshold values of mid-follicular serum LH proposed in the literature (<1, < or =0.7, <0.5 IU/l) to discriminate between women with 'low' or 'normal' LH were applied to our study population. No significant differences were found with respect to ovarian response, IVF/ICSI outcome, implantation, and the outcome of pregnancy between 'low' and 'normal' S7 LH women as defined by those threshold values. Our results do not support the need for additional exogenous LH supplementation in down-regulated women receiving a recombinant FSH-only preparation.

A retrospective analysis of ovarian stimulation with letrozole in women undergoing artificial insemination by donor.

PubMed

Sun, X J; Jiang, L; Ji, L C; Nie, R; Chen, H; Jin, L; Zhu, G J; Qian, K

2017-04-01

The aim of this retrospective study was to determine the clinical pregnancy rate in women undergoing letrozole ovarian stimulation and artificial insemination by donor (AID). Between 2012 and 2015, 130 natural cycles, 939 letrozole cycles and 130 letrozole plus gonadotrophin cycles were conducted. Letrozole cycles were divided into three groups according to LH concentration on the day of HCG administration (LH <10 mIU/ml and follicle size ≥18 cm; LH ≤10 to <20 mIU/ml; and LH ≥20 mIU/ml). Pregnancy rates were 17.3%, 22.4% and 26.8%, respectively (P = 0.012). In women given 10 mIU/ml LH or more, logistic regression identified oestradiol (OR 1.002, 95% CI, 1.000 to 1.004, P = 0.029) and leading follicle size (OR 0.861, 95% CI, 0.772 to 0.960, P = 0.007) as significant predictive factors of pregnancy rate; the higher the oestradiol and the smaller the follicles, the better the pregnancy rate. The pregnancy rate was significantly higher in the letrozole plus gonadotrophin group than the letrozole group (P = 0.04). Better pregnancy rates can be achieved if LH surge occurs before HCG administration, especially with higher oestradiol and lower follicle size; treatment with letrozole plus gonadotrophin was significantly more effective than letrozole alone in AID. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Does prolonged pituitary down-regulation with gonadotropin-releasing hormone agonist improve the live-birth rate in in vitro fertilization treatment?

PubMed

Ren, Jianzhi; Sha, Aiguo; Han, Dongmei; Li, Ping; Geng, Jie; Ma, Chaihui

2014-07-01

To evaluate the effects of a prolonged duration of gonadotropin-releasing hormone agonist (GnRH-a) in pituitary down-regulation for controlled ovarian hyperstimulation (COH) on the live-birth rate in nonendometriotic women undergoing in vitro fertilization and embryo transfer (IVF-ET). Retrospective cohort study. University-affiliated hospital. Normogonadotropic women undergoing IVF. Three hundred seventy-eight patients receiving a prolonged pituitary down-regulation with GnRH-a before ovarian stimulation and 422 patients receiving a GnRH-a long protocol. Live-birth rate per fresh ET. In comparison with the long protocol, the prolonged down-regulation protocol required a higher total dose of gonadotropins. A lower serum luteinizing hormone (LH) level on the starting day of gonadotropin and the day of human chorionic gonadotropin (hCG) and a fewer number of oocytes and embryos were observed in the prolonged down-regulation protocol. However, the duration of stimulation and number of high-quality embryos were comparable between the two groups. A statistically significantly higher implantation rate (50.27% vs. 39.69%), clinical pregnancy rate (64.02% vs. 56.87%) and live-birth rate per fresh transfer cycle (55.56% vs. 45.73%) were observed in the prolonged protocol. Prolonged down-regulation in a GnRH-a protocol might increase the live-birth rates in normogonadotropic women. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Relationships between ovarian blood flow and ovarian response to eCG-treatment of dairy cows.

PubMed

Honnens, A; Niemann, H; Herzog, K; Paul, V; Meyer, H H D; Bollwein, H

2009-07-01

The goal of the present study was to investigate ovarian blood flow and ovarian response in cows undergoing a gonadotropin treatment to induce a superovulatory response, using transrectal colour Doppler sonography. Forty-two cows including 19 cross-bred, 14 German Holstein and 9 German Black Pied cows were examined sonographically before hormonal stimulation on Day 10 of the oestrous cycle, three days after administration of eCG (Day 13) and seven days after artificial insemination (Day 7(p.i.)). After each Doppler examination, blood was collected for determination of total oestrogens (E) and progesterone (P4) in peripheral plasma. The blood flow volume (BFV) and pulsatility index (PI), which is a measure for blood flow resistance, were determined in the ovarian artery, and B-mode sonography was used to count dominant follicles and corpora lutea. Important criteria to assess the ovarian response following the hormonal treatment were the number of follicles >5mm in diameter on Day 13 and the number of corpora lutea on Day 7(p.i.) per cow. The number of follicles ranged from 2 to 61 (mean+/-S.E.M.: 17.5+/-1.7) and corpora lutea from 0 to 50 (mean+/-S.E.M.: 17.0+/-1.6). The BFV increased from 28.4 to 45.0 ml/min between Days 10 and 13 and reached a maximum of 108.5 ml/min on Day 7(p.i.) The PI decreased from 6.25 on Day 10 to 4.70 on Day 13 and to 2.10 on Day 7(p.i.) The BFV and PI on Day 13 did not correlate with the number of follicles (P>0.05). However, on Day 7(p.i.) the number of corpora lutea correlated positively with the BFV (r=0.64; P<0.0001), and an inverse relationship was found for the PI (r=-0.51; P=0.0005). There were no correlations (P>0.05) between the BFV and PI on Day 10 and the number of follicles on Day 13 or the number of corpora lutea on Day 7(p.i.) Results of the present study show that in cows, a hormonal treatment to induce a superovulatory response yielded a marked increase in BFV and a marked decrease in PI in the ovarian artery. However, there was no correlation between BFV and PI in the ovarian arteries before hormonal stimulation and the number of follicles and corpora lutea that developed after stimulation. Thus BFV and PI measured in the ovarian arteries have limited diagnostic value to predict the outcome of a gonadotropin treatment.

Fertility after breast cancer treatment.

PubMed

Kasum, Miro; Beketić-Orešković, Lidija; Peddi, Parvin F; Orešković, Slavko; Johnson, Rebecca H

2014-02-01

In many countries of the developed world, there is an increasing trend toward delay in childbearing from 30 to 40 years of age for various reasons. This is unfortunately concordant with an increasing incidence of breast cancer in women who have not yet completed their family. The current choice for premenopausal women with breast cancer is adjuvant therapy which includes cytotoxic chemotherapy, ovarian ablation (by surgery, irradiation, or chemical ovarian suppression), anti-estrogen therapy, or any combination of these. Although the use of adjuvant therapies with cytotoxic drugs can significantly reduce mortality, it raises issues of the long-term toxicity, such as induction of an early menopause and fertility impairment. The risk of infertility is a potential hardship to be faced by the patients following treatment of breast cancer. The offspring of patients who became pregnant after completion of chemotherapy have shown no adverse effects and congenital anomalies from the treatment, but sometimes high rates of abortion (29%) and premature deliveries with low birth weight (40%) have been demonstrated. Therefore, the issue of recent cytotoxic treatment remains controversial and further research is required to define a "safety period" between cessation of treatment and pregnancy. Preservation of fertility in breast cancer survivors of reproductive age has become an important issue regarding the quality of life. Currently, there are several potential options, including all available assisted technologies, such as in vitro fertilization and embryo transfer, in vitro maturation, oocyte and embryo cryopreservation, and cryopreservation of ovarian tissue. Because increased estrogen levels are thought to be potentially risky in breast cancer patients, recently developed ovarian stimulation protocols with the aromatase inhibitor letrozole and tamoxifen appear to provide safe stimulation with endogenous estrogen. Embryo cryopreservation seems to be the most established fertility preservation strategy, providing a 25-35% chance of pregnancy. In addition, oocyte freezing can be considered as an alternative in patients who are single and in those who do not wish a sperm donor. Although ovarian tissue harvesting appears to be safe, experience regarding ovarian transplantation is still limited due to low utilization, so the true value of this procedure remains to be determined. Nevertheless, in clinical situations in which chemotherapy needs to be started in young patients facing premature ovarian failure, ovarian tissue preservation seems to be a promising option for restoring fertility, especially in conjunction with other options like immature oocyte retrieval, in vitro maturation of oocytes, oocyte vitrification, or embryo cryopreservation. It seems that in vitro maturation is a useful strategy because it improves oocyte or cryopreservation outcome in breast cancer patients undergoing ovarian stimulation for fertility preservation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Anti-Müllerian hormone concentrations and antral follicle counts for the prediction of pregnancy outcomes after intrauterine insemination.

PubMed

Moro, Francesca; Tropea, Anna; Scarinci, Elisa; Leoncini, Emanuele; Boccia, Stefania; Federico, Alex; Alesiani, Ornella; Lanzone, Antonio; Apa, Rosanna

2016-04-01

To evaluate anti-Müllerian hormone (AMH) concentrations and antral follicle counts (AFCs) in the prediction of pregnancy outcomes after controlled ovarian stimulation among women undergoing intrauterine insemination. A retrospective study included women with unexplained infertility aged 41years or younger who attended a fertility clinic in Italy between December 2009 and May 2014. Ovarian stimulation was achieved with recombinant follicle-stimulating hormone or highly purified human menopausal gonadotropin. Receiver operating characteristic curves were generated to predict ongoing pregnancy. The primary outcome was the association between AMH/AFC and ongoing pregnancy, and was assessed by logistic regression. Overall, 276 women were included, of whom 43 (15.6%) achieved ongoing pregnancy. Multivariate analysis showed that women with a serum day-3 concentration of AMH higher than 2.3ng/mL were more likely to have ongoing pregnancy than were those with a concentration lower than 2.3ng/mL (odds ratio 5.84, 95% confidence interval 2.38-14.31; P<0.001). No associations were recorded for AFCs. AMH should be used to predict the pregnancy outcome of intrauterine insemination. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Does the Ovarian Stimulation Phase Length Predict In vitro Fertilization Outcomes?

PubMed Central

Alport, Brie; Case, Allison; Lim, Hyun; Baerwald, Angela

2011-01-01

Background Bi-directional communication between the follicle and oocyte is necessary to regulate follicle and oocyte development. Currently, it is not practical to monitor the serial growth of individual follicles during assisted reproduction. The ovarian stimulation phase length (SPL) is an indirect measure of mean follicular growth rate. The objective of this study was to test the hypothesis that a short or long SPL would be associated with suboptimal outcomes in women undergoing in vitro fertilization (IVF). Materials and Methods A retrospective cohort study was conducted in 140 women who underwent IVF. Follicle development was monitored every 2-3 days during ovarian stimulation using transvaginal ultrasonography. Once > 3 follicles reached ≥ 17 mm, human chorionic gonadotropin (hCG) was administered. Oocyte retrieval was performed approximately 35 hours after hCG. Oocytes underwent IVF on the day of collection and were evaluated daily thereafter. Embryos were transferred on days 3 or 5, depending on the number and quality of embryos available. Associations between SPL, age, follicle, oocyte, embryo and pregnancy outcomes were evaluated (SPSS version 17.0; SPSS Inc., Chicago, IL, USA). Results A SPL of 11 days was associated with an optimal number of follicles that developed to ≥ 6 mm, ≥ 10 mm and ≥ 15 mm; serum estradiol concentrations; and number of oocytes collected (p<0.05). Gradual reductions in the number of developing follicles, serum estradiol concentrations and number of oocytes collected occurred with SPL less than or greater than 11 days (p<0.05). The SPL did not influence endometrial, embryo or pregnancy outcomes (p>0.05). Associations between SPL and outcomes were not influenced by age (p>0.05). Conclusion The ovarian SPL can be used to predict the number of follicles that develop, oocytes collected and serum estradiol concentrations, but not embryo or pregnancy outcomes. PMID:25101156

[First line management without IVF of infertility related to endometriosis: Result of medical therapy? Results of ovarian superovulation? Results of intrauterine insemination? CNGOF-HAS Endometriosis Guidelines].

PubMed

Boujenah, J; Santulli, P; Mathieu-d'Argent, E; Decanter, C; Chauffour, C; Poncelet, P

2018-03-01

Using the structured methodology of French guidelines (HAS-CNGOF), the aim of this chapter was to formulate good practice points (GPP), in relation to optimal non-ART management of endometriosis related to infertility, based on the best available evidence in the literature. This guideline was produced by a group of experts in the field including a thorough systematic search of the literature (from January 1980 to March 2017). Were included only women with endometriosis related to infertility. For each recommendation, a grade (A-D, where A is the highest quality) was assigned based on the strength of the supporting evidence. Management of endometriosis related to infertility should be multidisciplinary and take account into the pain, the global evaluation of infertile couple and the different phenotypes of endometriotic lesions (good practice point). Hormonal treatment for suppression of ovarian function should not prescribe to improve fertility (grade A). After laproscopy for endometriosis related to infertility, the Endometriosis Fertility Index should be used to counsel patients regarding duration of conventional treatments before undergoing ART (grade C). After laparoscopy surgery for infertile women with AFS/ASRM stage I/II endometriosis or superficial peritoneal endometriosis, controlled ovarian stimulation with or without intrauterine insemination could be used to enhance non-ART pregnancy rate (grade C). Gonadotrophins should be the first line therapy for the stimulation (grade B). The number of cycles before referring ART should not exceed up to 6 cycles (good practice point). No recommendation can be performed for non-ART management of deep infiltrating endometriosis or endometrioma, as suitable evidence is lacking. Non-ART management is a possible option for the management of endometriosis related to infertility. Endometriosis Fertilty Index could be a useful tool for subsequent postoperative fertility management. Controlled ovarian stimulation can be proposed. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Live birth and perinatal outcomes following stimulated and unstimulated IVF: analysis of over two decades of a nationwide data.

PubMed

Sunkara, Sesh Kamal; LaMarca, Antonio; Polyzos, Nikolaos P; Seed, Paul T; Khalaf, Yakoub

2016-10-01

Does ovarian stimulation affect perinatal outcomes of preterm birth (PTB) and low birth weight (LBW) following IVF treatment. Despite no significant differences in the risks of PTB and LBW between stimulated and unstimulated IVF in the present study, the study cannot exclude the effect of ovarian stimulation on the perinatal outcomes following IVF. Pregnancies resulting from assisted reproductive treatments (ART) are associated with a higher risk of pregnancy complications compared to spontaneously conceived pregnancies attributed to the underlying infertility and the in vitro fertilization techniques. It is of interest to determine the effect size of ovarian stimulation use in achieving a live birth and whether ovarian stimulation that is routinely used in IVF, affects perinatal outcomes of birth weight and gestational age at delivery compared to unstimulated IVF. Anonymous data were obtained from the Human Fertilisation and Embryology Authority (HFEA), the statutory regulator of ART in the UK. The HFEA has collected data prospectively on all ART performed in the UK since 1991. Data from 1991 to 2011 comprising a total of 591 003 fresh IVF ± ICSI cycles involving 584 835 stimulated IVF cycles and 6168 unstimulated IVF cycles were analyzed. Data on all women undergoing either stimulated or unstimulated fresh IVF ± ICSI cycles during the period from 1991 to 2011 were analyzed to compare live birth rates, singleton live birth rates, perinatal outcomes of PTB, early PTB (<32 weeks), LBW and very LBW (<1500 grams) among singleton live births. Adjusted logistic regression was performed for each perinatal outcome for confounding factors: female age, period of treatment, cause of infertility, number of previous IVF cycles and previous live birth. Analysis of the large nationwide data demonstrated 3.5 times (95% confidence interval (CI): 3.1-3.9) as many unstimulated IVF cycles being required to achieve one live birth compared to stimulated IVF and 2.9 times (95% CI: 2.6-3.2) as many unstimulated IVF cycles being required to achieve one singleton live birth compared to stimulated IVF. There was no significant difference in the unadjusted odds for PTB (odds ratio (OR) 1.27, 95% CI: 0.80-2.00) and LBW (OR 1.48, 95% CI: 0.90-2.42) between stimulated and unstimulated IVF cycles. There was no significant difference in the risk of the adverse perinatal outcomes after adjusting for potential confounders; PTB (adjusted odds ratio (aOR) 1.43, 95% CI: 0.91-2.26) and LBW (aOR 1.58, 95% CI: 0.96-2.58). Although the analysis was adjusted for a number of important confounders, the dataset had no information on smoking, body mass index (BMI) and the medical history of women during pregnancy to allow adjustment. Anonymized nature of the dataset did not make it permissible to analyse one cycle per woman. Given the smaller number of perinatal events with unstimulated IVF, a larger study is needed to investigate further. Analysis of this large dataset demonstrates that ovarian stimulation has a vital role in maximizing efficacy of IVF. Although there were no significant differences for PTB and LBW following stimulated compared to unstimulated IVF, the CIs were wide enough to include possible clinically important effects. No funding was obtained. There are no competing interests to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

New advances in ovarian autotransplantation to restore fertility in cancer patients

PubMed Central

2016-01-01

Human ovary autotransplantation is a promising option for fertility preservation of young women and girls undergoing gonadotoxic treatments for cancer or some autoimmune diseases. Although experimental, it resulted in at least 42 healthy babies worldwide. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review was performed for all relevant full-text articles published in English from 1 January 2000 to 01 October 2015 in PubMed to explore the latest clinical and research advances of human ovary autotransplantation. Human ovary autotransplantation involves ovarian tissue extraction, freezing/thawing, and transplantation back into the same patient. Three major forms of human ovary autotransplantation exist including (a) transplantation of cortical ovarian tissue, (b) transplantation of whole ovary, and (c) transplantation of ovarian follicles (artificial ovary). According to the recent guidelines, human ovary autotransplantation is still considered experimental; however, it has unique advantages in comparison to other options of female fertility preservation. Human ovary autotransplantation (i) does not need prior ovarian stimulation, (ii) allows immediate initiation of cancer therapy, (iii) can restore both endocrine and reproductive ovarian functions, and (iv) may be the only fertility preservation option suitable for prepubertal girls or for young women with estrogen-sensitive malignancies. As any other fertility preservation option, human ovary autotransplantation has both advantages and disadvantages and may not be feasible for all cases. The major challenges facing this option are how to avoid the risk of reintroducing malignant cells and how to prolong the lifespan of ovarian transplant as well as how to improve artificial ovary results. PMID:26589603

New advances in ovarian autotransplantation to restore fertility in cancer patients.

PubMed

Salama, Mahmoud; Woodruff, Teresa K

2015-12-01

Human ovary autotransplantation is a promising option for fertility preservation of young women and girls undergoing gonadotoxic treatments for cancer or some autoimmune diseases. Although experimental, it resulted in at least 42 healthy babies worldwide. According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature review was performed for all relevant full-text articles published in English from 1 January 2000 to 01 October 2015 in PubMed to explore the latest clinical and research advances of human ovary autotransplantation. Human ovary autotransplantation involves ovarian tissue extraction, freezing/thawing, and transplantation back into the same patient. Three major forms of human ovary autotransplantation exist including (a) transplantation of cortical ovarian tissue, (b) transplantation of whole ovary, and (c) transplantation of ovarian follicles (artificial ovary). According to the recent guidelines, human ovary autotransplantation is still considered experimental; however, it has unique advantages in comparison to other options of female fertility preservation. Human ovary autotransplantation (i) does not need prior ovarian stimulation, (ii) allows immediate initiation of cancer therapy, (iii) can restore both endocrine and reproductive ovarian functions, and (iv) may be the only fertility preservation option suitable for prepubertal girls or for young women with estrogen-sensitive malignancies. As any other fertility preservation option, human ovary autotransplantation has both advantages and disadvantages and may not be feasible for all cases. The major challenges facing this option are how to avoid the risk of reintroducing malignant cells and how to prolong the lifespan of ovarian transplant as well as how to improve artificial ovary results.

Genetic and clinical predictors of ovarian response in assisted reproductive technology

NASA Astrophysics Data System (ADS)

Wiweko, B.; Damayanti, I.; Suryandari, D.; Natadisastra, M.; Pratama, G.; Sumapraja, K.; Meutia, K.; Iffanolia, P.; Harzief, A. K.; Hestiantoro, A.

2017-08-01

Several factors are known to influence ovarian response to rFSH stimulation such as age, antral follicle count (AFC), and basal FSH level, Mutation of allele Ser680Asn in FSHR gene was responsible to ovarian resistance toward exogenous FSH. The aim of this study is to develop a prediction model of ovarian response to COS in IVF. This study was a prospective cohort study. One hundred and thirteen women undergoing their first cycle of IVF in Yasmin IVF Clinic Jakarta were recruited to this study. Clinical datas included were age, BMI, and AFC. Basal FSH and E2 as well as serum AMH was measured from peripheral blood taken at second day of cycle. Bsr-1 enzyme is used to identify the polymorphism in exon 10 position 680 with RFLP technique. Three genotype polymorphism, Asn/Asn (255 bp ribbon), Asn/Ser (97 bp and 158 bp), and Ser/Ser (97 bp, 158 bp, and 255 bp). AFC has the highest predictor for ovarian response with AUC 0.922 (CI 95% 0.833-1.000). AMH also showed high predicting value (AUC 0.843 CI 95% 0.663-1.000). The multivariate analysis revealed combination of AFC, AMH, age, and basal FSH is a good model for ovarian response prediction (AUC=0.97). No significant relation between Asn/Asn, Asn/Ser, or Ser/Ser genotype FSHR polymorphism with ovarian response (p = 0.866) and total dose of rRSH (p = 0.08). This study showed that model combination of AFC, AMH, patient’s age and basal FSH are very good to predict number of mature oocytes.

Milder is better? advantages and disadvantages of "mild" ovarian stimulation for human in vitro fertilization

PubMed Central

2011-01-01

In the last decades, several steps have been made aiming at rendering human IVF more successful on one side, more tolerable on the other side. The "mild" ovarian stimulation approach, in which a lower-than-average dose of exogenous gonadotropins is given and gonadotropin treatment is started from day 2 to 7 of the cycle, represents a significant step toward a more patient's friendly IVF. However, a clear view of its virtues and defects is still lacking, because only a few prospective randomized trials comparing "mild" vs. conventional stimulation exist, and they do not consider some important aspects, such as, e.g., thawing cycles. This review gives a complete panorama of the "mild" stimulation philosophy, showing its advantages vs. conventional ovarian stimulation, but also discussing its disadvantages. Both patients with a normal ovarian responsiveness to exogenous gonadotropins and women with a poor ovarian reserve are considered. Overall, we conclude that the level of evidence supporting the use of "mild" stimulation protocols is still rather poor, and further, properly powered prospective studies about "mild" treatment regimens are required. PMID:21324155

Quality of Life and Survivorship Care in Patients Undergoing Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

ClinicalTrials.gov

2017-05-25

Advanced Malignant Mesothelioma; Carcinoma of the Appendix; Ovarian Sarcoma; Ovarian Stromal Cancer; Pseudomyxoma Peritonei; Recurrent Colon Cancer; Recurrent Malignant Mesothelioma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Stage III Colon Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage IV Colon Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Unspecified Childhood Solid Tumor, Protocol Specific

Does obesity compromise ovarian reserve markers? A clinician's perspective.

PubMed

Malhotra, Neena; Bahadur, Anupama; Singh, Neeta; Kalaivani, Mani; Mittal, Suneeta

2013-01-01

The aim of the study was to ascertain if increasing body mass index (BMI) adversely affects ovarian reserve among infertile women of Asian origin undergoing in vitro fertilization (IVF). This prospective study on 183 women was carried out in the infertility clinic of All India Institute of Medical Sciences, New Delhi, India. Blood hormonal assay in all patients including follicle-stimulating hormone (FSH), luteinizing hormone (LH) and inhibin B was performed on day 2/3 of a spontaneous cycle. A transvaginal ultrasonographic examination on day 2-5 of the menstrual cycle was done for antral follicle count (AFC) and ovarian volume. A correlation between BMI and ovarian reserve parameters like FSH, LH, inhibin B, antral follicle count and ovarian volume was noted. Age was comparable in the three BMI groups. The mean duration of infertility was 8.38 years. Compared to the normal weight, the overweight and obese women had a statistically significantly low inhibin B (p < 0.0259). The AFC when taken together on both sides was not statistically significant between the groups; however, the overweight and obese women had a significantly low AFC (p < 0.0129) on the right side. Incorporating anti-mullerian hormone, a newer marker for ovarian reserve, may benefit these obese infertile women. Further work is required to elucidate the mechanisms underlying the effect of obesity on inhibin B as a marker of ovarian reserve in infertile women. The best marker to check the ovarian reserve is perhaps the woman's performance during an IVF cycle. However, considering the psychological and financial stress of the procedure, it may seem wise to consider counseling of obese women on their expected performance in the first cycle of IVF through such studies.

Comparison of estradiol and progesterone priming/antagonist/letrozole and microdose flare-up protocols for poor responders undergoing intracytoplasmic sperm injection.

PubMed

Yucel, Oguz; Ekin, Murat; Cengiz, Hüseyin; Zebitay, Ali Galip; Yalcinkaya, Sener; Karahuseyinoglu, Sercin

2014-09-01

To compare the effect of the GnRH antagonist/letrozole/gonadotropin protocol with the microdose GnRH agonist flare-up protocol in poor ovarian responders for intracytoplasmic sperm injection. One hundred twenty-one consecutive patients suspected of having or with a history of poor ovarian response between January 2009 and June 2010, who were undergoing ICSI were enrolled. The microdose flareup (MF) protocol was used in 79 patients and the estradiol + progesterone/letrozole + gonadotropin and GnRH antagonist (EP/ALG) protocol was used in 42 patients. Age of the patients, duration of infertility, basal FSH, the total gonadotropin consumption, duration of stimulation, E2 level on the day of hCG administration, the number of embryo transferred, the fertilization rate, implantation rate, clinical pregnancy rate and the live birth rate were not statistically different (p > 0.05). Only the number of oocytes retrieved was significantly higher in the EP/LGA group (1.7 ± 0.7 versus 2.6 ± 0.6). The EP/LGA protocol has no significant improvement against the microdose flare-up protocol in poor responder patients.

Dual ovarian stimulation and random start in assisted reproductive technologies: from ovarian biology to clinical application.

PubMed

Vaiarelli, Alberto; Venturella, Roberta; Vizziello, Damiano; Bulletti, Francesco; Ubaldi, Filippo M

2017-06-01

The opportunity to use gonadotropins to stimulate the growth of antral follicles coming from different follicular waves available in different moment of the menstrual cycle allowed the implementation of innovative protocols in assisted reproductive technologies. The purpose of this review is to explore the possible advantages related to these new controlled ovarian stimulation (COS) strategies. Women exhibit major and minor wave patterns of ovarian follicular development during the menstrual cycle, as it is in animal species. These observations led to the introduction of two new strategies for COS: the random start and the double ovarian stimulation within a single menstrual cycle. The use of gonadotropin-releasing hormone antagonist COS protocols, started randomly at any day of the menstrual cycle, is today a standard procedure in those cases where obtaining oocytes is an urgent task, such as in case of fertility preservation for malignant diseases or other medical indications.On the other hand, in poor prognosis patients, double ovarian stimulation has been suggested with the aim of maximizing the number of oocytes retrieved within a single menstrual cycle and, in turn increasing the chance to obtain a reproductively competent embryo. Randomized control trials are necessary to confirm these preliminary findings.

Association of uterine fibroids and pregnancy outcomes after ovarian stimulation-intrauterine insemination for unexplained infertility.

PubMed

Styer, Aaron K; Jin, Susan; Liu, Dan; Wang, Baisong; Polotsky, Alex J; Christianson, Mindy S; Vitek, Wendy; Engmann, Lawrence; Hansen, Karl; Wild, Robert; Legro, Richard S; Coutifaris, Christos; Alvero, Ruben; Robinson, Randal D; Casson, Peter; Christman, Gregory M; Christy, Alicia; Diamond, Michael P; Eisenberg, Esther; Zhang, Heping; Santoro, Nanette

2017-03-01

To investigate the association of non-cavity-distorting uterine fibroids and pregnancy outcomes after ovarian stimulation-intrauterine insemination (OS-IUI) in couples with unexplained infertility. Secondary analysis from a prospective, randomized, multicenter clinical trial investigating fertility outcomes after OS-IUI. Reproductive Medicine Network clinical sites. Nine hundred couples with unexplained infertility who participated in the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial. Participants were randomized to one of three arms (clomiphene citrate, letrozole, or gonadotropins), and treatment was continued for up to four cycles or until pregnancy was achieved. Conception (serum hCG increase), clinical pregnancy (fetal cardiac activity), and live birth rates. A total of 102/900 participants (11.3%) had at least one documented fibroid and a normal uterine cavity. Women with fibroids were older, more likely to be African American, had a greater uterine volume, lower serum antimüllerian hormone levels, and fewer antral follicles than women without fibroids. In conception cycles, clinical pregnancy rates were significantly lower in participants with fibroids than in those without uterine fibroids. Pregnancy loss before 12 weeks was more likely in African American women with fibroids compared with non-African American women with fibroids. There was no difference in conception and live birth rates in subjects with and without fibroids. No differences were observed in conception and live birth rates in women with non-cavity-distorting fibroids and those without fibroids. These findings provide reassurance that pregnancy success is not impacted in couples with non-cavity-distorting fibroids undergoing OS-IUI for unexplained infertility. NCT01044862. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Feasibility of corifollitropin alfa/GnRH antagonist protocol combined with GnRH agonist triggering and freeze-all strategy in polycystic ovary syndrome patients.

PubMed

Hwang, Jiann-Loung; Chen, Shee-Uan; Chen, Hen-Ju; Chen, Hsin-Fu; Yang, Yu-Shih; Chang, Chin-Hao; Seow, Kok-Min; Tzeng, Chii-Ruey; Lin, Yu-Hung

2018-06-01

The long-acting corifollitropin alfa is comparable to FSH in terms of pregnancy outcomes in normal responders and poor responders. Corifollitropin alfa has never been studied in polycystic ovary syndrome (PCOS) patients because of concerns of excessive ovarian stimulation and ovarian hyperstimulation syndrome (OHSS). The purpose of the study was to evaluate if corifollitropin alfa can be used in PCOS patients. Forty PCOS patients who were going to undergo in vitro fertilization were enrolled in this study. A single injection of corifollitropin alfa was administered on cycle day 2 or day 3. From stimulation day 8 onwards, daily FSH was administered until the day of final oocyte maturation. Cetrorelix was administered from stimulation day 5 to prevent premature LH surge. Final oocyte maturation was triggered by: acetate. All embryos were cryopreserved and replaced in subsequent cycles. All 40 patients were subjected to oocyte retrieval, and none developed moderate or severe ovarian hyperstimulation syndrome (0%, 95% CI 0-0.088). For each patient, an average of 23.4 (±7.4; 95% CI 21.0-25.7) oocytes were retrieved and a mean of 11.7 (±6.4; 95% CI 9.6-13.8) embryos were frozen. Mean serum estradiol level on the day of GnRHa triggering was 7829.9 pg/ml (±3297; 95% CI 6775-8885). The cumulated ongoing pregnancy rate after 3 frozen-thawed embryo transfers was 75.0% (95% CI 61.6%-88.4%). The results suggest that corifollitropin alfa/GnRH antagonist protocol can be used in PCOS patients, in combination with GnRHa triggering and embryo cryopreservation. Copyright © 2017. Published by Elsevier B.V.

Transforming growth factor-β1 and its receptor soluble endoglin are altered in polycystic ovary syndrome during controlled ovarian stimulation.

PubMed

Tal, Reshef; Seifer, David B; Shohat-Tal, Aya; Grazi, Richard V; Malter, Henry E

2013-08-01

To evaluate the relationship between transforming growth factor (TGF)-β1 and its receptor, soluble endoglin (sENG), in the serum and follicular fluid of women with polycystic ovarian syndrome (PCOS) compared with that of non-PCOS normal ovulating women during controlled ovarian stimulation (COS). Prospective case-control study. Academic-affiliated assisted reproductive technology unit. Fourteen PCOS and 14 matched non-PCOS control women undergoing COS. Serum was collected on day 3 (baseline), day of hCG, and day of retrieval. Follicular fluid (FF) was collected on day of oocyte retrieval. ELISA was performed to determine TGF-β1 and sENG protein levels. Serum and FF levels of TGF-β1 and sENG. Serum TGF-β1 did not change significantly during COS but was increased in PCOS compared with non-PCOS women on day 3 and days of hCG administration and oocyte retrieval. Serum sENG increased after hCG administration only in the non-PCOS control group. In addition, serum sENG was decreased in PCOS compared with non-PCOS control women on the days of hCG and retrieval. Accordingly, the bioavailability of TGF-β1 (TGF-β1/sENG ratio) was increased in women with PCOS compared with non-PCOS controls at all three time points. No differences in either factor were noted in FF between groups. The increased TGF-β1 bioavailability in PCOS is not only due to increased TGF-β1 levels but also to decreased levels of its receptor, sENG. These data suggest that increased TGF-β1 bioavailability may contribute to the pathogenesis of PCOS and its increased risk for ovarian hyperstimulation. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Highly purified hMG versus recombinant FSH plus recombinant LH in intrauterine insemination cycles in women ≥35 years: a RCT.

PubMed

Moro, Francesca; Scarinci, Elisa; Palla, Carola; Romani, Federica; Familiari, Alessandra; Tropea, Anna; Leoncini, Emanuele; Lanzone, Antonio; Apa, Rosanna

2015-01-01

Is the treatment with recombinant FSH (rFSH) plus recombinant LH (rLH) more effective than highly purified (HP)-hMG in terms of ongoing pregnancy rate (PR) in women ≥35 years of age undergoing intrauterine insemination (IUI) cycles? The ongoing PR was not significantly different in women treated with rFSH plus rLH or with HP-hMG. Although previous studies have shown beneficial effects of the addition of LH activity to FSH, in terms of PR in patients aged over 34 years having ovulation induction, no studies have compared two different gonadotrophin preparations containing LH activity in women ≥35 years of age in IUI cycles. A single-centre RCT was performed between May 2012 and September 2013 with 579 women ≥35 years of age undergoing IUI cycles. The patients were randomly assigned to one of the two groups, rFSH in combination with rLH group or HP-hMG (Meropur) group, by giving them a code number from a computer generated randomization list, in order of enrolment. The randomization visit took place on the first day of ovarian stimulation. Five hundred and seventy-nine patients with unexplained infertility or mild male factor undergoing IUI cycles were recruited in a university hospital setting. All women were enrolled in this study only for one cycle of treatment. Five hundred and seventy-nine cycles were included in the final analysis. Two hundred and ninety patients were treated with rFSH in combination with rLH and 289 patients were treated with HP-hMG. The ovarian stimulation cycle started on the third day of the menstrual cycle and the starting gonadotrophin doses used were 150 IU/day of rFSH plus 150 IU/day of rLH or 150 IU/day of HP-hMG. The drug dose was adjusted according to the individual follicular response. A single IUI per cycle was performed 34-36 h after hCG injection. The main outcome measures were ongoing PR and number of interrupted cycles for high risk of ovarian hyperstimulation syndrome (OHSS). Ongoing pregnancy rates were 48/290 (17.3%) in the recombinant group versus 35/289 (12.2%) in the HP-hMG group [(odds ratio (OR) 1.50, 95% CI 0.94-2.41, P = 0.09]. The number of interrupted cycles for high risk of OHSS was 13/290 (4.5%) in the rFSH plus rLH group and 2/289 (0.7%) in the HP-hMG group (OR 6.73, 95% CI 1.51-30.12, P = 0.013). One of the limitations of this study was the early closure and the ongoing PR could be overestimated. Both patient and gynaecologist were informed of the assigned treatment. Our results demonstrated the lack of differences in terms of ongoing PR between recombinant product and HP-hMG, in women ≥35 years undergoing controlled ovarian stimulation for IUI cycles. HP-hMG was safer than recombinant gonadotrophin concerning the risk of OHSS. None. NCT01604044. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of high ovarian response on the expression of endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in peri-implantation endometrium in IVF women

PubMed Central

Xu, Li-Zhen; Gao, Min-Zhi; Yao, Li-Hua; Liang, A-Juan; Zhao, Xiao-Ming; Sun, Zhao-Gui

2015-01-01

Objective: To investigate the effect of ovarian stimulation on the expression of EG-VEGF mRNA and protein in peri-implantation endometrium in women undergoing IVF and its relation with endometrial receptivity (ER). Design: Prospective laboratory study. Setting: University hospital. Patients: Eighteen women in stimulated cycles (SC) as study subjects and 18 women in natural cycles (NC) as controls. Women in SC group were classified with two subgroups, high ovarian response (SC1, n=9) with peak serum E2>5,000 pg/mL and moderate ovarian response (SC2, n=9) with peak serum E2 1,000-5,000 pg/mL. Intervention(s): Endometrial biopsies were collected 6 days after ovulation in NC or after oocyte retrieval in SC. Main outcome measure(s): Endometrium histological dating was observed with HE staining. EG-VEGF mRNA expression levels determined by real-time polymerase chain reaction analysis, and protein levels by immunohistochemistry. Results: All endometrial samples were in the secretory phase. The endometrial development in SC1 was 1 to 2 days advanced to NC, and with dyssynchrony between glandular and stromal tissue. Immunohistochemistry analysis showed that EG-VEGF protein was predominantly expressed in the glandular epithelial cells and endothelial cells of vessels, and also presented in the stroma. The image analysis confirmed that both the gland and stroma of endometrium in SC1 had a significantly lower EG-VEGF protein expression than that in SC2 and NC endometrium. Moreover, EG-VEGF mRNA levels were significantly lower in SC1 than in NC. Both EG-VEGF protein and mRNA levels had no significant difference between SC2 and NC. Conclusion: Decreased expression of EG-VEGF in the peri-implantation is associated with high ovarian response, which may account for the impaired ER and lower implantation rate in IVF cycles. PMID:26464631

Effect of high ovarian response on the expression of endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in peri-implantation endometrium in IVF women.

PubMed

Xu, Li-Zhen; Gao, Min-Zhi; Yao, Li-Hua; Liang, A-Juan; Zhao, Xiao-Ming; Sun, Zhao-Gui

2015-01-01

To investigate the effect of ovarian stimulation on the expression of EG-VEGF mRNA and protein in peri-implantation endometrium in women undergoing IVF and its relation with endometrial receptivity (ER). Prospective laboratory study. University hospital. Eighteen women in stimulated cycles (SC) as study subjects and 18 women in natural cycles (NC) as controls. Women in SC group were classified with two subgroups, high ovarian response (SC1, n=9) with peak serum E2>5,000 pg/mL and moderate ovarian response (SC2, n=9) with peak serum E2 1,000-5,000 pg/mL. Endometrial biopsies were collected 6 days after ovulation in NC or after oocyte retrieval in SC. Endometrium histological dating was observed with HE staining. EG-VEGF mRNA expression levels determined by real-time polymerase chain reaction analysis, and protein levels by immunohistochemistry. All endometrial samples were in the secretory phase. The endometrial development in SC1 was 1 to 2 days advanced to NC, and with dyssynchrony between glandular and stromal tissue. Immunohistochemistry analysis showed that EG-VEGF protein was predominantly expressed in the glandular epithelial cells and endothelial cells of vessels, and also presented in the stroma. The image analysis confirmed that both the gland and stroma of endometrium in SC1 had a significantly lower EG-VEGF protein expression than that in SC2 and NC endometrium. Moreover, EG-VEGF mRNA levels were significantly lower in SC1 than in NC. Both EG-VEGF protein and mRNA levels had no significant difference between SC2 and NC. Decreased expression of EG-VEGF in the peri-implantation is associated with high ovarian response, which may account for the impaired ER and lower implantation rate in IVF cycles.

Metabolomics analysis of follicular fluid in women with ovarian endometriosis undergoing in vitro fertilization.

PubMed

Karaer, Abdullah; Tuncay, Gorkem; Mumcu, Akın; Dogan, Berat

2018-05-28

The purpose of this study was to investigate whether a change in the follicular fluid metabolomics profile due to endometrioma is identifiable. Twelve women with ovarian endometriosis (aged<40 years, with a body mass index [BMI] of <30 kg/m 2 ) and 12 age- and BMI-matched controls (women with infertility purely due to a male factor) underwent ovarian stimulation for intracytoplasmic sperm injection (ICSI). Follicular fluid samples were collected from both of groups at the time of oocyte retrieval for ICSI. Next, nuclear magnetic resonance (NMR) spectroscopy was performed for the collected follicular fluids. The metabolic compositions of the follicular fluids were then compared using univariate and multivariate statistical analyses of NMR data. Univariate and multivariate statistical analyses of NMR data showed that the metabolomic profiles of the follicular fluids obtained from the women with ovarian endometriosis were distinctly different from those obtained from the control group. In comparison with the controls, the follicular fluids of the women with ovarian endometriosis had statistically significant elevated levels of lactate, β-glucose, pyruvate, and valine. We conclude that the levels of lactate, β-glucose, pyruvate, and valine in the follicular fluid of the women with endometrioma were higher than those of the controls. ASRM: American Society for Reproductive Medicine; BMI: body mass index; CPMG: Carr-Purcell-Meiboom-Gill; E 2 : estradiol; ESHRE: European Society of Human Reproduction and Embryology; ERETIC: electronic to access in vivo concentration; FF: follicular fluid; FSH: follicle-stimulating hormone; hCG: human chorionic gonadotropin; HEPES: 2-hydroxyethyl-1-piperazineethanesulfonic acid; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilization; NMR: nuclear magnetic resonance spectroscopy; PCA: principal component analysis; PCOS: polycystic ovary syndrome; PLS-DA: partial least squares discriminant analysis; ppm: parts per million; PULCON: pulse length-based concentration determination; TSP: 3-(trimethylsilyl)-1-propanesulfonic acid sodium salt; VIP: variable importance in projection.

Melatonin in human preovulatory follicular fluid

NASA Technical Reports Server (NTRS)

Brzezinski, Amnon; Seibel, Machelle M.; Lynch, Harry J.; Deng, Mei-Hua; Wurtman, Richard J.

1987-01-01

Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCG to stimulate follicle formation. Blood samples were obtained by venipuncture 30 rain or less after follicular aspiration. All of the follicular fluids contained melatonim, in concentrations substantially higher than those in the corresponding serum. A positive correlation was found between follicular fluid and serum melatonin levels in each woman; these observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.

Endocrinology of recurrent pregnancy loss.

PubMed

Arredondo, Francisco; Noble, Luis S

2006-02-01

Following implantation, the maintenance of the pregnancy is dependent on a multitude of endocrinological events that will eventually aid in the successful growth and development of the fetus. Although the great majority of pregnant women have no pre-existing endocrine abnormalities, a small number of women can have certain endocrine alterations that could potentially lead to recurrent pregnancy losses. It is estimated that approximately 8 to 12% of all pregnancy losses are the result of endocrine factors. During the preimplantation period, the uterus undergoes important developmental changes stimulated by estrogen, and more importantly, progesterone. Progesterone is essential for the successful implantation and maintenance of pregnancy. Therefore, disorders related to inadequate progesterone secretion by the corpus luteum are likely to affect the outcome of the pregnancy. Luteal phase deficiency, hyperprolactinemia, and polycystic ovarian syndrome are some examples. Several other endocrinological abnormalities such as thyroid disease, hypoparathyroidism, uncontrolled diabetes, and decreased ovarian reserve have been implicated as etiologic factors for recurrent pregnancy loss.

[IVF and endometriosis, oocyte donation and fertility preservation].

PubMed

d'Argent, Emmanuelle Mathieu; Antoine, Jean-Marie

2017-12-01

Endometriosis is a common condition, causing pain and infertility. In infertile woman with superficial peritoneal endometriosis and patent tubes, laparoscopy is recommended, followed by ovarian stimulation alone or in combination with intrauterine inseminations. In case of ovarian or deep endometriosis, the indications of surgery and assisted reproductive technologies remain to be defined precisely. In vitro fertilization is generally proposed after the failure of up to three inseminations, directly for ovarian or deep endometriosis, or in case of an associated factor of infertility, mainly male. Before ovarian stimulation in view to in vitro fertilization, a pretreatment by GnRH agonist for 2 to 6 months or combined contraceptive for 6 to 8 weeks would improve the pregnancy rate. Egg donation is effective in patients with advanced ovarian failure or lack of ovarian response to stimulation. Fertility preservation, especially by oocytes vitrified, must be proposed preventively to women with endometriosis at risk of ovarian failure, without close wish to be pregnant. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Does gravidity influence the success of in vitro fertilization-embryo transfer cycles?

PubMed

Rabinson, Jacob; Bar-Hava, Itai; Meltcer, Simion; Zohav, Efraim; Anteby, Eyal; Orvieto, Raoul

2006-04-01

To evaluate the influence of gravidity on the results of in vitro fertilization (IVF)-embryo transfer (ET) cycles. All consecutive women aged <35 years admitted to our IVF unit from January 2002 to December 2004 were enrolled in the study. Only patients undergoing one of their first three IVF cycle attempts were included. Gravidity, ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and clinical pregnancy rate were assessed. Three hundred and forty-two consecutive IVF cycles were evaluated. One hundred and sixty-one cycles were from nulligravidas and 181 from women with a history of at least one previous clinical pregnancy. Forty-eight (29.8%) clinical pregnancies were observed in the nulligravida group and 56 (30.9%) in the gravida group. There were no differences between nulligravidas and gravidas in causes of infertility, length of ovarian stimulation, peak estradiol and progesterone levels, number of oocytes retrieved, fertilization rate and number of embryos transferred. Gravidas were significantly older (30.4 vs. 27.6 years, p < 0.001) and used more gonadotropin ampoules (36.1 vs. 31.8, p < 0.004) compared with the nulligravidas. Patient gravidity has no influence on the likelihood of achieving pregnancy in IVF-ET cycles.

Comparison of oral dydrogesterone with vaginal progesteronefor luteal support in IUI cycles: a randomized clinical trial.

PubMed

Khosravi, Donya; Taheripanah, Robabeh; Taheripanah, Anahita; Tarighat Monfared, Vahid; Hosseini-Zijoud, Seyed-Mostafa

2015-07-01

The aim of this study, we have compared the advantages of oral dydrogestrone with vaginal progesterone (cyclogest) for luteal support in intrauterine insemination (IUI) cycles. Progesterone supplementation is the first line treatment when luteal phase deficiency (LPD) can reasonably be assumed. This study was conduct to compare the effect of oral dydrogestrone with vaginal Cyclogest on luteal phase support in the IUI cycles. This prospective, randomized, double blind study was performed in a local infertility center from May 2013 to May 2014. It consisted of 150 infertile women younger than35years old undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with oral dydrogesterone (20 mg) as group A and vaginal cyclogest (400 mg) as group B in preparation for the IUI cycles. Clinical pregnancy and abortion rates, mid luteal progesterone (7daysafter IUI) and patient satisfaction were compared between two groups. The mean serum progesterone levels was significantly higher in group A in comparison with group B (p=0.001). Pregnancy rates in group A was not statistically different in comparison with group B (p =0.58). Abortion rate in two groups was not statistically different (p =0.056) although rate of abortion was higher in group B in comparison with A group. Satisfaction rates were significantly higher in group A compared to group B (p<0.001). We concluded that oral dydrogestrone is effective as vaginal progesterone for luteal-phase support in woman undergoing IUI cycles. Moreover, the mean serum progesterone levels and satisfaction rates in dydrogestrone group were higher than cyclogest group.

Lipidomic Components Alterations of Human Follicular Fluid Reveal the Relevance of Improving Clinical Outcomes in Women Using Progestin-Primed Ovarian Stimulation Compared to Short-Term Protocol.

PubMed

Wen, Xiaowei; Kuang, Yanping; Zhou, Lixia; Yu, Baofeng; Chen, Qiuju; Fu, Yonglun; Yan, Zheng; Guo, Haiyan; Lyu, Qifeng; Xie, Jun; Chai, Weiran

2018-05-21

BACKGROUND Increasing the success rate of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is a duty of clinicians that has made many seek a variety of protocols. This study was undertaken to use a liquid chromatography-mass spectrometry (LC-MS) to define the alterations of follicular fluid (FF) lipid metabolites in patients undergoing progestin-primed ovarian stimulation (PPOS) compared with short-term protocol, revealing potential correlations between the differentially expressed lipids and ameliorative clinical outcomes. MATERIAL AND METHODS Ninety-three infertile women undergoing IVF/ICSI treatment with PPOS (n=62) or a short-term protocol (n=31) were prospectively enrolled in a randomized controlled trial. FF samples were obtained from dominant follicles at the time of oocyte retrieval. Lipid metabolism profiles were analyzed using LC-MS. RESULTS Twelve lipids were found to be higher in patients treated with the PPOS protocol than in those receiving the short-term protocol, including triacylglycerols (TAG-34: 1+NH4, TAG-58: 0+NH4, TAG-64: 3+NH4, and TAG-64: 8+NH4), diacylglycerol DAG-38: 6+NH4, phosphatidylglycerols (PG-26: 0, PG-30: 2, and PG-40: 5), phosphatidylethanolamine PE-32: 2, lysophosphatidylethanolamine LPE-14: 1, lysophosphatidylinositol LPI-12: 0, and lysophosphatidylcholine LPC-16: 0. CONCLUSIONS Our data demonstrate that the PPOS protocol increases the levels of 12 lipids in FF, which reveals a strong association between the differentially elevated lipids and better IVF/ICSI outcomes.

Ovarian hyperstimulation syndrome in gonadotropin-treated laboratory South African clawed frogs (Xenopus laevis).

PubMed

Green, Sherril L; Parker, John; Davis, Corrine; Bouley, Donna M

2007-05-01

Ovarian hyperstimulation syndrome (OHS) is a rare but sometimes fatal iatrogenic complication of ovarian stimulation associated with the administration of exogenous gonadotropins to women undergoing treatment for infertility. Laboratory Xenopus spp are commonly treated with human chorionic gonadotropin (hCG) to stimulate ovulation and optimize the number of oocytes harvested for use in biomedical research. Here we report cases of OHS in 2 gonadotropin-treated laboratory Xenopus laevis. After receiving hCG, the frogs developed severe subcutaneous accumulation of fluid, coelomic distention, and whole-body edema and were unable to dive, although they continued to eat and swim. At postmortem examination, extensive subcutaneous edema was present; ascites and massive numbers of free-floating eggs were found in the coelomic cavity and in aberrant locations: around the heart-sac and adhered to the liver capsule. Whole-body edema, gross enlargement of the ovaries, ascites, and abdominal distention are findings comparable to those observed in women with OHS. The pathophysiology of OHS is thought to be related to hormonally induced disturbances of vasoactive mediators, one of which may be vascular endothelial growth factor secreted by theca and granulosa cells. We know of no other report describing OHSlike symptoms in gonadotropin-treated frogs, and the cases described here are 2 of the 3 we have observed at our respective institutions over the last 6 y. According to these results, OHS appears to be rare in gonadotropin-treated laboratory Xenopus. However, the condition should be included in the differential diagnosis for the bloated frog.

Prevalence of and markers for the attenuated form of congenital adrenal hyperplasia and hyperprolactinemia masquerading as polycystic ovarian disease.

PubMed

Benjamin, F; Deutsch, S; Saperstein, H; Seltzer, V L

1986-08-01

To determine the prevalence of the attenuated form of congenital adrenal hyperplasia (CAH) and hyperprolactinemia (HPPN) relative to polycystic ovarian disease (PCOD), 100 consecutive women presenting with the classic clinical features of PCOD were evaluated by basal hormonal profiles and subsequent adrenocorticotropic hormone (ACTH) stimulation tests. The study also sought biochemical markers for CAH other than ACTH stimulation. The prevalences were found to be as follows: PCOD, 65%; PCOD with HPPN, 9%; HPPN, 3%, end-organ hypersensitivity (EOH), 4%; homozygotic CAH, 4%; and heterozygotic CAH, 15%. Other than the differential response to ACTH, the only other biochemical markers observed for homozygotic CAH were significantly higher basal levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17-OHP). Luteinizing hormone/follicle-stimulating hormone ratio, androstenedione, and dehydroepiandrosterone sulfate all showed no significant differences between homozygotic CAH, heterozygotic CAH, HPPN, PCOD, and EOH. This study establishes the relative prevalences of the syndromes commonly mimicking PCOD. We also conclude that the observed low incidence of CAH does not justify routine ACTH testing on all patients presenting with features of PCOD--however, our data suggest that patients with basal serum levels of T and 17-OHP greater than 50% above the upper limit of normal should undergo this dynamic test, especially if there are also certain clinical features suggestive of CAH.

Effect of endometrial biopsy on intrauterine insemination outcome in controlled ovarian stimulation cycle.

PubMed

Wadhwa, Leena; Pritam, Amrita; Gupta, Taru; Gupta, Sangeeta; Arora, Sarika; Chandoke, Rajkumar

2015-01-01

The objective was to evaluate the effect of endometrial biopsy (EB) on intrauterine insemination (IUI) outcome in controlled ovarian stimulation (COS) cycle. Prospective randomized control study. Tertiary care center. A total of 251 subjects were enrolled in the study. Subjects undergoing COS with IUI were randomly allocated into three groups. Group A: EB was taken between D19 and 24 of the spontaneous menstrual cycles that precedes the fertility treatment and IUI, which was done in next cycle (n = 86). Group B: EB was taken before D6 of the menstrual cycle, and fertility treatment and IUI was done in the same cycle (n = 90). Group C: (control group) no EB in previous 3 cycle (n = 75). Clinical pregnancy rate (CPR). Clinical pregnancy rate was 19.77%, 31.11%, and 9.3% for Group A, Group B, and Group C, respectively. The results show a highly significant value for the paired t-test of intervention Group B and control Group C of the cases (P = 0.000957). CPR was maximum after first cycle of ovulation induction and IUI following EB scratch in both Groups A and in Group B (P < 0.001). Endometrial biopsy done in early follicular phase in the same cycle of stimulation with IUI gives better CPR as compared with EB done in the luteal phase of the previous cycle.

Pretreatment with myo-inositol in non polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: a pilot study

PubMed Central

2012-01-01

Background Aim of this pilot study is to examine the effects of myo-inositol administration on ovarian response and oocytes and embryos quality in non PolyCystic Ovary Syndrome (PCOS) patients undergoing multiple follicular stimulation and in vitro insemination by conventional in vitro fertilization or by intracytoplasmic sperm injection. Methods One hundred non-PCOS women aged <40 years and with basal FSH <10 mUI/ml were down-regulated with triptorelin acetate from the mid-luteal phase for 2 weeks, before starting the stimulation protocol for oocytes recovery. All patients received rFSH, at a starting dose of 150 IU for 6 days. The dose was subsequently adjusted according to individual response. Group B (n = 50) received myo-inositol and folic acid for 3 months before the stimulation period and then during the stimulation itself. Group A (n-50) received only folic acid as additional treatment in the 3 months before and through treatment. Results Total length of the stimulation was similar between the two groups. Nevertheless, total amount of gonadotropins used to reach follicular maturation was found significantly lower in group B. In addition, the number of oocytes retrieved was significantly reduced in the group pretreated with myo-inositol. Clinical pregnancy and implantation rate were not significantly different in the two groups. Conclusions Our findings suggest that the addition of myo-inositol to folic acid in non PCOS-patients undergoing multiple follicular stimulation for in-vitro fertilization may reduce the numbers of mature oocytes and the dosage of rFSH whilst maintaining clinical pregnancy rate. Further, a trend in favor of increased incidence of implantation in the group pretreated with myo-inositol was apparent in this study. Further investigations are warranted to clarify this pharmacological approach, and the benefit it may hold for patients. PMID:22823904

Prediction of different ovarian responses using anti-Müllerian hormone following a long agonist treatment protocol for IVF.

PubMed

Heidar, Z; Bakhtiyari, M; Mirzamoradi, M; Zadehmodarres, S; Sarfjoo, F S; Mansournia, M A

2015-09-01

The purpose of this study was to predict the poor and excessive ovarian response using anti-Müllerian hormone (AMH) levels following a long agonist protocol in IVF candidates. Through a prospective cohort study, the type of relationship and appropriate scale for AMH were determined using the fractional polynomial regression. To determine the effect of AMH on the outcomes of ovarian stimulation and different ovarian responses, the multi-nominal and negative binomial regression models were fitted using backward stepwise method. The ovarian response of study subject who entered a standard long-term treatment cycle with GnRH agonist was evaluated using prediction model, separately and in combined models with (ROC) curves. The use of standard long-term treatments with GnRH agonist led to positive pregnancy test results in 30% of treated patients. With each unit increase in the log of AMH, the odds ratio of having poor response compared to normal response decreases by 64% (OR 0.36, 95% CI 0.19-0.68). Also the results of negative binomial regression model indicated that for one unit increase in the log of AMH blood levels, the odds of releasing an oocyte increased 24% (OR 1.24, 95% CI 1.14-1.35). The optimal cut-off points of AMH for predicting excessive and poor ovarian responses were 3.4 and 1.2 ng/ml, respectively, with area under curves of 0.69 (0.60-0.77) and 0.76 (0.66-0.86), respectively. By considering the age of the patient undergoing infertility treatment as a variable affecting ovulation, use of AMH levels showed to be a good test to discriminate between different ovarian responses.

Biological Basis for Chemoprevention of Ovarian Cancer

DTIC Science & Technology

2000-10-01

potent apoptotic effect on ovarian epithelial cells, the use of levonorgestrel in chemoprevention of ovarian cancer is being explored in chickens and women...A chemoprevention trial is ongoing in chickens and we will begin a trial to determine whether levonorgestrel induces apoptosis in the ovarian epithelium of women undergoing oophorectomy.

Vanishing large ovarian cyst with thyroxine therapy.

PubMed

Dharmshaktu, Pramila; Kutiyal, Aditya; Dhanwal, Dinesh

2013-01-01

A 21-year-old female patient recently diagnosed with severe hypothyroidism was found to have a large ovarian cyst. In view of the large ovarian cyst, she was advised to undergo elective laparotomy in the gynaecology department. She was further evaluated in our medical out-patient department (OPD), and elective surgery was withheld. She was started on thyroxine replacement therapy, and within a period of 4 months, the size of the cyst regressed significantly, thereby improving the condition of the patient significantly. This case report highlights the rare and often missed association between hypothyroidism and ovarian cysts. Although very rare, profound hypothyroidism that can cause ovarian cysts in an adult should always be kept in the differential diagnosis to avoid unnecessary ovarian surgery. Hypothyroidism should be considered in the differential diagnosis of adult females presenting with multicystic ovarian tumours.Adequate thyroid hormone replacement therapy can prevent these patients from undergoing unnecessary and catastrophic ovarian resection.Surgical excision should be considered only when adequate thyroid replacement therapy fails to resolve ovarian enlargement.In younger women with ovarian cysts, it is also desirable to avoid unnecessary surgery so as to not compromise fertility in the future.

Vanishing large ovarian cyst with thyroxine therapy

PubMed Central

Dharmshaktu, Pramila; Kutiyal, Aditya; Dhanwal, Dinesh

2013-01-01

Summary A 21-year-old female patient recently diagnosed with severe hypothyroidism was found to have a large ovarian cyst. In view of the large ovarian cyst, she was advised to undergo elective laparotomy in the gynaecology department. She was further evaluated in our medical out-patient department (OPD), and elective surgery was withheld. She was started on thyroxine replacement therapy, and within a period of 4 months, the size of the cyst regressed significantly, thereby improving the condition of the patient significantly. This case report highlights the rare and often missed association between hypothyroidism and ovarian cysts. Although very rare, profound hypothyroidism that can cause ovarian cysts in an adult should always be kept in the differential diagnosis to avoid unnecessary ovarian surgery. Learning points Hypothyroidism should be considered in the differential diagnosis of adult females presenting with multicystic ovarian tumours.Adequate thyroid hormone replacement therapy can prevent these patients from undergoing unnecessary and catastrophic ovarian resection.Surgical excision should be considered only when adequate thyroid replacement therapy fails to resolve ovarian enlargement.In younger women with ovarian cysts, it is also desirable to avoid unnecessary surgery so as to not compromise fertility in the future. PMID:24683475

Diagnostic evaluation of ovarian torsion: An analysis of pediatric patients using the Nationwide Emergency Department Sample.

PubMed

Rialon, Kristy L; Wolf, Steven; Routh, Jonathan C; Adibe, Obinna O

2017-04-01

Ultrasonography (US) is the diagnostic modality of choice during work-up for ovarian torsion, although computed tomography (CT) may be used. We examined the utilization of CT in girls with ovarian torsion, and determined which patients are most likely to undergo this study. The Nationwide Emergency Department Sample dataset was searched for patients <18 years who presented with ovarian torsion from 2006 to 2012. Hospitals were categorized by the volume of pediatric patients seen. A total of 1279 patients were identified. Seven hundred twelve (56%) were seen at adult hospitals, 154 (12%) at pediatric privileged, and 413 (32%) at pediatric hospitals. Patients cared for in a pediatric or pediatric privileged hospital had more US alone performed to diagnose ovarian torsion (p < 0.01). Girls seen at pediatric hospitals are more likely to undergo US for work-up of ovarian torsion. Copyright © 2016 Elsevier Inc. All rights reserved.

XM17 Follitropin Alfa (Ovaleap(®)): A Review in Reproductive Endocrine Disorders.

PubMed

Hoy, Sheridan M

2016-08-01

The subcutaneous recombinant human follicle-stimulating hormone XM17 follitropin alfa (Ovaleap(®)) is approved in the EU as a biosimilar of follitropin alfa (Gonal-f(®)) for use in all indications for which the reference product is approved, including as a multifollicular stimulant in women undergoing superovulation for assisted reproductive technology (ART) treatment. In a nonblind, phase I study in healthy female volunteers, the pharmacokinetic profile of XM17 follitropin alfa was bioequivalent to that of reference follitropin alfa following single dosing. Moreover, in a multinational, phase III study, the efficacy of XM17 follitropin alfa as a multifollicular stimulant was equivalent to that of reference follitropin alfa in terms of the number of retrieved oocytes (primary endpoint) in women undergoing controlled ovarian stimulation for ART treatment. There were no clinically relevant differences in oocyte quality between XM17 follitropin alfa and reference follitropin alfa, with biochemical, clinical and ongoing pregnancy rates and take-home baby rates not significantly differing between the treatment groups. XM17 follitropin alfa was generally well tolerated in this patient population, with its tolerability profile generally similar to that of reference follitropin alfa and with no new unexpected tolerability concerns identified. Thus, XM17 follitropin alfa is an effective treatment option in patients requiring follitropin alfa therapy for various reproductive endocrine disorders, providing a useful alternative to reference follitropin alfa.

How FSH and AMH reflect probabilities of oocyte numbers in poor prognosis patients with small oocyte yields.

PubMed

Gleicher, Norbert; Darmon, Sarah K; Kushnir, Vitaly A; Weghofer, Andrea; Wang, Qi; Zhang, Lin; Albertini, David F; Barad, David H

2016-11-01

In poor prognosis patients undergoing in vitro fertilization, advance determinations of likely oocyte yields are especially important since oocyte numbers to large degree determine in vitro fertilization cycle outcomes. Based on baseline follicle stimulating hormone and anti-müllerian hormone levels at time of initial presentation, we here, therefore, determined at all ages the probabilities of obtaining 1-≥5 oocytes in a retrospective analysis of 1554 consecutive patients undergoing in vitro fertilization cycles at an academically affiliated private fertility center. At lowest levels (≤2.5 mIU/mL), Follicle stimulating hormone at all ages was highly predictable for ≥1 oocyte (88-96 %). Probabilities declined and diverged between ages with increasing follicle stimulating hormone, though narrowed again at high follicle stimulating hormone. Anti-Müllerian hormone demonstrated at higher levels (2.5-≥5 ng/ml) at all ages almost perfect probabilities (99-100 %). With declining anti-Müllerian hormone, age categories, however, increasingly diverged, though to lesser degree than follicle stimulating hormone. In poor prognosis patients, follicle stimulating hormone and anti-Müllerian hormone, thus, offer at different ages very specific probabilities for retrieval of 1-≥5 oocytes. Since oocyte numbers are associated with embryo numbers, and numbers of transferable embryos with live birth rates, here presented probability tables should facilitate improved prognostication of poor prognosis patients. Discrepancies in here reported probabilities between follicle stimulating hormone and anti-müllerian hormone also further define follicle stimulating hormone and anti-müllerian hormone in their respective abilities to represent functional ovarian reserve at different ages.

Oocyte cryopreservation for fertility preservation in postpubertal female children at risk for premature ovarian failure due to accelerated follicle loss in Turner syndrome or cancer treatments.

PubMed

Oktay, K; Bedoschi, G

2014-12-01

To preliminarily study the feasibility of oocyte cryopreservation in postpubertal girls aged between 13 and 15 years who were at risk for premature ovarian failure due to the accelerated follicle loss associated with Turner syndrome or cancer treatments. Retrospective cohort and review of literature. Academic fertility preservation unit. Three girls diagnosed with Turner syndrome, 1 girl diagnosed with germ-cell tumor. and 1 girl diagnosed with lymphoblastic leukemia. Assessment of ovarian reserve, ovarian stimulation, oocyte retrieval, in vitro maturation, and mature oocyte cryopreservation. Response to ovarian stimulation, number of mature oocytes cryopreserved and complications, if any. Mean anti-müllerian hormone, baseline follical stimulating hormone, estradiol, and antral follicle counts were 1.30 ± 0.39, 6.08 ± 2.63, 41.39 ± 24.68, 8.0 ± 3.2; respectively. In Turner girls the ovarian reserve assessment indicated already diminished ovarian reserve. Ovarian stimulation and oocyte cryopreservation was successfully performed in all female children referred for fertility preservation. A range of 4-11 mature oocytes (mean 8.1 ± 3.4) was cryopreserved without any complications. All girls tolerated the procedure well. Oocyte cryopreservation is a feasible technique in selected female children at risk for premature ovarian failure. Further studies would be beneficial to test the success of oocyte cryopreservation in young girls. Copyright © 2014 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Comparison of results of cycles treated with modified mild protocol and short protocol for ovarian stimulation.

PubMed

Coelho, F; Aguiar, L F; Cunha, G S P; Cardinot, N; Lucena, E

2014-01-01

The ovarian stimulation has been applied in order to increase the number of oocytes to compensate for the poor results of in vitro fertilization, allowing the selection of one or more embryos to be transferred. Our aim is to compare the results obtained in IVF/ICSI cycles using the short protocol for controlled ovarian stimulation to the results from the modified mild protocol used in our department. A total of 240 cycles were conducted from January 2010 to December 2011. When comparing both protocols, it could be observed that there was a significant difference in the quantity of gonadotropins doses in the mild protocol and in the short protocol. No significant difference was observed regarding pregnancy rates per cycle, 22% and 26.2%, in short and mild protocols, respectively. The protocols of controlled ovarian stimulation are often associated with high risk of complications such as ovarian hyperstimulation syndrome, excessive emotional stress, high rates of treatment dropouts, and abdominal discomfort. With the data obtained in this study, one can conclude that there are less risks and complications for the patient when using the mild stimulation protocol. It was also observed that in this group there was a slightly higher rate.

Reference values in ovarian response to controlled ovarian stimulation throughout the reproductive period.

PubMed

La Marca, Antonio; Grisendi, Valentina; Spada, Elena; Argento, Cindy; Milani, Silvano; Plebani, Maddalena; Seracchioli, Renato; Volpe, Annibale

2014-01-01

Abstract The age-related decline in ovarian response to gonadotropins has been well known since the beginning of ovarian stimulation in IVF cycles and has been considered secondary to the age-related decline in ovarian reserve. The objective of this study was to establish reference values and to construct nomograms of ovarian response for any specific age to gonadotropins in IVF/ICSI cycles. We analyzed our database containing information on IVF cycles. According to inclusion and exclusion criteria, a total of 703 patients were selected. Among inclusion criteria, there were regular menstrual cycle, treatment with a long GnRH agonist protocol and starting follicle-stimulating hormone (FSH) dose of at least 200 IU per day. To estimate the reference values of ovarian response, the CG-LMS method was used. A linear decline in the parameters of ovarian response with age was observed: the median number of oocytes decreases approximately by one every three years, and the median number of follicles >16 mm by one every eight years. The number of oocytes and growing follicles corresponding to the 5th, 25th, 50th, 75th and 95th centiles has been calculated. This study confirmed the well known negative relationship between ovarian response to FSH and female ageing and permitted the construction of nomograms of ovarian response.

Lysophosphatidic Acid Initiates Epithelial to Mesenchymal Transition and Induces β-Catenin-mediated Transcription in Epithelial Ovarian Carcinoma*

PubMed Central

Burkhalter, Rebecca J.; Westfall, Suzanne D.; Liu, Yueying; Stack, M. Sharon

2015-01-01

During tumor progression, epithelial ovarian cancer (EOC) cells undergo epithelial-to-mesenchymal transition (EMT), which influences metastatic success. Mutation-dependent activation of Wnt/β-catenin signaling has been implicated in gain of mesenchymal phenotype and loss of differentiation in several solid tumors; however, similar mutations are rare in most EOC histotypes. Nevertheless, evidence for activated Wnt/β-catenin signaling in EOC has been reported, and immunohistochemical analysis of human EOC tumors demonstrates nuclear staining in all histotypes. This study addresses the hypothesis that the bioactive lipid lysophosphatidic acid (LPA), prevalent in the EOC microenvironment, functions to regulate EMT in EOC. Our results demonstrate that LPA induces loss of junctional β-catenin, stimulates clustering of β1 integrins, and enhances the conformationally active population of surface β1 integrins. Furthermore, LPA treatment initiates nuclear translocation of β-catenin and transcriptional activation of Wnt/β-catenin target genes resulting in gain of mesenchymal marker expression. Together these data suggest that LPA initiates EMT in ovarian tumors through β1-integrin-dependent activation of Wnt/β-catenin signaling, providing a novel mechanism for mutation-independent activation of this pathway in EOC progression. PMID:26175151

Oocyte-triggering day progesterone levels and endometrial appearance in normoresponders undergoing IVF/ICSI cycles: a hypothesis and a study protocol.

PubMed

Siristatidis, Charalampos; Drakopoulos, Panagiotis; Vogiatzi, Paraskevi; Karageorgiou, Vasilios; Daskalakis, George

2018-05-16

In this report, we propose a study protocol capable of improving IVF outcomes in subfertile women with expected normal ovarian response. This proposal derives from conflicting published data and observations in our daily practice, concerning the negative impact of progesterone (P4) elevation at the day of oocyte triggering on pregnancy outcomes. Our hypothesis points to the combination of two previous "suspects" of reduced success after assisted reproduction techniques (ART) - the endometrium ultrasonographic parameters and P4 elevation at the day of oocyte triggering on their impact on pregnancy outcomes. Up-to-the minute data show that, there is a different impact of elevated P4 in fresh, frozen and donor cycles, whereas there are plenty of reports pointing to a different endometrial gene expression on different P4 measurements. Gaps in the literature are linked with a variation of the measurements of P4, its cycle-to-cycle reproducibility, the different cut-off levels used, the impact of various protocols of ovarian stimulation and the limitations of systematic reviews originating from the initial studies. Our hypothesis states that the combination of P4 values and endometrial ultrasound parameters at the day of oocyte triggering can affect clinical pregnancy rates in normal responders undergoing ART.

Maternal age and ovarian stimulation independently affect oocyte mtDNA copy number and cumulus cell gene expression in bovine clones.

PubMed

Cree, Lynsey M; Hammond, Elizabeth R; Shelling, Andrew N; Berg, Martin C; Peek, John C; Green, Mark P

2015-06-01

Does maternal ageing and ovarian stimulation alter mitochondrial DNA (mtDNA) copy number and gene expression of oocytes and cumulus cells from a novel bovine model for human IVF? Oocytes collected from females with identical nuclear genetics show decreased mtDNA copy number and increased expression of an endoplasmic reticulum (ER) stress gene with repect to ovarian stimulation, whilst differences in the expression of genes involved in mitochondrial function, antioxidant protection and apoptosis were evident in relation to maternal ageing and the degree of ovarian stimulation in cumulus cells. Oocyte quality declines with advancing maternal age; however, the underlying mechanism, as well as the effects of ovarian stimulation are poorly understood. Human studies investigating these effects are often limited by differences in age and ovarian stimulation regimens within a patient cohort, as well as genetic and environmental variability. A novel bovine cross-sectional maternal age model for human IVF was undertaken. Follicles were aspirated from young (3 years of age; n = 7 females) and old (10 years of age; n = 5 females) Holstein Freisian clones following multiple unstimulated, mild and standard ovarian stimulation cycles. These bovine cloned females were generated by the process of somatic cell nuclear transfer (SCNT) from the same founder and represent a homogeneous population with reduced genetic and environmental variability. Maternal age and ovarian stimulation effects were investigated in relation to mtDNA copy number, and the expression of 19 genes involved in mitochondrial function, antioxidant protection, oocyte-cumulus cell signalling and follicle development in both oocytes and cumulus cells. Young (3 years of age; n = 7 females) and old (10 years of age; n = 5 females) Holstein Freisian bovine clones were maintained as one herd. Stimulation cycles were based on the long GnRH agonist down-regulation regimen used in human fertility clinics. Follicle growth rates, numbers and diameters were monitored by ultrasonography and aspirated when the lead follicles were >14 mm in diameter. Follicle characteristics were analysed using a mixed model procedure. Quantitative PCR (qPCR) was used to determine mtDNA copy number and reverse transcriptase-qPCR (RT-qPCR) was used to measure gene expression in oocytes and cumulus cells. Method of ovarian stimulation (P = 0.04), but not maternal age (P > 0.1), was associated with a lower mtDNA copy number in oocytes. Neither factor affected mtDNA copy number in cumulus cells. In oocytes, maternal age had no effect on gene expression; however, ovarian stimulation in older females increased the expression of GRP78 (P = 0.02), a gene involved in ER stress. In cumulus cells, increasing maternal age was associated with the higher expression of genes involved in mitochondrial maintenance (TXN2 P = 0.008 and TFAM P = 0.03), whereas ovarian stimulation decreased the expression of genes involved in mitochondrial oxidative stress and apoptosis (TXN2 P = 0.002, PRDX3 P = 0.03 and BAX P = 0.03). The low number of oocyte and cumulus cell samples collected from the unstimulated cycles limited the analysis. Fertilization and developmental potential of the oocytes was not assessed because these were used for mtDNA and gene expression quantification. Delineation of the independent effects of maternal age and ovarian stimulation regimen on mtDNA copy number gene expression in oocytes and cumulus cells was enabled by the removal of genetic and environmental variability in this bovine model for human IVF. Therefore, these extend upon previous knowledge and findings provide relevant insights that are applicable for improving human ovarian stimulation regimens. Funding was provided by Fertility Associates and the University of Auckland. J.C.P. is a shareholder of Fertility Associates and M.P.G. received a fellowship from Fertility Associates. The other authors of this manuscript declare no conflict of interest that could be perceived as prejudicing the impartiality of the reported research. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparison of oral dydrogesterone with vaginal progesteronefor luteal support in IUI cycles: a randomized clinical trial

PubMed Central

Khosravi, Donya; Taheripanah, Robabeh; Taheripanah, Anahita; Tarighat Monfared, Vahid; Hosseini-Zijoud, Seyed-Mostafa

2015-01-01

Background: The aim of this study, we have compared the advantages of oral dydrogestrone with vaginal progesterone (cyclogest) for luteal support in intrauterine insemination (IUI) cycles. Progesterone supplementation is the first line treatment when luteal phase deficiency (LPD) can reasonably be assumed. Objective: This study was conduct to compare the effect of oral dydrogestrone with vaginal Cyclogest on luteal phase support in the IUI cycles. Materials and Methods: This prospective, randomized, double blind study was performed in a local infertility center from May 2013 to May 2014. It consisted of 150 infertile women younger than35years old undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with oral dydrogesterone (20 mg) as group A and vaginal cyclogest (400 mg) as group B in preparation for the IUI cycles. Clinical pregnancy and abortion rates, mid luteal progesterone (7daysafter IUI) and patient satisfaction were compared between two groups. Results: The mean serum progesterone levels was significantly higher in group A in comparison with group B (p=0.001). Pregnancy rates in group A was not statistically different in comparison with group B (p =0.58). Abortion rate in two groups was not statistically different (p =0.056) although rate of abortion was higher in group B in comparison with A group. Satisfaction rates were significantly higher in group A compared to group B (p<0.001). Conclusion: We concluded that oral dydrogestrone is effective as vaginal progesterone for luteal-phase support in woman undergoing IUI cycles. Moreover, the mean serum progesterone levels and satisfaction rates in dydrogestrone group were higher than cyclogest group. PMID:26494991

[Do poor-responder patients benefit from increasing the daily gonadotropin dose from 300 to 450 IU during controlled ovarian hyperstimulation for IVF?].

PubMed

Haas, Jigal; Zilberberg, Eran; Kedem, Alon; Dar, Shir; Orvieto, Raoul

2015-02-01

We aim to evaluate the IVF-ET outcome in patients receiving a high daily dose (300 IU) of gonadotropins during controlled ovarian hyperstimulation (COH) for IVF and to assess the role of increasing the daily dose to 450 IU on improving outcome. All consecutive women admitted to our IVF unit during an 11 year period who underwent COH consisting of daily gonadotropin dose of 300 IU were included in the study. The ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate were assessed. We also evaluated the subsequent cycle, using daily gonadotropin doses of 450 IU, among those patients who did not conceive using the 300 IU daily gonadotropin dose. Nine hundred and forty-nine consecutive IVF cycles were evaluated. Patients who conceived using the daily gonadotropin dose of 300 IU (n = 133, 14% pregnancy rate) had significantly longer stimulation, yielded higher numbers of oocytes retrieved, fertilization rate and number of embryos transferred, compared to those who did not conceive. Moreover, while comparing IVF cycles using daily gonadotropin doses of 300 IU to 450 IU (n = 117), no in-between group differences were observed, except for significantly higher yields of oocytes retrieved. Moreover, cycles using daily gonadotropin doses of 450 IU resulted in a 7.7 live-birth rate. In poor responders undergoing COH with a daily gonadotropin dose of 300 IU, increasing the dose to 450 IU resulted in significantly higher oocyte yields and a reasonable live birth rate.

IGFBP-2 Vaccine and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Undergoing Surgery

ClinicalTrials.gov

2018-05-01

Stage III Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Functional genetic polymorphisms and female reproductive disorders: Part I: polycystic ovary syndrome and ovarian response

PubMed Central

Simoni, M.; Tempfer, C.B.; Destenaves, B.; Fauser, B.C.J.M.

2008-01-01

BACKGROUND The identification of polymorphisms associated with a disease can help to elucidate its pathogenesis, and this knowledge can be used to improve prognosis for women with a particular disorder, such as polycystic ovary syndrome (PCOS). Since an altered response to ovarian stimulation is also a characteristic of the disease, further knowledge about its aetiology could help in defining the parameters that determine the response of an individual to ovarian stimulation. METHODS PubMed and EMBASE databases were systematically searched for gene association studies published until the end of August 2007, using search criteria relevant to PCOS and ovarian response to stimulation. Data from additional papers identified through hand searches were also included; 139 publications were reviewed. RESULTS Several genes involved in ovarian function and metabolism are associated with increased susceptibility to PCOS, but none is strong enough to correlate alone with susceptibility to the disease, or response to therapy. A single-nucleotide polymorphism in exon 10 of the FSH receptor (FSHR) gene, FSHR p.N680S, was consistently identified as having a significant association with ovarian response to FSH. CONCLUSIONS No consistent association between gene polymorphism and PCOS could be identified. The FSHR gene may play a significant role in the success of ovarian stimulation, and can be used as a marker to predict differences in FSHR function and ovarian response to FSH. Genotyping the FSHR p.N680S polymorphism may provide a means of identifying a population of poor responders before in vitro fertilization procedures are initiated. PMID:18603647

High progesterone levels during the luteal phase related to the use of an aromatase inhibitor in breast cancer patients.

PubMed

Alviggi, C; Marci, R; Vallone, R; Conforti, A; Di Rella, F; Strina, I; Picarelli, S; De Rosa, P; De Laurentiis, M; Yding Andersen, C; De Placido, G

2017-07-01

To evaluate the hormonal profile in three breast cancer patients who underwent controlled ovarian stimulation in the presence of the aromatase inhibitor letrozole. In IVF University referral center, a case series of three breast cancer patients who underwent controlled ovarian stimulation (COS) with recombinant FSH and letrozole were investigated. Ovulation was induced with hCG (case No. 1) or with GnRH agonist (case No. 2-3). The primary outcome of our study was the detection of progesterone levels in the luteal phase. Very high progesterone values (mean 186.6 ± 43.6 ng/mL) during the luteal phase were recorded in all three cases. High progesterone levels can be related to the use of letrozole independently of the most commonly used trigger regimen. Although progesterone has long been considered a protective factor against breast cancer, several studies have demonstrated that progesterone could expand a transformation-sensitive stem cell population in the mammary glands. The estrogen negative feedback effect on the hypothalamus-pituitary axis and the disruption of steroid biosynthesis and could represent an intriguing reason behind this phenomenon. Our results highlight the need to evaluate further the increase in progesterone levels in the luteal phase in women with breast cancer undergoing COS with letrozole.

Effect of endometrial biopsy on intrauterine insemination outcome in controlled ovarian stimulation cycle

PubMed Central

Wadhwa, Leena; Pritam, Amrita; Gupta, Taru; Gupta, Sangeeta; Arora, Sarika; Chandoke, Rajkumar

2015-01-01

OBJECTIVE: The objective was to evaluate the effect of endometrial biopsy (EB) on intrauterine insemination (IUI) outcome in controlled ovarian stimulation (COS) cycle. DESIGN: Prospective randomized control study. SETTING: Tertiary care center. MATERIALS AND METHODS: A total of 251 subjects were enrolled in the study. Subjects undergoing COS with IUI were randomly allocated into three groups. Group A: EB was taken between D19 and 24 of the spontaneous menstrual cycles that precedes the fertility treatment and IUI, which was done in next cycle (n = 86). Group B: EB was taken before D6 of the menstrual cycle, and fertility treatment and IUI was done in the same cycle (n = 90). Group C: (control group) no EB in previous 3 cycle (n = 75). MAIN OUTCOME MEASURE: Clinical pregnancy rate (CPR). RESULTS: Clinical pregnancy rate was 19.77%, 31.11%, and 9.3% for Group A, Group B, and Group C, respectively. The results show a highly significant value for the paired t-test of intervention Group B and control Group C of the cases (P = 0.000957). CPR was maximum after first cycle of ovulation induction and IUI following EB scratch in both Groups A and in Group B (P < 0.001). CONCLUSIONS: Endometrial biopsy done in early follicular phase in the same cycle of stimulation with IUI gives better CPR as compared with EB done in the luteal phase of the previous cycle. PMID:26538858

Pretreatment with oral contraceptives in infertile anovulatory patients with polycystic ovary syndrome who receive gonadotropins for controlled ovarian stimulation.

PubMed

Palomba, Stefano; Falbo, Angela; Orio, Francesco; Russo, Tiziana; Tolino, Achille; Zullo, Fulvio

2008-06-01

This study was intended to assess the effects of oral contraceptives given before treatment in infertile anovulatory patients with polycystic ovary syndrome who receive gonadotropins for controlled ovarian stimulation. Pretreatment with oral contraceptives increased the mono-ovulatory cycles, the duration of stimulation for noncanceled cycles, and the number of vials of gonadotropins used. It also reduced the number of dominant follicles and the peak E(2) levels for dominant follicles. No effect was observed in rates of cycle cancellation, pregnancy, abortion, live birth, multiple pregnancies, and ovarian hyperstimulation syndrome.

Comparison of Results of Cycles Treated with Modified Mild Protocol and Short Protocol for Ovarian Stimulation

PubMed Central

Aguiar, L. F.; Cunha, G. S. P.; Cardinot, N.; Lucena, E.

2014-01-01

The ovarian stimulation has been applied in order to increase the number of oocytes to compensate for the poor results of in vitro fertilization, allowing the selection of one or more embryos to be transferred. Our aim is to compare the results obtained in IVF/ICSI cycles using the short protocol for controlled ovarian stimulation to the results from the modified mild protocol used in our department. A total of 240 cycles were conducted from January 2010 to December 2011. When comparing both protocols, it could be observed that there was a significant difference in the quantity of gonadotropins doses in the mild protocol and in the short protocol. No significant difference was observed regarding pregnancy rates per cycle, 22% and 26.2%, in short and mild protocols, respectively. The protocols of controlled ovarian stimulation are often associated with high risk of complications such as ovarian hyperstimulation syndrome, excessive emotional stress, high rates of treatment dropouts, and abdominal discomfort. With the data obtained in this study, one can conclude that there are less risks and complications for the patient when using the mild stimulation protocol. It was also observed that in this group there was a slightly higher rate. PMID:25763398

New stimulation regimens: endogenous and exogenous progesterone use to block the LH surge during ovarian stimulation for IVF.

PubMed

Massin, Nathalie

2017-03-01

The advent of embryo and oocyte vitrification today gives reproductive specialists an opportunity to consider new strategies for improving the practice and results of IVF attempts. As the freezing of entire cohorts does not compromise, and may even improve, the results of IVF attempts, it is possible to break away from the standard sequence of stimulation-retrieval-transfer. The constraints associated with ovarian stimulation in relation to the potential harmful effects of the hormonal environment on endometrial receptivity can be avoided. This review will look at the new stimulation protocols where progesterone is used to block the LH surge. Thanks to 'freeze all' strategies, the increase in progesterone could actually be no longer a cause for concern. There are two ways of using progesterone, whether it be endogenous, as in luteal phase stimulation, or exogenous, as in the use of progesterone in the follicular phase i.e. progestin primed ovarian stimulation. A literature search was carried out (until September 2016) on MEDLINE. The following text words were utilized to generate the list of citations: progestin primed ovarian stimulation, luteal phase stimulation, luteal stimulation, duostim, double stimulation, random start. Articles and their references were then examined in order to identify other potential studies. All of the articles are reported in this review. The use of progesterone during ovarian stimulation is effective in blocking the LH surge, whether endogenous or exogenous, and it does not affect the number of oocytes collected or the quality of the embryos obtained. Its main constraint is that it requires total freezing and delayed transfer. A variety of stimulation protocols can be derived from these two methods, and their implications are discussed, from fertility preservation to ovarian response profiles to organization for the patients and clincs. These new regimens enable more flexibility and are of emerging interest in daily practice. However, their medical and economic significance remains to be demonstrated. The use of luteal phase or follicular phase protocols with progestins could rapidly develop in the context of oocyte donation and fertility preservation not related to oncology. Their place could develop even more in the general population of patients in IVF programs. The strategy of total freezing continues to develop, thanks to technical improvements, in particular vitrification and PGS on blastocysts, and thanks to studies showing improvements in embryo implantation when the transfer take place far removed from the hormonal changes caused by ovarian stimulation. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Preconception folic acid use modulates estradiol and follicular responses to ovarian stimulation.

PubMed

Twigt, John M; Hammiche, Fatima; Sinclair, Kevin D; Beckers, Nicole G; Visser, Jenny A; Lindemans, Jan; de Jong, Frank H; Laven, Joop S E; Steegers-Theunissen, Régine P

2011-02-01

Folate is a methyl donor. Availability of folate affects DNA methylation profiles and thereby gene expression profiles. We investigated the effects of low-dose folic acid use (0.4 mg/d) on the ovarian response to mild and conventional ovarian stimulation in women. In a randomized trial among subfertile women, 24 and 26 subjects received conventional and mild ovarian stimulation, respectively. Blood samples were taken during the early follicular phase of the cycle prior to treatment and on the day of human chorionic gonadotropin administration for determination of serum total homocysteine, anti-Müllerian hormone (AMH), estradiol, and folate. Folic acid use was validated by questionnaire and serum folate levels. Preovulatory follicles were visualized, counted, and diameters recorded using transvaginal ultrasound. The relation between folic acid use and ovarian response was assessed using linear regression analysis. Folic acid use modified the ovarian response to ovarian stimulation treatment. The estradiol response was higher in nonfolic acid users receiving conventional treatment [β(interaction) = 0.52 (0.07-0.97); P = 0.03], and this effect was independent of serum AMH levels and the preovulatory follicle count. In the conventional treatment, the mean follicle number was also greater in nonusers compared with the users group (14.1 vs. 8.9, P = 0.03). Low-dose folic acid use attenuates follicular and endocrine responses to conventional stimulation, independent of AMH and follicle count. The nature of this observation suggests that the effect of folic acid is most prominent during early follicle development, affecting immature follicles. Deleterious effects of folate deficiency, like DNA hypomethylation and oxidative stress, can help to explain our observations.

Comparison of mild and microdose GnRH agonist flare protocols on IVF outcome in poor responders.

PubMed

Karimzadeh, Mohammad Ali; Mashayekhy, Mehri; Mohammadian, Farnaz; Moghaddam, Fatemeh Mansoori

2011-05-01

To compare the IVF outcome of clomiphene citrate/gonadotropin/antagonist (mild protocol) and microdose GnRH agonist flare protocols for poor responders undergoing in vitro fertilization. 159 poor responder patients were randomized and ovarian stimulation was performed with clomiphene citrate, gonadotropin and antagonist (group I) or microdose GnRH agonist flare (group II) protocols. Main outcome was clinical pregnancy rate and secondary outcomes were doses of gonadotropin administration and duration of stimulation. There were no significant differences in age, causes of infertility, basal FSH, BMI, duration of infertility, E(2) level on the day of hCG injection in both groups. Although the cancellation, fertilization, and clinical pregnancy rates were similar in both groups, the endometrial thickness, number of retrieved oocytes, mature oocytes and implantation rate were significantly higher in mild protocol. The doses of gonadotropin administration and duration of stimulation were significantly lower in mild protocol. We recommend mild protocol in assisted reproductive technology cycles for poor responders based on our results regarding less doses of used gonadotropin and a shorter duration of stimulation.

Glutathione S-transferase activity in follicular fluid from women undergoing ovarian stimulation: role in maturation.

PubMed

Meijide, Susana; Hernández, M Luisa; Navarro, Rosaura; Larreategui, Zaloa; Ferrando, Marcos; Ruiz-Sanz, José Ignacio; Ruiz-Larrea, M Begoña

2014-10-01

Female infertility involves an emotional impact for the woman, often leading to a state of anxiety and low self-esteem. The assisted reproduction techniques (ART) are used to overcome the problem of infertility. In a first step of the in vitro fertilization therapy women are subjected to an ovarian stimulation protocol to obtain mature oocytes, which will result in competent oocytes necessary for fertilization to occur. Ovarian stimulation, however, subjects the women to a high physical and psychological stress, thus being essential to improve ART and to find biomarkers of dysfunction and fertility. GSH is an important antioxidant, and is also used in detoxification reactions, catalysed by glutathione S-transferases (GST). In the present work, we have investigated the involvement of GST in follicular maturation. Patients with fertility problems and oocyte donors were recruited for the study. From each woman follicles at two stages of maturation were extracted at the preovulatory stage. Follicular fluid was separated from the oocyte by centrifugation and used as the enzyme source. GST activity was determined based on its conjugation with 3,4-dichloronitrobenzene and the assay was adapted to a 96-well microplate reader. The absorbance was represented against the incubation time and the curves were adjusted to linearity (R(2)>0.990). Results showed that in both donors and patients GST activity was significantly lower in mature oocytes compared to small ones. These results suggest that GST may play a role in the follicle maturation by detoxifying xenobiotics, thus contributing to the normal development of the oocyte. Supported by FIS/FEDER (PI11/02559), Gobierno Vasco (Dep. Educación, Universiades e Investigación, IT687-13), and UPV/EHU (CLUMBER UFI11/20 and PES13/58). The work was approved by the Ethics Committee of the UPV/EHU (CEISH/96/2011/RUIZLARREA), and performed according to the UPV/EHU and IVI-Bilbao agreement (Ref. 2012/01). Copyright © 2014. Published by Elsevier Inc.

[Which ovarian stimulation to which women: The polycystic ovary syndrome (PCOS)].

PubMed

Merviel, P; Bouée, S; Ménard, M; Le Martelot, M-T; Roche, S; Lelièvre, C; Chabaud, J-J; Jacq, C; Drapier, H; Beauvillard, D

2017-11-01

Polycystic ovarian syndrome (PCOS) is a frequent pathology in the young woman, linking infertility to a metabolic disease. Initial support will include a plan (in the case of overweight or obesity) to lose at least 5 to 10% of the weight. Subsequently, clomiphene citrate is the first treatment for ovulation induction with pregnancy rates of 40 to 80% after 6 cycles. If there is resistance to clomiphene citrate, the choice will be between the ovarian drilling (50-60% of pregnancy in the year following, including the half spontaneous) or ovarian stimulation with gonadotropins. The risk of ovarian stimulation in these women is hyperstimulation and multiple pregnancies. We also discuss the place of the GnRH pulsatile administration, insulin-sensitizers, in vitro fertilization and in vitro maturation in these women. Once infertility support, these women should be long-term followed because of the neoplasic and cardiovascular risks they present. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Should luteal phase support be introduced in ovarian stimulation/IUI programmes? An evidence-based review.

PubMed

Cohlen, B J

2009-01-01

World-wide, intrauterine insemination (IUI) is still one of the most applied techniques to enhance the probability of conception in couples with longstanding subfertility. The outcome of this treatment option depends on many confounding factors. One of the confounding factors receiving little attention is the quality of the luteal phase. From IVF studies, it is known that ovarian stimulation causes luteal phase deficiency. Based on the best available evidence, this short review summarizes the indications for mild ovarian stimulation combined with IUI and the optimal stimulation programme. While it has been established that stimulated IVF/intracytoplasmic sperm injection cycles have deficient luteal phases, the question remains whether the quality of the luteal phase when only two or three corpora lutea are present (as is the case in stimulated IUI cycles) is impaired as well. There are too few large non-IVF trials studying luteal phase quality to answer this question. Recently a randomized trial has been published that investigated luteal phase support in an IUI programme. This study is discussed in detail. It is recommended to apply luteal phase support in stimulated IUI cycles only when proven costeffective. Further trials are mandatory to investigate both endometrial and hormonal profile changes in the luteal phase after mild ovarian stimulation, and the cost-effectiveness of luteal support in IUI programmes.

A Retrospective Study of Letrozole Treatment Prior to Human Chorionic Gonadotropin in Women with Polycystic Ovary Syndrome Undergoing In Vitro Fertilization at Risk of Ovarian Hyperstimulation Syndrome.

PubMed

Chen, Yilu; Yang, Tanchu; Hao, Cuifang; Zhao, Junzhao

2018-06-20

BACKGROUND Women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) are given letrozole before a trigger injection of human chorionic gonadotropin (hCG) to lower estrogen (E2) levels, but can experience ovarian hyperstimulation syndrome (OHSS). The aim of this study was to evaluate the effect of oral letrozole, prior to administration of hCG, on the outcome of IVF and development of OHSS. MATERIAL AND METHODS Retrospective clinical review included 181 cases of women with PCOS who underwent IVF cycles with intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) (IVF/ICSI-ET). The day before the use of hCG, cases were divided into a letrozole-treated group (N=78) and a non-letrozole group (N=103). An oral dose of 2.5 mg qd of letrozole was given when the peak level of E2 was ≥4000 pg/ml during ovarian stimulation and ceased before the day of egg retrieval. RESULTS The letrozole-treated group had a significant increase in the number of retrieved oocytes, viable embryos, and fresh ET rate (P>0.05); peak levels of E2, and E2 levels on the day of the egg retrieval, were significantly higher, and the fertilization rate was significantly lower (P<0.001). No significant differences were found in the rates of pregnancy, abortion, or ectopic pregnancy between the two groups (P>0.05). The incidence OHSS was lower in the letrozole-treated group, but this difference did not reach statistical significance (P>0.05). CONCLUSIONS Women with PCOS who underwent IVF, oral treatment with letrozole a day prior to treatment with hCG lowered E2 levels, but did not significantly reduce the incidence of OHSS.

Effect of estradiol on the expression of angiogenic factors in epithelial ovarian cancer.

PubMed

Valladares, Macarena; Plaza-Parrochia, Francisca; Lépez, Macarena; López, Daniela; Gabler, Fernando; Gayan, Patricio; Selman, Alberto; Vega, Margarita; Romero, Carmen

2017-11-01

Ovarian cancer presents a high angiogenesis (formation of new blood vessels) regulated by pro-angiogenic factors, mainly vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). An association between endogenous levels of estrogen and increased risk of developing ovarian cancer has been reported. Estrogen action is mediated by the binding to its specific receptors (ERα and ERβ), altered ERα/ERβ ratio may constitute a marker of ovarian carcinogenesis progression. To determine the effect of estradiol through ERα on the expression of NGF and VEGF in epithelial ovarian cancer (EOC). Levels of phosphorylated estrogen receptor alpha (pERα) were evaluated in well, moderate and poorly differentiated EOC samples (EOC-I, EOC-II, EOC-III). Additionally, ovarian cancer explants were stimulated with NGF (0, 10 and 100 ng/ml) and ERα, ERβ and pERα levels were detected. Finally, human ovarian surface epithelial (HOSE) and epithelial ovarian cancer (A2780) cell lines were stimulated with estradiol, where NGF and VEGF protein levels were evaluated. In tissues, ERs were detected being pERα levels significantly increased in EOC-III samples compared with EOC-I (p<0.05). Additionally, ovarian explants treated with NGF increased pERα levels meanwhile total ERα and ERβ levels did not change. Cell lines stimulated with estradiol revealed an increase of NGF and VEGF protein levels (p<0.05). Estradiol has a positive effect on pro-angiogenic factors such as NGF and VEGF expression in EOC, probably through the activation of ERα; generating a positive loop induced by NGF increasing pERα levels in epithelial ovarian cells.

[Smoothing Gan Reinforcing Shen Method Adjuvantly Treated Poor Response of Diminished Ovari- an Reserve Patients in in vitro Fertilization and Embryo Transfer: a Clinical Study].

PubMed

Zhang, Zheng; Zhang, Xue-hong; He, Tian-you

2015-10-01

To study clinical efficacy of smoothing Gan reinforcing Shen (SGRS) method in treating poor response of diminished ovarian reserve (DOR) patients in in vitro fertilization and embryo, transfer (IVF-ET). Totally 84 DOR patients undergoing IVF-ET were assigned to the experimental group (SGRS Chinese herbs as adjuvant therapy) and the control group according to random digit table, 42 in each group. Patients in the control group received controlled ovarian hyperstimulation (COH) and IVF-ET. Those in the experimental group additionally received basic formula of SGRS method, one dose per day. The dose and use time of recombinant follicle-stimulating hormone (r-FSH) were recorded during ovarian stimulation process. On the injection day of human chorionic gonadotropin (HCG) and serum levels of estradiol (E2) on the oocyte retrieval day were determined using chemiluminescent method. E2 contents in the follicular fluid on the oocyte retrieval day were detected using ELISA. The total number of retrieved oocytes, the number of mature oocytes in metaphase II (M II), the number of normal fertilization [with two pronucleus (2PN)], the number of portable embryos, and the number of good quality embryos were recorded. The correlation between Chinese medical adjuvant therapy and the aforesaid indices were observed. The clinical pregnancy rate and the abortion rate were finally compared between the two groups. The total dose of r-FSH, the E2 level on HCG injection day, the serum E2 level on the oocyte retrieval day, the number of retrieved oocyte, the number of oocytes in M II the number of oocytes with 2PN, the number of portable embryos, and the number of good quality embryos were all positively correlated with Chinese medical adjuvant therapy (P < 0.05, P < 0.01). Compared with the control group, serum E2 levels on the HCG injection day and the oocyte retrieval day obviously increased, the number of retrieved oocytes, the number of oocytes in M II, and the number of portable embryos were increased more in the experimental group with statistical difference (P < 0.05, P < 0.01). There was no statistical significance in the clinical pregnancy rate or the abortion rate between the two groups (P > 0.05). SGRS Chinese herbs as adjuvant therapy could improve ovarian responsiveness of DOR patients undergoing IVF-ET, increase the number of retrieved oocytes, elevate the quality of oocytes and the number of embryos.

Exploratory study of the association of steroid profiles in stimulated ovarian follicular fluid with outcomes of IVF treatment.

PubMed

Kushnir, Mark M; Naessén, Tord; Wanggren, Kjell; Hreinsson, Julius; Rockwood, Alan L; Meikle, A Wayne; Bergquist, Jonas

2016-09-01

Steroid concentrations in stimulated follicular fluid (sFF) samples have been linked to the quality of oocytes used in IVF treatments. Most of the published studies focused on evaluating the association of the IVF outcomes with only a few of the steroids, measured by immunoassays (IA). We performed a treatment outcome, prospective cohort study using stimulated FF sampled from 14 infertile women undergoing IVF treatment; single oocyte was used per IVF cycle. Fourteen endogenous steroids were analyzed in 22 ovarian follicle aspirations, which corresponded to the embryos used in the IVF. Ten oocytes were associated with live birth (LB) and 12 with no pregnancy (NP). Steroids were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Differences in distribution of concentrations in association with the pregnancy outcome (LB or NP), and receiver operating characteristic (ROC) curves analysis were performed for the entire cohort and for within-women data. The predominant androgen and estrogen in stimulated sFF were androstenedione (A4) and estradiol (E2), respectively. Lower concentrations of pregnenolone (Pr), lower ratios of A4/ dehydroepiandrosterone (DHEA), testosterone (Te)/DHEA, and greater ratios of E2/Te, and estrone/A4 were observed in sFF samples associated with LB. Among the oocytes associated with NP, in four out of 12 samples total concentration of androgens was above the distribution of the concentrations in the oocytes corresponding to the LB group. Observations of the study indicated increased consumption of precursors and increased biosynthesis of estrogens in the follicles associated with LB. Our data suggest that potentially steroid profiles in sFF obtained during oocyte retrieval may serve as biomarkers for selection of the best embryo to transfer after IVF. Copyright © 2015 Elsevier Ltd. All rights reserved.

EF5 in Finding Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Cervical, Endometrial, or Ovarian Epithelial Cancer

ClinicalTrials.gov

2013-01-15

Primary Peritoneal Cavity Cancer; Stage I Endometrial Carcinoma; Stage I Ovarian Epithelial Cancer; Stage IA Cervical Cancer; Stage IB Cervical Cancer; Stage II Endometrial Carcinoma; Stage II Ovarian Epithelial Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Endometrial Carcinoma; Stage IV Ovarian Epithelial Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

Symptom clusters of ovarian cancer patients undergoing chemotherapy, and their emotional status and quality of life.

PubMed

Hwang, Kyung-Hye; Cho, Ok-Hee; Yoo, Yang-Sook

2016-04-01

We conducted a descriptive study to identify the symptoms, emotional status, and quality of life experienced by hospitalized ovarian cancer patients undergoing chemotherapy, and influencing the factors of symptom clusters on their quality of life. A total of 192 patients who had been diagnosed with ovarian cancer and received adjuvant chemotherapy after surgery more than once from 2 university hospitals with over 800 beds located in the Seoul and Gyeonggi areas of South Korea were included in this study. Using a structured questionnaire, the symptoms, emotional status, and quality of life by these patients were investigated from May 2012 to June 2013. We identified the following 7 symptom clusters among ovarian cancer patients undergoing chemotherapy: psychological distress, fatigue-pain, abdominal discomfort, flu-like symptoms, fluid accumulation, and peripheral neuropathy. Patients with a high level of anxiety or depression experienced all symptoms at a higher level, and the 7 symptom clusters influenced all aspects of the patients' quality of life. This study provides to need interventions for the quality of life of ovarian cancer patients need to include the management of not only the physical symptoms and treatment-related side effects, but also the changes in their emotional status and daily lives. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prevention and management of ovarian hyperstimulation syndrome.

PubMed

Nelson, Scott M

2017-03-01

Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic complication of ovarian stimulation. It is feasible to identify patients at risk, modify stimulation strategies to ameliorate risk, and initiate out-patient treatments that alter disease pathophysiology to reduce disease severity. Mitigation of OHSS risk and severity, through innovative approaches prior to treatment, during treatment and after treatment should now be standard care. This review summarizes recent developments and provides recommendations on the prevention and treatment of OHSS. © 2017 Elsevier Ltd. All rights reserved.

[Evolution of ovarian stimulation in in vitro fertilization].

PubMed

Delbaere, A; Devreker, F; Hannes, M; Koenig, I; Holoye, A; Englert, Y

1999-10-01

This paper reviews the different treatments of ovarian stimulation for in vitro fertilization (IVF). It emphasizes the recent development of new molecules, including recombinant gonadotrophins and GnRH antagonists. Because of their higher purity, recombinant gonadotrophins are theoretically less immunogenic than the urinary forms. Their preparation mode ensures a better batch to batch consistency. Their clinical use in IVF seems to be associated with a higher number of developing follicules and retrieved oocytes, but pregnancy rates are comparable to those obtained after ovarian stimulation with urinary gonadotrophins. The GnRH antagonists induce a direct inhibition of the pituitary gonadotrophin secretion. In association with an ovarian stimulation with gonadotrophins, they efficiently prevent premature LH surges when administered during the end of the follicular phase. The GnRH antagonists are still in clinical evaluation phase and the optimal protocol and dose still to be defined. They should become available in the coming year. The risks related to the controlled hyperstimulation together with the reduction of the number of transferred embryos has recently led "soft stimulation" to a reevaluation of the stimulation protocols towards a simplified procedure. However, the validity of this attitude could be in opposition with the wish to limit the number of transferred embryos since embryo quality seems to be directly related to the total number of embryos.

Evaluation of results obtained with corifollitropin alfa after poor ovarian response in previous cycle using recombinant follicular stimulating hormone in the long-term protocol.

PubMed

Salgueiro, Lister L; Rolim, Juliana R; Moura, Bernardo R L; Machado, Suelen P P; Haddad, Carolina

2016-08-01

This study evaluated the use of Corifollitropin alfa in patients with previous poor response to recombinant follicle stimulating hormone in long-term protocols using gonadotropin-releasing hormone. Twenty-seven poor responders to previous treatment with the long term protocol using the recombinant follicle stimulating hormone (Group 1) were selected and then submitted to a second attempt using the same long term protocol with Corifollitropin alfa instead of the recombinant follicle stimulating hormone (Group 2).Ovarian down-regulation was achieved using subcutaneous administration of Leuprolide Acetate. Ovarian stimulation was performed with recombinant follicle stimulating hormone until the administration of human chorionic gonadotropin, followed by follicular aspiration (Group 1). Group 2 was submitted to this same protocol using Corifollitropin alfa instead of recombinant follicle stimulating hormone. There were significant differences in the number of aspirated oocytes, percentage of mature oocytes, amount of injected oocytes and transferred embryos - with all of these parameters being increased in the Corifollitropin alfa group. In addition, the rates of pregnancy and ongoing pregnancy were also significantly higher in the Corifollitropin alfa group. The present study demonstrated that the use of Corifollitropin alfa in the long-term protocol could be a highly effective alternative for patients with poor ovarian response, who were unsuccessful in a previous treatment with In Vitro Fertilization - Intracytoplasmic Sperm Injection.

Maternal thyroid function in women undergoing controlled ovarian hyperstimulation during in-vitro fertilization and its relation to reproductive outcome.

PubMed

Abdul Karim, Abdul K; Azrai Abu, Muhammad; Chelliah, Buvanes; Mohd Razi, Zainul R; Omar, Mohd H; Othman, Hanita; Man, Zuraidah C

2017-10-01

We conducted a study to evaluate the changes in thyroid function during controlled ovarian hyperstimulation (COH) and its association with the outcome of assisted reproductive technique (ART). This is a prospective cohort study done in University Hospital Fertility Clinic for one year duration. A total of 88 euthyroid women who underwent COH as part of planned in-vitro fertilization (IVF) were invited to participate in this study. Serum thyroid function of each women will be monitored before stimulation (T1), day 10-13 of cycle (T2), during oocyte retrieval (T3), one week following embryo transfer (T4), and at four weeks after embryo transfer (T5). Reproductive outcome of IVF will be observed and documented. Nine women had ongoing singleton pregnancy, seven suffered from miscarriage, while the rest had implantation failure. Serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) increased throughout stimulation, peaking at 32-36 hours after hCG administration compared to baseline (1.250 vs. 1.740 mIU/L and 13.94 vs. 15.25 pmol/L). It remains elevated until one week following embryo transfer. The increment of serum TSH exceeded the upper limit, acceptable for first trimester (<1.60 mIU/L). However, the evolution of serum TSH and fT4 did not significantly differ with pregnancy outcome. In euthyroid women, thyroid function changed significantly during COH, but these changes were not different between the three reproductive outcomes. Thus, we do not suggest continuous thyroid function monitoring during COH.

The effects of superovulation with gonadotropins on autoantibody levels in patients undergoing assisted reproductive cycles.

PubMed

Ashrafi, Mahnaz; Amirchaghmaghi, Elham; Arabipoor, Arezoo; Vesali, Samira; Salman-Yazdi, Reza

2018-04-25

To evaluate the effect of controlled ovarian stimulation (COH) with gonadotropins on the serum levels of autoantibodies in the women who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles and to compare basal levels of these autoantibodies between groups according to history of COH. This prospective cohort study was performed from October 2014 to March 2016 in the Royan Institute. The volunteered infertile women with regard to the inclusion criteria, who underwent IVF/ICSI cycles, were recruited. The COH was performed according to standard long GnRH agonist protocol. The mean levels of the autoantibodies including anti-nuclear, anti-smooth muscle, anti-ovarian, anti-mitochondrial, anti β 2 -glycoprotein I, anti-parietal cell and anti-follicle-stimulating hormone antibodies were measured at three time points: on the 3-5 days of the menstrual cycle, 1 week after starting of COH and the ovum pick-up (OPU) day. Of all participants (n = 189), 73 women had history of COH (group B) and 116 women did not have such history (group A). The analysis indicated that the autoantibodies changes during COH were similar in both groups. COH has no significant impact on the level of autoantibodies during the stimulation cycle. Multiple logistic regression analysis showed that the serum levels of anti-smooth muscle antibody on OPU day was the positive predictive factors for live birth following ART cycles in the studied population. No significant effect of COH on the studied autoantibodies by the time of OPU was found but further studies are required to interpret these results.

Dose-dense paclitaxel with carboplatin for advanced ovarian cancer: a feasible treatment alternative.

PubMed

Glaze, Sarah; Teitelbaum, Lisa; Chu, Pamela; Ghatage, Prafull; Nation, Jill; Nelson, Gregg

2013-01-01

Epithelial ovarian cancer is the leading cause of death from gynaecologic cancers in the Western world. If possible, initial cytoreductive surgery is the treatment of choice, followed by adjuvant chemotherapy, usually with a platinum/taxane combination. Increased survival has been recently reported in women who were given adjuvant chemotherapy weekly rather than at three-week intervals, which has been the standard. At our centre, we have been treating patients with advanced ovarian cancer with a dose-dense protocol since March 2010. Treatment is given in an outpatient setting on days 1, 8, and 15 of a 21-day cycle for six cycles. Carboplatin for an AUC of 5 mg/mL/min and paclitaxel 80mg/m² are given on day 1, followed by paclitaxel 80mg/m² on days 8 and 15. Our objective was to determine whether this protocol is a feasible alternative treatment in our population and whether or not the toxicity profile is acceptable. We performed a chart review of 46 patients undergoing treatment with dose-dense chemotherapy for advanced ovarian cancer. Demographic information, patient characteristics, adverse events, and treatment endpoints were recorded. Sixty-one percent of women completed the six-cycle protocol as planned with minimal interruption, which is comparable to the only previously reported trial using this regimen. The most common side effects of treatment were fatigue, neuropathy, and neutropenia. Supplementation with regular magnesium and granulocyte colony-stimulating factor reduced delays. Dose-dense paclitaxel with carboplatin chemotherapy for the treatment of advanced ovarian cancer shows promise in terms of progression-free and overall survival. We have shown this protocol to be practical and feasible in our population.

Serum anti-Mullerian hormone assessment of ovarian reserve and polycystic ovary syndrome status over the reproductive lifespan.

PubMed

Tremellen, Kelton; Zander-Fox, Deidre

2015-08-01

To determine normal ranges for serum anti-Mullerian hormone (AMH) using the new automated Elecsys AMH assay platform, with a view to establishing values that signify premature loss of ovarian reserve, increased risk for an excessive response during IVF stimulation and a likely diagnosis of polycystic ovary syndrome (PCOS). Serum AMH was measured by the Elecsys automated electrochemiluminescence assay in 654 women undergoing gynaecological assessment. Serum AMH levels peaked before 25 years of age, with mean AMH levels halving by 36 and falling to a quarter of their peak by 40 years of age. Overall, AMH results of 95% of patients with PCOS exceeded the 50th percentile for their age, with 72.1% having an AMH result in the top quartile for age. ROC analysis suggested that a serum AMH ≥36 pmol L(-1) is the best determinant of PCOS status (sensitivity 83.7% and specificity 82.3%). Serum AMH exhibited an excellent correlation with ultrasound-assessed antral follicle count (AFC) (r = 0.836, P < 0.0001), with a result of 20 pmol L(-1) corresponding to an AFC of 16 and, therefore, increased risk of ovarian hyperstimulation syndrome (OHSS) during IVF treatment. Serum AMH is a sensitive marker of age-related decline in ovarian reserve status. A serum AMH result >36 pmol L(-1) , or above the 75th percentile for age, is highly suggestive of a diagnosis of PCOS. A serum AMH result below the 10th percentile for age suggests accelerated loss of ovarian reserve, while an AMH result exceeding 20 pmol L(-1) suggests an increased risk of OHSS during IVF treatment. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Large, comparative, randomized double-blind trial confirming noninferiority of pregnancy rates for corifollitropin alfa compared with recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist controlled ovarian stimulation protocol in older patients undergoing in vitro fertilization.

PubMed

Boostanfar, Robert; Shapiro, Bruce; Levy, Michael; Rosenwaks, Zev; Witjes, Han; Stegmann, Barbara J; Elbers, Jolanda; Gordon, Keith; Mannaerts, Bernadette

2015-07-01

To compare corifollitropin alfa with recombinant FSH treatment in terms of the vital pregnancy rate in older patients undergoing IVF. Phase 3 randomized, double-blind, noninferiority trial. Multicenter trial. A total of 1,390 women aged 35-42 years. A single injection of 150 μg of corifollitropin alfa or daily 300 IU of recombinant FSH for the first 7 days then daily recombinant FSH until three follicles reach ≥17 mm in size. Ganirelix was started on stimulation day 5 up to and including the day of recombinant hCG administration. If available, two good quality embryos were transferred on day 3. Vital pregnancy rate (PR), number of oocytes, and live birth rate. Vital PRs per started cycle were 23.9% in the corifollitropin alfa group and 26.9% in the recombinant FSH group, with an estimated difference (95% confidence interval) of -3.0% (-7.4 to 1.4). The mean (SD) number of recovered oocytes per started cycle was 10.7 (7.2) and 10.3 (6.8) in the corifollitropin alfa and the recombinant FSH groups, respectively, with an estimated difference of 0.5 (-0.2 to 1.2). The live birth rates per started cycle were 21.3% in the corifollitropin alfa group and 23.4% in the recombinant FSH group, with an estimated difference (95% confidence interval) -2.3% (-6.5 to 1.9). The incidence of serious adverse events was 0.4% versus 2.7% in the corifollitropin alfa and recombinant FSH groups, respectively, and of ovarian hyperstimulation syndrome (OHSS; all grades) was 1.7% in both groups. Treatment with corifollitropin alfa was proven noninferior to daily recombinant FSH with respect to vital PRs, number of oocytes retrieved, and live birth rates, and was generally well tolerated. NCT01144416. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Randomized controlled trial of the effect of endometrial injury on implantation and clinical pregnancy rates during the first ICSI cycle.

PubMed

Maged, Ahmed M; Rashwan, Hamsa; AbdelAziz, Suzy; Ramadan, Wafaa; Mostafa, Walaa A I; Metwally, Ahmed A; Katta, Maha

2018-02-01

To assess whether endometrial injury in the cycle preceding controlled ovarian hyperstimulation during intracytoplasmic sperm injection (ICSI) improves the implantation and pregnancy rates. Between January 1, 2016, and March 31, 2017, a randomized controlled trial was conducted at a center in Egypt among 300 women who met inclusion criteria (first ICSI cycle, aged <40 years, day-3 follicle-stimulating hormone <10 IU/L, normal serum prolactin, no uterine cavity abnormality). The women were randomly allocated using a web-based system to undergo endometrial scratch in the cycle preceding controlled ovarian hyperstimulation (n=150) or to a control group (n=150). Only data analysts were masked to group assignment. The primary outcomes were the implantation and clinical pregnancy rates at 14 days and 4 weeks after embryo transfer, respectively. Analyses were by intention to treat. The implantation rate was significantly higher in the endometrial scratch group (41.3% [90/218]) than in the control group (30.0% [63/210]; P<0.001). The clinical pregnancy rate was also significantly higher in the endometrial scratch group (44.2% [61/138]) than in the control group (30.4% [41/135]; P<0.001). Endometrial injury in the cycle preceding the stimulation cycle improved implantation and pregnancy rates during ICSI. CLINICALTRIALS.GOV: NCT02660125. © 2017 International Federation of Gynecology and Obstetrics.

Chemotherapy-Induced Cognitive Impairment: A Novel Prospective Study of the Cognitive Effects of Platinum Taxane-Based Chemotherapy in Ovarian Cancer Patients

DTIC Science & Technology

2016-09-01

hope to generate new data on neurocognitive testing for CICI in gynecologic cancers, provide validation for counseling gynecologic oncology patients...cytoreductive surgery and adjuvant therapy are not included in this group .” Patients undergoing neoadjuvant chemotherapy will now be included in this group , as...representative group of patients to undergoing treatment for ovarian cancer and enhance accrual for this study. 4. Deleted exclusion criterion (previously

Stimulation of ovarian stem cells by follicle stimulating hormone and basic fibroblast growth factor during cortical tissue culture.

PubMed

Parte, Seema; Bhartiya, Deepa; Manjramkar, Dhananjay D; Chauhan, Anahita; Joshi, Amita

2013-04-01

Cryopreserved ovarian cortical tissue acts as a source of primordial follicles (PF) which can either be auto-transplanted or cultured in vitro to obtain mature oocytes. This offers a good opportunity to attain biological parenthood to individuals with gonadal insufficiency including cancer survivors. However, role of various intra- and extra-ovarian factors during PF growth initiation still remain poorly understood. Ovarian biology has assumed a different dimension due to emerging data on presence of pluripotent very small embryonic-like stem cells (VSELs) and ovarian germ stem cells (OGSCs) in ovary surface epithelium (OSE) and the concept of postnatal oogenesis. The present study was undertaken to decipher effect of follicle stimulating hormone (FSH) and basic fibroblast growth factor (bFGF) on the growth initiation of PF during organ culture with a focus on ovarian stem cells. Serum-free cultures of marmoset (n=3) and human (young and peri-menopausal) ovarian cortical tissue pieces were established. Cortical tissue pieces stimulated with FSH (0.5 IU/ml) or bFGF (100 ng/ml) were collected on Day 3 for histological and molecular studies. Gene transcripts specific for pluripotency (Oct-4A, Nanog), early germ cells (Oct-4, c-Kit, Vasa) and to reflect PF growth initiation (oocyte-specific Gdf-9 and Lhx8, and granulosa cells specific Amh) were studied by q-RTPCR. A prominent proliferation of OSE (which harbors stem cells) and transition of PF to primary follicles was observed after FSH and bFGF treatment. Ovarian stem cells were found to be released on the culture inserts and retained the potential to spontaneously differentiate into oocyte-like structures in extended cultures. q-RTPCR analysis revealed an increased expression of gene transcripts specific for VSELs, OGSCs and early germ cells suggestive of follicular transition. The present study shows that both FSH and bFGF stimulate stem cells present in OSE and also lead to PF growth initiation. Thus besides being a source of PF, cryopreserved ovarian cortical tissue could also be a source of stem cells which retain the ability to spontaneously differentiate into oocyte-like structures in vitro. Results provide a paradigm shift in the basic understanding of FSH action and also offer a new perspective to the field of oncofertility research.

Ovarian Cancer Is an Imported Disease: Fact or Fiction?

PubMed Central

Kuhn, Elisabetta; Kurman, Robert J.

2012-01-01

The cell of origin of ovarian cancer has been long debated. The current paradigm is that epithelial ovarian cancer (EOC) arises from the ovarian surface epithelium (OSE). OSE is composed of flat, nondescript cells more closely resembling the mesothelium lining the peritoneal cavity, with which it is continuous, rather than the various histologic types of ovarian carcinoma (serous, endometrioid, and clear cell carcinoma), which have a Müllerian phenotype. Accordingly, it has been argued that the OSE undergoes a process termed “metaplasia” to account for this profound morphologic transformation. Recent molecular and clinicopathologic studies not only have failed to support this hypothesis but also have provided evidence that EOC stems from Müllerian-derived extraovarian cells that involve the ovary secondarily, thereby calling into question the very existence of primary EOC. This new model of ovarian carcinogenesis proposes that fallopian tube epithelium (benign or malignant) implants on the ovary to give rise to both high-grade and low-grade serous carcinomas, and that endometrial tissue implants on the ovary and produces endometriosis, which can undergo malignant transformation into endometrioid and clear cell carcinoma. Thus, ultimately EOC is not ovarian in origin but rather is secondary, and it is logical to conclude that the only true primary ovarian neoplasms are germ cell and gonadal stromal tumors analogous to tumors in the testis. If this new model is confirmed, it has profound implications for the early detection and treatment of “ovarian cancer.” PMID:22506137

Comparison of luteal estradiol patch and gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation versus microdose gonadotropin-releasing hormone agonist protocol for patients with a history of poor in vitro fertilization outcomes.

PubMed

Weitzman, Vanessa N; Engmann, Lawrence; DiLuigi, Andrea; Maier, Donald; Nulsen, John; Benadiva, Claudio

2009-07-01

To compare IVF outcomes in poor-responder patients undergoing stimulation after luteal phase E(2) patch/GnRH antagonist (LPG) protocol versus microdose GnRH agonist protocol. Retrospective analysis. University-based IVF center. Forty-five women undergoing ovarian stimulation for IVF using the LPG protocol were compared with 76 women stimulated with the microdose GnRH agonist protocol from May 2005 to April 2006. Cancellation rate, number of oocytes retrieved, and clinical pregnancy rates. The mean number of oocytes (9.1 +/- 4.1 vs. 8.9 +/- 4.3) and mature oocytes (6.7 +/- 3.5 vs. 6.8 +/- 3.1) retrieved were similar, as were the fertilization rates (70.0% +/- 24.2% vs. 69.9% +/- 21.5%) and the number of embryos transferred (2.5 +/- 1.1 vs. 2.7 +/- 1.3). The cancellation rate was not significantly different between the groups (13/45, 28.9% vs. 23/76, 30.3%). Likewise, there were no significant differences among the implantation rate (15.0% vs. 12.5%), clinical pregnancy rate (43.3% vs. 45.1%), and ongoing pregnancy rate per transfer (33.3% vs. 26.0%) between both groups. This study demonstrates that the use of an E(2) patch and a GnRH antagonist during the preceding luteal phase in patients with a history of failed cycles can provide similar IVF outcomes when compared with the microdose GnRH agonist protocol.

Overexpression of SnoN/SkiL, amplified at the 3q26.2 locus, in ovarian cancers: A role in ovarian pathogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nanjundan, Meera; Cheng, Kwai Wa; Zhang, Fan

2008-07-18

High-resolution array comparative genomic hybridization of 235 serous epithelial ovarian cancers demonstrated a regional increase at 3q26.2 encompassing SnoN/SkiL, a coregulator of SMAD/TGF{beta} signaling. SnoN RNA transcripts were elevated in {approx}80% of advanced stage serous epithelial ovarian cancers. In both immortalized normal (TIOSE) and ovarian carcinoma cell lines (OVCA), SnoN RNA levels were increased by TGF{beta} stimulation and altered by LY294002 and JNK II inhibitor treatment suggesting that the PI3K and JNK signaling pathways may regulate TGF{beta}-induced increases in SnoN RNA. In TIOSE, SnoN protein levels were reduced 15min post TGF{beta}-stimulation, likely by proteosome-mediated degradation. In contrast, in OVCA, SnoNmore » levels were elevated 3h post-stimulation potentially as a result of inhibition of the proteosome. To elucidate the role of SnoN in ovarian tumorigenesis, we explored the effects of both increasing and decreasing SnoN levels. In both TIOSE and OVCA, SnoN siRNA decreased cell growth between 20 and 50% concurrent with increased p21 levels. In TIOSE, transient expression of SnoN repressed TGF{beta} induction of PAI-1 promoters with little effect on the p21 promoter or resultant cell growth. In contrast to the effects of transient expression, stable expression of SnoN in TIOSE led to growth arrest through induction of senescence. Collectively, these results implicate SnoN levels in multiple roles during ovarian carcinogenesis: promoting cellular proliferation in ovarian cancer cells and as a positive mediator of cell cycle arrest and senescence in non-transformed ovarian epithelial cells.« less

Short-term changes in hormonal profiles after laparoscopic ovarian laser evaporation compared with diagnostic laparoscopy for PCOS.

PubMed

Hendriks, M L; König, T; Korsen, T; Melgers, I; Dekker, J; Mijatovic, V; Schats, R; Hompes, P G A; Homburg, R; Kaaijk, E M; Twisk, J W R; Lambalk, C B

2014-11-01

Which reproductive endocrine changes are attributed exclusively to laparoscopic ovarian drilling in polycystic ovarian syndrome (PCOS)? Laser evaporation-specific endocrine effects were the prevention of an immediate increase in inhibin B and a sustained decrease in testosterone, androstenedione and anti-Müllarian hormone (AMH). All ovarian drilling procedures result in reproductive endocrine changes. It is not known which of these changes are the result of ovarian drilling and which are related to the surgery per se. This prospective controlled study was performed at an outpatient academic fertility clinic. Between 2007 and 2010, a total of 21 oligo- or amenorrheic PCOS patients were included. Included were oligo- or amenorrheic PCOS patients with all three of the Rotterdam criteria and luteinizing hormone (LH) >6.5 U/l. All PCOS patients had an indication for diagnostic surgery due to subfertility. There were 12 PCOS patients who chose to undergo ovarian laser evaporation (CO2 laser, 25 W, 20 times/ovary) and 9 PCOS who chose a diagnostic laparoscopy only (controls). Reproductive endocrinology was measured before, and until 5 days after, surgery, and four gonadotrophin-releasing hormone (GnRH) 'double pulse' tests were included. The main outcome measures were changes in reproductive endocrinology and pituitary sensitivity/priming to GnRH after laser evaporation compared with diagnostic laparoscopy only. In the first hours after surgery, both groups showed an increase in LH, follicle stimulating hormone, estrogen and a decrease in testosterone, androstenedione, AMH and insulin growth factor-1 (P < 0.05). Inhibin B increased in the laparoscopy only group (P < 0.05). In the first days after surgery, testosterone, androstenedione and AMH remained at lower than baseline levels exclusively in the laser group (P < 0.05). Pituitary sensitivity/priming to GnRH was not altered after either laser evaporation or laparoscopy only. The limitations of this study are the short follow-up period and the relatively small groups. The strength of this study is the integrally measured endocrine profiles in combination with an optimal control group of PCOS patients undergoing diagnostic laparoscopy only. Interestingly, most of the immediate endocrine changes after laser evaporation could be related to the surgical context and not to the ovarian drilling procedure itself. The study was funded by the Foundation of Scientific Research in Obstetrics and Gynaecology and the study medication, Lutrelef, was donated by Ferring, The Netherlands, Hoofdorphe There were no conflicts of interests mentioned by the authors. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Concurrent risk-reduction surgery in patients with increased lifetime risk for breast and ovarian cancer: an analysis of the National Surgical Quality Improvement Program (NSQIP) database.

PubMed

Elmi, Maryam; Azin, Arash; Elnahas, Ahmad; McCready, David R; Cil, Tulin D

2018-05-14

Patients with genetic susceptibility to breast and ovarian cancer are eligible for risk-reduction surgery. Surgical morbidity of risk-reduction mastectomy (RRM) with concurrent bilateral salpingo-oophorectomy (BSO) is unknown. Outcomes in these patients were compared to patients undergoing RRM without BSO using a large multi-institutional database. A retrospective cohort analysis was conducted using the American College of Surgeon's National Surgical Quality Improvement Program (NSQIP) 2007-2016 datasets, comparing postoperative morbidity between patients undergoing RRM with patients undergoing RRM with concurrent BSO. Patients with genetic susceptibility to breast/ovarian cancer undergoing risk-reduction surgery were identified. The primary outcome was 30-day postoperative major morbidity. Secondary outcomes included surgical site infections, reoperations, readmissions, length of stay, and venous thromboembolic events. A multivariate analysis was performed to determine predictors of postoperative morbidity and the adjusted effect of concurrent BSO on morbidity. Of the 5470 patients undergoing RRM, 149 (2.7%) underwent concurrent BSO. The overall rate of major morbidity and postoperative infections was 4.5% and 4.6%, respectively. There was no significant difference in the rate of postoperative major morbidity (4.5% vs 4.7%, p = 0.91) or any of the secondary outcomes between patients undergoing RRM without BSO vs. those undergoing RRM with concurrent BSO. Multivariable analysis showed Body Mass Index (OR 1.05; p < 0.001) and smoking (OR 1.78; p = 0.003) to be the only predictors associated with major morbidity. Neither immediate breast reconstruction (OR 1.02; p = 0.93) nor concurrent BSO (OR 0.94; p = 0.89) were associated with increased postoperative major morbidity. This study demonstrated that RRM with concurrent BSO was not associated with significant additional morbidity when compared to RRM without BSO. Therefore, this joint approach may be considered for select patients at risk for both breast and ovarian cancer.

The effects of cetrorelix and triptorelin on the viability and steroidogenesis of cultured human granulosa luteinized cells.

PubMed

Metallinou, Chryssa; Köster, Frank; Diedrich, Klaus; Nikolettos, Nikos; Asimakopoulos, Byron

2012-01-01

We investigated the effects of the gonadotropin-releasing hormone (GnRH) agonist triptorelin as well the GnRH antagonist cetrorelix those of on the viability and steroidogenesis in human granulosa luteinized (hGL) cell cultures. The hGL cells were obtained from 34 women undergoing ovarian stimulation for IVF treatment. The cells were cultured for 48 h with or without 1 nM or 3 nM of cetrorelix or triptorelin in serum-free media. The cell viability was evaluated by the MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assay. The concentrations of estradiol and progesterone in culture supernatants were measured by ELISA. Treatment with triptorelin slightly increased cell viability, whereas treatment with 3 nM cetrorelix led to a significant decrease. Estradiol concentrations were reduced with 3 nM triptorelin. Cultures treated with high-dose of either cetrorelix or triptorelin tended to secrete less progesterone than controls. Cetrorelix significantly reduces the viability of hGL cells. Triptorelin and cetrorelix may have minor effects on steroidogenesis. These results suggest that GnRH analogues may influence ovarian functions.

Melatonin in human preovulatory follicular fluid

NASA Technical Reports Server (NTRS)

Brzezinski, Amnon; Seibel, Machelle M.; Lynch, Harry J.; Deng, Mei-Hua; Wurtman, Richard J.

1987-01-01

Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCG to stimulate follicle formation. Blood samples were obtained by venipuncture 30 min or less after follicular aspiration. All of the follicular fluids contained melatonin, in concentrations (35.6 plus or minus 4.8 (plus or minus SEM) pg/mL) substantially higher than those in the corresponding serum (10.0 plus or minus 1.4 pg/mL). A positive correlation was found between follicular fluid and serum melatonin levels in each woman (r = 0.770; P less than 0.001). These observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.

Fatal ovarian hyperstimulation syndrome in an anonymous egg donor.

PubMed

Pooniya, Shashank; Behera, C; Mridha, A R; Bhardwaj, D N; Millo, Tabin

2016-12-01

Ovarian hyperstimulation syndrome is a rare, but potentially life-threatening iatrogenic disorder arising from ovulation induction or ovarian hyperstimulation for assisted reproduction techniques. We report a case of a 26-year-old multiparous woman, an anonymous egg donor, who died a few hours after undergoing a procedure to donate eggs at an in vitro fertilization clinic. Her husband alleged that medical negligence had led to her death. The autopsy confirmed death due to ovarian hyperstimulation syndrome. We know of no previous descriptions of fatal ovarian hyperstimulation syndrome in an anonymous egg donor in medico-legal literature. © The Author(s) 2016.

Estrogen Responsiveness of the TFIID Subunit TAF4B in the Normal Mouse Ovary and in Ovarian Tumors1

PubMed Central

Wardell, Jennifer R.; Hodgkinson, Kendra M.; Binder, April K.; Seymour, Kimberly A.; Korach, Kenneth S.; Vanderhyden, Barbara C.; Freiman, Richard N.

2013-01-01

ABSTRACT Estrogen signaling in the ovary is a fundamental component of normal ovarian function, and evidence also indicates that excessive estrogen is a risk factor for ovarian cancer. We have previously demonstrated that the gonadally enriched TFIID subunit TAF4B, a paralog of the general transcription factor TAF4A, is required for fertility in mice and for the proliferation of ovarian granulosa cells following hormonal stimulation. However, the relationship between TAF4B and estrogen signaling in the normal ovary or during ovarian tumor initiation and progression has yet to be defined. Herein, we show that Taf4b mRNA and TAF4B protein, but not Taf4a mRNA or TAF4A protein, are increased in whole ovaries and granulosa cells of the ovary after exposure to 17beta-estradiol or the synthetic estrogen diethylstilbestrol and that this response occurs within hours after stimulation. Furthermore, this increase occurs via nuclear estrogen receptors both in vivo and in a mouse granulosa cancer cell line, NT-1. We observe a significant increase in Taf4b mRNA in estrogen-supplemented mouse ovarian tumors, which correlates with diminished survival of these mice. These data highlight the novel response of the general transcription factor TAF4B to estrogen in the normal ovary and during ovarian tumor progression in the mouse, suggesting its potential role in regulating actions downstream of estrogen stimulation. PMID:24068106

Estrogen responsiveness of the TFIID subunit TAF4B in the normal mouse ovary and in ovarian tumors.

PubMed

Wardell, Jennifer R; Hodgkinson, Kendra M; Binder, April K; Seymour, Kimberly A; Korach, Kenneth S; Vanderhyden, Barbara C; Freiman, Richard N

2013-11-01

Estrogen signaling in the ovary is a fundamental component of normal ovarian function, and evidence also indicates that excessive estrogen is a risk factor for ovarian cancer. We have previously demonstrated that the gonadally enriched TFIID subunit TAF4B, a paralog of the general transcription factor TAF4A, is required for fertility in mice and for the proliferation of ovarian granulosa cells following hormonal stimulation. However, the relationship between TAF4B and estrogen signaling in the normal ovary or during ovarian tumor initiation and progression has yet to be defined. Herein, we show that Taf4b mRNA and TAF4B protein, but not Taf4a mRNA or TAF4A protein, are increased in whole ovaries and granulosa cells of the ovary after exposure to 17beta-estradiol or the synthetic estrogen diethylstilbestrol and that this response occurs within hours after stimulation. Furthermore, this increase occurs via nuclear estrogen receptors both in vivo and in a mouse granulosa cancer cell line, NT-1. We observe a significant increase in Taf4b mRNA in estrogen-supplemented mouse ovarian tumors, which correlates with diminished survival of these mice. These data highlight the novel response of the general transcription factor TAF4B to estrogen in the normal ovary and during ovarian tumor progression in the mouse, suggesting its potential role in regulating actions downstream of estrogen stimulation.

Protein concentration in pre-ovulatory follicular fluid related to ovarian stimulation.

PubMed

Suchanek, E; Mujkic-Klaric, A; Grizelj, V; Simunic, V; Kopjar, B

1990-05-01

Sixty follicular fluids obtained from 26 women with either clomiphene citrate and human menopausal gonadotropins (hMG) or hMG-induced ovulation were analyzed for the contents of total proteins, fibrinogen, plasminogen, antithrombin III, ceruloplasmin, alpha-2 macroglobulin, alpha-1 antitrypsin and immunoglobulins (IgG, IgA, IgM). Concentrations of these proteins was correlated to the type of ovarian follicle growth induction. Follicular fluids from patients stimulated with clomiphene citrate-hMG contained significantly higher concentrations of ceruloplasmin than those treated with hMG alone. No significant differences in the concentrations of other proteins were noted between the two types of ovarian induction. A multivariate data analysis resulted in three Varimax factors (VRX I) suggesting that proteins with antiprotease activity in the follicular fluid may play a role in human follicle maturation. Follicular fluid Ig may reflect the degree of follicular wall permeability under hMG treatment. Accordingly, it may be assumed that a combination of different proteins described by VRX factors could be used for evaluation of ovarian stimulation.

[Corifollitropin alfa compared to daily FSH in controlled ovarian stimulation for oocyte donors].

PubMed

Benchabane, M; Santulli, P; Maignien, C; Bourdon, M; De Ziegler, D; Chapron, C; Gayet, V

2017-02-01

To demonstrate that corifollitropin alfa is as effective as daily FSH in controlled ovarian stimulation of oocyte donors. From January 2013 to October 2015, 77 cycles controlled ovarian stimulation, derived from a continuous cohort of 77 oocyte donors, were analyzed. After synchronization by oestroprogestatif or estrogens, ovarian stimulation was started by corifollitropin alfa (Group corifollitropin alfa) or by daily FSH (Group daily FSH). In both groups, a GnRH antagonist was used for the prevention of premature surge of luteinizing hormone (LH). The induction of ovulation was induced by a GnRH agonist. The duration of treatment, estradiol rate, numbers of mature oocytes, fertilization rate, clinical and ongoing pregnancies rates were evaluated in the two groups. There is no difference for the age, the markers of ovarian reserve and the duration of treatment. The average rate of estradiol on the eighth day of the stimulation is lower for the corifollitropin alfa (845±694.5 vs 1742±1177.3, P<0.001), there is no difference in the number of mature oocytes retrieved (14.4 vs 13.4, P=0.979), with a fertilization rate significantly higher in the corifollitropin alfa group (59.8% vs 49.3%, P<0.001). The rate of ongoing pregnancies is higher but without reaching significant difference in this same group (36.6% vs 26%, P=0.277). As compared to daily FSH, corifollitropin alfa, in oocyte donors offers, advantages in terms of ease of use with identical efficiency. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Association of Exon 10A and 10B inactivating mutation of follicle stimulating hormone receptor gene (FSHR) and Polycystic Ovarian Syndrome in Vellore cohort

NASA Astrophysics Data System (ADS)

Sekar, Nishu; Kulkarni, Rucha; Ozalkar, Sharvari; Prabhu, Yogamaya D.; Renu, Kaviyarasi; Ramgir, Shalaka S.; Abilash, V. G.

2017-11-01

Polycystic ovarian syndrome is the most common heterogenous endocrine disorder in women. Follicle stimulating hormone receptor is associated with normal development as well as maturation of follicles and triggers estrogen production in granulosa cells of the ovary. Inactivating mutation in FSHR gene correlated with reduction of ovarian function in women is due to damage to receptor function. This study aims to investigate whether inactivating mutations, in follicle stimulating hormone receptor gene is related to polycystic ovarian morphology in women with PCOS. Genomic DNA isolated from 15 subjects from Sandhya Hospital, Vellore (10 patients with PCOS and 5 healthy controls) was taken for this study. Patient data included a clinical report, hormonal levels, and ovarian morphological details. DNA isolation was followed by DNA amplification by polymerase chain reaction using Exon 10 A and Exon 10 B primers. The PCR-RFLP analysis was performed using Dde1 restriction enzyme. Here we discuss inactivating mutation found in Exon 10 of FSHR gene in patients with PCOS.The absence of inactivating mutation was observed through PCR-RFLP study on Exon 10A and Exon 10B.

Induction of ovarian function by using short-term human menopausal gonadotrophin in patients with ovarian failure following cytotoxic chemotherapy for haematological malignancy.

PubMed

Chatterjee, R; Mills, W; Katz, M; McGarrigle, H H; Goldstone, A H

1993-07-01

Currently no treatment has proved successful in inducing ovarian steroidogenic and/or gametogenic recovery in patients with haematological malignancies treated by cytotoxic chemotherapy once biochemical failure becomes manifest i.e., when FSH levels exceed 40 IU/L. This paper reports two such cases with classical biochemical ovarian failure in which ovarian function was induced by brief stimulation with Human Menopausal Gonadotrophin (HMG).

Activation of dormant ovarian follicles to generate mature eggs.

PubMed

Li, Jing; Kawamura, Kazuhiro; Cheng, Yuan; Liu, Shuang; Klein, Cynthia; Liu, Shu; Duan, En-Kui; Hsueh, Aaron J W

2010-06-01

Although multiple follicles are present in mammalian ovaries, most of them remain dormant for years or decades. During reproductive life, some follicles are activated for development. Genetically modified mouse models with oocyte-specific deletion of genes in the PTEN-PI3K-Akt-Foxo3 pathway exhibited premature activation of all dormant follicles. Using an inhibitor of the Phosphatase with TENsin homology deleted in chromosome 10 (PTEN) phosphatase and a PI3K activating peptide, we found that short-term treatment of neonatal mouse ovaries increased nuclear exclusion of Foxo3 in primordial oocytes. After transplantation under kidney capsules of ovariectomized hosts, treated follicles developed to the preovulatory stage with mature eggs displaying normal epigenetic changes of imprinted genes. After in vitro fertilization and embryo transfer, healthy progeny with proven fertility were delivered. Human ovarian cortical fragments from cancer patients were also treated with the PTEN inhibitor. After xeno-transplantation to immune-deficient mice for 6 months, primordial follicles developed to the preovulatory stage with oocytes capable of undergoing nuclear maturation. Major differences between male and female mammals are unlimited number of sperm and paucity of mature oocytes. Thus, short-term in vitro activation of dormant ovarian follicles after stimulation of the PI3K-Akt pathway allows the generation of a large supply of mature female germ cells for future treatment of infertile women with a diminishing ovarian reserve and for cancer patients with cryo-preserved ovaries. Generation of a large number of human oocytes also facilitates future derivation of embryonic stem cells for regenerative medicine.

Kisspeptin regulates ovarian steroidogenesis during delayed embryonic development in the fruit bat, Cynopterus sphinx.

PubMed

Anuradha; Krishna, Amitabh

2017-11-01

Cynopterus sphinx, a fruit bat, undergoes delayed embryonic development during the winter months, a period that corresponds to low levels of progesterone and estradiol synthesis by the ovary. Kisspeptins (KPs) are a group of neuropeptide hormones that act via G-protein coupled receptor 54 (GPR54) to stimulate hypothalamic secretion of Gonadotropin-releasing hormone, thereby regulating ovarian steroidogenesis, folliculogenesis, and ovulation. GPR54 is also expressed in the ovary, suggesting a direct role for KPs in ovarian steroidogenesis. The aim of present study was to determine if a low serum level of KP is responsible for reduced progesterone and estradiol levels during the period of delayed embryonic development in C. sphinx. Indeed, low serum KP abundance corresponded to reduced expression of GPR54 in ovarian luteal cells during the period of delayed development compared to normal development. In vitro and in vivo treatment with KP increased GPR54 abundance, via Extracellular signal regulated kinase and its downstream mediators, leading to increased progesterone synthesis in the ovary during delayed embryonic development. KP treatment also increased cholesterol uptake and elevated expression of Luteinizing hormone receptor and Steroid acute regulatory protein in the ovary, suggesting that elevation in circulating KP during delayed embryonic development may reactivate luteal activity. KPs may also enhance cell survival (BCL-2, reduced Caspase 3 activity) and angiogenesis (Vascular endothelium growth factor) during this period. The findings of this study thus demonstrate a regulatory role for KPs in the maintenance of luteal steroidogenesis during pregnancy in C. sphinx. © 2017 Wiley Periodicals, Inc.

Thalidomide results in diminished ovarian reserve in reproductive age female IBD patients

PubMed Central

Peng, Xiang; Zhi, Min; Wei, Ming; Li, Ting-Ting; Zhang, Min; Zhang, Yuan-Qi; He, Huan; Su, Mingli; Wang, Wei; Chen, Jun-rong; Tang, Jian; Gao, Xiang; Hu, Pin-Jin; Liang, Xiao-Yan

2017-01-01

Abstract The effectiveness of thalidomide in treating inflammatory bowel disease (IBD) has been widely recognized. Meanwhile, many serious adverse drug reactions have been observed, but no know reports on ovarian reserve function. Female patients, ranging in age between 18 and 40, were referred to our institution to undergo sex hormone detection and ultrasonic scanning for ovarian function assessment, between February 1, 2016 and September 31, 2016. Thirty-three patients treated with thalidomide (group A), 73 patients without thalidomide (group B), and 78 healthy women as control were studied. Menstrual disorder was higher in group A than group B (78.8% vs 57.2%, P < 0.05), and both groups were higher than control group 33.3%, P < 0.05. Anti-Mullerian hormone (AMH) levels and antral follicle count (AFC) in group A were lower than group B, P < 0.05, while estradiol (E2) and follicle-stimulating hormone (FSH) levels were no different between 2 groups. Crohn Disease Endoscopic Index of Severity (CDEIS) and thalidomide were the independent risk factors in diminished ovarian reserve (DOR), and when dose reached 75 mg/day, 5 g total, or when treatment time reached 10 months respectively. These influence may increasing (P < 0.05), but they may recover after stopping (P < 0.05). Thalidomide was an independent risk factor leading to DOR in female IBD patients, the influence may increasing when daily dose and accumulated dose reached 75 mg/day and 5 g total dose, but may be reversed by stopping. PMID:28538364

Controlled ovarian hyperstimulation with sequential letrozole co-treatment in normo/high responders.

PubMed

Ecemis, Tolga; Tasci, Yasemin; Caglar, Gamze Sinem

2016-01-01

To investigate the effect of co-administration of letrozole in an ovarian stimulation protocol using recombinant FSH and GnRH antagonists for ICSI in normo/high responders. Computerized data of 320 antagonist ICSI/ET cycles with or without letrozole were retrospectively analyzed. In 105 cases, letrozole (5 mg/day) was started at the second day of the cycle continued for 5 days. At the second day of letrozole, gonadotropins were added. The remaining 215 cases were stimulated with recombinant FSH only. In all cases on day 6, GnRH antagonist was started. Ovarian stimulation protocols with or without letrozole were compared for cycle outcome parameters. In cycles with letrozole, significantly lower gonadotropin consumption and lower peak estradiol levels were found. In cycles with letrozole, mean number of metaphase II and fertilized oocytes retrieved were significantly higher compared to cycles without letrozole. The pregnancy and clinical pregnancy rates were similar. Should the number of oocytes retrieved being higher in letrozole group might indicate that letrozole might contribute to successful ovarian stimulation with a lower dosage of gonadotropins. Despite the lower peak estradiol levels, pregnancy rates being similar to other group also support the idea that letrozole can contribute to normal potential of implantation.

Comparison of corifollitropin alfa and daily recombinant follicle-stimulating hormone in poor responder patients undergoing in vitro fertilization cycles.

PubMed

Akarsu, Süleyman; Demir, Sibel; Gode, Funda; Işık, Ahmet Zeki

2017-12-01

The aim of this study was to compare the effect of corifollitropin alfa (CFA) and recombinant follicle-stimulating hormone (rFSH) in poor-responder patients undergoing antagonist cycles. The study was a retrospective analysis of the treatment results of 214 poor responder patients who had been admitted to the In Vitro Fertilization Unit of İzmir Medical Park Hospital between November 2014 and November 2016. Intracytoplasmic sperm injections were performed in 38 patients (group 1) with CFA, and the remaining 176 (group 2) with rFSH for controlled ovarian hyperstimulation. The age, body mass index, anti-müllerian hormone level, duration of infertility, duration of induction and antral follicle number were similar in the two groups. There was no difference in the total aspirated oocyte counts, mature oocyte ratio, fertilization rate, implantation rate, and clinical pregnancy rates between the two groups. The implantation rate was 9/38 (23.6%) in group 1 and 42/176 (23.8%) in group 2, whereas the clinical pregnancy rates were 16.3% and 17.2%, respectively. No difference was found in terms of oocyte count, fertilization rate, implantation rate, and clinical pregnancy rates of CFA or rFSH use in the antagonist cycles in poor-responder patients.

Symptom clustering and quality of life in patients with ovarian cancer undergoing chemotherapy.

PubMed

Nho, Ju-Hee; Reul Kim, Sung; Nam, Joo-Hyun

2017-10-01

The symptom clusters in patients with ovarian cancer undergoing chemotherapy have not been well evaluated. We investigated the symptom clusters and effects of symptom clusters on the quality of life of patients with ovarian cancer. We recruited 210 ovarian cancer patients being treated with chemotherapy and used a descriptive cross-sectional study design to collect information on their symptoms. To determine inter-relationships among symptoms, a principal component analysis with varimax rotation was performed based on the patient's symptoms (fatigue, pain, sleep disturbance, chemotherapy-induced peripheral neuropathy, anxiety, depression, and sexual dysfunction). All patients had experienced at least two domains of concurrent symptoms, and there were two types of symptom clusters. The first symptom cluster consisted of anxiety, depression, fatigue, and sleep disturbance symptoms, while the second symptom cluster consisted of pain and chemotherapy-induced peripheral neuropathy symptoms. Our subgroup cluster analysis showed that ovarian cancer patients with higher-scoring symptoms had significantly poorer quality of life in both symptom cluster 1 and 2 subgroups, with subgroup-specific patterns. The symptom clusters were different depending on age, age at disease onset, disease duration, recurrence, and performance status of patients with ovarian cancer. In addition, ovarian cancer patients experienced different symptom clusters according to cancer stage. The current study demonstrated that there is a specific pattern of symptom clusters, and symptom clusters negatively influence the quality of life in patients with ovarian cancer. Identifying symptom clusters of ovarian cancer patients may have clinical implications in improving symptom management. Copyright © 2017 Elsevier Ltd. All rights reserved.

Progestin-primed milder stimulation with clomiphene citrate yields fewer oocytes and suboptimal pregnancy outcomes compared with the standard progestin-primed ovarian stimulation in infertile women with polycystic ovarian syndrome.

PubMed

Ye, Hongjuan; Tian, Hui; He, Wen; Lyu, Qifeng; Kuang, Yanping; Chen, Qiuju; Sun, Lihua

2018-05-28

Oral progestin has recently been used to prevent premature LH surges in ovarian stimulation, and this progestin-primed ovarian stimulation (PPOS) is effective and safe in patients with different ovarian reserves. The current data are lacking regarding how to individualize the gonadotropin dose and regimen for women with polycystic ovarian syndrome (PCOS). A retrospective cohort trial was performed to evaluate the efficacy of progestin-primed milder stimulation with clomiphene citrate (CC) compared to the standard progestin-primed ovarian stimulation (PPOS) protocol for infertile women with PCOS. A total of 220 PCOS women were collected and classified into the study group (HMG 150 IU/d + CC 50 mg/d + MPA 10 mg/d) and control group (HMG 225 IU/d + MPA 10 mg/d). Ovulation was triggered by GnRH agonist 0.1 mg and hCG 1000 IU when dominant follicles matured. Viable embryos were cryopreserved for later transfer. The primary endpoint was the ongoing pregnancy rate. Secondary outcomes included the cycle characteristics and the live birth rate. The study group consumed less HMG (1470.0 ± 360.1 IU vs 1943.8 ± 372.0 IU, P < 0.001) and harvested fewer oocytes than the control group (12.2 ± 7.4 vs 18.2 ± 9.7, P < 0.001). The study group showed a higher mid-follicular LH concentration (4.49 ± 2.49 mIU/ml vs 2.52 ± 2.09 mIU/ml, P < 0.05) but no endogenous LH surge. No between-group difference was found in the incidence of ovarian hyperstimulation syndrome (OHSS) (0.91% vs 0.91%, P > 0.05). The cumulative ongoing pregnancy rate and live birth rate per patient were lower but did not reach significance compared with the control group (71.8% vs 81.8 and 64.5% vs 75.5%, respectively, both P > 0.05). The milder PPOS with CC in PCOS women led to lower oocyte yields and suboptimal pregnancy outcomes compared to the standard PPOS treatment. The two regimens both achieved a low incidence of OHSS. The results from the CC combination regimen provide a new insight for developing a more patient-friendly protocol for PCOS women.

Fertility preservation in the transgender patient: expanding oncofertility care beyond cancer.

PubMed

Wallace, Sumer Allensworth; Blough, Kiara L; Kondapalli, Laxmi A

2014-01-01

While the field of oncofertility raised awareness about fertility concerns in oncology patients, new applications for fertility preservation are emerging, such as transgender medicine. As transgender medicine evolves, the number of individuals seeking gender reassignment hormone therapy is drastically increasing, generating a population of patients with unmet fertility needs and unknown reproductive potential. We present the first case report of a female-to-male (FtM) transgender patient to undergo oocyte cryopreservation before initiating androgen therapy. Our patient is a 17-year-old FtM transgender person undergoing gender transition throughout adolescence with an endocrinologist. The patient wished to complete androgen therapy before starting his first year of college to avoid gender ambiguity. After extensive consultation and psychological assessment, the patient was considered an appropriate candidate and proceeded with oocyte cryopreservation. He underwent baseline fertility testing followed by successful ovarian stimulation and surgical retrieval. We recommend that a discussion of reproductive health concerns and fertility preservation options be incorporated into the comprehensive care of transgender patients.

The use of berberine for women with polycystic ovary syndrome undergoing IVF treatment.

PubMed

An, Yuan; Sun, Zhuangzhuang; Zhang, Yajuan; Liu, Bin; Guan, Yuanyuan; Lu, Meisong

2014-03-01

Previous studies have indicated that berberine is an effective insulin sensitizer with comparable activity to metformin (Diabetes 2006, 55, 2256). Reduced insulin sensitivity is reportedly a factor adversely affecting the outcome of IVF in patients with polycystic ovary syndrome (PCOS) (Human Reproduction 2006, 21, 1416). Our objective was to evaluate the clinical, metabolic and endocrine effects of berberine vs metformin in PCOS women scheduled for IVF treatment and to explore the potential benefits to the IVF process. We performed a prospective study in 150 infertile women with PCOS undergoing IVF treatment. Patients were randomized to receive berberine, metformin or placebo tablets for 3 months before ovarian stimulation. The clinical, endocrine, metabolic parameters and the outcome of IVF. Compared with placebo, greater reductions in total testosterone, free androgen index, fasting glucose, fasting insulin and HOMA-IR, and increases in SHBG, were observed in the berberine and metformin groups. Three months of treatment with berberine or metformin before the IVF cycle increased the pregnancy rate and reduced the incidence of severe ovarian hyperstimulation syndrome. Furthermore, treatment with berberine, in comparison with metformin, was associated with decreases in BMI, lipid parameters and total FSH requirement, and an increase in live birth rate with fewer gastrointestinal adverse events. Berberine and metformin treatments prior to IVF improved the pregnancy outcome by normalizing the clinical, endocrine and metabolic parameters in PCOS women. Berberine has a more pronounced therapeutic effect and achieved more live births with fewer side effects than metformin. © 2013 John Wiley & Sons Ltd.

Enlightenment about the new Architect-i2000 estradiol (Abbott Laboratories) immunoassay during in vitro fertilization.

PubMed

Taieb, Joëlle; Mendez Lozano, Daniel H; Benattar, Clarisse; Messaoudi, Chérif; Poüs, Christian

2007-12-01

We assessed a new estradiol (E2) immunoassay on the Architect-i2000 (Abbott Laboratories) for monitoring ovulation stimulation for IVF-ET and re-establishing clinical cut-off points. The method has been modified to improve E2 measurements especially at normal and low concentrations. E2 was determined for 552 samples, from 83 women, presenting normal follicular status and undergoing 100 cycles of IVF treatment. We assessed the value of this assay for down-regulation of E2 concentration limit using gonadoliberin-releasing hormone agonist (GnRHa), and monitoring of the ovarian hyperstimulation, expected range of E2 per mature follicle prior to the administration of exogenous hCG and day 3 concentration limit. We compared results with our routine method (E2-6II Advia-Centaur; Siemens-Diagnostics) for which decision-making values were known. Considering E2 concentrations obtained with the new Architect-i2000 assay for patients treated with GnRHa for 2 weeks, the cutoff-point for ovarian down-regulation should be set down at 110 pmol/L to maintain 100% of sensitivity. Considering day 3 concentration limit determination, results were not significantly different from those obtained with our routine method. The mean E2 values per mature follicle fell into the range generally expected. E2 determination with the new E2 Architect-i2000 assay could be used to monitor ovulation, in patients undergoing IVF-ET, in combination with transvaginal ultrasound.

Antral follicle counts are strongly associated with live-birth rates after assisted reproduction, with superior treatment outcome in women with polycystic ovaries.

PubMed

Holte, Jan; Brodin, Thomas; Berglund, Lars; Hadziosmanovic, Nermin; Olovsson, Matts; Bergh, Torbjörn

2011-09-01

To evaluate the association of antral follicle count (AFC) with in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) outcome in a large unselected cohort of patients covering the entire range of AFC. Prospective observational study. University-affiliated private infertility center. 2,092 women undergoing 4,308 IVF-ICSI cycles. AFC analyzed for associations with treatment outcome and statistically adjusted for repeated treatments and age. Pregnancy rate, live-birth rate, and stimulation outcome parameters. The AFC was log-normally distributed. Pregnancy rates and live-birth rates were positively associated with AFC in a log-linear way, leveling out above AFC ∼30. Treatment outcome was superior among women with polycystic ovaries, independent from ovulatory status. The findings were significant also after adjustment for age and number of oocytes retrieved. Pregnancy and live-birth rates are log-linearly related to AFC. Polycystic ovaries, most often excluded from studies on ovarian reserve, fit as one extreme in the spectrum of AFC; a low count constitutes the other extreme, with the lowest ovarian reserve and poor treatment outcome. The findings remained statistically significant also after adjustment for the number of oocytes retrieved, suggesting this measure of ovarian reserve comprises information on oocyte quality and not only quantity. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Role of GPER on proliferation, migration and invasion in ligand-independent manner in human ovarian cancer cell line SKOV3.

PubMed

Yan, Yan; Jiang, Xueli; Zhao, Ying; Wen, Haixia; Liu, Guoyi

2015-12-01

G protein-coupled estrogen receptor (GPER) is identified as a critical estrogen receptor, in addition to the classical estrogen receptors ERα and ERβ. In ERα-negative ovarian cancer cells, our previous studies have found that estrogen stimulated cell proliferation and metastasis via GPER. However, the ligand-independent function of GPER in ovarian cancer cells is still not clear. Herein, we describe that GPER has a co-expression with ERα and ERβ, which are first determined in SKOV3 ovarian cancer cell line. In the absence of estrogen, GPER depletion by specific siRNA inhibits the proliferation, migration and invasion of SKOV3 cells. Whereas abrogation of ERα or ERβ by specific antagonist MPP and PHTPP has the opposite effects for stimulation of cell growth. Markedly, GPER knockdown attenuates MPP or PHTPP-induced cell proliferation, migration and invasion. Furthermore, GPER modulates protein expression of the cell cycle critical components, c-fos and cyclin D1 and factors for cancer cell invasion and metastasis, matrix metalloproteinase 2 (MMP-2) and MMP-9. These findings establish that GPER ligand-independently stimulates the proliferation, migration and invasion of SKOV3 cells. Knockdown of GPER attenuates the progression of ovarian cancer that caused by functional loss of ERα or ERβ. Targeting GPER provides new aspect as a potential therapeutic strategy in ovarian cancer. Copyright © 2015 John Wiley & Sons, Ltd.

Minimally Invasive Surgical Staging for Ovarian Carcinoma: A Propensity-Matched Comparison With Traditional Open Surgery.

PubMed

Ditto, Antonino; Bogani, Giorgio; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Scaffa, Cono; Indini, Alice; Leone Roberti Maggiore, Umberto; Lorusso, Domenica; Raspagliesi, Francesco

2017-01-01

Growing evidence supports the safety of a laparoscopic approach for patients affected by apparent early-stage ovarian cancer. However, no well-designed studies comparing laparoscopic and open surgical staging are available. In the present investigation we aimed to provide a balanced long-term comparison between these 2 approaches. Retrospective study (Canadian Task Force classification II-2). Tertiary center. Data of consecutive patients affected by early-stage ovarian cancer who had laparoscopic staging were matched 1:1 with a cohort of patients undergoing open surgical staging. The matching was conducted by a propensity-score comparison. Laparoscopic and open surgical staging. Fifty patient pairs (100 patients: 50 undergoing laparoscopic staging vs 50 undergoing open surgical staging) were included. Demographic and baseline oncologic characteristics were balanced between groups (p > .2). We observed that patients undergoing laparoscopic staging experienced longer operative time (207.2 [71.6] minutes vs 180.7 [47.0] minutes; p = .04), lower blood loss (150 [52.7] mL vs 339.8 [225.9] mL; p < .001), and shorter length of hospital stay (4.0 [2.6] days vs 6.1 [1.6] days; p < .001) compared with patients undergoing open surgical staging. No conversion to open surgery occurred. Complication rate was similar between groups. No difference in survival outcomes were observed, after a mean (SD) follow-up of 49.5 (64) and 52.6 (31.7) months after laparoscopic and open surgical staging, respectively. Our findings suggest that the implementation of minimally invasive staging does not influence survival outcomes of patients affected by early-stage ovarian cancer. Laparoscopic staging improved patient outcomes, reducing length of hospital stay. Further large prospective studies are warranted. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance

PubMed Central

Meirelles, Katia; Benedict, Leo Andrew; Dombkowski, David; Pepin, David; Preffer, Frederic I.; Teixeira, Jose; Tanwar, Pradeep Singh; Young, Robert H.; MacLaughlin, David T.; Donahoe, Patricia K.; Wei, Xiaolong

2012-01-01

Women with late-stage ovarian cancer usually develop chemotherapeutic-resistant recurrence. It has been theorized that a rare cancer stem cell, which is responsible for the growth and maintenance of the tumor, is also resistant to conventional chemotherapeutics. We have isolated from multiple ovarian cancer cell lines an ovarian cancer stem cell-enriched population marked by CD44, CD24, and Epcam (3+) and by negative selection for Ecadherin (Ecad−) that comprises less than 1% of cancer cells and has increased colony formation and shorter tumor-free intervals in vivo after limiting dilution. Surprisingly, these cells are not only resistant to chemotherapeutics such as doxorubicin, but also are stimulated by it, as evidenced by the significantly increased number of colonies in treated 3+Ecad− cells. Similarly, proliferation of the 3+Ecad− cells in monolayer increased with treatment, by either doxorubicin or cisplatin, compared with the unseparated or cancer stem cell-depleted 3−Ecad+ cells. However, these cells are sensitive to Mullerian inhibiting substance (MIS), which decreased colony formation. MIS inhibits ovarian cancer cells by inducing G1 arrest of the 3+Ecad− subpopulation through the induction of cyclin-dependent kinase inhibitors. 3+Ecad− cells selectively expressed LIN28, which colocalized by immunofluorescence with the 3+ cancer stem cell markers in the human ovarian carcinoma cell line, OVCAR-5, and is also highly expressed in transgenic murine models of ovarian cancer and in other human ovarian cancer cell lines. These results suggest that chemotherapeutics may be stimulative to cancer stem cells and that selective inhibition of these cells by treating with MIS or targeting LIN28 should be considered in the development of therapeutics. PMID:22308459

Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance.

PubMed

Meirelles, Katia; Benedict, Leo Andrew; Dombkowski, David; Pepin, David; Preffer, Frederic I; Teixeira, Jose; Tanwar, Pradeep Singh; Young, Robert H; MacLaughlin, David T; Donahoe, Patricia K; Wei, Xiaolong

2012-02-14

Women with late-stage ovarian cancer usually develop chemotherapeutic-resistant recurrence. It has been theorized that a rare cancer stem cell, which is responsible for the growth and maintenance of the tumor, is also resistant to conventional chemotherapeutics. We have isolated from multiple ovarian cancer cell lines an ovarian cancer stem cell-enriched population marked by CD44, CD24, and Epcam (3+) and by negative selection for Ecadherin (Ecad-) that comprises less than 1% of cancer cells and has increased colony formation and shorter tumor-free intervals in vivo after limiting dilution. Surprisingly, these cells are not only resistant to chemotherapeutics such as doxorubicin, but also are stimulated by it, as evidenced by the significantly increased number of colonies in treated 3+Ecad- cells. Similarly, proliferation of the 3+Ecad- cells in monolayer increased with treatment, by either doxorubicin or cisplatin, compared with the unseparated or cancer stem cell-depleted 3-Ecad+ cells. However, these cells are sensitive to Mullerian inhibiting substance (MIS), which decreased colony formation. MIS inhibits ovarian cancer cells by inducing G1 arrest of the 3+Ecad- subpopulation through the induction of cyclin-dependent kinase inhibitors. 3+Ecad- cells selectively expressed LIN28, which colocalized by immunofluorescence with the 3+ cancer stem cell markers in the human ovarian carcinoma cell line, OVCAR-5, and is also highly expressed in transgenic murine models of ovarian cancer and in other human ovarian cancer cell lines. These results suggest that chemotherapeutics may be stimulative to cancer stem cells and that selective inhibition of these cells by treating with MIS or targeting LIN28 should be considered in the development of therapeutics.

Changes in ovarian reserve and ovarian blood flow in patients with polycystic ovary syndrome following laparoscopic ovarian drilling.

PubMed

Kamal, Nasser; Sanad, Zakaria; Elkelani, Osama; Rezk, Mohamed; Shawky, Mohamed; Sharaf, Abd-Elbar

2018-04-10

This prospective cohort study was conducted on 80 patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome undergoing laparoscopic ovarian drilling (LOD). Pre- and post-LOD ovarian reserve parameters (anti-Mullerian hormone: AMH, ovarian volume: OV, and antral follicle count: AFC) and ovarian stromal blood flow indices (Vascularization index: VI, flow index: FI, and vascularization flow index: VFI) were measured to explore the effect of LOD and to find out the correlation between serum AMH and different clinical, hormonal, and ultrasonic variables. There was a highly significant reduction of the serum AMH (p < .001) after LOD with significant reduction in OV, AFC and vascular indices (VI, FI and VFI) of the right and left ovaries (p < .05). LOD significantly reduced ovarian reserve parameters (AMH, OV and AFC) and ovarian stromal blood flow indices (VI, FI and VFI) with no observed correlation between AMH levels and Doppler indices.

Hepatocyte growth factor secreted by ovarian cancer cells stimulates peritoneal implantation via the mesothelial-mesenchymal transition of the peritoneum.

PubMed

Nakamura, Michihiko; Ono, Yoshihiro J; Kanemura, Masanori; Tanaka, Tomohito; Hayashi, Masami; Terai, Yoshito; Ohmichi, Masahide

2015-11-01

A current working model for the metastatic process of ovarian carcinoma suggests that cancer cells are shed from the ovarian tumor into the peritoneal cavity and attach to the layer of mesothelial cells that line the inner surface of the peritoneum, and several studies suggest that hepatocyte growth factor (HGF) plays an important role in the dissemination of ovarian cancer. Our objectives were to evaluate the HGF expression of ovarian cancer using clinical data and assess the effect of HGF secreted from human ovarian cancer cells to human mesothelial cells. HGF expression was immunohistochemically evaluated in 165 epithelial ovarian cancer patients arranged as tissue microarrays. HGF expression in four ovarian cancer cell lines was evaluated by using semi-quantitative polymerase chain reaction, Western blotting and enzyme-linked immunosorbent assay. The effect of ovarian cancer cell derived HGF to the human mesothelial cells was assessed by using morphologic analysis, Western blotting and cell invasion assay. The effect of HGF on ovarian cancer metastasis was assessed by using in vivo experimental model. The clinical data showed a significantly high correlation between the HGF expression and the cancer stage. The in vivo and in vitro experimental models revealed that HGF secreted by ovarian cancer cells induces the mesothelial-to-mesenchymal transition and stimulates the invasion of mesothelial cells. Furthermore, manipulating the HGF activity affected the degree of dissemination and ascite formation. We demonstrated that HGF secreted by ovarian cancer cells plays an important role in cancer peritoneal implantation. Copyright © 2015 Elsevier Inc. All rights reserved.

Update on fertility preservation in young women undergoing breast cancer and ovarian cancer therapy.

PubMed

Lambertini, Matteo; Ginsburg, Elizabeth S; Partridge, Ann H

2015-02-01

The purpose of the article is to review the available options for fertility preservation in patients with breast and ovarian cancer, and the special issues faced by BRCA mutation carriers. Future fertility is an important consideration for many young patients with cancer. There are both experimental and standard available strategies for patients with breast and ovarian cancer to preserve fertility, and each has potential advantages and disadvantages. Embryo cryopreservation is widely available with a highly successful track record. Improvements in laboratory techniques have led to oocyte cryopreservation recently being recategorized as nonexperimental. Conservative gynecologic surgery is a standard consideration for patients with stage I ovarian cancer who desire future fertility. Ovarian tissue cryopreservation as well as ovarian suppression with luteinizing hormone-releasing hormone analogs during chemotherapy are considered experimental methods at this time, although recent data suggest both safety and efficacy for the use of luteinizing hormone-releasing hormone analogs in women receiving (neo)adjuvant chemotherapy for breast cancer. Special issues should be considered for women with BRCA mutations because of the need to undergo preventive surgery at young age. Multidisciplinary teams and well functioning relationships between the oncology and reproductive units are crucial to manage the fertility issues of young women with cancer.

Association of infertility and fertility treatment with mammographic density in a large screening-based cohort of women: a cross-sectional study.

PubMed

Lundberg, Frida E; Johansson, Anna L V; Rodriguez-Wallberg, Kenny; Brand, Judith S; Czene, Kamila; Hall, Per; Iliadou, Anastasia N

2016-04-13

Ovarian stimulation drugs, in particular hormonal agents used for controlled ovarian stimulation (COS) required to perform in vitro fertilization, increase estrogen and progesterone levels and have therefore been suspected to influence breast cancer risk. This study aims to investigate whether infertility and hormonal fertility treatment influences mammographic density, a strong hormone-responsive risk factor for breast cancer. Cross-sectional study including 43,313 women recruited to the Karolinska Mammography Project between 2010 and 2013. Among women who reported having had infertility, 1576 had gone through COS, 1429 had had hormonal stimulation without COS and 5958 had not received any hormonal fertility treatment. Percent and absolute mammographic densities were obtained using the volumetric method Volpara™. Associations with mammographic density were assessed using multivariable generalized linear models, estimating mean differences (MD) with 95 % confidence intervals (CI). After multivariable adjustment, women with a history of infertility had 1.53 cm(3) higher absolute dense volume compared to non-infertile women (95 % CI: 0.70 to 2.35). Among infertile women, only those who had gone through COS treatment had a higher absolute dense volume than those who had not received any hormone treatment (adjusted MD 3.22, 95 % CI: 1.10 to 5.33). No clear associations were observed between infertility, fertility treatment and percent volumetric density. Overall, women reporting infertility had more dense tissue in the breast. The higher absolute dense volume in women treated with COS may indicate a treatment effect, although part of the association might also be due to the underlying infertility. Continued monitoring of cancer risk in infertile women, especially those who undergo COS, is warranted.

Cost-effectiveness of a mild compared with a standard strategy for IVF: a randomized comparison using cumulative term live birth as the primary endpoint.

PubMed

Polinder, S; Heijnen, E M E W; Macklon, N S; Habbema, J D F; Fauser, B J C M; Eijkemans, M J C

2008-02-01

BACKGROUND Conventional ovarian stimulation and the transfer of two embryos in IVF exhibits an inherent high probability of multiple pregnancies, resulting in high costs. We evaluated the cost-effectiveness of a mild compared with a conventional strategy for IVF. METHODS Four hundred and four patients were randomly assigned to undergo either mild ovarian stimulation/GnRH antagonist co-treatment combined with single embryo transfer, or standard stimulation/GnRH agonist long protocol and the transfer of two embryos. The main outcome measures are total costs of treatment within a 12 months period after randomization, and the relationship between total costs and proportion of cumulative pregnancies resulting in term live birth within 1 year of randomization. RESULTS Despite a significantly increased average number of IVF cycles (2.3 versus 1.7; P < 0.001), lower average total costs over a 12-month period (8333 versus euro10 745; P = 0.006) were observed using the mild strategy. This was mainly due to higher costs of the obstetric and post-natal period for the standard strategy, related to multiple pregnancies. The costs per pregnancy leading to term live birth were euro19 156 in the mild strategy and euro24 038 in the standard. The incremental cost-effectiveness ratio of the standard strategy compared with the mild strategy was euro185 000 per extra pregnancy leading to term live birth. CONCLUSIONS Despite an increased mean number of IVF cycles within 1 year, from an economic perspective, the mild treatment strategy is more advantageous per term live birth. It is unlikely, over a wide range of society's willingness-to-pay, that the standard treatment strategy is cost-effective, compared with the mild strategy.

Treatment outcome of women with a single ovary undergoing in vitro fertilisation cycles.

PubMed

Hendricks, M S; Chin, H; Loh, S F

2010-09-01

Women with a single ovary present a unique problem in assisted reproductive techniques. The aim of our study was to compare the ovarian response and pregnancy rates of women with one ovary and those with two ovaries in assisted reproduction. A total of 18 consecutive women with a single ovary (n is 22 cycles) were identified. The control group included 44 women with two ovaries and mechanical infertility, who were selected as frequency-matched samples (2:1) to meet the distribution of age at treatment and race in the single ovary group. All patients underwent controlled ovarian hyperstimulation treatment via the long down-regulation protocol using a gonadotropin-releasing hormone agonist. Standard procedures were carried out for gamete-embryo handling, and embryo transfer was performed using a soft catheter on day two in all cases. The luteal phase was supported by progesterone or Pregnyl after oocyte pick-up. The duration of stimulation (11.3 +/- 1.7 versus 10.1 +/- 1.4 days) and the total follicle stimulating hormone (FSH) consumption (3906.8 +/- 1860.6 mIU/ml versus 2900.0 +/- 1440.0 mIU/ml) were significantly higher, and the mean number of oocytes (10.8 +/- 4.5 versus 16.8 +/- 10.9) and metaphase II oocytes collected (9.5 +/- 4.5 versus 13.3 +/- 7.7) were significantly lower in the single ovary group (p is less than 0.05). The clinical pregnancy rates (31.8 percent versus 43.2 percent) were comparable between the two groups. Although women with a single ovary required significantly higher doses of FSH and a longer duration of stimulation, as well as produced less oocytes, their clinical pregnancy rates were comparable to those of women with two ovaries in assisted reproduction.

Association of basal serum androgen levels with ovarian response and ICSI cycle outcome.

PubMed

Abide Yayla, C; Ozkaya, E; Kayatas Eser, S; Sanverdi, I; Devranoglu, B; Kutlu, T

2018-05-01

The purpose of this study was to assess the predictive value of basal serum testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) levels during follicular phase for ovarian response and outcome in intracytoplasmic sperm injection (ICSI) cycles of women with diminished ovarian reserve. We prospectively gathered data of basal serum androgen levels and ICSI cycle characteristics of 120 women with diminished ovarian reserve. Association of basal serum T and DHEAS levels with ovarian response was analyzed. Basal T and DHEAS levels were similar between pregnant and non-pregnant cases (P > 0.05). There were significant differences between groups with and without successful embryo implantation in terms of serum follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), gonadotropin starting and total dose, and peak estradiol level (P < 0.05). There were 58 (49.2%) cases who did not reach to the embryo transfer stage due to several reasons including cancelation of stimulation due to unresponsiveness (n = 26, 21.7%), no oocyte at oocyte pickup (n = 11, 9.2%), no mature oocyte (n = 6, 5%), and failure of fertilization or embryo development (n = 15, 12.5%). Basal androgen levels were not significant predictors for any of the cycle outcome. AMH level was a significant predictor for failure of fertilization or embryo development (AUC 0.722, P = 0.01) and cancelation of stimulation (AUC 0.801, P < 0.001). FSH was a significant predictor for cancelation of stimulation (AUC 0.774, P < 0.001). In women with diminished ovarian reserve, basal T and DHEAS levels have no value in predicting any of the cycle outcome parameters.

ANDRO-IVF: a novel protocol for poor responders to IVF controlled ovarian stimulation

PubMed Central

Bercaire, Ludmila; Nogueira, Sara MB; Lima, Priscila CM; Alves, Vanessa R; Donadio, Nilka; Dzik, Artur; Cavagna, Mario; Fanchin, Renato

2018-01-01

Objective This study aimed to assess a novel protocol designed to improve poor ovarian response through intra-ovarian androgenization. The endpoints were: number of oocytes and mature oocytes retrieved, fertilization, cancellation and pregnancy rates. Methods This prospective crossover study enrolled poor responders from previous ovarian stimulation cycles submitted to a novel protocol called ANDRO-IVF. The protocol included pretreatment with transdermal AndroGel(r) (Besins) 25 mg, oral letrozole 2.5 mg and subcutaneous hCG 2500 IU; cycle control was performed with estradiol valerate and micronized progesterone; ovarian stimulation was attained with gonadotropins FSH/LH 450 IU, GnRH antagonist and hCG 5000 IU. Results Fourteen poor responders were enrolled. One patient did not meet the inclusion criteria. Thirteen patients previously summited to the standard protocol were offered the ANDRO-IVF Protocol.-Standard Protocol: Mean age: 35.30 years; cancellation rate: 61.53%; mean number of MII oocytes retrieved per patient: 1.8; fertilization rate: 33.33%. Only two patients had embryo transfers, and none got pregnant.-ANDRO-IVF Protocol: Mean age: 35.83 years; cancellation rate: 7.69%; mean number of oocytes retrieved per patient: 5.58, MII oocytes: 3.91. ICSI was performed in 84.61% of the patients and a mean of 1.5 embryos were transferred per patient. Fertilization rate: 62.5%; cumulative pregnancy rate: 16.66%; mean duration of stimulation: 9.77 days. Conclusion ANDRO-IVF allows intra-ovarian androgenization by increasing serum and intra-follicular androgen levels and preventing androgen aromatization. This protocol apparently improved clinical outcomes of poor responders in parameters such as number of oocytes retrieved and clinical pregnancy rates. Further randomized controlled trials are needed to confirm these findings. PMID:29303236

Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice.

PubMed

La Marca, Antonio; Sunkara, Sesh Kamal

2014-01-01

The main objective of individualization of treatment in IVF is to offer every single woman the best treatment tailored to her own unique characteristics, thus maximizing the chances of pregnancy and eliminating the iatrogenic and avoidable risks resulting from ovarian stimulation. Personalization of treatment in IVF should be based on the prediction of ovarian response for every individual. The starting point is to identify if a woman is likely to have a normal, poor or a hyper response and choose the ideal treatment protocol tailored to this prediction. The objective of this review is to summarize the predictive ability of ovarian reserve markers, such as antral follicle count (AFC) and anti-Mullerian hormone (AMH), and the therapeutic strategies that have been proposed in IVF after this prediction. A systematic review of the existing literature was performed by searching Medline, EMBASE, Cochrane library and Web of Science for publications in the English language related to AFC, AMH and their incorporation into controlled ovarian stimulation (COS) protocols in IVF. Literature available to May 2013 was included. The search generated 305 citations of which 41 and 25 studies, respectively, reporting the ability of AMH and AFC to predict response to COS were included in this review. The literature review demonstrated that AFC and AMH, the most sensitive markers of ovarian reserve identified to date, are ideal in planning personalized COS protocols. These sensitive markers permit prediction of the whole spectrum of ovarian response with reliable accuracy and clinicians may use either of the two markers as they can be considered interchangeable. Following the categorization of expected ovarian response to stimulation clinicians can adopt tailored therapeutic strategies for each patient. Current scientific trend suggests the elective use of the GnRH antagonist based regimen for hyper-responders, and probably also poor responders, as likely to be beneficial. The selection of the appropriate and individualized gonadotrophin dose is also of paramount importance for effective COS and subsequent IVF outcomes. Personalized IVF offers several benefits; it enables clinicians to give women more accurate information on their prognosis thus facilitating counselling especially in cases of extremes of ovarian response. The deployment of therapeutic strategies based on selective use of GnRH analogues and the fine tuning of the gonadotrophin dose on the basis of potential ovarian response in every single woman can allow for a safer and more effective IVF practice.

Pharmacogenetic algorithm for individualized controlled ovarian stimulation (iCOS) in assisted reproductive technology cycles.

PubMed

Roque, Matheus; Bianco, Bianca; Christofolini, Denise M; Cordts, Emerson B; Vilarino, Fabia L; Carvalho, Waldemar; Valle, Marcello; Sampaio, Marcos; Geber, Selmo; Esteves, Sandro C; Barbosa, Caio P

2018-06-14

Controlled ovarian stimulation (COS) is crucial for optimizing in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) success. Multiple factors influence the ovarian response to COS, making predictions about oocyte yields not so straightforward. As a result, the ovarian response may be poor or suboptimal, or even excessive, all of which have negative consequences for the affected patient. There is a group of patients that present with a suboptimal response to COS despite normal biomarkers of ovarian reserve, such as AFC and AMH. These patients have a lower number of retrieved oocytes than what was expected based on their ovarian reserve, thus showing the inadequacy of using only the traditional ovarian reserve biomarkers to predict the ovarian response. Suboptimal response to COS might be related to ovarian sensitivity to exogenous gonadotropins modulated by genetic factors. The understanding of the gene polymorphisms related to reproductive function can help to improve the clinical management of this patient population and to explain some of the individual patient variability in response to COS. The development of a pharmacogenetic approach concerning COS in the context of assisted reproduction seems attractive as it might help to understand the relationship between genetic variants and ovarian response to exogenous gonadotropins. The patient ́s genetic profile could be used to select the most appropriate gonadotropin type, predict the optimal dosage for each drug, develop a cost-effective treatment plan, maximize the success rates, and lastly, decrease the time-to-pregnancy.

Clinical Value of Basal Serum Progesterone Prior to Initiate Ovarian Hyper-Stimulation with GnRH Antagonists: A Retrospective Cohort Study.

PubMed

Faulisi, Sonia; Reschini, Marco; Borroni, Raffaella; Paffoni, Alessio; Busnelli, Andrea; Somigliana, Edgardo

2017-01-01

The routine assessment of day 3 serum progesterone prior to initiation of ovarian hyper-stimulation with the use of GnRH antagonists is under debate. In this study, we evaluated the clinical utility of this policy. Retrospective cohort study of women undergoing in vitro fertilization (IVF) with the use of GnRH antagonists aimed at determining the frequency of cases with progesterone levels exceeding the recommended threshold of 1,660 pg/ml and at evaluating whether this assessment may be predictive of pregnancy. Serum progesterone exceeded the recommended threshold in one case (0.3%, 95% CI 0.01-1.5). The median (interquartile range) basal progesterone in women who did (n = 95) and did not (n = 217) become pregnant were 351 (234-476) and 380 (237-531) pg/ml, respectively (p = 0.28). The 90th percentile of the basal progesterone distribution in women who became pregnant was 660 pg/ml. Cases with serum progesterone exceeding this threshold in successful and unsuccessful cycles were 10 (10%) and 30 (14%), respectively (p = 0.47). The capacity of basal progesterone to predict pregnancy was evaluated using receiver operating characteristic curve (area under the curve = 0.54, 95% CI 0.47-0.61, p = 0.28). No graphically evident threshold emerged. Routine day 3 serum progesterone assessment in IVF cycles with the use of GnRH antagonists is not justified. Further evidence is warranted prior to claiming its systematic use. © 2016 S. Karger AG, Basel.

Ovarian tissue cryopreservation in girls undergoing haematopoietic stem cell transplant: experience of a single centre.

PubMed

Biasin, E; Salvagno, F; Berger, M; Nesi, F; Quarello, P; Vassallo, E; Evangelista, F; Marchino, G L; Revelli, A; Benedetto, C; Fagioli, F

2015-09-01

Fertility after childhood haemopoietic stem cell transplant (HSCT) is a major concern. Conditioning regimens before HSCT present a high risk (>80%) of ovarian failure. Since 2000, we have proposed cryopreservation of ovarian tissue to female patients undergoing HSCT at our centre, to preserve future fertility. After clinical and haematological evaluation, the patients underwent ovarian tissue collection by laparoscopy. The tissue was analysed by histologic examination to detect any tumour contamination and then frozen following the slow freezing procedure and cryopreserved in liquid nitrogen. From August 2000 to September 2013, 47 patients planned to receive HSCT, underwent ovarian tissue cryopreservation. The median age at diagnosis was 11.1 years and at the time of procedure it was 13 years, respectively. Twenty-four patients were not pubertal at the time of storage, whereas 23 patients had already experienced menarche. The median time between laparoscopy and HSCT was 25 days. Twenty-six out of 28 evaluable patients (93%) developed hypergonadotropic hypogonadism at a median time of 23.3 months after HSCT. One patient required autologous orthotopic transplantation that resulted in one live birth. Results show a very high rate of iatrogenic hypergonadotropic hypogonadism, highlighting the need for fertility preservation in these patients.

Subfertility factors rather than assisted conception factors affect cognitive and behavioural development of 4-year-old singletons.

PubMed

Schendelaar, Pamela; La Bastide-Van Gemert, Sacha; Heineman, Maas Jan; Middelburg, Karin J; Seggers, Jorien; Van den Heuvel, Edwin R; Hadders-Algra, Mijna

2016-12-01

Research on cognitive and behavioural development of children born after assisted conception is inconsistent. This prospective study aimed to explore underlying causal relationships between ovarian stimulation, in-vitro procedures, subfertility components and child cognition and behaviour. Participants were singletons born to subfertile couples after ovarian stimulation IVF (n = 63), modified natural cycle IVF (n = 53), natural conception (n = 79) and singletons born to fertile couples (reference group) (n = 98). At 4 years, cognition (Kaufmann-ABC-II; total IQ) and behaviour (Child Behavior Checklist; total problem T-score) were assessed. Causal inference search algorithms and structural equation modelling was applied to unravel causal mechanisms. Most children had typical cognitive and behavioural scores. No underlying causal effect was found between ovarian stimulation and the in-vitro procedure and outcome. Direct negative causal effects were found between severity of subfertility (time to pregnancy) and cognition and presence of subfertility and behaviour. Maternal age and maternal education acted as confounders. The study concludes that no causal effects were found between ovarian stimulation or in-vitro procedures and cognition and behaviour in childrenaged 4 years born to subfertile couples. Subfertility, especially severe subfertility, however, was associated with worse cognition and behaviour. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

YAP forms autocrine loops with the ERBB pathway to regulate ovarian cancer initiation and progression

PubMed Central

He, Chunbo; Lv, Xiangmin; Hua, Guohua; Lele, Subodh M; Remmenga, Steven; Dong, Jixin; Davis, John S; Wang, Cheng

2014-01-01

Mechanisms underlying ovarian cancer initiation and progression are unclear. Herein, we report that the Yes-associated protein (YAP), a major effector of the Hippo tumor suppressor pathway, interacts with ERBB signaling pathways to regulate the initiation and progression of ovarian cancer. Immunohistochemistry studies indicate that YAP expression is associated with poor clinical outcomes in patients. Overexpression or constitutive activation of YAP leads to transformation and tumorigenesis in human ovarian surface epithelial cells, and promotes growth of cancer cells in vivo and in vitro. YAP induces expression of EGF receptors (EGFR, ERBB3) and production of EGF-like ligands (HBEGF, NRG1 and NRG2). HBEGF or NRG1, in turn, activates YAP and stimulates cancer cell growth. Knockdown of ERBB3 or HBEGF eliminates YAP effects on cell growth and transformation, while knockdown of YAP abrogates NRG1- and HBEGF-stimulated cell proliferation. Collectively, our study demonstrates the existence of HBEGF&NRGs/ERBBs/YAP/HBEGF&NRGs autocrine loop that controls ovarian cell tumorigenesis and cancer progression. PMID:25798835

Effect of Acupuncture vs Sham Acupuncture on Live Births Among Women Undergoing In Vitro Fertilization: A Randomized Clinical Trial.

PubMed

Smith, Caroline A; de Lacey, Sheryl; Chapman, Michael; Ratcliffe, Julie; Norman, Robert J; Johnson, Neil P; Boothroyd, Clare; Fahey, Paul

2018-05-15

Acupuncture is widely used by women undergoing in vitro fertilization (IVF), although the evidence for efficacy is conflicting. To determine the efficacy of acupuncture compared with a sham acupuncture control performed during IVF on live births. A single-blind, parallel-group randomized clinical trial including 848 women undergoing a fresh IVF cycle was conducted at 16 IVF centers in Australia and New Zealand between June 29, 2011, and October 23, 2015, with 10 months of pregnancy follow-up until August 2016. Women received either acupuncture (n = 424) or a sham acupuncture control (n = 424). The first treatment was administered between days 6 to 8 of follicle stimulation, and 2 treatments were administered prior to and following embryo transfer. The sham control used a noninvasive needle placed away from the true acupuncture points. The primary outcome was live birth, defined as the delivery of 1 or more living infants at greater than 20 weeks' gestation or birth weight of at least 400 g. Among 848 randomized women, 24 withdrew consent, 824 were included in the study (mean [SD] age, 35.4 [4.3] years); 371 [45.0%] had undergone more than 2 previous IVF cycles), 607 proceeded to an embryo transfer, and 809 (98.2%) had data available on live birth outcomes. Live births occurred among 74 of 405 women (18.3%) receiving acupuncture compared with 72 of 404 women (17.8%) receiving sham control (risk difference, 0.5% [95% CI, -4.9% to 5.8%]; relative risk, 1.02 [95% CI, 0.76 to 1.38]). Among women undergoing IVF, administration of acupuncture vs sham acupuncture at the time of ovarian stimulation and embryo transfer resulted in no significant difference in live birth rates. These findings do not support the use of acupuncture to improve the rate of live births among women undergoing IVF. anzctr.org.au Identifier: ACTRN12611000226909.

Expression of neurokinin B/NK3 receptor and kisspeptin/KISS1 receptor in human granulosa cells.

PubMed

García-Ortega, J; Pinto, F M; Fernández-Sánchez, M; Prados, N; Cejudo-Román, A; Almeida, T A; Hernández, M; Romero, M; Tena-Sempere, M; Candenas, L

2014-12-01

Are neurokinin B (NKB), NK3 receptor (NK3R), kisspeptin (KISS1) and kisspeptin receptor (KISS1R) expressed in human ovarian granulosa cells? The NKB/NK3R and kisspeptin/KISS1R systems are co-expressed and functionally active in ovarian granulosa cells. The NKB/NK3R and KISS1/KISS1R systems are essential for reproduction. In addition to their well-recognized role in hypothalamic neurons, these peptide systems may contribute to the control of fertility by acting directly on the gonads, but such a direct gonadal role remains largely unknown. This study analyzed matched mural granulosa cells (MGCs) and cumulus cells (CCs) collected from preovulatory follicles of oocyte donors at the time of oocyte retrieval. The samples were provided by 56 oocyte donor women undergoing ovarian stimulation treatment. Follicular fluid samples containing MGCs and cumulus-oocyte complexes were collected after transvaginal ultrasound-guided oocyte retrieval. RT-PCR, quantitative real-time PCR, immunocytochemistry and western blot were used to investigate the pattern of expression of the NKB/NK3R and KISS/KISS1R systems in MGCs and CCs. Intracellular free Ca(2+) levels, [Ca(2+)]i, in MGCs after exposure to NKB or KISS1, in the presence or not of tachykinin receptor antagonists, were also measured. NKB/NK3R and KISS1/KISS1R systems were expressed, at the mRNA and protein levels, in MGCs and CCs, with significantly higher expression in CCs. Kisspeptin increased the [Ca(2+)]i in the cytosol of human MGCs while exposure to NKB failed to induce any change in [Ca(2+)]i. However, the [Ca(2+)]i response to kisspeptin was reduced in the presence of NKB. The inhibitory effect of NKB was only partially mimicked by the NK3R agonist, senktide and marginally suppressed by the NK3R-selective antagonist SB 222200. Yet, a cocktail of antagonists selective for the NK1, NK2 and NK3 receptors blocked the effect of NKB. The granulosa and cumulus cells were obtained from oocyte donors undergoing ovarian stimulation, which in comparison with natural cycles, may have affected gene and protein expression in granulosa cells. Our data demonstrate that, in addition to their indispensable effects at the central nervous system, the NKB/NK3R and kisspeptin/KISS1R systems are co-expressed and are functionally active in non-neuronal reproductive cells of the female gonads, the ovarian granulosa cells. This work was supported by grants from Ministerio de Economía y Competitividad (CTQ2011-25564 and BFI2011-25021) and Junta de Andalucía (P08-CVI-04185), Spain. J.G.-O., F.M.P., M.F.-S., N.P., A.C.-R., T.A.A., M.H., M.R., M.T.-S. and L.C. have nothing to declare. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Co-expression of the Follicle Stimulating Hormone Receptor and Stem Cell Markers: A Novel Approach to Target Ovarian Cancer Stem Cells

DTIC Science & Technology

2012-09-01

ovarian cancer stem cell markers to consider it as a new experimental target for novel nanotechnology approaches capable of destroying ovarian cancer stem...FSHR mRNA after several generations in an amount consistent with stem cell characteristics. Nude mouse experiments to confirm co-expression in vivoare

Use of a GnRH antagonist in controlled ovarian hyperstimulation for assisted conception in women with polycystic ovary disease: a randomized, prospective, pilot study.

PubMed

Bahçeci, Mustafa; Ulug, Ulun; Ben-Shlomo, Izhar; Erden, Halit Firat; Akman, Mehmet Ali

2005-02-01

To compare the outcome of using gonadotropin-releasing hormone (GnRH) antagonists versus agonists in women with polycystic ovary disease (PCOD) who underwent controlled ovarian hyperstimulation (COH) for assisted reproductive techniques (ART). A total of 129 patients with PCOD were randomly allocated to undergo COH with a GnRH antagonist (59 patients) and GnRH agonist (leuprolide acetate) (70 patients) to prevent a premature luteinizing hormone (LH) surge. Assisted fertilization following oocyte retrieval and embryo transfer was performed. None of the cycles were cancelled due to a premature LH surge. There was no significant difference between the antagonist and agonist arms in the number of gonadotropin ampules consumed per cycle. However, in the antagonist arm a shorter duration of ovarian stimulation was recorded as compared to the agonist arm. Although similar numbers of oocytes was retrieved from both groups of patients, the quality of the oocytes, as measured by metaphase 2/total oocyte ratio, was lower in the antagonist arm as compared to the agonist arm. Pregnancy rates were 57.6% and 58.5% in the antagonist and agonist arms, respectively (p > 0.05). Implantation rates were not different (34.0% and 34.6%, respectively). The frequency of ovarian hyperstimulation syndrome also did not differ between the treatment groups (5% and 7.1%, respectively). The size of our study, on a specific subgroup of patients, does not allow a reliable conclusion regarding ART outcomefollowing the use of a GnRH antagonist versus agonist. Nevertheless, the protocol with the antagonist gave results that were as good as those of the protocol with the agonist in this PCOD patient population.

IVF endocrinology: the Edwards era.

PubMed

Hillier, Stephen G

2013-12-01

Through pioneering human IVF as a global infertility treatment, Robert Edwards and his clinical partner Patrick Steptoe launched the field of IVF endocrinology. Following repeated failures with oocytes collected in human menopausal gonadotrophin (HMG) primed cycles timed to injection of human chorionic gonadotrophin (HCG), the first successful IVF pregnancy came from a spontaneous menstrual cycle. Intensive endocrine monitoring was used to track pre-ovulatory follicular development and collect a single ripe egg timed to the natural LH surge. Despite this groundbreaking achievement, ovulation induction was clearly required to make IVF treatment clinically robust and reliable. Ovarian stimulation with clomiphene citrate was used to achieve the first maternity from a superovulated human IVF cycle in 1980. HMG/HCG regimens were then successfully introduced-including substitution of 'pure' follicle-stimulating hormone as the principal ovarian stimulant. The application and success of IVF treatment were dramatically enhanced by the introduction of gonadotrophin-releasing hormone analogues that enabled elective control of endogenous gonadotrophin release during ovarian stimulation. Programmed gonadotrophin regimes yielding double-digit oocyte numbers became normal: 'more is better' was the ethos. Bob Edwards expressed increasing concern over the cost, complexity and potential long-term health risks of such high-order ovarian stimulation. In later life he repeatedly called for a return to minimalist approaches based on the natural menstrual cycle to improve oocyte quality over quantity. This article reviews the application of ovulation induction to human IVF and celebrates Edwards' abiding impact on the field, which firmly grounds him in the reproductive endocrinology pantheon.

Ovarian preservation in locally advanced cervical cancer undergoing neoadjuvant chemotherapy and radical surgery: our experience and analysis of the literature.

PubMed

Signorelli, Mauro; Bogani, Giorgio; Chiappa, Valentina; Ditto, Antonino; Scaffa, Cono; Martinelli, Fabio; Lorusso, Domenica; Raspagliesi, Francesco

2018-03-30

The aim of this study was to estimate the rate of ovarian metastases and recurrences among patients affected by locally advanced stage cancer patients (LACC), undergoing neoadjuvant chemotherapy (NACT) and radical surgery with conservation of ovaries. Retrospective evaluation of consecutive patients affected by LACC (stage IB2- IIB), treated by NACT followed by radical surgery at National Cancer Institute, Milan, Italy, between 1990-2015. Overall, 331 patients were included. Stage at presentation included stage IB2, IIA and IIB in 120 (36.3%), 63 (19%) and 148 (44.7%) patients, respectively. Main histotype was squamous cell carcinoma (n=265, 80.1%) followed by adenocarcinoma/adenosquamous (n=51, 15.4%), and more than half of patients had a grade 3 carcinoma . Overall, 102 (30.8%) women had at least one ovary preserved during surgery, while 229 (69.2%) had bilateral salpingo-oophorectomy. Comparing patients who had ovarian preservation with patients who had not, we observed that the two groups were comparable in terms of baseline characteristics. Survival outcomes were not influenced by ovarian preservation (disease-free (p=0.93) and overall (p=0.65) survivals). One (1%) woman had a localized ovarian recurrence. Our data suggest that ovarian preservation at the time of surgery is a safe option among women with LACC after NACT with no detrimental impact on oncologic outcome. Further prospective studies are warranted.

Ovulation induction in polycystic ovary syndrome.

PubMed

Tanbo, Tom; Mellembakken, Jan; Bjercke, Sverre; Ring, Eva; Åbyholm, Thomas; Fedorcsak, Peter

2018-06-11

The objective of this narrative review is to suggest a rational order of treatment choices in anovulatory women with polycystic ovary syndrome (PCOS), for whom a multitude of treatment options exist. In obese/overweight PCOS patients the importance of weight reduction should be stressed. Inositol, a dietary supplement with a documented effect on ovulation and without side effects in the doses recommended, may be suggested. Additional first line medical alternatives include insulin sensitizers, selective estrogen receptor modulators and aromatase inhibitors. Of these, the aromatase inhibitor letrozole and the combination of clomiphene citrate and metformin have the highest rates of ovulation and live birth. Second line treatments are ovarian electrocautery and low-dose follicle stimulating hormone stimulation. Controlled ovarian stimulation with in vitro fertilization, should be considered the last option since it carries a significant risk of ovarian hyperstimulation syndrome in patients with PCOS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A Higher Ovarian Response after Stimulation for IVF Is Related to a Higher Number of Euploid Embryos.

PubMed

Labarta, Elena; Bosch, Ernesto; Mercader, Amparo; Alamá, Pilar; Mateu, Emilia; Pellicer, Antonio

2017-01-01

This study has analysed the relationship between ovarian response and the number of euploid embryos. This is a post hoc analysis of a subset of data generated during a prospective cohort study previously published. Forty-six oocyte donors were subjected to ovarian stimulation with 150 IU of rFSH and 75 IU of hp-hMG in a GnRH agonist long protocol. Preimplantation genetic screening was performed in all viable embryos. We observed a positive relationship between ovarian response and the number of euploid embryos. When ovarian response was above the median (≥17 oocytes), the mean number of euploid embryos per donor was 5.0 ± 2.4, while when <17 oocytes were obtained the mean number of euploid embryos was 2.7 ± 1.4 ( p = 0.000). Aneuploidy rate did not increase with ovarian response or gonadotropin doses. Also, the number of euploid embryos was inversely related to the amount of gonadotropins needed per oocyte obtained (ovarian sensitivity index). These results suggest that the number of euploid embryos available for embryo transfer increases as the number of oocytes obtained does. Considering the total number of euploid embryos seems more relevant than the aneuploidy rate.

Consistent high clinical pregnancy rates and low ovarian hyperstimulation syndrome rates in high-risk patients after GnRH agonist triggering and modified luteal support: a retrospective multicentre study.

PubMed

Iliodromiti, Stamatina; Blockeel, Christophe; Tremellen, Kelton P; Fleming, Richard; Tournaye, Herman; Humaidan, Peter; Nelson, Scott M

2013-09-01

Are clinical pregnancy rates satisfactory and the incidence of OHSS low after GnRH agonist trigger and modified intensive luteal support in patients with a high risk of ovarian hyperstimulation syndrome (OHSS)? GnRH agonist trigger combined with 1500 IU hCG at the time of oocyte retrieval and subsequent estradiol and progesterone replacement in OHSS high-risk patients can facilitate fresh embryo transfer with high clinical pregnancy rates and a low risk of severe OHSS. Conventional luteal support packages are inadequate to facilitate a fresh transfer after a GnRH agonist trigger. A low dose of hCG (1500 IU) after oocyte aspiration can be used to replace the actions of early luteal LH to sustain implantation and the function of the early corpus luteum, although the level of risk of severe OHSS with this strategy is unclear. This international multicentre retrospective case study, including 275 women at high risk of OHSS, was undertaken during the period January 2011-December 2012. Women were identified as at high risk of OHSS, based on IVF response, ovarian reserve characteristics and previous history of having had treatment, in three clinical IVF centres in UK, Belgium and Australia. All three centres used a GnRH agonist trigger followed by one bolus of 1500 IU hCG 1h after oocyte retrieval. Moreover, the luteal phase was supported with daily vaginal progesterone and twice daily estradiol valerate. A total of 275 autologous cycles with fresh transfer were undertaken in a cohort of high-risk women as defined by baseline characteristics [median (interquartile range)]: age 31.6 (29-35) years, antral follicle count median 25 (18-34) and anti-Müllerian hormone median 49.1 pmol/l (35.2-69.3). At the end of stimulation, the peak estradiol median of 12 000 pmol/l (9400-15 914) and the mean oocyte yield of 17.8 ± 8.4 confirmed a high response. The overall clinical pregnancy rate was 41.8% per cycle started, with only two cases of severe OHSS reported (0.72%). No significant differences in clinical pregnancy rates between centres were identified. This is a retrospective study and future randomized controlled trials will be able to compare whether these outcomes can be improved upon by either segmentation of the stimulation cycle and embryo transfer or alternative aggressive luteal support strategies. In women who are undergoing ovarian stimulation and who develop an excessive ovarian response, the use of a GnRH agonist trigger combined with modified luteal support can provide the opportunity to proceed to fresh embryo transfer with adequate clinical pregnancy rates. However, this procedure will not completely eliminate the risk of OHSS and for women with an extreme ovarian response or with significant comorbidity, where the possibility of severe OHSS is unacceptable, we recommend GnRH agonist trigger followed by a freeze-all policy to completely avoid OHSS.

GPER-1 acts as a tumor suppressor in ovarian cancer

PubMed Central

2013-01-01

Background It is known that the new membrane-bound estrogen receptor GPER-1 acts suppressive in breast cancer cells and its expression decreases during disease progression. This study was conducted to evaluate the GPER-1 expression in ovarian cancer and its correlation with progression. Its function was tested in vitro in ovarian cancer cells. Patients and methods GPER-1 expression was analyzed by immunohistochemistry in 35 benign ovarian tumors, 35 tumors of low-malignant potential and in 124 ovarian cancers. GPER-1 expression was correlated to the prospectively evaluated disease-free survival of ovarian cancer patients. We also tested GPER-1 expression in ovarian cancer cells and the effect of GPER-1 stimulation on cell growth. Results GPER-1 expression was significantly lower in ovarian cancer tissue than in benign and low-malignant ovarian tumors. GPER-1 expression was observed in 83.1% of malignant tumors and was higher in early stage cancers and tumors with high histological differentiation. GPER-1 expression was associated with favourable clinical outcome. The difference in 2-year disease-free survival by GPER-1 expression was significant, 28.6% for GPER-1 negative and 59.2% for GPER-1 positive cases (p = 0.002). GPER-1 expression was observed in SKOV-3 and OVCAR-3 ovarian cancer cell lines. G-1, a selective GPER-1 agonist, suppressed proliferation of the two cell types via inhibition of cell cycle progression in G2/M phase and stimulation of caspase-dependent apoptosis. The blockade in G2/M phase was associated with increased expression of cyclin B1 and Cdc2 and phosphorylation of histone 3. Conclusion GPER-1 emerges as a new tumor suppressor with unsuspected therapeutic potential for ovarian cancer. PMID:23849542

Ovarian stimulation length, number of follicles higher than 17 mm and estradiol on the day of human chorionic gonadotropin administration are risk factors for multiple pregnancy in intrauterine insemination

PubMed Central

MELO, MARCO A.B.; SIMÓN, CARLOS; REMOHÍ, JOSÉ; PELLICER, ANTONIO; MESEGUER, MARCOS

2007-01-01

Aim:  The aim of the present study was to identify the risk factors, their prognostic value on multiple pregnancies (MP) prediction and their thresholds in women undergoing controlled ovarian hyperstimulation (COH) with follicle stimulating hormone (FSH) and intrauterine insemination (IUI). Methods:  A case‐control study was carried out by identifying in our database all the pregnancies reached by donor and conjugal IUI (DIUI and CIUI, respectively), and compared cycle features, patients’ characteristics and sperm analysis results between women achieving single pregnancy (SP) versus MP. The number of gestational sacs, follicular sizes and estradiol levels on the human chorionic gonadotropin (hCG) administration day, COH length and semen parameters were obtained from each cycle and compared. Student's t‐tests for mean comparisons, receiver–operator curve (ROC) analysis to determine the predictive value of each parameter on MP achievement and multiple regression analysis to determine single parameter influence were carried out. Results:  Women with MP in IUI stimulated cycles reached the adequate size of the dominant follicle (17 mm) significantly earlier than those achieving SP. Also, the mean follicles number, and estradiol levels on the hCG day were higher in the CIUI and DIUI MP group. Nevertheless, only ROC curve analysis revealed good prognostic value for estradiol and follicles higher than 17 mm. Multiple regression analysis confirmed these results. No feature of the basic sperm analysis, either in the ejaculate or in the prepared sample, was different or predictive of MP. When using donor sperm, different thresholds of follicle number, stimulation length and estradiol in the prediction of MP were noted, in comparison with CIUI. Conclusions:  MP in stimulated IUI cycles are closely associated to stimulation length, number of developed follicles higher than 17 mm on the day of hCG administration and estradiol levels. Also, estradiol has a good predictive value over MP in IUI stimulated cycles. The establishment of clinical thresholds will certainly help in the management of these couples to avoid undesired multiple pregnancies by canceling cycles or converting them into in vitro fertilization procedures. (Reprod Med Biol 2007; 6: 19–26) PMID:29699262

Dehydroepiandrosterone (DHEA) supplementation and IVF outcome in poor responders.

PubMed

Triantafyllidou, Olga; Sigalos, George; Vlahos, Nikos

2017-06-01

Ovarian stimulation of poor ovarian responders still remains a challenging issue. The incidence of poor responders among infertile women is reported in 9-24% IVF cycles and is associated with very low clinical pregnancy rates. Different treatments have been reported in the literature in an attempt to identify the best stimulation protocol for those patients. Administration of dehydroepiandrosterone acetate (DHEA) was suggested as a promising treatment. It is well known that androgens can influence ovarian follicular growth, augment steroidogenesis, promote follicular recruitment and increase the number of primary and pre-antral follicles. The purpose of this review is to evaluate the effect of DHEA supplementation on women with diminished ovarian reserve. Because of the uncertainty of published data, we suggest that well-designed multicentre RCTs are required to provide more insight on the effectiveness of DHEA. The absence of significant side effects should not be considered as an argument to support DHEA treatment.

Cumulative live birth rates after IVF in patients with polycystic ovaries: phenotype matters.

PubMed

De Vos, Michel; Pareyn, Stéphanie; Drakopoulos, Panagiotis; Raimundo, José M; Anckaert, Ellen; Santos-Ribeiro, Samuel; Polyzos, Nikolaos P; Tournaye, Herman; Blockeel, Christophe

2018-05-07

Do cumulative live birth rates (CLBR) vary among women with different polycystic ovary syndrome (PCOS) phenotypes who undergo IVF/intracytoplasmic sperm injection (ICSI) treatment? In this retrospective cohort study, data from 567 patients undergoing an assisted reproductive technology (ART) cycle between January 2010 and December 2015 were collected. Demographical traits, cycle characteristics and clinical and laboratory data were analysed. After conventional ovarian stimulation using a gonadotrophin-releasing hormone antagonist protocol, the median number of oocytes retrieved ranged between 11 and 13.5 and did not differ significantly among the studied groups. Live birth rate (LBR) after fresh embryo transfer and CLBR after transfer of all fresh and vitrified embryos were significantly lower in women with hyperandrogenic PCOS phenotypes A (LBR 16.7%, CLBR 25.8%) and C (LBR 18.5%, CLBR 27.8%) compared with women with normoandrogenic PCOS phenotype D (LBR 33.7%, CLBR 48%) (P-value for LBR 0.01 and 0.03, respectively; P-value for CLBR 0.002 and 0.01, respectively) and controls with a polycystic ovarian morphology (LBR 37.1%, CLBR 53.3%) (P-value for LBR 0.002 and 0.01, respectively; P-value for CLBR <0.001 and 0.001, respectively). Multivariate regression analysis indicated that after adjustment for relevant confounders, PCOS phenotype was an independent predictor for CLBR. Hyperandrogenic PCOS phenotypes confer significantly lower CLBR compared with their normoandrogenic counterparts. These findings may imply the need for adapted counselling and tailored approaches when treating PCOS patients with hyperandrogenism who require ART. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Origin of estradiol fatty acid esters in human ovarian follicular fluid.

PubMed

Pahuja, S L; Kim, A H; Lee, G; Hochberg, R B

1995-03-01

The estradiol fatty acid esters are the most potent of the naturally occurring steroidal estrogens. These esters are present predominantly in fat, where they are sequestered until they are hydrolyzed by esterases. Thus they act as a preformed reservoir of estradiol. We have previously shown that ovarian follicular fluid from patients undergoing gonadotropin stimulation contains very high amounts of estradiol fatty acid esters (approximately 10(-7) M). The source of these esters is unknown. They can be formed by esterification of estradiol in the follicular fluid by lecithin:cholesterol acyltransferase (LCAT), or in the ovary by an acyl coenzyme A:acyltransferase. In order to determine which of these enzymatic processes is the source of the estradiol esters in the follicular fluid, we incubated [3H]estradiol with follicular fluid and cells isolated from human ovarian follicular fluid and characterized the fatty acid composition of the [3H]estradiol esters biosynthesized in each. In addition, we characterized the endogenous estradiol fatty acid esters in the follicular fluid and compared them to the biosynthetic esters. The fatty acid composition of the endogenous esters was different than those synthesized by the cellular acyl coenzyme A:acyltransferase, and the same as the esters synthesized by LCAT, demonstrating that the esters are produced in situ in the follicular fluid. Although the role of these estradiol esters in the ovary is not known, given their remarkable estrogenic potency it is highly probable that they have an important physiological role.

Incorporating spirituality in psychosocial group intervention for women undergoing in vitro fertilization: a prospective randomized controlled study.

PubMed

Chan, Celia H Y; Chan, Cecilia L W; Ng, Ernest H Y; Ho, P C; Chan, Timothy H Y; Lee, G L; Hui, W H C

2012-12-01

This study examined the efficacy of a group intervention, the Integrative Body-Mind-Spirit (I-BMS) intervention, which aims at improving the psychosocial and spiritual well-being of Chinese women undergoing their first IVF treatment cycle. The I-BMS intervention facilitates the search of meaning of life in the context of family and childbearing, as well as the letting go of high IVF expectations. A randomized controlled study of 339 women undergoing first IVF treatment cycle in a local Hong Kong hospital was conducted (intervention: n= 172; no-intervention control: n= 167). Assessments of anxiety, perceived importance of childbearing, and spiritual well-being were made at randomization (T(0) ), on the day starting ovarian stimulations (T(1)), and on the day undertaking embryo transfer (T(2)). Comparing T(0) and T(2), interaction analyses showed women who had received the intervention reported lower levels of physical distress, anxiety, and disorientation. They reported being more tranquil and satisfied with their marriage, and saw childbearing as less important compared to women in the control group. These findings suggest that I-BMS intervention was successful at improving the psychosocial and spiritual well-being of women undergoing their first IVF treatment cycle. This study highlights the importance of providing integrative fertility treatment that incorporates psychosocial and spiritual dimensions. ©2011 The British Psychological Society.

Coexpression of the Follicle Stimulating Hormone Receptor and Stem Cell Markers: A Novel Approach to Target Ovarian Cancer Stem Cells

DTIC Science & Technology

2016-03-01

1 AD_____________ Award Number: W81XWH-11-1-0623 TITLE: Coexpression of the Follicle Stimulating Hormone Receptor and Stem Cell Markers: A...Novel Approach to Target Ovarian Cancer Stem Cells PRINCIPAL INVESTIGATOR: David W. Schomberg, PhD CONTRACTING ORGANIZATION: Duke University...Durham, NC 27705 REPORT DATE: March 2016 TYPE OF REPORT: Final PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick

Moderate Ovarian Stimulation Does Not Increase the Incidence of Human Embryo Chromosomal Abnormalities in in Vitro Fertilization Cycles

PubMed Central

Bosch, Ernesto; Alamá, Pilar; Rubio, Carmen; Rodrigo, Lorena; Pellicer, Antonio

2012-01-01

Context: A high chromosomal abnormalities rate has been observed in human embryos derived from in vitro fertilization (IVF) treatments. The real incidence in natural cycles has been poorly studied, so whether this frequency may be induced by external factors, such as use of gonadotropins for ovarian stimulation, remains unknown. Design: We conducted a prospective cohort study in a University-affiliated private infertility clinic with a comparison between unstimulated and stimulated ovarian cycles in the same women. Preimplantation genetic screening by fluorescence in situ hybridization was performed in all viable d 3 embryos. Objective: The primary objective was to compare the incidence of embryo chromosomal abnormalities in an unstimulated cycle and in an ulterior moderate ovarian stimulated cycle. Secondary outcome measures were embryo quality, blastocyst rate of biopsied embryos, number of normal blastocysts per donor, type of chromosomal abnormalities, and clinical outcome. Results: One hundred eighty-five oocyte donors were initially recruited for the unstimulated cycle, and preimplantation genetic screening could be performed in 51 of them, showing 35.3% of embryo chromosomal abnormalities. Forty-six of them later completed a stimulated cycle. The sperm donor sample was the same for both cycles. The proportion of embryos displaying abnormalities in the unstimulated cycle was 34.8% (16 of 46), whereas it was 40.6% (123 of 303) in the stimulated cycle with risk difference = 5.8 [95% confidence interval (CI) = −20.6–9.0], and relative risk = 1.17 (95% CI = 0.77–1.77) (P = 0.45). When an intrasubject comparison was made, the abnormalities rate was 34.8% (95% CI = 20.5–49.1) in the unstimulated cycle and 38.2% (95% CI = 30.5–45.8) in the stimulated cycle [risk difference = 3.4 (95% CI = −17.9–11.2); P = 0.64]. No differences were observed for embryo quality and type of chromosomal abnormalities. Conclusions: Moderate ovarian stimulation in young normo-ovulatory women does not significantly increase the embryo aneuploidies rate in in vitro fertilization-derived human embryos as compared with an unstimulated cycle. Whether these results can be extrapolated to infertile patients is still unknown. PMID:22865900

The influence of sarcopenia on survival and surgical complications in ovarian cancer patients undergoing primary debulking surgery.

PubMed

Rutten, I J G; Ubachs, J; Kruitwagen, R F P M; van Dijk, D P J; Beets-Tan, R G H; Massuger, L F A G; Olde Damink, S W M; Van Gorp, T

2017-04-01

Sarcopenia, severe skeletal muscle loss, has been identified as a prognostic factor in various malignancies. This study aims to investigate whether sarcopenia is associated with overall survival (OS) and surgical complications in patients with advanced ovarian cancer undergoing primary debulking surgery (PDS). Ovarian cancer patients (n = 216) treated with PDS were enrolled retrospectively. Total skeletal muscle surface area was measured on axial computed tomography at the level of the third lumbar vertebra. Optimum stratification was used to find the optimal skeletal muscle index cut-off to define sarcopenia (≤38.73 cm 2 /m 2 ). Cox-regression and Kaplan-Meier analysis were used to analyse the relationship between sarcopenia and OS. The effect of sarcopenia on the development of major surgical complications was studied with logistic regression. Kaplan-Meier analysis showed a significant survival disadvantage for patients with sarcopenia compared to patients without sarcopenia (p = 0.010). Sarcopenia univariably predicted OS (HR 1.536 (95% CI 1.105-2.134), p = 0.011) but was not significant in multivariable Cox-regression analysis (HR 1.362 (95% CI 0.968-1.916), p = 0.076). Significant predictors for OS in multivariable Cox-regression analysis were complete PDS, treatment in a specialised centre and the development of major complications. Sarcopenia was not predictive of major complications. Sarcopenia was not predictive of OS or major complications in ovarian cancer patients undergoing primary debulking surgery. However a strong trend towards a survival disadvantage for patients with sarcopenia was seen. Future prospective studies should focus on interventions to prevent or reverse sarcopenia and possibly increase ovarian cancer survival. Complete cytoreduction remains the strongest predictor of ovarian cancer survival. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

YAP forms autocrine loops with the ERBB pathway to regulate ovarian cancer initiation and progression.

PubMed

He, C; Lv, X; Hua, G; Lele, S M; Remmenga, S; Dong, J; Davis, J S; Wang, C

2015-12-10

Mechanisms underlying ovarian cancer initiation and progression are unclear. Herein, we report that the Yes-associated protein (YAP), a major effector of the Hippo tumor suppressor pathway, interacts with ERBB signaling pathways to regulate the initiation and progression of ovarian cancer. Immunohistochemistry studies indicate that YAP expression is associated with poor clinical outcomes in patients. Overexpression or constitutive activation of YAP leads to transformation and tumorigenesis in human ovarian surface epithelial cells, and promotes growth of cancer cells in vivo and in vitro. YAP induces the expression of epidermal growth factor (EGF) receptors (EGFR, ERBB3) and production of EGF-like ligands (HBEGF, NRG1 and NRG2). HBEGF or NRG1, in turn, activates YAP and stimulates cancer cell growth. Knockdown of ERBB3 or HBEGF eliminates YAP effects on cell growth and transformation, whereas knockdown of YAP abrogates NRG1- and HBEGF-stimulated cell proliferation. Collectively, our study demonstrates the existence of HBEGF & NRGs/ERBBs/YAP/HBEGF & NRGs autocrine loop that controls ovarian cell tumorigenesis and cancer progression.

A prospective outcomes analysis of palliative procedures performed for malignant intestinal obstruction due to recurrent ovarian cancer.

PubMed

Chi, Dennis S; Phaëton, Rebecca; Miner, Thomas J; Kardos, Steven V; Diaz, John P; Leitao, Mario M; Gardner, Ginger; Huh, Jae; Tew, William P; Konner, Jason A; Sonoda, Yukio; Abu-Rustum, Nadeem R; Barakat, Richard R; Jaques, David P

2009-08-01

To obtain prospective outcomes data on patients (pts) undergoing palliative operative or endoscopic procedures for malignant bowel obstruction due to recurrent ovarian cancer. An institutional study was conducted from July 2002 to July 2003 to prospectively identify pts who underwent an operative or endoscopic procedure to palliate the symptoms of advanced cancer. This report focuses on pts with malignant bowel obstruction due to recurrent ovarian cancer. Procedures performed with an upper or lower gastrointestinal (GI) endoscope were considered "endoscopic." All other cases were classified as "operative." Following the procedure, the presence or absence of symptoms was determined and followed over time. All pts were followed until death. Palliative interventions were performed on 74 gynecologic oncology pts during the study period, of which 26 (35%) were for malignant GI obstruction due to recurrent ovarian cancer. The site of obstruction was small bowel in 14 (54%) cases and large bowel in 12 (46%) cases. Palliative procedures were operative in 14 (54%) pts and endoscopic in the other 12 (46%). Overall, symptomatic improvement or resolution within 30 days was achieved in 23 (88%) of 26 patients, with 1 (4%) postprocedure mortality. At 60 days, 10 (71%) of 14 pts who underwent operative procedures and 6 (50%) of 12 pts who had endoscopic procedures had symptom control. Median survival from the time of the palliative procedure was 191 days (range, 33-902) for those undergoing an operative procedure and 78 days (range, 18-284) for those undergoing an endoscopic procedure. Patients with malignant bowel obstructions due to recurrent ovarian cancer have a high likelihood of experiencing relief of symptoms with palliative procedures. Although recurrence of symptoms is common, durable palliation and extended survival are possible, especially in those patients selected for operative intervention.

G protein-coupled receptor 30 (GPR30) mediates gene expression changes and growth response to 17beta-estradiol and selective GPR30 ligand G-1 in ovarian cancer cells.

PubMed

Albanito, Lidia; Madeo, Antonio; Lappano, Rosamaria; Vivacqua, Adele; Rago, Vittoria; Carpino, Amalia; Oprea, Tudor I; Prossnitz, Eric R; Musti, Anna Maria; Andò, Sebastiano; Maggiolini, Marcello

2007-02-15

Estrogens play a crucial role in the development of ovarian tumors; however, the signal transduction pathways involved in hormone action are still poorly defined. The orphan G protein-coupled receptor 30 (GPR30) mediates the nongenomic signaling of 17beta-estradiol (E2) in a variety of estrogen-sensitive cancer cells through activation of the epidermal growth factor receptor (EGFR) pathway. Whether estrogen receptor alpha (ERalpha) also contributes to GPR30/EGFR signaling is less understood. Here, we show that, in ERalpha-positive BG-1 ovarian cancer cells, both E2 and the GPR30-selective ligand G-1 induced c-fos expression and estrogen-responsive element (ERE)-independent activity of a c-fos reporter gene, whereas only E2 stimulated an ERE-responsive reporter gene, indicating that GPR30 signaling does not activate ERalpha-mediated transcription. Similarly, both ligands up-regulated cyclin D1, cyclin E, and cyclin A, whereas only E2 enhanced progesterone receptor expression. Moreover, both GPR30 and ERalpha expression are required for c-fos stimulation and extracellular signal-regulated kinase (ERK) activation in response to either E2 or G-1. Inhibition of the EGFR transduction pathway inhibited c-fos stimulation and ERK activation by either ligand, suggesting that in ovarian cancer cells GPR30/EGFR signaling relays on ERalpha expression. Interestingly, we show that both GPR30 and ERalpha expression along with active EGFR signaling are required for E2-stimulated and G-1-stimulated proliferation of ovarian cancer cells. Because G-1 was able to induce both c-fos expression and proliferation in the ERalpha-negative/GPR30-positive SKBR3 breast cancer cells, the requirement for ERalpha expression in GPR30/EGFR signaling may depend on the specific cellular context of different tumor types.

Avoiding OHSS: Controlled Ovarian Low-Dose Stimulation in Women with PCOS.

PubMed

Fischer, D; Reisenbüchler, C; Rösner, S; Haussmann, J; Wimberger, P; Goeckenjan, M

2016-06-01

The polycystic ovary syndrome is a common endocrine disorder which influences outcome and potential risks involved with controlled ovarian stimulation for artificial reproductive techniques (ART). Concrete practical recommendations for the dosage of gonadotropins, the preferred protocol and preventive methods to avoid ovarian hyperstimulation syndrome (OHSS) are lacking. We present retrospective data of 235 individually calculated gonadotropin low-dose stimulations for ART in a single center from 2012 to 2014. Clinical data and outcome parameter of patients diagnosed with PCOS according to Rotterdam criteria (n = 39) were compared with patients without PCOS (n = 196). The starting dose of gonadotropins was individually calculated depending on patients' age, BMI, ovarian reserve, ovarian response in previous cycles, and diagnostic criteria of PCOS. Mean age and duration of infertility did not differ between the groups, whereas mean BMI (p = 0.007) and AMH (p < 0.001) were higher in the PCOS-group. A lower mean FSH-starting and maximum dose was administered to women with PCOS (p < 0.001). The biochemical pregnancy rate of 42.4 % and the clinical pregnancy rate of 32.2 % for PCOS-patients did not differ from those of the control group (42.2 % and 34.4 % respectively). Neither mild, nor moderate or severe manifestation of OHSS occurred significantly more often in patients with PCOS. Our study supports the use of a calculated low-dose FSH-stimulation strategy in ART for patients with PCOS. Further randomized clinical trials should confirm this strategy and lead to define individual risk factors for OHSS, which can be used for recommendation of safer ART-techniques like in vitro maturation.

Recombinant human follicle-stimulating hormone (r-hFSH) plus recombinant luteinizing hormone versus r-hFSH alone for ovarian stimulation during assisted reproductive technology: systematic review and meta-analysis.

PubMed

Lehert, Philippe; Kolibianakis, Efstratios M; Venetis, Christos A; Schertz, Joan; Saunders, Helen; Arriagada, Pablo; Copt, Samuel; Tarlatzis, Basil

2014-02-20

The potential benefit of adding recombinant human luteinizing hormone (r-hLH) to recombinant human follicle-stimulating hormone (r-hFSH) during ovarian stimulation is a subject of debate, although there is evidence that it may benefit certain subpopulations, e.g. poor responders. A systematic review and a meta-analysis were performed. Three databases (MEDLINE, Embase and CENTRAL) were searched (from 1990 to 2011). Prospective, parallel-, comparative-group randomized controlled trials (RCTs) in women aged 18-45 years undergoing in vitro fertilization, intracytoplasmic sperm injection or both, treated with gonadotrophin-releasing hormone analogues and r-hFSH plus r-hLH or r-hFSH alone were included. The co-primary endpoints were number of oocytes retrieved and clinical pregnancy rate. Analyses were conducted for the overall population and for prospectively identified patient subgroups, including patients with poor ovarian response (POR). In total, 40 RCTs (6443 patients) were included in the analysis. Data on the number of oocytes retrieved were reported in 41 studies and imputed in two studies. Therefore, data were available from 43 studies (r-hFSH plus r-hLH, n=3113; r-hFSH, n=3228) in the intention-to-treat (ITT) population (all randomly allocated patients, including imputed data). Overall, no significant difference in the number of oocytes retrieved was found between the r-hFSH plus r-hLH and r-hFSH groups (weighted mean difference -0.03; 95% confidence interval [CI] -0.41 to 0.34). However, in poor responders, significantly more oocytes were retrieved with r-hFSH plus r-hLH versus r-hFSH alone (n=1077; weighted mean difference +0.75 oocytes; 95% CI 0.14-1.36). Significantly higher clinical pregnancy rates were observed with r-hFSH plus r-hLH versus r-hFSH alone in the overall population analysed in this review (risk ratio [RR] 1.09; 95% CI 1.01-1.18) and in poor responders (n=1179; RR 1.30; 95% CI 1.01-1.67; ITT population); the observed difference was more pronounced in poor responders. These data suggest that there is a relative increase in the clinical pregnancy rates of 9% in the overall population and 30% in poor responders. In conclusion, this meta-analysis suggests that the addition of r-hLH to r-hFSH may be beneficial for women with POR.

Association between preconception maternal beverage intake and in vitro fertilization outcomes.

PubMed

Machtinger, Ronit; Gaskins, Audrey J; Mansur, Abdallah; Adir, Michal; Racowsky, Catherine; Baccarelli, Andrea A; Hauser, Russ; Chavarro, Jorge E

2017-12-01

To study whether maternal intake of beverage type affects IVF outcomes. A prospective study. Tertiary, university-affiliated center. Three hundred forty women undergoing IVF from 2014 through 2016 for infertility as well as for pregenetic diagnosis for autosomal recessive diseases were enrolled during ovarian stimulation and completed a questionnaire describing their usual beverage consumption. None. IVF outcomes were abstracted from medical records. Total caffeine intake was estimated by summing the caffeine content for specific beverages multiplied by frequency of intake. Associations between specific types of beverages and IVF outcomes were analyzed using Poisson and logistic regression models adjusting for possible confounders. Higher intake of sugared soda was associated with lower total, mature, and fertilized oocytes and top-quality embryos after ovarian stimulation. Women who consumed sugared soda had, on average, 1.1 fewer oocytes retrieved, 1.2 fewer mature oocytes retrieved, 0.6 fewer fertilized oocytes, and 0.6 fewer top-quality embryos compared with women who did not consume sugared soda. Furthermore, compared with women who did not drink sugared soda, the adjusted difference in percent of cycles resulting in live birth for women consuming 0.1-1 cups/day and >1 cup/day were -12% and -16%, respectively. No associations were found between consumption of coffee, caffeine, or diet sodas and IVF outcome. Sugared beverages, independent of their caffeine content, may be a bigger threat to reproductive success than caffeine and caffeinated beverages without added sugar. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Conversion to IUI versus continuance with IVF in low responder patients: A systematic review.

PubMed

Fujii, Dennis T; Quesnell, Jodi L; Heitmann, Ryan J

2018-06-01

Poor response to ovarian hyper-stimulation can be difficult to predict prior to stimulation even when factoring in patient age and ovarian reserve testing. When faced with the situation of poor response, patients and providers have the difficult decision to proceed with oocyte retrieval, convert to intrauterine insemination (IUI), or cancel the cycle. Although this is not an uncommon scenario, there is little data available to assist with the counseling of these patients. We performed a systematic review of published studies comparing clinical pregnancy and live births between those patients continuing with in-vitro fertilization (IVF) and those converting to IUI. PubMed and Ovid were searched for all retrospective and randomized studies using the Keywords 'in-vitro fertilization', 'intrauterine insemination', 'poor responders', 'clinical pregnancy' and 'live birth rates'. A total of seven retrospective studies and one randomized control trial were reviewed. When evaluating poor responders as a group, six studies reported higher overall clinical pregnancy rates and five studies reported overall increased live birth rates with continuance of IVF. When stratified by the number of follicles produced, continuance of IVF demonstrated higher clinical pregnancy and live birth rates with ≥ 2 follicles. When only one follicle developed there were no significant differences in clinical pregnancy or live birth rates between the two groups. In patients undergoing IVF with ≤4 follicles, continuance with IVF may lead to higher clinical pregnancy and live birth compared to conversion to IUI except in patients with monofollicular development, although additional randomized controlled trials are needed to confirm these findings. Published by Elsevier B.V.

Pituitary-adrenal and sympathetic nervous system responses to psychiatric disorders in women undergoing in vitro fertilization treatment.

PubMed

An, Yuan; Wang, Zhuoran; Ji, Hongping; Zhang, Yajuan; Wu, Kun

2011-08-01

To evaluate whether psychological variables as well as changes in hypothalamus-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) at baseline and in response to a psychosocial stressor affect the chance of achieving pregnancy in women undergoing a first in vitro fertilization (IVF) cycle. Prospective study. Private IVF center. 264 women undergoing IVF or intracytoplasmic sperm injection (ICSI) treatment. Oocyte retrieval after ovarian stimulation. Standardized psychological questionnaires to assess anxiety and depression, and norepinephrine and cortisol in serum or follicular fluid measured by specific assays. Only a trend increase was found in psychological scores during treatment, which did not affect the ongoing pregnancy rates. On the oocyte retrieval day, a statistically significant increase in norepinephrine and cortisol concentrations was found. Lower concentrations of norepinephrine and cortisol, both in serum and follicular fluid, were found in women whose treatments were successful. Concentrations of steroid in serum before treatment and in follicular fluid were positively associated with the State Anxiety scores. Norepinephrine and cortisol concentrations may negatively influence the clinical pregnancy rate in IVF treatment. These biological stress markers could be one of the links in the complex relationship between psychosocial stress and outcome after IVF-ICSI. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Progress in understanding human ovarian folliculogenesis and its implications in assisted reproduction.

PubMed

Yang, Dong Zi; Yang, Wan; Li, Yu; He, Zuanyu

2013-02-01

To highlight recent progress in understanding the pattern of follicular wave emergence of human menstrual cycle, providing a brief overview of the new options for human ovarian stimulation and oocyte retrieval by making full use of follicular physiological waves of the patients either with normal or abnormal ovarian reserve. Literature review and editorial commentary. There has been increasing evidence to suggest that multiple (two or three) antral follicular waves are recruited during human menstrual cycle. The treatment regimens designed based on the theory of follicular waves, to promote increased success with assisted reproduction technology (ART) and fertility preservation have been reported. These new options for human ovarian stimulation and oocyte retrieval by making full use of follicular waves of the patients either with normal or abnormal ovarian reserve lead to new thinking about the standard protocols in ART and challenge the traditional theory that a single wave of antral follicles grows only during the follicular phase of the menstrual cycle. The understanding of human ovarian folliculogenesis may have profound implications in ART and fertility preservation. Further studies are needed to evaluate the optimal regimens in ART based on the theory of follicular waves and to identify non-invasive markers for predicting the outcome and the potential utilities of follicles obtained from anovulatory follicular waves in ART.

Willingness to pay and conjoint analysis to determine women's preferences for ovarian stimulating hormones in the treatment of infertility in Spain.

PubMed

Palumbo, A; De La Fuente, P; Rodríguez, M; Sánchez, F; Martínez-Salazar, J; Muñoz, M; Marqueta, J; Hernández, J; Espallardo, O; Polanco, C; Paz, S; Lizán, L

2011-07-01

Despite many advances in assisted reproductive techniques (ART), little is known about preferences for technological developments of women undergoing fertility treatments. The aims of this study were to investigate the preferences of infertile women undergoing ART for controlled ovarian stimulation (COS) treatments; to determine the utility values ascribed to different attributes of COS treatments; and to estimate women's willingness to pay (WTP) for COS. A representative sample of ambulatory patients ready to receive, or receiving, COS therapies for infertility were recruited from seven specialized private centres in six autonomous communities in Spain. Descriptive, inferential and conjoint analyses (CA) were used to elicit preferences and WTP. Attributes and levels of COS treatments were identified by literature review and two focus groups with experts and patients. WTP valuations were derived by a combination of double-bounded (closed-ended) and open questions and contingent ranking methods. In total, 160 patients [mean (standard deviation; SD) age: 35.8 (4.2) years] were interviewed. Over half of the participants (55.0%) had a high level of education (university degree), most (78.8%) were married and half (50.0%) had an estimated net income of >€1502 per month and had paid a mean (SD) €1194.17 (€778.29) for their most recent hormonal treatment. The most frequent causes of infertility were related to sperm abnormalities (50.3%). In 30.6% of cases, there were two causes of infertility. The maximum WTP for COS treatment was €800 (median) per cycle; 35.5% were willing to pay an additional €101-€300 for a 1-2% effectiveness gain in the treatment. Utility values (CA) showed that effectiveness was the most valued attribute (39.82), followed by costs (18.74), safety (17.75) and information sharing with physicians (14.93). WTP for COS therapies exceeds current cost. Additional WTP exists for 1-2% effectiveness improvement. Effectiveness and costs were the most important determinants of preferences, followed by safety and information sharing with physicians.

Willingness to pay and conjoint analysis to determine women's preferences for ovarian stimulating hormones in the treatment of infertility in Spain

PubMed Central

Palumbo, A.; De La Fuente, P.; Rodríguez, M.; Sánchez, F.; Martínez-Salazar, J.; Muñoz, M.; Marqueta, J.; Hernández, J.; Espallardo, O.; Polanco, C.; Paz, S.; Lizán, L.

2011-01-01

BACKGROUND Despite many advances in assisted reproductive techniques (ART), little is known about preferences for technological developments of women undergoing fertility treatments. The aims of this study were to investigate the preferences of infertile women undergoing ART for controlled ovarian stimulation (COS) treatments; to determine the utility values ascribed to different attributes of COS treatments; and to estimate women's willingness to pay (WTP) for COS. METHODS A representative sample of ambulatory patients ready to receive, or receiving, COS therapies for infertility were recruited from seven specialized private centres in six autonomous communities in Spain. Descriptive, inferential and conjoint analyses (CA) were used to elicit preferences and WTP. Attributes and levels of COS treatments were identified by literature review and two focus groups with experts and patients. WTP valuations were derived by a combination of double-bounded (closed-ended) and open questions and contingent ranking methods. RESULTS In total, 160 patients [mean (standard deviation; SD) age: 35.8 (4.2) years] were interviewed. Over half of the participants (55.0%) had a high level of education (university degree), most (78.8%) were married and half (50.0%) had an estimated net income of >€1502 per month and had paid a mean (SD) €1194.17 (€778.29) for their most recent hormonal treatment. The most frequent causes of infertility were related to sperm abnormalities (50.3%). In 30.6% of cases, there were two causes of infertility. The maximum WTP for COS treatment was €800 (median) per cycle; 35.5% were willing to pay an additional €101–€300 for a 1–2% effectiveness gain in the treatment. Utility values (CA) showed that effectiveness was the most valued attribute (39.82), followed by costs (18.74), safety (17.75) and information sharing with physicians (14.93). CONCLUSIONS WTP for COS therapies exceeds current cost. Additional WTP exists for 1–2% effectiveness improvement. Effectiveness and costs were the most important determinants of preferences, followed by safety and information sharing with physicians. PMID:21558333

Economic impact of ovarian stimulation with corifollitropin alfa versus conventional daily gonadotropins in oocyte donors: a randomized study.

PubMed

Cruz, María; Alamá, Pilar; Muñoz, Manuel; Collado, Diana; Blanes, Carlos; Solbes, Enrique; Requena, Antonio

2017-06-01

Assisted reproductive technologies are well-established treatments for many types of subfertility representing substantial economic and healthcare implications for patients, healthcare providers and society as a whole. In order to optimize outcomes according to the type of gonadotrophins within an oocyte donor programme, we performed an economic evaluation based on data collected in a multicentre, prospective, randomized study within three private clinics belonging to the IVI Group. Results showed no relevant between-group differences in the clinical variables. According to the economic analysis, ovarian stimulation with corifollitropin alfa increased the overall cost of the treatment as well as the cost per retrieved and effective oocyte, although the differences were not statistically significant. In conclusion, cost savings can be achieved using cheaper gonadotrophins during ovarian stimulation. The cost of corifollitropin alfa compared with recombinant FSH and highly purified human menopausal gonadotrophin should be considered when making treatment decisions. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Ovarian function during puberty in girls with type 1 diabetes mellitus: response to leuprolide.

PubMed

Codner, Ethel; Mook-Kanamori, Dennis; Bazaes, Rodrigo A; Unanue, Nancy; Sovino, Hugo; Ugarte, Francisca; Avila, Alejandra; Iñiguez, German; Cassorla, Fernando

2005-07-01

An increased prevalence of polycystic ovary syndrome (PCOS) has been reported in adult women with type 1 diabetes mellitus (DM1). We investigated whether these hormonal abnormalities begin during puberty by evaluating the ovarian steroidogenic response to leuprolide acetate. We studied 56 adolescent girls with DM1 (aged 12.3 +/- 0.2 yr) and 64 healthy girls (C) (aged 11.9 +/- 0.2 yr) up to 2 yr post menarche, matched by age, body mass index, and pubertal development. We evaluated anthropometrical data and Ferriman-Gallway score and performed a leuprolide test (500 microg sc) to study ovarian function. Ovarian volume was determined by transabdominal ultrasonography. We found five DM1 but no C girls with abnormally located terminal hair (Fisher's exact, P < 0.05). Free androgen index increased throughout puberty in girls with DM1 (ANOVA, P < 0.0001), which was associated with a decrease in SHBG levels in girls with DM1 (ANOVA, P < 0.0001). Stimulated 17OH progesterone (17OHProg) increased throughout puberty only in girls with DM1 (ANOVA, P < 0.01). Girls with DM1 at Tanner stage 5 had higher stimulated LH to FSH ratio, testosterone, and 17OHProg levels than girls at Tanner stage 4. In contrast, in C girls the stimulated testosterone, 17OHProg, and LH to FSH ratio were similar at Tanner stages 4 and 5. Ovarian volumes and uterine length were larger in girls with DM1 (analysis of covariance, P < 0.05). These data suggest that patients with DM1 have differences in ovarian steroidogenic response to leuprolide, compared with C girls during puberty. Future studies in young women should clarify whether these findings are related to the pathogenesis of hyperandrogenism later in life.

Successful ovarian autotransplant with no vascular reanastomosis in rats.

PubMed

Barros, Flávio S V; de Oliveira, Rodrigo M; Alves, Felipe M T; Sampaio, Marcos; Geber, Selmo

2008-12-15

Preservation of ovarian functions in woman with premature ovarian failure remains an issue in reproductive medicine. Hormone replacement therapy for maintaining endocrine functions, and cryopreservation of embryos or oocytes for those who wish pregnancy, are some of the choices. However, ovarian transplantation is a more physiological alternative, although problems related to ovarian ischemia have been reported. Herein, we investigated the viability of autologous transplantation of the ovarian tissue into the rat peritoneum, without vascular reanastomosis. Twenty animals in the study group had both ovaries excised, and each ovary was dissected into two halves. A half of an ovary was autotransplanted to the peritoneal surface, closely located to the left epigastric vessels. This simple procedure does not require surgical vascular reanastomosis while it maintains appropriate follicular growth and therefore should be further considered as an alternative for women undergoing oophorectomy, not only to maintain endocrine functions but also for fertility preservation.

Outcomes and Recommendations of an Indian Expert Panel for Improved Practice in Controlled Ovarian Stimulation for Assisted Reproductive Technology

PubMed Central

Ahemmed, Baiju; Sundarapandian, Vani; Gutgutia, Rohit; Balasubramanyam, Sathya; Jagtap, Richa; Biliangady, Reeta; Gupta, Priti; Jadhav, Sachin; Satwik, Ruma; Thakor, Priti

2017-01-01

Purpose. To improve success of in vitro fertilization (IVF), assisted reproductive technology (ART) experts addressed four questions. What is optimum oocytes number leading to highest live birth rate (LBR)? Are cohort size and embryo quality correlated? Does gonadotropin type affect oocyte yield? Should “freeze-all” policy be adopted in cycles with progesterone >1.5 ng/mL on day of human chorionic gonadotropin (hCG) administration? Methods. Electronic database search included ten studies on which panel gave opinions for improving current practice in controlled ovarian stimulation for ART. Results. Strong association existed between retrieved oocytes number (RON) and LBRs. RON impacted likelihood of ovarian hyperstimulation syndrome (OHSS). Embryo euploidy decreased with age, not with cohort size. Progesterone > 1.5 ng/dL did not impair cycle outcomes in patients with high cohorts and showed disparate results on day of hCG administration. Conclusions. Ovarian stimulation should be designed to retrieve 10–15 oocytes/treatment. Accurate dosage, gonadotropin type, should be selected as per prediction markers of ovarian response. Gonadotropin-releasing hormone (GnRH) antagonist based protocols are advised to avoid OHSS. Cumulative pregnancy rate was most relevant pregnancy endpoint in ART. Cycles with serum progesterone ≥1.5 ng/dL on day of hCG administration should not adopt “freeze-all” policy. Further research is needed due to lack of data availability on progesterone threshold or index. PMID:28246628

Outcomes and Recommendations of an Indian Expert Panel for Improved Practice in Controlled Ovarian Stimulation for Assisted Reproductive Technology.

PubMed

Ahemmed, Baiju; Sundarapandian, Vani; Gutgutia, Rohit; Balasubramanyam, Sathya; Jagtap, Richa; Biliangady, Reeta; Gupta, Priti; Jadhav, Sachin; Satwik, Ruma; Dewda, Pavitra Raj; Thakor, Priti; Esteves, Sandro C

2017-01-01

Purpose. To improve success of in vitro fertilization (IVF), assisted reproductive technology (ART) experts addressed four questions. What is optimum oocytes number leading to highest live birth rate (LBR)? Are cohort size and embryo quality correlated? Does gonadotropin type affect oocyte yield? Should "freeze-all" policy be adopted in cycles with progesterone >1.5 ng/mL on day of human chorionic gonadotropin (hCG) administration? Methods. Electronic database search included ten studies on which panel gave opinions for improving current practice in controlled ovarian stimulation for ART. Results. Strong association existed between retrieved oocytes number (RON) and LBRs. RON impacted likelihood of ovarian hyperstimulation syndrome (OHSS). Embryo euploidy decreased with age, not with cohort size. Progesterone > 1.5 ng/dL did not impair cycle outcomes in patients with high cohorts and showed disparate results on day of hCG administration. Conclusions. Ovarian stimulation should be designed to retrieve 10-15 oocytes/treatment. Accurate dosage, gonadotropin type, should be selected as per prediction markers of ovarian response. Gonadotropin-releasing hormone (GnRH) antagonist based protocols are advised to avoid OHSS. Cumulative pregnancy rate was most relevant pregnancy endpoint in ART. Cycles with serum progesterone ≥1.5 ng/dL on day of hCG administration should not adopt "freeze-all" policy. Further research is needed due to lack of data availability on progesterone threshold or index.

The VEGF and PEDF levels in the follicular fluid of patients co- treated with LETROZOLE and gonadotropins during the stimulation cycle.

PubMed

Haas, Jigal; Bassil, Rawad; Gonen, Noa; Meriano, Jim; Jurisicova, Andrea; Casper, Robert F

2018-05-29

Previous studies have shown that androgens, in addition to serving as precursors for ovarian estrogen synthesis, also have a fundamental role in primate ovarian follicular development by augmentation of FSH receptor expression on granulosa cells. Recent studies have shown that aromatase inhibitor, letrozole, improves ovarian response to FSH in normal and poor responder patients, possibly by increasing intraovarian androgen levels. Studies in mice also showed an effect of letrozole to increase pigment epithelium-derived factor (PEDF) and to lower vascular epithelial growth factor (VEGF), which might be expected to reduce the risk of ovarian hyperstimulation syndrome (OHSS) with stimulation. The aim of this study was to compare the VEGF and PEDF levels in the follicular fluids of normal responders treated with letrozole and gonadotropins during the ovarian stimulation with patients treated with gonadotropins only. A single center, prospective clinical trial. We collected follicular fluid from 26 patients, on a GnRH antagonist protocol, dual triggered with hCG and GnRH agonist. The patients in one group were co-treated with letrozole and gonadotropins during the ovarian stimulation and the patients in the other group were treated with gonadotropins only. VEGF, PEDF, estrogen, progesterone and testosterone levels were measured by ELISA kits. The age of the patients, the total dose of gonadotropins and the number of oocytes were comparable between the two groups. In the follicular fluid, the estrogen levels (2209 nmol/l vs. 3280 nmol/l, p = 0.02) were significantly decreased, and the testosterone levels (246.5 nmol/l vs. 40.7 nmol/l, p < 0.001) were significantly increased in the letrozole group compared to the gonadotropin only group. The progesterone levels (21.4 μmol/l vs. 17.5 p = NS) were comparable between the two groups. The VEGF levels (2992 pg/ml vs. 1812 pg/ml p = 0.02) were significantly increased and the PEDF levels (9.7 ng/ml vs 17.3 ng/ml p < 0.001) were significantly decreased in the letrozole group. Opposite to observations in the mouse, we found that VEGF levels were increased and PEDF levels were decreased in the follicular fluid in patients treated with letrozole during the stimulation cycles. Further investigation is required to determine if patients treated with letrozole during the IVF stimulation protocol are at increased risk for developing OHSS as a result of these findings.

Ovarian transposition in young women and fertility sparing.

PubMed

Mossa, B; Schimberni, M; Di Benedetto, L; Mossa, S

2015-09-01

Ovarian transposition is a highly effective surgical procedure used to preserve ovarian function in premenopausal patients with cancers requiring postoperative or primary pelvic radiotherapy. Pelvic irradiation determines severe damage of ovarian DNA and iatrogenic ovarian failure with premature menopause, necessity of long-term hormone replacement therapy and infertility. We conducted an extensive research of the literature in Medline between January 2000 and April 2015 using the key-words "ovarian transposition radiotherapy", "radiotherapy gonadal function", radiotherapy fertility sparing". The population included young women with normal ovarian function affected by cancers that required pelvic radiotherapy. We have examined 32 articles reporting on 1189 women undergoing ovarian transposition. Median age was 32.5 years, follow up was median 48 months. The procedure has been performed in patients less than 40 years of age. Surgery has been achieved by laparotomy or laparoscoy. We have analyzed effects of radiotherapy on ovarian function. The proportion of women treated by ovarian transposition preserved ovarian function was 70%. About 86% of patients did not develop ovarian cysts and in 98-99% of cases did not occur any metastatic disease. Ovarian transposition is associated with significant preservation of ovarian function and a low frequency of complications as cysts and metastasis. In 31% of cases the procedure can fail. Further studies are needed to evaluate the efficacy of ovarian transposition and the follow up. Ovarian transposition should be discussed at the time of cancer diagnosis in every premenopausal woman requiring pelvic radiotherapy.

Observational Study to Assess the Therapeutic Value of Four Ovarian Hyperstimulation Protocols in IVF After Pituitary Suppression with GnRH Antagonists in Normally Responding Women.

PubMed

Ana, Monzó; Vicente, Montañana; María, Rubio José; Trinidad, García-Gimeno; Alberto, Romeu

2011-02-22

To compare the clinical results of four different protocols of COH for IVF-ICSI in normovulatory women, using in all cases pituitary suppression with GnRH antagonists. A single center, open label, parallel-controlled, prospective, post-authorization study under the approved conditions for use where 305 normal responders women who were candidates to COH were assigned to r-FSH +hp-hMG (n = 51, Group I), hp-hMG (n = 61, Group II), fixed-dose r-FSH (n = 118, Group III), and r-FSH with potential dose adjustment (n = 75, Group IV) to subsequently undergo IVF-ICSI. During stimulation, Group IV needed significantly more days of stimulation as compared to Group II [8.09 ± 1.25 vs. 7.62 ± 1.17; P < 0.05], but was the group in which more oocytes were recovered [Group I: 9.43 ± 4.99 vs. Group II: 8.96 ± 4.82 vs. Group III: 8.78 ± 3.72 vs. Group IV: 11.62 ± 5.80; P < 0.05]. No significant differences were seen between the groups in terms of clinical and ongoing pregnancy, but among patients in whom two embryos with similar quality parameters (ASEBIR) were transferred, the group treated with hp-hMG alone achieved a significantly greater clinical pregnancy rate as compared to all other groups [Group I: 31.6%, Group II: 56.4%, Group III: 28.7%, Group IV: 32.7%; P < 0.05]. Although randomized clinical trials should be conducted to achieve a more reliable conclusion, these observations support the concept that stimulation with hp-hMG could be beneficial in normal responders women undergoing pituitary suppression with GnRH antagonists.

Prospective evaluation of basal stromal Doppler studies in women with good ovarian reserve and infertility undergoing in vitro fertilization-embryo transfer treatment: patients with polycystic ovary syndrome versus ovulatory patients.

PubMed

Younis, Johnny S; Jadaon, Jimmy E; Haddad, Sami; Izhaki, Ido; Ben-Ami, Moshe

2011-04-01

To gain insight into the ovarian stromal blood flow in women with polycystic ovary syndrome (PCOS) as compared with women with normal ovulation, good ovarian reserve, and infertility and to evaluate the role of stromal flow in these patients to predict clinical pregnancy in an assisted reproductive technologies setting. A prospective observational cohort study. A university-affiliated reproductive medicine unit. Eighteen consecutive patients with PCOS (study) compared with 101 patients with normal ovulation and infertility (control), undergoing their first IVF-ET treatment at our unit. Women with low ovarian reserve were excluded a priori from evaluation. Basal ovarian reserve parameters and stromal flow studies were conducted as routinely performed in our unit, in a natural cycle before starting treatment. None. Basal ovarian endocrine, sonographic, and stromal flow studies were compared between the groups. After completion of treatment, the stromal flow studies were compared between conception and nonconception cycles. Patients' characteristics and basal ovarian reserve, including endocrine and sonographic parameters, were similar between the PCOS and control groups. Only antral follicle count and LH/FSH ratio were higher in the PCOS as compared with the control group, corresponding to 15.11 ± 6.05 versus 9.05 ± 4.77 and 1.14 ± 0.64 versus 0.79 ± 0.37, respectively. Basal stromal flow indices were similar between the PCOS group and the group with normal ovulation and good ovarian reserve. Clinical pregnancy rate per initiated cycle was 50.0% and 39.6% in the PCOS and control groups, respectively, with no significant difference. Flow indices were similar between conception cycles in the PCOS and control groups. As well, the indices did not differ significantly between conception and nonconception cycles within the PCOS and control groups. Basal ovarian stromal blood flow does not differ between women with PCOS and women with normal ovulation, good ovarian reserve, and infertility. Moreover, stromal flow has no predictive value, in these patients, for clinical pregnancy achievement in an IVF-ET setting. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Aspiration and ethanol sclerotherapy to treat recurrent ovarian endometriomas prior to in vitro fertilization - a pilot study.

PubMed

André, Gustavo Mendonça; Vilarino, Fábia Lima; Christofolini, Denise Maria; Bianco, Bianca; Barbosa, Caio Parente

2011-12-01

To describe the evolution of controlled ovarian hyperstimulation in women with recurrent ovarian endometriomas treated with sclerotherapy. Twenty-one patients with a laparoscopic diagnosis of stage III or IV endometriosis who had an endometrioma larger than 3 cm before ovarian hyperstimulation for in vitro fertilization were included in the study. After using a GnRH agonist analog for at least 20 days, the cysts were punctured using ultrasound guidance and subsequent ethanol sclerotherapy was performed. Then, the patients were stimulated with 100 or 200 U/day of recombinant follicle stimulating hormone, varying the dose according to the patient's age or history of a previous unilateral oophorectomy. The ovarian cysts had an average diameter of 4.7 ± 1.4 cm and did not recur after aspiration during the ovulation induction. Oocyte extraction occurred after 11 days of hyperstimulation, with 3.95 ± 3.30 oocytes obtained per cycle, on average. Embryo transfer occurred in 71.4% (15/21) of patients, and the pregnancy rate after transfer was 20% (3/15). Aspiration followed by ethanol sclerotherapy prior to in vitro fertilization can be an option for patients who desire a pregnancy and have recurrent endometriomas.

Shifting paradigms in diminished ovarian reserve and advanced reproductive age in assisted reproduction: customization instead of conformity.

PubMed

Reed, Beverly G; Babayev, Samir N; Bukulmez, Orhan

2015-05-01

As women are increasingly delaying childbearing into their 30s and beyond, diminished ovarian reserve (DOR) and advanced reproductive age (ARA) patients are bound to become a large proportion of all assisted reproductive technology practices. Traditional controlled ovarian stimulation (COS) protocols for DOR and/or ARA have had some limited success, but pregnancy rates are lower and cycle cancellation rates are higher than their younger counterparts with normal ovarian reserve. Though many physicians have a selection of favorite standard protocols that they use, patients with DOR may require closer monitoring and customization of the treatment cycle to address the common problems that come with low ovarian reserve. Frequent issues that surface in women with DOR and/or ARA include poor follicular response, premature luteinizing hormone surge, and poor embryo quality. Limited published evidence exists to guide treatment for DOR. However, use of minimal or mild doses of gonadotropins, avoidance of severe pituitary suppression, and consideration for luteal phase stimulation and a "freeze all" approach are possible customized treatment options that can be considered for such patients who have failed more traditional COS protocols. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Expression of the Homeobox Gene HOXA9 in Ovarian Cancer Induces Peritoneal Macrophages to Acquire an M2 Tumor-Promoting Phenotype

PubMed Central

Ko, Song Yi; Ladanyi, Andras; Lengyel, Ernst; Naora, Honami

2015-01-01

Tumor-associated macrophages (TAMs) exhibit an M2 macrophage phenotype that suppresses anti-tumor immune responses and often correlates with poor outcomes in patients with cancer. Patients with ovarian cancer frequently present with peritoneal carcinomatosis, but the mechanisms that induce naïve peritoneal macrophages into TAMs are poorly understood. In this study, we found an increased abundance of TAMs in mouse i.p. xenograft models of ovarian cancer that expressed HOXA9, a homeobox gene that is associated with poor prognosis in patients with ovarian cancer. HOXA9 expression in ovarian cancer cells stimulated chemotaxis of peritoneal macrophages and induced macrophages to acquire TAM-like features. These features included induction of the M2 markers, CD163 and CD206, and the immunosuppressive cytokines, IL-10 and chemokine ligand 17, and down-regulation of the immunostimulatory cytokine, IL-12. HOXA9-mediated induction of TAMs was primarily due to the combinatorial effects of HOXA9-induced, tumor-derived transforming growth factor-β2 and chemokine ligand 2 levels. High HOXA9 expression in clinical specimens of ovarian cancer was strongly associated with increased abundance of TAMs and intratumoral T-regulatory cells and decreased abundance of CD8+ tumor-infiltrating lymphocytes. Levels of immunosuppressive cytokines were also elevated in ascites fluid of patients with tumors that highly expressed HOXA9. HOXA9 may, therefore, stimulate ovarian cancer progression by promoting an immunosuppressive microenvironment via paracrine effects on peritoneal macrophages. PMID:24332016

Association Between Progesterone Elevation on the Day of Human Chronic Gonadotropin Trigger and Pregnancy Outcomes After Fresh Embryo Transfer in In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles.

PubMed

Esteves, Sandro C; Khastgir, Gautam; Shah, Jatin; Murdia, Kshitiz; Gupta, Shweta Mittal; Rao, Durga G; Dash, Soumyaroop; Ingale, Kundan; Patil, Milind; Moideen, Kunji; Thakor, Priti; Dewda, Pavitra

2018-01-01

Progesterone elevation (PE) during the late follicular phase of controlled ovarian stimulation in fresh embryo transfer in vitro fertilization (IVF)/intracytoplasmic sperm injection cycles has been claimed to be associated with decreased pregnancy rates. However, the evidence is not unequivocal, and clinicians still have questions about the clinical validity of measuring P levels during the follicular phase of stimulated cycles. We reviewed the existing literature aimed at answering four relevant clinical questions, namely (i) Is gonadotropin type associated with PE during the follicular phase of stimulated cycles? (ii) Is PE on the day of human chorionic gonadotropin (hCG) associated with negative fresh embryo transfer IVF/intracytoplasmic sperm injection (ICSI) cycles outcomes in all patient subgroups? (iii) Which P thresholds are best to identify patients at risk of implantation failure due to PE in a fresh embryo transfer? and (iv) Should a freeze all policy be adopted in all the cycles with PE on the day of hCG? The existing evidence indicates that late follicular phase progesterone rise in gonadotropin releasing analog cycles is mainly caused by the supraphysiological stimulation of granulosa cells with exogenous follicle-stimulating hormone. Yet, the type of gonadotropin used for stimulation seems to play no significant role on progesterone levels at the end of stimulation. Furthermore, PE is not a universal phenomenon with evidence indicating that its detrimental consequences on pregnancy outcomes do not affect all patient populations equally. Patients with high ovarian response to control ovarian stimulation are more prone to exhibit PE at the late follicular phase. However, in studies showing an overall detrimental effect of PE on pregnancy rates, the adverse effect of PE on endometrial receptivity seems to be offset, at least in part, by the availability of good quality embryo for transfer in women with a high ovarian response. Given the limitations of the currently available assays to measure progesterone at low ranges, caution should be applied to adopt specific cutoff values above which the effect of progesterone rise could be considered detrimental and to recommend "freeze-all" based solely on pre-defined cutoff points.

Vitrification: an effective new approach to oocyte banking and preserving fertility in cancer patients.

PubMed

Cobo, A; Domingo, J; Pérez, S; Crespo, J; Remohí, J; Pellicer, A

2008-05-01

Oocyte cryopreservation is a useful tool for preserving the fertility of cancer patients at risk of losing ovarian function due to undergoing potentially sterilising therapies. Results obtained with different cryopreservation protocols have been disappointing, particularly those obtained with slow cooling procedures. The efficacy of vitrification as an application in clinical practice has recently been demonstrated. The aim of this study is to report results obtained with the Cryotop method of oocyte vitrification in a population of healthy women and to point out its potential usefulness for fertility preservation in oncological patients. The study population consisting of non-oncological patients included 47 oocyte donors and 57 recipients undergoing an oocyte donation cycle of assisted reproductive technology (ART). A total of 693 mature metaphase II oocytes were collected following ovarian stimulation using long protocol down-regulation plus gonadotropin administration. Vitrification was carried out by means of the Cryotop method. Oocytes were donated to a compatible recipient after endometrial preparation. Of the 693 oocytes, 666 (96.1%) survived. A total of 487 (73.1%) were fertilised successfully. One hundred and seventeen embryos were transferred to 57 recipients. Pregnancy rate per transfer and implantation rates were 63.2% and 38.5% respectively. Twenty-eight healthy babies were later born. Oocyte cryo-banking by means of the Cryotop vitrification method represents a viable option for healthy women, producing excellent survival rates and a clinical outcome similar to that obtained with fresh oocytes. This approach could potentially be used in cancer patients who want to safeguard their fertility. Cancer patients could potentially benefit from this approach by storing their oocytes before the onset of the oncological therapy.

Hair mercury concentrations and in vitro fertilization (IVF) outcomes among women from a fertility clinic

PubMed Central

Ehrlich, Shelley; Smith, Kristen; Williams, Paige L.; Chavarro, Jorge E.; Batsis, Maria; Toth, Thomas L.; Hauser, Russ

2015-01-01

Total hair mercury (Hg) was measured among 205 women undergoing in vitro fertilization (IVF) treatment and the association with prospectively collected IVF outcomes (229 IVF cycles) was evaluated. Hair Hg levels (median=0.62 ppm, range: 0.03-5.66 ppm) correlated with fish intake (r=0.59), and exceeded the recommended EPA reference of 1ppm in 33% of women. Generalized linear mixed models with random intercepts accounting for within-woman correlations across treatment cycles were used to evaluate the association of hair Hg with IVF outcomes adjusted for age, body mass index, race, smoking status, infertility diagnosis, and protocol type. Hair Hg levels were not related to ovarian stimulation outcomes (peak estradiol levels, total and mature oocyte yields) or to fertilization rate, embryo quality, clinical pregnancy rate or live birth rate. PMID:25601638

Preoperative Gabapentin to Prevent Postoperative Shoulder Pain After Laparoscopic Ovarian Cystectomy: A Randomized Clinical Trial.

PubMed

Valadan, Mehrnaz; Banifatemi, Sakineh; Yousefshahi, Fardin

2015-12-01

Patients undergoing gynecology laparoscopy frequently experience shoulder pain as a common postoperative complication. Considering diaphragm stimulation in its pathophysiology, there are some advice to prevent or control this special form of referral pain. The current study aimed to assess the prophylactic effect of preoperative administration of oral gabapentin to prevent Post Laparoscopic Shoulder Pain (PLSP) after laparoscopic ovarian cystectomy. In a randomized, double blind, placebo controlled trial 40 female patients who were candidates to have elective laparoscopic ovarian cystectomy, received uniformed capsules containing gabapentin 600 mg or placebo 30 minutes before anesthesia induction. All patients had the American Society of Anesthesiologists (ASA) Physical Status of I-II and none had pervious abdominal surgery. Thereafter, the presence of side effects and PLSP and its severity was assessed by Visual Analog Scale (VAS) in the beginning of surgery and 2, 6, 12 hours after the surgery. Comparing the gabapentin (n = 20) and placebo (n = 20) groups, basic characteristics including age (P = 0.446), Body Mass Index (BMI) (P = 0.876), pregnancy history (P = 0.660), and surgery time (P = 0.232) were statistically similar. PLSP occurrence was less frequent in the gabapentin group (45%) compared with the placebo group (75%) (P = 0.053), while In gabapentin group the VAS scores were lower in 2(P = 0.004), 6 (P = 0.132), and 12 (P = 0.036) hours, post operatively. Prophylactic gabapentin administration could be considered as an effective and safe intervention to reduce occurrence and severity of PLSP after gynecologic laparoscopic cystectomy.

Preoperative Gabapentin to Prevent Postoperative Shoulder Pain After Laparoscopic Ovarian Cystectomy: A Randomized Clinical Trial

PubMed Central

Valadan, Mehrnaz; Banifatemi, Sakineh; Yousefshahi, Fardin

2015-01-01

Background: Patients undergoing gynecology laparoscopy frequently experience shoulder pain as a common postoperative complication. Considering diaphragm stimulation in its pathophysiology, there are some advice to prevent or control this special form of referral pain. Objectives: The current study aimed to assess the prophylactic effect of preoperative administration of oral gabapentin to prevent Post Laparoscopic Shoulder Pain (PLSP) after laparoscopic ovarian cystectomy. Patients and Methods: In a randomized, double blind, placebo controlled trial 40 female patients who were candidates to have elective laparoscopic ovarian cystectomy, received uniformed capsules containing gabapentin 600 mg or placebo 30 minutes before anesthesia induction. All patients had the American Society of Anesthesiologists (ASA) Physical Status of I-II and none had pervious abdominal surgery. Thereafter, the presence of side effects and PLSP and its severity was assessed by Visual Analog Scale (VAS) in the beginning of surgery and 2, 6, 12 hours after the surgery. Results: Comparing the gabapentin (n = 20) and placebo (n = 20) groups, basic characteristics including age (P = 0.446), Body Mass Index (BMI) (P = 0.876), pregnancy history (P = 0.660), and surgery time (P = 0.232) were statistically similar. PLSP occurrence was less frequent in the gabapentin group (45%) compared with the placebo group (75%) (P = 0.053), while In gabapentin group the VAS scores were lower in 2(P = 0.004), 6 (P = 0.132), and 12 (P = 0.036) hours, post operatively. Conclusions: Prophylactic gabapentin administration could be considered as an effective and safe intervention to reduce occurrence and severity of PLSP after gynecologic laparoscopic cystectomy. PMID:26705527

Estimating the net effect of progesterone elevation on the day of hCG on live birth rates after IVF: a cohort analysis of 3296 IVF cycles.

PubMed

Venetis, Christos A; Kolibianakis, Efstratios M; Bosdou, Julia K; Lainas, George T; Sfontouris, Ioannis A; Tarlatzis, Basil C; Lainas, Tryfon G

2015-03-01

What is the proper way of assessing the effect of progesterone elevation (PE) on the day of hCG on live birth in women undergoing fresh embryo transfer after in vitro fertilization (IVF) using GnRH analogues and gonadotrophins? This study indicates that a multivariable approach, where the effect of the most important confounders is controlled for, can lead to markedly different results regarding the association between PE on the day of hCG and live birth rates after IVF when compared with the bivariate analysis that has been typically used in the relevant literature up to date. PE on the day of hCG is associated with decreased pregnancy rates in fresh IVF cycles. Evidence for this comes from observational studies that mostly failed to control for potential confounders. This is a retrospective analysis of a cohort of fresh IVF/intracytoplasmic sperm injection cycles (n = 3296) performed in a single IVF centre during the period 2001-2013. Patients in whom ovarian stimulation was performed with gonadotrophins and GnRH analogues. Natural cycles and cycles where stimulation involved the administration of clomiphene were excluded. In order to reflect routine clinical practice, no other exclusion criteria were imposed on this dataset. The primary outcome measure for this study was live birth defined as the delivery of a live infant after 24 weeks of gestation. We compared the association between PE on the day of hCG (defined as P > 1.5 ng/ml) and live birth rates calculated by simple bivariate analyses with that derived from multivariable logistic regression. The multivariable analysis controlled for female age, number of oocytes retrieved, number of embryos transferred, developmental stage of embryos at transfer (cleavage versus blastocyst), whether at least one good-quality embryo was transferred, the woman's body mass index, the total dose of FSH administered during ovarian stimulation and the type of GnRH analogues used (agonists versus antagonists) during ovarian stimulation. In addition, an interaction analysis was performed in order to assess whether the ovarian response (<6, 6-18, >18 oocytes) has a moderating effect on the association of PE on the day of hCG with live birth rates after IVF. Live birth rates were not significantly different between cycles with and those without PE when a bivariate analysis was performed [odds ratio (OR): 0.78, 95% confidence interval (CI): 0.56-1.09]. However, when a multivariable analysis was performed, controlling for the effect of the aforementioned confounders, live birth rates (OR: 0.68, 95% CI: 0.48-0.97) were significantly decreased in the group with PE on the day of hCG. The number of oocytes retrieved was the most potent confounder, causing a 29.4% reduction in the OR for live birth between the two groups compared. Furthermore, a moderating effect of ovarian response on the association between PE and live birth rates was not supported in the present analysis since no interaction was detected between PE and the type of ovarian response (<6, 6-18, >18 oocytes). This is a retrospective analysis of data collected during a 12-year period, and although the effect of the most important confounders was controlled for in the multivariable analysis, the presence of residual bias cannot be excluded. This analysis highlights the need for a multivariable approach when researchers or clinicians aim to evaluate the impact of PE on pregnancy rates in their own clinical setting. Failure to do so might explain why many past studies have failed to identify the detrimental effect of PE in fresh IVF cycles. None. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

GnRH Analogues in the Prevention of Ovarian Hyperstimulation Syndrome

PubMed Central

Alama, Pilar; Bellver, Jose; Vidal, Carmen; Giles, Juan

2013-01-01

The GnRH analogue (agonist and antagonist GnRH) changed ovarian stimulation. On the one hand, it improved chances of pregnancy to obtain more oocytes and better embryos. This leads to an ovarian hyper-response, which can be complicated by the ovarian hyperstimulation syndrome (OHSS). On the other hand, the GnRH analogue can prevent the incidence of OHSS: GnRH antagonist protocols, GnRH agonist for triggering final oocyte maturation, either together or separately, coasting, and the GnRH analogue may prove useful for avoiding OHSS in high-risk patients. We review these topics in this article. PMID:23825982

Impact of presence of antiphospholipid antibodies on in vitro fertilization outcome

PubMed Central

Hong, Yeon Hee; Kim, Se Jeong; Moon, Kyoung Yong; Kim, Seul Ki; Lee, Won Don; Kim, Seok Hyun

2018-01-01

Objective To investigate prevalence of antiphospholipid antibody (APA) in Korean infertile women undergoing the first in vitro fertilization (IVF) treatment and to evaluate the influence of APA on the subsequent IVF outcomes. Method Two hundred nineteen infertile women who destined the first IVF were prospectively enrolled in 2 infertility centers. Male factor or uterine factor infertility and women with past or current endocrine or immunologic disorders were completely excluded. Plasma concentration of lupus anticoagulant was measured by clot-based method, and anticardiolipin antibody (IgG/IgM), and anti-β2-glycoprotein 1 antibody (IgG/IgM) was measured by enzyme-linked immunosorbent assay method before starting ovarian stimulation for IVF. Results APA was positive in 13 women (5.9%). Lupus anticoagulant was positive in 2 women (0.9%), anticardiolipin antibody was positive in 7 women (3.2%), and anti-β2-glycoprotein 1 antibody was positive in 4 women (1.8%). In 193 women entering embryo transfer, clinical characteristics and stimulation outcomes were comparable between APA-positive (n=12) and APA-negative group (n=181). The clinical pregnancy rate (66.7% vs. 45.9%), ongoing pregnancy rate (58.3% vs. 37.0%), and miscarriage rate (12.5% vs. 19.3%) were all similar between APA-positive and APA-negative group. Conclusion The prevalence of APA is low in Korean infertile women undergoing the first IVF cycle, and the presence of APA appears to neither decrease their first IVF success nor increase abortion rate. PMID:29780778

DYNAMIC BEHAVIOR OF A DELAY-DIFFERENTIAL EQUATION MODEL FOR THE HORMONAL REGULATION OF THE MENSTRUAL CYCLE

EPA Science Inventory

During the menstrual cycle, pituitary hormones stimulate the growth and development of ovarian follicles and the release of an ovum to be fertilized. The ovarian follicles secrete hormones during the cycle that regulate the production of the pituitary hormones creating positi...

Comparison of letrazole and clomiphene citrate in women with polycystic ovaries undergoing ovarian stimulation.

PubMed

Sharief, Maysoon; Nafee, Najlaa Rasmee

2015-11-01

To compare the efficacy of letrazole in the induction of ovulation with clomiphene citrate in patients with polycystic ovary syndrome and primary infertility. The prospective clinical trial was conducted at Basrah Maternity and Child Hospital, Basrah, Iraq, between January 2012 and April 2013, and comprised women with polycystic ovarian syndrome and primary infertility who were randomised into 2 groups. Group A received100-200mg clomiphene citrate daily while group 2 received letrazole (2.5-5mg) daily. Both groups were followed by ultrasound until the dominant follicle reached a diameter >18mm, human chorionic gonadotropin10.000 U/L was given and timed intercourse was advised. Of the 75 subjects in the study, 40(53.3%) were in group A and 35(46.6%) in group B. The mean age in group A was 25.3+2.1 years versus 26.1+1.3 years in group B (p=0.05). The number of mature follicles was significantly lower, but the endometrial thickness and ovulation were significantly higher in group B than in group A (p<0.05 each). There was no significant difference in pregnancy rate between the two groups (p>0.05). Letrazole may have a role as the first-line treatment for unovulatory patients with polycystic ovary syndrome.

COX-1 Suppression and Follicle Depletion in the Etiology of Menopause-Associated Ovarian Cancer

DTIC Science & Technology

2009-10-01

Increased parity and oral contraceptive use are the clearest examples of factors that decrease ovarian cancer risk, both of which limit ovulation. Two...act by suppressing ovulation decrease the risk of ovarian cancer by about 40% after 3 years of use .10,11 Why pregnancy and oral contraceptives ...regular use of progestin-containing oral contraceptives is a protective factor, and the benefi t decreases after time.13 Gonadotropin stimulation in

Autofluorescence imaging can identify preinvasive or clinically occult lesions in fallopian tube epithelium: a promising step towards screening and early detection.

PubMed

McAlpine, J N; El Hallani, S; Lam, S F; Kalloger, S E; Luk, M; Huntsman, D G; MacAulay, C; Gilks, C B; Miller, D M; Lane, P M

2011-03-01

Optical imaging systems are robust, portable, relatively inexpensive, and have proven utility in detecting precancerous lesions in the lung, esophagus, colon, oral cavity and cervix. We describe the use of light-induced endogenous fluorescence (autofluorescence) in identifying preinvasive and occult carcinomas in ex vivo samples of human fallopian tube (FT) epithelium. Women undergoing surgery for an i) ovarian mass, ii) a history suggestive of hereditary breast-ovarian cancer, or iii) known serous ovarian cancer following neoadjuvant chemotherapy (NAC) were approached for informed consent. Immediately following surgery, FT's were photographed in reflectance and fluorescence at high resolution. Images included: (1) white-light reflectance of luminal/epithelial surface; (2) narrow-band green reflectance (570 nm) (3) green autofluorescence (405/436 nm excitation); and (4) blue autofluorescence (405 nm excitation). Areas revealing a loss of natural tissue fluorescence or marked increase in tissue microvasculature were recorded and compared to final histopathologic diagnosis (SEE-FIM protocol). Fifty-six cases involving one or both fallopian tubes underwent reflectance and fluorescence visualization. Nine cases were excluded, either secondary to non-ovarian primary pathology (7) or excessive trauma (2) rendering tissue interpretation impossible. Of the 47 cases remaining, there were 11 high grade serous (HGS) and 9 non-serous ovarian carcinomas undergoing primary debulking surgery, 5 serous carcinomas having received NAC, 8 benign ovarian tumors, and 14 women undergoing risk-reducing bilateral salpingo-oophorectomy (RRBSO). Methodology was feasible, efficient, and reproducible. TIC or carcinoma was identified in 7/11 HGS, 3/5 NAC, and 1/14 RRBSO. Optical images were reviewed to determine test positive or negative based on standardized criteria. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the entire cohort (73%; 83%; 57%; 91%) and in a subgroup that excluded non-serous histology (87.5%; 92%; 78%; 96%). Abnormal FT lesions can be identified using ex vivo optical imaging technologies. With this platform, we will move towards genomic interrogation of identified lesions, and developing in vivo screening modalities via falloposcopy. Copyright © 2010 Elsevier Inc. All rights reserved.

Ovarian reserve and subsequent ART outcomes following methotrexate therapy for ectopic pregnancy and pregnancy of unknown location

PubMed Central

Hill, Micah J.; Cooper, Janelle C.; Levy, Gary; Alford, Connie; Richter, Kevin S.; DeCherney, Alan H.; Katz, Charles; Levens, Eric D.; Wolff, Erin F.

2013-01-01

Objective It is unclear whether the stimulated state of the ovaries as part of ART results in an increased vulnerability to the effects of methotrexate. The objective of this study was to assess ovarian reserve following methotrexate treatment for ectopic pregnancy or pregnancy of unknown location after ART. Design Retrospective cohort study. Setting Large ART practice. Patients Methotrexate or surgery following ART. Interventions None. Main Outcome Measures Follicle stimulating hormone (FSH), antral follicle count (AFC), and oocyte yield were compared between subjects treated with methotrexate and surgery. Secondary outcomes were clinical pregnancy and live birth. Results There were 153 patients in the methotrexate group and 36 patients in the surgery group. Neither group demonstrated differences in ovarian reserve or oocyte yield comparing before and after treatment values. The change in ovarian reserve and oocyte yield after treatment were similar between the two groups. The number of doses of methotrexate was not correlated with changes in ovarian reserve, indicating no dose-dependent effect. Time between treatment and repeat ART was not correlated with outcomes. Live birth in subsequent cycles was similar in the two groups. Conclusions Ovarian reserve and subsequent ART cycle outcomes were reassuring following methotrexate and surgical management of ectopic pregnancy. An adverse impact of methotrexate was not detected in this large fertility cohort as has been previously described. PMID:24269042

Comparing long term impact on ovarian reserve between laparoscopic ovarian cystectomy and open laprotomy for ovarian endometrioma

PubMed Central

2013-01-01

Objective To compare the long term impact on ovarian reserve between laparoscopic ovarian cystectomy with bipolar electrocoagulation and laparotomic cystectomy with suturing for ovarian endometrotic cyst. Patient and method(s) 121 patients with benign ovarian endometroitic cysts were randomised to either laparoscopic ovarian cystectomy using bipolar electrocoagulation (61 patients) or laparotomic ovarian cystectomy using sutures (60 patients). Serum follicle-stimulating hormone, Antimullerian hormon, Basal antral follicle Count, mean ovarian diameter, and ovarian stromal blood flow velocity were measured at 6, 12 and 18 months after surgery and compared in both groups. Result(s) A statistically significant increase of serum FSH was found in the laproscopic bipolar group at 6-, 12 and 18-month postoperativly compared to open laparotomy suture group. Also, a statistically significant decrease of the mean AMH value occurred in laproscopic bipolar group at 6-, 12 and 18-month follow- up compared to open laparotomy suture group. Basal antral follicle number, mean ovarian diameter and peak systolic velocity were significantly decreased during the 6-, 12,18 -month follow-up in laproscopic bipolar group compared to open laparotomy suture group. Conclusion(s) After laproscopic ovarian cystecomy for endometrioma all pareameter of ovarian reseve are significantly decreased on long term follow up as compared to open laprotomy. PMID:24180348

Ovarian Conservation and Overall Survival in Young Women With Early-Stage Cervical Cancer.

PubMed

Matsuo, Koji; Machida, Hiroko; Shoupe, Donna; Melamed, Alexander; Muderspach, Laila I; Roman, Lynda D; Wright, Jason D

2017-01-01

To identify predictors of ovarian conservation at hysterectomy and to examine the association of ovarian conservation and survival of young women with early-stage cervical cancer. This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results Program to identify hysterectomy-based surgically treated patients with stage I cervical cancer diagnosed between 1983 and 2012 (N=16,511). Multivariable models were used to identify independent factors associated with ovarian conservation. Among the subgroup of 9,419 women younger than 50 years of age with stage I disease, survival outcomes and causes of death were examined for 3,908 (41.5%) women who underwent ovarian conservation at hysterectomy without radiotherapy. On multivariable analysis, age younger than 50 years, stage IA disease, and squamous histology were independent factors associated with ovarian conservation (all, P<.001). Among 5,526 women younger than 50 years of age with stage IA disease who underwent hysterectomy without radiotherapy, overall survival was significantly higher in patients undergoing ovarian conservation than in those undergoing oophorectomy (20-year rate, 93.5% compared with 86.8%, P<.001); cervical cancer-specific survival was similar between the patients who underwent ovarian conservation and those who underwent oophorectomy (98.8% compared with 97.8%, P=.12). On multivariable analysis, ovarian conservation remained an independent prognostic factor for improved overall survival (adjusted hazard ratio 0.63, 95% confidence interval [CI] 0.49-0.82, P=.001) and was independently associated with lower cumulative risks of death resulting from cardiovascular disease (20-year cumulative rate, 1.2% compared with 3.3%, adjusted hazard ratio 0.47, 95% CI 0.26-0.86, P=.014) and other chronic disease (0.5% compared with 1.4%, adjusted hazard ratio 0.24, 95% CI 0.09-0.65, P=.005) compared with oophorectomy. Both cervical cancer-specific survival (20-year rate, 93.1% compared with 92.0%, P=.37) and overall survival (86.7% compared with 84.6%, P=.12) were similar between ovarian conservation and oophorectomy among 3,893 women younger than 50 years of age with stage IB disease who underwent hysterectomy without radiotherapy. Among young women with stage IA cervical cancer, ovarian conservation at hysterectomy is associated with decreased all-cause mortality including death resulting from cardiovascular disease and other chronic diseases.

Optimal cutoff value of basal anti-mullerian hormone in iranian infertile women for prediction of ovarian hyper-stimulation syndrome and poor response to stimulation.

PubMed

Aghssa, Malek Mansour; Tarafdari, Azam Manshadi; Tehraninejad, Ensieh Shahrokh; Ezzati, Mohammad; Bagheri, Maryam; Panahi, Zahra; Mahdavi, Saeed; Abbasi, Mehrshad

2015-09-10

We intended to establish the threshold of Anti-Mullerian Hormone (AMH) for detection of Ovarian Hyper-Stimulation Syndrome (OHSS) and poor response to treatment in Iranian infertile women. Pre-stimulation menstrual cycle day-3 hormonal indices including basal AMH values were measured in 105 infertile women aged 32.5 ± 4.3 years. Patients underwent long GnRH agonist Controlled Ovarian Hyperstimulation (COH) in a referral infertility center (Tehran, Iran). The gonadotropin dose was determined based on the age and basal serum Follicular Stimulating Hormone (FSH) level. The IVF/ICSI cycles were followed and the clinical and sonographic data were recorded. Sixteen cases developed OHSS. The prevalence of PCOS was higher in subjects with OHSS [62.5 % (38.8-86.2) vs. 17 % (9.2-24.9)]. The patients with OHSS had higher ovarian follicular count [23.7 (3.2) vs. 9.1 (0.5); p < 0.05], collected oocytes [13.5 (1.9) vs. 6.9 (0.5); p < 0.05] and AMH level [7.9 (0.7) vs. 3.6 (0.3); p < 0.05]. Basal AMH level and oocyte yields (but not age, BMI, and PCOS) correlated with occurrence of OHSS; and only the AMH levels were associated with poor ovarian response (oocytes yield ≤ 4). The optimal cutoff value for the prediction of OHSS was 6.95 ng/ml (area under the receiver operating characteristics curve: 0.86; CI: 0.78-0.95; sensitivity: 75 %; specificity: 84 %; odds ratio for occurrence of OHSS: 9 and p < 0.001). The optimal cut point to discriminate poor response (oocytes ≤4) was 1.65 ng/ml ( AUC : 0.8; CI: 0.69-0.91; sensitivity: 89 % specificity : 71 %; and OR = 23.8 and P value <0.001). Iranian women with basal AMH level > 6.95 ng/ml are at high risk of developing OHSS and those with AMH level < 1.65 ng/ml are poor responders.

17β-Estradiol Reverses Leptin-Inducing Ovarian Cancer Cell Migration by the PI3K/Akt Signaling Pathway.

PubMed

Hoffmann, Marta; Fiedor, Elżbieta; Ptak, Anna

2016-11-01

Accumulating evidence suggests that leptin is expressed at higher levels in obese women and stimulates cell migration in epithelial cancers. However, the biology of ovarian cancer is different from others, mainly due to the production of estrogens because of the involvement of ovarian tissue, which is the main source of estrogens; as a result, the levels are at least 100- to 1000-fold higher than normal circulating levels. Thus, ovarian cancer tissues are exposed to 17β-estradiol, which promotes ovarian cancer cell migration and may modulate the effect of other hormones. Therefore, this study investigated the effects of 17β-estradiol (1 nmol/L) with leptin (1-40 ng/mL) at physiological levels, on the migration of OVCAR-3 and SKOV-3 ovarian cancer cells, and the expression levels and activity of metalloproteinases (MMPs) 2 and 9. Here, we found that leptin stimulated ovarian cancer cell line migration, which is mediated via the expression and activity of MMP-9 in the OVCAR-3 but not in the SKOV-3 cells. After the administration of 17β-estradiol and leptin, we observed antagonistic effects of 17β-estradiol on leptin-induced OVCAR-3 cell migration and MMP-9 expression and activity. Moreover, the antagonistic effect of 17β-estradiol on leptin-induced cancer cell migration was reversed by pretreatment of the cells with the phosphatidylinositol 3-kinase (PI3K) pathway inhibitor. Taken together, our results, for the first time, show that in ovarian cancer cells ObR + /ER + , 17β-estradiol has an antagonistic effect on leptin-induced cell migration as well as MMP-9 expression and activity, which is mediated by the PI3K pathway. © The Author(s) 2016.

No increased risk of major congenital anomalies or adverse pregnancy or neonatal outcomes following letrozole use in assisted reproductive technology.

PubMed

Tatsumi, T; Jwa, S C; Kuwahara, A; Irahara, M; Kubota, T; Saito, H

2017-01-01

Does letrozole use increase the risk of major congenital anomalies and adverse pregnancy and neonatal outcomes in fresh, single-embryo transfer? Letrozole significantly decreases the risk of miscarriage and does not increase the risk of major congenital anomalies or adverse pregnancy or neonatal outcomes compared with natural cycles in patients undergoing ART. Letrozole is the most commonly used aromatase inhibitor for mild ovarian stimulation in ART. However, its safety in terms of pregnancy and neonatal outcomes is unclear. This retrospective cohort study used data from the Japanese national ART registry from 2011 to 2013. A total of 3136 natural cycles and 792 letrozole-induced cycles associated with fresh, single-embryo transfer and resulting in a clinical pregnancy were included in the analysis. The main pregnancy outcomes were miscarriage, ectopic pregnancy and still birth, and the neonatal outcomes were preterm delivery, low birth weight, small/large for gestational age and major congenital anomalies. Terminated pregnancies were included in the analysis of major congenital anomalies. Odds ratios (ORs) and 95% CIs were calculated using multivariate logistic regression analysis adjusted for maternal age and calendar year. The risk of miscarriage was significantly lower in women administered letrozole (adjusted OR [aOR], 0.37, 95% CI, 0.30-0.47, P < 0.001). There was no significant difference in the overall risk of major congenital anomalies between the two groups (natural cycle 1.5% vs letrozole 1.9%, aOR, 1.24, 95% CI, 0.64-2.40, P = 0.52), and no increased risk for any specific organ system. Subgroup analysis demonstrated that the risk of major congenital anomalies was not increased in patients who underwent either in vitro fertilization or ICSI, or in those who received early cleavage stage or blastocyst embryo transfer. All other pregnancy and neonatal outcomes were comparable between the two groups. Despite the large sample size, we were only able to rule out the possibility that letrozole might cause large increases in birth-defect risks in ART patients. The results suggest that letrozole stimulation reduces the risk of miscarriage, with no increase in the risk of major congenital anomalies or adverse pregnancy or neonatal outcomes compared with natural cycles in women undergoing ART. Letrozole may thus be a safe option for mild ovarian stimulation. None. Not applicable. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The role of ovarian hormones in sexual reward states of the female rat.

PubMed

Parada, Mayte; Vargas, Erica Barbosa; Kyres, Maria; Burnside, Kimberly; Pfaus, James G

2012-09-01

To what extent does the reward value of sexual stimulation in females depend on ovarian hormones? The effects of estradiol benzoate (EB) and progesterone (P) were examined on the acquisition and expression of sexual reward induced by paced copulation and clitoral stimulation (CLS) in ovariectomized (OVX) rats. In experiment 1 we examined the expression of a pacing-induced conditioned place preference (CPP). Ovariectomized, hormone-primed rats were given experience with paced copulation associated with one side of a CPP apparatus. Changing hormonal status prior to the final CPP test did not alter pacing-induced CPP. However, subsequent partial extinction of CPP was observed only in rats primed with EB+P, a treatment previously shown to induce sexual desire and receptivity. In Experiment 2, significant CLS-induced CPP developed in ovariectomized rats regardless of hormone priming. Our results show that the expression of the sexual reward state induced by paced copulation, and CLS in particular, is independent of hormone priming. We propose that ovarian hormones sensitize sensory and motor pathways necessary for sexual behavior and stimulation to induce reward. Copyright © 2012 Elsevier Inc. All rights reserved.

Fertility drugs and breast cancer risk.

PubMed

Lo Russo, G; Tomao, F; Spinelli, G P; Prete, A A; Stati, V; Panici, P Benedetti; Papa, A; Tomao, S

2015-01-01

Female infertility is a widespread problem in Western countries. During past years, an association between ovarian stimulation in unfertile women and breast cancer risk has been hypothesized. Purpose of the present investigation was to comment the most updated studies about an eventual relationship between fertility drugs and breast cancer risk. The authors performed a review of the current literature regarding the possible association between the use of fertility drugs and the enhanced risk of breast cancer. They searched digital databases including Pubmed, EMBASE, and the Cochrane Library. The literature search was performed using various combinations of keywords. They carefully analyzed only the full versions of all relevant studies. Using various combination of keywords, the authors examined 930 papers. They considered only papers written in English. With these criteria they selected the studies that had been discussed in detail on the text. None of the works commented provides an indisputable evidence about a link between ovarian stimulation and breast cancer risk. On the contrary, most of them actually suggest a lack of interaction between them or even a protective role of ovarian stimulation.

Follicular aspiration versus coasting for ovarian hyper-stimulation syndrome prevention

PubMed Central

Bushaqer, Nayla J.; Dayoub, Nawal M.; AlHattali, Khalsa K.; Ayyoub, Hisham A.; AlFaraj, Samaher S.; Hassan, Samar N.

2018-01-01

Objectives: To compare follicular reduction prior to human chorionic gonadotropin (HCG) trigger and coasting in terms of ovarian hyper-stimulation syndrome (OHSS) reduction, pregnancy, and cancellation rates in in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods: This study was designed as a prospective study. The setting was the IVF unit at King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia. A total of 39 patients undergoing IVF/ICSI cycles, who were at risk of OHSS, 20 were put into a coasting group and 19 had follicular reduction instead. This occurred between October 2010 and January 2011. Our main outcome was OHSS reduction. Results: Six (30%) women developed OHSS in the coasting group and 2 (10.5%) women developed OHSS in the follicular group (p-value=0.235). The pregnancy rates in the cycles were similar for both groups: 4/20 (20%) in the coasting group and 3/19 (15.8%) in the follicular group (p-value=1.000). The cancellation rate of the cycles was similar for both groups, 6/20 (30%) in the coasting group and 1/19 (5.3%) in the follicular group (p-value=0.09). The median number of punctured follicles was significantly lower in the follicular group (16 follicles, interquartile range (IQR)=21-12) compared to the coasting group (29 follicles, IQR=37.8-19.8, p-value=0.001). The retrieved, fertilized, and cleaved oocytes, as well as the number of embryos transferred, were similar amongst both groups. Conclusion: There was no difference between follicular reduction prior to HCG and coasting, in terms of OHSS reduction, pregnancy, and cancellation rates in both the IVF and ICSI cycles. PMID:29543308

Impact of Chemotherapy on Retroperitoneal Lymph Nodes in Ovarian Cancer.

PubMed

Keyver-Paik, Mignon-Denise; Arden, Janne Myriam; Lüders, Christine; Thiesler, Thore; Abramian, Alina; Hoeller, Tobias; Hecking, Thomas; Ayub, Tiyasha Hosne; Doeser, Anna; Kaiser, Christina; Kuhn, Walther

2016-04-01

Complete cytoreduction is the most important prognostic factor in ovarian cancer. However, there exist conflicting data on whether the removal of microscopic tumor metastasis in macroscopically unsuspicious retroperitoneal lymph nodes is beneficial. Ovarian cancer tissues and tissues from lymph node metastasis of 30 patients with FIGO IIIC or IV disease undergoing neoadjuvant chemotherapy (NACT) were obtained and assessed using a validated regression score. Histopathological markers, size of largest tumor focus, and overall score were evaluated in lymph node and ovarian tissue. Regression and known prognostic factors were analyzed for influence on survival. No difference in the overall score between lymph nodes and ovarian tissue was shown, however, single parameters such as fibrosis and pattern of tumor infiltration, were significantly different. The pattern of tumor regression in lymph nodes and ovarian tissue are of prognostic value. Lymph node dissection even of unsuspicious nodes should, therefore, be performed. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Improved selection of cortical ovarian strips for autotransplantation of ovarian tissue using full-field optical coherence tomography (FFOCT)

NASA Astrophysics Data System (ADS)

Stegehuis, Paulien L.; Peters, Inge T. A.; Eggermont, Jeroen; Kuppen, Peter J. K.; Trimbos, J. Baptist; Lelieveldt, Boudewijn P. F.; van de Velde, Cornelis J. H.; Bosse, Tjalling; Dijkstra, Jouke; Vahrmeijer, Alexander L.

2016-02-01

Premature ovarian failure is a major concern in women of reproductive age who undergo gonadotoxic cancer treatment. Autotransplantation of frozen-thawed cortical ovarian tissue allows the immediate start of cancer treatment, but risks reintroduction of cancer. Current tumor detection methods compromise the ovarian tissue's viability and can therefore only be used to exclude the presence of metastases in the cortical ovarian strips that are not transplanted. A non-invasive method is needed that can be used to exclude metastases in the actual ovarian autografts without affecting the tissue's viability. In this study we applied FFOCT - a non-fixative technique that uses white light interferometry to make highresolution images (1μm isotropic) of fresh tissue - to study healthy and malignant ovarian tissue. We created an image atlas of healthy ovarian tissues from premenopausal patients and ovarian tissues with breast cancer metastases. To get the best possible match between hematoxylin-and-eosin stained slides and FFOCT images formalinfixed paraffin-embedded tissue samples were deparaffinized and FFOCT images were acquired within a few minutes. FFOCT images were compared with histology images. All normal structures such as follicles in all phases, inclusion cysts, blood vessels, corpora lutea, and corpora albicantia were clearly recognizable. Ovarian metastases could be well distinguished from normal ovarian tissue. FFOCT is a promising technique in the field of fertility preservation: metastases can be detected and additionally cortical ovarian strips can be selected on the basis of high follicle density.

Cells of origin of ovarian cancer: ovarian surface epithelium or fallopian tube?

PubMed

Klotz, Daniel Martin; Wimberger, Pauline

2017-12-01

Ovarian cancer is the fifth most common cancer in women and one of the leading causes of death from gynecological malignancies. Despite of its clinical importance, ovarian tumorigenesis is poorly understood and prognosis remains poor. This is particularly true for the most common type of ovarian cancer, high-grade serous ovarian cancer. Two models are considered, whether it arises from the ovarian surface epithelium or from the fallopian tube. The first model is based on (1) the pro-inflammatory environment caused by ovulation events, (2) the expression pattern of ovarian inclusion cysts, and (3) biomarkers that are shared by the ovarian surface epithelium and malignant growth. The model suggesting a non-ovarian origin is based on (1) tubal precursor lesions, (2) genetic evidence of BRCA1/2 mutation carriers, and (3) recent animal studies. Neither model has clearly demonstrated superiority over the other. Therefore, one can speculate that high-grade serous ovarian cancer may arise from two different sites that undergo similar changes. Both tissues are derived from the same embryologic origin, which may explain how progenitor cells from different sites can respond similar to stimuli within the ovaries. However, distinct molecular drivers, such as BRCA deficiency, may still preferentially arise from one site of origin as precancerous mutations are frequently seen in the fallopian tube. Confirming the origin of ovarian cancer has important clinical implications when deciding on cancer risk-reducing prophylactic surgery. It will be important to identify key biomarker to uncover the sequence of ovarian tumorigenesis.

Fertility Preservation and Pregnancy in Women With and Without BRCA Mutation–Positive Breast Cancer

PubMed Central

Rodriguez-Wallberg, Kenny A.

2012-01-01

Women with breast cancer face many challenges when considering fertility preservation. Delayed referral results in the limitation of fertility preservation options because most established methods, such as embryo and oocyte cryopreservation, require several weeks to complete. Women with BRCA mutations, on the other hand, may be more aware of fertility issues and motivated to see fertility preservation specialists earlier. Fear of exposure to estrogen limits access to fertility preservation via embryo or oocyte cryopreservation; however, the use of aromatase inhibitors as ovarian stimulants reduces such concern. Ovarian cryopreservation can be used when there is insufficient time to perform ovarian stimulation because this technique does not require hormonal stimulation, but there are safety concerns both in women with BRCA mutations and in patients with hormone receptor–positive disease as well. There does not seem to be a proven ovarian suppression strategy to preserve fertility in women with breast cancer. Pregnancy appears to be safe for breast cancer survivors but studies specific for women with BRCA mutations are lacking. Women with BRCA mutations may elect to use preimplantation genetic diagnosis during in vitro fertilization to avoid transmitting the mutation, but there may be psychosocial difficulties in entertaining this option. Overall, the last decade has brought many options for women with breast cancer considering fertility preservation, but numerous challenges remain. The presence of BRCA mutations further contributes to these challenges. PMID:23006497

Endometriosis and Ovarian Cancer: A Review of Clinical, Pathologic, and Molecular Aspects

PubMed Central

Wei, Jian-Jun; William, Josette; Bulun, Serdar

2014-01-01

Summary Endometriosis is a chronic disease that affects millions of reproductive-age women. Despite the destructive and invasive nature of endometrioses, most cases are perpetually benign or eventually regress; however, atypical endometriosis is a precursor lesion and can lead to certain types of ovarian cancer. Endometriosis induced inflammation and auto- and paracrine production of sex steroid hormones contribute to ovarian tumorigenesis. These changes provide microenvironment necessary to accumulate enough genetic alterations for endometriosis associated malignant transformation. It takes years for endometriosis to undergo the pathophysiological progression that begins with atypical epithelial proliferation (atypical endometriosis and metaplasia), and then is followed by the formation of well-defined borderline tumors, and finally culminates in fully malignant ovarian cancer. This study is a review of the natural history of endometriosis and the role of microenvironments that favor the accumulation of genetic alterations and endometriosis-associated ovarian cancer progression. PMID:21979592

Implantation in assisted reproduction: a look at endometrial receptivity.

PubMed

Fatemi, H M; Popovic-Todorovic, B

2013-11-01

Implantation failure in assisted reproduction is thought to be mainly due to impaired uterine receptivity. With normal uterine anatomy, changes in endocrine profile during ovarian stimulation and medical conditions of the mother (i.e. thrombophilia and abnormal immunological response) could result in a non-receptive endometrium. High oestradiol concentrations during ovarian stimulation lead to premature progesterone elevation, causing endometrial advancement and hampering implantation, which can be overcome by a freeze-all approach and embryo transfer in natural cycles or by milder stimulation protocols. Patients with recurrent implantation failure (RIF) should be tested for inherited and acquired thrombophilias. Each patient should be individually assessed and counselled regarding therapy with low-molecular-weight heparin (LMWH). Empirical treatment with LMWH, aspirin or corticosteroids is not effective for women with RIF who have negative thrombophilic tests. If thrombophilic tests are normal, patients should be tested for immunological causes. If human leukocyte antigen dissimilarity is proven, treatment with intravenous immunoglobulin might be beneficial. Preliminary observational studies using intralipid infusion in the presence of increased natural killer cytotoxic activity are interesting but the proposed rationale is controversial and randomized controlled trials are needed. Hysteroscopy and/or endometrial scratching in the cycle preceding ovarian stimulation should become standard for patients with RIF. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Oxygen consumption is a quality marker for human oocyte competence conditioned by ovarian stimulation regimens.

PubMed

Tejera, Aberto; Herrero, Javier; de Los Santos, M J; Garrido, Nicolás; Ramsing, Niels; Meseguer, Marcos

2011-09-01

To evaluate the effect of different ovarian stimulation protocols on oocyte respiration and to investigate the relationship between oocyte oxygen consumption and reproductive outcome. Prospective observational cohort study. Infertility clinic in a university hospital. A total of 349 oocytes from 56 IVF treatment cycles in our oocyte donation program. None. Average oocyte oxygen consumption rate in fmol/s. We correlated oxygen consumption values with ovarian stimulation features, fertilization, embryo quality on days 2 and 3, and implantation. Differences in the measured oxygen consumption rates were found depending on which type of gonadotropins were used in the stimulation protocol. Higher consumption rates were found for oocytes that underwent normal fertilization compared with rates from nonfertilized or abnormal oocytes (odds ratio = 1.340; 95% confidence intervals = 1.037-1.732). Furthermore, higher oxygen consumption was observed for those oocytes which generated embryos that implanted compared with those that did not implant (6.21 ± 0.849 fmol/s vs. 5.23 ± 0.345 fmol/s. Measurement of oxygen consumption rates for individual oocytes before fertilization provides a noninvasive marker of oocyte quality and hence a quantitative assessment of the reproductive potential for the oocyte. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Simultaneous multiplane imaging of human ovarian cancer by volume holographic imaging

PubMed Central

Orsinger, Gabriel V.; Watson, Jennifer M.; Gordon, Michael; Nymeyer, Ariel C.; de Leon, Erich E.; Brownlee, Johnathan W.; Hatch, Kenneth D.; Chambers, Setsuko K.; Barton, Jennifer K.; Kostuk, Raymond K.; Romanowski, Marek

2014-01-01

Abstract. Ovarian cancer is the most deadly gynecologic cancer, a fact which is attributable to poor early detection and survival once the disease has reached advanced stages. Intraoperative laparoscopic volume holographic imaging has the potential to provide simultaneous visualization of surface and subsurface structures in ovarian tissues for improved assessment of developing ovarian cancer. In this ex vivo ovarian tissue study, we assembled a benchtop volume holographic imaging system (VHIS) to characterize the microarchitecture of 78 normal and 40 abnormal tissue specimens derived from ovarian, fallopian tube, uterine, and peritoneal tissues, collected from 26 patients aged 22 to 73 undergoing bilateral salpingo-oophorectomy, hysterectomy with bilateral salpingo-oophorectomy, or abdominal cytoreductive surgery. All tissues were successfully imaged with the VHIS in both reflectance- and fluorescence-modes revealing morphological features which can be used to distinguish between normal, benign abnormalities, and cancerous tissues. We present the development and successful application of VHIS for imaging human ovarian tissue. Comparison of VHIS images with corresponding histopathology allowed for qualitatively distinguishing microstructural features unique to the studied tissue type and disease state. These results motivate the development of a laparoscopic VHIS for evaluating the surface and subsurface morphological alterations in ovarian cancer pathogenesis. PMID:24676382

Racial and ethnic disparities over time in the treatment and mortality of women with gynecological malignancies.

PubMed

Rauh-Hain, J Alejandro; Melamed, Alexander; Schaps, Diego; Bregar, Amy J; Spencer, Ryan; Schorge, John O; Rice, Laurel W; Del Carmen, Marcela G

2018-04-01

To examine temporal trends in treatment and survival among black, Asian, Hispanic, and white women diagnosed with endometrial, ovarian, cervical, and vulvar cancer. Using the National Cancer Database (2004-2014), we identified women diagnosed with endometrial, ovarian, cervical, and vulvar cancer. For each disease site, we analyzed race/ethnicity-specific trends in receipt of evidence-based practices. Professional societies' recommendations were used to define these practices. Using data from the Surveillance, Epidemiology, and End Results Program (2000-2009) we analyzed trends in 5-year survival. Throughout the study period black (64.8%) and Hispanic (68.3%) women were less likely to undergo lymphadenectomy for stage I ovarian cancer compared to Asian (79.5%) and white patients (74.6%). Black women were the least likely group to undergo lymphadenectomy in all periods. Among patients with stage II-IV ovarian cancer, 76.6% of white and Asian women received both surgery and chemotherapy, compared to 70.8% of black and 73.9% Hispanic women. Hispanic women with deeply invasive or high-grade stage I endometrial cancer underwent lymphadenectomy less frequently (74.5%) than all other groups (80.7%). Black women were less likely to have chemo-radiotherapy for stage IIB-IVA cervical cancer (75.6% versus 80.4% of all others). Black women were also less likely to have a surgical lymph node evaluation for vulvar cancer (58.8% versus 63.5% of all others). Among women diagnosed with ovarian, endometrial, and cervical cancer, black women had lower five-year survival than other groups. Significant racial disparities persist in the delivery of evidence-based care. Black women with ovarian, endometrial, and cervical cancer continue to experience higher cancer-specific mortality than other groups. Copyright © 2017 Elsevier Inc. All rights reserved.

A new way of setting rFSH deposit: a case of severe injection error in IVF/ICSI cycle ending with live birth.

PubMed

Mayer, Richard Bernhard; Ebner, Thomas; Shebl, Omar; Tews, Gernot

2012-01-01

a 25- year old woman with secondary infertility caused by a male factor was enrolled in our IVF/ICSI-ET program. Stimulation was performed in a long- protocol and ovarian stimulation, using rFSH follitropin beta, starting on the third day of the menstrual cycle. The rFSH dose per day was 900 IU-0 IU-0 IU-0 IU. Due to normal ovarian response and follicle growth, stimulation was continued and there was no detriment in oocyte quality and no symptoms of OHSS. Following blastocyte transfer cesarean section was unpreventable at 37+5 weeks of gestation due to an impacted transverse lie. Different stimulation protocols are needed for appropriate treatment of various patients provided that the administration of treatment was done correctly. In the case of injection errors, continuing stimulation protocol seems to be achievable in certain cases considering hormone levels and the process of follicle growth.

A new way of setting rFSH deposit: a case of severe injection error in IVF/ICSI cycle ending with live birth

PubMed Central

Mayer, Richard Bernhard; Ebner, Thomas; Shebl, Omar; Tews, Gernot

2012-01-01

We present a case with a severe injection error: a 25- year old woman with secondary infertility caused by a male factor was enrolled in our IVF/ICSI-ET program. Stimulation was performed in a long- protocol and ovarian stimulation, using rFSH follitropin beta, starting on the third day of the menstrual cycle. The rFSH dose per day was 900 IU-0 IU-0 IU-0 IU. Due to normal ovarian response and follicle growth, stimulation was continued and there was no detriment in oocyte quality and no symptoms of OHSS. Following blastocyte transfer cesarean section was unpreventable at 37+5 weeks of gestation due to an impacted transverse lie. Different stimulation protocols are needed for appropriate treatment of various patients provided that the administration of treatment was done correctly. In the case of injection errors, continuing stimulation protocol seems to be achievable in certain cases considering hormone levels and the process of follicle growth. PMID:24592042

Modulation of male mouse genital sniff, attack, and mount behaviors by urogenital substances from estrous females.

PubMed

Weinhold, L L; Ingersoll, D W

1988-09-01

The modulation of attacks, genital sniffs, and mounts in male SJL/J mice by ovarian-dependent urogenital substances in the urine voided by estrous females was examined. Urogenital substances were applied onto the external urogenital areas of ovariectomized mice. When compared with urine voided by estrous females, which stimulated genital sniffing, mounting, and reduced aggression, bladder urine was ineffective. Genital sniffing and mounting was stimulated by estradiol-17 beta, vaginal fluids, and preputial extract. Aggression was reduced by estradiol-17 beta, urethral catheterized urine, and vaginal fluids. Preputialectomy reduced, but did not eliminate, urinary stimulation of genital sniffing and mounting. Preputial extract stimulated aggression. Urogenital substances from ovariectomized females were ineffective in reducing attacks and stimulating genital sniffs and mounts. It was concluded that the ovarian-dependent chemosignals in the urine voided by estrous females are contributed by the urethra, vagina, and preputial gland, perhaps in part through the excretion of unconjugated estrogens.

Potential role of follicle-stimulating hormone (FSH) and transforming growth factor (TGFβ1) in the regulation of ovarian angiogenesis.

PubMed

Kuo, Shih-Wei; Ke, Ferng-Chun; Chang, Geen-Dong; Lee, Ming-Ting; Hwang, Jiuan-Jiuan

2011-06-01

Angiogenesis occurs during ovarian follicle development and luteinization. Pituitary secreted FSH was reported to stimulate the expression of endothelial mitogen VEGF in granulosa cells. And, intraovarian cytokine transforming growth factor (TGF)β1 is known to facilitate FSH-induced differentiation of ovarian granulosa cells. This intrigues us to investigate the potential role of FSH and TGFβ1 regulation of granulosa cell function in relation to ovarian angiogenesis. Granulosa cells were isolated from gonadotropin-primed immature rats and treated once with FSH and/or TGFβ1 for 48 h, and the angiogenic potential of conditioned media (granulosa cell culture conditioned media; GCCM) was determined using an in vitro assay with aortic ring embedded in collagen gel and immunoblotting. FSH and TGFβ1 increased the secreted angiogenic activity in granulosa cells (FSH + TGFβ1 > FSH ≈ TGFβ1 >control) that was partly attributed to the increased secretion of pro-angiogenic factors VEGF and PDGF-B. This is further supported by the evidence that pre-treatment with inhibitor of VEGF receptor-2 (Ki8751) or PDGF receptor (AG1296) throughout or only during the first 2-day aortic ring culture period suppressed microvessel growth in GCCM-treated groups, and also inhibited the FSH + TGFβ1-GCCM-stimulated release of matrix remodeling-associated gelatinase activities. Interestingly, pre-treatment of AG1296 at late stage suppressed GCCM-induced microvessel growth and stability with demise of endothelial and mural cells. Together, we provide original findings that both FSH and TGFβ1 increased the secretion of VEGF and PDGF-B, and that in turn up-regulated the angiogenic activity in rat ovarian granulosa cells. This implicates that FSH and TGFβ1 play important roles in regulation of ovarian angiogenesis during follicle development. Copyright © 2010 Wiley-Liss, Inc.

Regulation of Ovarian Cancer Stem Cells or Tumor-Initiating Cells

PubMed Central

Kwon, Mi Jeong; Shin, Young Kee

2013-01-01

Cancer stem cells or tumor-initiating cells (CSC/TICs), which can undergo self-renewal and differentiation, are thought to play critical roles in tumorigenesis, therapy resistance, tumor recurrence and metastasis. Tumor recurrence and chemoresistance are major causes of poor survival rates of ovarian cancer patients, which may be due in part to the existence of CSC/TICs. Therefore, elucidating the molecular mechanisms responsible for the ovarian CSC/TICs is required to develop a cure for this malignancy. Recent studies have indicated that the properties of CSC/TICs can be regulated by microRNAs, genes and signaling pathways which also function in normal stem cells. Moreover, emerging evidence suggests that the tumor microenvironments surrounding CSC/TICs are crucial for the maintenance of these cells. Similarly, efforts are now being made to unravel the mechanism involved in the regulation of ovarian CSC/TICs, although much work is still needed. This review considers recent advances in identifying the genes and pathways involved in the regulation of ovarian CSC/TICs. Furthermore, current approaches targeting ovarian CSC/TICs are described. Targeting both CSC/TICs and bulk tumor cells is suggested as a more effective approach to eliminating ovarian tumors. Better understanding of the regulation of ovarian CSC/TICs might facilitate the development of improved therapeutic strategies for recurrent ovarian cancer. PMID:23528891

Progesterone signaling mediated through progesterone receptor membrane component-1 in ovarian cells with special emphasis on ovarian cancer.

PubMed

Peluso, John J

2011-08-01

Various ovarian cell types including granulosa cells and ovarian surface epithelial cells express the progesterone (P4) binding protein, progesterone receptor membrane component-1 (PGRMC1). PGRMC1 is also expressed in ovarian tumors. PGRMC1 plays an essential role in promoting the survival of both normal and cancerous ovarian cell in vitro. Given the clinical significance of factors that regulate the viability of ovarian cancer, this review will focus on the role of PGRMC1 in ovarian cancer, while drawing insights into the mechanism of PGRMC1's action from cell lines derived from healthy ovaries as well as ovarian tumors. Studies using PGRMC1siRNA demonstrated that P4's ability to inhibit ovarian cells from undergoing apoptosis in vitro is dependent on PGRMC1. To confirm the importance of PGRMC1, the ability of PGRMC1-deplete ovarian cancer cell lines to form tumors in intact nude mice was assessed. Compared to PGRMC1-expressing ovarian cancer cells, PGRMC1-deplete ovarian cancer cells formed tumors in fewer mice (80% compared to 100% for controls). Moreover, the number of tumors derived from PGRMC1-deplete ovarian cancer cells was 50% of that observed in controls. Finally, the tumors that formed from PGRMC1-deplete ovarian cancer cells were about a fourth the size of tumors derived from ovarian cancer cells with normal levels of PGRMC1. One reason for PGRMC1-deplete tumors being smaller is that they had a poorly developed microvasculature system. How PGRMC1 regulates cell viability and in turn tumor growth is not known but part of the mechanism likely involves the regulation of genes that promote cell survival and inhibit apoptosis. Copyright © 2011 Elsevier Inc. All rights reserved.

Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial.

PubMed

Xu, Yangying; Nisenblat, Victoria; Lu, Cuiling; Li, Rong; Qiao, Jie; Zhen, Xiumei; Wang, Shuyu

2018-03-27

Management of women with reduced ovarian reserve or poor ovarian response (POR) to stimulation is one of the major challenges in reproductive medicine. The primary causes of POR remain elusive and oxidative stress was proposed as one of the important contributors. It has been suggested that focus on the specific subpopulations within heterogeneous group of poor responders could assist in evaluating optimal management strategies for these patients. This study investigated the effect of anti-oxidant treatment with coenzyme Q10 (CoQ10) on ovarian response and embryo quality in young low-prognosis patients with POR. This prospective, randomized controlled study included 186 consecutive patients with POR stratified according to the POSEIDON classification group 3 (age < 35, poor ovarian reserve parameters). The participants were randomized to the CoQ10 pre-treatment for 60 days preceding IVF-ICSI cycle or no pre-treatment. The number of high quality embryos was a primary outcome measure. A total of 169 participants were evaluated (76 treated with CoQ10 and 93 controls); 17 women were excluded due to low compliance with CoQ10 administration. The baseline demographic and clinical characteristics were comparable between the groups. CoQ10 pretreatment resulted in significantly lower gonadotrophin requirements and higher peak E2 levels. Women in CoQ10 group had increased number of retrieved oocytes (4, IQR 2-5), higher fertilization rate (67.49%) and more high-quality embryos (1, IQR 0-2); p < 0.05. Significantly less women treated with CoQ10 had cancelled embryo transfer because of poor embryo development than controls (8.33% vs. 22.89%, p = 0.04) and more women from treatment group had available cryopreserved embryos (18.42% vs. 4.3%, p = 0.012). The clinical pregnancy and live birth rates per embryo transfer and per one complete stimulation cycle tended to be higher in CoQ10 group but did not achieve statistical significance. Pretreatment with CoQ10 improves ovarian response to stimulation and embryological parameters in young women with poor ovarian reserve in IVF-ICSI cycles. Further work is required to determine whether there is an effect on clinical treatment endpoints.

The Unexpected Ovarian Pregnancy at Laparoscopy: A Review of Management.

PubMed

Tabassum, Meher; Atmuri, Kiran

2017-01-01

Ovarian ectopic pregnancies are a rare occurrence; however the incidence is on the rise. Preoperative diagnosis remains difficult due to nonspecific clinical symptoms and USS findings. Most patients undergo diagnostic laparoscopy with subsequent surgical management. We present the case of a 32-year-old female who presented with vaginal bleeding and an unsited pregnancy, with a BhCG of 24693. Formal USS described unruptured right tubal ectopic with ovarian pregnancy being diagnosed at laparoscopy. A wedge resection was conducted to preserve ovarian function. Postoperative recovery was uneventful and BhCG levels returned to zero (nonpregnant) in an outpatient setting. Although laparoscopy remains the gold standard of diagnosis and treatment, in this case report we discuss benefits of early diagnosis for fertility conserving management, including nonsurgical options.

The follicular hormonal profile in low-responder patients undergoing unstimulated cycles: Is it hypoandrogenic?

PubMed

de los Santos, M J; García-Laez, V; Beltrán, D; Labarta, E; Zuzuarregui, Jose Luis; Alamá, P; Gámiz, P; Crespo, J; Bosch, E; Pellicer, A

2013-01-01

What is the final hormonal milieu of pre-ovulatory follicles of low-responder (LR) patients undergoing unstimulated cycles? Neither androgen secretion nor LH was impaired in pre-ovulatory follicles of LR women. Therapies currently used to improve ovarian response in LR women have an impact on the final hormonal follicular milieu, and these changes are believed to be partially responsible for determining the success rate in these women. Surprisingly, as far as we know, there is no report of the final hormonal profile of LR women undergoing unstimulated cycles or evidence that follicular androgen secretion in LR women is impaired. A prospective case-control study including 94 women, 36 normal controls and 58 LR patients (19 Young ≤ 35 years LR and 39 Aged >35 years LR) from 2009 to 2011. Fifty-eight LR women were divided into two groups: Young LR (age ≤ 35; n = 19) and Aged LR (ALR; age >35; n = 39). The control group (group C) comprised 36 egg donors undergoing an unstimulated cycle in our IVF unit. Serum and follicular fluid hormonal concentrations for estradiol (E₂), progesterone, testosterone and androstendione were measured. The spindle parameters of metaphase II oocytes generated from these groups were also analysed. Pre-ovulatory follicles from LR patients had similar androgenic and LH concentrations to those observed in the control group. However, higher intrafollicular concentrations of FSH and progesterone were observed in ALR. Moreover, no differences were found for the spindle evaluation of oocytes between groups by the Oosight technology. The controls were younger and had a lower BMI than the LR women. The sample size available restricted statistical power. This study suggests that the problem with LR women is not the final pre-ovulatory follicular androgen concentration since this is similar to normal responders, but in the ability to respond to controlled ovarian stimulation protocols. Therefore, efforts should be focused on long-interval androgen priming to potentially increase the recruitment of small antral follicles rather than increasing the intraovarian androgen levels within the current cycle. The present project has been supported by the R+D programme from the Generalitat Valenciana (Regional Valencian Government) IMPIVA MIDTF/2010/95. The authors have no conflict of interest to declare.

Altered Sex Hormone Concentrations and Gonadal mRNA Expression Levels of Activin Signaling Factors in Hatchling Alligators From a Contaminated Florida Lake

PubMed Central

MOORE, BRANDON C.; KOHNO, SATOMI; COOK, ROBERT W.; ALVERS, ASHLEY L.; HAMLIN, HEATHER J.; WOODRUFF, TERESA K.; GUILLETTE, LOUIS J.

2014-01-01

Activins and estrogens participate in regulating the breakdown of ovarian germ cell nests and follicle assembly in mammals. In 1994, our group reported elevated frequencies of abnormal, multioocytic ovarian follicles in 6 month old, environmental contaminant-exposed female alligators after gonadotropin challenge. Here, we investigated if maternal contribution of endocrine disrupting contaminants to the egg subsequently alters estrogen/inhibin/activin signaling in hatchling female offspring, putatively predisposing an increased frequency of multioocytic follicle formation. We quantified basal and exogenous gonadotropin-stimulated concentrations of circulating plasma steroid hormones and ovarian activin signaling factor mRNA abundance in hatchling alligators from the same contaminated (Lake Apopka) and reference (Lake Woodruff) Florida lakes, as examined in 1994. Basal circulating plasma estradiol and testosterone concentrations were greater in alligators from the contaminated environment, whereas activin/inhibin βA subunit and follistatin mRNA abundances were lower than values measured in ovaries from reference lake animals. Challenged, contaminant-exposed animals showed a more robust increase in plasma estradiol concentration following an acute follicle stimulating hormone (FSH) challenge compared with reference site alligators. Aromatase and follistatin mRNA levels increased in response to an extended FSH challenge in the reference site animals, but not in the contaminant-exposed animals. In hatchling alligators, ovarian follicles have not yet formed; therefore, these endocrine differences are likely to affect subsequent ovarian development, including ovarian follicle assembly. PMID:20166196

Wide excision of soft tissues adjacent to the ovary and fallopian tube does not impair the ovarian reserve in women undergoing prophylactic bilateral salpingectomy: results from a randomized, controlled trial.

PubMed

Venturella, Roberta; Morelli, Michele; Lico, Daniela; Di Cello, Annalisa; Rocca, Morena; Sacchinelli, Angela; Mocciaro, Rita; D'Alessandro, Pietro; Maiorana, Antonio; Gizzo, Salvatore; Zullo, Fulvio

2015-11-01

To study the effects of the wide excision of soft tissues adjacent to the ovary and fallopian tube on ovarian function and surgical outcomes in women undergoing laparoscopic bilateral prophylactic salpingectomy. Randomized, controlled trial. Teaching hospital. One hundred eighty-six women undergoing laparoscopic surgery for uterine myoma (n = 143) or tubal surgical sterilization (n = 43). Patients were randomly divided into two groups. In group A (n = 91), standard salpingectomy was performed. In group B (n = 95), the mesosalpinx was removed within the tubes. Prior to and 3 months after surgery, antimüllerian hormone (AMH), FSH, three-dimensional antral follicle count (AFC), vascular index (VI), flow index (FI), vascular-flow index (VFI), and OvAge were recorded for each patient. Ovarian reserve modification (Δ) before and after surgery was assessed as the primary outcome. Operative time, variation of the hemoglobin level (ΔHb), postoperative hospital stay, postoperative return to normal activity, and complication rate were assessed as secondary outcomes. No significant difference was observed between groups for ΔAMH, ΔFSH, ΔAFC, ΔVI, ΔFI, ΔVFI, and ΔOvAge. Moreover, the groups were similar for operative time, ΔHb, postoperative hospital stay, postoperative return to normal activity, and complication rate. Even when the surgical excision includes the removal of the mesosalpinx, salpingectomy does not damage the ovarian reserve. Moreover, wide salpingectomy with excision of the mesosalpinx did not alter blood loss, hospitalization stay, or return to normal activities. NCT02086370. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Analysis of postoperative complications associated with the use of anti-adhesion sodium hyaluronate-carboxymethylcellulose (HA-CMC) barrier after cytoreductive surgery for ovarian, fallopian tube and peritoneal cancers.

PubMed

Krill, Lauren S; Ueda, Stefanie M; Gerardi, Melissa; Bristow, Robert E

2011-02-01

To evaluate the risk of postoperative complications related to HA-CMC use in patients undergoing optimal cytoreductive surgery for primary and recurrent ovarian, fallopian tube, and peritoneal cancers. A single institution retrospective review identified all patients undergoing optimal (≤1 cm) cytoreductive surgery for primary or recurrent ovarian, fallopian tube, and peritoneal cancers between 1/95 and 12/08. Operative details and post-operative complications (<30 days) were extracted from the medical record. Fisher's exact test, Mann-Whitney-U, and multiple regression analyses were performed to identify factors, including HA-CMC use, associated with post-operative complications. Three hundred seventy-five cases were analyzed: HA-CMC was utilized in 168 debulking procedures. There was no difference in the incidence of overall morbidity for patients with HA-CMC compared to those without HA-CMC (OR 1.07; 95% CI: 0.68-1.67). On univariate analysis, application of HA-CMC increased the risk of pelvic abscess (OR 2.66; 95% CI: 1.21-5.86), particularly in the primary surgery setting (OR 4.65; 95% CI: 1.67-12.98) and in patients undergoing hysterectomy (OR 3.36; 95% CI: 1.18-9.53). After controlling for confounding factors using multiple linear regression, HA-CMC use approached statistical significance in predicting an increased risk of pelvic abscess but not major postoperative morbidity. HA-CMC adhesion barrier placement at the time of optimal cytoreductive surgery for ovarian, fallopian tube, and peritoneal cancer is not associated with major postoperative complications but may be associated with increased risk of pelvic abscess. Copyright © 2010 Elsevier Inc. All rights reserved.

Hair mercury concentrations and in vitro fertilization (IVF) outcomes among women from a fertility clinic.

PubMed

Wright, Diane L; Afeiche, Myriam C; Ehrlich, Shelley; Smith, Kristen; Williams, Paige L; Chavarro, Jorge E; Batsis, Maria; Toth, Thomas L; Hauser, Russ

2015-01-01

Total hair mercury (Hg) was measured among 205 women undergoing in vitro fertilization (IVF) treatment and the association with prospectively collected IVF outcomes (229 IVF cycles) was evaluated. Hair Hg levels (median=0.62ppm, range: 0.03-5.66ppm) correlated with fish intake (r=0.59), and exceeded the recommended EPA reference of 1ppm in 33% of women. Generalized linear mixed models with random intercepts accounting for within-woman correlations across treatment cycles were used to evaluate the association of hair Hg with IVF outcomes adjusted for age, body mass index, race, smoking status, infertility diagnosis, and protocol type. Hair Hg levels were not related to ovarian stimulation outcomes (peak estradiol levels, total and mature oocyte yields) or to fertilization rate, embryo quality, clinical pregnancy rate or live birth rate. Copyright © 2015 Elsevier Inc. All rights reserved.

Association Between Progesterone Elevation on the Day of Human Chronic Gonadotropin Trigger and Pregnancy Outcomes After Fresh Embryo Transfer in In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles

PubMed Central

Esteves, Sandro C.; Khastgir, Gautam; Shah, Jatin; Murdia, Kshitiz; Gupta, Shweta Mittal; Rao, Durga G.; Dash, Soumyaroop; Ingale, Kundan; Patil, Milind; Moideen, Kunji; Thakor, Priti; Dewda, Pavitra

2018-01-01

Progesterone elevation (PE) during the late follicular phase of controlled ovarian stimulation in fresh embryo transfer in vitro fertilization (IVF)/intracytoplasmic sperm injection cycles has been claimed to be associated with decreased pregnancy rates. However, the evidence is not unequivocal, and clinicians still have questions about the clinical validity of measuring P levels during the follicular phase of stimulated cycles. We reviewed the existing literature aimed at answering four relevant clinical questions, namely (i) Is gonadotropin type associated with PE during the follicular phase of stimulated cycles? (ii) Is PE on the day of human chorionic gonadotropin (hCG) associated with negative fresh embryo transfer IVF/intracytoplasmic sperm injection (ICSI) cycles outcomes in all patient subgroups? (iii) Which P thresholds are best to identify patients at risk of implantation failure due to PE in a fresh embryo transfer? and (iv) Should a freeze all policy be adopted in all the cycles with PE on the day of hCG? The existing evidence indicates that late follicular phase progesterone rise in gonadotropin releasing analog cycles is mainly caused by the supraphysiological stimulation of granulosa cells with exogenous follicle-stimulating hormone. Yet, the type of gonadotropin used for stimulation seems to play no significant role on progesterone levels at the end of stimulation. Furthermore, PE is not a universal phenomenon with evidence indicating that its detrimental consequences on pregnancy outcomes do not affect all patient populations equally. Patients with high ovarian response to control ovarian stimulation are more prone to exhibit PE at the late follicular phase. However, in studies showing an overall detrimental effect of PE on pregnancy rates, the adverse effect of PE on endometrial receptivity seems to be offset, at least in part, by the availability of good quality embryo for transfer in women with a high ovarian response. Given the limitations of the currently available assays to measure progesterone at low ranges, caution should be applied to adopt specific cutoff values above which the effect of progesterone rise could be considered detrimental and to recommend “freeze-all” based solely on pre-defined cutoff points. PMID:29755412

Safety and usefulness of cryopreservation of ovarian tissue to preserve fertility: a 12-year retrospective analysis.

PubMed

Imbert, R; Moffa, F; Tsepelidis, S; Simon, P; Delbaere, A; Devreker, F; Dechene, J; Ferster, A; Veys, I; Fastrez, M; Englert, Y; Demeestere, I

2014-09-01

Do the benefits of ovarian tissue cryopreservation outweigh the risks for patients seeking to preserve fertility before gonadotoxic treatment in various indications? In >90% of the patients undergoing cryopreservation of ovarian tissue, oncological treatment was associated with a reduced ovarian reserve and in 30% of patients, premature ovarian failure (POF) occurred within 5 years. Ovarian tissue cryopreservation is an effective fertility preservation option, especially for pre-pubertal patients and patients who have a short time between diagnosis of a disease and gonadotoxic treatment. This study retrospectively analysed ovarian function and fertility recovery rates, as well as ovarian tissue characteristics, of patients who underwent ovarian tissue cryopreservation at Erasme Hospital between 1999 and 2011. A total of 225 patients referred from 15 Belgian oncological units underwent cryopreservation of ovarian tissue before gonadotoxic therapy for malignant or benign diseases. There were 28 patients (12.4%) who died during follow-up due to recurrence of disease. One severe adverse event occurred during anaesthesia for ovarian tissue collection, leading to the death of the patient. Ovarian function and fertility outcomes were available for 114 patients including 13 girls who were pre-pubertal at the time of the procedure. Eight patients had undergone ovarian tissue transplantation in order to restore their fertility after remission of the disease. Breast cancer and haematological disease were the most frequent indications for ovarian tissue cryopreservation. Overall, 90% of post-pubertal patients were diagnosed with poor ovarian reserve (AMH < 0.5 ng/ml) after a mean of 50 months of follow-up (11-125 months), including 30% with POF (FSH > 40 IU/ml). Breast cancer patients had a lower rate of POF than did post-pubertal patients with haematological diseases (11 versus 34.5%, respectively), despite the older age (mean 31 versus 23.5 years old, respectively) of the breast cancer patients. Ovarian function returned in 71 post-pubertal patients without the need for grafts of cryopreserved tissue. Spontaneous pregnancies were reported for 33 of them, leading to 34 live births. Among the 13 pre-pubertal patients who reached pubertal age during the follow-up, 10 had POF. Eight patients received cryopreserved ovarian grafts to reverse POF and three of them have already become pregnant. This study is a retrospective analysis. The cohort was not compared with a control group of patients who did not undergo the procedure. After careful evaluation of the surgical risks, ovarian tissue cryopreservation can be proposed as an efficient option to preserve the fertility of children and young adults facing gonadotoxic therapies. However, alternative procedures such as oocyte or embryo cryopreservation should be considered as first options especially for older patients or if there is high risk of neoplastic cells within the ovaries. This study was supported by the Télévie, FNRS-FRSM and Fondation Belge contre le cancer. There are no competing interests to report. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Temporary ovarian failure in thyroid cancer patients after thyroid remnant ablation with radioactive iodine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raymond, J.P.; Izembart, M.; Marliac, V.

We studied ovarian function retrospectively in 66 women who had regular menstrual cycles before undergoing complete thyroidectomy for differentiated thyroid cancer and subsequent thyroid remnant ablation with /sup 131/I. Eighteen women developed temporary amenorrhea accompanied by increased serum gonadotropin concentrations during the first year after /sup 131/I therapy. No correlation was found between the radioactive iodine dose absorbed, thyroid uptake before treatment, oral contraceptive use, or thyroid autoimmunity. Only age was a determining factor, with the older women being the most affected. We conclude that radioiodine ablation therapy is followed by transient ovarian failure, especially in older women.

Anti-Mullerian hormone-tailored stimulation protocols improve outcomes whilst reducing adverse effects and costs of IVF.

PubMed

Yates, A P; Rustamov, O; Roberts, S A; Lim, H Y N; Pemberton, P W; Smith, A; Nardo, L G

2011-09-01

Anti-Müllerian hormone (AMH) is increasingly used to quantify ovarian reserve, but it has not yet realized its full clinical potential in assisted reproduction technology. We investigated the possible benefits of using novel, stratified ovarian hyperstimulation protocols, tailored to individual AMH levels, compared with conventional stimulation. Retrospective data were collected from 769 women (first cycle of IVF, using fresh embryos), in a UK tertiary care unit: 346 women using conventional stimulation protocols; 423 women treated under new AMH-tailored protocols. Embryo transfer rates increased significantly (79-87%: P= 0.002) after the introduction of AMH-tailored stimulation protocols. Pregnancy rate per cycle started and live birth rate also increased significantly compared with conventionally treated women (17.9-27.7%, P= 0.002 and 15.9-23.9%, P = 0.007, respectively). Moreover, in the AMH group, the incidence of the ovarian hyperstimulation syndrome (OHSS) fell significantly (6.9-2.3%, P = 0.002) and failed fertilization fell from 7.8 to 4.5%. The cost of fertility drug treatment fell by 29% per patient and the overall cost of clinical management of OHSS fell by 43% in the AMH group. GnRH antagonist protocols, introduced as part of AMH-tailored treatment, may have contributed to the observed improvements: however, within the AMH-tailored group, the live birth rate was not significantly different between agonist and antagonist-treated groups. Although large, prospective, multicentre studies are indicated, we have clearly demonstrated that individualized, AMH-guided, controlled ovarian hyperstimulation protocols significantly improved positive clinical outcomes, reduced the incidence of complications and reduced the financial burden associated with assisted reproduction.

The rate of high ovarian response in women identified at risk by a high serum AMH level is influenced by the type of gonadotropin.

PubMed

Arce, Joan-Carles; Klein, Bjarke M; La Marca, Antonio

2014-06-01

The aim was to compare ovarian response and clinical outcome of potential high-responders after stimulation with highly purified menotropin (HP-hMG) or recombinant follicle-stimulating hormone (rFSH) for in vitro fertilisation/intracytoplasmic sperm injection. Retrospective analysis was performed on data collected in two randomized controlled trials, one conducted following a long GnRH agonist protocol and the other with an antagonist protocol. Potential high-responders (n = 155 and n = 188 in the agonist and antagonist protocol, respectively) were defined as having an initial anti-Müllerian hormone (AMH) value >75th percentile (5.2 ng/ml). In both protocols, HP-hMG stimulation in women in the high AMH category was associated with a significantly lower occurrence of high response (≥15 oocytes retrieved) than rFSH stimulation; 33% versus 51% (p = 0.025) and 31% versus 49% (p = 0.015) in the long agonist and antagonist protocol, respectively. In the potential high-responder women, trends for improved live birth rate were observed with HP-hMG compared with rFSH (long agonist protocol: 33% versus 20%, p = 0.074; antagonist protocol: 34% versus 23%, p = 0.075; overall population: 34% versus 22%, p = 0.012). In conclusion, the type of gonadotropin used for ovarian stimulation influences high-response rates and potentially clinical outcome in women identified as potential high-responders.

Premature Ovarian Failure in French Canadian Leigh Syndrome.

PubMed

Ghaddhab, Chiraz; Morin, Charles; Brunel-Guitton, Catherine; Mitchell, Grant A; Van Vliet, Guy; Huot, Céline

2017-05-01

In all surviving girls with Leigh syndrome, French Canadian variety, a mitochondrial disease, we detected premature ovarian failure, manifested as absent or arrested breast development, lack of menarche, high follicle-stimulating hormone, a prepubertal uterus, and small ovaries. Pubertal onset and progression should be evaluated in girls with mitochondrial diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Anti-Müllerian hormone levels and antral follicle count in women enrolled in in vitro fertilization cycles: relationship to lifestyle factors, chronological age and reproductive history.

PubMed

Nardo, Luciano G; Christodoulou, Dimitra; Gould, Della; Roberts, Steve A; Fitzgerald, Cheryl T; Laing, Ian

2007-01-01

The aims of this prospective study were to investigate the relationship between anti-Müllerian hormone (AMH) and antral follicle count (AFC), and to determine whether these markers of ovarian reserve correlate with lifestyle factors, ethnicity, chronological age and reproductive history. Participants were 136 normo-ovulatory women undergoing infertility work-up within 3 months of their first ovarian stimulation cycle for in vitro fertilization. On day 3 of a spontaneous menstrual cycle, a blood sample for measurement of plasma AMH levels was taken and a transvaginal ultrasound scan to determine the AFC (follicles measuring 2-5 mm in diameter) was performed. Information about smoking, body mass index, alcohol consumption, ethnic origin, chronological age, age at menarche, years since menarche and gravidity were recorded using a case report form. The main outcome measures were plasma AMH concentrations and total number of small antral follicles (AFC). Median plasma levels of AMH were 2.0 ng/ml (interquartile range 1.1-3.6) and AFC was 10 (interquartile range 7-15). A positive correlation between AMH and AFC (r = 0.54, p < 0.0001) was found. AMH and AFC correlated negatively with age (r = -0.30, p < 0.001 and r = -0.27, p = 0.001 respectively) and number of years since menarche (r = -0.23, p = 0.007 and r = -0.21, p = 0.015 respectively), but not with any of the other measures. Circulating AMH levels and AFC correlated with each other and declined significantly with age. There were only weak, non-significant, correlations with lifestyle factors and reproductive history. These putative markers could be used individually or together to assess the age-related decline of ovarian function in normo-ovulatory candidates for IVF.

Female age, serum antimüllerian hormone level, and number of oocytes affect the rate and number of euploid blastocysts in in vitro fertilization/intracytoplasmic sperm injection cycles.

PubMed

La Marca, Antonio; Minasi, Maria Giulia; Sighinolfi, Giovanna; Greco, Pierfrancesco; Argento, Cindy; Grisendi, Valentina; Fiorentino, Francesco; Greco, Ermanno

2017-11-01

To study the relative role of female age and ovarian reserve, measured through serum antimüllerian hormone (AMH) in determining the rate and number of euploid blastocysts in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Retrospective analysis of cycles performed in 2014-2015. Tertiary referral IVF center. A total of 578 infertile couples undergoing IVF/ICSI and preimplantation genetic screening (PGS) analysis. All embryos were cultured and biopsied at the blastocyst stage. The method involved whole-genome amplification followed by array comparative genome hybridization. Serum AMH was measured by means of the modified Beckman Coulter AMH Gen II assay. The rate and number of euploid blastocysts and their correlation with ovarian reserve and response to stimulation. The mean (±SD) age of patients was 37.6 ± 4.1 years, and the mean number of blastocysts per patient was 3.1 ± 2. The total number of blastocysts available to the analysis was 1,814, and 36% of them were euploid after PGS. Age and serum AMH were significantly and independently related to the rate of euploid blastocysts available for patients. As an effect of the cohort size, the number of mature oocytes positively affected the total number of euploid blastocysts per patient. A strong positive age-independent relationship between AMH level and the rate of euploid blastocysts was found. This confirms that the measurement of ovarian reserve by means of AMH has high relevance when counseling infertile patients. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Ovarian function after uterine artery embolization and hysterectomy.

PubMed

Healey, Sarah; Buzaglo, Karen; Seti, Laurent; Valenti, David; Tulandi, Togas

2004-08-01

To evaluate the effect of uterine artery embolization (UAE) and hysterectomy on ovarian function. Prospective case control study (Canadian Task Force classification II-2). University teaching hospital. Eighty-four healthy premenopausal women with symptomatic uterine myoma(s) undergoing UAE or hysterectomy. Patients had blood drawn to measure follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels and underwent transvaginal ultrasound to measure volume of the myoma(s) and uterus on cycle day 3 before the procedures. These measurements were repeated 3 and 6 months after treatment. The main outcome was the differences in serum FSH, LH, E2, and ultrasound findings before and after UAE or hysterectomy. Of the 68 patients who underwent UAE and 16 who underwent hysterectomy, 48 and 13 respectively, completed 6-month follow-up. The mean age of the patients in the UAE group was 44.9 +/- 3.8 years and 43.7 +/- 5.6 years in the hysterectomy group. There was no significant difference in serum FSH before (8.9 +/- 0.7 IU/L) and 6 months after UAE (9.9 +/- 1.0 lU/L), and between the baseline (10.4 +/- 1.8 lU/L) and 6 months posthysterectomy (7.8 +/- 1.8 lU/L). The uterine volume 6 months after UAE (361 +/- 50 mL) was significantly smaller than before UAE(538 +/- 38mL; p =.005, 95% CI 44-241). Compared with baseline (154 +/- 20 mL), the dominant myoma volume was smaller at 6 months after UAE (97 +/- 16 mL; p <.05, 95% CI 1.57-62). Uterine artery embolization is associated with a significant reduction in myoma and uterine volume. Ovarian function at 6 months, as indicated by day 3 FSH levels, is not affected by UAE or hysterectomy.

Follicle dynamics: visualization and analysis of follicle growth and maturation using murine ovarian tissue culture.

PubMed

Murase, Tomohiko; Iwase, Akira; Komatsu, Kouji; Bayasula; Nakamura, Tomoko; Osuka, Satoko; Takikawa, Sachiko; Goto, Maki; Kotani, Tomomi; Kikkawa, Fumitaka

2018-02-01

To visualize and analyze follicle development in ovarian tissue culture using physiological concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in order to establish an ovarian tissue culture system that enables efficient in vitro growth of follicles. Ovarian tissues from 4-week-old female ICR mice were sliced and cultured. Images of ovarian tissues in culture were obtained at 24-h or 30-min intervals by using a microscope. The area of each follicle observed in the ovarian tissue slices was tracked and analyzed in association with oocyte maturation. We were able to track the development of each follicle using this culture system. Follicle growth was associated with oocyte maturation. Meiotically matured oocytes (MII) were obtained from 33% of all follicles investigated. Approximately, a quarter of follicles (24%) did not grow and resulted in atresia. Follicle dynamics were successfully visualized and analyzed in murine ovarian tissue culture. We were able to obtain mature oocytes from the fully grown follicles in vitro. This culture system would be helpful for efficient in vitro culturing of ovarian tissues.

Circulating gonadotropins and ovarian adiponectin system are modulated by acupuncture independently of sex steroid or β-adrenergic action in a female hyperandrogenic rat model of polycystic ovary syndrome.

PubMed

Maliqueo, Manuel; Benrick, Anna; Alvi, Asif; Johansson, Julia; Sun, Miao; Labrie, Fernand; Ohlsson, Claes; Stener-Victorin, Elisabet

2015-09-05

Acupuncture with combined manual and low-frequency electrical stimulation, or electroacupuncture (EA), reduces endocrine and reproductive dysfunction in women with polycystic ovary syndrome (PCOS), likely by modulating sympathetic nerve activity or sex steroid synthesis. To test this hypothesis, we induced PCOS in rats by prepubertal implantation of continuous-release letrozole pellets (200 µg/day) or vehicle. Six weeks later, rats were treated for 5-6 weeks with low-frequency EA 5 days/week, subcutaneous injection of 17β-estradiol (2.0 µg) every fourth day, or a β-adrenergic blocker (propranolol hydrochloride, 0.1 mg/kg) 5 days/week. Letrozole controls were handled without needle insertion or injected with sesame oil every fourth day. Estrous cyclicity, ovarian morphology, sex steroids, gonadotropins, insulin-like growth factor I, bone mineral density, and gene and protein expression in ovarian tissue were measured. Low-frequency EA induced estrous-cycle changes, decreased high levels of circulating luteinizing hormone (LH) and the LH/follicle-stimulating hormone (FSH) ratio, decreased high ovarian gene expression of adiponectin receptor 2, and increased expression of adiponectin receptor 2 protein and phosphorylation of ERK1/2. EA also increased cortical bone mineral density. Propranolol decreased ovarian expression of Foxo3, Srd5a1, and Hif1a. Estradiol decreased circulating LH, induced estrous cycle changes, and decreased ovarian expression of Adipor1, Foxo3, and Pik3r1. Further, total bone mineral density was higher in the letrozole-estradiol group. Thus, EA modulates the circulating gonadotropin levels independently of sex steroids or β-adrenergic action and affects the expression of ovarian adiponectin system. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Fertility Preservation in Endocrine Disorders during Transition for Girls.

PubMed

Bénard, Julie; Sermondade, Nathalie; Grynberg, Michaël

2018-01-01

Recent advances in fertility preservation (FP) techniques have led to a wide spread of indications. FP should now be discussed not only for young girls having to receive gonadotoxic treatments for cancer, but also for those with genetic or endocrine disorders, as well as benign ovarian diseases at risk of premature ovarian insufficiency. For premenarchal girls, ovarian tissue cryopreservation is still the only available technique. Oocyte cryopreservation after ovarian stimulation could be offered to postmenarchal girls. Whenever possible, the parents and the young patient should be informed of the benefits to be expected, as well as of the risks and limits of FP for children. © 2018 S. Karger AG, Basel.

Loss of c-myc repression coincides with ovarian cancer resistance to transforming growth factor beta growth arrest independent of transforming growth factor beta/Smad signaling.

PubMed

Baldwin, Rae Lynn; Tran, Hang; Karlan, Beth Y

2003-03-15

Many epithelial carcinomas, including ovarian, are refractory to the antiproliferative effects of transforming growth factor (TGF) beta. In some cancers, TGF-beta resistance has been linked to TGF-beta receptor II (TbetaR-II) and Smad4 mutations; however, in ovarian cancer, the mechanism of resistance remains unclear. Primary ovarian epithelial cell cultures were used as a model system to determine the mechanisms of TGF-beta resistance. To simulate in vivo responses to TGF-beta, primary cultures derived from normal human ovarian surface epithelium (HOSE) and from ovarian carcinomas (CSOC) were grown on collagen I gel, the predominant matrix molecule in the ovarian tumor milieu. When treated with 5 ng/ml TGF-beta for 72 h, HOSE (n = 11) proliferation was inhibited by 20 +/- 21% on average. In contrast, CSOC (n = 10) proliferation was stimulated 5 +/- 10% in response to TGF-beta (a statistically significant difference in response when compared with HOSE; P = 0.001). To dissect the TGF-beta/Smad signaling pathway we used a quantitative RNase protection assay (RPA) for measuring mRNA levels of TGF-beta pathway components in 20 HOSE and 20 CSOC cultures. Basal mRNA levels of TGF-beta receptors I and II, downstream signaling components Smad2, 3, 4, 6, 7, and the transcriptional corepressors Ski and SnoN did not show a statistically significant difference between HOSE and CSOC, and cannot explain their differential susceptibility to TGF-beta-induced cell cycle arrest. To assess functional differences of the TGF-beta pathway in TGF-beta-sensitive HOSE and TGF-beta-resistant CSOC, we measured Smad2/4 and 3/4 complex induction after TGF-beta treatment. HOSE and CSOC showed equivalent Smad2/4 and 3/4 complex induction after TGF-beta exposure for 0, 0.5, 2, and 4 h. It has been proposed that SnoN and Ski are corepressors of the TGF-beta/Smad pathway and undergo TGF-beta-induced degradation followed by reinduction of SnoN mRNA. However, our data show equivalent SnoN degradation in HOSE and CSOC, and equivalent SnoN mRNA induction after TGF-beta treatment. Surprising, TGF-beta-induced Ski degradation was not observed in HOSE or CSOC, suggesting that Ski may not function as a TGF-beta/Smad corepressor in ovarian epithelial cells. These data implied that the TGF-beta/Smad pathway remains functional in CSOC, although CSOC cells are resistant to antimitogenic TGF-beta effects. CSOC resistance to TGF-beta coincided with the loss of c-myc down-regulation. These data suggest that TGF-beta/Smad signaling is blocked downstream of Smad complex formation or that an alternate signaling pathway other than TGF-beta/Smad may transmit TGF-beta-induced cell cycle arrest in the ovarian epithelium.

There is a Positive Correlation Between Socioeconomic Status and Ovarian Reserve in Women of Reproductive Age.

PubMed

Barut, Mert Ulas; Agacayak, Elif; Bozkurt, Murat; Aksu, Tarık; Gul, Talip

2016-11-16

BACKGROUND The purpose of this study was to investigate the potential association between socioeconomic status and ovarian reserve, anti-Mullerian hormone level, antral follicle count, and follicle stimulating hormone level in women of reproductive age. MATERIAL AND METHODS A total of 101 married women between 20-35 years of age who presented to the Department of Obstetrics and Gynecology, Health Research System In Vitro Fertilization (HRS IVF) Center between October 2014 and November 2015 and met the inclusion criteria were included in this study. The participants were divided into three socioeconomic groups using Kuppuswamy's socioeconomic status scale. Thirty-one participants were assigned to the low socioeconomic status group, 37 to the middle socioeconomic status group, and 33 to the high socioeconomic status group. On days 3-6 of the menstrual cycle, 10 mL of blood was collected from the participants for follicle stimulating hormone and anti-Mullerian hormone measurements. Transvaginal ultrasonography was performed for both ovaries for the purpose of counting antral follicles measuring 2-10 mm in diameter. RESULTS Both ovarian reserve parameters, namely anti-Mullerian hormone level and antral follicle count, exhibited a significant association with socioeconomic status (p=0.000 and p=0.000, respectively). The association between follicle stimulating hormone level and socioeconomic status was also significant (p=0.000). CONCLUSIONS A low socioeconomic status aggravated by sources of stress such as undernutrition and financial hardships affects ovarian reserve, which should be remembered in approaching infertile patients.

Perfluorooctanoic acid stimulates ovarian cancer cell migration, invasion via ERK/NF-κB/MMP-2/-9 pathway.

PubMed

Li, Xiaozhao; Bao, Chunyu; Ma, Zhinan; Xu, Boqun; Liu, Xiaoqiu; Ying, Xiaoyan; Zhang, Xuesen

2018-05-09

As widely used in consumer products, perfluorooctanoic acid (PFOA) has become a common environmental pollutant, which has been detected in human serum and associated with cancers. Our previous study showed that PFOA is a carcinogen that promotes endometrial cancer cell migration and invasion through activation of ERK/mTOR signaling. Here, we showed that PFOA (≥100 nM) treatment also stimulated A2780 ovarian cancer cell invasion and migration, which correlated with increased matrix metalloproteinases MMP-2/-9 expression, important proteases associated with tumor invasion and migration. Notably, PFOA treatment induced activation of ERK1/2/ NF-κB signaling. Pre-treatment with U0126, an ERK1/2inhibitor；or JSH-23, a NF-kB inhibitor, can reverse the PFOA-induced cell migration and invasion. Consistent with these results, inhibiting ERK1/2 or NF-κB signaling abolished PFOA-induced up-regulation of MMP-2/-9 expression. These results indicate that PFOA can stimulate ovarian cancer cell migration, invasion and MMP-2/-9 expression by up-regulating ERK/NF-κB pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

Physical-chemical and biological characterization of different preparations of equine chorionic gonadotropin

PubMed Central

Natal, Fabio Luis Nogueira; Ribela, Maria Teresa Carvalho Pinto; de Almeida, Beatriz Elane; de Oliveira, João Ezequiel; Bartolini, Paolo

2016-01-01

Ovarian stimulation with commercial preparations of equine chorionic gonadotropin (eCG) produces extremely variable responses in domestic animals, ranging from excessive stimulation to practically no stimulation, when applied on the basis of their declared unitage. This study was conducted to analyze four commercial preparations from different manufacturers via reversed-phase HPLC (RP-HPLC) in comparison with a reference preparation and an official International Standard from the World Health Organization. The peaks obtained by this qualitative and quantitative physical–chemical analysis were compared using an in vivo bioassay based on the ovarian weight gain of prepubertal female rats. The RP-HPLC data showed one or two peaks close to a main peak (tR = 27.9 min), which were related to the in vivo bioactivity. Commercial preparations that have this altered peak showed very little or no in vivo activity, as demonstrated by rat ovarian weight and in peripubertal gilts induced to ovulate. Overall, these findings indicate that RP-HPLC can be a rapid and reliable tool to reveal changes in the physicochemical profile of commercial eCG that is apparently related to decreased biological activity of this hormone. PMID:27297410

Role of Fallopian Tubes in the Development of Ovarian Cancer.

PubMed

Corzo, Camila; Iniesta, Maria D; Patrono, Maria Guadalupe; Lu, Karen H; Ramirez, Pedro T

2017-02-01

Ovarian cancer is the leading cause of death from gynecologic malignancy and the fifth cause of cancer death in women in the United States. The most common and lethal histologic subtype of epithelial ovarian cancer is high-grade serous carcinoma (HGSC), which generally presents at an advanced stage. HGSC may be associated with BRCA1 and BRCA2 mutations. Historically, HGSC was believed to originate from the ovarian epithelial cells. However, more recent evidence supports the idea that most ovarian cancers originate in the fallopian tube epithelium in both high-risk women and in the general population. Serous tubal intraepithelial carcinomas may ultimately evolve into ovarian or peritoneal cancer. As a result, prophylactic salpingectomy with conservation of the ovaries has become an increasingly more common practice for premenopausal women undergoing risk-reducing surgery. Because the fallopian tube is now recognized as the most common potential site of origin of ovarian carcinoma, there is ongoing research to explore molecular and genetic factors that may be critical in the development of this disease. Further research is needed to identify novel opportunities for early detection and screening of ovarian cancer with the ultimate goal of increasing overall survival. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Role of Ovarian Transposition Based on the Dosimetric Effects of Craniospinal Irradiation on the Ovaries: A Case Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitchell, James D.; Hitchen, Christine; Vlachaki, Maria T.

2007-10-01

In this study, we present a case of laparoscopic ovarian transposition to preserve ovarian function in an adult female patient treated with craniospinal irradiation for standard risk medulloblastoma. The prescribed dose to the craniospinal axis was 2340 cGy at 180 cGy per fraction and was delivered with 6-MV photons. Before ovarian transposition, magnetic resonance imaging (MRI) of the pelvis was obtained for localization of the ovaries and was registered with the planning computed tomography (CT) scan. Surgical clips allowed for CT localization of the ovaries after transposition. As a result of ovarian transposition, mean and maximum radiation doses decreased frommore » 983 to 68 cGy and 1624 to 84 cGy for the left ovary and from 166 to 87 cGy and 723 to 103 cGy for the right ovary, respectively. Review of the literature indicates that such radiation doses are below the threshold that causes ovarian dysfunction and infertility. We conclude that ovarian localization with an MRI of the pelvis can be offered to females undergoing craniospinal irradiation. Transposition of the ovaries provides an option to preserve ovarian function in cases where the ovaries would otherwise be included within the radiation field.« less

Accuracy and safety verification of ovarian reserve assessment technique for ovarian tissue transplantation using optical coherence tomography in mice ovary

NASA Astrophysics Data System (ADS)

Takae, Seido; Tsukada, Kosuke; Sato, Yorino; Okamoto, Naoki; Kawahara, Tai; Suzuki, Nao

2017-03-01

Except for histological study, there are currently no suitable techniques available for the detection and identification of primordial follicles in ovary of primary ovarian insufficiency patients who have undetectable AMH levels. Also, the ability to locate and quantify follicles on ovarian cortex strips, without fixation, is valuable for patients who could undergo subsequent successful ovarian tissue transplantation. Although optical coherence tomography (OCT) is a well-established high resolution imaging technique without fixation commonly applied in biomedicine, few reports are available on ovarian tissue imaging. In present study, we established standard OCT follicle images at each developmental stage, including the primordial follicle, and demonstrated the efficacy of OCT to estimate IVF outcome in transplanted mice ovary like ovarian reserve tests. Unfortunately, the current commercial OCT could not be used to accurate follicle count the number of follicles for whole ovary, because the maximum depth of examination was 100 μm. And we demonstrated the safety of OCT examination, it did not affect IVF outcome and birth defect rate, and reproductive ability. Although there is room for improvement, these findings will be first step to bring OCT examination a step closer to clinical application for measuring true ovarian reserve and localizing follicles.

Short-Term PTEN Inhibition Improves In Vitro Activation of Primordial Follicles, Preserves Follicular Viability, and Restores AMH Levels in Cryopreserved Ovarian Tissue From Cancer Patients.

PubMed

Novella-Maestre, Edurne; Herraiz, Sonia; Rodríguez-Iglesias, Beatriz; Díaz-García, César; Pellicer, Antonio

2015-01-01

In vitro activation and growth of primordial dormant follicles to produce fertilizable oocytes would provide a useful instrument for fertility preservation. The employment of Phosphatase and TENsin homolog (PTEN) inhibitors, in combination with Protein kinase B (Akt) stimulating molecules, has been previously employed to increase follicular activation through the stimulation of the PTEN-Akt pathway. We aim to establish improved in vitro activation also for cancer patients whose ovarian tissue has already been cryopreserved. Fresh and previously cryopreserved human ovarian cortex were exposed to short-term, low-concentration and ovary-specific treatment with only a PTEN inhibitor. Our in vitro activation protocol enhances the activation mechanisms of primordial follicles in both fresh and cryopreserved samples, and enlarges growing populations without inducing apoptosis in either follicles or the surrounding stroma. Treatment augments estradiol secretion and restores the expression levels of the previously diminished Anti-Müllerian hormone by means of cryopreservation procedures. Genomic modulation of the relative expression of PTEN pathway genes was found in treated samples. The in vitro activation protocol offers new alternatives for patients with cryopreserved tissue as it increases the pool of viable activated follicles available for in vitro growth procedures. The combination of ovarian tissue cryopreservation and in vitro activation of primordial follicles, the main ovarian reserve component, will be a major advancement in fertility preservation.

Thirty-day unplanned hospital readmission in ovarian cancer patients undergoing primary or interval cytoreductive surgery: systematic literature review.

PubMed

Clark, Rachel M; Rice, Laurel W; Del Carmen, Marcela G

2018-06-18

Thirty-day readmission rate has been proposed as metric of quality and remains an ongoing clinical concern in the primary treatment of patients with advanced-stage ovarian epithelial ovarian cancer. We conducted a review of the literature to identify rates, risk factors, and predictors for 30-day readmission in this population. A 10-year period MEDLINE (PubMed) search of English literature studies published between January 01, 2008-January 01, 2018 was performed to identify appropriate studies for review. Thirty -day readmission rates for ovarian cancer patients undergoing primary treatment ranged from 2.5-19.3%. Neoadjuvant chemotherapy and interval cytoreductive surgery (NACT-ICS) surgery was associated with lower readmission rates, when compared to primary debulking surgery (PDS). The most frequently reported adverse events resulting in readmission include inpatient management of ileus/small bowel obstruction, wound-related complications, and thromboembolic events. Readmission predictors included the presence of other medical comorbidities, re-operation, and major complications occurring after initial hospital discharge. Some studies reported lower rates of readmission and survival in patients treated by NACT-ICS. Policies and programs should be designed to measure short- and long-term outcomes in this patient population to avoid bias in assigning patients to NACT-ICS to maintain low 30-day readmission rates. Copyright © 2018 Elsevier Inc. All rights reserved.

Analysis of secondary cytoreduction for recurrent ovarian cancer by robotics, laparoscopy and laparotomy.

PubMed

Magrina, Javier F; Cetta, Rachel L; Chang, Yu-Hui; Guevara, Gregory; Magtibay, Paul M

2013-05-01

Analysis of perioperative outcomes and survival of patients with recurrent ovarian cancer undergoing secondary cytoreduction by robotics, laparoscopy, or laparotomy. Retrospective analysis of 52 selected patients with recurrent ovarian cancer undergoing secondary cytoreduction by laparoscopy (9), laparotomy (33) or robotics (10) between January 2006 and December 2010. Comparison was made by a total of 21 factors including age, BMI, number of previous surgeries, tumor type and grade, number of procedures, and 15 types of procedures performed at secondary cytoreduction. For all patients, the mean operating time was 213.8 min, mean blood loss 657.4 ml; and mean hospital stay 7.5 days. Complete debulking was achieved in 75% of patients. Postoperative complications were noted in 36.5% of patients. Overall and progression-free survival at 3-years were 58.8% and 34.1%, respectively. Laparoscopy and robotics had reduced blood loss and hospital stay, while no differences were observed among the three groups for operating time, complications, complete debulking, and survival. Selected patients with recurrent ovarian cancer benefit from a laparoscopic or robotic secondary cytoreduction without compromising survival. Robotics and laparoscopy provide similar perioperative outcomes, and reduced blood loss and shorter hospital stay as compared to laparotomy. Laparotomy seems preferable for patients with widespread peritoneal implants, multiple sites of recurrence, and/or extensive adhesions. Copyright © 2013 Elsevier Inc. All rights reserved.

Increased abundance of aromatase and follicle stimulating hormone receptor mRNA and decreased insulin-like growth factor-2 receptor mRNA in small ovarian follicles of cattle selected for twin births

USDA-ARS?s Scientific Manuscript database

Cattle genetically selected for twin ovulations and births (Twinner) exhibit increased ovarian follicular development, increased ovulation rate, and greater blood and follicular fluid IGF 1 concentrations compared with contemporary cattle not selected for twins (Control). Experimental objectives wer...

[Using an ovarian drilling by hydrolaparoscopy or recombinant follicle stimulating hormone plus metformin to treat polycystic ovary syndrome: Why a randomized controlled trial fail?].

PubMed

Fernandez, H; Cedrin-Durnerin, I; Gallot, V; Rongieres, C; Watrelot, A; Mayenga-Mankezi, J-M; Arnoux, A

2015-10-01

To evaluate pregnancy rates after randomized controlled trial (RCT) between ovarian drilling by fertiloscopy or ovarian hyperstimulation+insemination+metformine after clomifène citrate (cc) treatment fails. Randomized controlled trial with 126 patients in each arm in 9 university centers. After 6-9 months of stimulation by cc, 2 groups were randomized: group 1, ovarian drilling with bipolar energy versus group 2: 3 months treatment by metformine followed by 3 hyperstimulation by FSH+insemination. The success rate was pregnancy rate above 12 weeks. RCT was stopped after the screening of 40 patients. In spite of the low number of patients, the pregnancy rate is significantly higher in medical group 8/16 versus 3/18 (p=0.04). The causes of fail of RCT were in relationship with difficulties of inclusion, with absence of final agreement by team included. Moreover, RCT between medical and surgical management is often root of difficulties for patients who decline surgical strategy. However, medical treatment appeared better than drilling in this RCT. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Randomized, double-blind, dose-escalation trial of triptorelin for ovary protection in childhood-onset systemic lupus erythematosus.

PubMed

Brunner, Hermine I; Silva, Clovis A; Reiff, Andreas; Higgins, Gloria C; Imundo, Lisa; Williams, Calvin B; Wallace, Carol A; Aikawa, Nadia E; Nelson, Shannen; Klein-Gitelman, Marisa S; Rose, Susan R

2015-05-01

To determine the dose of triptorelin that is sufficient to maintain complete ovarian suppression in female patients with childhood-onset systemic lupus erythematosus (SLE) who require cyclophosphamide therapy, to determine the length of time needed to achieve ovarian suppression after initiation of triptorelin treatment, and to investigate the safety of triptorelin. In this randomized, double-blind, placebo-controlled, dose-escalation study, female patients ages <21 years were randomized 4:1 to receive triptorelin (n = 25) or placebo (n = 6). The starting doses of triptorelin were 25, 50, 75, and 100 μg/kg, and the dose was escalated until complete ovarian suppression was maintained. The primary outcome was the weight-adjusted dose of triptorelin that provided complete ovarian suppression in at least 90% of the patients, as determined by gonadotropin-releasing hormone agonist stimulation testing. The secondary outcome was the period of time required to achieve ovarian suppression, as measured by unstimulated follicle-stimulating hormone and luteinizing hormone levels after the initiation of triptorelin treatment. Treatment with triptorelin at a weight-adjusted dose of 120 μg/kg body weight provided sustained complete ovarian suppression in 90% of the patients. After administration of the initial dose of triptorelin, 22 days were required to achieve complete ovarian suppression. The rates of adverse events (AEs) and serious adverse events (SAEs) per 100 patient-months of followup were not higher in the triptorelin group compared with the placebo group (for AEs, 189 versus 362; for SAEs, 2.1 versus 8.5). High doses of triptorelin are needed to achieve and maintain complete ovarian suppression, but such doses appear to be well tolerated in adolescent female patients with childhood-onset SLE. Our data suggest that a lag time of 22 days after initiation of triptorelin treatment is required before cyclophosphamide therapy is started or continued. © 2015, American College of Rheumatology.

Basal progesterone level as the main determinant of progesterone elevation on the day of hCG triggering in controlled ovarian stimulation cycles.

PubMed

Papaleo, Enrico; Corti, Laura; Vanni, Valeria Stella; Pagliardini, Luca; Ottolina, Jessica; De Michele, Francesca; La Marca, Antonio; Viganò, Paola; Candiani, Massimo

2014-07-01

Modest increases of serum progesterone at human chorionic gonadotrophin (hCG) administration in controlled ovarian hyperstimulation (COH) cycles have been shown to have a negative impact on pregnancy outcomes. The aim of this study was to identify early predictors of progesterone elevation at hCG. Pregnancy outcome of 303 consecutive patients undergoing COH and fresh day-3 embryo transfer was analysed. Considering the non-linear relationship between progesterone at hCG triggering and pregnancy outcomes, partial area under the curve (pAUC) analysis was used to implement marker identification potential of receiver operating characteristic (ROC) curve analysis. Multivariate logistic analysis was then performed to identify predictors of progesterone rise. Pregnancy outcomes could be predicted by pAUC analysis (pAUC = 0.58, 95 % CI 0.51-0.66, p = 0.02) and a significant detrimental cut-off could be calculated (progesterone at hCG > 1.35 ng/ml). Total dose of rFSH administered, E2 level at hCG but mostly basal progesterone level (OR = 12.21, 95 % CI 1.82-81.70) were predictors of progesterone rise above the cut-off. Basal progesterone is shown to be the main prognostic factor for progesterone elevation. This observation should be taken into consideration in the clinical management of IVF/ICSI cycles to improve pregnancy outcomes.

Comparison of GnRH agonist, GnRH antagonist, and GnRH antagonist mild protocol of controlled ovarian hyperstimulation in good prognosis patients.

PubMed

Stimpfel, Martin; Vrtacnik-Bokal, Eda; Pozlep, Barbara; Virant-Klun, Irma

2015-01-01

The reports on how to stimulate the ovaries for oocyte retrieval in good prognosis patients are contradictory and often favor one type of controlled ovarian hyperstimulation (COH). For this reason, we retrospectively analyzed data from IVF/ICSI cycles carried out at our IVF Unit in good prognosis patients (aged <38 years, first and second attempts of IVF/ICSI, more than 3 oocytes retrieved) to elucidate which type of COH is optimal at our condition. The included patients were undergoing COH using GnRH agonist, GnRH antagonist or GnRH antagonist mild protocol in combination with gonadotrophins. We found significant differences in the average number of retrieved oocytes, immature oocytes, fertilized oocytes, embryos, transferred embryos, embryos frozen per cycle, and cycles with embryo freezing between studied COH protocols. Although there were no differences in live birth rate (LBR), miscarriages, and ectopic pregnancies between compared protocols, pregnancy rate was significantly higher in GnRH antagonist mild protocol in comparison with both GnRH antagonist and GnRH agonist protocols and cumulative LBR per cycle was significantly higher in GnRH antagonist mild protocol in comparison to GnRH agonist protocol. Our data show that GnRH antagonist mild protocol of COH could be the best method of choice in good prognosis patients.

Effect of cryopreservation and transplantation on the expression of kit ligand and anti-Mullerian hormone in human ovarian tissue.

PubMed

David, Anu; Van Langendonckt, Anne; Gilliaux, Sébastien; Dolmans, Marie-Madeleine; Donnez, Jacques; Amorim, Christiani A

2012-04-01

Although cryopreservation and transplantation of ovarian tissue represent a promising alternative to safeguard fertility in cancer patients, low recovery rates of oocytes aspirated from antral follicles and a significant number of empty follicles have been observed in women with transplanted frozen-thawed ovarian tissue. In order to understand how freezing and/or grafting may affect follicular development, the follicular expression of kit ligand (KL) and anti-Müllerian hormone (AMH), two key factors activating and inhibiting follicle growth, were assessed after long-term grafting in severe combined immunodeficient (SCID) mice. Ovarian biopsies from eight patients were used for fresh and frozen-thawed tissue xenografting in 13 SCID mice for a period of 28 weeks, including 2 weeks of gonadotrophin stimulation. KL, AMH and proliferating cell nuclear antigen (PCNA) immunostaining were quantified before and after grafting in the two treatment groups (fresh and frozen-thawed grafted ovarian tissue). Lower expression of KL was found in primordial and primary follicles after grafting of both fresh and frozen-thawed tissue. Consistent expression of AMH was found in most growing follicles at a similar rate in both graft types. In fresh and frozen-thawed grafts, 13-14% of primordial follicles were PCNA-positive, indicating a similar maintenance of quiescent follicles despite follicle activation. Grafting and/or gonadotrophin stimulation appear to affect the follicular expression of KL, which may alter oocyte quality. AMH expression in growing follicles after ovarian tissue transplantation may be one of the factors contributing to the preservation of resting follicles in 28-week-old grafts.

Highly purified human-derived follicle-stimulating hormone (Bravelle®) has equivalent efficacy to follitropin-beta (Follistim ®) in infertile women undergoing in vitro fertilization

PubMed Central

Dickey, Richard P; Nichols, John E; Steinkampf, Michael P; Gocial, Benjamin; Thornton, Melvin; Webster, Bobby W; Bello, Sandra M; Crain, Jack; Marshall, Dennis C

2003-01-01

Background These data compare the efficacy and safety of highly purified human-derived follicle-stimulating hormone (Bravelle(R)) and recombinant follitropin-β (Follistim(R)) in women undergoing in vitro fertilization. Methods This report describes the pooled data from two, nearly identical, randomized, controlled, parallel-group, multicenter studies conducted in a total of 19 academic and private IVF-ET centers in the United States. Infertile premenopausal women underwent pituitary down-regulation using leuprolide acetate followed by a maximum of 12 days of subcutaneous Bravelle(R) (n = 120) or Follistim(R) (n = 118), followed by administration of human chorionic gonadotropin, oocyte retrieval and embryo transfer. The primary efficacy measure was the mean number of oocytes retrieved; secondary efficacy measures included the total dose and duration of gonadotropin treatment; peak serum estradion levels; embryo transfer and implantation rates; chemical, clinical and continuing pregnancies; and live birth rates. All adverse events were recorded and injection site pain was recorded daily using a patient, self-assessment diary. Results Similar efficacy responses were observed for all outcome parameters in the two treatment groups. Although patients receiving Bravelle(R) consistently reported a greater number of chemical, clinical and continuing pregnancies, as well as an increased rate of live birth, the data did not attain statistical significance (P > 0.05). The overall incidence of adverse events was similar in both groups, but compared to Follistim(R), injections of Bravelle(R) were reported by patients to be significantly less painful (P < 0.001). Conclusions Bravelle(R) and Follistim(R) had comparable efficacy in controlled ovarian hyperstimulation in women undergoing IVF-ET. There were no differences in the nature or number of adverse events between the treatment groups although Bravelle(R) injections were reported to be significantly less painful. PMID:14609434

Surgical technique of diaphragm full-thickness resection and trans-diaphragmatic decompression of pneumothorax during cytoreductive surgery for ovarian cancer.

PubMed

Bashir, Shazia; Gerardi, Melissa A; Giuntoli, Robert L; Montes, Teresa P Diaz; Bristow, Robert E

2010-11-01

To describe the technique and short-term post-operative outcomes associated with diaphragm full-thickness resection (FTR) and intraoperative trans-diaphragmatic decompression of the resultant pneumothorax (TDDP). All patients undergoing cytoreductive surgery for primary or recurrent ovarian cancer between 8/1/98 and 7/30/09 were retrospectively identified from the tumor registry database. Patients undergoing diaphragm FTR were selected for detailed review of the operative technique and post-operative outcomes. The operative technique of TDDP using a fenestrated Robinson catheter is described. A total of 45 patients met study inclusion criteria. Diaphragm FTR surgery was performed exclusively by gynecologic oncologists in 73.3% of cases. The median patient age was 60 years, and the majority (75.6%) of cases were performed for primary cytoreduction of Stage IIIC (n=27) or Stage IV (n=18) disease. The two-dimensional surface area of tumor involvement ranged from 9 cm(2) to 192 cm(2). The right hemi-diaphragm alone was involved in 71.1% of cases, while both the right and left hemi-diaphragms were involved in 24.4%. TDDP was performed in 41 of the 45 patients undergoing diaphragm FTR, while 4 patients had intraoperative thoracostomy tubes placed. Among the 41 TDDP patients, post-operative days 3-4 radiographic imaging revealed that 56% had a small residual pleural effusion and 9.8% had a residual pneumothorax; however, only 2 patients (4.9%) required post-operative thoracostomy tube placement or thoracentesis. The technique of TDDP eliminates the need of intraoperative and post-operative thoracostomy tube/thoracentesis in 95.1% of patients undergoing diaphragm FTR as a component of ovarian cancer cytoreductive surgery. Copyright © 2010 Elsevier Inc. All rights reserved.

Single embryo transfer: the role of natural cycle/minimal stimulation IVF in the future.

PubMed

Nygren, Karl-Gösta

2007-05-01

There are several good reasons to assume that single embryo transfer (SET) eventually will become the norm internationally in IVF treatments. A tendency is clearly visible, as demonstrated in the latest IVF World Report. The Nordic countries and Belgium have been leading the way. Sweden at present has 70% SET, with 5% twins and a pregnancy rate per transfer remaining constant at about 30%. As a consequence, recent data show a drastic reduction of the risk of prematurity and therefore of child morbidity and perinatal mortality. It is now time to discuss alternatives to the current clinical policy of quite an aggressive ovarian stimulation in settings where SET is the norm. When and at what proportion could natural cycle/soft stimulation be used? What group of patients would benefit? What will the consequences be in terms of efficacy, safety, cost, time and quality of life? Selection of the most beneficial, rather than the most aggressive, ovarian stimulation protocol by clinicians and by the couples themselves in the future may well include a much wider use of natural cycle/soft stimulation in IVF.

Co-existence of breast and ovarian cancers in BRCA germ-line mutation carriers

PubMed Central

Dilawari, A; Cangiarella, J; Smith, J; Huang, A; Downey, A; Muggia, F

2008-01-01

The co-existence of breast and ovarian cancers in the same individual should raise suspicion of a hereditary process. Patients with either BRCA1 or BRCA2 germ-line mutations have an average risk of 39% and 11% respectively of developing ovarian cancer by the age of 70; they have a risk of 35–85% of developing breast cancer in their lifetime. We report here unusual pathologic features in a BRCA2 germ-line mutation carrier recently diagnosed with synchronous breast and ovarian cancers, and summarize the findings in six other women who were diagnosed with ovarian cancer either simultaneously with the diagnosis of breast cancer or at varying times after the diagnosis. While in most instances this may be a coincidental occurrence in highly susceptible individuals, the patient we highlight raises the provocative hypothesis that at times breast cancer metastasizes to the ovaries of mutation carriers and stimulates the development of an ovarian cancer as well as other cancers. In addition, these ovarian cancers may have different mechanisms of metastases predisposing them to travel to unusual sites. PMID:22275985

In vitro fertilization surrogate pregnancy in a patient who underwent radical hysterectomy followed by ovarian transposition, lower abdominal wall radiotherapy, and chemotherapy.

PubMed

Steigrad, Stephen; Hacker, Neville F; Kolb, Bradford

2005-05-01

To describe an IVF surrogate pregnancy from a patient who had a radical hysterectomy followed by excision of a laparoscopic port site implantation with ovarian transposition followed by abdominal wall irradiation and chemotherapy, which resulted in premature ovarian failure from which there was partial recovery. Case report. Tertiary referral university women's hospital in Sydney, Australia and private reproductive medicine clinic in California. A 34-year-old woman who underwent laparoscopy for pelvic pain, shortly afterward followed by radical hysterectomy and pelvic lymph node dissection, who subsequently developed a laparoscopic port site recurrence, which was excised in association with ovarian transposition before abdominal wall irradiation and chemotherapy. Modified IVF treatment, transabdominal oocyte retrieval, embryo cryopreservation in Australia, and transfer to a surrogate mother in the United States. Pregnancy. Miscarriage in the second cycle and a twin pregnancy in the fourth cycle. This is the first case report of ovarian stimulation and oocyte retrieval performed on transposed ovaries after a patient developed premature ovarian failure after radiotherapy and chemotherapy with subsequent partial ovarian recovery.

Impact of food restriction on ovarian development, RFamide-related peptide-3 and the hypothalamic-pituitary-ovarian axis in pre-pubertal ewes.

PubMed

Li, H; Song, H; Huang, M; Nie, H; Wang, Z; Wang, F

2014-10-01

RFamide-related peptide-3 (RFRP-3), the mammalian ortholog of gonadotropin-inhibiting hormone, has been implicated as a mediator between reproduction and energy balance. This study aimed to investigate the physiological effects of RFRP-3 on the process of ovarian development in food-restricted pre-pubertal ewes. The results showed that food restriction significantly inhibited the ovarian development and follicular growth. The data of qPCR in the hypothalamic-pituitary-ovarian (HPO) axis showed that food restriction not only upregulated RFRP-3 mRNA expression but also downregulated the mRNA expression of gonadotropin-releasing-hormone receptor, follicle-stimulating hormone receptor and luteinizing hormone receptor (LHR). Immunohistochemistry of RFRP-3 in the ovaries suggested that RFRP-3 may regulate the follicular development. These results suggested that the changes of RFRP-3 in response to food restriction might influence the HPO axis and inhibit ovarian development. © 2014 Blackwell Verlag GmbH.

First pregnancies, live birth, and in vitro fertilization outcomes after transplantation of frozen-banked ovarian tissue with a human extracellular matrix scaffold using robot-assisted minimally invasive surgery.

PubMed

Oktay, Kutluk; Bedoschi, Giuliano; Pacheco, Fernanda; Turan, Volkan; Emirdar, Volkan

2016-01-01

Ovarian tissue cryopreservation is an experimental fertility preservation method and the transplantation techniques are still evolving. We attempted to improve the technique with the utility of a human decellularized extracellular tissue matrix (ECTM) scaffold, robot-assisted minimally invasive surgery, and perioperative pharmacological support. We prospectively studied 2 subjects with hemophagocytic lymphohistiocytosis (patient A) and non-Hodgkin lymphoma (patient B) who underwent ovarian tissue cryopreservation at the age of 23 years, before receiving preconditioning chemotherapy for hematopoietic stem cell transplantation. Both experienced ovarian failure postchemotherapy and we transplanted ovarian cortical tissues to the contralateral menopausal ovary 7 and 12 years later, using a human ECTM scaffold and robotic assistance. The ECTM scaffold tissue compatibility was shown in preclinical studies. Patients also received estrogen supplementation and baby aspirin preoperatively to aid in the revascularization process. Ovarian follicle development was observed approximately 10 (patient A) and 8 (patient B) weeks after ovarian tissue transplantation. Following 8 and 7 cycles of in vitro fertilization, 9 and 10 day-3 embryos were cryopreserved (patients A and B, respectively). While the baseline follicle-stimulating hormone (range 3.6-15.4 mIU/mL) levels near normalized by 7 months and remained steady postovarian transplantation in patient A, patient B showed improved but elevated follicle-stimulating hormone levels throughout (range 21-31 mIU/mL). Highest follicle yield was achieved 14 (8 follicles; patient A) and 11 (6 follicles; patient B) months postintervention. Patient A experienced a chemical pregnancy after the third frozen embryo transfer attempt. She then conceived following her first fresh in vitro fertilization embryo transfer and the pregnancy is currently ongoing. Patient B conceived after the first frozen embryo transfer attempt and delivered a healthy girl at term. We report the first pregnancies after the minimally invasive transplantation of previously cryopreserved ovarian tissue with an ECTM scaffold. This approach seems to be associated with steady ovarian function after a follow-up of up to 2 years. Copyright © 2016 Elsevier Inc. All rights reserved.

Transdermal testosterone pretreatment in poor responders undergoing ICSI: a randomized clinical trial.

PubMed

Bosdou, J K; Venetis, C A; Dafopoulos, K; Zepiridis, L; Chatzimeletiou, K; Anifandis, G; Mitsoli, A; Makedos, A; Messinis, I E; Tarlatzis, B C; Kolibianakis, E M

2016-05-01

Does pretreatment with transdermal testosterone increase the number of cumulus-oocyte complexes (COCs) retrieved by more than 1.5 in poor responders undergoing intracytoplasmic sperm injection (ICSI), using recombinant follicle stimulating hormone (FSH) and gonadotrophin releasing hormone agonists (GnRHa)? Testosterone pretreatment failed to increase the number of COCs by more than 1.5 as compared with no pretreatment in poor responders undergoing ICSI (difference between medians: 0.0, 95% CI: -1.0 to +1.0). Androgens are thought to play an important role in early follicular development by enhancing ovarian sensitivity to FSH. In a recent meta-analysis, testosterone pretreatment resulted in an increase of 1.5 COCs as compared with no pretreatment. However, this effect was based on the analysis of only two randomized controlled trials (RCTs) including 163 patients. Evidently, there is a need for additional RCTs that will allow firmer conclusions to be drawn. The present RCT was designed to detect a difference of 1.5 COCs (sample size required = 48 patients). From 02/2014 until 04/2015, 50 poor responders fulfilling the Bologna criteria have been randomized (using a randomization list) to either testosterone pretreatment for 21 days ( ITALIC! n = 26) or no pretreatment ( ITALIC! n = 24). All patients underwent a long follicular GnRHa protocol. Recombinant FSH stimulation was started on Day 22 following GnRHa initiation. In the testosterone pretreatment group, a daily dose of 10 mg of testosterone gel was applied transdermally for 21 days starting from GnRHa initiation. Results are expressed as median (interquartile range). No differences in baseline characteristics were observed between the two groups compared. Testosterone levels [median (interquartile range)] were significantly higher in the testosterone pretreatment on the day of initiation of FSH stimulation [114 (99.5) ng/dl versus 20 (20) ng/dl, respectively, ITALIC! P < 0.001]. Duration of FSH stimulation [median (interquartile range)] was similar between the groups compared [12.5 (3.0) days versus 12 (3.0) days, respectively, ITALIC! P = 0.52]. The number of COCs retrieved [median (interquartile range)] was not different between the testosterone pretreatment and the no pretreatment groups [3.5 (4.0) versus 3.0 (3.0), 95% CI for the median: 2.0-5.0 versus 2.7-4.3, respectively; difference between medians: 0.0, 95% CI: +1.0 to -1.0). Similarly no differences were observed regarding fertilization rates [median (interquartile range)] [66.7% (32.5) versus 66.7% (42.9), respectively, ITALIC! P = 0.97] and live birth rates per randomized patient (7.7% versus 8.3%, respectively, rate difference: -0.6%, 95% CI: -19.0 to +16.9). The study was not powered to detect differences less than 1.5 COCs, although it is doubtful whether these differences would be clinically relevant. Moreover, due to sample size restrictions, no conclusions can be drawn regarding the probability of live birth. The results of this randomized clinical trial, suggesting that pretreatment with 10 mg of transdermal testosterone for 21 days does not improve ovarian response by more than 1.5 oocytes, could be used to more accurately consult patients with poor ovarian response. However, an improvement in IVF outcome using a higher dose of testosterone or a longer pretreatment period cannot be excluded. The study was partially funded by a Scholarship from the Academy of Athens. C.A.V. reports personal fees and non-financial support from Merck, Sharp and Dome, personal fees and non-financial support from Merck Serono, personal fees and non-financial support from IPSEN Hellas S.A., outside the submitted work. B.C.T. reports grants from Merck Serono, grants from Merck Sharp & Dohme, personal fees from Merck Serono, personal fees from Merck Sharp & Dohme, personal fees from IBSA & Ferring, outside the submitted work. NCT01961336. 10 October 2013. 02/2014. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Is the flexible GnRH antagonist protocol better suited for fresh eSET cycles?

PubMed

Dahdouh, Elias M; Gomes, Francisco L A F; Granger, Louis; Carranza-Mamane, Belina; Faruqi, Faez; Kattygnarath, Tiao-Virirak; St-Michel, Pierre

2014-10-01

This study was performed to evaluate the efficacy of the flexible GnRH antagonist protocol in comparison with the long GnRH agonist protocol in elective single embryo transfer (eSET) practice. It was conducted in a publicly funded in vitro fertilization program. We performed a prospective cohort analysis of data from a private infertility clinic from August 2010 to August 2011. Three hundred fourteen women with normal ovarian reserve and undergoing fresh eSET cycles were included. Sixty-four women underwent follicular stimulation using a flexible GnRH antagonist protocol, and 250 underwent stimulation with a standard long mid-luteal GnRH agonist protocol. Implantation rates (35.9% in the GnRH antagonist group and 29.6% in the GnRH agonist group, P = 0.5) and ongoing pregnancy rates (32.8% in the GnRH antagonist group and 28.8% in the GnRH agonist group, P = 0.5) were equivalent in both groups. The duration of stimulation (9.8 ± 2 days vs. 10.7 ± 1.8 days, P < 0.001) and total FSH dose required (2044 vs. 2775 IU, P < 0.001) were lower in the GnRH antagonist group than in the GnRH agonist group. The number of mature oocytes (6.0 vs. 10.0, P < 0. 001) and number of embryos (5.0 vs. 7.0, P < 0.001) were also lower in GnRH antagonist group. However, the number of embryos cryopreserved was similar in both groups (median 2.0, P = 0.3). In women undergoing in vitro fertilization, the flexible GnRH antagonist protocol yields implantation and ongoing pregnancy rates that are similar to the long GnRH agonist protocol, and requires lower doses of gonadotropins and a shorter duration of treatment. The flexible GnRH antagonist protocol appears to be the protocol of choice for an eSET IVF program.

Oocyte cryopreservation: a feasible fertility preservation option for reproductive age cancer survivors

PubMed Central

Labella, Patty Ann; Grifo, James; Knopman, Jaime M.

2010-01-01

Purpose To compare oocyte cryopreservation cycles performed in cancer patients to those of infertile women. Methods Cancer patients referred for fertility preservation underwent counseling in compliance with the ASRM; those electing oocyte cryopreservation were included. Ovarian stimulation was achieved with injectable gonadotropins and freezing was performed using slow-cooling and vitrification methods. Results Fifty cancer patients (mean age 31 y) underwent oocyte cryopreservation; adequate ovarian stimulation was achieved in 10 ± 0.3 days. The outcome from these cycles included a mean peak estradiol of 2,376 pg/ml and an average of 19 oocytes retrieved (15 mature oocytes were cryopreserved/cycle). All patients tolerated ovarian hyperstimulation. There were no significant differences noted between cryopreservation cycles performed in cancer patients and in women without malignancy. Conclusions Oocyte cryopreservation appears to be a feasible fertility preservation method for reproductive-age women diagnosed with cancer. This modality is not only effective but also, providing a multidiscipline effort, can be completed in timely fashion. PMID:20480389

The duration of gonadotropin stimulation does not alter the clinical pregnancy rate in IVF or ICSI cycles.

PubMed

Purandare, N; Emerson, G; Kirkham, C; Harrity, C; Walsh, D; Mocanu, E

2017-08-01

Ovarian stimulation is an essential part of assisted reproduction treatments. Research on whether the duration of stimulation alters the success in assisted reproduction has not been conclusive. The purpose of the study was to establish whether the duration of ovarian stimulation alters the success in assisted reproduction treatments. All fresh (non-donor) stimulation cycles performed in an academic tertiary referral ART centre over a period of 18 years, between 1st January 1997 and 31st December 2014, were identified. Data were prospectively and electronically collected. IVF and ICSI cycles were analysed independently. Each category was then subdivided into assisted reproduction cycles where the antagonist, long (down regulation) and flare protocol were used. Clinical pregnancy was the main outcome measured. A total of 10,478 stimulation cycles (6011 fresh IVF and 4467 fresh ICSI) reaching egg collection were included. We showed no significant difference in CP rates in IVF cycles for the long (p = 0.082), antagonist (p = 0.217) or flare (p = 0.741) protocol cycles or in ICSI cycles with the long (p = 0.223), antagonist (p = 0.766) or the flare (p = 0.690) protocol with regards the duration of stimulation. The duration of stimulation does not alter the CP rate in ICSI or IVF cycles using the long, antagonist or flare stimulation protocol.

Efficiency of metaphase II oocytes following minimal/mild ovarian stimulation in vitro fertilization.

PubMed

Zhang, John J; Yang, Mingxue; Merhi, Zaher

2016-01-01

An inverse relationship between oocyte efficiency and ovarian response was reported in conventional IVF. The purpose of this study was to report metaphase II (MII) oocyte efficiency according to oocyte yield in minimal/mild stimulation IVF (mIVF) and to assess whether oocyte yield affects live birth rate (LBR). Infertile women ( n  = 264) aged < 39 years old with normal ovarian reserve who had mIVF were recruited. All participants received the same protocol for ovarian stimulation. All the embryos were cultured to the blastocyst stage and vitrified using a freeze-all approach. This was followed by a single blastocyst transferred to each participant in subsequent cycles over a 6-month period. Ovarian response was categorized according to the number of MII oocyte yield (low: 1-2, intermediate: 3-6 and high ≥ 7 MII oocytes). MII oocyte utilization rate was calculated as the number of live births divided by the number of MII oocytes produced after only one oocyte retrieval and subsequent transfers of vitrified/warmed blastocysts. The main outcome measure was cumulative LBR over a 6-month period. Among all the participants, 1173 total retrieved oocytes (4.4 ± 0.2 per patient) resulted in 1019 (3.9 ± 0.2 per patient) total MII oocytes, a clinical pregnancy rate of 48.1 % and a LBR of 41.2 %. Oocyte utilization rate was inversely related to ovarian response where it was 30.3 % in the "low" vs. 9.3 % in the "intermediate" vs. 4.3 % in the "high" oocyte yield groups ( p  < 0.05). Implantation rate significantly dropped as the number of MII oocytes increased and was highest in the "low" oocyte yield group ( p  < 0.0001). Cumulative LBR was similar in "low," "intermediate," and "high" oocyte yield groups ( p  > 0.05). The number of MII oocytes had poor sensitivity and specificity for predicting a live birth. These data extend the hypothesis of oocyte efficiency reported in conventional IVF protocols to mIVF protocols. Registration clinicaltrials.gov: NCT00799929.

Ravuconazole in Preventing Fungal Infections in Patients Undergoing Allogeneic Stem Cell Transplantation

ClinicalTrials.gov

2012-03-07

Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Infection; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

Effect of preemptive analgesia with intravenous oxycodone in the patients undergoing laparoscopic resection of ovarian tumor

PubMed Central

Wang, Na; Wang, Yuantao; Pang, Lei; Wang, Jinguo

2015-01-01

Objective: To evaluate the efficacy of preemptive intravenous oxycodone in the patients undergoing laparoscopic resection of ovarian tumor. Methods: Sixty ASA I or II patients undergoing elective laparoscopic resection of ovarian tumor were randomly allocated to one of two groups: Group O (n=30) received intravenous oxycodone (0.1 mg·kg-1) 10 minutes before surgery over 2 minutes, and Group N (n=30) received an equivalent volume of normal saline. All patients received a standardized general anesthesia. MBP and HR at the time of arrival of the operating room (T1), 5 min before pneumoperitoneum (T2), 5 minutes (T3), 10 minutes (T4), and 15 minutes after pneumoperitoneum (T5), and VAS scores at postoperative 2, 4, 8, 12 and 24 hour were recorded. The tramadol consumption and side effects in 24 h after surgery were recorded. Results: VAS pain scores at 2, 4, 8 and 12 hour after operation were significantly lower in Group O (P<0.05). MBP and HR increased significantly due to pneumoperitoneum at T3, T4 and T5, compared with T1 and T2 within Group N, and were higher at T3, T4 and T5 in Group N than at the same time points in Group O. Tramadol consumption was statistically lower in Group O (P=0.0003). Conclusions: Preemptive intravenous oxycodone was an efficient and safe method to reduce intraoperative haemodynamic effect and postoperative pain. PMID:26101479

Exercise Among Women With Ovarian Cancer: A Feasibility and Pre-/Post-Test Exploratory Pilot Study.

PubMed

Zhang, Xiaochen; McClean, Daniel; Ko, Emily; Morgan, Mark A; Schmitz, Kathryn

2017-05-01

To establish the feasibility and acceptability of completing a higher dose of the planned physical activity volume among women with ovarian cancer, including those undergoing active treatment. 
. A pre-/post-test exercise intervention. All participants were asked to complete 225 minutes per week of physical activity for 26 weeks. Multiple supports were provided, including exercise DVDs, self-reported logs, and an objective physical activity tracker (Fitbit®).
. Home-based exercise intervention with in-person training and telephone follow-ups.
. 10 women with ovarian cancer who were treated within Penn Medicine in Philadelphia, Pennsylvania.
. Home-based, in-person exercise counseling was provided by an exercise trainer weekly for the first six weeks and then monthly for a total of 26 weeks. Weekly follow-up telephone calls were used to assess exercise adherence and barriers to completing exercise, review symptom changes, and provide behavioral support. 
. Feasibility and acceptability.
. Eight participants completed the study and achieved at least 80% of the prescribed exercise dose. Five participants were undergoing chemotherapy simultaneously. Participants experienced no adverse events during the 26-week intervention. Compared to baseline, average steps increased by 1,593 per day and moderate-intensity physical activity increased by 15 minutes per day. 
. A 225-minutes-per-week exercise program is feasible and acceptable in a population of patients with ovarian cancer. Participants significantly improved their physical activity during the 26-week intervention.
. The findings suggest that nursing professionals could recommend that women with ovarian cancer exercise 225 minutes per week regardless of cancer and/or treatment trajectory. For those experiencing aches and pains, behavioral supports and suggestions of a lower exercise dose are needed to maintain physical activity.

Microdose Flare-up Gonadotropin-releasing Hormone (GnRH) Agonist Versus GnRH Antagonist Protocols in Poor Ovarian Responders Undergoing Intracytoplasmic Sperm Injection

PubMed Central

Boza, Aysen; Cakar, Erbil; Boza, Barıs; Api, Murat; Kayatas, Semra; Sofuoglu, Kenan

2016-01-01

Background: Microdose flare-up GnRH agonist and GnRH antagonist have become more popular in the management of poor ovarian responders (POR) in recent years; however, the optimal protocol for POR patients undergoing in vitro fertilization has still been a challenge. Methods: In this observational study design, two hundred forty four poor ovarian responders were retrospectively evaluated for their response to GnRH agonist protocol (group-1, n=135) or GnRH antagonist protocol (group-2, n=109). Clinical pregnancy rate was the primary end point and was compared between the groups. Student t-test, Mann Whitney U test and χ2-test were used to compare the groups. The p<0.05 was considered to show a statistically significant result. Results: The mean total gonadotropin doses were 3814±891 IU in group 1 and 3539±877 IU in group 2 (p=0.02). The number of metaphase-II oocytes (3.6±2.4 vs. 2.8±1.9, p=0.005) and implantation rates (27.8% vs. 18.8%, p=0.04) in group 1 and group 2, respectively were significantly different. The fertilization rate in group 1 and group 2 was 73% vs. 68%, respectively (p=0.5) and clinical pregnancy rate was 19.8% vs. 14.4%, respectively (p=0.13). Conclusion: The GnRH agonist microdose flare-up protocol has favorable outcomes with respect to the number of oocytes retrieved and implantation rate; nevertheless, the clinical pregnancy rate was found to be similar in comparison to GnRH antagonist protocol in poor ovarian responders. GnRH antagonist protocol appears to be promising with significantly lower gonadotropin requirement and lower treatment cost in poor ovarian responders. PMID:27478770

Microdose Flare-up Gonadotropin-releasing Hormone (GnRH) Agonist Versus GnRH Antagonist Protocols in Poor Ovarian Responders Undergoing Intracytoplasmic Sperm Injection.

PubMed

Boza, Aysen; Cakar, Erbil; Boza, Barıs; Api, Murat; Kayatas, Semra; Sofuoglu, Kenan

2016-01-01

Microdose flare-up GnRH agonist and GnRH antagonist have become more popular in the management of poor ovarian responders (POR) in recent years; however, the optimal protocol for POR patients undergoing in vitro fertilization has still been a challenge. In this observational study design, two hundred forty four poor ovarian responders were retrospectively evaluated for their response to GnRH agonist protocol (group-1, n=135) or GnRH antagonist protocol (group-2, n=109). Clinical pregnancy rate was the primary end point and was compared between the groups. Student t-test, Mann Whitney U test and χ (2)-test were used to compare the groups. The p<0.05 was considered to show a statistically significant result. The mean total gonadotropin doses were 3814±891 IU in group 1 and 3539±877 IU in group 2 (p=0.02). The number of metaphase-II oocytes (3.6±2.4 vs. 2.8±1.9, p=0.005) and implantation rates (27.8% vs. 18.8%, p=0.04) in group 1 and group 2, respectively were significantly different. The fertilization rate in group 1 and group 2 was 73% vs. 68%, respectively (p=0.5) and clinical pregnancy rate was 19.8% vs. 14.4%, respectively (p=0.13). The GnRH agonist microdose flare-up protocol has favorable outcomes with respect to the number of oocytes retrieved and implantation rate; nevertheless, the clinical pregnancy rate was found to be similar in comparison to GnRH antagonist protocol in poor ovarian responders. GnRH antagonist protocol appears to be promising with significantly lower gonadotropin requirement and lower treatment cost in poor ovarian responders.

Relationship Between 17-Hydroxyprogesterone Responses to Human Chorionic Gonadotropin and Markers of Ovarian Follicle Morphology in Women With Polycystic Ovary Syndrome

PubMed Central

Maas, Kevin H.; Chuan, Sandy S.; Cook-Andersen, Heidi; Su, H. Irene; Duleba, A.

2015-01-01

Context: Women with polycystic ovary syndrome (PCOS) have increased 17-hydroxyprogesterone (17-OHP) responses to gonadotropin stimulation although individual variability is substantial, as reflected by exaggerated as well as normal responses. The relationship between 17-OHP responses to gonadotropin stimulation and markers of ovarian function has not been assessed. Objective: To determine whether 17-OHP responses are associated with antral follicle count (AFC), anti-Mullerian hormone (AMH), or inhibin B (Inh B) levels in PCOS and normal women. Design: Prospective study. Setting: Research center at an academic medical center. Participants: Women with PCOS (n = 18) and normal controls (n = 18). Interventions: Blood samples were obtained before and 24 hours after administration of 25 μg recombinant-human chorionic gonadotropin. Ovarian imaging was conducted with three-dimensional pelvic ultrasound. Main Outcome Measures: Basal and stimulated levels of 17-OHP, androgens, estrogen, AMH, Inh B, and AFC. Results: In women with PCOS, 17-OHP responses were heterogeneous and inversely correlated with AMH and Inh B levels, but not AFC. In a subgroup of PCOS women with exaggerated 17-OHP responses, AMH levels were equivalent to that of normal women. In PCOS women with normal 17-OHP responses, AMH levels were markedly elevated. Conclusion: Based on heterogeneous 17-OHP responses to human chorionic gonadotropin in women with PCOS, AMH levels are inversely linked to ovarian androgen production while positively correlated with AFC. These findings suggest that in PCOS, AMH production may reflect redistribution of the follicle population or regulation by intraovarian mechanisms. PMID:25313914

Enhanced insulin sensitivity and acute regulation of metabolic genes and signaling pathways after a single electrical or manual acupuncture session in female insulin-resistant rats.

PubMed

Benrick, Anna; Maliqueo, Manuel; Johansson, Julia; Sun, Miao; Wu, Xiaoke; Mannerås-Holm, Louise; Stener-Victorin, Elisabet

2014-12-01

To compare the effect of a single session of acupuncture with either low-frequency electrical or manual stimulation on insulin sensitivity and molecular pathways in the insulin-resistant dihydrotestosterone-induced rat polycystic ovary syndrome (PCOS) model. Both stimulations cause activation of afferent nerve fibers. In addition, electrical stimulation causes muscle contractions, enabling us to differentiate changes induced by activation of sensory afferents from contraction-induced changes. Control and PCOS rats were divided into no-stimulation, manual-, and electrical stimulation groups and insulin sensitivity was measured by euglycemic hyperinsulinemic clamp. Manually stimulated needles were rotated 180° ten times every 5 min, or low-frequency electrical stimulation was applied to evoke muscle twitches for 45 min. Gene and protein expression were analyzed by real-time PCR and Western blot. The glucose infusion rate (GIR) was lower in PCOS rats than in controls. Electrical stimulation was superior to manual stimulation during treatment but both methods increased GIR to the same extent in the post-stimulation period. Electrical stimulation decreased mRNA expression of Adipor2, Adrb1, Fndc5, Erk2, and Tfam in soleus muscle and increased ovarian Adrb2 and Pdf. Manual stimulation decreased ovarian mRNA expression of Erk2 and Sdnd. Electrical stimulation increased phosphorylated ERK levels in soleus muscle. One acupuncture session with electrical stimulation improves insulin sensitivity and modulates skeletal muscle gene and protein expression more than manual stimulation. Although electrical stimulation is superior to manual in enhancing insulin sensitivity during stimulation, they are equally effective after stimulation indicating that it is activation of sensory afferents rather than muscle contraction per se leading to the observed changes.

The accuracy of serum interleukin-6 and tumour necrosis factor as markers for ovarian torsion.

PubMed

Cohen, S B; Wattiez, A; Stockheim, D; Seidman, D S; Lidor, A L; Mashiach, S; Goldenberg, M

2001-10-01

The aim of this study was to investigate a possible role for interleukin-6 (IL-6) and tumour necrosis factor (TNF-alpha) as pre-operative markers for the diagnosis of ovarian torsion. Twenty consecutive patients admitted to the gynaecological emergency room with suspected clinical diagnosis of ovarian torsion were prospectively assigned to the study. Blood samples were drawn pre-operatively and examined for serum concentrations of IL-6 and TNF-alpha. Surgeons were blinded to laboratory results prior to laparoscopy. The pre-operative diagnosis of ovarian torsion was confirmed during an urgent diagnostic laparoscopy in 8 (40%) patients. The surgical diagnosis among the remaining 12 patients was a large ovarian cyst not in torsion. In six out of eight (75.0%) patients with ovarian torsion serum IL-6 concentrations were elevated. None of the 12 patients without torsion had elevated serum IL-6 concentrations. This difference was statistically significant (P < 0.001). There was no significant difference in the proportion of women with elevated serum TNF-alpha concentrations, two of eight (25.0%) patients with torsion and four of 12 (33.3%) control cases. Elevated serum IL-6 concentrations, but not serum TNF-alpha concentrations, were significantly associated with the occurrence of ovarian torsion. In patients with vague clinical signs of ovarian torsion, serum IL-6 might help to distinguish which patients should undergo diagnostic laparoscopy.

Preservation of human ovarian follicles within tissue frozen by vitrification in a xeno-free closed system using only ethylene glycol as a permeating cryoprotectant.

PubMed

Sheikhi, Mona; Hultenby, Kjell; Niklasson, Boel; Lundqvist, Monalill; Hovatta, Outi

2013-07-01

To study the preservation of follicles within ovarian tissue vitrified using only one or a combination of three permeating cryoprotectants. Experimental study. University hospital. Ovarian tissue was donated by consenting women undergoing elective cesarean section. Ovarian tissue was vitrified in closed sealed vials using either a combination of dimethyl sulfoxide, 1,2-propanediol, and ethylene glycol (EG), or only EG as permeating cryoprotectants. Ovarian tissue was vitrified with the use of two vitrification methods. Tissue from the same donor was used for comparison of two different solutions. The morphology of the follicles was evaluated after vitrification, warming, and culture by light microscopy and transmission electron microscopy. Apoptosis was assessed by immunohistochemistry for active caspase-3 in fresh and vitrified tissue. Light and electron microscopic analysis showed equally well preserved morphology of oocytes, granulosa cells, and ovarian stroma when either of the vitrification solutions was used. No apoptosis was observed in primordial and primary follicles. Using only EG as a permeating cryoprotectant in a closed tube gives as good ultrastructural preservation of ovarian follicles as a more complicated system using several cryoprotectants. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Influence of body weight changes on survival in patients undergoing chemotherapy for epithelial ovarian cancer.

PubMed

Mardas, M; Stelmach-Mardas, M; Zalewski, K; Grabowski, J P; Czapka-Matyasik, M; Steffen, A; Boeing, H; Mądry, R

2016-05-01

Epithelial ovarian cancer is a highly fatal gynecologic malignancy with a poor prognosis. Therefore, identification of new modifiable prognostic factors is important. Due to the fact that the effect of body weight changes during chemotherapy for EOC is still not very well known we aimed to describe, considering evidence, role of body weight changes in relation to survival. Between October 2014 and August 2015 we systematically searched the following databases: Medline, Scopus, Web of Science and EMBASE to identify the studies describing the influence of body weight changes on survival in patients undergoing chemotherapy for EOC. We identified 601 potentially relevant publications, however finally only one article was included for data extraction and analysis. The overall survival in the selected paper was significantly associated with body weight changes during the first-line chemotherapy. Nevertheless, no influence on progression free survival was found. The analyzed data provides initial evidence, showing poorer overall survival  associated with body weight loss and improved overall survival associated with body weight gain during primary chemotherapy for epithelial ovarian cancer. Prospective and retrospective trials are an urgent calling to confirm this conclusion.

Successful ongoing pregnancies after vitrification of oocytes.

PubMed

Lucena, Elkin; Bernal, Diana Patricia; Lucena, Carolina; Rojas, Alejandro; Moran, Abby; Lucena, Andrés

2006-01-01

To demonstrate the efficiency of vitrifying mature human oocytes for different clinical indications. Descriptive case series. Cryobiology laboratory, Centro Colombiano de Fertilidad y Esterilidad-CECOLFES LTDA. (Bogotá, Colombia). Oocyte vitrification was offered as an alternative management for patients undergoing infertility treatment because of ovarian hyperstimulation syndrome, premature ovarian failure, natural ovarian failure, male factor, poor response, or oocyte donation. Mature oocytes were obtained from 33 donor women and 40 patients undergoing infertility treatment. Oocytes were retrieved by ultrasound-guided transvaginal aspiration and vitrified with the Cryotops method, with 30% ethylene glycol, 30% dimethyl sulfoxide, and 0.5 mol/L sucrose. Viability was assessed 3 hours after thawing. The surviving oocytes were inseminated by intracytoplasmic sperm injection. Fertilization was evaluated after 24 hours. The zygotes were further cultured in vitro for up to 72 hours until time of embryo transfer. Recovery, viability, fertilization, and pregnancy rates. Oocyte vitrification with the Cryotop method resulted in high rates of recovery, viability, fertilization, cleavage, and ongoing pregnancy. Vitrification with the Cryotop method is an efficient, fast, and economical method for oocyte cryopreservation that offers high rates of survival, fertilization, embryo development, and ongoing normal pregnancies, providing a new alternative for the management of female infertility.

The Increased Expression of Connexin and VEGF in Mouse Ovarian Tissue Vitrification by Follicle Stimulating Hormone

PubMed Central

Yang, Yanzhou; Chen, Jie; Wu, Hao; Pei, Xiuying; Chang, Qing; Ma, Wenzhi; Ma, Huiming; Hei, Changchun; Zheng, Xiaomin; Cai, Yufang; Zhao, Chengjun; Yu, Jia; Wang, Yanrong

2015-01-01

Ovarian follicular damages were caused by cryoinjury during the process of ovarian vitrification and ischemia/reperfusion during the process of ovarian transplantation. And appropriate FSH plays an important role in antiapoptosis during ovarian follicle development. Therefore, in this study, 0.3 IU/mL FSH was administered into medium during mouse ovarian cryopreservation by vitrification to ascertain the function of FSH on ovarian vitrification and avascular transplantation. The results suggested that the expressions of Cx37, Cx43, apoptotic molecular caspase-3, and angiogenesis molecular VEGF were confirmed using immunohistochemistry, western blotting, and real-time PCR, and the results suggested that the treatment with FSH remarkably increased the number of morphologically normal follicles in vitrified/warmed ovaries by upregulating the expression of Cx37, Cx43, VEGF, and VEGF receptor 2, but downregulating the expression of caspase-3. In addition, the vitrified/warmed ovaries were transplanted, and the related fertility was analyzed, and the results suggested that the fertility, neoangiogenesis, and follicle reserve were remarkably increased in the FSH administrated group. Taken together, administration of 0.3 IU/mL FSH during ovarian cryopreservation by vitrification can maintain ovarian survival during ovarian vitrification and increases the blood supply with avascular transplantation via upregulation of Cx43, Cx37, and VEGF/VEGFR2, as well as through its antiapoptotic effects. PMID:26539488

MiR-376a promotion of proliferation and metastases in ovarian cancer: Potential role as a biomarker.

PubMed

Yang, Liu; Wei, Qing-Min; Zhang, Xin-Wen; Sheng, Qiu; Yan, Xiao-Ting

2017-03-15

Ovarian cancer is the fifth most deadly cancer in women, and is usually diagnosed too late. Exploring specific and sensitive biomarkers will be helpful to early detection and will improve the survival rates of ovarian cancer patients. Realtime PCR was used to detect the expression of miR-376a. Wound healing and transwell assays were used to examined the migration and invasion abilities of ovarian cancer cells. Tumor xenograft experiments were employed to test the in vivo malignancy of ovarian cancer cells. Western Blotting and luciferase report assays were conducted for the target genes analysis. Using a cohort of 32 cases of ovarian cancer and 10 cases of healthy control samples, we found that miR-376 expression is increased in ovarian cancer tissues. The serum level of miR-376a is significantly higher in ovarian cancer patients and is associated with the clinical stages of ovarian cancer. Over expression of miR-376a stimulated the proliferation, migration, and invasion of ovarian cancer cells, while inhibition of miR-376a expression blocked the proliferation, migration, and invasion. Data from nude mice further demonstrated the stimulatory role of miR-376a in ovarian cancer progression. Mechanically, miR-376a played its role by targeting KLF15 and Caspase-8. Our findings enrich the knowledge of miR-376a in ovarian cancer formation and progression, providing a possibility of using miR-376a as a diagnostic and prognostic biomarker for ovarian cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Adrenocorticotropic Hormone Suppresses Gonadotropin-Stimulated Estradiol Release from Zebrafish Ovarian Follicles

PubMed Central

Alsop, Derek; Ings, Jennifer S.; Vijayan, Mathilakath M.

2009-01-01

While stress is known to impact reproductive performance, the pathways involved are not entirely understood. Corticosteroid effects on the functioning of the hypothalamus-pituitary-gonadal axis are thought to be a key aspect of stress-mediated reproductive dysfunction. A vital component of the stress response is the pituitary secretion of adrenocorticotropic hormone (ACTH), which binds to the melanocortin 2 receptor (MC2R) in the adrenal glands and activates cortisol biosynthesis. We recently reported MC2R mRNA abundance in fish gonads leading to the hypothesis that ACTH may be directly involved in gonadal steroid modulation. Using zebrafish (Danio rerio) ovarian follicles, we tested the hypothesis that acute ACTH stimulation modulates cortisol and estradiol (E2) secretion. ACTH neither affected cortisol nor unstimulated E2 release from ovarian follicles. However, ACTH suppressed human chorionic gonadotropin (hCG)-stimulated E2 secretion in a dose-related manner, with a maximum decrease of 62% observed at 1 I.U. ACTH mL−1. This effect of ACTH on E2 release was not observed in the presence of either 8-bromo-cAMP or forskolin, suggesting that the mechanism(s) involved in steroid attenuation was upstream of adenylyl cyclase activation. Overall, our results suggest that a stress-induced rise in plasma ACTH levels may initiate a rapid down-regulation of acute stimulated E2 biosynthesis in the zebrafish ovary, underscoring a novel physiological role for this pituitary peptide in modulating reproductive activity. PMID:19649243

Sympathetic innervation regulates macrophage activity in rats with polycystic ovary.

PubMed

Figueroa, Florencia; Mendoza, Gisela; Cardozo, Darío; Mohamed, Fabián; Oliveros, Liliana; Forneris, Myriam

2018-07-01

Polycystic ovarian syndrome (PCOS) is a low-grade inflammatory disease characterized by hyperandrogenism and ovarian hyperinnervation. The aim of this work is to investigate whether in vivo bilateral superior ovarian nerve (SON) section in adult rats with estradiol valerate-induced PCOS (PCO rats) affects macrophage spleen cells (MФ) and modifies the steroidogenic ability of their secretions. Culture media of MФ from PCO rats and PCO rats with SON section (PCO-SON rats) were used to stimulate in vitro intact ovaries. Compared with macrophages PCO, macrophages from PCO-SON rats released less tumor necrosis factor-α and nitric oxide, expressed lower Bax and Nfkb mRNA and showed reduced TUNEL staining. Also, in PCO rats, the SON section decreased kisspeptin and nerve growth factor mRNA expressions, without changes in Trka receptor mRNA levels. Macrophage secretions from PCO-SON rats decreased androstenedione and stimulated progesterone release in PCO ovaries, compared to macrophage secretions from PCO rats. No changes were observed in ovarian estradiol response. These findings emphasize the importance of the SON in spleen MΦ, since its manipulation leads to secondary modifications of immunological and neural mediators, which might influence ovarian steroidogenesis. In PCO ovaries, the reduction of androstenedione and the improvement of progesterone release induced by PCO-SON MΦ secretion, might be beneficial considering the hormonal anomalies characteristic of PCOS. We present functional evidence that modulation of the immune-endocrine function by peripheral sympathetic nervous system might have implications for understanding the pathophysiology of PCOS. © 2018 Society for Endocrinology.

Short-Term PTEN Inhibition Improves In Vitro Activation of Primordial Follicles, Preserves Follicular Viability, and Restores AMH Levels in Cryopreserved Ovarian Tissue From Cancer Patients

PubMed Central

Novella-Maestre, Edurne; Herraiz, Sonia; Rodríguez-Iglesias, Beatriz; Díaz-García, César; Pellicer, Antonio

2015-01-01

Introduction In vitro activation and growth of primordial dormant follicles to produce fertilizable oocytes would provide a useful instrument for fertility preservation. The employment of Phosphatase and TENsin homolog (PTEN) inhibitors, in combination with Protein kinase B (Akt) stimulating molecules, has been previously employed to increase follicular activation through the stimulation of the PTEN-Akt pathway. Methods We aim to establish improved in vitro activation also for cancer patients whose ovarian tissue has already been cryopreserved. Fresh and previously cryopreserved human ovarian cortex were exposed to short-term, low-concentration and ovary-specific treatment with only a PTEN inhibitor. Results Our in vitro activation protocol enhances the activation mechanisms of primordial follicles in both fresh and cryopreserved samples, and enlarges growing populations without inducing apoptosis in either follicles or the surrounding stroma. Treatment augments estradiol secretion and restores the expression levels of the previously diminished Anti-Müllerian hormone by means of cryopreservation procedures. Genomic modulation of the relative expression of PTEN pathway genes was found in treated samples. Conclusion The in vitro activation protocol offers new alternatives for patients with cryopreserved tissue as it increases the pool of viable activated follicles available for in vitro growth procedures. The combination of ovarian tissue cryopreservation and in vitro activation of primordial follicles, the main ovarian reserve component, will be a major advancement in fertility preservation. PMID:26024525

Gallic acid sensitizes paclitaxel-resistant human ovarian carcinoma cells through an increase in reactive oxygen species and subsequent downregulation of ERK activation.

PubMed

Sánchez-Carranza, Jessica Nayelli; Díaz, J Fernando; Redondo-Horcajo, Mariano; Barasoain, Isabel; Alvarez, Laura; Lastres, Pedro; Romero-Estrada, Antonio; Aller, Patricio; González-Maya, Leticia

2018-06-01

Paclitaxel (PTX) is currently used as a front-line chemotherapeutic agent for several types of cancer, including ovarian carcinoma; however, PTX-resistance frequently arises through multiple mechanisms. The development of new strategies using natural compounds and PTX in combination has been the aim of several prior studies, in order to enhance the efficacy of chemotherapy. In this study, we found the following: (i) gallic acid (GA), a phenolic compound, potentiated the capacity of PTX to decrease proliferation and to cause G2/M cycle arrest in the PTX-resistant A2780AD ovarian cancer cell line; (ii) GA exerted a pro-oxidant action by increasing the production of reactive oxygen species (ROS), and co-treatment with the antioxidant agent N‑acetyl-L‑cysteine (NAC) prevented GA+PTX-induced cell proliferation inhibition and G2/M phase arrest; (iii) PTX stimulated ERK phosphorylation/activation, and co-treatment with the MEK/ERK inhibitor PD98049 potentiated the proliferation inhibition and G2/M phase arrest; (iv) and finally, GA abrogated the PTX-induced stimulation of ERK phosphorylation, a response that was prevented by co-treatment with NAC. Taken together, these results indicate that GA sensitizes PTX-resistant ovarian carcinoma cells via the ROS‑mediated inactivation of ERK, and suggest that GA could represent a useful co-adjuvant to PTX in ovarian carcinoma treatment.

Endocrine disruptor & nutritional effects of heavy metals in ovarian hyperstimulation.

PubMed

Dickerson, E H; Sathyapalan, T; Knight, R; Maguiness, S M; Killick, S R; Robinson, J; Atkin, S L

2011-12-01

There is increasing concern that environmental chemicals have a direct effect on fertility. Heavy metals such as mercury have been shown to affect various organ systems in humans including nervous system and skin, however they could also act as endocrine disrupting chemicals adversely affecting fertility. Metals such as zinc and selenium are essential micronutrients with diverse functions that may be important for reproductive outcomes. We measured mercury, zinc and selenium levels in the hair, a reliable reflection of long term environmental exposure and dietary status, to correlate with the outcome of ovarian hyperstimulation for in vitro fertilisation (IVF) treatment. We analysed the hair of 30 subfertile women for mercury, zinc and selenium using inductively coupled mass spectrometry. Each woman underwent one cycle of IVF treatment. Correlation between the levels of these trace metals and treatment outcomes was investigated. Thirty women were recruited with mean (±SD) age of 32.7(4.4) years and BMI of 25.4(5.0)kg/m(2). Hair mercury concentration showed a negative correlation with oocyte yield (p < 0.05,βcoefficient 0.38) and follicle number (p = 0.03,β coefficient0.19) after ovarian stimulation. Zinc and selenium levels in hair correlated positively with oocyte yield after ovarian stimulation (p < 0.05,β coefficient0.15) and (p = 0.03,β coefficient0.21) respectively. Selenium levels in hair correlated significantly with follicle number following stimulation (p = 0.04, βcoefficient0.22). There was no correlation between mercury, zinc and selenium in hair and their corresponding serum levels. These data suggest that mercury had a deleterious effect whilst there was a positive effect for zinc and selenium in the ovarian response to gonadotrophin therapy for IVF. Hair analysis offers a novel method of investigating the impact of long-term exposure to endocrine disruptors and nutritional status on reproductive outcomes.

Alginate: A Versatile Biomaterial to Encapsulate Isolated Ovarian Follicles.

PubMed

Vanacker, Julie; Amorim, Christiani A

2017-07-01

In vitro culture of ovarian follicles isolated or enclosed in ovarian tissue fragments and grafting of isolated ovarian follicles represent a potential alternative to restore fertility in cancer patients who cannot undergo cryopreservation of embryos or oocytes or transplantation of frozen-thawed ovarian tissue. In this regard, respecting the three-dimensional (3D) architecture of isolated follicles is crucial to maintaining their proper follicular physiology. To this end, alginate hydrogel has been widely investigated using follicles from numerous animal species, yielding promising results. The goal of this review is therefore to provide an overview of alginate applications utilizing the biomaterial as a scaffold for 3D encapsulation of isolated ovarian follicles. Different methods of isolated follicle encapsulation in alginate are discussed in this review, as its use of 3D alginate culture systems as a tool for in vitro follicle analysis. Possible improvements of this matrix, namely modification with arginine-glycine-aspartic acid peptide or combination with fibrin, are also summarized. Encouraging results have been obtained in different animal models, and particularly with isolated follicles encapsulated in alginate matrices and grafted to mice. This summary is designed to guide the reader towards development of next-generation alginate scaffolds, with enhanced properties for follicle encapsulation.

Blood Cell Mitochondrial DNA Content and Premature Ovarian Aging

PubMed Central

Cacciatore, Chiara; Busnelli, Marta; Rossetti, Raffaella; Bonetti, Silvia; Paffoni, Alessio; Mari, Daniela; Ragni, Guido; Persani, Luca; Arosio, M.; Beck-Peccoz, P.; Biondi, M.; Bione, S.; Bruni, V.; Brigante, C.; Cannavo`, S.; Cavallo, L.; Cisternino, M.; Colombo, I.; Corbetta, S.; Crosignani, P.G.; D'Avanzo, M.G.; Dalpra, L.; Danesino, C.; Di Battista, E.; Di Prospero, F.; Donti, E.; Einaudi, S.; Falorni, A.; Foresta, C.; Fusi, F.; Garofalo, N.; Giotti, I.; Lanzi, R.; Larizza, D.; Locatelli, N.; Loli, P.; Madaschi, S.; Maghnie, M.; Maiore, S.; Mantero, F.; Marozzi, A.; Marzotti, S.; Migone, N.; Nappi, R.; Palli, D.; Patricelli, M.G.; Pisani, C.; Prontera, P.; Petraglia, F.; Radetti, G.; Renieri, A.; Ricca, I.; Ripamonti, A.; Rossetti, R.; Russo, G.; Russo, S.; Tonacchera, M.; Toniolo, D.; Torricelli, F.; Vegetti, W.; Villa, N.; Vineis, P.; Wasniewsk, M.; Zuffardi, O.

2012-01-01

Primary ovarian insufficiency (POI) is a critical fertility defect characterized by an anticipated and silent impairment of the follicular reserve, but its pathogenesis is largely unexplained. The frequent maternal inheritance of POI together with a remarkable dependence of ovarian folliculogenesis upon mitochondrial biogenesis and bioenergetics suggested the possible involvement of a generalized mitochondrial defect. Here, we verified the existence of a significant correlation between blood and ovarian mitochondrial DNA (mtDNA) content in a group of women undergoing ovarian hyperstimulation (OH), and then aimed to verify whether mtDNA content was significantly altered in the blood cells of POI women. We recruited 101 women with an impaired ovarian reserve: 59 women with premature ovarian failure (POF) and 42 poor responders (PR) to OH. A Taqman copy number assay revealed a significant mtDNA depletion (P<0.001) in both POF and PR women in comparison with 43 women of similar age and intact ovarian reserve, or 53 very old women with a previous physiological menopause. No pathogenic variations in the mitochondrial DNA polymerase γ (POLG) gene were detected in 57 POF or PR women with low blood mtDNA content. In conclusion, blood cell mtDNA depletion is a frequent finding among women with premature ovarian aging, suggesting that a still undetermined but generalized mitochondrial defect may frequently predispose to POI which could then be considered a form of anticipated aging in which the ovarian defect may represent the first manifestation. The determination of mtDNA content in blood may become an useful tool for the POI risk prediction. PMID:22879975

Impact of laparoscopic ovarian drilling on serum anti-mullerian hormone levels in patients with anovulatory Polycystic Ovarian syndrome.

PubMed

Paramu, Sobhana

2016-12-01

Anti-mullerian hormone (AMH) is a marker of the activity of recruitable ovarian follicles. It is useful in the prediction of ovarian reserve. Women with polycystic ovarian syndrome (PCOS) have elevated circulating and intrafollicular AMH levels. Laparoscopic ovarian drilling (LOD) in patients with PCOS destroys ovarian androgen-producing tissue and reduces their peripheral conversion to estrogens. Identifying factors that determine the response of patients with PCOS to LOD will help in selecting the patients who would likely benefit from this treatment. AMH is one such marker that can predict the response to LOD. To evaluate the effect of LOD on serum AMH levels among PCOS responders and non-responders and the usefulness of AMH as a tool in predicting the response to LOD, and to whether there was loss of ovarian function after LOD. This is a prospective cohort study including 30 clomiphene-resistant women with anovulatory PCOS undergoing LOD. Statistical analysis was performed to evaluate the effect of LOD on serum levels of AMH on these women. A significant fall in the levels of AMH was observed after LOD in both responders and non-responders (p<0.001). Women with AMH >8.3 ng/mL showed a significantly lower ovulation rate (33.3%). LOD was not associated with a risk of diminished ovarian reserve. LOD is an effective first-line treatment for women with PCOS who are clomiphene resistant. LOD has no negative effect on ovarian reserve. AMH is a useful marker in predicting the outcome of LOD.

Blood cell mitochondrial DNA content and premature ovarian aging.

PubMed

Bonomi, Marco; Somigliana, Edgardo; Cacciatore, Chiara; Busnelli, Marta; Rossetti, Raffaella; Bonetti, Silvia; Paffoni, Alessio; Mari, Daniela; Ragni, Guido; Persani, Luca

2012-01-01

Primary ovarian insufficiency (POI) is a critical fertility defect characterized by an anticipated and silent impairment of the follicular reserve, but its pathogenesis is largely unexplained. The frequent maternal inheritance of POI together with a remarkable dependence of ovarian folliculogenesis upon mitochondrial biogenesis and bioenergetics suggested the possible involvement of a generalized mitochondrial defect. Here, we verified the existence of a significant correlation between blood and ovarian mitochondrial DNA (mtDNA) content in a group of women undergoing ovarian hyperstimulation (OH), and then aimed to verify whether mtDNA content was significantly altered in the blood cells of POI women. We recruited 101 women with an impaired ovarian reserve: 59 women with premature ovarian failure (POF) and 42 poor responders (PR) to OH. A Taqman copy number assay revealed a significant mtDNA depletion (P<0.001) in both POF and PR women in comparison with 43 women of similar age and intact ovarian reserve, or 53 very old women with a previous physiological menopause. No pathogenic variations in the mitochondrial DNA polymerase γ (POLG) gene were detected in 57 POF or PR women with low blood mtDNA content. In conclusion, blood cell mtDNA depletion is a frequent finding among women with premature ovarian aging, suggesting that a still undetermined but generalized mitochondrial defect may frequently predispose to POI which could then be considered a form of anticipated aging in which the ovarian defect may represent the first manifestation. The determination of mtDNA content in blood may become an useful tool for the POI risk prediction.

Lactobacillus in Preventing Infection in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer or Myelodysplastic Syndrome

ClinicalTrials.gov

2017-02-02

Breast Cancer; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

A Web-Based Stem Cell Transplant Support System or Standard Care in Young Patients Undergoing Stem Cell Transplant and Their Families

ClinicalTrials.gov

2011-07-11

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neuroblastoma; Ovarian Cancer; Psychosocial Effects of Cancer and Its Treatment; Sarcoma

Fertility after uterine artery embolization: a review.

PubMed

McLucas, Bruce; Voorhees, William D; Elliott, Stephanie

2016-01-01

Uterine artery embolization (UAE) research has largely been focused on women over 40 years, yet women of reproductive age undergo UAE without any increased morbidity. Some physicians refrain from recommending UAE to women in this age group because of some research findings showing a negative effect on fertility. This review presents a comprehensive discussion of the fertility potential of women undergoing UAE, in terms of pregnancy rates and complications as well as ovarian function and reserve. Findings indicate many benefits for women desiring fertility who undergo UAE over traditional myomectomy.

Predictors of survival in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery based on the pooled analysis of an international collaborative cohort

PubMed Central

Zang, R Y; Harter, P; Chi, D S; Sehouli, J; Jiang, R; Tropé, C G; Ayhan, A; Cormio, G; Xing, Y; Wollschlaeger, K M; Braicu, E I; Rabbitt, C A; Oksefjell, H; Tian, W J; Fotopoulou, C; Pfisterer, J; du Bois, A; Berek, J S

2011-01-01

Background: This study aims to identify prognostic factors and to develop a risk model predicting survival in patients undergoing secondary cytoreductive surgery (SCR) for recurrent epithelial ovarian cancer. Methods: Individual data of 1100 patients with recurrent ovarian cancer of a progression-free interval at least 6 months who underwent SCR were pooled analysed. A simplified scoring system for each independent prognostic factor was developed according to its coefficient. Internal validation was performed to assess the discrimination of the model. Results: Complete SCR was strongly associated with the improvement of survival, with a median survival of 57.7 months, when compared with 27.0 months in those with residual disease of 0.1–1 cm and 15.6 months in those with residual disease of >1 cm, respectively (P<0.0001). Progression-free interval (⩽23.1 months vs >23.1 months, hazard ratio (HR): 1.72; score: 2), ascites at recurrence (present vs absent, HR: 1.27; score: 1), extent of recurrence (multiple vs localised disease, HR: 1.38; score: 1) as well as residual disease after SCR (R1 vs R0, HR: 1.90, score: 2; R2 vs R0, HR: 3.0, score: 4) entered into the risk model. Conclusion: This prognostic model may provide evidence to predict survival benefit from secondary cytoreduction in patients with recurrent ovarian cancer. PMID:21878937

Massive Broad Ligament Cellular Leiomyoma with Cystic Change: A Diagnostic Dilemma.

PubMed

Sharma, Preeti; Zaheer, Sufian; Yadav, Amit Kumar; Mandal, Ashish Kumar

2016-04-01

Leiomyomas are known to arise from uterus, but rarely from broad ligament. Further, cellular leiomyoma of broad ligament is the least common variant reported in literature. The diagnostic dilemma arises when leiomyomas undergo degenerative changes. This poses both clinical and radiological difficulty in differentiating with an ovarian tumour. We present an unusual case of a huge broad ligament mass measuring 29x19x09cm, mimicking an ovarian tumour both clinically and radiologically. Histopathology revealed cellular leiomyoma of broad ligament with cystic and myxoid degeneration hereby being the second case reported in literature. This case is being presented not only because of the rare incidence but also due to its diagnostic confusion with ovarian malignancy on clinical evaluation and radiological findings.

In vitro culture of early secondary preantral follicles in hanging drop of ovarian cell-conditioned medium to obtain MII oocytes from outbred deer mice.

PubMed

Choi, Jung Kyu; Agarwal, Pranay; He, Xiaoming

2013-12-01

The ovarian follicle (each contains a single oocyte) is the fundamental functional tissue unit of mammalian ovaries. In humans, it has been long held true that females are born with a maximum number of follicles (or oocytes) that are not only nonrenewable, but also undergoing degeneration with time with a sharply decreased oocyte quality after the age of ∼35. Therefore, it is of importance to isolate and bank ovarian follicles for in vitro culture to obtain fertilizable oocytes later, to preserve the fertility of professional women who may want to delay childbearing, young and unmarried women who may lose gonadal function because of exposure to environmental/occupational hazards or aggressive medical treatments, such as radiation and chemotherapy, and even endangered species and breeds. Although they contributed significantly to the understanding of follicle science and biology, most studies reported to date on this topic were done using the man-made, unnatural inbred animal species. It was found in this study that the conventional two-dimensional microliter drop and three-dimensional hanging drop (HD) methods, reported to be effective for in vitro culture of preantral follicles from inbred mice, are not directly transferrable to outbred deer mice. Therefore, a modified HD method was developed in this study to achieve a much higher (>5 times compared to the best conventional methods) percentage of developing early secondary preantral follicles from the outbred mice to the antral stage, for which, the use of an ovarian cell-conditioned medium and multiple follicles per HD were identified to be crucial. It was further found that the method for in vitro maturation of oocytes in antral follicles obtained by in vitro culture of preantral follicles could be very different from that for oocytes in antral follicles obtained by hormone stimulation in vivo. Therefore, this study should provide important guidance for establishing effective protocols of in vitro follicle culture to preserve the fertility of wildlife and humans outbred by nature.

In Vitro Culture of Early Secondary Preantral Follicles in Hanging Drop of Ovarian Cell-Conditioned Medium to Obtain MII Oocytes from Outbred Deer Mice

PubMed Central

Choi, Jung Kyu; Agarwal, Pranay

2013-01-01

The ovarian follicle (each contains a single oocyte) is the fundamental functional tissue unit of mammalian ovaries. In humans, it has been long held true that females are born with a maximum number of follicles (or oocytes) that are not only nonrenewable, but also undergoing degeneration with time with a sharply decreased oocyte quality after the age of ∼35. Therefore, it is of importance to isolate and bank ovarian follicles for in vitro culture to obtain fertilizable oocytes later, to preserve the fertility of professional women who may want to delay childbearing, young and unmarried women who may lose gonadal function because of exposure to environmental/occupational hazards or aggressive medical treatments, such as radiation and chemotherapy, and even endangered species and breeds. Although they contributed significantly to the understanding of follicle science and biology, most studies reported to date on this topic were done using the man-made, unnatural inbred animal species. It was found in this study that the conventional two-dimensional microliter drop and three-dimensional hanging drop (HD) methods, reported to be effective for in vitro culture of preantral follicles from inbred mice, are not directly transferrable to outbred deer mice. Therefore, a modified HD method was developed in this study to achieve a much higher (>5 times compared to the best conventional methods) percentage of developing early secondary preantral follicles from the outbred mice to the antral stage, for which, the use of an ovarian cell-conditioned medium and multiple follicles per HD were identified to be crucial. It was further found that the method for in vitro maturation of oocytes in antral follicles obtained by in vitro culture of preantral follicles could be very different from that for oocytes in antral follicles obtained by hormone stimulation in vivo. Therefore, this study should provide important guidance for establishing effective protocols of in vitro follicle culture to preserve the fertility of wildlife and humans outbred by nature. PMID:23789595

Ovarian adipocytokines are associated with early in vitro human embryo development independent of the action of ovarian insulin.

PubMed

Li, Liyun; Ferin, Michel; Sauer, Mark V; Lobo, Roger A

2012-12-01

We aimed to characterize the association between levels of serum and follicular fluid (FF) adipocytokines, reflected by the leptin to adiponectin ratio (L:A ratio), and oocyte quality and in vitro embryo development in women undergoing assisted reproduction. We also aimed to assess whether follicular hormonal pathways mediate this interaction. We prospectively collected FF from up to four individual preovulatory follicles (n = 76) and fasting sera from women (n = 31) without endocrinopathies undergoing in vitro fertilization (IVF) at a university-based center for assisted reproduction. Leptin, total adiponectin, insulin, insulin-like growth factor 1 (IGF-1), and ovarian steriods were measured using enzyme immunoassay. Oocyte maturity, fertilization, and embryo development were assessed. FF leptin was similar to serum levels while FF adiponectin was lower. FF leptin (27.10 ± 4.05 ng/mL) and the L:A ratio (11.48E-3 ± 2.57E-3) were related to FF insulin (R (2) = 0.370 and 0.419, p < 0.001) but not to ovarian steroids or IGF-1, whereas FF adiponectin ( 4.22 ± 0.52 ug/mL) correlated only with leptin (R (2) = -0.138, p = 0.001). Oocytes from a high FF L:A ratio environment were 81 % (RR 1.81 [95%CI 0.97-3.37]) more likely to undergo successful cleavage and 117 % (RR 2.17 [95 % CI 1.06-4.44]) more likely to obtain viable cleavage morphology compared to a low FF L:A ratio environment, even when adjusted for FF insulin, an independent predictor of cleavage. Certain adipocytokines, particularly the L:A ratio in the FF of the preovulatory follicle, are related to successful in vitro embryo development. This action may be independent of FF insulin.

Expression of regulator of G-protein signaling protein-2 gene in the rat ovary at the time of ovulation.

PubMed

Ujioka, T; Russell, D L; Okamura, H; Richards, J S; Espey, L L

2000-11-01

The ovulatory process in mammals begins when an endogenous surge in LH circulates to the ovary and couples with receptors in the plasma membranes of granulosa cells in mature ovarian follicles. This study provides evidence that the ovulatory stimulus includes induction of the gene for regulator of G-protein signaling protein-2 (RGS2). Immature Wistar rats were primed with 10 IU eCG s.c., and 48 h later the 12-h ovulatory process was initiated by 10 IU hCG (a homolog of LH) s.c. Ovarian RNA was extracted at 0, 2, 4, 8, 12, and 24 h after injecting the animals with hCG. The RNA extracts were used for reverse transcription-polymerase chain reaction differential display to detect gene expression in the stimulated ovarian tissue. Two of the amplified cDNAs that were upregulated within 2 h after the ovaries had been stimulated by hCG were homologous to segments of the mouse gene for RGS2. In situ hybridization indicated that the RGS2 mRNA was expressed in the granulosa layer of mature follicles. In conclusion, the gene for RGS2, which is known to regulate membrane signaling pathways, is transcribed in ovarian follicles in response to an ovulatory dose of gonadotropin.

Clinical relevance of genetic variants of gonadotrophins and their receptors in controlled ovarian stimulation: a systematic review and meta-analysis.

PubMed

Alviggi, Carlo; Conforti, Alessandro; Santi, Daniele; Esteves, Sandro C; Andersen, Claus Yding; Humaidan, Peter; Chiodini, Paolo; De Placido, Giuseppe; Simoni, Manuela

2018-06-18

Genotype has been implicated in the outcome of ovarian stimulation. The analysis of patient-specific genotypes might lead to an individualized pharmacogenomic approach to controlled ovarian stimulation (COS). However, the validity of such an approach remains to be established. To define the impact of specific genotype profiles of follicle-stimulating hormone, luteinizing hormone and their receptors (FSHR, LHR and LHCGR) on ovarian stimulation outcome. Specifically, our aim was to identify polymorphisms that could be useful in clinical practice, and those that need further clinical investigation. A systematic review followed by a meta-analysis was performed according to the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines without time restriction. We searched the PubMed/MEDLINE, Cochrane Library, SCOPUS and EMBASE databases to identify all relevant studies published before January 2017. Only clinical trials published as full-text articles in peer-reviewed journals were included. The primary outcome was the number of oocytes retrieved. Fifty-seven studies were assessed for eligibility, 33 of which were included in the qualitative and quantitative analyses. Data were independently extracted using quality indicators. COS outcomes related to seven polymorphisms (FSHR [rs6165], FSHR [rs6166], FSHR [rs1394205], LHB [rs1800447], LHB [rs1056917], LHCGR [rs2293275] and LHCGR [rs13405728]) were evaluated. More oocytes were retrieved from FSHR (rs6165) AA homozygotes (five studies, 677 patients, weighted mean difference [WMD]: 1.85, 95% CI: 0.85-2.85, P < 0.001; I2 = 0%) than from GG homozygotes and AG heterozygotes (four studies, 630 patients, WMD: 1.62, 95% CI: 0.28-2.95, P = 0.020; I2 = 56%). Moreover, stimulation duration was shorter in FSHR (rs6165) AA homozygotes than in AG carriers (three studies, 588 patients, WMD -0.48, 95% CI: -0.87 to -0.10, P = 0.010, I2 = 44%). A higher number of oocytes (21 studies, 2632 patients WMD: 0.84, 95% CI: 0.19 to 1.49, P = 0.01, I2 = 76%) and metaphase II oocytes (five studies, 608 patients, WMD: 1.03, 95% CI: 0.01-2.05, P = 0.050, I2 = 0%) was observed in AA than in GG homozygote carriers. FSH consumption was significantly lower in FSHR (rs1394205) GG homozygotes (three studies, 411 patients, WMD: -1294.61 IU, 95% CI: -593.08 to -1996.14 IU, P = 0.0003, I2 = 99%) and AG heterozygotes (three studies, 367 patients, WMD: -1014.36 IU, 95% CI: -364.11 to -1664.61 IU, P = 0.002, I2 = 99%) than in AA homozygotes. These results support the clinical relevance of specific genotype profiles on reproductive outcome. Further studies are required to determine their application in a pharmacogenomic approach to ovarian stimulation.

BRCA1 mutation carriers have a lower number of mature oocytes after ovarian stimulation for IVF/PGD.

PubMed

Derks-Smeets, I A P; van Tilborg, T C; van Montfoort, A; Smits, L; Torrance, H L; Meijer-Hoogeveen, M; Broekmans, F; Dreesen, J C F M; Paulussen, A D C; Tjan-Heijnen, V C G; Homminga, I; van den Berg, M M J; Ausems, M G E M; de Rycke, M; de Die-Smulders, C E M; Verpoest, W; van Golde, R

2017-11-01

The aim of this study was to determine whether BRCA1/2 mutation carriers produce fewer mature oocytes after ovarian stimulation for in vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD), in comparison to a PGD control group. A retrospective, international, multicenter cohort study was performed on data of first PGD cycles performed between January 2006 and September 2015. Data were extracted from medical files. The study was performed in one PGD center and three affiliated IVF centers in the Netherlands and one PGD center in Belgium. Exposed couples underwent PGD because of a pathogenic BRCA1/2 mutation, controls for other monogenic conditions. Only couples treated in a long gonadotropin-releasing hormone (GnRH) agonist-suppressive protocol, stimulated with at least 150 IU follicle stimulating hormone (FSH), were included. Women suspected to have a diminished ovarian reserve status due to chemotherapy, auto-immune disorders, or genetic conditions (other than BRCA1/2 mutations) were excluded. A total of 106 BRCA1/2 mutation carriers underwent PGD in this period, of which 43 (20 BRCA1 and 23 BRCA2 mutation carriers) met the inclusion criteria. They were compared to 174 controls selected by frequency matching. Thirty-eight BRCA1/2 mutation carriers (18 BRCA1 and 20 BRCA2 mutation carriers) and 154 controls proceeded to oocyte pickup. The median number of mature oocytes was 7.0 (interquartile range (IQR) 4.0-9.0) in the BRCA group as a whole, 6.5 (IQR 4.0-8.0) in BRCA1 mutation carriers, 7.5 (IQR 5.5-9.0) in BRCA2 mutation carriers, and 8.0 (IQR 6.0-11.0) in controls. Multiple linear regression analysis with the number of mature oocytes as a dependent variable and adjustment for treatment center, female age, female body mass index (BMI), type of gonadotropin used, and the total dose of gonadotropins administered revealed a significantly lower yield of mature oocytes in the BRCA group as compared to controls (p = 0.04). This finding could be fully accounted for by the BRCA1 subgroup (BRCA1 mutation carriers versus controls p = 0.02, BRCA2 mutation carriers versus controls p = 0.50). Ovarian response to stimulation, expressed as the number of mature oocytes, was reduced in BRCA1 but not in BRCA2 mutation carriers. Although oocyte yield was in correspondence to a normal response in all subgroups, this finding points to a possible negative influence of the BRCA1 gene on ovarian reserve.

The effect of endometrial injury on ongoing pregnancy rate in unselected subfertile women undergoing in vitro fertilization: a randomized controlled trial.

PubMed

Yeung, Tracy Wing Yee; Chai, Joyce; Li, Raymond Hang Wun; Lee, Vivian Chi Yan; Ho, Pak Chung; Ng, Ernest Hung Yu

2014-11-01

Does endometrial injury in the cycle preceding ovarian stimulation for in vitro fertilization (IVF) improve the ongoing pregnancy rate in unselected subfertile women? Endometrial injury induced by endometrial aspiration in the preceding cycle does not improve the ongoing pregnancy rate in unselected subfertile women undergoing IVF. Implantation failure remains one of the major limiting factors for IVF success. Mechanical endometrial injury in the cycle preceding ovarian stimulation of IVF treatment has been shown to improve implantation and pregnancy rates in women with repeated implantation failures. There is limited data on unselected subfertile women, especially those undergoing their first IVF treatment. This randomized controlled trial recruited 300 unselected subfertile women scheduled for IVF/ICSI treatment between March 2011 and August 2013. Subjects were randomized into endometrial aspiration (EA) (n = 150) and non-EA (n = 150) groups according to a computer-generated randomization list. Subjects were recruited and randomized in the assisted reproductive unit at the University of Hong Kong. In the preceding cycle, women in the EA group underwent endometrial aspiration using a Pipelle catheter in mid-luteal phase. All women were treated with a cycle of IVF/ICSI. Pregnancy outcomes were compared. There were no significant differences in baseline or cycle characteristics between the groups. There were 209 subjects (69.7%) who were undergoing their first IVF cycle and 91 (30.3%) subjects who had repeated cycles. There was no significant difference in ongoing pregnancy rates [26.7% (40/150) versus 32.0% (48/150); RR 0.833 (95% CI 0.585-1.187), P = 0.375] in the EA and non-EA groups. The implantation rates [32.8% (67/204) versus 29.7% (68/229); RR 1.080 (95% CI 0.804-1.450), P = 0.120], clinical pregnancy rates [34.0% (51/150) versus 38.0 (57/150); RR 0.895 (95% CI 0.661-1.211), P = 0.548], miscarriage rates [30.3% (17/56) versus 18.6% (11/59), RR 1.628 (95% CI 0.838-3.164), P = 0.150] and multiple pregnancy rates [31.3% (16/51) versus 19.3% (11/57), RR 1.626 (95% CI 0.833-3.172), P = 0.154] were all comparable between the EA and non-EA groups. Subgroup analysis in women having first embryo transfer (n = 209) also demonstrated no significant difference in ongoing pregnancy rates, but for women undergoing repeated cycles (n = 91), the on-going pregnancy rate was significantly lower in the EA group than in the non-EA group. The study aimed at assessing an unselected population of subfertile women by recruiting consecutive women attending our fertility clinic. However, since the majority of the recruited women (69.7%) were having their first IVF treatments, the results may not be generalizable to all women undergoing IVF. Previous RCTs and meta-analyses have suggested improved pregnancy rates after pretreatment endometrial injury in women with repeated implantation failure. A recent RCT also showed increased pregnancy rates in unselected subfertile women after endometrial injury, although that study was terminated early and thus underpowered. Our study showed with adequate power that no significant improvement in pregnancy rates was observed after endometrial injury in unselected women undergoing IVF treatment. The study was supported by the Small Project Funding 201309176012 of the Committee on Research and Conference Grants, University of Hong Kong. The authors have nothing to disclose. HKCTR-1646 and NCT 01977976. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

LINE1 CpG-DNA Hypomethylation in Granulosa Cells and Blood Leukocytes Is Associated With PCOS and Related Traits.

PubMed

Sagvekar, Pooja; Mangoli, Vijay; Desai, Sadhana; Patil, Anushree; Mukherjee, Srabani

2017-04-01

Altered global DNA methylation is indicative of epigenomic instability concerning chronic diseases. Investigating its incidence and association with polycystic ovary syndrome (PCOS) is essential to understand the etiopathogenesis of this disorder. We assessed global DNA methylation differences in peripheral blood leukocytes (PBLs) and cumulus granulosa cells (CGCs) of controls and women with PCOS; and their association with PCOS and its traits. This study included a total of 102 controls and women with PCOS. Forty-one women undergoing controlled ovarian hyperstimulation (COH) and 61 women not undergoing COH were recruited from in vitro fertilization (IVF) and infertility clinics. DNA methylation was measured by ELISA for 5'-methyl-cytosine content and bisulfite sequencing of 5'-untranslated region (5'-UTR) of long interspersed nucleotide element-1 (LINE1/L1). Total 5'-methyl-cytosine and L1 methylation levels in PBLs and CGCs were similar between controls and women with PCOS. Methylation assessed at CpG sites of L1 5'-UTR revealed a single CpG-site (CpG-4) to be consistently hypomethylated in PBLs of both PCOS groups and CGCs of stimulated PCOS group. In unstimulated women, hypomethylation at CpG-4 was strongly associated with PCOS susceptibility, whereas in stimulated group it showed strong associations with PCOS and its hormonal traits. Furthermore, CGCs demonstrated consistent global and CpG-DNA hypomethylation relative to PBLs, irrespective of normal or disease states. Our study revealed strong association of single hypomethylated CpG-site with PCOS. Identification and characterization of more such methyl-CpG signatures in repetitive elements in larger study populations would provide valuable epigenetic insights into PCOS. Copyright © 2017 by the Endocrine Society

T Cells in Predicting Acute Graft-Versus-Host Disease in Patients Undergoing Donor Stem Cell Transplant

ClinicalTrials.gov

2017-06-26

Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

Palifermin in Preventing Oral Mucositis Caused by Chemotherapy and/or Radiation Therapy in Young Patients Undergoing Stem Cell Transplant

ClinicalTrials.gov

2013-05-30

Breast Cancer; Graft Versus Host Disease; Kidney Cancer; Leukemia; Lymphoma; Mucositis; Multiple Myeloma; Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor

Surrogate pregnancy in a patient who underwent radical hysterectomy and bilateral transposition of ovaries.

PubMed

Azem, Foad; Yovel, Israel; Wagman, Israel; Kapostiansky, Rita; Lessing, Joseph B; Amit, Ami

2003-05-01

To evaluate IVF-surrogate pregnancy in a patient with ovarian transposition after radical hysterectomy for carcinoma of the cervix. Case report. A maternity hospital in Tel Aviv that is a major tertiary care and referral center. A 29-year-old woman who underwent Wertheim's hysterectomy for carcinoma of the uterine cervix and ovarian transposition before total pelvic irradiation. Standard IVF treatment, transabdominal oocyte retrieval, and transfer to surrogate mother. Outcome of IVF cycle. A twin pregnancy in the first cycle. This is the second reported case of controlled ovarian stimulation and oocyte retrieval performed on a transposed ovary.

Repeated use of mifepristone and levonorgestrel and their effect on the ovarian function in mice.

PubMed

Chen, Yuanyuan; Shi, Xiaobo

2016-11-01

To investigate the effects of repeated mifepristone and levonorgestrel use on estrous cycle and expression of ovarian follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) in mice. Ovarian FSHR and LHR mRNA expression was measured using real-time quantitative reverse transcription-polymerase chain reaction, while the protein levels were measured using immunohistochemistry. Repeated use of mifepristone and levonorgestrel significantly lengthened the estrous cycle and decreased FSHR and LHR mRNA and protein expression in the ovaries of mice at 4, 24, and 48 days after discontinuing drug use. Repeated use of mifepristone and levonorgestrel had significant main effects on estrous cycle length and the mRNA expression and protein level of ovarian FSHR and LHR. Repeated mifepristone and levonorgestrel use and withdrawal time had a significant interaction with mouse estrous cycle (F = 16.65, P < 0.05), ovarian LHR and FSHR mRNA expression (F = 563.072, P < 0.05), and protein level (F = 6.536, P < 0.05). Repeated use of mifepristone and levonorgestrel can lead to sustained damage to ovarian function through inhibition of ovarian FSHR and LHR expression in mice. © 2016 Japan Society of Obstetrics and Gynecology.

Exploiting Uptake of Nanoparticles by Phagocytes for Cancer Treatment.

PubMed

Sheen, Mee Rie; Fiering, Steven

2017-01-01

Many cancers including ovarian, pancreatic, colon, liver, and stomach cancers are largely confined to the peritoneal cavity. Peritoneal tumors are directly accessible by intraperitoneal injections. Previously we demonstrated that intraperitoneal injection of nanoparticles and subsequent ingestion by tumor-associated phagocytes can be used to either directly impact tumors or stimulate antitumor immune responses. Here we outline methods to specifically utilize iron oxide nanoparticles with the ID8-Defb29/Vegf-A murine ovarian cancer model and discuss the tendency of phagocytes to ingest nanoparticles and the potential of phagocytes to carry nanoparticles to tumors resulting in direct killing of tumor cells or stimulate antitumor immune responses in peritoneal cancers. This basic approach can be modified as needed for different types of tumors and nanoparticles.

Laparoscopic ovarian cystectomy of endometriomas does not affect the ovarian response to gonadotropin stimulation.

PubMed

Marconi, Guillermo; Vilela, Martín; Quintana, Ramiro; Sueldo, Carlos

2002-10-01

To evaluate the ovarian response cycles of IVF-ET in patients who previously underwent laparoscopic cystectomy for endometriomas. Retrospective study with prospective selection of participants and controls. Instituto de Ginecología y Fertilidad Buenos Aires, Argentina. Thirty-nine patients underwent an operation for ovarian endometriomas by atraumatic removal of the pseudocapsule with minimal bipolar cauterization of small bleeders and an IVF-ET cycle (group A) and 39 control patients of similar age underwent an IVF-ET cycle for tubal factor infertility (group B). Laparoscopic endometrioma cystectomy, IVF-ET cycle. E(2) levels, number of gonadotropin ampoules, follicles, oocytes retrieved, number and quality of embryos transferred, and clinical pregnancy rate. There were no differences in all the parameters studied (E(2) levels, number of follicles, oocytes retrieved, number and quality of embryos transferred, and clinical pregnancy rate) except for the number of gonadotropin ampoules needed for ovarian hyperstimulation, which was significantly higher in group A than in group B. Our results indicate that laparoscopic cystectomy for endometriomas is an appropriate treatment since it did not negatively affect the ovarian response for IVF-ET.

Microdose GnRH Agonist Flare-Up versus Ultrashort GnRH Agonist Combined with Fixed GnRH Antagonist in Poor Responders of Assisted Reproductive Techniques Cycles.

PubMed

Eftekhar, Maryam; Mohammadian, Farnaz; Yousefnejad, Fariba; Khani, Parisa

2013-01-01

This study compares the microdose flare-up protocol to the ultrashort gonadotropinreleasing hormone (GnRH) agonist flare combined with the fixed multidose GnRH antagonist protocol in poor responders undergoing ovarian stimulation. In this randomized clinical trial, 120 women who were candidates for assisted reproductive techniques (ART) and had histories of one or more failed in vitro fertilization (IVF) cycles with three or fewer retrieved oocytes were prospectively randomized into two groups. Group I (60 patients) received the microdose flare-up regimen and group II (60 patients) received the ultrashort GnRH agonist combined with fixed GnRH antagonist. There were no significant differences between the groups in the number of used gonadotropin ampoules (p=0.591), duration of stimulation (p=0.610), number of retrieved oocytes (p=0.802), fertilization rate (p=0.456), and the number of transferred embryos (p=0.954). The clinical pregnancy rates were statistically similar in group I (10%) compared with group II (13.3%, p=0.389). According to our results, there is no significant difference between these protocols for improving the ART outcome in poor responders. Additional prospective, randomized studies with more patients is necessary to determine the best protocol (Registration Number: IRCT201105096420N1).

The use of recombinant human LH (lutropin alfa) in the late stimulation phase of assisted reproduction cycles: a double-blind, randomized, prospective study.

PubMed

Tarlatzis, B; Tavmergen, E; Szamatowicz, M; Barash, A; Amit, A; Levitas, E; Shoham, Z

2006-01-01

The effect of recombinant human LH (r-hLH; lutropin alfa) in women undergoing controlled ovarian stimulation with recombinant human FSH (r-hFSH) prior to IVF was investigated. After down-regulation with the GnRH agonist, buserelin, 114 normo-ovulatory women (aged 18-37 years) received r-hFSH alone until the lead follicle reached a diameter of 14 mm. Patients were then randomized in a double-blind fashion to receive r-hFSH in addition to r-hLH, 75 IU s.c., or placebo daily for a maximum of 10 days prior to oocyte retrieval and IVF. The primary end-point was the number of metaphase II oocytes. There were no significant differences between treatment groups for the primary end-point. Serum estradiol concentrations on the day of HCG administration were significantly higher in the group receiving r-hLH plus r-hFSH than in the group receiving r-hFSH alone (P = 0.0001), but there were no significant differences between the groups in dose and duration of r-hFSH treatment required, oocyte maturation, fertilization rate, pregnancy rate and live birth rate. In this patient population, the addition of r-hLH during the late follicular phase of a long GnRH agonist and r-hFSH stimulation cycle provides no further benefit in terms of oocyte maturation or other end-points.

A rare case report of squamous-cell carcinoma arising from mature cystic teratoma of ovary.

PubMed

Kalampokas, E; Boutas, I; Kairi-Vasilatou, E; Salakos, N; Panoulis, K; Aravantinos, L; Damaskos, C; Kalampokas, T; Deligeoroglou, E

2014-01-01

The most frequent ovarian germ cell tumors are mature cystic teratomas (MCTs), composing 10-25% of all ovarian neoplasms. MCTs have the potential of undergoing malignant transformation, typically in postmenopausal women, with a frequency of 0.17-3%, with squamous cell carcinoma being the most common malignant tumor arising from MCT. We present the rare clinical entity of a squamous cell carcinoma arising from a mature cystic teratoma in a 56-year-old premenopausal woman as well as diagnostic and therapeutic route followed.

Influence of TP53 Codon 72 Polymorphism Alone or in Combination with HDM2 SNP309 on Human Infertility and IVF Outcome.

PubMed

Chan, Ying; Zhu, Baosheng; Jiang, Hongguo; Zhang, Jinman; Luo, Ying; Tang, Wenru

2016-01-01

To evaluate the association of the TP53 codon 72 (rs 1042522) alone or in combination with HDM2 SNP309 (rs 2279744) polymorphisms with human infertility and IVF outcome, we collected 1450 infertility women undergoing their first controlled ovarian stimulation for IVF treatment and 250 fertile controls in the case-control study. Frequencies, distribution, interaction of genes, and correlation with infertility and IVF outcome of clinical pregnancy were analyzed. We found a statistically significant association between TP53 codon 72 polymorphism and IVF outcome (52.10% vs. 47.40%, OR = 0.83, 95%CI:0.71-0.96, p = 0.01). No significant difference was shown between TP53 codon 72, HDM2 SNP309 polymorphisms, human infertility, and between the combination of two genes polymorphisms and the clinical pregnancy outcome of IVF. The data support C allele as a protective factor for IVF pregnancy outcome. Further researches should be focused on the mechanism of these associations.

DNA Methylation in Embryo Development: Epigenetic Impact of ART (Assisted Reproductive Technologies).

PubMed

Canovas, Sebastian; Ross, Pablo J; Kelsey, Gavin; Coy, Pilar

2017-11-01

DNA methylation can be considered a component of epigenetic memory with a critical role during embryo development, and which undergoes dramatic reprogramming after fertilization. Though it has been a focus of research for many years, the reprogramming mechanism is still not fully understood. Recent results suggest that absence of maintenance at DNA replication is a major factor, and that there is an unexpected role for TET3-mediated oxidation of 5mC to 5hmC in guarding against de novo methylation. Base-resolution and genome-wide profiling methods are enabling more comprehensive assessments of the extent to which ART might impair DNA methylation reprogramming, and which sequence elements are most vulnerable. Indeed, as we also review here, studies showing the effect of culture media, ovarian stimulation or embryo transfer on the methylation pattern of embryos emphasize the need to face ART-associated defects and search for strategies to mitigate adverse effects on the health of ART-derived children. © 2017 WILEY Periodicals, Inc.

Metabolic and hormonal changes induced by pioglitazone in polycystic ovary syndrome: a randomized, placebo-controlled clinical trial.

PubMed

Aroda, Vanita R; Ciaraldi, Theodore P; Burke, Paivi; Mudaliar, Sunder; Clopton, Paul; Phillips, Susan; Chang, R Jeffrey; Henry, Robert R

2009-02-01

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, compensatory hyperinsulinemia, increased prevalence of impaired glucose tolerance, and increased ovarian androgen biosynthesis. The aim of the study was to evaluate effects of pioglitazone on whole body insulin action and ovarian androgen biosynthesis in PCOS. We performed a randomized placebo-controlled trial. The study was conducted at the Special Diagnostic and Treatment Unit of the Veterans Affairs Medical Center, San Diego, and the University of California, San Diego, General Clinical Research Center. A total of 23 subjects with PCOS were evaluated at baseline and end of treatment. Six age- and body mass index-matched women without PCOS were normal controls for baseline evaluation. Subjects with PCOS were randomized to oral placebo or pioglitazone 45 mg daily for 6 months. The primary outcome measures were whole body insulin action as measured by hyperinsulinemic euglycemic clamp and ovarian androgen biosynthesis as measured by leuprolide-stimulated production of 17-hydroxyprogesterone (17-OHP). Compared with placebo, pioglitazone treatment significantly improved multiple measures of insulin action, including glucose disposal rate (P < 0.01), 2-h glucose during 75-g oral glucose tolerance test (P < 0.01), area under the curve glucose during oral glucose tolerance test (P < 0.01), serum adiponectin (P < 0.01), and fasting hyperinsulinemia (P < 0.01). Compared to placebo, pioglitazone treatment reduced the increment of leuprolide-stimulated 17-OHP (P < 0.02). Improvements in glucose disposal rate correlated with reductions in 17-OHP stimulation (P < 0.02). Compared to placebo, pioglitazone treatment in PCOS was associated with improvements in insulin action and glucose homeostasis and ameliorated the hyperandrogenic ovarian response.

Cryopreservation of human ovarian tissue.

PubMed

Fabbri, Raffaella; Pasquinelli, Gianandrea; Bracone, Graziella; Orrico, Catia; Di Tommaso, Barbara; Venturoli, Stefano

2006-01-01

New and often aggressive treatment schemes allow the successful healing of many young patients with cancer, but the price the young women have to pay is high: many of them lose ovarian function and fertility. Due to the improved long-term survival of adolescents and young women with malignancies undergoing gonadotoxic chemotherapy, preservation of future fertility has been the focus of recent ubiquitarian interest. A feasible solution is the cryopreservation of ovarian tissue. Ovarian tissue, after thawing, can be used in three different ways: 1. grafted into its normal site (orthotopic); 2. grafted into a site other than its normal position (heterotopic), necessitating recourse to in vitro fertilization (IVF); 3. grown and in vitro matured in order to obtain metaphase II oocytes for an IVF program. It is believed that protein supplementation, in cryopreservation solution, is essential for improving ovarian tissue cryopreservation. The aim of this study was to evaluate the ultrastructural appearance of human ovarian tissue cryopreserved in 1.5 M 1,2 propanediol (PROH), 0.2 M sucrose using different protein sources: fetal calf serum (FCS), plasmanate or syntetic serum substitute (SSS). Fresh and frozen/thawed ovarian tissues were compared by transmission electron microscope (TEM), to evaluate the appearance of stromal and follicle cells as affected by different protein sources. Our data indicate that FCS is a better protein support for ovarian tissue cryopreservation when compared to SSS or Plasmanate. In addition the follicles are more resistant to the cryopreservation with respect to stroma.

Comparison of the effects of letrozole and cabergoline on vascular permeability, ovarian diameter, ovarian tissue VEGF levels, and blood PEDF levels, in a rat model of ovarian hyperstimulation syndrome.

PubMed

Şahin, Nur; Apaydın, Nesin; Töz, Emrah; Sivrikoz, Oya Nermin; Genç, Mine; Turan, Gülüzar Arzu; Cengiz, Hakan; Eskicioğlu, Fatma

2016-05-01

To evaluate the effects of letrozole and cabergoline in a rat model of ovarian hyperstimulation syndrome (OHSS). In this prospective, controlled experimental study, the 28 female Wistar rats were divided into four subgroups (one non-stimulated control and three OHSS-positive groups: placebo, letrozole, and cabergoline). To induce OHSS, rats were injected with 10 IU of pregnant mare serum gonadotropin from day 29 to day 32 of life, followed by subcutaneous injection of 30 IU hCG on day 33. Letrozole rats received with a single dose of 0.1 mg/kg letrozole via oral gavage, on the hCG day. Cabergoline rats received with a single dose of 100 µg/kg cabergoline via oral gavage, on the hCG day. All animals were compared in terms of body weight, vascular permeability (VP), ovarian diameter, ovarian tissue VEGF expression (assessed via immunohistochemical staining), and blood pigment epithelium-derived growth factor (PEDF) levels. The OHSS-positive placebo group (group 2) exhibited the highest VP, ovarian diameter, extent of VEGF staining, and lowest PEDF level, as expected. No significant difference was evident between the letrozole and cabergoline groups in terms of any of body weight; VP; PEDF level; ovarian diameter; or the staining intensity of, or percentage staining for, VEGF in ovarian tissues. Letrozole and cabergoline were equally effective to prevent OHSS, reducing the ovarian diameter, VP, and PEDF and VEGF levels to similar extents.

IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer

PubMed Central

Felices, M.; Chu, S.; Kodal, B.; Bendzick, L.; Ryan, C.; Lenvik, A.J.; Boylan, K.L.M.; Wong, H.C.; Skubitz, A.P.N.; Miller, J.S.; Geller, M.A.

2017-01-01

Objective Natural killer (NK) cells represent a powerful immunotherapeutic target as they lyse tumors directly, do not require differentiation, and can elicit potent inflammatory responses. The objective of these studies was to use an IL-15 super-agonist complex, ALT-803 (Altor BioScience Corporation), to enhance the function of both normal and ovarian cancer patient derived NK cells by increasing cytotoxicity and cytokine production. Methods NK cell function from normal donor peripheral blood mononuclear cells (PBMCs) and ovarian cancer patient ascites was assessed using flow cytometry and chromium release assays +/− ALT-803 stimulation. To evaluate the ability of ALT-803 to enhance NK cell function in vivo against ovarian cancer, we used a MA148-luc ovarian cancer NOD scid gamma (NSG) xenogeneic mouse model with transferred human NK cells. Results ALT-803 potently enhanced functionality of NK cells against all ovarian cancer cell lines with significant increases seen in CD107a, IFNγ and TNFα expression depending on target cell line. Function was also rescued in NK cells derived from ovarian cancer patient ascites. Finally, only animals treated with intraperitoneal ALT-803 displayed an NK dependent significant decrease in tumor. Conclusions ALT-803 enhances NK cell cytotoxicity against ovarian cancer in vitro and in vivo and is able to rescue functionality of NK cells derived from ovarian cancer patient ascites. These findings suggest that ALT-803 has the potential to enhance NK-cell-based immunotherapeutic approaches for the treatment of ovarian cancer. PMID:28236454

Histologic and ultrastructural evaluation of fresh and frozen-thawed human ovarian xenografts in nude mice.

PubMed

Nisolle, M; Casanas-Roux, F; Qu, J; Motta, P; Donnez, J

2000-07-01

To compare histologic and ultrastructural characteristics of fresh and frozen-thawed human ovarian cortical tissue grafted into nude mice. Experimental prospective study. An academic research environment. Ovarian biopsy specimens were obtained from 13 women undergoing laparoscopy for tubal ligation or infertility. Forty nude mice. A minilaparotomy was performed to place fresh and frozen-thawed ovarian grafts subcutaneously (sc) or intraperitoneally (ip). Removal of the ovarian grafts was performed at 24 days. [1] the follicular population, [2] fibrosis, [3] vascularization of the grafted tissue, and [4] ultrastructural evaluation. A greater fibrosis relative surface area was noted in frozen-thawed transplanted tissue than in fresh transplants. Regardless of this fibrosis, a similar follicular density was observed in fresh and frozen-thawed ovarian tissue 24 days after transplantation. Active angiogenesis was proved by both immunohistochemical study of the vascular endothelial growth factor and morphometric study of the vascular network. Normal ultrastructural characteristics were noted in frozen-thawed ovarian biopsies. Angiogenesis allows implantation of the graft even if it has been cryopreserved and thawed similarly to implantation of fresh tissue. The greater fibrosis observed in grafts after cryopreservation and implantation does not seem to affect the primordial and primary ovocyte population and their ultrastructural characteristics, but further studies must be conducted to prove that after cryopreservation and transplantation, ovocytes may achieve full maturation and fertilization.

Collecting and Storing Tissue and DNA Samples From Patients Undergoing a Donor Stem Cell Transplant

ClinicalTrials.gov

2012-11-04

Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Graft Versus Host Disease; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

Ginsenoside Rg1 improves fertility and reduces ovarian pathological damages in premature ovarian failure model of mice.

PubMed

He, Lianli; Ling, Li; Wei, Tianqin; Wang, Yaping; Xiong, Zhengai

2017-04-01

This study aims to investigate the effect as well as mechanism of ginsenoside Rg1 (Rg1) on premature ovarian failure (POF) induced by d-galactose (d-gal) in mice. C57BL/6 female mice were divided into four groups randomly, which were the saline group, the d-gal group, the d-gal + Rg1 group, and the Rg1 group. Body weight was recorded. Overall ovarian function including estrous cycles, sex hormone secretion, ovarian follicle development, and ovarian morphology was analyzed by H&E staining and ELISA. Effect of Rg1 on aging was determined by analyzing the activities of oxidation-associated biomarkers, pro-inflammatory cytokine secretion, expression of senescence-associated proteins, and fertility. Compared with the d-gal group, in Rg1 + d-gal group, body weight was increased significantly, estrous cycle block was released, and fertility and the morphology of ovaries were restored. And, Rg1 treatment after d-gal administration significantly reduced senescence-associated protein expression, increased the activity of total superoxide dismutase and glutathione peroxidase from bovine erythrocyte, and induced higher follicle stimulating hormone receptor protein expression. Additionally, the expression levels of malondialdehyde, interleukin-1β, tumor necrosis factor-α, and interleukin-6 were significantly decreased. Together, Rg1 improves mouse fertility and reduces ovarian pathological damage in d-gal-induced POF model possibly through enhancing anti-inflammatory and antioxidant capacities and reducing expression of senescence signal pathway proteins. Impact statement Ginsenoside Rg1 (Rg1) is a kind of natural estrogen and it has antioxidation and antiaging effects. However, whether Rg1 has effects on premature ovarian failure (POF) is still not clear. In this study, aging model induced by d-galactose was used to mimic POF. The effect and possible mechanism of Rg1 on ovary aging was investigated. We found that Rg1 treatment up-regulated the expression of follicle stimulating hormone receptor and down-regulated senescence-associated protein expression in granule cells of POF mice. Particularly, Rg1 improved fertility ability and reduced ovarian pathological damages by its antioxidative and anti-inflammation capacity. Thus, Rg1 enhances the antiaging ability of ovary and fertility ability of POF mice through enhancing the anti-inflammatory and antioxidant capacities of ovary.

Ovarian aging: latest thoughts on assessment and management.

PubMed

Younis, Johnny S

2011-12-01

In the past few decades, women have been intentionally delaying pregnancy and ovarian aging has become one of the most detrimental factors of pregnancy achievement. This review will discuss contemporary methods of ovarian aging assessment and present an overview of current management strategies. Antimullerian hormone (AMH) and antral follicle count (AFC) seem to be the most reliable predictors of ovarian aging appraisal. Nevertheless, they have not been shown to predict pregnancy achievement in assisted reproduction. Heritability has a high impact on ovarian aging. Employing several genetic approaches, it is now being widely investigated, but the task is far from being accomplished. Although multivariate models have not been proven to be superior to AFC, new data support the notion that chronological age and genetic markers inclusion may increase their reliability. Several strategies have been suggested to treat ovarian aging in assisted reproductive technology (ART) settings. None of the stimulation protocol manipulations have been found to be advantageous and individualization of treatment is still recommended. Ovarian priming by different androgen preparations has been shown to be promising but more randomized controlled trials are needed to support these findings. Except for oocyte donation other ART strategies have not shown a convincing benefit for ovarian aging. The new development of oocyte vitrification may well introduce opportunities for fertility preservation to women at risk of ovarian aging. Proper assessment and detection of ovarian aging, employing current or developing predictors of ovarian reserve, especially genetic tests, may enable health providers to recommend, at appropriate biological time, early pregnancy achievement or fertility preservation in women at risk.

High ovarian response in Yoruba African women during ovulation induction for assisted conception.

PubMed

Wada, I; Matson, P L; Macnamee, M C; Brinsden, P R; Lieberman, B A

1994-06-01

Fertile Yoruba women from western Nigeria have a much higher incidence of naturally conceived multizygotic twin and triplet pregnancies than Caucasians. The objective of the present study was to determine whether there are differences between infertile Yoruba and Caucasian women in terms of ovarian response in stimulate cycles for assisted conception. A total of 11 Yoruba women were scheduled for 14 in-vitro fertilization (IVF) and one gamete intra-Fallopian transfer (GIFT) cycles from 1990 to 1992. The Caucasian group consisted of 209 women scheduled for 213 IVF and 22 GIFT cycles during the same period. Buserelin, 500 micrograms subcutaneously daily, was started in the mid-luteal phase to achieve pituitary desensitization. Ovarian stimulation was with variable amounts of menopausal gonadotrophins. Human chorionic gonadotrophin (HCG) was given to trigger the ovulatory process. The Yoruba and Caucasian groups were similar in age and body weight, but significantly more Yorubas (45 versus 11%; P < 0.005) had ultrasound features of polycystic ovary syndrome (PCOS). The serum oestradiol concentration (3024 versus 2058 pg/ml; P < 0.05) and number of follicles > 14 mm in diameter (15.5 versus 9.5; P < 0.05) on the day of HCG were higher in the Yoruba group. The ovarian hyperstimulation syndrome (OHSS) was also more prevalent in the Yoruba group (20 versus 5%; P < 0.05). No difference was found in clinical pregnancy or embryo implantation rates. These results show a higher tendency toward exaggerated ovarian response in infertile Yoruba than Caucasian women, associated with a higher prevalence of PCOS. The risk of developing symptomatic OHSS is higher in Yoruba women.

Hormonal Changes After Laparoscopic Ovarian Diathermy in Patients with Polycystic Ovarian Syndrome.

PubMed

Elnaggar, Elsayed A; Elwan, Youssef Abo; Ibrahim, Safaa A; Abdalla, Mena M

2016-10-01

To assess the changes in hormonal profile (serum FSH, LH, prolactin and total testosterone) following laparoscopic ovarian drilling (LOD) in patients with polycystic ovarian syndrome. Fifty patients with PCOS have been included in this study. Serum prolactin, total testosterone, follicular-stimulating hormone (FSH) and luteinizing hormone (LH) levels have been used as biochemical markers, before and after procedures. Laparoscopic ovarian drilling was successfully employed without any surgical complications and on an average follow-up time of 24 weeks after the procedure. During the follow-up serum values for prolactin, total testosterone and LH have decreased significantly and FSH levels remained unchanged after the procedure. The LOD in patients with PCOS may avoid or reduce the risk of OHSS and the multiple pregnancy rate induced by gonadotropin therapy. The high pregnancy rate and the economic aspect of the procedure offer an attractive management for patients with PCOS. However, LOD can be considered as second-line treatment after clomiphene citrate treatment failure and/or resistance.

Altered ovarian function affects skeletal homeostasis independent of the action of follicle-stimulating hormone.

PubMed

Gao, Jianjun; Tiwari-Pandey, Rashmi; Samadfam, Rana; Yang, Yinzhi; Miao, Dengshun; Karaplis, Andrew C; Sairam, M Ram; Goltzman, David

2007-06-01

Osteoporosis is a leading public health problem. Although a major cause in women is thought to be a decline in estrogen, it has recently been proposed that FSH or follitropin is required for osteoporotic bone loss. We examined the FSH receptor null mouse (FORKO mouse) to determine whether altered ovarian function could induce bone loss independent of FSH action. By 3 months of age, FORKO mice developed age-dependent declines in bone mineral density and trabecular bone volume of the lumbar spine and femur, which could be partly reversed by ovarian transplantation. Bilateral ovariectomy reduced elevated circulating testosterone levels in FORKO mice and decreased bone mass to levels indistinguishable from those in ovariectomized wild-type controls. Androgen receptor blockade and especially aromatase inhibition each produced bone volume reductions in the FORKO mouse. The results indicate that ovarian secretory products, notably estrogen, and peripheral conversion of ovarian androgen to estrogen can alter bone homeostasis independent of any bone resorptive action of FSH.

Amygdala Kindling Alters Estrus Cycle and Ovarian Morphology in the Rat.

PubMed

Pan, Juan; Zhang, Lingwu; Wang, Feng; Liu, Dan; Li, P Andy; Sun, Tao

2013-11-01

The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral seizures were recorded and ovarian morphology was evaluated by light and electron microscopies. Our results showed that the kindled rats lost their ovarian periodicity displayed significant ovarian enlargement. H&E staining revealed increased number of growing follicles and total follicles, as well as polycysts in the ovaries of the kindled animals compared to sham and control animals. Ultrastructural study detected numerous apoptotic granulosa cells in growing follicles and thecal cell hyperplasia with secretary granules in the thecal cells in the kindled rats. The results suggest that amygdala kindling is a risk factor for the development of polycystic ovary syndrome.

Effect of medroxyprogesterone acetate (Provera) on ovarian radiosensitivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarrell, J.; YoungLai, E.V.; McMahon, A.

1989-04-01

Medroxyprogesterone acetate (Provera) is a drug that is commonly given to young women with cancer during chemotherapy and radiation to control heavy bleeding associated with anovulation. Because hypothalamic-pituitary-ovarian suppression has been associated with ovarian protection from the effects of chemotherapy and medroxyprogesterone acetate has been identified as a radiosensitizing agent, we explored the effects of medroxyprogesterone acetate on a rat model with known radiation injury characteristics. Sprague-Dawley rats were treated with medroxyprogesterone acetate or vehicle from day 22 to day 37 of life and were either irradiated or sham-irradiated on day 30 of life and then killed on day 44.more » Radiation with medroxyprogesterone acetate administration produced a greater loss in preantral and healthy control follicles than in control follicles. No suppression of luteinizing hormone or follicle-stimulating hormone had occurred by day 30 but ovarian glutathione content was reduced. These findings indicate that the administration of medroxyprogesterone acetate with radiotherapy may enhance ovarian injury.« less

The effect of FT500 Plus(®) on ovarian stimulation in PCOS women.

PubMed

Alviggi, Carlo; Cariati, Federica; Conforti, Alessandro; De Rosa, Pasquale; Vallone, Roberta; Strina, Ida; Pivonello, Rosario; De Placido, Giuseppe

2016-01-01

Both oxidative stress and polycystic ovary syndrome have been involved in several aspects of female reproduction. In this retrospective observational study, the outcome of controlled ovarian stimulation and follicular microenvironment of twenty-five women affected by PCOS (Group A) have been explored, evaluating the effects of myo-inositol in association with antioxidant activities (FT500 Plus(®)). Twenty-five untreated-PCOS women (Group B) with similar characteristics served as control group. Although there was no difference in ovarian volume at time zero, this parameter was significantly smaller at the 5-month follow-up in the Group A (11.1±0.9 versus 13.5±1; P=0.0001). Group A showed a significant increase in the number of MII oocytes (6.3±2.5 versus 4.5±2; P=0.03) and glutathione peroxidase activity in follicular fluid (15.4±6.2 versus 11±2.2; P=0.04). FT500 Plus(®) may be considered in PCOS patient for improving oocyte quality. Copyright © 2015 Elsevier Inc. All rights reserved.

Serum magnesium and calcium levels in infertile women during a cycle of reproductive assistance.

PubMed

Grossi, Elena; Castiglioni, Sara; Moscheni, Claudia; Antonazzo, Patrizio; Cetin, Irene; Savasi, Valeria Maria

2017-05-01

Magnesium (Mg) and calcium (Ca) are essential cations for women's preconception health. It is well known that, in blood, the concentration of ionized form of these two cations is temporally altered during menstrual cycle, suggesting a correlation between sex steroid hormones and serum calcium and magnesium levels. Evidence from literature suggests that in assisted reproductive technology increasing estrogens during ovarian hyperstimulation may also modulate serum magnesium and calcium levels. Therefore, we first examined total serum magnesium and calcium levels during follicular phase in a large population of infertile patients who underwent intrauterine insemination (IUI). The results were compared to a group of fertile women. Successively, we studied the total serum magnesium and calcium concentrations in infertile patients before and after ovarian hyperstimulation for in vitro fertilization (IVF). Results highlight that total serum concentration of magnesium and calcium does not seem altered in infertile women. During stimulation with gonadotropins, the values of the two cations do not change significantly in ovarian-stimulated women. However, we found a downward trend in the total magnesium and calcium levels in relation to the rising estrogens.

The use of serum anti-Mullerian hormone (AMH) levels and antral follicle count (AFC) to predict the number of oocytes collected and availability of embryos for cryopreservation in IVF.

PubMed

Kotanidis, L; Nikolettos, K; Petousis, S; Asimakopoulos, B; Chatzimitrou, E; Kolios, G; Nikolettos, N

2016-12-01

To investigate the predictive value of anti-Mullerian hormone (AMH) and antral follicle count (AFC) on the final number of oocytes retrieved and the availability of embryos for cryopreservation in in vitro fertilization (IVF) cycles. In this prospective study, one hundred and twenty women in their first IVF treatment were enrolled. The short stimulation agonist protocol was used for controlled ovarian hyperstimulation in all cases. Serum AMH levels were measured during the menstrual cycle preceding treatment. AFC was measured in cycle day 2, just before starting ovarian stimulation. A strong, positive correlation between AMH, AFC and the number of collected oocytes was found. The patients with available and suitable supplementary embryos for cryopreservation had higher levels of AMH and larger numbers of AFC. AMH and AFC appear to be valuable markers mainly for ovarian reserve and response to IVF treatment. Serum AMH levels and AFC are significantly associated with the number of retrieved oocytes. Also, a positive correlation with the availability of supernumerary embryos suitable for cryopreservation was observed.

Pregnancy outcome in women with polycystic ovary syndrome comparing the effects of laparoscopic ovarian drilling and clomiphene citrate stimulation in women pre-treated with metformin: a retrospective study

PubMed Central

2010-01-01

Background Ovarian stimulation in women with polycystic ovary syndrome (PCOS) increases the risk for perinatal complications. Ovulation induction by laparoscopic ovarian drilling (LOD) might improve the overall pregnancy outcomes. The aim of our study was to assess the adverse events or effects on pregnancy of LOD and clomiphene citrate (CC) stimulation in patients who received metformin. Methods Setting: Academic research institution. We retrospectively analyzed the courses of 40 spontaneous pregnancies after LOD for CC-resistance, 40 pregnancies after CC stimulation, and 40 pregnancies after metformin treatment alone. Patients in the LOD and the CC groups had been pre-treated with Metformin. Primary outcome parameters were: the rate of multiple pregnancies; the rate of early pregnancy losses/miscarriages; the development of gestational diabetes, pregnancy-induced hypertension, and preeclampsia/HELLP-syndrome; premature delivery; and birth weight. Results The rate of twin pregnancies did not differ between the CC group (12.5%), the LOD group (7.5%), and the metformin only group (2.5%, p = 0.239). Seventeen women suffered an early miscarriage. There were no differences with regard to the rates of gestational diabetes, pregnancy-induced hypertension, preeclampsia, and preterm delivery. By analyzing all pregnancy complications together, the overall pregnancy complication rate was highest in the CC group (70.0%, 28/40), followed by the LOD group (45.0%, 18/40), and the metformin only group (47.5%, 19/40; p = 0.047). Conclusions CC, but not LOD, increases the complication rate in pregnant patients who received metformin. PMID:20465786

Pregnancy outcome in women with polycystic ovary syndrome comparing the effects of laparoscopic ovarian drilling and clomiphene citrate stimulation in women pre-treated with metformin: a retrospective study.

PubMed

Ott, Johannes; Kurz, Christine; Nouri, Kazem; Wirth, Stefan; Vytiska-Binstorfer, Elisabeth; Huber, Johannes C; Mayerhofer, Klaus

2010-05-13

Ovarian stimulation in women with polycystic ovary syndrome (PCOS) increases the risk for perinatal complications. Ovulation induction by laparoscopic ovarian drilling (LOD) might improve the overall pregnancy outcomes. The aim of our study was to assess the adverse events or effects on pregnancy of LOD and clomiphene citrate (CC) stimulation in patients who received metformin. Academic research institution. We retrospectively analyzed the courses of 40 spontaneous pregnancies after LOD for CC-resistance, 40 pregnancies after CC stimulation, and 40 pregnancies after metformin treatment alone. Patients in the LOD and the CC groups had been pre-treated with Metformin. Primary outcome parameters were: the rate of multiple pregnancies; the rate of early pregnancy losses/miscarriages; the development of gestational diabetes, pregnancy-induced hypertension, and preeclampsia/HELLP-syndrome; premature delivery; and birth weight. The rate of twin pregnancies did not differ between the CC group (12.5%), the LOD group (7.5%), and the metformin only group (2.5%, p=0.239). Seventeen women suffered an early miscarriage. There were no differences with regard to the rates of gestational diabetes, pregnancy-induced hypertension, preeclampsia, and preterm delivery. By analyzing all pregnancy complications together, the overall pregnancy complication rate was highest in the CC group (70.0%, 28/40), followed by the LOD group (45.0%, 18/40), and the metformin only group (47.5%, 19/40; p=0.047). CC, but not LOD, increases the complication rate in pregnant patients who received metformin.

National survey of the current management of endometriomas in women undergoing assisted reproductive treatment.

PubMed

Raffi, F; Shaw, R W; Amer, S A

2012-09-01

What is the current management of women with ovarian endometriomas undergoing assisted reproductive treatment (ART) in the UK? It appears that the majority of gynaecologists in the UK offer surgery (mostly cystectomy) for endometriomas prior to ART, regardless of the presence of symptoms. The ideal management of endometriomas in women undergoing ART remains controversial and presents a dilemma to reproductive specialists. This was a national cross-sectional survey. A total of 388 gynaecologists completed the questionnaire. All clinicians fully registered with the Royal College of Obstetricians and Gynaecologists were contacted. An 11-item survey was administered electronically using Survey Monkey software. Quantitative data were analysed using descriptive and comparative statistics. The majority of responders were consultants (65%), 25% practiced ART and 65% performed laparoscopic surgery. Overall, 95% of responders would offer surgery for endometriomas in women undergoing ART, either on the basis of the size (>3-5 cm) of the endometrioma (52%), the presence of symptoms (16%), the presence of multiple/bilateral endometriomas (2%), regardless of the size and symptoms (19%) or only to women undergoing IVF (6%). The remaining 5% of responders would not offer surgery before ART. Excision was the most common surgical modality (68%), followed by ablation (25%). Laparoscopic surgeons were almost twice as likely to 'offer surgery to all patients with endometriomas prior to ART' compared with clinicians performing laparotomy (22 versus 12%, P < 0.001). Our overall response rate, with answers to the questionnaire, was low (15%). However, the response rate amongst reproductive specialists was estimated at 60%. It is possible that there might have been an element of bias towards over-representation of responders who are more concerned about 'normalization' of the pelvic anatomy. Furthermore, our survey relied on self-reporting of practice and it is possible that being presented with a list of 'ideal' options may have resulted in respondent bias. Despite the available evidence that surgery for endometriomas does not improve the outcome of ART and may damage ovarian reserve, it seems that the majority of gynaecologists in the UK offer ovarian cystectomy to their patients.

Accidental ovarian autograft after a laparoscopic surgery: case report.

PubMed

Marconi, G; Quintana, R; Rueda-Leverone, N G; Vighi, S

1997-08-01

To report an autograft of ovarian tissue in the incision of the surgical trocar during laparoscopic surgery and to assess the potentiality of grafting of ovarian parenchyma in nonpelvic tissue in humans. A case report. Instituto de Fertilidad y Ginecología de Buenos Aires (IFER), Buenos Aires, Argentina. Infertile patient undergoing surgery due to an endometriotic cyst of the left ovary. Laparoscopic cystectomy. Accidental retention of a portion of the capsule and adjacent ovarian tissue of the endometrioma in SC cellular tissue. Months after surgery, a SC tumor was formed under the surgical incision. It was subsequently excised. Observation of tumor growth during menstrual cycles and ovulation induction; anatomopathologic study of the tissue after its extirpation. The tumor grew spontaneously in the periovulatory period and during treatments of ovulation induction. The anatomopathologic report of the tumor, removed 15 months after the first surgery, revealed functioning ovarian tissue with vessels of neoformation. This is the first description of autografted ovarian tissue in humans. We describe that the ovary can maintain its ovulatory function even in the absence of its pedicel. Also, we suggest that extirpation of surgical material through the incision of the trocar is not recommended, as the possibility of "sowing" or of autografts may occur.

Effectiveness of acupuncture in women with polycystic ovarian syndrome undergoing in vitro fertilisation or intracytoplasmic sperm injection: a systematic review and meta-analysis.

PubMed

Jo, Junyoung; Lee, Yoon Jae

2017-06-01

The aim of this systematic review was to assess the evidence from randomised controlled trials (RCTs) on the efficacy, effectiveness and safety of acupuncture in women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). We searched a total of 15 databases through October 2015. The participants were women with PCOS (diagnosed using the Rotterdam criteria) undergoing IVF or ICSI. Eligible trials were those with intervention groups receiving manual acupuncture (MA) or electroacupuncture (EA), and control groups receiving sham acupuncture, no treatment or other treatments. Outcomes included the clinical pregnancy rate (CPR), live birth rate (LBR), ongoing pregnancy rate (OPR) and incidence of ovarian hyperstimulation syndrome (OHSS) and adverse events (AEs). For statistical pooling, the risk ratio (RR) and its 95% (confidence interval) CI was calculated using a random effects model. Four RCTs including 430 participants were selected. All trials compared acupuncture (MA/EA) against no treatment. Acupuncture significantly increased the CPR (RR 1.33, 95% CI 1.03 to 1.71) and OPR (RR 2.03, 95% CI 1.08 to 3.81) and decreased the risk of OHSS (RR 0.63, 95% CI 0.42 to 0.94); however, there was no significant difference in the LBR (RR 1.61, 95% CI 0.73 to 3.58). None of the RCTs reported on AEs. Acupuncture may increase the CPR and OPR and decrease the risk of OHSS in women with PCOS undergoing IVF or ICSI. Further studies are needed to confirm the efficacy and safety of acupuncture as an adjunct to assisted reproductive technology in this particular population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

A new surgical approach of temporary ovarian transposition for children undergoing brachytherapy: technical assessment and dose evaluation.

PubMed

de Lambert, Guénolée; Haie-Meder, Christine; Guérin, Florent; Boubnova, Julia; Martelli, Hélène

2014-07-01

We developed a new technique of temporary ovarian transposition (OT) for prepubertal girls undergoing brachytherapy. The aim of this study was to describe it, assess its feasibility and safety and calculate the dose delivered to the ovary in order to prove its efficacy. Sixteen prepubertal patients underwent temporary OT for brachytherapy at our center from March 2001 to December 2012. OT was done either by laparotomy or by laparoscopy. In all patients, the ovaries were grasped with an atraumatic forceps and mobilized above the iliac crest level as high as possible without any dissection or division of the ovarian ligaments or of the fallopian tube. They were sutured to the anterior abdominal wall by a transfixing stitch of non-dissolvable suture knotted on the outside of the patient on a pledget. Median age at surgery was 3 years (range: 2-9 years). The integrity of the fallopian tube was respected and not a single ligament was dissected or divided. None of the patients had intraoperative or postoperative complications. The stitches were retrieved after completion of irradiation and the ovaries in all the patients fell back into the pelvis. The calculated median radiation dose to the ovary was 1.4 Gy (range: 0.4-2.4 Gy). This surgical technique is simple and safe, either by laparotomy or by laparoscopy. It meets the radiation and physical constraints in prepubertal girls with vaginal or bladder RMS. However, longer follow-up is required to assess the ovarian function. Copyright © 2014 Elsevier Inc. All rights reserved.

[Effects of electroacupuncture of "Guanyuan" (CV 4)-"Zhongji" (CV 3) on ovarian P450 arom and P450c 17alpha expression and relevant sex hormone levels in rats with polycystic ovary syndrome].

PubMed

Sun, Jie; Zhao, Ji-meng; Ji, Rong; Liu, Hui-rong; Shi, Yin; Jin, Chun-lan

2013-12-01

To observe the effect of electroacupuncture (EA) on ovarian P 450 arom and P 450 c 17 alpha (aromatases) expression and related sex hormone levels in polycystic ovary syndrome (PCOS) rats. Thirty SD rats were randomly divided into normal control group, model group and EA group (10 rats/group). PCOS model was made by intragastric administration of letrozole at 1 mg/kg per day for consecutive 21 days. "Guanyuan" (CV 4) and "Zhongji" (CV 3) acupoints were stimulated 20 min by EA (2 mA, 2 Hz), once daily for consecutive 14 days. The damp ovarian weight was weighed and the pathological changes of the ovarian tissue were observed after H. E. staining. Ultrastructural changes of the ovarian tissue were observed by transmission electron microscope. Immunohistochemical staining was adopted to detect ovarian follicle granulosa cell P 450 arom and follicle membrane cell P 450 c 17 alpha expression. The contents of estradiol (E 2), estrone (E 1), androstenedione (ASD), testosterone (T), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the ovarian tissue were measured by ELISA. Compared with the normal group, there was a significant increase in the damp weight of both left and right ovarian tissues in the model group (P < 0.01). After EA, the ovarian weight was remarkably reduced (P < 0.01). Pathological changes of the ovarian tissue such as thickening of the superficial albugineous coat of the ovary, thinning of the granular cell layer, and disappearance of the intraovular oocytes and coronaradiata under light microscope, and mitochondrion swelling, fracture or disappearance of mitochondrial cristae, and enlargement of the endoplasmic reticulum, etc. after modeling were obviously improved in the EA group. In comparison to the control group, the expression of the follicle granulosa cell P450 arom was significantly down-regulated and that of follicle membrane cell P 450 c 17 alpha was significantly upregulated in the model group (P < 0.01). After EA intervention these changes were obviously reversed (P < 0.05, P < 0.01). In the model group, there was a significant increase in the levels of ASD, T and LH in the ovarian tissues (P < 0.01) and a marked decrease in the contents of ovarian E 1 and E2 (P < 0.01) in comparison to the control group. After EA, the ovarian ASD, T and LH levels were notably decreased (P < 0.05, P < 0.01) and the E 1 and E 2 levels apparently increased (P < 0.01) compared with the model group. EA can improve letrozole-induced pathological changes of ovarian morphology and ultrastructure and obviously promote P 450 arom expression in the follicle granulosa cell layer and inhibit P 450 c 17 alpha expression in the follicle membrane cell layer, as well as regulate sex hormone levels in PCOS rats, facilitating the normal transformation of ovarian androgen to estrogen and restoring the local endocrine disorders.

Comparisons of mRNA expression for insulin-like growth factor (IGF) type 2 receptor (IGF2R) and IGF-1 in small ovarian follicles between cattle selected and not selected for twin ovulations

USDA-ARS?s Scientific Manuscript database

Both IGF-1 and -2 stimulate ovarian follicular cell proliferation and antral follicle development. Actions of IGF-1 and -2 are mediated through the IGF type 1 receptor, whereas binding of IGF-2 to the IGF2R results in its degradation. Information on the role of IGF2R in regulating bovine follicula...

Inhibition of the CSF-1 receptor sensitizes ovarian cancer cells to cisplatin.

PubMed

Yu, Rong; Jin, Hao; Jin, Congcong; Huang, Xuefeng; Lin, Jinju; Teng, Yili

2018-03-01

Ovarian cancer is one of the most common female malignancies, and cisplatin-based chemotherapy is routinely used in locally advanced ovarian cancer patients. Acquired or de novo cisplatin resistance remains the barrier to patient survival, and the mechanisms of cisplatin resistance are still not well understood. In the current study, we found that colony-stimulating-factor-1 receptor (CSF-1R) was upregulated in cisplatin-resistant SK-OV-3 and CaoV-3 cells. Colony-stimulating-factor-1 receptor knockdown suppressed proliferation and enhanced apoptosis in cisplatin-resistant SK-OV-3 and CaoV-3 cells. However, CSF-1R overexpression had inverse effects. While parental SK-OV-3 and CaoV-3 cells were more resistant to cisplatin after CSF-1R overexpression, CSF-1R knockdown in SK-OV-3 and CaoV-3 cells promoted cisplatin sensitivity. Overexpression and knockdown studies also showed that CSF-1R significantly promoted active AKT and ERK1/2 signalling pathways in cisplatin-resistant cells. Furthermore, a combination of cisplatin and CSF-1R inhibitor effectively inhibited tumour growth in xenografts. Taken together, our results provide the first evidence that CSF-1R inhibition can sensitize cisplatin-refractory ovarian cancer cells. This study may help to increase understanding of the molecular mechanisms underlying cisplatin resistance in tumours. Copyright © 2018 John Wiley & Sons, Ltd.

Patients' Views of Treatment-Focused Genetic Testing (TFGT): Some Lessons for the Mainstreaming of BRCA1 and BRCA2 Testing.

PubMed

Wright, Sarah; Porteous, Mary; Stirling, Diane; Lawton, Julia; Young, Oliver; Gourley, Charlie; Hallowell, Nina

2018-05-11

This paper explores patients' views and experiences of undergoing treatment-focused BRCA1 and BRCA2 genetic testing (TFGT), either offered following triaging to clinical genetics (breast cancer) or as part of a mainstreamed care pathway in oncology (ovarian cancer). Drawing on 26 in-depth interviews with patients with breast or ovarian cancer who had undergone TFGT, this retrospective study examines patients' views of genetic testing at this point in their care pathway, focusing on issues, such as initial response to the offer of testing, motivations for undergoing testing, and views on care pathways. Patients were amenable to the incorporation of TFGT at an early stage in their cancer care irrespective of (any) prior anticipation of having a genetic test or family history. While patients were glad to have been offered TFGT as part of their care, some questioned the logic of the test's timing in relation to their cancer treatment. Crucially, patients appeared unable to disentangle the treatment role of TFGT from its preventative function for self and other family members, suggesting that some may undergo TFGT to obtain information for others rather than for self.

Progesterone levels in letrozole associated controlled ovarian stimulation for fertility preservation in breast cancer patients.

PubMed

Goldrat, O; Gervy, C; Englert, Y; Delbaere, A; Demeestere, I

2015-09-01

Are progesterone levels after letrozole-associated controlled ovarian stimulation (COS) for fertility preservation in breast cancer patients, lower than after standard in vitro fertilization (IVF) cycles? During the luteal phase of letrozole-associated COS cycles (triggered with human chorionic gonadotrophin (hCG)) progesterone levels are similarly elevated to those obtained after standard COS without letrozole. Current fertility preservation strategies for breast cancer patients include association of COS with the aromatase inhibitor letrozole to harvest several mature oocytes while maintaining low estradiol levels. Data on progesterone levels are however lacking despite growing evidence of the role of progesterone in breast tumorigenesis. This is a prospective observational study comparing estradiol and progesterone levels of 21 breast cancer patients undergoing letrozole-associated COS with 21 infertile patients undergoing standard COS for IVF and/or intra cytoplasmic sperm injection (ICSI). All patients underwent COS with a GnRH antagonist protocol. In the fertility preservation group, ovulation induction was started in the follicular or luteal phase depending on the chemotherapy schedule and in 10 cases a GnRH antagonist was administered during luteal phase to induce luteolysis. Final oocyte maturation was induced by hCG in all patients. Estradiol and progesterone levels were measured on the day of hCG, at oocyte retrieval, and on days 3 and 8 after oocyte retrieval. Hormone levels in fertility preservation patients were compared with those observed in infertility patients. While estradiol levels were significantly lower in the fertility preservation group compared with the control group (P < 0.001), progesterone levels were similar at all times, including patients receiving a GnRH antagonist during the luteal phase. The studied populations (breast cancer and infertile patients) are different, which may induce selection bias. The small sample size limits the study's statistical power and the possibility to perform multivariate analysis. Recruitment of the study and control patients was completed at the same time; however, enrollment of controls started at a later time. While the use of letrozole in fertility preservation patients has a favorable effect on estrogen levels, no benefit is seen for progesterone levels which are high and comparable with progesterone levels after standard COS in IVF patients. As progesterone has been associated with tumor cell proliferation, caution is mandatory. Modified protocols including GnRH agonist triggering should be investigated. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Genetic aspects of premature ovarian failure].

PubMed

Warenik-Szymankiewicz, Alina; Słopień, Radosław

2005-01-01

Among the causes of premature ovarian failure (POF) two groups of factors are reported: factors which lead to decrease of follicular number and factors which stimulate follicular atresia. In the first group genetic factors are the most important whereas in the second: enzymatic autoimmunological, iatrogenic, toxins and infections are reported. In 1986 familiar POF on the background of long arm of chromosome X deletion was reported. Other chromosomes which are important for normal ovarian function are: chromosome 21 (AIRE gene), chromosome 11 (gene of beta FSH, ATM gene), chromosome 3 (gene responsible for BEPS syndrome) and chromosome 2 (genes of FSH and LH receptors). In this review the role of these genes and results of several epidemiological studies are reported.

Interleukin-8 stimulates progesterone production via the MEK pathway in ovarian theca cells.

PubMed

Shimizu, Takashi; Imamura, Eri; Magata, Fumie; Murayama, Chiaki; Miyamoto, Akio

2013-02-01

Interleukin 8 (IL-8) is a chemoattractant associated with ovulation in the mammalian ovary. This chemokine is also involved in the recruitment and activation of neutrophils. Using bovine tissue, we examined the possible role of IL-8 in steroid production by theca cells of the large ovarian follicles. IL-8 promoted progesterone production and stimulated StAR expression in cultured theca cells. The inhibitor of p38 did not disturb the P4 production and StAR expression in IL-8-treated theca cells. On the other hand, the inhibitor of MEK disturbed the P4 production and expression of StAR in theca cells treated with IL-8. These results suggest that IL-8 is associated with progesterone production in bovine theca cells via the MEK pathway.

Microenvironment mesenchymal cells protect ovarian cancer cell lines from apoptosis by inhibiting XIAP inactivation

PubMed Central

Castells, M; Milhas, D; Gandy, C; Thibault, B; Rafii, A; Delord, J-P; Couderc, B

2013-01-01

Epithelial ovarian carcinoma is characterized by high frequency of recurrence (70% of patients) and carboplatin resistance acquisition. Carcinoma-associated mesenchymal stem cells (CA-MSC) have been shown to induce ovarian cancer chemoresistance through trogocytosis. Here we examined CA-MSC properties to protect ovarian cancer cells from carboplatin-induced apoptosis. Apoptosis was determined by Propidium Iodide and Annexin-V-FITC labelling and poly-ADP-ribose polymerase cleavage analysis. We showed a significant increase of inhibitory concentration 50 and a 30% decrease of carboplatin-induced apoptosis in ovarian cancer cells incubated in the presence of CA-MSC-conditioned medium (CM). A molecular analysis of apoptosis signalling pathway in response to carboplatin revealed that the presence of CA-MSC CM induced a 30% decrease of effector caspases-3 and -7 activation and proteolysis activity. CA-MSC secretions promoted Akt and X-linked inhibitor of apoptosis protein (XIAP; caspase inhibitor from inhibitor of apoptosis protein (IAP) family) phosphorylation. XIAP depletion by siRNA strategy permitted to restore apoptosis in ovarian cancer cells stimulated by CA-MSC CM. The factors secreted by CA-MSC are able to confer chemoresistance to carboplatin in ovarian cancer cells through the inhibition of effector caspases activation and apoptosis blockade. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway and the phosphorylation of its downstream target XIAP underlined the implication of this signalling pathway in ovarian cancer chemoresistance. This study reveals the potentialities of targeting XIAP in ovarian cancer therapy. PMID:24176845

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI).

PubMed

Kwan, Irene; Bhattacharya, Siladitya; Kang, Angela; Woolner, Andrea

2014-08-24

Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) treatment has included transvaginal ultrasonography (TVUS) plus serum estradiol levels to ensure safe practice by reducing the incidence and severity of ovarian hyperstimulation syndrome (OHSS) whilst achieving the good ovarian response needed for assisted reproduction treatment. The need for combined monitoring (using TVUS and serum estradiol) during ovarian stimulation in assisted reproduction is controversial. It has been suggested that combined monitoring is time consuming, expensive and inconvenient for women and that simplification of IVF and ICSI therapy by using TVUS only should be considered. To assess the effect of monitoring controlled ovarian hyperstimulation (COH) in IVF and ICSI cycles in subfertile couples with TVUS only versus TVUS plus serum estradiol concentration, with respect to rates of live birth, pregnancy and OHSS. We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, the National Research Register, and web-based trial registers such as Current Controlled Trials. The last search was conducted in May 2014. There was no language restriction applied. All references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data. Only randomised controlled trials that compared monitoring with TVUS only versus TVUS plus serum estradiol concentrations in women undergoing COH for IVF and ICSI treatment were included. Three review authors independently selected the studies, extracted data and assessed risk of bias. They resolved disagreements by discussion with the rest of the authors. Outcomes data were pooled and summary statistics were presented when appropriate. The quality of the evidence was rated using the GRADE methods. With this update, four new studies were identified resulting in a total of six trials including 781 women undergoing monitoring of COH with either TVUS alone or a combination of TVUS and serum estradiol concentration during IVF or ICSI treatment.None of the six studies reported our primary outcome of live birth rate. Pooled data showed no evidence of a difference in clinical pregnancy rate per woman between monitoring with TVUS only and combined monitoring (odds ratio (OR) 1.10; 95% confidence interval (CI) 0.79 to 1.54; four studies; N = 617; I² = 5%; low quality evidence). This suggests that compared with women with a 34% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate in women using TVUS only was between 29% and 44%.There was no evidence of a difference between the groups in the reported cases of OHSS (OR 1.03; 95% CI 0.48 to 2.20; six studies; N = 781; I² = 0%; low quality evidence), suggesting that compared with women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate in women monitored by TVUSS only was between 2% and 8%.There was no evidence of a difference between the groups in the mean number of oocytes retrieved pre woman (mean difference (MD) 0.32; 95% CI -0.60 to 1.24; five studies; N = 596; I² = 17%; low quality evidence).The evidence was low quality for all comparisons. Limitations included imprecision and potential bias due to unclear randomisation methods, allocation concealment and blinding, as well as differences in treatment protocols. Quality assessment was hampered by the lack of methodological descriptions in several studies. This review update found no evidence from randomised trials to suggest that combined monitoring by TVUS and serum estradiol is more efficacious than monitoring by TVUS alone with regard to clinical pregnancy rates and the incidence of OHSS. The number of oocytes retrieved appeared similar for both monitoring protocols. The data suggest that both these monitoring methods are safe and reliable. However, these results should be interpreted with caution because the overall quality of the evidence was low. Results were compromised by imprecision and poor reporting of study methodology. A combined monitoring protocol including both TVUS and serum estradiol may need to be retained as precautionary good clinical practice and as a confirmatory test in a subset of women to identify those at high risk of OHSS. An economic evaluation of the costs involved with the two methods and the views of the women undergoing cycle monitoring would be welcome.

Repeated superovulation increases the risk of osteoporosis and cardiovascular diseases by accelerating ovarian aging in mice.

PubMed

Zhang, Jinjin; Lai, Zhiwen; Shi, Liangyan; Tian, Yong; Luo, Aiyue; Xu, Zheyuan; Ma, Xiangyi; Wang, Shixuan

2018-05-22

Superovulation procedures and assisted reproductive technologies have been widely used to treat couples who have infertility problems. Although generally safe, the superovulation procedures are associated with a series of complications, such as ovarian hyper-stimulation syndrome, thromboembolism, and adnexal torsion. The role of long-term repeated superovulation in ovarian aging and especially in associated disorders such as osteoporosis and cardiovascular diseases is still unclear. In this study, we sought to determine if repeated superovulation by ten cycles of treatment with pregnant mare serum gonadotropin/human chorionic gonadotropin could affect ovarian reserve, ovarian function, bone density and heart function. Ovarian reserve and function were reflected by the size of the primordial follicle pool, anti-Mullerian hormone expressions, hormone levels and fertility status. Furthermore, we examined bone density and heart function by microCT and cardiovascular ultrasonography, respectively. After repeated superovulation, the size of the primordial follicle pool and the expression of anti-mullerian hormone decreased, along with the concentrations of estrogen and progesterone. Mice exposed to repeated superovulation showed an obvious decrease in fertility and fecundity. Furthermore, both bone density and heart ejection fraction significantly decreased. These results suggest that repeated superovulation may increase the risk of osteoporosis and cardiovascular diseases by accelerating ovarian aging.

Anti-Mullerian Hormone: A Marker of Ovarian Reserve and its Association with Polycystic Ovarian Syndrome.

PubMed

Verma, Anil Kumar; Rajbhar, Sarita; Mishra, Jyoti; Gupta, Mayank; Sharma, Mratunjai; Deshmukh, Geeta; Ali, Wahid

2016-12-01

Anti-Mullerian Hormone (AMH) is a useful endocrine marker for assessing the ovarian reserve. AMH serum level reflects the number of follicles that have made the transition from the primordial pool into the growing follicle pool, and it is not controlled by gonadotropins. The present study was conducted to correlate serum AMH levels with Polycystic Ovarian Syndrome (PCOS) and type of treatment protocol. Serum AMH levels were performed in the early follicular phase (on 2 nd day of menstrual cycle) both in infertile females including PCOS and control women. The results were analyzed in relation to age, Body Mass Index (BMI), ovarian volume, serum Follicle Stimulating Hormone (FSH) levels, Antral Follicle Count (AFC), type of treatment protocols and also in association with PCOS patients. The serum levels of AMH were measured in all the participants on 2 nd day of menstrual cycle using ultra sensitive Enzyme Linked Immunosorbent Assay (ELISA). The plasma AMH levels were significantly higher in women with polycystic ovarian syndrome. The significant association was seen between FSH and AFC with AMH. However, no significant association was observed between AMH levels with age, BMI, ovarian volume and type of treatment protocols. The serum AMH measurement was significantly higher in PCOS patients. No association with type of treatment protocol was obtained.

Evaluation of the effects of hyaluronic acid-carboxymethyl cellulose barrier on ovarian tumor progression

PubMed Central

2014-01-01

Background Hyaluronic acid is a prognostic factor in ovarian cancers. It is also a component of Hyaluronic Acid-Carboxymethyl Cellulose (HA-CMC) barrier, an anti-adhesion membrane widely used during abdominal surgeries in particular for ovarian carcinosis. 70% of patients who undergo ovarian surgery will relapse due to the persistence of cancer cells. This study’s objective was to determine the oncological risk from use of this material, in the presence of residual disease, despite the benefit gained by it decreasing post-surgical adhesions in order to provide an unambiguous assessment of its appropriateness for use in ovarian surgical management. Methods We assessed the effects of HA-CMC barrier on the in vitro proliferation of human ovarian tumor cell lines (OVCAR-3, IGROV-1 and SKOV-3). We next evaluated, in vivo in nude mice, the capacity of this biomaterial to regulate the tumor progression of subcutaneous and intraperitoneal models of ovarian tumor xenografts. Results We showed that HA-CMC barrier does not increase in vitro proliferation of ovarian cancer cell lines compared to control. In vivo, HA-CMC barrier presence with subcutaneous xenografts induced neither an increase in tumor volume nor cell proliferation (Ki67 and mitotic index). With the exception of an increased murine carcinosis score in peritoneum, the presence of HA-CMC barrier with intraperitoneal xenografts modified neither macro nor microscopic tumor growth. Finally, protein analysis of survival (Akt), proliferation (ERK) and adhesion (FAK) pathways highlighted no activation on the xenografts imputable to HA-CMC barrier. Conclusions For the most part, our results support the lack of tumor progression activation due to HA-CMC barrier. We conclude that the benefits gained from using HA-CMC barrier membrane during ovarian cancer surgeries seem to outweigh the potential oncological risks. PMID:24739440

Differential roles of MAPK-Erk1/2 and MAPK-p38 in insulin or insulin-like growth factor-I (IGF-I) signaling pathways for progesterone production in human ovarian cells.

PubMed

Seto-Young, D; Avtanski, D; Varadinova, M; Park, A; Suwandhi, P; Leiser, A; Parikh, G; Poretsky, L

2011-06-01

Insulin and insulin like-growth factor-I (IGF-I) participate in the regulation of ovarian steroidogenesis. In insulin resistant states ovaries remain sensitive to insulin because insulin can activate alternative signaling pathways, such as phosphatidylinositol-3-kinase (PI-3 kinase) and mitogen-activated protein-kinase (MAPK) pathways, as well as insulin receptors and type 1 IGF receptors. We investigated the roles of MAPK-Erk1/2 and MAPK-p38 in insulin and IGF-I signaling pathways for progesterone production in human ovarian cells. Human ovarian cells were cultured in tissue culture medium in the presence of varying concentrations of insulin or IGF-I, with or without PD98059, a specific MAPK-Erk1/2 inhibitor, with or without SB203580, a specific MAPK-p38 inhibitor or with or without a specific PI-3-kinase inhibitor LY294002. Progesterone concentrations were measured using radioimmunoassay. PD98059 alone stimulated progesterone production in a dose-dependent manner by up to 65% (p<0.001). Similarly, LY294002 alone stimulated progesterone production by 13-18% (p<0.005). However, when used together, PD98059 and LY294002 inhibited progesterone production by 17-20% (p<0.001). SB203580 alone inhibited progesterone production by 20-30% (p<0.001). Insulin or IGF-I alone stimulated progesterone production by 40-60% (p<0.001). In insulin studies, PD98059 had no significant effect on progesterone synthesis while SB203580 abolished insulin-induced progesterone production. Either PD98059 or SB203580 abolished IGF-I-induced progesterone production. Both MAPK-Erk1/2 and MAPK-p38 participate in IGF-I-induced signaling pathways for progesterone production, while insulin-induced progesterone production requires MAPK-p38, but not MAPK-Erk1/2. These studies provide further evidence for divergence of insulin and IGF-I signaling pathways for human ovarian cell steroidogenesis. © Georg Thieme Verlag KG Stuttgart · New York.

Molecular profiling and commercial predication assays in ovarian cancer: still not ready for prime time?

PubMed

Kohn, Elise C

2014-01-01

Short of early detection to allow curative primary intervention, the other major barrier to further success in treatment of ovarian cancers is matching the best treatment to the proper ovarian cancer type and to the individual patient. There are several decades of experience applying in vitro chemoresponse testing for solid tumors including ovarian cancer. This concept, first described in 1979, has yet to receive level one evidence supporting its application, despite the testing of numerous assays commercially as well as in academic centers and its use for tens of thousands of patients at a significant cost. The approach-rather than undergoing rigorous scientific examination-is now being muddied by the development of commercial molecular profiling assays from which treatment suggestions are provided. Molecular profiling as a research tool has added value to our understanding and treatment of patients with ovarian cancer. Morphologic and histochemical characterizations coupled now with increasing knowledge of ovarian cancer type-specific molecular patterns is improving our ability to properly diagnosis ovarian cancer type and thus guide therapy. With the exception of the role of germ-line and possibly somatic BRCA1 and BRCA2 mutations and their true predictiveness for probable response to poly(ADP-ribose) polymerase inhibition, molecular typing and profiling has yet to identify druggable molecular targets in ovarian cancer. Its use should be continued as a research and learning tool, and its results should be subjected to clinical trial validation. For very different reasons, neither chemoresponse assays nor molecular profiling are ready for prime time, yet.

Long-term follow-up of patients with an isolated ovarian recurrence after conservative treatment of epithelial ovarian cancer: review of the results of an international multicenter study comprising 545 patients.

PubMed

Bentivegna, Enrica; Fruscio, Robert; Roussin, Stephanie; Ceppi, Lorenzo; Satoh, Toyomi; Kajiyama, Hiroaki; Uzan, Catherine; Colombo, Nicoletta; Gouy, Sebastien; Morice, Philippe

2015-11-01

To determine the long-term outcomes of patients with an isolated ovarian recurrence after fertility sparing surgery (FSS) for epithelial ovarian cancer (EOC) and to evaluate the recurrence rates (and location) according to the new 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system. Retrospective multicenter study. Teams having reported recurrence after FSS for EOC. Four series comprising 545 patients undergoing FSS and 63 (12%) recurrences. FSS (salpingo-oophorectomy for a majority of cases) for EOC. Recurrences rates and characteristics of recurrent disease. Among 63 recurrent patients, 24 (38%) recurrences were isolated on the spared ovary, and 39 (62%) arose at an extraovarian site. Among the patients with an isolated ovarian recurrence, three patients died after a median follow-up period of 186 months (range: 28-294 months). Among the patients with recurrent extraovarian disease, 24 died and 7 were alive with persistent disease after a median follow-up period of 34 months (range: 3-231 months). The overall rate of isolated ovarian and extrapelvic recurrences was higher for grade 3 tumors (compared with grades 1/2). The long-term survival of patients with an isolated ovarian recurrence after FSS for EOC remains favorable. The prognosis of patients with an extraovarian recurrence is poor compared with those who have an isolated recurrent ovarian tumor. Grade 3 tumors (compared to grades 1/2) give rise to a higher rate of extraovarian recurrences. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Examination of diagnostic features in multiphoton microscopy and optical coherence tomography images of ovarian tumorigenesis in a mouse model

NASA Astrophysics Data System (ADS)

Watson, Jennifer M.

Ovarian cancer is a deadly disease owing to the non-specific symptoms and suspected rapid progression, leading to frequent late stage detection and poor prognosis. Medical imaging methods such as CT, MRI and ultrasound as well as serum testing for cancer markers have had extremely poor performance for early disease detection. Due to the poor performance of available screening methods, and the impracticality and ineffectiveness of taking tissue biopsies from the ovary, women at high risk for developing ovarian cancer are often advised to undergo prophylactic salpingo-oophorectomy. This surgery results in many side effects and is most often unnecessary since only a fraction of high risk women go on to develop ovarian cancer. Better understanding of the early development of ovarian cancer and characterization of morphological changes associated with early disease could lead to the development of an effective screening test for women at high risk. Optical imaging methods including optical coherence tomography (OCT) and multiphoton microscopy (MPM) are excellent tools for studying disease progression owing to the high resolution and depth sectioning capabilities. Further, these techniques are excellent for optical biopsy because they can image in situ non-destructively. In the studies described in this dissertation OCT and MPM are used to identify cellular and tissue morphological changes associated with early tumor development in a mouse model of ovarian cancer. This work is organized into three specific aims. The first aim is to use the images from the MPM phenomenon of second harmonic generation to quantitatively examine the morphological differences in collagen structure in normal mouse ovarian tissue and mouse ovarian tumors. The second aim is to examine the differences in endogenous two-photon excited fluorescence in normal mouse ovarian tissue and mouse ovarian tumors. The third and final aim is to identify changes in ovarian microstructure resulting from early disease development by imaging animals in vivo at three time points during a long-term survival study.

Induction of a menopausal state alters the growth and histology of ovarian tumors in a mouse model of ovarian cancer.

PubMed

Laviolette, Laura A; Ethier, Jean-François; Senterman, Mary K; Devine, Patrick J; Vanderhyden, Barbara C

2011-05-01

Ovarian cancer is often diagnosed in women after menopause when the levels of the serum gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are increased because of the depletion of growing follicles within the ovary. The ability of FSH and LH to modulate the disease has not been well studied owing to a lack of physiologically relevant models of ovarian cancer. In this study, 4-vinylcyclohexene diepoxide (VCD) was used to deplete ovarian follicles and increase the levels of circulating FSH and LH in the tgCAG-LS-TAg mouse model of ovarian cancer. VCD-induced follicle depletion was performed either before or after induction of the oncogene SV40 large and small T-antigens in the ovarian surface epithelial cells of tgCAG-LS-TAg mice, which was mediated by the intrabursal delivery of an adenovirus expressing Cre recombinase (AdCre). tgCAG-LS-TAg mice injected with AdCre developed undifferentiated ovarian tumors with mixed epithelial and stromal components and some features of sex cord stromal tumors. Treatment with VCD before or after AdCre injection yielded tumors of similar histology, but with the unique appearance of Sertoli cell nests. In mice treated with VCD before the induction of tumorigenesis, the ovarian tumors tended to grow more slowly. The human ovarian cancer cell lines SKOV3 and OVCAR3 responded similarly to increased levels of gonadotropins in a second model of menopause, growing more slowly in ovariectomized mice compared with cycling controls. These results suggest that follicle depletion and increased gonadotropin levels can alter the histology and the rate of growth of ovarian tumors.

Development of molecular markers for zebrafish (Danio rerio) ovarian follicle growth assessment following in-vitro culture in cryopreservation studies.

PubMed

Anil, Siji; Rawson, David; Zhang, Tiantian

2018-05-29

Development of in vitro culture protocol for early stage ovarian follicles of zebrafish is important since cryopreserved early stage ovarian follicles would need to be matured in vitro following cryopreservation before they can be fertilised. Development of molecular markers for zebrafish (Danio rerio) ovarian follicle growth assessment following in vitro culture of early stage zebrafish ovarian follicles in ovarian tissue fragments is reported here for the first time although some work has been reported for in vitro culture of isolated early stage zebrafish ovarian follicles. The main aim of the present study was to develop molecular markers in an optimised in vitro culture protocol for stage I and stage II zebrafish ovarian follicles in ovarian tissue fragments. The effect of concentration of the hormones human chorionic gonadotropin and follicle stimulating hormones, and additives such as Foetal Bovine Serum and Bovine Serum Albumin were studied. The results showed that early stage zebrafish ovarian fragments containing stage I and stage II follicles which are cultured in vitro for 24 h in 20% FBS and 100mIU/ml FSH in 90% L-15 medium at 28 °C can grow to the size of stage II and stage III ovarian follicles respectively. More importantly the follicle growth from stage I to stage II and from stage II to stage III were confirmed using molecular markers such as cyp19a1a (also known as P450aromA) and vtg1 genes respectively. However, no follicle growth was observed following cryopreservation and in vitro culture. Copyright © 2018 Elsevier Inc. All rights reserved.

Thalidomide distinctly affected TNF-α, IL-6 and MMP secretion by an ovarian cancer cell line (SKOV-3) and primary ovarian cancer cells.

PubMed

Piura, Benjamin; Medina, Liat; Rabinovich, Alex; Dyomin, Victor; Huleihel, Mahmoud

2013-01-01

Thalidomide inhibits TNF-α production in lipopolysaccharide-stimulated monocytes. The aim of this study was to evaluate the effect of thalidomide on TNF-α, IL-6 and MMP secretion in epithelial ovarian carcinoma cells. SKOV-3 cells and primary epithelial ovarian carcinoma cells were cultured in the presence of various concentrations of thalidomide. Cell proliferation was examined by MTT proliferation assay. TNF-α and IL-6 levels were determined in the supernatants of the cell cultures by ELISA, and MMP activity was examined by gelatin zymography. Thalidomide did not significantly affect the proliferation and growth of SKOV-3 cells. However, it decreased significantly the capacity of SKOV-3 cells and primary epithelial ovarian carcinoma cells to secrete TNF-α. Thalidomide also significantly decreased the capacity of SKOV-3 cells, but not primary epithelial ovarian carcinoma cells, to secrete MMP-9 and MMP-2. However, thalidomide did not affect IL-6 secretion in SKOV-3 cells or primary epithelial ovarian carcinoma cells. Our study suggests that thalidomide distinctly affected TNF-α, IL-6 and MMPs secretion by an ovarian carcinoma cell line (SKOV-3) and primary ovarian cancer cells. This might suggest a different susceptibility of these two types of cells to thalidomide, and/or that the mechanisms of secretion of the factors examined are differently regulated in these cells. Our results may deepen our understanding the mechanism/s of action of thalidomide in ovarian carcinoma cells. The results might have important implications in future therapeutic strategies that will incorporate thalidomide and other cytokine inhibitors in the treatment of epithelial ovarian carcinoma.

Ovarian Damage in Young Premenopausal Women Undergoing Chemotherapy for Cancer

ClinicalTrials.gov

2012-03-16

Leukemia; Long-term Effects Secondary to Cancer Therapy in Adults; Long-term Effects Secondary to Cancer Therapy in Children; Lymphoma; Sexual Dysfunction and Infertility; Sexuality and Reproductive Issues; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

The Anti-Mullerian hormone and ovarian cancer.

PubMed

La Marca, Antonio; Volpe, Annibale

2007-01-01

The Anti-Mullerian hormone (AMH), which is produced by fetal Sertoli cells, is responsible for regression of Mullerian ducts, the anlagen for uterus and Fallopian tubes, during male sex differentiation. Ovarian granulosa cells also secrete AMH from late in fetal life. The patterns of expression of AMH and its type II receptor in the post-natal ovary indicate that AMH may play an important role in ovarian folliculogenesis. Recent advances in the physiological role of AMH has stimulated interest in the significance of AMH as a diagnostic marker and therapeutic agent for ovarian cancer. Currently, AMH has been shown to be a circulating marker specifically for granulosa cell tumour (GCT). Its diagnostic performance seems to be very good, with a sensitivity ranging between 76 and 93%. In patients treated for GCT, AMH may be used post-operatively as marker for the efficacy of surgery and for disease recurrence. Based on the physiological inhibitory role of AMH in the Mullerian ducts, it has been proposed that AMH may inhibit epithelial ovarian cancer cell both in vitro and in vivo. These observations will be the basis for future research aiming to investigate the possible clinical role of AMH as neo-adjuvant, or most probably adjuvant, therapy for ovarian cancer.

The novel POSEIDON stratification of 'Low prognosis patients in Assisted Reproductive Technology' and its proposed marker of successful outcome.

PubMed

Humaidan, Peter; Alviggi, Carlo; Fischer, Robert; Esteves, Sandro C

2016-01-01

In reproductive medicine little progress has been achieved regarding the clinical management of patients with a reduced ovarian reserve or poor ovarian response (POR) to stimulation with exogenous gonadotropins -a frustrating experience for clinicians as well as patients. Despite the efforts to optimize the definition of this subgroup of patients, the existing POR criteria unfortunately comprise a heterogeneous population and, importantly, do not offer any recommendations for clinical handling. Recently, the POSEIDON group ( P atient- O riented S trategies E ncompassing I ndividualize D O ocyte N umber) proposed a new stratification of assisted reproductive technology (ART) in patients with a reduced ovarian reserve or unexpected inappropriate ovarian response to exogenous gonadotropins. In brief, four subgroups have been suggested based on quantitative and qualitative parameters, namely, i. Age and the expected aneuploidy rate; ii. Ovarian biomarkers (i.e. antral follicle count [AFC] and anti-Müllerian hormone [AMH]), and iii. Ovarian response - provided a previous stimulation cycle was performed. The new classification introduces a more nuanced picture of the "low prognosis patient" in ART, using clinically relevant criteria to guide the physician to most optimally manage this group of patients. The POSEIDON group also introduced a new measure for successful ART treatment, namely, the ability to retrieve the number of oocytes needed for the specific patient to obtain at least one euploid embryo for transfer. This feature represents a pragmatic endpoint to clinicians and enables the development of prediction models aiming to reduce the time-to-pregnancy (TTP). Consequently, the POSEIDON stratification should not be applied for retrospective analyses having live birth rate (LBR) as endpoint. Such an approach would fail as the attribution of patients to each Poseidon group is related to specific requirements and could only be made prospectively. On the other hand, any prospective approach (i.e. RCT) should be performed separately in each specific group.

Ovarian response to controlled ovarian stimulation in women with different polycystic ovary syndrome phenotypes.

PubMed

Cela, Vito; Obino, Maria Elena Rosa; Alberga, Ylenia; Pinelli, Sara; Sergiampietri, Claudia; Casarosa, Elena; Simi, Giovanna; Papini, Francesca; Artini, Paolo Giovanni

2018-06-01

Controlled ovarian stimulation (COH) in PCOS is a challenge for fertility expert both ovarian hyperstimulation syndrome (OHSS) and oocytes immaturity are the two major complication. Ovarian response to COH vary widely among POCS patients and while some patients are more likely to show resistance to COH, other experienced an exaggerated response. The aim of our study is to investigate a possible correlation between PCOS phenotypes and the variety of ovarian response to COH and ART outcomes in patients with different PCOS phenotypes. We retrospectively analyzed a total of 71 cycles performed in 44 PCOS infertile patients attending ART at Centre of Infertility and Assisted Reproduction of Pisa University between January 2013 and January 2016. Patientsundergoing IVF with GnRH-antagonist protocol and 150-225 UI/days of recombinant FSH; triggering was carried out using 250 mg of recombinant hCG or a GnRH analogous on the basis of the risk to OHSS. We observed that Phenotype B had a tendency to have a greater doses of gonadotropins used respect to all phenotypes. Phenotype A group showed a greater serum estrogen levels compared to all phenotypes groups, a greater number of follicles of diameter between 8-12 mm found by ultrasound on the day of triggering and a greater mean number of freeze embryo. Additionally serum AMH and antral follicles count (AFC) follow the same trend in the different phenotypes ad they were significantly higher in phenotype A and in phenotype D. In conclusion this study shows that the features of PCOS phenotypes reflect the variety of ovarian response to COH as well as the risks to develop OHSS. Serum AMH and AFC are related to the degree of ovulatory dysfunction making these 'added values' in identifying the different PCOS phenotypes. Phenotype A seems to be the phenotype with the higher risk to develop OHSS and the use of GnRH as a trigger seems to improve oocyte quality. To classify PCOS phenotype at diagnosis might help clinicians to identify patients at greater risk of OHSS, customize therapy and subsequently plan the trigger agent.

Photoacoustic characterization of ovarian tissue

NASA Astrophysics Data System (ADS)

Aguirre, Andres; Gamelin, John; Guo, Puyun; Yan, Shikui; Sanders, Mary; Brewer, Molly; Zhu, Quing

2009-02-01

Ovarian cancer has the highest mortality of all gynecologic cancers with a five-year survival rate of only 30%. Because current imaging techniques (ultrasound, CT, MRI, PET) are not capable of detecting ovarian cancer early, most diagnoses occur in later stages (III/IV). Thus many women are not correctly diagnosed until the cancer becomes widely metastatic. On the other hand, while the majority of women with a detectable ultrasound abnormality do not harbor a cancer, they all undergo unnecessary oophorectomy. Hence, new imaging techniques that can provide functional and molecular contrasts are needed for improving the specificity of ovarian cancer detection and characterization. One such technique is photoacoustic imaging, which has great potential to reveal early tumor angiogenesis through intrinsic optical absorption contrast from hemoglobin or extrinsic contrast from conjugated agents binding to appropriate molecular receptors. To better understand the cancer disease process of ovarian tissue using photoacoustic imaging, it is necessary to first characterize the properties of normal ovarian tissue. We have imaged ex-vivo ovarian tissue using a 3D co-registered ultrasound and photoacoustic imaging system. The system is capable of volumetric imaging by means of electronic focusing. Detecting and visualizing small features from multiple viewing angles is possible without the need for any mechanical movement. The results show strong optical absorption from vasculature, especially highly vascularized corpora lutea, and low absorption from follicles. We will present correlation of photoacoustic images from animals with histology. Potential application of this technology would be the noninvasive imaging of the ovaries for screening or diagnostic purposes.

Body weight changes in patients undergoing chemotherapy for ovarian cancer influence progression-free and overall survival.

PubMed

Mardas, Marcin; Stelmach-Mardas, Marta; Madry, Radosław

2017-03-01

The aim of this study was to evaluate whether body weight changes in patients undergoing chemotherapy for epithelial ovarian cancer (EOC) influence progression-free survival (PFS) and overall survival (OS). An analysis of 190 patients diagnosed with ovarian cancer after first-line chemotherapy was conducted. Changes in body weight were assessed by comparing measurements at baseline to those of the third and sixth cycles of chemotherapy. PFS and OS were calculated with the Kaplan-Meier method and multivariate Cox model. Significant reduction in body weight in advanced EOC was observed with no changes in early EOC. Significant differences in PFS were observed in advanced EOC patients that lost more than 5 % of their body weight (6 months), maintained weight (13 months), or gained more than 5 % of their body weight (15 months). Similarly, significant differences in OS were noted in advanced EOC at the following time points: 24.3, 42.4, and 66.2 months. No effect was reported for early EOC patients. The multivariate Cox analysis showed significant body weight changes from the first to the sixth chemotherapy cycle for PFS (HR = 0.97; 95 % CI 0.95-0.99) and OS (HR = 0.94; 95 % CI 0.91-0.97) as well as from the first to the third chemotherapy cycle for OS (HR = 0.93; 95 % CI 0.88-0.98). Body weight changes can be recognized as a prognostic factor for PFS and OS in advanced EOC patients undergoing chemotherapy. Weight loss is associated with poorer survival while weight gain improved outcomes.

A score system for complete cytoreduction in selected recurrent ovarian cancer patients undergoing secondary cytoreductive surgery: predictors- and nomogram-based analyses.

PubMed

Bogani, Giorgio; Tagliabue, Elena; Signorelli, Mauro; Ditto, Antonino; Martinelli, Fabio; Chiappa, Valentina; Mosca, Lavinia; Sabatucci, Ilaria; Leone Roberti Maggiore, Umberto; Lorusso, Domenica; Raspagliesi, Francesco

2018-05-01

To test the applicability of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) and Memorial Sloan Kettering (MSK) criteria in predicting complete cytoreduction (CC) in patients undergoing secondary cytoreductive surgery (SCS) for recurrent ovarian cancer (ROC). Data of consecutive patients undergoing SCS were reviewed. The Arbeitsgemeinschaft Gynäkologische Onkologie OVARian cancer study group (AGO-OVAR) and MSK criteria were retrospectively applied. Nomograms, based on AGO criteria, MSK criteria and both AGO and MSK criteria were built in order to assess the probability to achieve CC at SCS. Overall, 194 patients met the inclusion criteria. CC was achieved in 161 (82.9%) patients. According to the AGO-OVAR criteria, we observed that CC was achieved in 87.0% of patients with positive AGO score. However, 45 out of 71 (63.4%) patients who did not fulfilled the AGO score had CC. Similarly, CC was achieved in 87.1%, 61.9% and 66.7% of patients for whom SCS was recommended, had to be considered and was not recommended, respectively. In order to evaluate the predictive value of the AGO-OVAR and MSK criteria we built 2 separate nomograms (c-index: 0.5900 and 0.5989, respectively) to test the probability to achieve CC at SCS. Additionally, we built a nomogram using both the aforementioned criteria (c-index: 0.5857). The AGO and MSK criteria help identifying patients deserving SCS. However, these criteria might be strict, thus prohibiting a beneficial treatment in patients who do not met these criteria. Further studies are needed to clarify factors predicting CC at SCS. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Reactive oxygen species level in follicular fluid--embryo quality marker in IVF?

PubMed

Das, S; Chattopadhyay, R; Ghosh, S; Ghosh, S; Goswami, S K; Chakravarty, B N; Chaudhury, K

2006-09-01

The impact of oxidative stress in female reproduction is not clear. Contradictory reports on the effect of various oxidative stress markers on follicular fluid, oocytes and embryo quality and fertilization potential exist. The objectives of this study were to examine reactive oxygen species (ROS) levels in follicular fluid of women undergoing IVF and to relate these levels to embryo formation and quality. A total of 208 follicular fluid samples were obtained from 78 women undergoing controlled ovarian stimulation and analysed for ROS and lipid peroxidation (LPO). These samples were divided into groups I and II which represented follicular fluid containing grade III and grade II oocytes, respectively. These groups were further subdivided into groups IA, IB, IIA and IIB according to embryo quality. Subgroups IA and IIA consisted of follicular fluid samples corresponding to grade I/II embryo formation. Subgroups IB and IIB represented fertilization failure/pro-nucleolus (PN) arrest/grade III embryos. No significant correlation was observed in ROS levels on comparing groups I and II (P > 0.05). However, ROS levels were observed to be significantly different on comparing groups IA and IB (P < or = 0.01) and groups IIA and IIB (P < or = 0.05). LPO levels further supported our results. ROS levels in follicular fluid appear to play a significant role in embryo formation and quality.

The effect of elevated progesterone levels before oocyte retrieval in women undergoing ovarian stimulation for IVF treatment on the genomic profile of peri-implantation endometrium.

PubMed

Liu, Liu; Huang, Jin; Li, Tin Chiu; Hong, Xu Tao; Laird, Susan; Dai, Yong Dong; Tong, Xiao Mei; Zhu, Hai Yan; Zhang, Songying

2017-06-01

To evaluate the effects of high progesterone prior to oocyte retrieval on the genomic profile of peri-implantation endometrium, we conducted this single-center, prospective cohort study. Depending on whether or not the progesterone level on the day of hCG administration and the day after hCG administration were elevated, a total of 20 women undergoing IVF treatment who did not have fresh embryo transfer were included: Group 1 refers to subjects with normal progesterone level on both days; Group 2 refers to subjects with normal progesterone level on the day of hCG administration and high progesterone level on the day after hCG administration; Group 3 refers to subjects with high progesterone level on the day of hCG administration and normal progesterone level on the day after hCG administration; Group 4 refers to subjects with high progesterone level on both days. Five subjects were included in each group. Endometrial samples were obtained 7days after hCG administration. We found that high progesterone level prior to oocyte retrieval predominantly affected components of the NK cell mediated cytotoxicity pathway in the endometrium and that significant differences were only seen when progesterone measurements on both the day of and day after hCG administration were considered together. Copyright © 2017 Elsevier B.V. All rights reserved.

The use of recombinant luteinizing hormone in patients undergoing assisted reproductive techniques with advanced reproductive age: a systematic review and meta-analysis.

PubMed

Hill, Micah J; Levens, Eric D; Levy, Gary; Ryan, Mary E; Csokmay, John M; DeCherney, Alan H; Whitcomb, Brian W

2012-05-01

To evaluate the effect of recombinant LH in assisted reproduction technology (ART) cycles in patients of advanced reproductive age. A systematic review and meta-analysis. Published randomized controlled clinical trials comparing recombinant LH plus recombinant FSH versus recombinant FSH only in patients of advanced reproductive age. Patients 35 years and older undergoing assisted reproduction. Recombinant LH plus recombinant FSH controlled ovarian hyperstimulation (COH) versus recombinant FSH stimulation only in assisted reproduction cycles. Implantation and clinical pregnancy. Seven trials were identified that met inclusion criteria and comprised 902 assisted reproduction technology cycles. No differences in serum E(2) on the day of hCG administration were reported in any trials. Two trials reported lower oocyte yield and one trial reported lower metaphase II oocyte yield in the recombinant LH-supplemented group. One trial reported higher fertilization rates in the recombinant LH-supplemented group. In a fixed effect model, implantation was higher in the recombinant LH-supplemented group (odds ratio 1.36, 95% confidence interval 1.05-1.78). Similarly, clinical pregnancy was increased in the recombinant LH-supplemented group (odds ratio 1.37, 95% confidence interval 1.03-1.83). The addition of recombinant LH to ART cycles may improve implantation and clinical pregnancy in patients of advanced reproductive age. Copyright © 2012 American Society for Reproductive Medicine. All rights reserved.

Assessment of imaging parameters correlated with the effects of cryopreservation on embryo development

NASA Astrophysics Data System (ADS)

Zarnescu, Livia; Abeyta, Mike; Baer, Thomas M.; Behr, Barry; Ellerbee, Audrey K.

2014-03-01

Embryo cryopreservation is an increasingly common technique that allows patients to undergo multiple cycles of in vitro fertilization (IVF) without being subjected to repeated ovarian stimulation and oocyte retrieval. There are two types of cryopreservation commonly used in IVF clinics today: slow freezing and vitrification. Because vitrification has been shown to result in higher rates of embryo survival post-thaw compared to slow freezing, it is rapidly gaining popularity in clinics worldwide. However, several studies have shown that vitrification can still cause damage to embryos in the form of DNA fragmentation, altered mitochondrial distribution and changes in transcriptional activity, all of which are impossible to assess noninvasively. In this paper we demonstrate a new method of quantitatively and noninvasively assessing changes in embryo appearance due to vitrification. Using full-field optical coherence tomography (FF-OCT), we show that vitrification causes striking changes in the appearance of the cytoplasm that are not visible under conventional brightfield microscopy. Using an automated algorithm that extracts parameters to describe these changes, we show that these parameters can also predict viability in embryos that have undergone vitrification. An automated, noninvasive assessment of embryo viability after vitrification and thawing could have significant clinical impact: allowing clinicians to more accurately choose the most viable embryos to transfer back to patients could reduce the average number of IVF cycles that patients must undergo to achieve pregnancy.

Intra-uterine insemination: pregnancy rate in relation to number, size of pre-ovulatory follicles and day of insemination.

PubMed

Karuppaswamy, J; Smedley, Mamin; Carter, Lindsay

2009-03-01

The objective of the study was to analyse the pregnancy rate in intra-uterine insemination (IUI) in relation to pre-ovulatory follicular number, size and day of insemination. A retrospective analysis of 216 completed IUI cycles was used in an attempt to identify significant variables predictive of treatment success. Couples with unexplained infertility and male factor infertility underwent IUI with or without ovarian stimulation. The mean number of IUI cycles per patient was 4.1, the overall pregnancy rate was 27.3% per patient, and the pregnancy rate per cycle was 6.9%. The pregnancy rate was 4.4% when one follicle was produced, whereas with more than two follicles, the rate increased to 21.2%. Hormonal stimulation using clomiphene citrate and/or human menopausal gonadotrophin/follicle stimulating hormone yielded a significant higher pregnancy rate compared to IUI in natural cycles (10.3% versus 3.3%). Although not statistically significant, the pregnancy rate decreased with advancing age of woman. The results suggest that IUI is a useful method of assisted conception in unexplained infertility and higher pregnancy rates can be achieved with good patient selection and ovarian stimulation.

Phosphoinositide 3-Kinase p110δ Mediates Estrogen- and FSH-Stimulated Ovarian Follicle Growth

PubMed Central

Li, Qian; He, Hui; Zhang, Yin-Li; Li, Xiao-Meng; Guo, Xuejiang; Huo, Ran; Bi, Ye; Li, Jing

2013-01-01

In the mammalian ovary, primordial follicles are generated early in life and remain dormant for prolonged periods. Their growth resumes via primordial follicle activation, and they continue to grow until the preovulatory stage under the regulation of hormones and growth factors, such as estrogen, FSH, and IGF-1. Both FSH and IGF-1 activate the phosphatidylinositol-3 kinase (PI3K)/Akt (acute transforming retrovirus thymoma protein kinase) signaling pathway in granulosa cells (GCs), yet it remains inconclusive whether the PI3K pathway is crucial for follicle growth. In this study, we investigated the p110δ isoform (encoded by the Pik3cd gene) of PI3K catalytic subunit expression in the mouse ovary and its function in fertility. Pik3cd-null females were subfertile, exhibited fewer growing follicles and more atretic antral follicles in the ovary, and responded poorly to exogenous gonadotropins compared with controls. Ovary transplantation showed that Pik3cd-null ovaries responded poorly to FSH stimulation in vitro; this confirmed that the follicle growth defect was intrinsically ovarian. In addition, estradiol (E2)-stimulated follicle growth and GC proliferation in preantral follicles was impaired in Pik3cd-null ovaries. FSH and E2 substantially activated the PI3K/Akt pathway in GCs of control mice but not in those of Pik3cd-null mice. However, primordial follicle activation and oocyte meiotic maturation were not affected by Pik3cd knockout. Taken together, our findings indicate that the p110δ isoform of the PI3K catalytic subunit is a key component of the PI3K pathway for both FSH and E2-stimulated follicle growth in ovarian GCs; however, it is not required for primordial follicle activation and oocyte development. PMID:23820902

The Role of Infertility Etiology in Success Rate of Intrauterine Insemination Cycles: An Evaluation of Predictive Factors for Pregnancy Rate

PubMed Central

Ashrafi, Mahnaz; Rashidi, Mandana; Ghasemi, Afsaneh; Arabipoor, Arezoo; Daghighi, Sara; Pourasghari, Parisa; Zolfaghari, Zahra

2013-01-01

Background: The objective of this study was to identify the prognostic factors that influence the outcome of ovarian stimulation with intrauterine insemination (IUI) cycles in couples with different infertility etiology. Materials and Methods: This retrospective study was performed in data of 1348 IUI cycles with ovarian stimulation by clomiphene citrate (CC) and/or gonadotropins in 632 women with five different infertility etiology subgroups at Akbarabbadi Hospital, Tehran, Iran. Results: The pregnancy rate (PR)/ cycle was highest (19.9%) among couples with unexplained infertility and lowest (10.6%) in couples with multiple factors infertility. In cases of unexplained infertility, the best PRs were seen after CC plus gonadotropins stimulation (26.3%) and with inseminated motile sperm count>30×106 (21.9%), but the tendency didn’t reach statistical significant. In the ovarian factor group, the best PRs were observed in women aged between 30 and 34 years (20.8%), with 2-3 preovulatory follicles (37.8%) and infertility duration between 1and 3 years (20.8%), while only infertility duration (p=0.03) and number of preovulatory follicles (p=0.01) were statistically significant. Multiple logistic regression analysis determined that number of preovulatory follicles (p=0.02), duration of infertility (p=0.015), age (p=0.019), infertility etiology (p=0.05) and stimulation regimen (p=0.01) were significant independent factors in order to predict overall clinical PR. Conclusion: The etiology of infertility is important to achieve remarkable IUI success. It is worth mentioning that within different etiologies of infertility, the demographic and cycles characteristics of couples did not show the same effect. Favorable variables for treatment success are as follows: age <40, duration of infertility ≤5 years and a cause of infertility except of multiple factors. PMID:24520471

[Effect of Transcutaneuos Acupoint Electrostimulation on Serum Sex Hormone Levels and Expression of Ovarian Steroid Hormone Metabolic Enzymes in Polycystic Ovary Syndrome Rats].

PubMed

Zhou, Jian-yong; Zhang, Xiao-yue; Yu, Mei-ling; Lu, Sheng-feng; Chen, Xia

2016-02-01

To observe the effect of transcutaneuos acupoint electrostimulation(TAES) on ovarian serum sex hormone levels and ovarian follicle granular cell aromatase cytochrome P 450 (P 450 arom) protein and follicle theca cell cytochrome P 450 17 α-hydroxylase/c 17-20 lyase cytochrome P 450 (P 450 c 17 α) protein expression in polycystic ovary syndrome (PCOS)rats, so as to explore its mechanisms underlying improvement of PCOS. METHODS Forty SD rats were randomly divided into four groups: normal control, model, medication and TAES (10 rats/group). The PCOS model was established by giving (gavage) the animals with letrozole solution (1.0 mg/kg, once daily for 21 consecutive days). Rats of the medication group were treated with Clomiphene (1 mg/kg) once daily for 7 days, and those of the TAES group were treated with electrical stimulation (2 Hz, 3 mA) of "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) areas for 30 min, once daily for 7 consecutive days. The rats body weight and bilateral ovarian weight were detected, and the ovarian structure and follicular development degree were observed under light microscope after H. E. stain, and the serum testosterone (T), estradiol (E2), luteotrophic hormone (LH) and follicle-stimulating hormone (FSH) contents were detected using radioimmunoassay. The expression of ovarian P 450 arom (for production of estrogen)protein and P 450 c 17 α (for production of androgen) protein was detected by using immunohistochemical stain and Western blot, respectively. The body weight, bilateral ovary weight, serum T and LH contents, and ratio of LH/FSH, and ovarian P 450 c 17 α immunoactivity and protein expression levels in the model group were all significantly increased compared with the normal control group (P < 0.01), and the levels of serum E2 and ovarian P 450 arom immunoactivity and protein expression were significantly decreased after modeling (P < 0.01). Following the treatment, the increased body weight, ovary weight, serum T and LH contents, ratio of LH/FSH, and ovarian P 450 c 17 α immunoactivity and protein expression levels, and the decreased ovarian P 450 arom immunoactivity and protein expression levels were reversed in the TAES group (P < 0.01, P < 0.05) rather than in the medication group, except serum T and ratio of LH/FSH in the medication group. No significant differences were found between the medication and TAES groups in the serum T and ratio of LH/FSH (P > 0.05). In addition, the increased vesicular follicle number, the decreased corepus luteum number and the thickness of granular cell layer were markedly improved in the TAES group. TAES intervention can reduce both body weight and ovarian weight and regulate the levels of serum sex hormones and ovarian P 450 c 17 α and P 450 arom protein expression levels in PCOS rats, which may contribute to its effect in improving PCOS.

The impact of luteal phase support on endometrial estrogen and progesterone receptor expression: a randomized control trial

PubMed Central

2012-01-01

Background To assess the impact of luteal phase support on the expression of estrogen receptor (ER) alpha and progesterone receptors B (PR-B) on the endometrium of oocyte donors undergoing controlled ovarian hyperstimulation (COH). Methods A prospective, randomized study was conducted in women undergoing controlled ovarian hyperstimulation for oocyte donation. Participants were randomized to receive no luteal support, vaginal progesterone alone, or vaginal progesterone plus orally administered 17 Beta estradiol. Endometrial biopsies were obtained at 4 time points in the luteal phase and evaluated by tissue microarray for expression of ER alpha and PR-B. Results One-hundred and eight endometrial tissue samples were obtained from 12 patients. No differences were found in expression of ER alpha and PR-B among all the specimens with the exception of one sample value. Conclusions The administration of progesterone during the luteal phase of COH for oocyte donor cycles, either with or without estrogen, does not significantly affect the endometrial expression of ER alpha and PR. PMID:22360924

[Sonographic ovarian vascularization and volume in women with polycystic ovary syndrome treated with clomiphene citrate and metformin].

PubMed

de la Fuente-Valero, Jesús; Zapardiel-Gutiérrez, Ignacio; Orensanz-Fernández, Inmaculada; Alvarez-Alvarez, Pilar; Engels-Calvo, Virginia; Bajo-Arenas, José Manuel

2010-01-01

To measure the vascularization and ovarian volume with three-dimensional sonography in patients diagnosed of polycystic ovary syndrome with stimulated ovulation treatment, and to analyse the differences between the patients treated with clomiphen citrate versus clomiphen citrate and metformin. Therty patients were studied. Twenty ovulation cycles were obtained with clomiphen citrate and 17 with clomiphen citrate plus merformin (added in case of obesity or hyperglucemy/hyperinsulinemia). Ovarian volumes and vascular indexes were studied with 3D-sonography and results were analysed by treatment. There were no statistical differences of ovarian volume by treatment along the cycles, although bigger volume were found in ovulatory cycles compared to non-ovulatory ones (20,36 versus 13,89 ml, p = 0,026). No statistical differences were also found concerning vascular indexes, neither by treatment nor by the obtention of ovulation in the cycle. Ovarian volume and vascular indexes measured with three-dimensional sonography in patients diagnosed of polycystic ovary syndrome do not show differents values in patients treated with clomiphen citrate alone versus clomiphen citrate plus metformin.

Bisphenol A and Ovarian Reserve among Infertile Women with Polycystic Ovarian Syndrome.

PubMed

Zhou, Wei; Fang, Fang; Zhu, Wenting; Chen, Zi-Jiang; Du, Yanzhi; Zhang, Jun

2016-12-27

To better understand possible effects of bisphenol A (BPA) exposure on ovarian reserve in women with polycystic ovary syndrome (PCOS), we measured creatinine adjusted urinary BPA (BPA_Cre) concentrations and used regression models to evaluate the association between urinary BPA level and antral follicle count (AFC), antimullerian hormone (AMH), day-3 follicle stimulating hormone levels (FSH) and inhibin B (INHB) in 268 infertile women diagnosed with PCOS. BPA was detected in all women with a median concentration of 2.35 ng/mL (the 25th and 75th percentiles of 1.47 ng/mL and 3.95 ng/mL). A unit increase in BPA_Cre was associated with a significant decrease of 0.34 in AFC (β = -0.34, 95% CI = -0.60, -0.08; p = 0.01). Likewise, BPA was negatively associated with AMH and day-3 FSH levels, but neither of them reached statistical significance. No association was observed between BPA and INHB. Our results suggest that in women with PCOS, BPA may affect ovarian follicles and, therefore, reduce ovarian reserve.

Amygdala Kindling Alters Estrus Cycle and Ovarian Morphology in the Rat

PubMed Central

Pan, Juan; Zhang, Lingwu; Wang, Feng; Liu, Dan

2014-01-01

The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral seizures were recorded and ovarian morphology was evaluated by light and electron microscopies. Our results showed that the kindled rats lost their ovarian periodicity displayed significant ovarian enlargement. H&E staining revealed increased number of growing follicles and total follicles, as well as polycysts in the ovaries of the kindled animals compared to sham and control animals. Ultrastructural study detected numerous apoptotic granulosa cells in growing follicles and thecal cell hyperplasia with secretary granules in the thecal cells in the kindled rats. The results suggest that amygdala kindling is a risk factor for the development of polycystic ovary syndrome. PMID:25285307

Spontaneous ovarian hyper stimulation syndrome and deep vein thrombosis in a non pregnant woman: case report.

PubMed

Attia, Leila; Azzabi, Samira; Ben Hassine, Lamia; Chachia, Abdelatif; Koubâa, Abdelhamid; Khalfallah, Narjes

2007-12-01

To assess aetiological factors and complications in a patient with severe ovarian hyperstimulation syndrome (OHSS) and internal jugular vein thrombosis. A 27-year-old non pregnant woman with bilateral ovarian masses who had underwent laparotomy for suspicion of malignant tumor. The pathological examination disclosed malignancy and the diagnosis of OHSS were confirmed. The postoperative evolution was complicated by internal jugular, subclavian vein thrombosis and pulmonary embolism. All biological parameters were negative. The evolution was good. The incidence of thromboembolism in women with OHSS is low and the typical finding is deep venous thrombosis in the neck area. Preventive measure of OHSS is very important, and the patients must be treated timely and correctly once OHSS occurs.

Successful surrogate pregnancy after ovarian transposition, pelvic irradiation and hysterectomy.

PubMed

Zinger, Michael; Liu, James H; Husseinzadeh, Nader; Thomas, Michael A

2004-07-01

Treatment of cervical cancer is often effective but at the cost of the woman's fertility. Ovarian transposition with subsequent oocyte retrieval and surrogate pregnancy can enable these patients to become genetic parents. We present the third reported such case. A 22-year-old woman was diagnosed with bulky, stage IB cervical cancer. Following transposition of both ovaries to the upper abdomen, she underwent pelvic irradiation followed by total abdominal hysterectomy. Eleven years later she presented for assisted reproduction. Two oocytes were retrieved following ovarian stimulation and transcutaneous, abdominal oocyte retrieval. One embryo was transferred to the gestational surrogate, resulting in a single intrauterine pregnancy and successful delivery at term. These procedures can preservefertility while successfully treating cervical cancer.

Fertility preservation treatment for young women with autoimmune diseases facing treatment with gonadotoxic agents.

PubMed

Elizur, S E; Chian, R C; Pineau, C A; Son, W Y; Holzer, H E G; Huang, J Y J; Gidoni, Y; Levin, D; Demirtas, E; Tan, S L

2008-10-01

To describe a case series of seven women with SLE and other systemic autoimmune rheumatic diseases (SARDs) who required cyclophosphamide therapy and underwent fertility preservation treatments. Of the seven patients reported here, five women had SLE with nephritis, the sixth had immune thrombocytopenia purpura (ITP) and the seventh had microscopic polyangiitis (MPA) with renal involvement. All women were nulliparous and younger than 35 yrs. Patients with SLE underwent in vitro maturation (IVM) of immature oocytes aspirated during a natural menstrual cycle followed by vitrification of the matured oocytes if a male partner was not available, or vitrification of embryos if one was available. The patient with ITP and the patient with MPA underwent gonadotropin ovarian stimulation followed by oocyte or embryo vitrification. All women completed fertility preservation treatment successfully and mature oocytes or embryos (36 and 13, respectively) were vitrified. No complications were associated with this treatment and cytotoxic therapy was initiated as scheduled in all cases. Oocyte or embryo cryopreservation should be considered for fertility preservation in young women with SARDs who face imminent gonadotoxic treatment. In patients, where gonadotropin ovarian stimulation is deemed unsafe, IVM of immature oocytes, aspirated during a natural menstrual cycle, followed by vitrification or fertilization of the mature oocytes, seems to be safe and feasible. For patients in whom hormonal ovarian stimulation is not contraindicated, this method may be considered depending on the urgency to start cytotoxic therapy.

Impaired Glucose Metabolism in Response to High Fat Diet in Female Mice Conceived by In Vitro Fertilization (IVF) or Ovarian Stimulation Alone

PubMed Central

Chen, Miaoxin; Wu, Linda; Wu, Fang; Wittert, Gary A.; Norman, Robert J.; Robker, Rebecca L.; Heilbronn, Leonie K.

2014-01-01

Individuals conceived by in vitro fertilization (IVF) may be at increased risk of cardio-metabolic disorders. We recently reported that IVF conceived male mice displayed impaired glucose metabolism at normal and high body weights. In this study, we examined glucose metabolism in mature female C57BL/6J mice that were conceived by natural conception (NC), by ovarian stimulation (OS) or by IVF following chow or high-fat diet (HFD) for 8 weeks. By design, litter size was comparable between groups, but interestingly the birth weight of IVF and OS females was lower than NC females (p≤0.001). Mature IVF female mice displayed increased fasting glucose as compared to NC and OS mice, irrespective of diet. Mature IVF and OS mice were also more susceptible to the metabolic consequences of high fat diet as compared with NC females, with impaired glucose tolerance (p≤0.01), whereas peripheral insulin resistance and increased hepatic expression of gluconeogenic genes Ppargc1α, Pck1 and G6pc was observed in IVF mice only (p<0.05). This study suggests that ovarian stimulation alone and IVF program distinct metabolic effects in females, but that high fat diet may be required to unmask these effects. This study adds to the growing body of literature that assisted reproduction procedures may increase the risk of developing type 2 diabetes in an obesity prone environment. PMID:25405530

Impact of ketorolac administration around ovarian stimulation on in vivo and in vitro fertilization and subsequent embryo development.

PubMed

Jee, Byung Chul; Youm, Hye Won; Lee, Jae Ho; Kim, Jee Hyun; Suh, Chang Suk; Kim, Seok Hyun

2013-05-01

We performed this study to investigate the effect of ketorolac (a non-steroidal anti-inflammatory drug) administration around ovarian stimulation on in vivo and in vitro fertilization process. Sixty-four female mice (ICR) were injected with ketorolac (0, 7.5, 15 and 30 µg/d) for 3 d starting from the day of eCG treatment. In experiment 1, 41 mice were triggered by hCG and then mated; two-cell embryos were obtained and in vitro development up to blastocyst was observed. In experiment 2, 23 mice were triggered by hCG and mature oocytes were collected; in vitro fertilization rate and subsequent embryo development up to blastocyst was recorded. In experiment 1, the blastocyst-forming rates per in vivo fertilized two-cell embryo showed an inverse relationship with a dosage of ketorolac (97.6%, 64.2%, 35.4% and 25.9%). In experiment 2, degenerated oocytes were frequently observed in a dose-dependent manner (4.3%, 22.9%, 22.4% and 75.0%). Lower fertilization rates were noted in all the three ketorolac-treating groups; blastocyst-forming rate was significantly lower in 30-µg-treating group when compared with the control group. Administration of ketorolac around ovarian stimulation significantly affects the development of in vivo fertilized embryo in a dose-dependent manner. High-dose ketorolac could result in a poor oocyte quality and decreased embryo developmental competence.

In vitro fertilization treatments with the use of clomiphene citrate or letrozole.

PubMed

Haas, Jigal; Casper, Robert F

2017-10-01

There has been increasing interest in combining the oral agents clomiphene citrate (CC) and letrozole with gonadotropins in IVF: for poor responders to reduce the amount of gonadotropins used, and in normal responders to reduce the incidence of ovarian hyperstimulation (OHSS). In normal responders, mild stimulation with the use of CC and gonadotropins was found to decrease the number of oocytes retrieved and result in good pregnancy rates, but in most studies the cumulative pregnancy rate was lower compared with conventional ovarian stimulation when frozen embryo transfers were considered. Coadministration of letrozole and gonadotropins has mainly been used in patients with breast cancer to prevent the massive elevation of serum E 2 concentrations with the use of standard controlled ovarian hyperstimulation. CC and letrozole have both been used with gonadotropins in poor responders and have been shown to reduce the amount of gonadotropin used without reducing the pregnancy rate. Letrozole use with gonadotropins in IVF cycles may increase endometrial receptivity by increasing integrin expression in the endometrium and by lowering estrogen concentrations to more physiologic levels. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The current challenges to efficient immature oocyte cryopreservation.

PubMed

Brambillasca, Fausta; Guglielmo, Maria Cristina; Coticchio, Giovanni; Mignini Renzini, Mario; Dal Canto, Mariabeatrice; Fadini, Rubens

2013-12-01

Oocyte cryopreservation represents an important tool for assisted reproductive technology. It offers the opportunity to preserve fertility in women at risk of loss of the ovarian function for various pathologies. It also represents a treatment alternative for couples that cannot benefit from embryo cryopreservation because of moral, religious, or legal constrains. On the other hand, in vitro oocyte maturation has a range of applications. It can be applied in patients with a contraindication to ovarian stimulation to prevent ovarian hyperstimulation syndrome or to eliminate the risk of stimulation of hormone-sensitive tumours in cancer patients. However, while mature oocyte cryopreservation has found wide-spread application and oocyte in vitro maturation has a place for the treatment of specific clinical conditions, data on the efficiency of freezing of immature or in vitro matured oocytes are poorer. In this review we will focus on the combination of oocyte in vitro maturation with oocyte cryopreservation with particular emphasis on the biological implications of the cryopreservation of immature or in vitro matured oocytes. The two cryopreservation approaches, slow freezing and vitrification, will be discussed in relation to possible cryodamage occurring to subcellular structures of the oocyte and the functional interaction between oocyte and cumulus cells.

The luteal phase after GnRH-agonist triggering of ovulation: present and future perspectives.

PubMed

Humaidan, Peter; Papanikolaou, E G; Kyrou, D; Alsbjerg, B; Polyzos, N P; Devroey, P; Fatemi, Human M

2012-02-01

In stimulated IVF/intracytoplasmic sperm injection cycles, the luteal phase is disrupted, necessitating luteal-phase supplementation. The most plausible reason behind this is the ovarian multifollicular development obtained after ovarian stimulation, resulting in supraphysiological steroid concentrations and consecutive inhibition of LH secretion by the pituitary via negative feedback at the level of the hypothalamic-pituitary axis. With the introduction of the gonadotrophin-releasing hormone-(GnRH) antagonist, an alternative to human chorionic gonadotrophin triggering of final oocyte maturation is the use of GnRH agonist (GnRHa) which reduces or even prevents ovarian hyperstimulation syndrome (OHSS). Interestingly, the current regimens of luteal support after HCG triggering are not sufficient to secure the early implanting embryo after GnRHa triggering. This review discusses the luteal-phase insufficiency seen after GnRHa triggering and the various trials that have been performed to assess the most optimal luteal support in relation to GnRHa triggering. Although more research is needed, GnRHa triggering is now an alternative to HCG triggering, combining a significant reduction in OHSS with high ongoing pregnancy rates. Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Effects of Combined General/Epidural Anesthesia on Hemodynamics, Respiratory Function, and Stress Hormone Levels in Patients with Ovarian Neoplasm Undergoing Laparoscopy.

PubMed

Xu, Qiang; Zhang, Hao; Zhu, Yan-Mei; Shi, Nian-Jun

2016-11-08

BACKGROUND The aim of this study was to evaluate the influence of combined general/epidural anesthesia (GEA) on hemodynamics, respiratory function and stress hormone levels in patients with ovarian neoplasm undergoing laparoscopy. MATERIAL AND METHODS A total of 177 patients with ovarian neoplasm (screened by inclusion/exclusion criteria) receiving laparoscopy were divided into groups G (general anesthesia alone), L1.0 (GEA with 1.0% lidocaine), and L1.5 (GEA with 1.5% lidocaine). Hemodynamics, respiratory parameters and stress hormone levels in the 3 groups were recorded and analyzed. RESULTS Hemodynamic indexes and PaO2/PaCO2 in group L1.0 showed no differences at each time point (all P>0.05). At the end of anesthesia tracheal intubation (T1), 10 min after pneumoperitoneum (T2) and the end of anesthesia tracheal extubation (T3), there were significant differences in hemodynamic indexes, respiratory parameters, epinephrine (E), and noradrenalin (NE) of group G/L1.5, compared with before anesthesia induction (T0) (all P<0.05). Compared with group G, there were big differences in dosage of anesthetics (sufentanil, vecuronium, and propofol) and pharmaceutic adjuvants (ephedrine, atropine, and nitroglycerin), postoperative recovery time, extubation time, and incidence of agitation in group L1.0/L1.5 (all P<0.05). CONCLUSIONS GEA can improve the quality and efficiency in laparoscopy for ovarian neoplasm, with the advantages of reduced anesthetics dosage, satisfactory postoperative analgesia, maintained hemodynamic stability, excellent uterine relaxation, and reduced time of anesthesia induction, surgery, recovery, and extubation. In addition, compared with group L1.5, group L1.0 was more secure and worthy of clinical promotion in laparoscopy.

The effect of personal medical history and family history of cancer on the uptake of risk-reducing salpingo-oophorectomy.

PubMed

van der Aa, Jessica E; Hoogendam, Jacob P; Butter, Els S F; Ausems, Margreet G E M; Verheijen, René H M; Zweemer, Ronald P

2015-12-01

Women with an increased lifetime risk of ovarian cancer are advised to undergo risk-reducing salpingo-oophorectomy (RRSO) to reduce risk of adnexal cancer. We investigated the uptake of RRSO and evaluated the influence of personal medical history of (breast) cancer, risk-reducing mastectomy (RRM) and family history of ovarian and/or breast cancer on the RRSO decision. This single center retrospective observational cohort study was performed in a tertiary multidisciplinary clinic for hereditary cancer of the University Medical Centre Utrecht, The Netherlands. Women ≥35 years old with an estimated lifetime risk of ovarian cancer ≥10%, who had completed childbearing, were eligible for RRSO. Uptake and timing of RRSO were analyzed. Influence of personal medical history and family history on RRSO decision making, were evaluated with logistic regression. The study population consisted of 218 women (45.0% BRCA1 mutation carrier, 28.0% BRCA2 mutation carrier, 27.0% with familial susceptibility) with 87.2% RRSO uptake. The median age at RRSO was 44.5 (range 28-73) years. Of the women undergoing RRSO, 78.3% needed ≤3 consultations to reach this decision. Multivariable analysis showed a significant difference in RRSO uptake for women with a history of RRM [OR 3.66 95% CI (1.12-11.98)], but no significant difference in women with a history of breast cancer [OR 1.38 95% CI (0.50-3.79)], nor with a family history of ovarian and/or breast cancer [OR 1.10 95% CI (0.44-2.76)]. We conclude that RRSO counseling, without the alternative of screening, is effective. The uptake is increased in women with a history of RRM.

Low-dose pressurized intraperitoneal aerosol chemotherapy (PIPAC) as an alternative therapy for ovarian cancer in an octogenarian patient.

PubMed

Giger-Pabst, Urs; Solass, Wiebke; Buerkle, Bernd; Reymond, Marc-André; Tempfer, Clemens B

2015-04-01

Octogenarians with ovarian cancer limited to the abdomen may not be willing or able to undergo systemic chemotherapy. Low-dose pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin is a form of intra-abdominal chemotherapy which can be applied repeatedly and potentially prevents from the systemic side-effects of chemotherapy. We present the case of an 84-year-old woman with laparoscopically and histologically confirmed ovarian cancer who refused to undergo systemic chemotherapy. She was treated with eight courses q 28-104 days of low-dose PIPAC with cisplatin at 7.5 mg/m(2) and doxorubicin at 1.5 mg/m(2) at 12 mmHg and 37 °C for 30 min. Objective tumor response was noted, defined as tumor regression on histology, and stable disease noted by peritoneal carcinomatosis index on repeated video-laparoscopy and abdominal computed tomographic scan. The treatment was well-tolerated with no Common Terminology Criteria for Adverse Events (CTCAE) CTCAE >2. With a follow-up of 15 months, the patient is alive and clinically stable. The quality of life measured by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 demonstrated improvement over 5-6 months (global physical score, global health score, global quality of live) without cumulative increase of gastrointestinal toxicity. Low-dose PIPAC is a new form of intraperitoneal chemotherapy which may be applied repeatedly in octogenarian patients. PIPAC may be an alternative and well-tolerated treatment for selected octogenarian patients with ovarian cancer limited to the abdomen who cannot be treated with systemic chemotherapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Akt2/ZEB2 may be a biomarker for exfoliant cells in ascitic fluid in advanced grades of serous ovarian carcinoma.

PubMed

Liu, Changmei; Yang, Fangmei

2015-09-01

Ovarian cancers present a mild clinical course when diagnosed early but an aggressive pathway when diagnosed in the peri- and postmenopausal periods. However, the predictability of tumor progression is stochastic and is difficult to predict. In the present study, we hypothesized to examine the key pathways that are dysregulated to promote epithelial-mesenchymal transition in serous ovarian carcinoma. Examination of these steps would help to identify ascitic fluid with cells poised for metastasis or otherwise. We focused on examining the Akt2 expression, mainly because of its report as being overamplified in the aggressive variants of ovarian cancer, as well as TGFbeta-sensitivity of Akt2 that forms the key basis for metastasis initiation of most kinds of carcinoma. We obtained primary ovarian carcinoma samples as well as ascitic fluid and distantly metastatic ovarian carcinoma to examine the expression of Akt2. The results of the study demonstrated that in malignant exfoliated ovarian cancer cells, Smad4 expression was tremendously increased in the nuclei, suggesting nuclear translocation of Smad, which thereafter may have activated ZEB2, and thereafter genomically affected the expression of E-cadherin, myosin II, and vimentin, key components for initiating and sustaining metastasis. All of these may have been stimulated by increased cellular expression of Akt2 in metastatic variants of the serous ovarian carcinoma. The reliance on Akt2 and TGF beta signaling may also potentiate the case for Akt inhibitors or small molecule inhibitors of TGFbeta signaling like doxycycline as adjunct chemotherapy in serous ovarian carcinoma, especially the metastatic variants.

GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type.

PubMed

Lambalk, C B; Banga, F R; Huirne, J A; Toftager, M; Pinborg, A; Homburg, R; van der Veen, F; van Wely, M

2017-09-01

Most reviews of IVF ovarian stimulation protocols have insufficiently accounted for various patient populations, such as ovulatory women, women with polycystic ovary syndrome (PCOS) or women with poor ovarian response, and have included studies in which the agonist or antagonist was not the only variable between the compared study arms. The aim of the current study was to compare GnRH antagonist protocols versus standard long agonist protocols in couples undergoing IVF or ICSI, while accounting for various patient populations and treatment schedules. The Cochrane Menstrual Disorders and Subfertility Review Group specialized register of controlled trials and Pubmed and Embase databases were searched from inception until June 2016. Eligible trials were those that compared GnRH antagonist protocols and standard long GnRH agonist protocols in couples undergoing IVF or ICSI. The primary outcome was ongoing pregnancy rate. Secondary outcomes were: live birth rate, clinical pregnancy rate, number of oocytes retrieved and safety with regard to ovarian hyperstimulation syndrome (OHSS). Separate comparisons were performed for the general IVF population, women with PCOS and women with poor ovarian response. Pre-planned subgroup analyses were performed for various antagonist treatment schedules. We included 50 studies. Of these, 34 studies reported on general IVF patients, 10 studies reported on PCOS patients and 6 studies reported on poor responders. In general IVF patients, ongoing pregnancy rate was significantly lower in the antagonist group compared with the agonist group (RR 0.89, 95% CI 0.82-0.96). In women with PCOS and in women with poor ovarian response, there was no evidence of a difference in ongoing pregnancy between the antagonist and agonist groups (RR 0.97, 95% CI 0.84-1.11 and RR 0.87, 95% CI 0.65-1.17, respectively). Subgroup analyses for various antagonist treatment schedules compared to the long protocol GnRH agonist showed a significantly lower ongoing pregnancy rate when the oral hormonal programming pill (OHP) pretreatment was combined with a flexible protocol (RR 0.74, 95% CI 0.59-0.91) while without OHP, the RR was 0.84, 95% CI 0.71-1.0. Subgroup analysis for the fixed antagonist schedule demonstrated no evidence of a significant difference with or without OHP (RR 0.94, 95% CI 0.79-1.12 and RR 0.94, 95% CI 0.83-1.05, respectively). Antagonists resulted in significantly lower OHSS rates both in the general IVF patients and in women with PCOS (RR 0.63, 95% CI 0.50-0.81 and RR 0.53, 95% CI 0.30-0.95, respectively). No data on OHSS was available from trials in poor responders. In a general IVF population, GnRH antagonists are associated with lower ongoing pregnancy rates when compared to long protocol agonists, but also with lower OHSS rates. Within this population, antagonist treatment prevents one case of OHSS in 40 patients but results in one less ongoing pregnancy out of every 28 women treated. Thus standard use of the long GnRH agonist treatment is perhaps still the approach of choice for prevention of premature luteinization. In couples with PCOS and poor responders, GnRH antagonists do not seem to compromise ongoing pregnancy rates and are associated with less OHSS and therefore could be considered as standard treatment. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

PAPP-A proteolytic activity enhances IGF bioactivity in ascites from women with ovarian carcinoma

PubMed Central

Thomsen, Jacob; Hjortebjerg, Rikke; Espelund, Ulrick; Ørtoft, Gitte; Vestergaard, Poul; Magnusson, Nils E.; Conover, Cheryl A.; Tramm, Trine; Hager, Henrik; Høgdall, Claus; Høgdall, Estrid; Oxvig, Claus; Frystyk, Jan

2015-01-01

Pregnancy-associated plasma protein-A (PAPP-A) stimulates insulin-like growth factor (IGF) action through proteolysis of IGF-binding protein (IGFBP)-4. In experimental animals, PAPP-A accelerates ovarian tumor growth by this mechanism. To investigate the effect of PAPP-A in humans, we compared serum and ascites from 22 women with ovarian carcinoma. We found that ascites contained 46-fold higher PAPP-A levels as compared to serum (P < 0.001). The majority (80%) of PAPP-A was enzymatically active. This is supported by the finding that ascites contained more cleaved than intact IGFBP-4 (P < 0.03). Ascites was more potent than serum in activating the IGF-I receptor (IGF-IR) in vitro (+31%, P < 0.05); in 8 of 22 patients by more than two-fold. In contrast, ascites contained similar levels of immunoreactive IGF-I, and lower levels of IGF-II (P < 0.001). Immunohistochemistry demonstrated the presence of IGF-IR in all but one tumor, whereas all tumors expressed PAPP-A, IGFBP-4, IGF-I and IGF-II. Addition of recombinant PAPP-A to ascites increased the cleavage of IGFBP-4 and enhanced IGF-IR activation (P < 0.05). In conclusion, human ovarian tumors express PAPP-A, IGFBP-4 and IGFs and these proteins are also present in ascites. We suggest that both soluble PAPP-A in ascites and tissue-associated PAPP-A serve to increase IGF bioactivity and, thereby, to stimulate IGF-IR-mediated tumor growth. PMID:26336825

Unilateral Versus Bilateral Laparoscopic Ovarian Drilling Using Thermal Dose Adjusted According to Ovarian Volume in CC-Resistant PCOS, A Randomized Study.

PubMed

El-Sayed, Mohamed Lotfy Mohamed; Ahmed, Mostafa Abdo; Mansour, Marwa Abdel Azim; Mansour, Shymma Abdel Azim

2017-10-01

This study aimed to evaluate the efficacy of unilateral laparoscopic ovarian drilling versus bilateral laparoscopic ovarian drilling with thermal dose adjusted according to ovarian volume in clomiphene citrate (CC)-resistant PCOS patients in terms of endocrine changes, menstrual cycle resumption, ovulation and pregnancy rates. This study was conducted in the Department of Obstetrics and Gynecology, Zagazig university hospitals. One hundred CC-resistant PCOS patients were divided into two groups. Group (I) (50 patients) underwent unilateral laparoscopic ovarian drilling with thermal dose adjusted according to ovarian volume (60 J/cm 3 of ovarian tissue), and group (II) (50 patients) underwent bilateral laparoscopic ovarian drilling using the same previously mentioned thermal dose. Endocrinal changes and menstrual cycle resumption were assessed within 8 weeks postoperatively, but the ovulation and pregnancy rates were estimated after 6-month follow-up period. There was no statistically significant difference between the two groups as regards demographic data ( p  > 0.05). As regards menstruation cycle resumption (62.5 vs. 81%) ( p  = 0.047), total ovulation rate (54.2 vs. 78.7%) ( p  = 0.011) and cumulative pregnancy rate (33.3 vs. 55.3%) ( p  = 0.031), there was statistically significant difference between both groups. After drilling, there were highly statistically significant decrease in the mean serum levels of luteinizing hormone (LH) and significant decrease in the mean serum levels of testosterone in both groups. Mean serum level of follicle stimulating hormone (FSH) did not change significantly in both groups after drilling. Bilateral laparoscopic ovarian drilling with thermal dose adjusted according to ovarian volume is more effective than the right-sided unilateral technique with thermal dose adjusted according to ovarian volume in terms of menstrual cycle resumption, ovulation and cumulative pregnancy rates in CC-resistant PCOS patients.

Ovarian parameters and ovarian blood flow of women living in the area of environmental crisis.

PubMed

Balmagambetova, Aru; Abdelazim, Ibrahim A; Bekmukhambetov, Erbol; Zhurabekova, Gulmira; Yehia, Amr H; AbuFaza, Mohannad

2016-05-01

Exposure to environmental hazards will destroy a number of ovarian primordial follicles, reduce ovarian reserve and subsequent reproductive ability. This study designed to evaluate ovarian parameters and ovarian blood flow of women living in the area of environmental crisis Shalkar city (Kazakhstan) compared to women living in Aktobe city (Kazakhstan). 220 women in their reproductive age studied and classified into two groups; study (Shalkar) group and control (Aktobe) group. Blood sample taken from studied women during follicular phase (day 3) for hormonal level evaluation including; follicle stimulating hormone (FSH) and anti-Mullerian hormone (AMH). Studied women evaluated using trans-vaginal ultrasound (TVS) to detect antral follicle count (AFC) during follicular scan and ovarian volume (OV), ovarian blood flow (OBF) using pulsatility index (PI) during follicular scan and luteal scan. Both ovaries AFC was significantly less in study (Shalkar) group compared to and control (Aktobe) group (p=0.0001). Mean ovarian volume was significantly less in Shalkar group in both follicular phase and luteal phase (5.86±0.23 and 6.19±0.22Cm(3); respectively) compared to Aktobe group (6.85±0.19 and 6.92±0.18Cm(3); respectively). In addition, mean ovarian pulsatility index was significantly high with subsequent decrease in ovarian blood flow in Shalkar group in both follicular phase and luteal phase (3.36±0.20 and 3.45±0.19Cm/s; respectively) compared to Aktobe group (2.96±0.16 and 2.92±0.15Cm/s; respectively). This study suggests definite environmental effect on ovarian parameters as indicated by decreased AFC, decreased both follicular and luteal OV and OBF in women living in environmental crisis Shalkar group compared to Aktobe group. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Randomized trial of adjuvant ovarian suppression in 926 premenopausal patients with early breast cancer treated with adjuvant chemotherapy.

PubMed

Arriagada, R; Lê, M G; Spielmann, M; Mauriac, L; Bonneterre, J; Namer, M; Delozier, T; Hill, C; Tursz, T

2005-03-01

The aim of this multicenter trial was to evaluate the role of ovarian suppression in patients with early breast cancer previously treated with local surgery and adjuvant chemotherapy. Nine hundred and twenty-six premenopausal patients with completely resected breast cancer and either axillary node involvement or histological grade 2 or 3 tumors were randomized after surgery to adjuvant chemotherapy alone (control arm) or adjuvant chemotherapy plus ovarian suppression (ovarian suppression arm). Ovarian suppression was obtained by either radiation-induced ovarian ablation or triptorelin for 3 years. The analyses were performed with Cox models stratified by center. Median follow-up was 9.5 years. Mean age was 43 years. Ninety per cent of patients had histologically proven positive axillary nodes, 63% positive hormonal receptors and 77% had received an anthracycline-based chemotherapy regimen. Ovarian suppression was by radiation-induced ovarian ablation (45% of patients) or with triptorelin (48%). At the time of randomization, all patients had regular menses or their follicle-stimulating hormone and estradiol levels indicated a premenopausal status. The 10-year disease-free survival rates were 49% [95% confidence interval (CI) 44% to 54%] in both arms (P = 0.51). The 10-year overall survival rates were 66% (95% CI 61% to 70%) for the ovarian suppression arm and 68% (95% CI 63% to 73%) for the control arm (P = 0.19). There were no variations in the treatment effect according to age, hormonal receptor status or ovarian suppression modality. However, in patients <40 years of age and with estrogen receptor-positive tumors, ovarian suppression significantly decreased the risk of recurrence (P = 0.01). The results of this trial, after at least 10 years of follow-up, do not favor the use of ovarian suppression after adjuvant chemotherapy. The potential beneficial effect in younger women with hormono-dependent tumors should be further assessed.

Ovarian tissue cryopreservation and transplantation among alternatives for fertility preservation in the Nordic countries - compilation of 20 years of multicenter experience.

PubMed

Rodriguez-Wallberg, Kenny A; Tanbo, Tom; Tinkanen, Helena; Thurin-Kjellberg, Ann; Nedstrand, Elizabeth; Kitlinski, Margareta Laczna; Macklon, Kirsten T; Ernst, Erik; Fedder, Jens; Tiitinen, Aila; Morin-Papunen, Laure; Einarsson, Snorri; Jokimaa, Varpu; Hippeläinen, Maritta; Lood, Mikael; Gudmundsson, Johannes; Olofsson, Jan I; Andersen, Claus Yding

2016-09-01

The aim of this study is to report the current status of ovarian tissue cryopreservation among alternatives for fertility preservation in the Nordic countries. A questionnaire was sent to 14 Nordic academic reproductive centers with established fertility preservation programs. It covered fertility preservation cases performed up to December 2014, standard procedures for ovarian tissue cryopreservation and oocyte cryopreservation and reproductive outcomes following ovarian tissue transplantation. Among the Nordic countries, Denmark and Norway practice ovarian tissue cryopreservation as a clinical treatment (822 and 164 cases, respectively) and their programs are centralized. In Sweden (457 cases), ovarian tissue cryopreservation is practiced at five of six centers and in Finland at all five centers (145 cases). Nearly all considered ovarian tissue cryopreservation to be experimental. In Iceland, embryo cryopreservation is the only option for fertility preservation. Most centers use slow-freezing methods for ovarian tissue cryopreservation. Most patients selected for ovarian tissue cryopreservation were newly diagnosed with cancer and the tissue was predominantly retrieved laparoscopically by unilateral oophorectomy. Only minor complications were reported. In total, 46 women have undergone ovarian tissue transplantation aiming at recovering fertility, 17 healthy children have been born and several additional pregnancies are currently ongoing. Whenever patients' clinical condition is permissive, oocyte cryopreservation after hormonal stimulation is preferred for fertility preservation. Between 2012 and 2014, a smaller proportion of females have undergone fertility preservation in the Nordic centers, in comparison to males (1:3). Overall, ovarian tissue cryopreservation was reported to be safe. Slow freezing methods are still preferred. Promising results of recovery of fertility have been reported in Nordic countries that have initiated ovarian tissue transplantation procedures. © 2016 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).

Delphinidin inhibits BDNF-induced migration and invasion in SKOV3 ovarian cancer cells.

PubMed

Lim, Won-Chul; Kim, Hyunhee; Kim, Young-Joo; Park, Seung-Ho; Song, Ji-Hye; Lee, Ki Heon; Lee, In Ho; Lee, Yoo-Kyung; So, Kyeong A; Choi, Kyung-Chul; Ko, Hyeonseok

2017-12-01

Brain-derived neurotrophic factor (BDNF), the TrkB ligand, is associated with aggressive malignant behavior, including migration and invasion, in tumor cells and a poor prognosis in patients with various types of cancer. Delphinidin is a diphenylpropane-based polyphenolic ring structure-harboring compound, which exhibits a wide range of pharmacological activities, anti-tumor, anti-oxidant, anti-inflammatory, anti-angiogenic and anti-mutagenic activity. However, the possible role of delphinidin in the cancer migration and invasion is unclear. We investigated the suppressive effect of delphinidin on the cancer migration and invasion. Thus, we found that BDNF enhanced cancer migration and invasion in SKOV3 ovarian cancer cell. To exam the inhibitory role of delphinidin in SKOV3 ovarian cancer migration and invasion, we investigated the use of delphinidin as inhibitors of BDNF-induced motility and invasiveness in SKOV3 ovarian cancer cells in vitro. Here, we found that delphinidin prominently inhibited the BDNF-induced increase in cell migration and invasion of SKOV3 ovarian cancer cells. Furthermore, delphinidin remarkably inhibited BDNF-stimulated expression of MMP-2 and MMP-9. Also, delphinidin antagonized the phosphorylation of Akt and nuclear translocation of NF-κB permitted by the BDNF in SKOV3 ovarian cancer cells. Taken together, our findings provide new evidence that delphinidin suppressed the BDNF-induced ovarian cancer migration and invasion through decreasing of Akt activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Office microlaparoscopic ovarian drilling (OMLOD) versus conventional laparoscopic ovarian drilling (LOD) for women with polycystic ovary syndrome.

PubMed

Salah, Imaduldin M

2013-02-01

This was a prospective controlled study to compare the beneficial effects of office microlaparoscopic ovarian drilling (OMLOD) under augmented local anesthesia, as a new modality treatment option, compared to those following ovarian drilling with the conventional traditional 10-mm laparoscope (laparoscopic ovarian drilling, LOD) under general anesthesia. The study included 60 anovulatory women with polycystic ovary syndrome (PCOS) who underwent OMLOD (study group) and 60 anovulatory PCOS women, in whom conventional LOD using 10-mm laparoscope under general anesthesia was performed (comparison group). Transvaginal ultrasound scan and blood sampling to measure the serum concentrations of LH, FSH, testosterone and androstenedione were performed before and after the procedure. Intraoperative and postoperative pain scores in candidate women were evaluated during the office microlaparoscopic procedure, in addition to the number of candidates who needed extra analgesia. Women undergoing OMLOD showed good intraoperative and postoperative pain scores. The number of patients discharged within 2 h after the office procedure was significantly higher, without the need for postoperative analgesia in most patients. The LH:FSH ratio, mean serum concentrations of LH and testosterone and free androgen index decreased significantly after both OMLOD and LOD. The mean ovarian volume decreased significantly (P < 0.05) a year after both OMLOD and LOD. There were no significant differences in those results after both procedures. Intra- and postoperatively augmented local anesthesia allows outpatient bilateral ovarian drilling by microlaparoscopy without general anesthesia. The high pregnancy rate, the simplicity of the method and the faster discharge time offer a new option for patients with PCOS who are resistant to clomiphene citrate. Moreover, ovarian drilling could be performed simultaneously during the routine diagnostic microlaparoscopy and integrated into the fertility workup of these patients.

Microdose GnRH Agonist Flare-Up versus Ultrashort GnRH Agonist Combined with Fixed GnRH Antagonist in Poor Responders of Assisted Reproductive Techniques Cycles

PubMed Central

Eftekhar, Maryam; Mohammadian, Farnaz; Yousefnejad, Fariba; Khani, Parisa

2013-01-01

Background: This study compares the microdose flare-up protocol to the ultrashort gonadotropinreleasing hormone (GnRH) agonist flare combined with the fixed multidose GnRH antagonist protocol in poor responders undergoing ovarian stimulation. Materials and Methods: In this randomized clinical trial, 120 women who were candidates for assisted reproductive techniques (ART) and had histories of one or more failed in vitro fertilization (IVF) cycles with three or fewer retrieved oocytes were prospectively randomized into two groups. Group I (60 patients) received the microdose flare-up regimen and group II (60 patients) received the ultrashort GnRH agonist combined with fixed GnRH antagonist. Results: There were no significant differences between the groups in the number of used gonadotropin ampoules (p=0.591), duration of stimulation (p=0.610), number of retrieved oocytes (p=0.802), fertilization rate (p=0.456), and the number of transferred embryos (p=0.954). The clinical pregnancy rates were statistically similar in group I (10%) compared with group II (13.3%, p=0.389). Conclusion: According to our results, there is no significant difference between these protocols for improving the ART outcome in poor responders. Additional prospective, randomized studies with more patients is necessary to determine the best protocol (Registration Number: IRCT201105096420N1). PMID:24520450

Attitudes to reproductive genetic testing in women who had a positive BRCA test before having children: a qualitative analysis

PubMed Central

Ormondroyd, Elizabeth; Donnelly, Louise; Moynihan, Clare; Savona, Cornelie; Bancroft, Elizabeth; Evans, D Gareth; Eeles, Rosalind; Lavery, Stuart; Watson, Maggie

2012-01-01

The scope of conditions for which preimplantation genetic diagnosis (PGD) is licensed has recently been expanded in the United Kingdom to include genetic predisposition to adult-onset cancer. This qualitative interview study explores reproductive decision making, knowledge of and attitudes to reproductive genetic testing (prenatal diagnosis and PGD) with 25 women aged 18–45 years who received a positive BRCA test in the United Kingdom before having children. In this cohort of younger women, BRCA testing was motivated by risk management decisions; for some, BRCA status has affected their later decisions about having children. The perceived severity of hereditary breast/ovarian cancer (HBOC) influences thoughts about passing on the mutation to children and willingness to consider reproductive genetic testing, but most participants do not believe HBOC is a condition for which pregnancy termination is justified. PGD is considered more acceptable and advantageous because it would prevent transmission to future generations, but women have concerns about selecting embryos and the fact that they and affected family members would not have been selected. Women would also be deterred by the need to undergo in vitro fertilisation (IVF) and ovarian stimulation for PGD. Awareness of reproductive testing options was very variable among the cohort. The findings highlight the complexities of reproductive decision making for young women who knowingly carry a BRCA mutation, and the dilemmas inherent to reproductive genetic testing when the condition being tested for also affects a prospective parent. Counselling and psychological support for BRCA-positive women and couples concerning reproductive options are strongly indicated. PMID:21811309

Long-term hormonal contraceptive use is associated with a reversible suppression of antral follicle count and a break from hormonal contraception may improve oocyte yield.

PubMed

Letourneau, Joseph M; Cakmak, Hakan; Quinn, Molly; Sinha, Nikita; I Cedars, Marcelle; Rosen, Mitchell P

2017-09-01

Unlike infertility, patients presenting for fertility preservation (FP) are often using combined hormonal contraceptives (CHC). We studied whether long-term (≥6 months) CHC use is associated with reversible suppression of antral follicle count (AFC). This is a longitudinal study of FP cycles from 2012 to 2016. We studied three groups: those without CHC exposure (NO CHC), those with CHC usage with a CHC break (BREAK), and without a break (NO BREAK) prior to ovarian stimulation. We assessed ovarian reserve by AFC at initial consultation and discussed the possibility of CHC suppression of AFC. Patients chose between ovarian stimulation with no CHC break versus ovarian stimulation after a CHC break. AFC was measured serially in the BREAK group. We assessed whether AFC suppression was reversed in the BREAK group. Total oocyte yield was compared among the NO CHC, BREAK, and NO BREAK groups. T tests, ANOVA, and linear/logistic regressions were used. Seven hundred forty-three women underwent FP. Twenty-one percent (n = 154) were taking long-term CHC (≥6 months). AFC suppression was more likely with CHC use (OR 1.6, 95% CI 1.1-2.4, P = 0.011). The BREAK group (n = 79) stopped CHC for an average of 4 months. AFC improvement started at 1 month and plateaued at approximately 6- to 7-month break. The BREAK group had approximately twice as many oocytes per initial AFC as NO BREAK (2.8 ± 3.8 vs. 1.4 ± 0.9, P < 0.001). When women present for FP on CHC, AFC may be suppressed. A CHC break of several months is associated with an increase in AFC and a potential improvement in overall egg yield.

The comparison of microdose flare-up and multiple dose antagonist protocols based on hCG day estradiol (E2), progesterone (P) and P/E2 ratio among poor responder patients in ICSI-ET cycles.

PubMed

Cicek, M N; Kahyaoglu, I; Kahyaoglu, S

2015-02-01

Elevated progesterone levels surpassing exact treshold values impede endometrial receptivity and decrease clinical pregnancy rates in different responder patients during assisted reproductive techniques. A progesterone (P): estradiol (E2) ratio of > 1 on the day of hCG administration has also been suggested to be a manifestation of low ovarian reserve. The clinical significance of P/E2 ratio on the day of hCG administration was investigated among poor responder patients. Based on the ESHRE Bologna consensus criteria related to poor ovarian response diagnosis, 48 poor responder patients were treated with the microdose flare-up regimen and 34 patients were treated with the multiple-dose GnRH antagonist protocol. All patients were destined to perform a ICSI-ET procedure at the end of the stimulation protocols. Progesterone levels and P/E2 ratios have been detected during controlled ovarian hyperstimulation. In the microdose flare-up group; the duration of stimulation, total gonadotropin dose used and hCG day E2 levels were significantly higher than the multiple dose antagonist group. However, the mean hCG day P/E2 rate in the microdose flare-up group was less than that in the multiple-dose antagonist group. The clinical pregnancy rates were non significantly higher in the multiple dose antagonist protocol group than in microdose flare-up group. Impaired endometrial receptivity caused by elevated P levels results with lower pregnancy rates. Regardless of the selected stimulation protocol, poor responder patients are not prone to exhibit high P and E2 secretion. Increased P/E2 ratio of > 1 on hCG day has limited value to predict cycle outcomes in poor responder patients because of ovarian follicle depletion.

The Drosophila ovarian and testis stem cell niches: similar somatic stem cells and signals.

PubMed

Decotto, Eva; Spradling, Allan C

2005-10-01

The stem cell niches at the apex of Drosophila ovaries and testes have been viewed as distinct in two major respects. While both contain germline stem cells, the testis niche also contains "cyst progenitor" stem cells, which divide to produce somatic cells that encase developing germ cells. Moreover, while both niches utilize BMP signaling, the testis niche requires a key JAK/STAT signal. We now show, by lineage marking, that the ovarian niche also contains a second type of stem cell. These "escort stem cells" morphologically resemble testis cyst progenitor cells and their daughters encase developing cysts before undergoing apoptosis at the time of follicle formation. In addition, we show that JAK/STAT signaling also plays a critical role in ovarian niche function, and acts within escort cells. These observations reveal striking similarities in the stem cell niches of male and female gonads, and suggest that they are largely governed by common mechanisms.

Live-Birth Rate Associated With Repeat In Vitro Fertilization Treatment Cycles.

PubMed

Smith, Andrew D A C; Tilling, Kate; Nelson, Scott M; Lawlor, Debbie A

The likelihood of achieving a live birth with repeat in vitro fertilization (IVF) is unclear, yet treatment is commonly limited to 3 or 4 embryo transfers. To determine the live-birth rate per initiated ovarian stimulation IVF cycle and with repeated cycles. Prospective study of 156,947 UK women who received 257,398 IVF ovarian stimulation cycles between 2003 and 2010 and were followed up until June 2012. In vitro fertilization, with a cycle defined as an episode of ovarian stimulation and all subsequent separate fresh and frozen embryo transfers. Live-birth rate per IVF cycle and the cumulative live-birth rates across all cycles in all women and by age and treatment type. Optimal, prognosis-adjusted, and conservative cumulative live-birth rates were estimated, reflecting 0%, 30%, and 100%, respectively, of women who discontinued due to poor prognosis and having a live-birth rate of 0 had they continued. Among the 156,947 women, the median age at start of treatment was 35 years (interquartile range, 32-38; range, 18-55), and the median duration of infertility for all 257,398 cycles was 4 years (interquartile range, 2-6; range, <1-29). In all women, the live-birth rate for the first cycle was 29.5% (95% CI, 29.3%-29.7%). This remained above 20% up to and including the fourth cycle. The cumulative prognosis-adjusted live-birth rate across all cycles continued to increase up to the ninth cycle, with 65.3% (95% CI, 64.8%-65.8%) of women achieving a live birth by the sixth cycle. In women younger than 40 years using their own oocytes, the live-birth rate for the first cycle was 32.3% (95% CI, 32.0%-32.5%) and remained above 20% up to and including the fourth cycle. Six cycles achieved a cumulative prognosis-adjusted live-birth rate of 68.4% (95% CI, 67.8%-68.9%). For women aged 40 to 42 years, the live-birth rate for the first cycle was 12.3% (95% CI, 11.8%-12.8%), with 6 cycles achieving a cumulative prognosis-adjusted live-birth rate of 31.5% (95% CI, 29.7%-33.3%). For women older than 42 years, all rates within each cycle were less than 4%. No age differential was observed among women using donor oocytes. Rates were lower for women with untreated male partner-related infertility compared with those with any other cause, but treatment with either intracytoplasmic sperm injection or sperm donation removed this difference. Among women in the United Kingdom undergoing IVF, the cumulative prognosis-adjusted live-birth rate after 6 cycles was 65.3%, with variations by age and treatment type. These findings support the efficacy of extending the number of IVF cycles beyond 3 or 4.

In Vitro Maturation in Women with vs. without Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis

PubMed Central

Siristatidis, Charalampos; Sergentanis, Theodoros N.; Vogiatzi, Paraskevi; Kanavidis, Prodromos; Chrelias, Charalampos; Papantoniou, Nikolaos; Psaltopoulou, Theodora

2015-01-01

Objective To evaluate in vitro maturation (IVM) in sub-fertile women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF), by comparing outcomes with a control group of non-PCOS. Study design A search strategy was developed for PubMed and studies reporting rates of the following outcomes (live birth; clinical pregnancy; implantation; cycle cancellation; oocyte maturation; oocyte fertilization; miscarriage) between patients with PCOS, PCO and controls undergoing IVM were deemed eligible. The review was conducted in accordance to the PRISMA guidelines and included studies quality was assessed through the Newcastle-Ottawa Quality scale. ORs with their corresponding 95% CIs were calculated for the main analysis and subgroup analyses were performed for PCOS cases vs. controls and PCOS vs. PCO cases. Alternative analyses were performed for live birth and clinical pregnancy, based on cycles and on women. Subgroup analyses for FSH stimulation, hCG priming and type of procedure (IVF/ICSI) were undertaken for all meta-analyses encompassing at least four study arms. Random effects models were used to calculate pooled effect estimates. Results Eleven studies were identified. A total of 268 PCOS patients (328 cycles), 100 PCO patients (110 cycles) and 440 controls (480 cycles) were included in the meta-analysis. A borderline trend towards higher birth rates among PCOS patients emerged (pooled OR = 1.74, 95%CI: 0.99–3.04) mainly reflected at the subgroup analysis vs. controls. Clinical pregnancy (pooled OR = 2.37, 95%CI: 1.53–3.68) and implantation rates (pooled OR = 1.73, 95%CI: 1.06–2.81) were higher, while cancellation rates lower (pooled OR = 0.18, 95%CI: 0.06-0.47) among PCOS vs. non-PCOS subjects; maturation and miscarriage rates did not differ between groups, while a borderline trend towards lower fertilization rates among PCOS patients was observed. Conclusion The present meta-analysis provides preliminary evidence on the effectiveness of IVM as a treatment option when offered in sub-fertile PCOS women, as the latter present at least as high outcome rates as those in non-PCOS. PMID:26241855

Withaferin A (WFA) inhibits tumor growth and metastasis by targeting ovarian cancer stem cells.

PubMed

Kakar, Sham S; Parte, Seema; Carter, Kelsey; Joshua, Irving G; Worth, Christopher; Rameshwar, Pranela; Ratajczak, Mariusz Z

2017-09-26

Ovarian cancer is the fifth leading cause of deaths due to cancer among women in the United States. In 2017, 22,440 women are expected to be diagnosed with ovarian cancer and 14,080 women will die with it. Currently used chemotherapies (Cisplatin or platinum/taxane combination) targets cancer cells, but spares cancer stem cells (CSCs), which are responsible for tumor relapse leading to recurrence of cancer. Aldehyde dehydrogenase I (ALDH1) positive cancer stem cells are one of the major populations in ovarian tumor and have been related to tumor progression and metastasis. In our studies, we observed expression of ALDH1 in both ovarian surface epithelium (OSE) and cortex with high levels of expression in OSE in normal ovary and benign (BN) tumor, compared to borderline (BL) and high grade (HG) ovarian tumors. In contrast, high levels of expression of ALDH1 were observed in cortex in BL and HG tumors compared to normal ovary and BN tumor. Withaferin A (WFA) alone or in combination with cisplatin (CIS) significantly inhibited the spheroid formation (tumorigenic potential) of isolated ALDH1 CSCs in vitro and significantly reduced its expression in tumors collected from mice bearing orthotopic ovarian tumor compared to control. Treatment of animals with CIS alone significantly increased the ALDH1 CSC population in tumors, suggesting that CIS targets cancer cells but spares cancer stem cells, which undergo amplification. WFA and CIS combination suppresses the expression of securin an "oncogene", suggesting that securin may serve as a downstream signaling gene to mediate the antitumor effects of WFA.

Efficacy of combined metformin-letrozole in comparison with bilateral ovarian drilling in clomiphene-resistant infertile women with polycystic ovarian syndrome.

PubMed

Abd Elgafor, Ibrahim

2013-07-01

To compare the hormonal-metabolic profiles and reproductive outcomes between women receiving metformin plus letrozole and women undergoing bilateral ovarian drilling in clomiphene citrate (CC)-resistant women with polycystic ovary syndrome (PCOS). In this randomized study, 146 patients were randomly allocated into group 1 (n = 73) who received metformin plus letrozole, and group 2 (n = 73) who underwent bilateral ovarian drilling. Comparison was done between the basal and after treatment biochemical values for each group, in addition reproductive outcomes after treatment were compared between both groups. There was significant reduction in testosterone (p ≤ 0.001), fasting insulin (p ≤ 0.001), and fasting glucose/fasting insulin ratio (p = 0.029) in metformin plus letrozole group, while there was significant reduction in FSH, LH and LH/FSH ratio in bilateral drilling group (p ≤ 0.001, 0.001 and 0.001). No significant difference in cycle regularity (p = 0.82), ovulation (p = 0.24), pregnancy rate (p = 0.32) and abortion rate (p = 0.51) between both groups. Both metformin plus letrozole and bilateral ovarian drilling are similarly effective as second-line strategies for the treatment of women with PCOS who do not conceive with CC.

Recurrence of Ovarian Cancer with Placental Metastasis: A Case Report

PubMed Central

Honda, Michiko; Yamada, Manabu; Kumasaka, Toshio; Samejima, Taiki; Satoh, Hirohisa; Sugimoto, Mitsuhiro

2017-01-01

A 39-year-old primiparous Japanese female was admitted to the obstetrical emergency department of our hospital because of respiratory distress resulting from a large amount of pleural effusion, soon after a caesarean delivery (CD) at another hospital. While she was undergoing the CD, a giant ovarian tumour was identified. However, the tumour could not be removed at that facility and she was transferred to our hospital. Three days after the CD, a left salpingo-oophorectomy was performed with the purpose of controlling pleural and peritoneal effusions. Based on her past treatment history and the information gathered from this surgery, recurrence of ovarian cancer was considered the final diagnosis. Earlier, at the age of 37 years, she had been diagnosed with stage IC ovarian adenocarcinoma arising from a mature cystic teratoma detected after a right salpingo-oophorectomy. These kinds of situations of accidental detection of recurrent advanced ovarian cancer in a newly pregnant patient in the emergency department are rare. Amongst them, we have identified an extremely rare case showing placental metastasis. The important lesson learnt from this case report is that detailed medical interviews and physical examinations are crucial when a pregnant woman visits a hospital without a letter of referral, especially in the third trimester of pregnancy. PMID:29070997

Mechanical Stimulation in Preventing Bone Density Loss in Patients Undergoing Donor Stem Cell Transplant

ClinicalTrials.gov

2012-07-05

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Plasma Cell Neoplasm; Poor Prognosis Metastatic Gestational Trophoblastic Tumor; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Neuroblastoma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; Stage II Ovarian Epithelial Cancer; Stage II Ovarian Germ Cell Tumor; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Malignant Testicular Germ Cell Tumor; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Small Lymphocytic Lymphoma; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Breast Cancer; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Small Lymphocytic Lymphoma

Targeting of follicle stimulating hormone peptide-conjugated dendrimers to ovarian cancer cells

NASA Astrophysics Data System (ADS)

Modi, Dimple A.; Sunoqrot, Suhair; Bugno, Jason; Lantvit, Daniel D.; Hong, Seungpyo; Burdette, Joanna E.

2014-02-01

Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side effects. To address these issues, we have designed poly(amidoamine) (PAMAM) dendrimers to selectively target the follicle stimulating hormone receptor (FSHR), which is overexpressed by tumorigenic ovarian cancer cells but not by immature primordial follicles and other non-tumorigenic cells. Fluorescein-labeled generation 5 (G5) PAMAM dendrimers were conjugated with the binding peptide domain of FSH (FSH33) that has a high affinity to FSHR. The targeted dendrimers exhibited high receptor selectivity to FSHR-expressing OVCAR-3 cells, resulting in significant uptake and downregulation of an anti-apoptotic protein survivin, while showing minimal interactions with SKOV-3 cells that do not express FSHR. The selectivity of the FSH33-targeted dendrimers was further validated in 3D organ cultures of normal mouse ovaries. Immunostaining of the conjugates revealed their selective binding and uptake by ovarian surface epithelium (OSE) cells that express FSHR, while sparing the immature primordial follicles. In addition, an in vivo study monitoring tissue accumulation following a single intraperitoneal (i.p.) injection of the conjugates showed significantly higher accumulation of FSH33-targeted dendrimers in the ovary and oviduct compared to the non-targeted conjugates. These proof-of-concept findings highlight the potential of these FSH33-targeted dendrimers to serve as a delivery platform for anti-ovarian cancer drugs, while reducing their systemic side effects by preventing nonspecific uptake by the primordial follicles.Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side effects. To address these issues, we have designed poly(amidoamine) (PAMAM) dendrimers to selectively target the follicle stimulating hormone receptor (FSHR), which is overexpressed by tumorigenic ovarian cancer cells but not by immature primordial follicles and other non-tumorigenic cells. Fluorescein-labeled generation 5 (G5) PAMAM dendrimers were conjugated with the binding peptide domain of FSH (FSH33) that has a high affinity to FSHR. The targeted dendrimers exhibited high receptor selectivity to FSHR-expressing OVCAR-3 cells, resulting in significant uptake and downregulation of an anti-apoptotic protein survivin, while showing minimal interactions with SKOV-3 cells that do not express FSHR. The selectivity of the FSH33-targeted dendrimers was further validated in 3D organ cultures of normal mouse ovaries. Immunostaining of the conjugates revealed their selective binding and uptake by ovarian surface epithelium (OSE) cells that express FSHR, while sparing the immature primordial follicles. In addition, an in vivo study monitoring tissue accumulation following a single intraperitoneal (i.p.) injection of the conjugates showed significantly higher accumulation of FSH33-targeted dendrimers in the ovary and oviduct compared to the non-targeted conjugates. These proof-of-concept findings highlight the potential of these FSH33-targeted dendrimers to serve as a delivery platform for anti-ovarian cancer drugs, while reducing their systemic side effects by preventing nonspecific uptake by the primordial follicles. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr05042d

Menstrual patterns, fertility and main pregnancy outcomes after allogeneic haematopoietic stem cell transplantation.

PubMed

Chiodi, Sandra; Spinelli, Simonetta; Bruzzi, Paolo; Anserini, Paola; Di Grazia, Carmen; Bacigalupo, Andrea

2016-08-01

Two-hundred and sixty-nine females aged ≤42 and undergoing an allogeneic stem cell transplant were retrospectively studied to assess the effect of age, conditioning regimen and chronic graft-versus-host disease (cGVHD) on resumption of stable menstrual cyclicity. Overall, a stable menstrual cyclicity was observed in 22% of cases. The cumulative probability of menses resumption was significantly age and conditioning regimen related. A statistically significant inverse correlation between cGVHD severity and menses resumption was observed only in univariate analysis. In patients with residual ovarian function, infertility was found in 43% and early menopause in 45%. An increased incidence of prematurity and low birth weight (LBW) was observed among the single spontaneous pregnancies. Follicle-stimulating hormone (FSH) and 17 beta-oestradiol levels were found to be inadequate to detect both early signs of menses resumption and menstrual stability. Our study confirms the crucial role of full dose total body irradiation (TBI) and age on menses recovery and fertility after haematopoietic stem cell transplantation (HSCT). The impact of severe cGVHD remains unclear.

GnRH in the Human Female Reproductive Axis.

PubMed

Limonta, Patrizia; Marelli, Marina Montagnani; Moretti, Roberta; Marzagalli, Monica; Fontana, Fabrizio; Maggi, Roberto

2018-01-01

Gonadotropin-releasing hormone (GnRH) is recognized as the central regulator of the functions of the pituitary-gonadal axis. The increasing knowledge on the mechanisms controlling the development and the function of GnRH-producing neurons is leading to a better diagnostic and therapeutic approach for hypogonadotropic hypogonadisms and for alterations of the puberty onset. During female life span, the function of the GnRH pulse generator may be affected by a number of inputs from other neuronal systems, offering alternative strategies for diagnostic and therapeutic interventions. Moreover, the identification of a GnRH/GnRH receptor system in both human ovary and endometrium has widened the spectrum of action of the peptide outside its hypothalamic functions. The pharmacological use of GnRH itself or its synthetic analogs (agonists and antagonists) provides a valid tool to either stimulate or block gonadotropin secretion and to modulate the female fertility in several reproductive disorders and in assisted reproduction technology. The use of GnRH agonists in young female patients undergoing chemotherapy is also considered a promising therapeutic approach to counteract iatrogenic ovarian failure. © 2018 Elsevier Inc. All rights reserved.

Role of rescue IVF-ET treatment in the management of high response in stimulated IUI cycles.

PubMed

Olufowobi, O; Sharif, K; Papaioannou, S; Mohamed, H; Neelakantan, D; Afnan, M

2005-02-01

Rescue in-vitro fertilisation and embryo transfer (IVF-ET) has been used in high response gonadotrophin intrauterine insemination (IUI) cycles to minimise the risks of ovarian hyperstimulation and multiple gestation. Such unplanned IVF treatment increases the cost of treatment. But can this added cost and the risks associated with IVF be justified? We present our experience with this treatment using clinical pregnancy and live birth rates as the primary outcomes. Between 1998 to 2001, 40 women undergoing IUI cycles who over responded (>3 follicles measuring >15 mm in diameter on the planned day of hCG administration) to gonadotrophin were offered the choice of conversion to IVF-ET or cancel the cycle. 17/40 declined rescue IVF/ET and had their cycles cancelled. 23/40 converted to IVF/ET and underwent transvaginal oocyte retrieval. 21/23 had embryo transferred. The clinical pregnancy and live birth rates were 52% and 48%, respectively. Rescue IVF-ET offers excellent clinical pregnancy and live birth rates in high responders. However, affordability can be an obstacle in the utilization of this treatment option.

[Increased risk of relapse in multiple sclerosis patients after ovarian stimulation for in vitro fertilization].

PubMed

Laplaud, D-A; Lefrère, F; Leray, E; Barrière, P; Wiertlewski, S

2007-10-01

In this preliminary study we analysed the impact of ovarian stimulations and the different protocols used for in vitro fertilizations (IVF) on the clinical activity of multiple sclerosis (MS). By matching the databases on MS and IVF of the past 10 years at the university hospital of Nantes, six patients have been found and, for five of them MS relapse rate seemed to be increased in the three-month period following IVF as compared to the previous three months and to two other control periods of three months (P<0.05, Friedman test). The increased relapse rate mainly concerned patients treated by GnRH agonists but not the patients treated by GnRH antagonists. This preliminary work suggests a possible impact of the treatments used for IVF on MS relapse rate. Further studies are now underway to validate these results on a larger scale, by including all cases reported in France.

Prediction of Poor Ovarian response by Biochemical and Biophysical Markers: A Logistic Regression Model.

PubMed

Jaiswar, S P; Natu, S M; Sujata; Sankhwar, P L; Manjari, Gupta

2015-12-01

To study correlation between ovarian reserve with biophysical markers (antral follicle count and ovarian volume) and biochemical markers (S. FSH, S. Inhibin B, and S. AMH) and use these markers to predict poor ovarian response to ovarian induction. This is a prospective observational study. One hundred infertile women attending the Obst & Gynae Dept, KGMU were recruited. Blood samples were collected on day 2/day 3 for assessment of S. FSH, S. Inhibin B, and S. AMH and TVS were done for antral follicle count and ovarian volume. Clomephene citrate 100 mg 1OD was given from day 2 to 6, and patients were followed up with serial USG measurements. The numbers of dominant follicles (> or = 14 mm) at the time of hCG administration were counted. Patients with <3 follicles in the 1st cycle were subjected to the 2nd cycle of clomephene 100 mg 1OD from day 2 to day 6 with Inj HMG 150 IU given i.m. starting from day 8 and every alternate day until at least one leading follicle attained ≥18 mm. Development of <3 follicles at end of the 2nd cycle was considered as poor response. Univariate analyses showed that s. inhibin B presented the highest (ROCAUC = 0.862) discriminating potential for predicting poor ovarian response, In multivariate logistic regression model, the variables age, FSH, AMH, INHIBIN B, and AFC remained significant, and the resulting model showed a predicted accuracy of 84.4 %. A derived multimarker computation by a logistic regression model for predicting poor ovarian response was obtained through this study. Thus, potential poor responders could be identified easily, and appropriate ovarian stimulation protocol could be devised for such pts.

Human umbilical cord mesenchymal stem cells improve the reserve function of perimenopausal ovary via a paracrine mechanism.

PubMed

Li, Jia; Mao, QiuXian; He, JingJun; She, HaoQing; Zhang, Zhi; Yin, ChunYan

2017-03-09

Human umbilical cord mesenchymal stem cells (hUCMSCs) are a type of pluripotent stem cell which are isolated from the umbilical cord of newborns. hUCMSCs have great therapeutic potential. We designed this experimental study in order to investigate whether the transplantation of hUCMSCs can improve the ovarian reserve function of perimenopausal rats and delay ovarian senescence. We selected naturally aging rats confirmed by vaginal smears as models of perimenopausal rats, divided into the control group and the treatment group, and selected young fertile female rats as normal controls. hUCMSCs were transplanted into rats of the treatment group through tail veins. Enzyme-linked immunosorbent assay (ELISA) detected serum levels of sex hormones, H&E staining showed ovarian tissue structure and allowed follicle counting, immunohistochemistry and western blot analysis revealed ovarian expression of hepatocyte growth factor (HGF), vascular endothelial cell growth factor (VEGF), and insulin-like growth factor-1 (IGF-1), polymerase chain reaction (PCR) and western blot analysis revealed hUCMSCs expression of HGF, VEGF, and IGF-1. At time points of 14, 21, and 28 days after hUCMSCs transplantation, estradiol (E 2 ) and anti-Müllerian hormone (AMH) increased while follicle-stimulating hormone (FSH) decreased; ovarian structure improved and follicle number increased; ovarian expression of HGF, VEGF, and IGF-1 protein elevated significantly. Meanwhile, PCR and western blot analysis indicated hUCMSCs have the capacity of secreting HGF, VEGF, and IGF-1 cytokines. Our results suggest that hUCMSCs can promote ovarian expression of HGF, VEGF, and IGF-1 through secreting those cytokines, resulting in improving ovarian reserve function and withstanding ovarian senescence.

Precocious pseudopuberty due to an autonomous ovarian follicular cyst: case report with a review of literatures

PubMed Central

2013-01-01

Background Small follicular cysts are commonly found in the ovaries of prepubertal girls, and in most cases, they are of no clinical importance. These cysts are usually self-limiting and resolve spontaneously. However, occasionally, these cysts may enlarge and continue to produce estrogen, resulting in signs of sexual precocity. Here, we report a case of precocious pseudopuberty associated with an autonomous ovarian follicular cyst. Case presentation A 5.9-year-old girl initially presented to a local clinic with vaginal bleeding and a large unilateral ovarian cyst. At 6 months after the initial acute episode, the patient visited our hospital as the ovarian cyst had persisted and increased in size. Endocrinological examination showed elevated estrogen levels and suppressed gonadotropin levels on GnRH stimulation test. Also, no skin pigmentation or bone anomaly was noted. Based on these observations, laparoscopic cystectomy was performed, and histologic analysis confirmed the diagnosis of a follicular cyst. After the laparoscopic cystectomy, the patient’s hormone levels returned to normal and no ovarian cyst was detected by ultrasound. Conclusions As autonomous ovarian cysts are usually self-limiting disorder, no treatment is necessary. Therefore, surgical management should be deferred as long as possible to avoid the risk of repeat surgery, as pseudoprecocious puberty due to autonomous ovarian cysts can resolve spontaneoulsy and frequently recurs. Precocious pseudopuberty with an ovarian cyst may be due to granulosa cell tumor or may be one symptom of the McCune-Albright Syndrome (MAS). A careful longer-term follow up of patients with autonomous ovarian cysts and/or molecular studies may be necessary in such cases. PMID:23937919

The Safety of Ovarian Preservation in Stage I Endometrial Endometrioid Adenocarcinoma Based on Propensity Score Matching.

PubMed

Hou, Ting; Sun, Yidi; Li, Junyi; Liu, Chenglin; Wang, Zhen; Li, Yixue; Lu, Yuan

2017-01-01

Most patients with early stage endometrial endometrioid adenocarcinoma (EEAC) are treated with hysterectomy and bilateral oophorectomy. But this surgical menopause leads to long-term sequelae for premenopausal women, especially for young women of childbearing age. This population-based study was to evaluate the safety of ovarian preservation in young women with stage I EEAC. Patients of age 50 or younger with stage I EEAC were explored from the Surveillance, Epidemiology and End Results program database during 2004 to 2013. Propensity score matching was used to randomize the data set and reduce the selection biases of doctors. Univariate analysis and multivariate cox proportional hazards model were utilized to estimate the safety of ovarian preservation. A total of 7183 patients were identified, and ovarian preservation was performed in 863 (12 %) patients. Compared with women treated with oophorectomy, patients with ovarian preservation significantly tend to be younger at diagnosis (P-value < 0.001) and more likely diagnosed as stage IA EEAC, to have better differentiated tumor tissues and smaller tumors, as well as less likely to undergo radiation and lymphadenectomy. 863 patients treated with oophorectomy were selected by propensity score matching. After propensity score matching, the differences of all characteristics between ovarian preservation and oophorectomy were not significant and potential confounders in the two groups decreased. In univariate analysis of matched population, ovarian preservation had no effect on overall (P-value=0.928) and cancer-specific (P-value=0.390) mortality. In propensityadjusted multivariate analysis, ovarian preservation was not significantly associated with overall (HR=0.69, 95%CI=0.41-1.68, P-value=0.611) and cancer-specific (HR=1.65, 95%CI=0.54-5.06, Pvalue= 0.379) survival. Ovarian preservation is safe for young women with stage I EEAC, which is not significantly associated with overall and cancer-specific mortality. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Occult Form of Premature Ovarian Insufficiency in Women with Infertility and Oligomenorrhea as Assessed by Poor Ovarian Response Criteria.

PubMed

Izhar, Rubina; Husain, Samia; Tahir, Suhaima; Husain, Sonia

2017-01-01

The purpose of this study was to evaluate the ability of poor ovarian response criteria to classify women presenting with infertility and oligomenorrhea as having "occult" premature ovarian insufficiency. This was a cross sectional study conducted at Aziz Medical Center, Karachi, Pakistan from 1st August 2015 to 31st July 2016. Women with infertility and oligomenorrhea were included. All eligible women underwent day 2 FSH level and an early follicular phase transvaginal ultrasound to assess the antral follicular count (AFC). All women then underwent the confirmatory test, of Anti-Mullerian Hormone (AMH) level. The main outcome measure was assignment to occult premature ovarian insufficiency (POI) after screening that used the criteria set out in fertility guideline for predicting the likely ovarian response to gonadotrophin stimulation. Another measure was to compare the sensitivity and specificity of the two index criteria, of FSH and AFC, relative to the emerging reference standard, of the AMH criterion. The three criteria together classified 59 (34.91%) women as occult POI in those with oligomenorrhea. The sensitivity, specificity, negative predictive value and positive predictive value of FSH relative to AMH for these women were 77.8%, 95.7%, 90.2% and 89.4%, respectively whereas the same values of AFC relative to AMH were 92.6%, 99.1 %, 96.6% and 98%, respectively. Women with menstrual irregularity and infertility are at a higher risk for satisfying criteria of poor ovarian response irrespective of age. A policy incorporating these surrogate markers can be used to screen these women for occult premature ovarian insufficiency.

Effects of previous ovarian surgery for endometriosis on the outcome of assisted reproduction treatment.

PubMed

Geber, Selmo; Ferreira, Daniela Parreiras; Spyer Prates, Luis Felipe Víctor; Sales, Liana; Sampaio, Marcos

2002-01-01

Endometriosis affects 2-50% of women at reproductive age. Surgery is an option for treatment, but there is no convincing evidence that it promotes a significant improvement in fertility. Also, the removal of ovarian endometrioma might lead to a reduction in the follicular reserve and response to stimulation. Therefore, the aim of this study was to evaluate the effect of previous ovarian surgery for endometriosis on the ovarian response in assisted reproduction treatment cycles and its pregnancy outcome. A total of 61 women, with primary infertility and previously having undergone ovarian surgery for endometriosis, who had received 74 IVF/intracytoplasmic sperm injection (ICSI) cycles, were studied (study group). A further 74 patients with primary infertility who underwent 77 IVF/ICSI cycles within#10; the same period of time, at the same clinic and without previous ovarian surgery or endometriosis were studied as a control group. Patients were matched for age and treatment performed. Patients 35 years with previous ovarian surgery needed more ampoules for ovulation induction (P = 0.017) and had fewer follicles and oocytes than women in the control group (P = 0.001). Duration of folliculogenesis was similar in both groups, as was fertilization rate. A total of 10 patients achieved pregnancy in the study group (34.5%) and 14 (48.3%) in the control group. Although a lower pregnancy rate was observed in patients who had undergone previous ovarian surgery, this difference was not statistically significant (P = 0.424). In conclusion, ovarian surgery for the treatment of endometriosis reduces the ovarian outcome in IVF/ICSI cycles in women >35 years old, and might also decrease pregnancy rates. Therefore, for infertile patients, non-surgical treatment might be a better option to avoid reduction of the ovarian response.

A proteomic analysis identifies candidate early biomarkers to predict ovarian hyperstimulation syndrome in polycystic ovarian syndrome patients.

PubMed

Wu, Lan; Sun, Yazhou; Wan, Jun; Luan, Ting; Cheng, Qing; Tan, Yong

2017-07-01

Ovarian hyperstimulation syndrome (OHSS) is a potentially life‑threatening, iatrogenic complication that occurs during assisted reproduction. Polycystic ovarian syndrome (PCOS) significantly increases the risk of OHSS during controlled ovarian stimulation. Therefore, a more effective early prediction technique is required in PCOS patients. Quantitative proteomic analysis of serum proteins indicates the potential diagnostic value for disease. In the present study, the authors revealed the differentially expressed proteins in OHSS patients with PCOS as new diagnostic biomarkers. The promising proteins obtained from liquid chromatography‑mass spectrometry were subjected to ELISA and western blotting assay for further confirmation. A total of 57 proteins were identified with significant difference, of which 29 proteins were upregulated and 28 proteins were downregulated in OHSS patients. Haptoglobin, fibrinogen and lipoprotein lipase were selected as candidate biomarkers. Receiver operating characteristic curve analysis demonstrated all three proteins may have potential as biomarkers to discriminate OHSS in PCOS patients. Haptoglobin, fibrinogen and lipoprotein lipase have never been reported as a predictive marker of OHSS in PCOS patients, and their potential roles in OHSS occurrence deserve further studies. The proteomic results reported in the present study may gain deeper insights into the pathophysiology of OHSS.

Pregnancy rate in women with adenomyosis undergoing fresh or frozen embryo transfer cycles following gonadotropin-releasing hormone agonist treatment.

PubMed

Park, Chan Woo; Choi, Min Hye; Yang, Kwang Moon; Song, In Ok

2016-09-01

To determine the preferred regimen for women with adenomyosis undergoing in vitro fertilization (IVF), we compared the IVF outcomes of fresh embryo transfer (ET) cycles with or without gonadotropin-releasing hormone (GnRH) agonist pretreatment and of frozen-thawed embryo transfer (FET) cycles following GnRH agonist treatment. This retrospective study included 241 IVF cycles of women with adenomyosis from January 2006 to January 2012. Fresh ET cycles without (147 cycles, group A) or with (105 cycles, group B) GnRH agonist pretreatment, and FET cycles following GnRH agonist treatment (43 cycles, group C) were compared. Adenomyosis was identified by using transvaginal ultrasound at the initial workup and classified into focal and diffuse types. The IVF outcomes were also subanalyzed according to the adenomyotic region. GnRH agonist pretreatment increased the stimulation duration (11.5±2.1 days vs. 9.9±2.0 days) and total dose of gonadotropin (3,421±1,141 IU vs. 2,588±1,192 IU), which resulted in a significantly higher number of retrieved oocytes (10.0±8.2 vs. 7.9±6.8, p=0.013) in group B than in group A. Controlled ovarian stimulation for freezing resulted in a significantly higher number of retrieved oocytes (14.3±9.2 vs. 10.0±8.2, p=0.022) with a lower dose of gonadotropin (2,974±1,112 IU vs. 3,421±1,141 IU, p=0.037) in group C than in group B. The clinical pregnancy rate in group C (39.5%) tended to be higher than those in groups B (30.5%) and A (25.2%) but without a significant difference. FET following GnRH agonist pretreatment tended to increase the pregnancy rate in patients with adenomyosis. Further large-scale prospective studies are required to confirm this result.

Inhibition of cyclooxygenase-2 (COX-2) by meloxicam decreases the incidence of ovarian hyperstimulation syndrome in a rat model.

PubMed

Quintana, Ramiro; Kopcow, Laura; Marconi, Guillermo; Young, Edgardo; Yovanovich, Carola; Paz, Dante A

2008-10-01

To investigate the effects of selective cyclooxygenase-2 (COX-2) inhibition on the ovarian hyperstimulation syndrome (OHSS) in an experimental model. Controlled laboratory study. University-affiliated fertility center. Female Wistar rats. Female Wistar rats (22 days old) were divided into four groups: group 1 (control group; n = 10) received 0.1 mL of intraperitoneal (IP) saline from days 22-26; group 2 (mild-stimulated group; n = 10) received 10 IU of pregnant mare serum gonadotropin (PMSG) on day 24 and 10 IU of hCG 48 hours later (day 26); group 3 (OHSS group; n = 10) was given 10 IU of PMSG for 4 consecutive days from day 22 and 30 IU hCG on the fifth day to induce OHSS; group 4 was treated the same as group 3, but received 2 muL (15 mg/mL) of meloxicam 2 hours before the PMSG injection for 4 consecutive days, and 2 hours before the hCG injection on the fifth day. All groups were killed on day 26. Number of antral and luteinized follicles, ovarian weight, semiquantitative vascular endothelial growth factor (VEGF) and COX-2 immunohistochemistry. There were no differences in the ovarian weight between groups 1 and 2. Group 3 showed significantly increased ovarian weight that was suppressed, in group 4, by meloxicam. There was no difference in the number of antral follicles among the four groups. In the mild-stimulated and OHSS groups, the granulosa cells (GC) of preovulatory follicles and the stromal cells showed intense VEGF immunoreactivity. The ovaries from the meloxicam-treated group showed less immunoreactivity than the OHSS group, indicating diminished VEGF expression associated with meloxicam treatment. Group 3 (OHSS group) showed increased COX-2 immunoreactivity that was diminished in the meloxicam-treated group. Meloxicam treatment did not affect the hormone-induced increase in serum E(2) levels seen in OHSS rats. Our results in a rat model suggest that meloxicam has a beneficial effect on OHSS by reducing the increases in ovarian weight and VEGF expression associated with OHSS. These effects may be mediated by the COX-2 inhibitory capacity of meloxicam.

3 to 5 Years Later: Long-term Effects of Prophylactic Bilateral Salpingectomy on Ovarian Function.

PubMed

Venturella, Roberta; Lico, Daniela; Borelli, Massimo; Imbrogno, Maria G; Cevenini, Gabriele; Zupi, Errico; Zullo, Fulvio; Morelli, Michele

2017-01-01

Preliminary data on the effects of prophylactic bilateral salpingectomy (PBS) show that postoperative ovarian function is preserved up to 3 months after surgery. The confirmation of PBS safety on ovarian function even many years after surgery is essential to reassure the medical community that this new strategy, recently proposed for the prevention of ovarian cancer, is at least able to avoid the risk of premature surgical menopause. We investigated whether the addition of PBS during total laparoscopic hysterectomy (TLH) causes long-term effects on ovarian function. An observational study (Canadian Task Force classification II-3). Department of Obstetrics and Gynecology, "Magna Graecia" University, Catanzaro, Italy. Seventy-nine patients who underwent TLH plus salpingectomy between September 2010 and September 2012 at our institution have been recalled to be submitted to ovarian reserve evaluation in February 2015. Eight of 79 women refused to participate in this follow-up study. The ovarian age of PBS patients has been determined through OvAge (OvAge sr., Catanzaro, Italy), a statistical model that combines antimüllerian hormone, follicle-stimulating hormone, 3-dimensional antral follicle count, vascular index, flow index, and vascular flow index values. The control group consisted of a large population of 652 healthy women (with intact uterus and adnexa) previously enrolled to build the OvAge model. Comparisons between ovarian ages of PBS patients and the control group have been assessed by analysis of covariance linear statistical modeling. The main outcome measurement was the differences in the behavior within OvAge/age relation between PBS and control women. Descriptive statistics of those 71 enrolled PBS patients are the following: age, 49.61 ± 2.15 years; OvAge, 49.22 ± 2.57 years; follicle-stimulating hormone, 43.02 ± 19.92 mU/mL; antimüllerian hormone, 0.12 ± 0.20 ng/mL; 3-dimensional antral follicle count, 1.91 ± 1.28; vascular index, 2.80% ± 5.32%; flow index, 19.37 ± 5.88; and vascular flow index, 0.56 ± 1.12. Analysis of covariance disclosed that PBS and control women do not exhibit different behaviors (p = .900) within OvAge/age relation. According to our model, the addition of PBS to TLH in the late reproductive years does not modify the ovarian age of treated women up to 3 to 5 years after surgery. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Maternal stress-associated cortisol stimulation may protect embryos from cortisol excess in zebrafish.

PubMed

Faught, Erin; Best, Carol; Vijayan, Mathilakath M

2016-02-01

Abnormal embryo cortisol level causes developmental defects and poor survival in zebrafish (Danio rerio). However, no study has demonstrated that maternal stress leads to higher embryo cortisol content in zebrafish. We tested the hypothesis that maternal stress-associated elevation in cortisol levels increases embryo cortisol content in this asynchronous breeder. Zebrafish mothers were fed cortisol-spiked food for 5 days, to mimic maternal stress, followed by daily breeding for 10 days to monitor temporal embryo cortisol content. Cortisol treatment increased mean embryo yield, but the daily fecundity was variable among the groups. Embryo cortisol content was variable in both groups over a 10-day period. A transient elevation in cortisol levels was observed in the embryos from cortisol-fed mothers only on day 3, but not on subsequent days. We tested whether excess cortisol stimulates 11βHSD2 expression in ovarian follicles as a means to regulate embryo cortisol deposition. Cortisol treatment in vitro increased 11β HSD2 levels sevenfold, and this expression was regulated by actinomycin D and cycloheximide suggesting tight regulation of cortisol levels in the ovarian follicles. We hypothesize that cortisol-induced upregulation of 11βHSD2 activity in the ovarian follicles is a mechanism restricting excess cortisol incorporation into the eggs during maternal stress.

The impact of type and number of bowel resections on anastomotic leakage risk in advanced ovarian cancer surgery.

PubMed

Grimm, Christoph; Harter, Philipp; Alesina, Pier F; Prader, Sonia; Schneider, Stephanie; Ataseven, Beyhan; Meier, Beate; Brunkhorst, Violetta; Hinrichs, Jakob; Kurzeder, Christian; Heitz, Florian; Kahl, Annett; Traut, Alexander; Groeben, Harald T; Walz, Martin; du Bois, Andreas

2017-09-01

To identify risk factors for anastomotic leakage (AL) in patients undergoing primary advanced ovarian cancer surgery and to evaluate the prognostic implication of AL on overall survival in these patients. We analyzed our institutional database for primary EOC and included all consecutive patients treated by debulking surgery including any type of full circumferential bowel resection beyond appendectomy between 1999 and 2015. We performed logistic regression models to identify risk factors for AL and log-rank tests and Cox proportional hazards models to evaluate the association between AL and survival. AL occurred in 36/800 (4.5%; 95% confidence interval [3%-6%]) of all patients with advanced ovarian cancer and 36/518 (6.9% [5%-9%]) patients undergoing bowel resection during debulking surgery. One hundred fifty-six (30.1%) patients had multiple bowel resections. In these patients, AL rate per patient was only slightly higher (9.0% [5%-13%]) than in patients with rectosigmoid resection only (6.9% [4%-10%]), despite the higher number of anastomosis. No independent predictive factors for AL were identified. AL was independently associated with shortened overall survival (HR 1.9 [1.2-3.4], p=0.01). In the present study, no predictive pre- and/or intraoperative risk factors for AL were identified. AL rate was mainly influenced by rectosigmoid resection and only marginally increased by additional bowel resections. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessing the Risk of Occult Cancer and 30-day Morbidity in Women Undergoing Risk-reducing Surgery: A Prospective Experience.

PubMed

Bogani, Giorgio; Tagliabue, Elena; Signorelli, Mauro; Chiappa, Valentina; Carcangiu, Maria Luisa; Paolini, Biagio; Casarin, Jvan; Scaffa, Cono; Gennaro, Massimiliano; Martinelli, Fabio; Borghi, Chiara; Ditto, Antonino; Lorusso, Domenica; Raspagliesi, Francesco

To investigate the incidence and predictive factors of 30-day surgery-related morbidity and occult precancerous and cancerous conditions for women undergoing risk-reducing surgery. A prospective study (Canadian Task Force classification II-1). A gynecologic oncology referral center. Breast-related cancer antigen (BRCA) mutation carriers and BRCAX patients (those with a significant family history of breast and ovarian cancer). Minimally invasive risk-reduction surgery. Overall, 85 women underwent risk-reducing surgery: 30 (35%) and 55 (65%) had hysterectomy plus bilateral salpingo-oophorectomy (BSO) and BSO alone, respectively. Overall, in 6 (7%) patients, the final pathology revealed unexpected cancer: 3 early-stage ovarian/fallopian tube cancers, 2 advanced-stage ovarian cancers (stage IIIA and IIIB), and 1 serous endometrial carcinoma. Additionally, 3 (3.6%) patients had incidental finding of serous tubal intraepithelial carcinoma. Four (4.7%) postoperative complications within 30 days from surgery were registered, including fever (n = 3) and postoperative ileus (n = 1); no severe (grade 3 or more) complications were observed. All complications were managed conservatively. The presence of occult cancer was the only factor predicting the development of postoperative complications (p = .02). Minimally invasive risk-reducing surgery is a safe and effective strategy to manage BRCA mutation carriers. Patients should benefit from an appropriate counseling about the high prevalence of undiagnosed cancers observed at the time of surgery. Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.

A non-pregnant woman with elevated beta-HCG: A case of para-neoplastic syndrome in ovarian cancer.

PubMed

Goldstein, Jennifer; Pandey, Prasamsa; Fleming, Nicole; Westin, Shannon; Piha-Paul, Sarina

2016-08-01

There is a broad range of possible diagnoses for an elevated beta human chorionic gonadotropin (β-hCG) in the absence of intrauterine or ectopic pregnancy. When women of child bearing potential undergo evaluation for clinical trial, it is often unclear what course of evaluation to take when a pregnancy test is positive. We describe the clinical course of a patient with widely metastatic mucinous ovarian carcinoma with metastasis to the peritoneum, lymph nodes and liver. The patient was found to have a mildly elevated β-hCG during initial evaluation for clinical trial. Extensive work up for ectopic pregnancy, trophoblastic disease, and phantom β-hCG were negative. The patient's β-hCG levels continued to rise until initiation of therapy. She was treated on a phase I protocol with restaging scans revealing a partial response. The β-hCG was retested and declined in conjunction with her response, consistent with paraneoplastic β-hCG. Here, we propose a decision making algorithm to evaluate a patient with an elevated β-hCG undergoing assessment for clinical trial.

Higher success rate with transcranial electrical stimulation of motor-evoked potentials using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery.

PubMed

Shigematsu, Hideki; Kawaguchi, Masahiko; Hayashi, Hironobu; Takatani, Tsunenori; Iwata, Eiichiro; Tanaka, Masato; Okuda, Akinori; Morimoto, Yasuhiko; Masuda, Keisuke; Tanaka, Yuu; Tanaka, Yasuhito

2017-10-01

During spine surgery, the spinal cord is electrophysiologically monitored via transcranial electrical stimulation of motor-evoked potentials (TES-MEPs) to prevent injury. Transcranial electrical stimulation of motor-evoked potential involves the use of either constant-current or constant-voltage stimulation; however, there are few comparative data available regarding their ability to adequately elicit compound motor action potentials. We hypothesized that the success rates of TES-MEP recordings would be similar between constant-current and constant-voltage stimulations in patients undergoing spine surgery. The objective of this study was to compare the success rates of TES-MEP recordings between constant-current and constant-voltage stimulation. This is a prospective, within-subject study. Data from 100 patients undergoing spinal surgery at the cervical, thoracic, or lumbar level were analyzed. The success rates of the TES-MEP recordings from each muscle were examined. Transcranial electrical stimulation with constant-current and constant-voltage stimulations at the C3 and C4 electrode positions (international "10-20" system) was applied to each patient. Compound muscle action potentials were bilaterally recorded from the abductor pollicis brevis (APB), deltoid (Del), abductor hallucis (AH), tibialis anterior (TA), gastrocnemius (GC), and quadriceps (Quad) muscles. The success rates of the TES-MEP recordings from the right Del, right APB, bilateral Quad, right TA, right GC, and bilateral AH muscles were significantly higher using constant-voltage stimulation than those using constant-current stimulation. The overall success rates with constant-voltage and constant-current stimulations were 86.3% and 68.8%, respectively (risk ratio 1.25 [95% confidence interval: 1.20-1.31]). The success rates of TES-MEP recordings were higher using constant-voltage stimulation compared with constant-current stimulation in patients undergoing spinal surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic risk assessment for women with epithelial ovarian cancer: referral patterns and outcomes in a university gynecologic oncology clinic.

PubMed

Petzel, Sue V; Vogel, Rachel Isaksson; Bensend, Tracy; Leininger, Anna; Argenta, Peter A; Geller, Melissa A

2013-10-01

Little is known about genetic service utilization and ovarian cancer. We identified the frequency and outcome of genetic counseling referral, predictors of referral, and referral uptake for ovarian cancer patients. Using pathology reports, we identified all epithelial ovarian cancer patients seen in a university gynecologic oncology clinic (1/04-8/06). Electronic medical records (EMR) were used to document genetic service referral, time from diagnosis-to-referral, point-in-treatment at referral, personal/family cancer history, demographics, and genetic test results. Groups were compared using chi-squared and Fisher's exact test for categorical variables and t-tests for continuous variables. The study population consisted of 376 women with ovarian cancer, 72 (19 %) of who were referred for genetic counseling/testing, primarily during surveillance. Of those referred, 42 (58 %) had personal or family genetic counseling and 34 (47 %) were ultimately tested or identified due to known family mutation. Family history and prior cancer were associated with referral. Family history, living in a larger community, higher-stage disease, and serous histology were associated with undergoing genetic counseling. Risk assessment identified 20 BRCA1/2 (5.3 %) and 1 HNPCC (0.3 %) mutation carriers. Based on recent estimates that 11.7-16.6 % of women with ovarian cancer are BRCA carriers and 2 % are HNPCC carriers, results suggest under-identification of carriers and under-utilization of genetic services by providers and patients. Interventions to increase medical providers' referrals, even in a specialized oncology clinic, are necessary and may include innovations in educating these providers using web-based methods. Ease of referral by the introduction of an electronic cancer genetic referral form represents another new direction that may increase genetic risk assessment for high-risk women with ovarian cancer.

New methods to improve the safety assessment of cryopreserved ovarian tissue for fertility preservation in breast cancer patients.

PubMed

Rodríguez-Iglesias, Beatriz; Novella-Maestre, Edurne; Herraiz, Sonia; Díaz-García, César; Pellicer, Nuria; Pellicer, Antonio

2015-12-01

To develop a novel molecular panel of markers to detect breast cancer (BC) disseminated malignant cells in ovarian tissue, and to improve the safety of ovarian tissue transplantation. Experimental study. University hospital. Ten ovarian biopsies from healthy patients, 13 biopsies with diagnosed BC metastasis, and 4 biopsies from primary BC tumor for designing a diagnostic panel of BC cell contamination; 60 ovarian biopsies from BC patients undergoing fertility preservation for validating the panel. Female nude mice. A novel panel for BC malignant cell detection by reverse-transcription polymerase chain reaction (RT-PCR), inmmunohistochemical analysis, in vitro invasion assay and xenotransplantation assayed in ovarian tissue from BC patients. Expression of GCDFP15, MGB1, SBEM, MUC1, WT-1, and NY-BR-01, selected as markers, assessed by quantitative RT-PCR in samples with confirmed BC metastasis. The most sensitive markers were confirmed by immunohistochemistry, and tested in vitro and in vivo. GCDFP15, MGB1, and SBEM were the most sensitive and specific markers to detect BC metastatic cells when at least one was expressed by quantitative RT-PCR. The panel was validated in 60 patients and confirmed in an in vitro invasion assay, where no invasive cells were observed. Samples negative for BC cells cannot develop disease when xenografted. GCDFP15, MGB1, and SBEM were the most sensitive molecules to create a diagnostic panel for BC malignant cell contamination, which may make ovarian tissue cryopreservation and transplantation a safe technique for fertility preservation in BC patients. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The importance of neuronal growth factors in the ovary.

PubMed

Streiter, S; Fisch, B; Sabbah, B; Ao, A; Abir, R

2016-01-01

The neurotrophin family consists of nerve growth factor (NGF), neurotrophin 3 (NT3) and neurotrophin 4/5 (NT4/5), in addition to brain-derived neurotrophic factor (BDNF) and the neuronal growth factors, glial cell line-derived neurotrophic factor (GDNF) and vasointestinal peptide (VIP). Although there are a few literature reviews, mainly of animal studies, on the importance of neurotrophins in the ovary, we aimed to provide a complete review of neurotrophins as well as neuronal growth factors and their important roles in normal and pathological processes in the ovary. Follicular assembly is probably stimulated by complementary effects of NGF, NT4/5 and BDNF and their receptors. The neurotrophins, GDNF and VIP and their receptors have all been identified in preantral and antral follicles of mammalian species, including humans. Transgenic mice with mutations in the genes encoding for Ngf, Nt4/5 and Bdnf and their tropomyosin-related kinase β receptor showed a reduction in preantral follicles and an abnormal ovarian morphology, whereas NGF, NT3, GDNF and VIP increased the in vitro activation of primordial follicles in rats and goats. Additionally, NGF, NT3 and GDNF promoted follicular cell proliferation; NGF, BDNF and VIP were shown to be involved in ovulation; VIP inhibited follicular apoptosis; NT4/5, BDNF and GDNF promoted oocyte maturation and NGF, NT3 and VIP stimulated steroidogenesis. NGF may also exert a stimulatory effect in ovarian cancer and polycystic ovarian syndrome (PCOS). Low levels of NGF and BDNF in follicular fluid may be associated with diminished ovarian reserve and high levels with endometriosis. More knowledge of the roles of neuronal growth factors in the ovary has important implications for the development of new therapeutic drugs (such as anti-NGF agents) for ovarian cancer and PCOS as well as various infertility problems, warranting further research. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Estradiol attenuates EGF-induced rapid uPAR mobilization and cell migration via the G-protein-coupled receptor 30 in ovarian cancer cells.

PubMed

Henic, Emir; Noskova, Vera; Høyer-Hansen, Gunilla; Hansson, Stefan; Casslén, Bertil

2009-02-01

Epidermal growth factor (EGF) stimulates proliferation and migration in ovarian cancer cells, and high tumor expression of the EGF system correlates with poor prognosis. Epidermal growth factor upregulates urokinase plasminogen activator receptor (uPAR) on the cell surface via 3 distinct mechanisms: rapid mobilization of uPAR from detergent-resistant domains, increased mRNA, and decreased degradation. G-protein-coupled receptor 30 (GPR30) is a newly identified membrane estrogen receptor (ER).The objective of this study was to explore the effects of 17beta-estradiol (E(2)) on uPAR expression and cell migration in ovarian cancer cells and further to identify the ER involved.We used 7 ovarian cancer cell lines, cell migration assay, cellular binding of (125)I-uPA, cellular degradation of (125)I-uPA/PAI-1 complex, enzyme-linked immunosorbent assay for uPAR, solid-phase enzyme immunoassay for ERalpha, and quantitative polymerase chain reaction. Estradiol attenuates the stimulatory effect of EGF on cell migration and uPAR expression. Specifically, E(2) reduces the very rapid increase of detergent extractable uPAR, which occurs within minutes of EGF stimulation and probably represents mobilization of uPAR from detergent-resistant domains such as lipid rafts. Estradiol influenced neither the amount of uPAR mRNA nor the rate of uPAR degradation or solubilization. The nuclear ER antagonists ICI 182780 and tamoxifen, which are GPR30 agonists, as well as the specifically constructed GPR30 agonist G1, mimicked the effect of E(2) on uPAR expression and cell migration. OVCAR-3 cells express mRNA for GPR30.Estradiol attenuates EGF-induced mobilization of ligated uPAR from detergent-resistant domains and subsequent migration in ovarian cancer cells. The response to various ER ligands indicates that this effect is mediated via the membrane ER GPR30.

The non-preventive effects of human menopausal gonadotropins on ovarian tissues in Nandrolone decanoate-treated female rats: A histochemical and ultra-structural study.

PubMed

Mesbah, Fakhroddin; Bordbar, Hossein; Talaei Khozani, Tahereh; Dehghani, Farzaneh; Mirkhani, Hossein

2018-03-01

The follicular growth and development may be affected by abused drugs. Nandrolone decanoate (ND) as an anabolic androgenic steroid can damage the morphological and functional features of the ovary and may lead to reproductive failure. This study was designed to evaluate the effects of synchronized and non-synchronized administration of Human Menopausal Gonadotropins (hMG) with ND on ovarian tissue and level of sex hormones in the adult female rat. Forty adult female Sprague Dawley rats were divided into eight groups. The five experimental groups received 3 and/or 10 mg/kg of ND synchronized and non-synchronized with 10 IU of hMG and hMG alone. The two shams and control groups received solvents of ND and hMG. The animals' serum levels of Follicle-stimulating hormone, Luteinizing hormone, progesterone and estrogen and the weight, volume and dimensions of the ovaries were measured. The ovaries were prepared for apoptosis assessment and morphological study. The ovarian volume and sex hormones in the experimental groups were decreased, but ovarian weight and dimensions didn't change. The rate of apoptosis was increased in the experimental groups as follows; a low and high dose of ND synchronized with hMG 48.80±18.70 and 65.20±14.20 respectively vs. Sham 1, 33.20±17.80, a low and high dose of ND non-synchronized with hMD 55.80±17.20 and 75.20±14.30 respectively vs. Sham 2, 31.60±32.40 groups, p˂0.01. Follicular and stromal cells were damaged in the experimental groups except for the hMG group. Administration of ND decreased the serum level of Luteinizing hormone, Follicle-stimulating hormone, progesterone and estrogen and damaged ovarian tissue irreversibly and irreparably and hMG cannot prevent the destruction of the follicles in the adult female rats. This can be a serious warning to women who abuse ND.

Relationship of ovarian stimulation response with vascular endothelial growth factor and degree of granulosa cell apoptosis.

PubMed

Quintana, R; Kopcow, L; Marconi, G; Sueldo, C; Speranza, G; Barañao, R I

2001-09-01

The aim of this study was to evaluate the concentration of vascular endothelial growth factor (VEGF) in follicular fluid and in granulosa cell cultures in relation to the degree of apoptosis in granulosa cells from patients with different types of ovarian response to controlled ovarian hyperstimulation. We studied 30 women who underwent controlled ovarian hyperstimulation and oocyte retrieval. Group A comprised patients with 1-4 follicles (n = 10), group B patients with 5-14 follicles (n = 10) and group C patients with >15 follicles (n = 10). Mean (+/-SD) VEGF concentrations in follicular fluid were 1232 +/- 209, 813 +/- 198 and 396 +/- 103 pg/ml for groups A, B and C respectively (P > 0.01). Concentrations of VEGF in granulosa cell supernatant were 684 +/- 316, 1101 +/- 295 and 1596 +/- 227 pg/ml respectively (P < 0.05). Percentages of apoptotic cells in granulosa cells culture was 55.02 +/- 7.5, 23.98 +/- 4.4 and 14.2 +/- 2.3% respectively (A versus B, P < 0.01, A versus C, P < 0.006, B versus C, NS). Our findings showed that in patients with decreased ovarian response to controlled ovarian hyperstimulation, follicular fluid VEGF concentration is elevated, the concentration from granulosa cells culture supernatant is decreased and the percentage of apoptotic granulosa cells is increased, while opposite findings occurred in patients with normal or hyper-responses.

[Corifollitropin alfa in women stimulated for the first time in in vitro fertilization programme].

PubMed

Vraná-Mardešićová, N; Vobořil, J; Melicharová, L; Jelínková, L; Vilímová, Š; Mardešić, T

2017-01-01

To compare results after stimulation with corifollitropin alfa (Elonva) in unselected group of women entering for the first time in in vitro fertilization programme (IVF) with results from Phase III randomized trials with selected groups of women. Prospective study. Sanatorium Pronatal, Praha. 40 unselected women with adequat ovarian reserve entering for the first time in IVF programme were stimulated with corifollitropin alfa and GnRH antagonists. Avarage age in the study group was 32,8 years (29-42 years), women younger then 36 and less then 60 kg received Elonva 100 µg , all others (age > 36 let, weight > 60 kg) Elonva 150 µg. Five days after egg retrieval one blastocyst was transferred (single embryo transfer - eSET). Our results were compared with the resuls in higly selected groups of women from Phase III randomized trials. After stimulation with corifollitropin alfa and GnRH antagonists on average 10,6 (9,2 ± 4,2) eggs could be retrieved, among them 7,3 (6,6 ± 3,9) were M II oocytes (68,9%) and fertilisation rate was 84,6%. After first embryo transfer ("fresh" embryos and embryos from "freeze all" cycles) 14 pregnancies were achieved (37,8%), three pregnancies were achieved later from transfer of frozen-thawed embryos (cumulative pregnancy rate 45,9%). There were three abortions. No severe hyperstimulation syndrom occured. Our results in unselected group of women stimulated for the first in an IVF programme with corifollitropin alfa are fully comparable with results published in randomized trials with selected group of patiens. Corifollitropin alfa in combination with daily GnRH antagonist can be successfully used in normal-responder patients stimulated for the first time in an IVF programmeKeywords: corifollitropin alfa, GnRH antagonists, ovarian stimulation, pregnancy.

Current approach to fertility preservation by embryo cryopreservation

PubMed Central

Bedoschi, Giuliano; Oktay, Kutluk

2013-01-01

The ovaries are susceptible to damage following treatment with gonadotoxic chemotherapy, pelvic radiotherapy, and/or ovarian surgery. Gonadotoxic treatments have also been used in patients with various nonmalignant systemic diseases. Any women of reproductive age with a sufficiently high risk of developing future ovarian failure due to those medical interventions may benefit from embryo cryopreservation though the tools of assessment of such a risk are still not very precise. Furthermore, the risk assessment can be influenced by many other factors such as the delay expected after chemotherapy and the number of children desired in the future. Embryo cryopreservation is an established and most successful method of fertility preservation when there is sufficient time available to perform ovarian stimulation. This publication will review the current state, approach, and indications of embryo cryopreservation for fertility preservation. PMID:23535505

Granulocyte colony-stimulating factor in repeated IVF failure, a randomized trial.

PubMed

Aleyasin, Ashraf; Abediasl, Zhila; Nazari, Atefeh; Sheikh, Mahdi

2016-06-01

Recent studies have revealed key roles for granulocyte colony-stimulating factor (GCSF) in embryo implantation process and maintenance of pregnancy, and some studies showed promising results by using local intrauterine infusion of GCSF in patients undergoing in vitro fertilization (IVF). This multicenter, randomized, controlled trial included 112 infertile women with repeated IVF failure to evaluate the efficacy of systemic single-dose subcutaneous GCSF administration on IVF success in these women. In this study, the Long Protocol of ovarian stimulation was used for all participants. Sealed, numbered envelopes assigned 56 patients to receive subcutaneous 300 µg GCSF before implantation and 56 in the control group. The implantation (number of gestational sacs on the total number of transferred embryos), chemical pregnancy (positive serum β-HCG), and clinical pregnancy (gestational sac and fetal heart) rates were compared between the two groups. This trial is registered at www.irct.ir (IRCT201503119568N11). The successful implantation (18% vs 7.2%, P=0.007), chemical pregnancy (44.6% vs 19.6%, P=0.005), and clinical pregnancy (37.5% vs 14.3%, P=0.005) rates were significantly higher in the intervention group than in the control group. After adjustment for participants' age, endometrial thickness, good-quality oocyte counts, number of transferred embryos, and anti-Mullerian hormone levels, GCSF treatment remained significantly associated with successful implantation (OR=2.63, 95% CI=1.09-6.96), having chemical pregnancy (OR= 2.74, 95% CI=1.11-7.38) and clinical pregnancy (OR=2.94, 95% CI=1.23-8.33). In conclusion, administration of single-dose systemic subcutaneous GCSF before implantation significantly increases the IVF success, implantation, and pregnancy rates in infertile women with repeated IVF failure. © 2016 Society for Reproduction and Fertility.

High frequency of discordance between antimüllerian hormone and follicle-stimulating hormone levels in serum from estradiol-confirmed days 2 to 4 of the menstrual cycle from 5,354 women in U.S. fertility centers.

PubMed

Leader, Benjamin; Hegde, Aparna; Baca, Quentin; Stone, Kimberly; Lannon, Benjamin; Seifer, David B; Broekmans, Frank; Baker, Valerie L

2012-10-01

To determine the frequency of clinical discordance between antimüllerian hormone (AMH, ng/mL) and follicle-stimulating hormone (FSH, IU/L) by use of cut points defined by response to controlled ovarian stimulation in the same serum samples drawn on estradiol-confirmed, menstrual cycle days 2 to 4. Retrospective analysis. Fertility centers in 30 U.S. states and a single reference laboratory with uniform testing protocols. 5,354 women, 20 to 45 years of age. None. Frequency of discordance between serum AMH and FSH values. Of the 5,354 women tested, 1 in 5 had discordant AMH and FSH values defined as AMH <0.8 (concerning) with FSH <10 (reassuring) or AMH ≥ 0.8 (reassuring) with FSH ≥ 10 (concerning). Of the women with reassuring FSH values (n = 4,469), the concerning AMH values were found in 1 in 5 women in a highly age-dependent fashion, ranging from 1 in 11 women under 35 years of age to 1 in 3 women above 40 years of age. On the other hand, of the women with reassuring AMH values (n = 3,742), 1 in 18 had concerning FSH values, a frequency that did not vary in a statistically significant fashion by age. Clinical discordance in serum AMH and FSH values was frequent and age dependent using common clinical cut points, a large patient population, one reference laboratory, and uniform testing methodology. This conclusion is generalizable to women undergoing fertility evaluation, although AMH testing has not been standardized among laboratories, and the cut points presented are specific to the laboratory in this study. Copyright © 2012. Published by Elsevier Inc.

The Protective Effects of Alpha-Lipoic Acid and Coenzyme Q10 Combination on Ovarian Ischemia-Reperfusion Injury: An Experimental Study.

PubMed

Tuncer, Ahmet Ali; Bozkurt, Mehmet Fatih; Koken, Tulay; Dogan, Nurhan; Pektaş, Mine Kanat; Baskin Embleton, Didem

2016-01-01

Objective. This study aims to evaluate whether alpha-lipoic acid and/or coenzyme Q10 can protect the prepubertal ovarian tissue from ischemia-reperfusion injury in an experimental rat model of ovarian torsion. Materials and Methods. Forty-two female preadolescent Wistar-Albino rats were divided into 6 equal groups randomly. The sham group had laparotomy without torsion; the other groups had torsion/detorsion procedure. After undergoing torsion, group 2 received saline, group 3 received olive oil, group 4 received alpha-lipoic acid, group 5 received coenzyme Q10, and group 6 received both alpha-lipoic acid and coenzyme Q10 orally. The oxidant-antioxidant statuses of these groups were compared using biochemical measurement of oxidized/reduced glutathione, glutathione peroxidase and malondialdehyde, pathological evaluation of damage and apoptosis within the ovarian tissue, and immunohistochemical assessment of nitric oxide synthase. Results. The left ovaries of the alpha-lipoic acid + coenzyme Q10 group had significantly lower apoptosis scores and significantly higher nitric oxide synthase content than the left ovaries of the control groups. The alpha-lipoic acid + coenzyme Q10 group had significantly higher glutathione peroxidase levels and serum malondialdehyde concentrations than the sham group. Conclusions. The combination of alpha-lipoic acid and coenzyme Q10 has beneficial effects on oxidative stress induced by ischemia-reperfusion injury related to ovarian torsion.

Effect of simultaneously started clomiphene citrate and gonadotropins in antagonist regimes, on cumulative live births, fresh-cycle live births and cost of stimulation in IVF cycles.

PubMed

Satwik, Ruma; Kochhar, Mohinder

2018-04-11

The aim of the study was to compare simultaneously started clomiphene citrate (CC) and gonadotropins (Gn) with gonadotropins alone in conventional antagonist regimes with respect to fresh-cycle live births, cumulative live births and cost of ovarian stimulation per started cycle. This was a single-center prospective cohort study conducted over 1 year. Women undergoing autologous in vitro fertilization (IVF) treatment in antagonist protocols and who consented to participate in the study were divided into two cohorts. The CC cohort (n = 86) received 50 mg CC for 5 days and individualized Gn daily until the hCG trigger, both starting from day 2 and antagonist daily from day 8 of menstrual cycle. The Gn-only cohort (n = 349) received individualized Gn from day 2 and the antagonist from day 7 of menstrual cycle. IVF outcomes and cost of stimulation were compared between two cohorts across expected ovarian response categories. The CC cohort used a mean lower dose of Gn (1741.38 ± 604.46 vs 1980.54 ± 686.42; MD = -239.16; 95%CI = -348.03 to -189.24; P = 0.003) over fewer days (8.54 ± 1.86 vs 9.25 ± 1.97; MD =-0.71;95% CI = -1.17 to -0.25; P = 0.0026) to achieve similar retrieved oocytes, (9.19 ± 5.92 vs 9.36 ± 6.96; MD = -0.17; 95%CI -1.77 to + 1.43; P = 0.83), positive bhCG rates (40% vs 29.6%, MD = 10.4%; OR = 1.65, 95%CI = 0.95-2.86; P = 0.078) and live births in fresh cycles (32.31% vs 21.30%; MD = 11.01%; OR = 1.76; 95%CI = 0.97-3.19; P = 0.06) and cumulative live births per initiated cycle (30.23% vs 20.34%; MD = 9.89%; OR = 1.697; 95%CI = 0.99-2.88; P = 0.0501). The dose lowering achieved a 28-40% reduction in the cost of stimulation, which was most noticeable in the hyper-responder category for both hMG cycles, (Rs.11 602.3 ± 3365.9 vs 19615 ± 2677.1; MD = -8012.7; %age reduction: 40.8%; P = 0.0007) and recombinant FSH cycles (Rs. 22 459.6 ± 6255.3 vs 33 022.1 ± 9891.2; MD: -10 562; %age reduction: -32%; P = 0.0001). CC started simultaneously with Gn in antagonist regimes helps lower the cost of stimulation without affecting IVF outcomes. © 2018 Japan Society of Obstetrics and Gynecology.