Elevated human chorionic gonadotropin levels in patients with chronic kidney disease: Case series and review of literature.

PubMed

Soni, S; Menon, M C; Bhaskaran, M; Jhaveri, K D; Molmenti, E; Muoio, V

2013-11-01

Women are often subjected to serum human chorionic gonadotropin (HCG) testing prior to diagnostic and therapeutic interventions. A positive result leads to further testing to rule out pregnancy and avoid possible fetal teratogenicity. The impact of chronic kidney disease (CKD) on HCG testing has not been studied. We report a series of 5 women out of 62 with CKD, who had a positive HCG test on routine pre-transplant screening at a single transplant center. We analyzed their case records retrospectively. Despite aggressive investigation, their elevated HCG levels remained unexplained. The positive test contributed to delays in transplantation and increased overall cost of treatment.

Expression of β human chorionic gonadotropin in the placenta of gestational diabetic mothers: an immunohistochemistry and ultrastructural study.

PubMed

Sak, Muhammed Erdal; Deveci, Engin; Evsen, Mehmet Siddik; Kalkanhi, Sevgi; Baran, Ozlem; Ozekinci, Selver; Seker, Uğur

2013-02-01

To investigate morphologic differences of the placenta in pregnancies complicated by gestational diabetes compared to nondiabetic pregnancies. This was a comparative morphological study of the placentas from 20 women with gestational diabetes and 20 healthy pregnancies at 28-35 weeks of gestation. The presence of lesions such as fibrinoid necrosis, villous edema, syncytial knot and vascular lesions like chorangiosis was apparent, mainly in the diabetes group. There was an apparent decrease in the intensity of the human chorionic gonadotropin (hCG) immunostaining in the syncytiotrophoblast from the 28th to 35th weeks of gestation in the placentas of the healthy control group. No hCG immunostaining was observed in the villous or intervillous areas of any of the placentas. In diabetic placentas the expression of hCG was homogeneous with a moderate to intense immunoreactivity in the syncytiotrophoblast. Several syncytiotrophoblast cells showed dilations of both rough and smooth endoplasmic reticulum and loss and alteration of microvilli, and large vacuoles were observed just below the plasma membrane, as well as irregularities in the mitochondria. Syncytial cells play an important role in the placental transition. Increased expression of beta-hCG, deterioration, degeneration of organelles and cell structure and the basal membrane disorder in chorionic vessels were seen in placentas with gestational diabetes. These changes can affect placental transfer. However, further studies are needed to clarify this issue.

Human Chorionic Gonadotropin Has Anti-Inflammatory Effects at the Maternal-Fetal Interface and Prevents Endotoxin-Induced Preterm Birth, but Causes Dystocia and Fetal Compromise in Mice1

PubMed Central

Furcron, Amy-Eunice; Romero, Roberto; Mial, Tara N.; Balancio, Amapola; Panaitescu, Bogdan; Hassan, Sonia S.; Sahi, Aashna; Nord, Claire; Gomez-Lopez, Nardhy

2016-01-01

Human chorionic gonadotropin (hCG) is implicated in the maintenance of uterine quiescence by down-regulating myometrial gap junctions during pregnancy, and it was considered as a strategy to prevent preterm birth after the occurrence of preterm labor. However, the effect of hCG on innate and adaptive immune cells implicated in parturition is poorly understood. Herein, we investigated the immune effects of hCG at the maternal-fetal interface during late gestation, and whether this hormone can safely prevent endotoxin-induced preterm birth. Using immunophenotyping, we demonstrated that hCG has immune effects at the maternal-fetal interface (decidual tissues) by: 1) increasing the proportion of regulatory T cells; 2) reducing the proportion of macrophages and neutrophils; 3) inducing an M1 → M2 macrophage polarization; and 4) increasing the proportion of T helper 17 cells. Next, ELISAs were used to determine whether the local immune changes were associated with systemic concentrations of progesterone, estradiol, and/or cytokines (IFNgamma, IL1beta, IL2, IL4, IL5, IL6, IL10, IL12p70, KC/GRO, and TNFalpha). Plasma concentrations of IL1beta, but not progesterone, estradiol, or any other cytokine, were increased following hCG administration. Pretreatment with hCG prevented endotoxin-induced preterm birth by 44%, proving the effectiveness of this hormone as an anti-inflammatory agent. However, hCG administration alone caused dystocia and fetal compromise, as proven by Doppler ultrasound. These results provide insight into the mechanisms whereby hCG induces an anti-inflammatory microenvironment at the maternal-fetal interface during late gestation, and demonstrate its effectiveness in preventing preterm labor/birth. However, the deleterious effects of this hormone on mothers and fetuses warrant caution. PMID:27146032

Determining an Optimal Cutoff of Serum β-Human Chorionic Gonadotropin for Assisting the Diagnosis of Intracranial Germinomas

PubMed Central

Zhang, Hui; Zhang, Peng; Fan, Jun; Qiu, Binghui; Pan, Jun; Zhang, Xi’an; Fang, Luxiong; Qi, Songtao

2016-01-01

Background Beta (β)-human chorionic gonadotropin (β-HCG) is used to confirm the diagnosis and plan treatment of intracranial germinomas. However, the cutoff values of serum β-HCG in diagnosis of intracranial germinomas reported in the literature are inconsistent. To establish an appropriate cutoff value of serum β-HCG for diagnosis of intracranial germinomas, we retrospectively reviewed the records of intracranial tumor patients who received serum β-HCG and α-fetoprotein (AFP) tests for diagnostic purposes at our hospital from 2005 to 2014. Methods A total of 93 intracranial germinomas and 289 intracranial non-germ cell tumors were included in this study. Receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of 3 cutoffs (0.1, 0.4, and 0.5 mIU/mL) for diagnosing intracranial germinomas. The serum β-HCG level of intracranial germinoma patients was further analyzed to investigate the effect of metastasis status and tumor location on serum β-HCG level. Results The area under the ROC curve was 0.81 (P < .001), suggesting β-HCG is an effective marker. Of the 3 cutoff values, 0.1 mIU/mL possessed a highest sensitivity (66.67%) and good specificity (91%). Although there was no β-HCG level difference between metastatic and non-metastatic intracranial germinoma patients, the diagnostic rate of metastatic neurohypophyseal germinomas was significantly higher than that of its non-metastatic counterpart (P < .05), implying that the location of the germinoma might need to be considered when β-HCG is used as a marker to predict metastasis. Conclusions Determining an optimal cutoff of serum β-HCG is helpful for assisting the diagnosis of intracranial germinoma. PMID:26771195

Modulation of rat testes lipid composition by hormones: Effect of PRL (prolactin) and hCG (human chorionic gonadotropin)

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

Sebokova, E.; Wierzbicki, A.; Clandinin, M.T.

1988-10-01

The effect of prolactin (PRL) and human chorionic gonadotropin (hCG) administration for 7 days on the composition and function of rat testicular plasma membrane was investigated. Refractory state in Leydig cells desensitized by hCG decreased the binding capacity for {sup 125}I-labeled hCG and also luteinizing hormone (LH)-induced adenosine 3{prime},5{prime}-cyclic monophosphate (cAMP) and testosterone production. In testicular membranes of hCG-treated animals, a depletion of cholesterol and an increase in total phospholipid content was observed after gonadotropin injection, thereby decreasing the cholesterol-to-phospholipid ratio. Injection of high doses of PRL had no effect on the binding capacity or affinity of the LH-hCG receptormore » but decreased the response of Leydig cells to LH in terms of cAMP and testosterone synthesis. PRL also increased total and esterified cholesterol and decreased free cholesterol and membrane phospholipid content. The fatty acid composition of testicular lipids was significantly and selectively influenced by both hormonal treatments. These observations suggest that metabolism of cholesterol and long-chain polyunsaturated fatty acids in testicular tissue is affected by chorionic gonadotropin and PRL and may provide the mechanism for regulating steroidogenic functions.« less

Thyroid Diseases Tests

MedlinePlus

... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... hormone production. Also, human chorionic gonadotropin (hCG) , the hormone that supports the growth of the fetus in pregnancy , can act like ...

21 CFR 862.1155 - Human chorionic gonadotropin (HCG) test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... intended to measure HCG, a placental hormone, in plasma or urine. (2) Classification. Class II. (b) Human... persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or...

21 CFR 862.1155 - Human chorionic gonadotropin (HCG) test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... intended to measure HCG, a placental hormone, in plasma or urine. (2) Classification. Class II. (b) Human... persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or...

21 CFR 862.1155 - Human chorionic gonadotropin (HCG) test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... intended to measure HCG, a placental hormone, in plasma or urine. (2) Classification. Class II. (b) Human... persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or...

21 CFR 862.1155 - Human chorionic gonadotropin (HCG) test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... intended to measure HCG, a placental hormone, in plasma or urine. (2) Classification. Class II. (b) Human... persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or...

21 CFR 862.1155 - Human chorionic gonadotropin (HCG) test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... intended to measure HCG, a placental hormone, in plasma or urine. (2) Classification. Class II. (b) Human... persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or...

Log-linear human chorionic gonadotropin elimination in cases of retained placenta percreta.

PubMed

Stitely, Michael L; Gerard Jackson, M; Holls, William H

2014-02-01

To describe the human chorionic gonadotropin (hCG) elimination rate in patients with intentionally retained placenta percreta. Medical records for cases of placenta percreta with intentional retention of the placenta were reviewed. The natural log of the hCG levels were plotted versus time and then the elimination rate equations were derived. The hCG elimination rate equations were log-linear in three cases individually (R (2) = 0.96-0.99) and in aggregate R (2) = 0.92). The mean half-life of hCG elimination was 146.3 h (6.1 days). The elimination of hCG in patients with intentionally retained placenta percreta is consistent with a two-compartment elimination model. The hCG elimination in retained placenta percreta is predictable in a log-linear manner that is similar to other reports of retained abnormally adherent placentae treated with or without methotrexate.

In vitro hCG and human recombinant FSH actions on testicular steroidogenesis in the toad Bufo arenarum.

PubMed

Canosa, L F; Ceballos, N R

2002-05-01

In order to study the regulation of testicular steroidogenesis in the toad Bufo arenarum, the effect of gonadotropins (hCG and hrFSH) on steroidogenic enzymes was determined using an in vitro system. 3beta-Hydroxysteroid dehydrogenase/isomerase activity was not affected by any of the gonadotropins, at any of the concentrations used. In contrast, 5alpha-reductase activity was strongly reduced by both hCG and hrFSH. Human chorionic gonadotropin inhibited the activity of cytochrome P450 17alpha-hydroxylase-C(17-20) lyase (P450(c17)), only at the highest concentration used, while hrFSH strongly reduced P450(c17) activity at all the doses assayed. In conclusion, these data suggest that LH (hCG) and FSH regulate steroidogenic enzymes such as 5alphaRed and P450(c17). The results also suggest that FSH could be involved in the regulation of the change in steroidogenesis undergone by the testis during the breeding season. In turn, the inhibition of P450(c17) activity could result in a reduction of androgen production and an increment of C21 steroids. (c) 2002 Elsevier Science (USA).

A review of luteinising hormone and human chorionic gonadotropin when used in assisted reproductive technology.

PubMed

Ezcurra, Diego; Humaidan, Peter

2014-10-03

Gonadotropins extracted from the urine of post-menopausal women have traditionally been used to stimulate folliculogenesis in the treatment of infertility and in assisted reproductive technology (ART). Products, such as human menopausal gonadotropin (hMG), consist not only of a mixture of the hormones, follicle-stimulating hormone (FSH), luteinising hormone (LH) and human chorionic gonadotropin (hCG), but also other biologically active contaminants, such as growth factors, binding proteins and prion proteins. The actual amount of molecular LH in hMG preparations varies considerably due to the purification process, thus hCG, mimicking LH action, is added to standardise the product. However, unlike LH, hCG plays a different role during the natural human menstrual cycle. It is secreted by the embryo and placenta, and its main role is to support implantation and pregnancy. More recently, recombinant gonadotropins (r-hFSH and r-hLH) have become available for ART therapies. Recombinant LH contains only LH molecules. In the field of reproduction there has been controversy in recent years over whether r-hLH or hCG should be used for ART. This review examines the existing evidence for molecular and functional differences between LH and hCG and assesses the clinical implications of hCG-supplemented urinary therapy compared with recombinant therapies used for ART.

Combined use of serum HCG and sonography in the diagnosis of ectopic pregnancy

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

Kadar, N.; Taylor, K.J.W.; Rosenfield, A.T.

1983-09-01

During an 18 month period, 320 patients were referred with clinical suspicion of an ectopic pregnancy. This study is based on 19 patients with ectopic pregnancy who had both a sonographic examination of the pelvis and determination of serum beta human chorionic gonadotropin (HCG) before surgery. Emphasis is focused on the spectrum of sonographic appearances that may occur in ectopic gestation. These are illustrated, and the sonographic criteria that have been used both for a positive diagnosis and for the exclusion of ectopic pregnancy in the past are analyzed. It is suggested that the accuracy of sonography can be increasedmore » by determining the serum HCG level on the day of the scan and by interpreting the findings with reference to the discriminatory HCG zone.« less

Human Chorionic Gonadotropin and Breast Cancer

PubMed Central

Schüler-Toprak, Susanne; Treeck, Oliver; Ortmann, Olaf

2017-01-01

Breast cancer is well known as a malignancy being strongly influenced by female steroids. Pregnancy is a protective factor against breast cancer. Human chorionic gonadotropin (HCG) is a candidate hormone which could mediate this antitumoral effect of pregnancy. For this review article, all original research articles on the role of HCG in breast cancer were considered, which are listed in PubMed database and were written in English. The role of HCG in breast cancer seems to be a paradox. Placental heterodimeric HCG acts as a protective agent by imprinting a permanent genomic signature of the mammary gland determining a refractory condition to malignant transformation which is characterized by cellular differentiation, apoptosis and growth inhibition. On the other hand, ectopic expression of β-HCG in various cancer entities is associated with poor prognosis due to its tumor-promoting function. Placental HCG and ectopically expressed β-HCG exert opposite effects on breast tumorigenesis. Therefore, mimicking pregnancy by treatment with HCG is suggested as a strategy for breast cancer prevention, whereas targeting β-HCG expressing tumor cells seems to be an option for breast cancer therapy. PMID:28754015

Myth vs. Fact: The Human Chorionic Gonadotropin (hCG) Diet

MedlinePlus

... given by injection (using a needle), and hCG dietary supplements, taken by mouth as drops or pills. Health professionals have concerns about both types. www.hormone.org Risks of Injected hCG Women Men • irregular periods and • ...

Human chorionic gonadotropin (HCG) treatment of obesity.

PubMed

Shetty, K R; Kalkhoff, R K

1977-02-01

After a nine-day control period, six hospitalized obese women were placed on 500 calorie diets and were given 125 IU of human chorionic gonadotropin (HCG) intramuscularly daily for 30 days. Another five obese women received injections of diluent only and consumed identical diets for the same period. Mean weight loss in the HCG-treated group was nearly identical to that achieved by women given the placebo. Reduction of triceps skinfold thickness or circumferential body measurements of the chest, waist, hips, and thighs were not different. Patters of change of a variety of plasma and urine substrates, electrolytes, and hormones were similar in the two groups and consistent with semistarvation and weight loss. These results indicate that HCG has no effects on chemical and hormonal parameters measured and offers no advantage over calorie restriction in promoting weight loss.

Different effects of chorionic gonadotropin on Taenia crassiceps and Taenia solium cysticerci cultured in vitro.

PubMed

Díaz-Orea, M A; de Aluja, A S; Erosa, M de L; Gomez-Conde, E; Castellanos Sánchez, V O; Willms, K; Sciutto, E; Fragoso, G

2007-12-01

Hormones play a significant role in murine Taenia crassiceps cysticercosis, and they may also participate in the susceptibility to Taenia solium cysticercosis. In the present study, in vitro effects are reported for human chorionic gonadotropin (hCG) on the larval stages of T. crassiceps (WFU strain) and T. solium. hCG effectively promotes parasite reproduction, i.e., it increases the number of buds on T. crassiceps cysticerci and the percentage of evagination and parasite length in T. solium. This is the first report in which a direct effect of hCG is reported for a parasite. hCG or mouse luteinizing hormone could be recognized by the cysticerci as mitogenic factors and contribute to the female and pregnancy bias toward susceptibility to T. crassiceps and T. solium cysticercosis, respectively.

A kinetic comparison of the processing and secretion of the alpha beta dimer and the uncombined alpha and beta subunits of chorionic gonadotropin synthesized by human choriocarcinoma cells.

PubMed

Peters, B P; Krzesicki, R F; Hartle, R J; Perini, F; Ruddon, R W

1984-12-25

Human choriocarcinoma cells (JAR) synthesize the alpha and beta subunits of the glycoprotein hormone chorionic gonadotropin (hCG) (R.W. Ruddon, C.A. Hanson, A. H. Bryan, G.J. Putterman, E.L. White, F. Perini, K. S. Meade, and P.H. Aldenderfer (1980) J. Biol. Chem. 255, 1000-1007). In addition to the hCG dimer (alpha beta), JAR cells secrete uncombined alpha and beta subunits into the culture medium (L.A. Cole, R.J. Hartle, J.A. Laferla, and R.W. Ruddon (1983) Endocrinology 113, 1176-1178). Pulse-chase studies with [35S]methionine or [3H]mannose were carried out in order to compare free alpha, free beta, and the alpha beta dimer with regard to the kinetics of synthesis, N-linked oligosaccharide processing, and secretion and to determine the kinetics of alpha-beta subunit combination. A panel of three antisera was used to immunoprecipitate directly the free subunits and the alpha beta dimer sequentially from the same cell lysates and culture media. The alpha subunit of hCG was synthesized in a slight molar excess (1.2-1.5-fold) over the beta subunit, and alpha beta dimer was rapidly formed by combination of the intracellular alpha and beta precursors. Dimer formation was already apparent in JAR cells following a 10-min biosynthetic labeling incubation with [35S]methionine. The combination of subunits ceased by 30 min of chase even though 51% of alpha and 44% of beta remained free within the cells. Combination of the alpha and beta precursors had occurred before their N-linked oligosaccharides were processed beyond the Man8GlcNAc2 structure. The initial trimming of glucosyl and mannosyl units from the high-mannose oligosaccharides of the hCG precursors occurred more rapidly for free alpha and CG-alpha than for free beta and CG-beta. JAR cells accumulated alpha precursors bearing mostly Man8GlcNAc2 units and beta precursors bearing Man8GlcNAc2 units that represent the substrates of the rate-limiting step in the secretory pathway. In spite of the fact that their N-linked oligosaccharides were trimmed at different rates, free alpha, free beta, and alpha beta dimer were all secreted into the medium at the same rate, with a half-time of 35 min. The secreted hCG forms were stable in the chase medium between 4 and 8h, indicating that extracellular degradation, combination of free subunits to form dimer, or dissociation of dimer to form free subunits did not occur.(ABSTRACT TRUNCATED AT 400 WORDS)

Gonadotropin Promotion of Adventitious Root Production on Cuttings of Begonia semperflorens and Vitis vinifera 1

PubMed Central

Leshem, Y.; Lunenfeld, B.

1968-01-01

Adventitious rooting of Begonia semperflorens cv. Indian Maid and Vitis vinifera cv. Semillon stem cuttings was significantly promoted by human chorionic gonadotropin (HCG). Basal sections of HCG treated cuttings upon which promoted rooting took place had markedly less endogenous gibberellin (GA) activity than non-treated controls or apical sections of treated ones, while changes in auxin levels were not found. HCG also inhibited GA3-induced reducing sugar release from embryoless barley endosperm halves. These findings are discussed in the light of a possible analogy to gonadotropin action in animal systems. PMID:5641189

Development of an assay for a biomarker of pregnancy and early fetal loss

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

Canfield, R.E.; O'Connor, J.F.; Birken, S.

1987-10-01

Human chorionic gonadotropin (hCG) is a glycoprotein hormone, secreted by the syncytiotrophoblast cells of the fertilized ovum, that enters the maternal circulation at the time of endometrial implantation. It is composed of two nonidentical subunits; ..cap alpha.. and ..beta.., with molecular weights of 14 kD and 23 kD, respectively. Human chorionic gonadotropin binds to the same receptor as hLH and displays the same biological response, namely, to stimulate the declining function of the corpus luteum to produce progestins and estrogen late in the menstrual cycle. The differences in the structures of hCG and hLH have been exploited to develop antibodiesmore » that can measure hCG specifically in the presence of hLH. Two-site antibody binding assays have been developed, based on a surface immunological concept of hCG epitopes, that involve four distinct regions to which antibodies against hCG can bind simultaneously. Antibody cooperative effects, in conjunction with kinetic advantages derived from the concentration factors by use of the sandwich assay technique (immunoradiometric assay, IRMA), have enabled development of extremely sensitive and specific measurement protocols for urinary hCG. The assay described herein permits the detection of pregnancy on an average 25.4 days after the first day of the preceding menses, as opposed to 29.5 days for conventional radioimmunoassay techniques. In addition, the greater sensitivity and specificity of this assay method has permitted the detection of episodes of fetal loss not detected by radioimmunoassay of urine specimens. A large scale epidemiological study is in progress using this assay technique as a way to identify pregnancies that are lost before becoming clinically apparent.« less

A facile and sensitive peptide-modulating graphene oxide nanoribbon catalytic nanoplasmon analytical platform for human chorionic gonadotropin.

PubMed

Liang, Aihui; Li, Chongning; Li, Dan; Luo, Yanghe; Wen, Guiqing; Jiang, Zhiliang

2017-01-01

The nanogold reaction between HAuCl 4 and citrate is very slow, and the catalyst graphene oxide nanoribbon (GONR) enhanced the nanoreaction greatly to produce gold nanoparticles (AuNPs) that exhibited strong surface plasmon resonance (SPR) absorption (Abs) at 550 nm and resonance Rayleigh scattering (RRS) at 550 nm. Upon addition of the peptide of human chorionic gonadotropin (hCG), the peptide could adsorb on the GONR surface, which inhibited the catalysis. When hCG was added, peptides were separated from the GONR surface due to the formation of stable peptide-hCG complex, which led to the activation of GONR catalytic effect. With the increase in hCG concentration, the RRS and Abs signal enhanced linearly. The enhanced RRS value showed a good linear relationship with hCG concentration in the range of 0.2-20 ng/mL, with a detection limit of 70 pg/mL. Accordingly, two new GONR catalytic RRS/Abs methods were established for detecting hCG in serum samples.

Thyrotropic action of human chorionic gonadotropin.

PubMed

Yoshimura, M; Hershman, J M

1995-10-01

Hyperthyroidism or increased thyroid function has been reported in many patients with trophoblastic tumors. In these cases, greatly increased human chorionic gonadotropin (hCG) levels and suppressed TSH levels suggest that hCG has thyrotropic activity. Recent investigations have clarified the structural homology not only in the hCG and TSH molecules but also in their receptors, and this homology suggests the basis for the reactivity of hCG with the TSH receptor. The clinical significance of the thyrotropic action of hCG is now also recognized in normal pregnancy and hyperemesis gravidarum. Highly purified hLH binds to recombinant hTSH receptor and is about 10 times as potent as purified hCG in increasing cAMP. The beta-subunits of hCG and hLH share 85% sequence identity in their first 114 amino acids but differ in the carboxy-terminal peptide because hCG beta contains a 31-amino acid extension (beta-CTP). A recombinant mutant hCG that lacks beta-CTP showed almost identical potency to LH on stimulation of recombinant hTSH receptor. If intact hCG were as potent as hLH in regard to its thyrotropic activity, most pregnant women would become thyrotoxic. One of the roles of the beta-CTP may be to prevent overt hyperthyroidism in the first trimester of pregnancy when a large amount of hCG is produced by the placenta. Nicked hCG preparations, obtained from patients with trophoblastic disease or by enzymatic digestion of intact hCG, showed approximately 1.5- to 2-fold stimulation of recombinant hTSH receptor compared with intact hCG. This suggests that the thyrotropic activity of hCG may be influenced by the metabolism of the hCG molecule itself. Deglycosylation and/or desialylation of hCG enhances its thyrotropic potency. Basic hCG isoforms with lower sialic acid content extracted from hydatidiform moles were more potent in activating adenylate cyclase, and showed high bioactivity/immunoactivity (B/I) ratio in CHO cells expressing human TSH receptors. This is consistent with the finding that the beta-CTP truncated hCG with higher thyrotropic potency is substantially deglycosylated and desialylated in the beta-subunit relative to intact hCG because all four O-linked glycosylation sites occur within the missing C-terminal extension. The desialylated hCG variant also interacts directly with recombinant hTSH receptors transfected into human thyroid cancer cells. There is thyroid-stimulating activity in sera of normal pregnant women, and this correlates with serum hCG levels. The thyroid gland of normal pregnant women may be stimulated by hCG to secrete slightly excessive quantities of T4 and induce a slight suppression of TSH, perhaps being about 1 mU/L less than nongravid levels, but not high enough to induce overt hyperthyroidism. Maternal thyroid glands may secrete more thyroid hormone during early pregnancy in response to the thyrotropic activity of hCG that overrides the normal operation of the hypothalamic-pituitary-thyroid feedback system. Biochemical hyperthyroidism associated with hyperemesis gravidarum has been attributed to hCG. In patients with hyperemesis gravidarum, thyrotropic in serum correlated with hCG immunoreactivity, and the severity of vomiting as indicated by clinical and biochemical parameters correlated with the degree of thyroid stimulation. To understand the thyrotropic action of hCG, it is necessary to know whether hCG activates the same domain of the TSH receptor as does TSH. The identification of the molecular structure of the hCG isoform with the highest thyrotropic potency will resolve the enigma of gestational thyrotoxicosis and the hyperthyroidism associated with trophoblastic disease and hCG-producing tumors.

Human chorionic gonadotropin-induced hyperthyroidism in germ cell cancer--a case presentation and review of the literature.

PubMed

Voigt, Wieland; Maher, Gita; Wolf, Hans-Heinrich; Schmoll, Hans-Joachim

2007-06-01

Human chorionic gonadotropin (hCG)-induced hyperthyroidism represents a rare paraneoplastic syndrome in hCG-secreting testicular cancer. In most cases, this hyperthyroidism remains subclinical. hCG belongs to the family of glycoprotein hormones with structural homology to thyroid- stimulating hormone (TSH). The thyrotropic potency and thereby the degree of cross reactivity of hCG is determined by several factors, such as content of sialic acid or lack of the C-terminal tail. In the absence of clinical signs of hyperthyroidism, treatment usually consists of specific antitumor therapy which will result in normalization of thyroid function if hCG declines. Where there are clinical signs of hyperthyroidism, overlapping thyreostatic treatment is recommended. Here, we report of a young man presenting biochemical signs of hyperthyroidism without clinical signs at the time of diagnosis of non-seminomatous germ cell cancer. Beta-hCG initially exceeded 1,000,000 IU/ml and declined close to normal at the end of cancer treatment. Concomitantly, thyroid hormones returned to the normal range without any thyreostatic therapy. We observed a significant correlation of neta-hCG and thyroid hormones in linear regression analysis (r2 = 0.98, p< 0.05). A concise overview of potential mechanisms of hCG-induced hyperthyroidism in germ cell cancer but also in pregnancy is given and the case discussed according to the cited literature.

Outpatient endometrial aspiration: an alternative to methotrexate for pregnancy of unknown location.

PubMed

Insogna, Iris G; Farland, Leslie V; Missmer, Stacey A; Ginsburg, Elizabeth S; Brady, Paula C

2017-08-01

Pregnancies of unknown location with abnormal beta-human chorionic gonadotropin trends are frequently treated as presumed ectopic pregnancies with methotrexate. Preliminary data suggest that outpatient endometrial aspiration may be an effective tool to diagnose pregnancy location, while also sparing women exposure to methotrexate. The purpose of this study was to evaluate the utility of an endometrial sampling protocol for the diagnosis of pregnancies of unknown location after in vitro fertilization. A retrospective cohort study of 14,505 autologous fresh and frozen in vitro fertilization cycles from October 2007 to September 2015 was performed; 110 patients were diagnosed with pregnancy of unknown location, defined as a positive beta-human chorionic gonadotropin without ultrasound evidence of intrauterine or ectopic pregnancy and an abnormal beta-human chorionic gonadotropin trend (<53% rise or <15% fall in 2 days). These patients underwent outpatient endometrial sampling with Karman cannula aspiration. Patients with a beta-human chorionic gonadotropin decline ≥15% within 24 hours of sampling and/or villi detected on pathologic analysis were diagnosed with failing intrauterine pregnancy and had weekly beta-human chorionic gonadotropin measurements thereafter. Those patients with beta-human chorionic gonadotropin declines <15% and no villi identified were diagnosed with ectopic pregnancy and treated with intramuscular methotrexate (50 mg/m 2 ) or laparoscopy. Across 8 years of follow up, among women with pregnancy of unknown location, failed intrauterine pregnancy was diagnosed in 46 patients (42%), and ectopic pregnancy was diagnosed in 64 patients (58%). Clinical variables that included fresh or frozen embryo transfer, day of embryo transfer, serum beta-human chorionic gonadotropin at the time of sampling, endometrial thickness, and presence of an adnexal mass were not significantly different between patients with failed intrauterine pregnancy or ectopic pregnancy. In patients with failed intrauterine pregnancy, 100% demonstrated adequate postsampling beta-human chorionic gonadotropin declines; villi were identified in just 46% (n=21 patients). Patients with failed intrauterine pregnancy had significantly shorter time to resolution (negative serum beta-human chorionic gonadotropin) after sampling compared with patients with ectopic pregnancy (12.6 vs 26.3 days; P<.001). With the use of this safe and effective protocol of endometrial aspiration with Karman cannula, a large proportion of women with pregnancy of unknown location are spared methotrexate, with a shorter time to pregnancy resolution than those who receive methotrexate. Copyright © 2017 Elsevier Inc. All rights reserved.

Presence and Possible Mode of Action of a Proteinaceous Gonadotropin-like Growth Regulating Factor in Plant Systems 1

PubMed Central

Leshem, Y.; Avtalion, R. R.; Schwarz, M.; Kahana, S.

1969-01-01

Antiserum to human chorionic gonadotropin (HCG) caused marked inhibition of adventitious rooting of Begonia semperflorens and Chrysanthemum morifolium stem cuttings. Immuno-absorption of crude protein extract from chrysanthemum foliage through a column of polymerized and unsolubilized HCG antibodies resulted in a significant reduction in adventitious root promoting activity of the extract. These results are discussed in the light of a hypothesis that an endogenous protein growth regulating substance which immunologically resembles HCG exists in plant systems. Further experimentation with HCG suggests that its mode of action is possibly via the regulation of peroxidase enzymatic control of auxin levels. PMID:5775851

The Effects of Fetal Gender on Serum Human Chorionic Gonadotropin and Testosterone in Normotensive and Preeclamptic Pregnancies

PubMed Central

Lorzadeh, Nahid; Kazemirad, Sirous

2012-01-01

Introduction. The aim of the present study was to evaluate the effects of fetal sex on serum human chorionic gonadotropin (hCG) and testosterone in normotensive and preeclamptic pregnancies. Materials and Methods. This is a cross-sectional study and 139 women with singleton pregnancies in the third trimester were studied. Seventy-one pregnancies were uncomplicated; among those were 35 male and 36 female fetuses. Sixty-eight pregnancies were complicated by preeclampsia; among those were 35 male and 33 female fetuses. Human chorionic gonadotropin and total testosterone were measured in maternal peripheral blood. Data analyzed by SPSS software. Results. In male-bearing pregnancies, maternal hCG and testosterone serum levels were significantly higher in preeclamptic than normotensive mothers (P < 0.001 and P < 0.001, resp.) in female-bearing pregnancies testosterone levels were significantly higher in preeclamptic than normotensive mothers (P < 0.001). Total testosterone levels were significantly higher in pregnancies with either gender and significantly higher in mlae-bearing than in female-bearing pregnancies. Conclusion. According to our results, there is a correlation between maternal serum hCG and testosterone levels and preeclampsia. Therefore these tests can be used as routine during 30–38 weeks of gestation. High maternal serum concentrations of these markers can predict preeclampsia. PMID:22518314

Hyperinsulinemia and human chorionic gonadotropin synergistically promote the growth of ovarian follicular cysts in rats.

PubMed

Poretsky, L; Clemons, J; Bogovich, K

1992-08-01

Tonically elevated serum luteinizing hormone (LH) and hyperinsulinemia are prominent features of polycystic ovary syndrome (PCO) in women, but the relative roles of LH and insulin in the pathogenesis of PCO is still unknown. The present study was undertaken to determine the effect(s) hyperinsulinemia might have on the induction of follicular cysts by LH/human chorionic gonadotropin (hCG) in the rat. Beginning on day 85 of age, adult female rats were given one of the following in vivo treatments: (1) vehicle alone; (2) a high-fat diet to control for the effects of weight-gain; (3) up to 6 U insulin per day; (4) 50 micrograms gonadotropin-releasing hormone (GnRH) antagonist (GnRHant) per day; (5) 1.5 IU hCG twice daily; (6) insulin + hCG; (7) insulin + GnRHant; (8) hCG + GnRHant; or (9) hCG + insulin + GnRHant. After 22 days of treatment, animals were killed on day 23, trunk blood was collected, and ovaries were excised for histological study. Regular cycles, assessed by vaginal smears, ceased after 10 days for most animals in treatment groups receiving hCG, but continued in all other treatment groups. All the animals in each hCG-treated group developed either unilateral or bilateral cystic ovaries, while no animals in the groups not receiving hCG developed follicular cysts. More animals from each group treated with both hCG and insulin possessed bilateral ovarian cysts than did rats treated with hCG alone: 80% and 60%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for, and Associated Risks with, the Human Chorionic Gonadotropin Supplemented Diet.

PubMed

Butler, Stephen A; Cole, Laurence A

2016-11-01

Trend diets can be commonplace amongst those who are trying to lose weight but in most cases there is some shred of evidence to suggest they might be of some benefit. Seldom is there a diet which is such a fad that it is not only completely unfounded but also potential harmful. The human chorionic gonadotropin or "hCG diet" is such a diet, which after half a century still has no evidence to support its efficacy; in fact all scientific publications subsequent to the original article counter these claims. In this short communication, we review the literature and present data on exactly what some of the hCG diet preparations actually contain and highlight that, based on current data, these may do more harm than good. It is worrying that more consideration is not given to the possible danger of administration of hCG preparations to individuals without an evidence-based rational.

The chorionic gonadotropin alpha-subunit gene is on human chromosome 18 in JEG cells.

PubMed Central

Hardin, J W; Riser, M E; Trent, J M; Kohler, P O

1983-01-01

The gene for the alpha subunit of human chorionic gonadotropin (hCG) has been tentatively assigned to human chromosome 18. This localization was accomplished through the use of Southern blot analysis. A full-length cDNA probe for the hCG alpha subunit and DNA isolated from a series of somatic hybrids between mouse and human cells were utilized to make this assignment. In addition, in situ hybridization with normal human peripheral blood lymphocytes as a source of human chromosomes and with the same cDNA probe confirmed this result. The presence of human chromosome 18 was required for the detection of DNA fragments characteristic of the alpha-hCG gene. These results are consistent with our previous observation that human chromosomes 10 and 18 are required for the production of hCG in cultured cells. Images PMID:6578509

Alpha or beta human chorionic gonadotropin knockdown decrease BeWo cell fusion by down-regulating PKA and CREB activation

PubMed Central

Saryu Malhotra, Sudha; Suman, Pankaj; Kumar Gupta, Satish

2015-01-01

The aim of the present study is to delineate the role of human chorionic gonadotropin (hCG) in trophoblast fusion. In this direction, using shRNA lentiviral particles, α- and β-hCG silenced ‘BeWo’ cell lines were generated. Treatment of both α- and β-hCG silenced BeWo cells with either forskolin or exogenous hCG showed a significant reduction in cell fusion as compared with control shRNA treated cells. Studies by qRT-PCR, Western blotting and immunofluorescence revealed down-regulation of fusion-associated proteins such as syncytin-1 and syndecan-1 in the α- and β-hCG silenced cells. Delineation of downstream signaling pathways revealed that phosphorylation of PKA and CREB were compromised in the silenced cells whereas, no significant changes in p38MAPK and ERK1/2 phosphorylation were observed. Moreover, β-catenin activation was unaffected by either α- or β-hCG silencing. Further, inhibition of PKA by H89 inhibitor led to a significant decrease in BeWo cell fusion but had no effect on β-catenin activation suggesting the absence of non-canonical β-catenin stabilization via PKA. Interestingly, canonical activation of β-catenin was associated with the up-regulation of Wnt 10b expression. In summary, this study establishes the significance of hCG in the fusion of trophoblastic BeWo cells, but there may be additional factors involved in this process. PMID:26053549

[Association of human chorionic gonadotropin level in embryo culture media with early embryo development].

PubMed

Wang, Haiying; Zhang, Renli; Han, Dong; Liu, Caixia; Cai, Jiajie; Bi, Yanling; Wen, Anmin; Quan, Song

2014-06-01

To investigate the association of human chorionic gonadotropin (HCG) level on day 3 of embryo culture with embryo development. Spent culture media were collected from individually cultured embryos on day 3 of in vitro fertilization and embryo transfer (IVF-ET) cycles. HCG concentration in the culture media was measured using an ELISA kit and its association with embryo development was assessed. In the 163 samples of embryo culture media from 60 patients, HCG was positive in 153 sample (93.8%) with a mean level of 0.85 ± 0.43 mIU/ml. The concentration of hCG in the culture media increased gradually as the number of blastomeres increased (F=2.273, P=0.03), and decreased as the morphological grade of the embryo was lowered (F=3.900, P=0.02). ELISA is capable of detecting HCG levels in spent culture media of embryos on day 3 of in vitro culture. The concentration of HCG in spent culture media is positively correlated with the status of early embryo development and implantation rate and thus serves as a useful marker for embryo selection in IVF-ET procedure.

Physical characteristics of the gonadotropin receptor-hormone complexes formed in vivo and in vitro.

PubMed Central

Dufau, M L; Podesta, E J; Catt, K J

1975-01-01

The physical properties of detergent-solubilized gonadotropin receptor-hormone complexes, determined by density gradient centrifugation and gel filtration, were compared after in vivo and in vitro labeling of specific ovarian binding sites with radioiodinated human chorionic gonadotropin (hCG). Following intravenous administration of biologically active 125I-labeled hCG, up to 50% of the gonadotropin tracer was bound to the luteinized ovaries of immature female rats treated with pregnant mare serum/human chorionic gonadotropin. Comparable binding of 125I-labeled hCG was observed after equilibration of ovarian particles with the labeled hormone in vitro. The sedimentation properties of the solubilized receptor-hormone complexes formed in vivo were identical with those derived for the corresponding complexes formed in vitro and extracted with Triton X-100 and Lubrol PX, with sedimentation constants of 8.8 S for the Triton-solubilized complex and 7.0 S for the complex extracted with Lubrol PX. During analytical gel filtration of the Triton-solubilized receptor-hormone complex on Sepharose 6B in 0.1% Triton X-100, the partition coefficient (Kav) of the "in vivo" complex (0.32) was not significantly different from that of the complex formed in vitro (0.29). Gel filtration of the Lubrol-solubilized ovarian particles on Sepharose 6B in 0.5% Lubrol PX gave Kav values for the "in vivo" and "in vitro" labeled complexes of 0.36 and 0.32, respectively. These findings demonstrate that the physical properties of size and shape which determine the partition coefficient and sedimentation characteristics of detergent-solubilized gonadotropin receptor-hormone complexes formed in vitro are not distinguishable from those of the complexes extracted after specific interaction of the ovarian gonadotropin receptors with radioiodinated hCG in vivo. PMID:165502

Inhibition of gonadotropin and prostaglandin stimulation of testicular steroidogenesis in malnourished rats.

PubMed

Nduka, E U; Dada, O A

1984-01-01

The effect of human chorionic gonadotropin (hCG) and prostaglandin E1 (PGE1) on testicular steroidogenesis in protein-deficient and refed rats was studied in vitro. The malnourished, refed, and control rats were found to secret testosterone in response to hCG and PGE1 stimulation. There was a significant reduction in the basal level of secretion in the malnourished rat testis (1.0 +/- 0.4 nMol/3 hr./Testis). Malnourished rats refed with adequate protein diet responded to hCG and PGE1 stimulation in a similar manner to normally-fed adult rats.

Regulation of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase expression and activity in the hypophysectomized rat ovary: Interactions between the stimulatory effect of human chorionic gonadotropin and the luteolytic effect of prolactin

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

Martel, C.; Labrie, C.; Dupont, E.

1990-12-01

The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) catalyzes an obligatory step in the conversion of pregnenolone and other 5-ene-3 beta-hydroxysteroids into progesterone as well as precursors of all androgens and estrogens in the ovary. Since 3 beta-HSD is likely to be an important target for regulation by pituitary hormones, we have studied the effect of chronic treatment with LH (hCG), FSH, and PRL on ovarian 3 beta-HSD expression and activity in hypophysectomized adult female rats. Human CG (hCG) (10 IU, twice a day (bid)), ovine FSH (0.5 microgram, bid), and ovine PRL (1 mg, bid) were administered,more » singly or in combination, for a period of 10 days starting 15 days after hypophysectomy. In hypophysectomized rats, PRL exerted a potent inhibitory effect on all the parameters studied. In fact, PRL caused a 81% decrease in ovarian 3 beta-HSD mRNA content accompanied by a similar decrease in 3 beta-HSD activity and protein levels. In addition, ovarian weight decreased by 40% whereas serum progesterone fell dramatically from 1.92 nmol/liter to undetectable levels after treatment with PRL. Whereas hCG alone had only slight stimulatory effects on 3 beta-HSD mRNA, protein content and activity levels, treatment with the gonadotropin partially or completely reversed the potent inhibitory effects of oPRL on all the parameters measured. FSH, on the other hand, had no significant effect on 3 beta-HSD expression and activity. In situ hybridization experiments using the 35S-labeled rat ovary 3 beta-HSD cDNA probe show that the inhibitory effect of PRL is exerted primarily on luteal cell 3 beta-HSD expression and activity. On the other hand, it can be seen that hCG stimulates 3 beta-HSD mRNA accumulation in interstitial cells.« less

Effects of luteinizing hormone and human chorionic gonadotropin on corpus luteum cells in a spheroid cell culture system.

PubMed

Walz, A; Keck, C; Weber, H; Kissel, C; Pietrowski, D

2005-09-01

The human corpus luteum (CL) is a highly vascularized, temporarily active endocrine gland and consists mainly of granulosa cells (GCs), theca cells (TCs), and endothelial cells (ECs). Its cyclic growth and development takes place under the influence of gonadotropic hormones. If pregnancy does occur, human chorionic gonadotropin (hCG) takes over the function of luteinizing hormone (LH) and, in contrast to LH, extends the functional life span of the CL. In this study, we investigated the effects of hCG and LH in a spheroidal cell culture model of CL development. Our data indicate that GCs secrete factors under the control of hCG that increase sprout formation of EC-spheroids. We demonstrate that the most prominent of these factors is VEGF-A. Furthermore, we found that both LH and hCG decrease sprout formation of GC-spheroids. After forming EC-GC coculture spheroids and consequently bringing GCs and ECs in close contact, sprouting increased under the influence of hCG, however not under LH. These experiments provide evidence for an hCG dependent functional switch in the GCs after coming in contact with ECs. Moreover, it demonstrates the considerably different effects of hCG and LH on GCs although their signaling is transmitted via the same receptor.

Crystallization and characterization of human chorionic gonadotropin in chemically deglycosylated and enzymatically desialylated states

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

Lustbader, J.W.; Birken, S.; Pileggi, N.F.

1989-11-28

Crystals suitable for X-ray diffraction studies at moderate resolution have been grown from two forms of human chorionic gonadotropin (hCG): HF-treated hCG and neuraminidase-treated hCG. The enzymatically desialylated form of hCG produced crystals that diffract to 2.8 {angstrom} as compared to the HF-treated hCG crystals that diffract to 3.0 {angstrom}. Although it was assumed that the high and heterogeneous carbohydrate content of the glycoprotein hormones inhibited their crystallization, this report suggests that it is the negatively charged surface sugars and neither the total carbohydrate content nor its heterogeneity which interferes with crystal formation. Chemical deglycosylation resulted in significantly increased proteinmore » degradation during crystal growth. Such peptide bond cleavages were observed to a much lesser extent in the crystals grown from neuraminidase-digested hCG. Sequence analysis of the HF-treated hCG crystals suggested that up to 45% of the molecules within the crystal had an acid-labile peptide bond cleaved. In contrast, the neuraminidase-treated hCG exhibited less than 9% of this type of cleavage. The manner in which hCG was treated prior to crystallization was found to be a very important factor in the extent of peptide bound cleavages occurring during crystal growth. HF treatment of glycoproteins may render glycoproteins more susceptible to peptide bond cleavage during crystal growth.« less

Effect of a single injection of gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) on testicular blood flow measured by color doppler ultrasonography in male Shiba goats

PubMed Central

SAMIR, Haney; SASAKI, Kazuaki; AHMED, Eman; KAREN, Aly; NAGAOKA, Kentaro; EL SAYED, Mohamed; TAYA, Kazuyoshi; WATANABE, Gen

2015-01-01

Although color Doppler ultrasonography has been used to evaluate testicular blood flow in many species, very little has been done in goat. Eight male Shiba goats were exposed to a single intramuscular injection of either gonadotropin-releasing hormone (GnRH group; 1 µg/kg BW) or human chorionic gonadotropin (hCG group; 25 IU/kg BW). Plasma testosterone (T), estradiol (E2) and inhibin (INH) were measured just before (0 hr) and at different intervals post injection by radioimmunoassay. Testis volume (TV) and Doppler indices, such as resistive index (RI) and pulsatility index (PI) of the supratesticular artery, were measured by B-mode and color Doppler ultrasonography, respectively. The results indicated an increase in testicular blood flow in both groups, as RI and PI decreased significantly (P<0.05), but this increase was significant higher and earlier in hCG group (1 hr) than in the GnRH group (2 hr). A high correlation was found for RI and PI with both T (RI, r= −0.862; PI, r= −0.707) and INH in the GnRH group (RI, r=0.661; PI, r=0.701). However, a significant (P<0.05) correlation was found between E2 and both RI (r= −0.610) and PI (r= −0.763) in hCG group. In addition, TV significantly increased and was highly correlated with RI in both groups (GnRH, r= −0.718; hCG, r= −0.779). In conclusion, hCG and GnRH may improve testicular blood flow and TV in Shiba goats. PMID:25715956

Use of ultrasound in the evaluation of trophoblastic disease and its response to therapy. [Comparison with HCG radioimmunoassay

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

Requard, C.K.; Mettler, F.A. Jr.

1980-05-01

Thirty-nine patients with trophoblastic disease were studied to determine the usefulness of ultrasound in identifying risk patterns and response to therapy. Serial measurements of serum human chorionic gonadotropin-beta subunit (HCG-BSU) were compared with ultrasonographic uterine and theca lutein cyst volumes. In 16 patients ultrasound demonstrated theca lutein cysts, many of which were not palpable on physical examination. Although there was a significant decrease in uterine volume and a change in the sonographic pattern following evacuation, volume slowly returned to normal over a period of several months. Persistent trophoblastic disease was more accurately detected by HCG-BSU measurements than by ultrasound. Persistentmore » disease developed in 44% of those patients who had theca lutein cysts and in 22% of those without cysts. Patients with theca lutein cysts did not consistently have higher HCG-BSU levels than patients without cysts, and it is concluded that ultrasound is the best method for detecting these cysts.« less

Production of specific antisera for radioimmunoassay of human luteinizing hormone (LH) in the presence of human chorionic gonadotropin (hCG). [/sup 125/I

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

Thorell, J.I.; Jeppsson, S.; Holmstrom, B.

1976-09-01

A specific radioimmunoassay for LH, which measures plasma LH in the presence of human chorionic gonadotropin (hCG) is described. Rabbits were immunized with highly purified native LH. One of the antisera with a difference in its reactivity against LH and hCG was further purified by affinity chromatography on a column with hCG coupled to Sepharose 4B. The adsorbed antiserum and /sup 125/I-LH was used in a double antibody assay. The LH standard (MRC/68/40) efficiently inhibited the binding of /sup 125/I-LH, and the standard curve showed a sensitivity of 0.5 ng/ml in the sample. hCG up to 10,000 ng/ml did notmore » inhibit the binding of /sup 125/I-LH. The plasma level of LH in pregnant women in the first trimester was low (1.3 +- 0.1 ng/ml). When LH was measured in fertile or menopausal women with or without stimulation with LH/FSH releasing hormone (LH-RH)/sup x/ the results agreed to those found with our conventional LH-assay based on antiserum against hCG.« less

A study of intrauterine infusion of human chorionic gonadotropin (hCG) before frozen-thawed embryo transfer after two or more implantation failures.

PubMed

Huang, Pinxiu; Wei, Lihong; Li, Xinlin

2017-01-01

To investigate the effect of intrauterine infusion of human chorionic gonadotropin (hCG) before frozen-thawed embryo transfer (FET) after two or more implantation failures (TIFs). The study was a prospective randomized single-blind study of 161 cycles in patients undergoing FET who had TIFs. The intervention group received an intrauterine injection of 1000 IU of hCG before embryo transfer (ET) (n = 62). A placebo group (n = 49) received an intrauterine injection of physiological saline before ET. A control group (n = 50) did not receive an intrauterine injection. Clinical pregnancy rates, abortion rates, and ongoing pregnancy rates were compared between the three groups. The clinical pregnancy rates were 59.68%, 53.06%, and 32.00% in the hCG group, placebo group, and control group, respectively. The clinical pregnancy rates were significantly higher in the hCG and placebo groups than in the control group. There were no significant differences in the abortion rates among the three groups. An intrauterine administration of hCG before FET significantly improved the pregnancy rates after TIFs. But local injury caused by the operation of intrauterine perfusion may play an important role in improving clinical pregnancy rates.

Human chorionic gonadotropin detection in cerebrospinal fluid of patients with a germinoma and its prognostic significance: assessment by using a highly sensitive enzyme immunoassay.

PubMed

Fukuoka, Kohei; Yanagisawa, Takaaki; Suzuki, Tomonari; Shirahata, Mitsuaki; Adachi, Jun-Ichi; Mishima, Kazuhiko; Fujimaki, Takamitsu; Katakami, Hideki; Matsutani, Masao; Nishikawa, Ryo

2016-11-01

OBJECTIVE Human chorionic gonadotropin (HCG) can be detected in a certain population of patients with a germinoma, but the frequency of germinoma HCG secretion and the prognostic value of HCG in the CSF are unknown. METHODS The authors measured HCG levels in sera and CSF in patients with a histologically confirmed germinoma by using a highly sensitive assay known as an immune complex transfer enzyme immunoassay (EIA), which is more than 100 times as sensitive as the conventional method, and they analyzed the correlation between HCG levels and the prognoses of patients with a germinoma. RESULTS HCG levels in sera and CSF of 35 patients with a germinoma were examined with the immune complex transfer EIA. The median CSF HCG levels in patients with a germinoma during the pretreatment and posttreatment evaluations were 192.5 pg/ml (range 1.2-13,116.5 pg/ml) and 18.7 pg/ml (1.2-283.9 pg/ml), respectively. Before treatment, the CSF HCG level was greater than the cutoff value in 85.7% of the patients with a germinoma. The authors compared survival rates among the patients by using a CSF HCG cutoff level of 1000 pg/ml, and the difference was statistically significant between the groups (p = 0.029, log-rank test). CONCLUSIONS Results of this study demonstrate that most germinomas secrete HCG. Patients with a germinoma that secretes higher amounts of HCG in their CSF experienced recurrence more frequently than those with lower CSF HCG levels.

Disulfide bond rearrangement during formation of the chorionic gonadotropin beta-subunit cystine knot in vivo.

PubMed

Wilken, Jason A; Bedows, Elliott

2004-05-04

The intracellular kinetic folding pathway of the human chorionic gonadotropin beta-subunit (hCG-beta) reveals the presence of a disulfide between Cys residues 38-57 that is not detected by X-ray analysis of secreted hCG-beta. This led us to propose that disulfide rearrangement is an essential feature of cystine knot formation during CG-beta folding. To test this, we used disulfide bond formation to monitor progression of intracellular folding intermediates of a previously uncharacterized protein, the CG-beta subunit of cynomolgous macaque (Macaca fascicularis). Like its human counterpart hCG-beta with which it shares 81% identity, macaque (m)CG-beta is a cystine knot-containing subunit that assembles with an alpha-subunit common to all glycoprotein hormone members of its species to form a biologically active heterodimer, mCG, which, like hCG, is required for pregnancy maintenance. An early mCG-beta folding intermediate, mpbeta1, contained two disulfide bonds, one between Cys34 and Cys88 and the other between Cys38 and Cys57. The subsequent folding intermediate, mpbeta2-early, was represented by an ensemble of folding forms that, in addition to the two disulfides mentioned above, included disulfide linkages between Cys9 and Cys57 and between Cys38 and Cys90. These latter two disulfides are those contained within the beta-subunit cystine knot and reveal that a disulfide exchange occurred during the mpbeta2-early folding step leading to formation of the mCG-beta knot. Thus, while defining the intracellular kinetic protein folding pathway of a monkey homologue of CG-beta, we detected the previously predicted disulfide exchange event crucial for CG-beta cystine knot formation and attainment of CG-beta assembly competence.

Luteal Coasting and Individualization of Human Chorionic Gonadotropin Dose after Gonadotropin-Releasing Hormone Agonist Triggering for Final Oocyte Maturation—A Retrospective Proof-of-Concept Study

PubMed Central

Lawrenz, Barbara; Samir, Suzan; Garrido, Nicolas; Melado, Laura; Engelmann, Nils; Fatemi, Human M.

2018-01-01

Ovarian stimulation in a gonadotropin-releasing hormone (GnRH) antagonist protocol with the use of GnRH agonist for final oocyte maturation is the state-of-the-art treatment in patients with an expected or known high response to avoid or at least reduce significantly the risk for development of ovarian hyperstimulation syndrome (OHSS). Due to a shortened LH surge after administration of GnRH agonist in most patients, the luteal phase will be characterized by luteolysis and luteal phase insufficiency. Maintaining a sufficient luteal phase is crucial for achievement of a pregnancy; however, the optimal approach is still under debate. Administration of human chorionic gonadotropin (hCG) within 72 h rescues the corpora lutea function; however, the so far often used 1,500 IU still bear the risk for development of OHSS. The recently introduced concept of “luteal coasting” individualizes the luteal phase support by monitoring the progesterone concentrations and administering a rescue dosage of hCG when progesterone concentrations drop significantly. This retrospective proof-of-concept study explored the correlation between hCG dosages ranging from 375 up to 1,500 IU and the progesterone levels in the early and mid-luteal phases as well as the likelihood of pregnancy, both early and ongoing. The chance of pregnancy is highest with progesterone level ≥13 ng/ml at 48 h postoocyte retrieval. Among the small sample size of 52 women studied, it appears that appropriate progesterone levels can be achieved with hCG dosages as low as 375 IU. This may well optimize the chance of pregnancy while reducing the risk of OHSS associated with higher doses of hCG supplementation in the luteal phase. PMID:29497400

Dynamics of progesterone, TNF-a and a metabolite of PGF2a in blood plasma of beef cows following embryo transfer

USDA-ARS?s Scientific Manuscript database

Lactating beef cows received an embryo along with no treatment (control; n = 16), controlled internal drug releasing device (CIDR; n = 16), human chorionic gonadotropin (hCG; n = 15), or gonadotropin releasing hormone (GnRH; n = 15) to assess the effectiveness of these treatments in increasing blood...

Human chorionic gonadotropin (hCG) concentrations during the late first trimester are associated with fetal growth in a fetal sex-specific manner.

PubMed

Barjaktarovic, Mirjana; Korevaar, Tim I M; Jaddoe, Vincent W V; de Rijke, Yolanda B; Visser, Theo J; Peeters, Robin P; Steegers, Eric A P

2017-02-01

Human chorionic gonadotropin (hCG) is a pregnancy-specific hormone that regulates placental development. hCG concentrations vary widely throughout gestation and differ based on fetal sex. Abnormal hCG concentrations are associated with adverse pregnancy outcomes including fetal growth restriction. We studied the association of hCG concentrations with fetal growth and birth weight. In addition, we investigated effect modification by gestational age of hCG measurement and fetal sex. Total serum hCG (median 14.4 weeks, 95 % range 10.1-26.2), estimated fetal weight (measured by ultrasound during 18-25th weeks and >25th weeks) and birth weight were measured in 7987 mother-child pairs from the Generation R cohort and used to establish fetal growth. Small for gestational age (SGA) was defined as a standardized birth weight lower than the 10th percentile of the study population. There was a non-linear association of hCG with birth weight (P = 0.009). However, only low hCG concentrations measured during the late first trimester (11th and 12th week) were associated with birth weight and SGA. Low hCG concentrations measured in the late first trimester were also associated with decreased fetal growth (P = 0.0002). This was the case for both male and female fetuses. In contrast, high hCG concentrations during the late first trimester were associated with increased fetal growth amongst female, but not male fetuses. Low hCG in the late first trimester is associated with lower birth weight due to a decrease in fetal growth. Fetal sex differences exist in the association of hCG concentrations with fetal growth.

Ineffectiveness of human chorionic gonadotropin in weight reduction: a double-blind study.

PubMed

Stein, M R; Julis, R E; Peck, C C; Hinshaw, W; Sawicki, J E; Deller, J J

1976-09-01

Our investigation was designed to retest the hypothesis of the efficacy of human chorionic gonadotropin (HCG) on weight reduction in obese women in a clinic setting. We sought to duplicate the Asher-Harper study (1973) which had found that the combination of 500 cal diet and HCG had a statistically significant benefit over the diet and placebo combination as evidenced by greater weight loss and decrease in hunger. Fifty-one women between the ages of 18 and 60 participated in our 32-day prospective, randomized, double-blind comparison of HCG versus placebo. Each patient was given the same diet (the one prescribed in the Asher-Harper study), was weighed daily Monday through Saturday and was counselled by one of the investigators who administered the injections. Laboratory studies were performed at the time of initial physical examinations and at the end of the study. Twenty of 25 in the HCG and 21 of 26 patients in the placebo groups completed 28 injections. There was no statistically significant difference in the means of the two groups in number of injections received, weight loss, percent of weight loss, hip and waist circumference, weight loss per injections, or in hunger ratings. HCG does not appear to enhance the effectiveness of a rigidly imposed regimen for weight reduction.

A simple and sensitive immunoassay for the determination of human chorionic gonadotropin by graphene-based chemiluminescence resonance energy transfer.

PubMed

Lei, Jiuqian; Jing, Tao; Zhou, Tingting; Zhou, Yusun; Wu, Wei; Mei, Surong; Zhou, Yikai

2014-04-15

In this study, we report a strategy of chemiluminescence resonance energy transfer (CRET) using graphene as an efficient long-range energy acceptor. Magnetic nanoparticles were also used in CRET for simple magnetic separation and immobilization of horseradish peroxidase (HRP)-labeled anti-HCG antibody. In the design of CRET system, the sandwich-type immunocomplex was formed between human chorionic gonadotropin (HCG, antigen) and two different antibodies bridged the magnetic nanoparticles and graphene (acceptors), which led to the occurrence of CRET from chemiluminescence light source to graphene. After optimizing the experimental conditions, the quenching of chemiluminescence signal depended linearly on the concentration of HCG in the range of 0.1 mIU mL(-1)-10 mIU mL(-1) and the detection limit was 0.06 mIU mL(-1). The proposed method was successfully applied for the determination of HCG levels in saliva and serum samples, and the results were in good agreement with the plate ELISA with colorimetric detection. It could also be developed for detection of other antigen-antibody immune complexes by using the corresponding antigens and respective antibodies. © 2013 Published by Elsevier B.V.

Human chorionic gonadotropin-administered natural cycle versus spontaneous ovulatory cycle in patients undergoing two pronuclear zygote frozen-thawed embryo transfer.

PubMed

Lee, You-Jung; Kim, Chung-Hoon; Kim, Do-Young; Ahn, Jun-Woo; Kim, Sung-Hoon; Chae, Hee-Dong; Kang, Byung-Moon

2018-03-01

To compare human chorionic gonadotropin (HCG)-administered natural cycle with spontaneous ovulatory cycle in patients undergoing frozen-thawed embryo transfer (FTET) in natural cycles. In this retrospective cohort study, we analyzed the clinical outcome of a total of 166 consecutive FTET cycles that were performed in either natural cycle controlled by HCG for ovulation triggering (HCG group, n=110) or natural cycle with spontaneous ovulation (control group, n=56) in 166 infertile patients between January 2009 and November 2013. There were no differences in patients' characteristics between the 2 groups. The numbers of oocytes retrieved, mature oocytes, fertilized oocytes, grade I or II embryos and frozen embryos in the previous in vitro fertilization (IVF) cycle in which embryos were frozen were comparable between the HCG and control groups. Significant differences were not also observed between the 2 groups in clinical pregnancy rate (CPR), embryo implantation rate, miscarriage rate, live birth rate and multiple CPR. However, the number of hospital visits for follicular monitoring was significantly fewer in the HCG group than in the control group ( P <0.001). Our results demonstrated that HCG administration for ovulation triggering in natural cycle reduces the number of hospital visits for follicular monitoring without any detrimental effect on FTET outcome when compared with spontaneous ovulatory cycles in infertile patients undergoing FTET in natural ovulatory cycles.

The role of human chorionic gonadotropin in regulation of naïve and memory T cells activity in vitro.

PubMed

Zamorina, S A; Litvinova, L S; Yurova, K A; Khaziakhmatova, O G; Timganova, V P; Bochkova, M S; Khramtsov, P V; Rayev, M B

2018-01-01

The role of human chorionic gonadotropin (hCG) in the regulation of molecular genetics factors determining the functional activity of human naïve and memory T cells in vitro was studied. It was found that hCG (10 and 100IU/ml) inhibited CD28 and CD25 expression on the naïve T cells (CD45RA+) and CD25 expression on the memory T cells (CD45R0+). hCG didn't affect the CD71 proliferation marker expression in total. Nevertheless, hCG reduced the percentage of proliferating memory T cells with simultaneous suppression of CD71 expression on proliferating CD45R0+cells. In parallel, expression of U2af1l4, Gfi1, and hnRNPLL genes, which are Ptprc gene alternative splicing regulators was evaluated. It was established that hCG stimulated the expression of U2af1l4 and hnRNPLL genes, responsible for the assembly of CD45R0 in memory T cells, but reduced the expression of Gfi1 in these cells. In general, hCG promotes the differentiation of memory T cells by increasing of CD45R0 expression, but inhibits proliferation and CD25 expression which reflects their functional activity. Copyright © 2017 Elsevier B.V. All rights reserved.

New methods of pregnancy testing in adolescent girls.

PubMed

Saxena, B B

1981-05-01

The knowledge and use of newer, more sensitive, and reliable pregnancy tests which are easily accessible and of moderate cost are the 1st steps in the early diagnosis and management of pregnancy, especially in adolescent girls. Accurate diagnosis of pregnancy soon after conception offers the option of abortion by simple, effective, and inexpensive procedures or early initiation of prenatal maternity care. Discussion focuses on the symptoms of pregnancy and the historical development and basis of pregnancy tests as well as the specific types of pregnancy tests. The most familiar sign of pregnancy is the missed period. Other symptoms that provide presumptive evidence of pregnancy include fatigue and lassitude, increased body temperature, and breast fullness or pain. Feelings of nausea, vomiting, and weight gain may appear after 2 weeks. The diagnosis of pregnancy by the detection of the human chorionic gonadotropin was initially described 53 years ago by Selmar Aschheim and Bernhardt Zondek. Improvements in the techniques for the measurement of human chorionic gonadotropin (hCG) have been directly related to the progress in the purification and isolation of hCG and elucidation of the amino acid sequence of the hormone-nonspecific alpha subunit and hormone-specific beta subunit of hCG. The history, physical examination, and pregnancy tests will generally provide sufficient information for a definite diagnosis of pregnancy. The presence of hCG in the urine or blood is the most accurate of all the indications of pregnancy. During the last century, 4 different techniques for the determination of hCG in blood and/or urine have been developed. These include the following and are reviewed in detail: 1) bioassays in intact laboratory animals; 2) immunologic tube or slide methods with heme- or latex-agglutination inhibition, as well as the more recently developed competitive protein binding method such as 3) radioimmunoassay (RIA) for the use of radioisotope labeled hormone and the specific antiserum against hCG; and 4) radioreceptorassay by the use of radioisotope-labeled hormone with biological activity and the specific receptors as the binding proteins.

The Role of HCG in Implantation: A Mini-Review of Molecular and Clinical Evidence

PubMed Central

Makrigiannakis, Antonis; Vrekoussis, Thomas; Zoumakis, Emmanouel; Kalantaridou, Sophia N.; Jeschke, Udo

2017-01-01

Embryo implantation is a complex process involving continuous molecular cross-talk between the embryo and the decidua. One of the key molecules during this process is human chorionic gonadotropin (HCG). HCG effectively modulates several metabolic pathways within the decidua contributing to endometrial receptivity. Herein, a brief overview of the molecular mechanisms regulated by HCG is presented. Furthermore, we summarize the existing evidence regarding the clinical impact on reproductive outcomes after endometrial priming with HCG prior to embryo transfer. Although promising, further evidence is needed to clarify the protocol that would lead to beneficial outcomes. PMID:28629172

Induction of puberty with human chorionic gonadotropin and follicle-stimulating hormone in adolescent males with hypogonadotropic hypogonadism.

PubMed

Barrio, R; de Luis, D; Alonso, M; Lamas, A; Moreno, J C

1999-02-01

To evaluate the clinical and hormonal responses of adolescent males with hypogonadotropic hypogonadism (HH) in response to gonadotropin replacement with the use of long-term combined hCG and FSH therapy. Prospective clinical study. Clinical pediatric department providing tertiary care. Seven prepubertal males with isolated HH with a mean (+/-SD) age of 15.44+/-1.97 years and seven prepubertal males with panhypopituitarism-associated HH with a mean (+/-SD) age of 18.1+/-3.24 years were studied. Human chorionic gonadotropin (1,000-1,500 IU IM) and FSH (75-100 IU SC) were administered every alternate day of the week until the total induction of puberty and spermatogenesis was achieved. Serum testosterone levels, testicular volume, penis length, and sperm count were evaluated after the administration of hCG and FSH. All patients achieved normal sexual maturation and normal or nearly normal adult male levels of testosterone. The increase in testicular size was significant in both groups. Positive sperm production was assessed in four of five patients with isolated HH and in three of three patients with panhypopituitarism-associated HH. Long-term combined hCG and FSH therapy is effective in inducing puberty, increasing testicular volume, and stimulating spermatogenesis in adolescent males with isolated HH and panhypopituitarism-associated HH.

The effect of administering equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG) post artificial insemination on fertility of lactating dairy cows.

PubMed

Bartolome, J A; Wallace, S Perez; de la Sota, R L; Thatcher, W W

2012-09-15

The objective was to evaluate the effect of equine chorionic gonadotropin (eCG) and hCG post artificial insemination (AI) on fertility of lactating dairy cows. In Experiment 1, cows were either treated with eCG on Day 22 post AI (400 IU; n = 80) or left untreated (n = 84). On Day 29, pregnant cows were either treated with hCG (2500 IU; n = 32) or left untreated (n = 36). Pregnancy and progesterone were evaluated on Days 29 and 45. In Experiment 2, cows (n = 28) were either treated with eCG on Day 22 (n = 13) or left untreated (n = 15) and either treated with hCG on Day 29 (n = 14) or left untreated (n = 14). Blood sampling and ultrasonography were conducted between Days 22 and 45. In Experiment 3, cows were either treated with eCG on Day 22 post AI (n = 229) or left untreated (n = 241). Pregnancy was evaluated on Days 36 and 85. In Experiment 1, eCG on Day 22 increased (P < 0.02) the number of pregnant cows on Day 29 (50.0 vs. 33.3%) and on Day 45, the increase was higher (P < 0.01) in cows with timed AI (41.2 vs. 6.5%) than in cows AI at detected estrus (50.0 vs. 37.8%). Pregnancy losses were reduced by eCG and hCG, but increased in cows that did not receive eCG but were given hCG (P < 0.01). Treatment with hCG tended (P < 0.06) to increase progesterone in control cows, but not in cows treated with eCG. In Experiment 2, hCG increased (P < 0.01) the number of accessory CLs on Day 35 (28.5 vs. 0.0%) and tended (P < 0.07) to increase progesterone. In Experiment 3, eCG increased the number of pregnant cows (P < 0.05) on Days 36 and 85, but only in cows with low body condition (eCG = 45.6 and 43.5%; Control = 22.9 and 22.9%). In conclusion, eCG at 22 days post insemination increased fertility, primarily in cows with low body condition and reduced pregnancy losses when given 7 days before hCG; hCG induced accessory CLs and slightly increased progesterone, but hCG given in the absence of a prior eCG treatment reduced fertility. Copyright © 2012 Elsevier Inc. All rights reserved.

Human Chorionic Gonadotropin: Unknown about Known.

PubMed

Borisova, M A; Moiseenko, D Yu; Smirnova, O V

2017-01-01

The last two decade discoveries shift the accent from consideration of human chorionic gonadotripin (hCG) as a hormone, that controls progesterone production by corpus luteum cells, to a powerful paracrine regulator which'in the tandem with its hyperglycozilated analog (hCG-H) induces successful implantation and coordinated dialog between blastocyst and uterus tissues. Ability of hCG to interact with TSH receptor and hCG-H with TGF-beta-RII extend significantly the spectrum of processes controlled by these molecules. Differences between intracellular pathways of signal transduction between hCG and LH mediated by the same receptor (LH/hCG-R) impugn unity of their effector mechanisms previously considered as obvious. Paracine properties-of hCG comprise control of fusing of trophoblasts into syncytiotrophoblasts, angiogenesis, immunity regulation and endometrium predisposition to implantation. Angiogenesis is associated with LH/hCG-R expressed on mural cells of uterine spiral arteries as well as induced secretion of soluble VEGF type by endometrial cells. hCG.regulates ratio between different forms of T-helper cells in maternal organism on the initial gestation stage determining high level of Th2 cells. hCG supports local immunotolerance acting as chemoattractant for T-suppressors (T-Treg) and apoptotic factor for T-lymphocytes. Endometrial susceptibility arises from activation of osteopantin secretion and decline of mucin secretion by epithelial cells. hCG-H acts on the same tissues as hCG as a paracrine agent regulating multiple cascades of cytokines. hCG-H plays the key role in trophoblast invasion into,uterine decidua as a result of gelatinase secretion by these cells.The degree of angiogenic effect of hCG-H is compatiblewith hCG but its signal transduction is mediated by TGF-beta signal transduction pathway that stimulates mural cell proliferation. hCG-H acts as mitogen on NK-cells and is able to activate them and direct to angiogenesis maintenance. In this article the attempt was made to elucidate the most important discoveries about the role of hCG and its hyperglycosylated analog yet accomplished and still upcoming.

Human Chorionic Gonadotrophin as a Possible Mediator of Leiomyoma Growth during Pregnancy: Molecular Mechanisms.

PubMed

Sarais, Veronica; Cermisoni, Greta Chiara; Schimberni, Matteo; Alteri, Alessandra; Papaleo, Enrico; Somigliana, Edgardo; Vigano', Paola

2017-09-20

Uterine fibroids are the most common gynecologic benign tumors. Studies supporting a strong pregnancy-related growth of leiomyomas generally claimed a crucial role of sex steroid hormones. However, sex steroids are unlikely the unique actors involved as estrogen and progesterone achieve a pick serum concentration in the last trimester while leiomyomas show a typical increase during the first trimester. Given the rapid exponential raise in serum human Chorionic Gonadotrophin (hCG) at the beginning of gestation, we conducted a review to assess the potential role of hCG in the striking growth of leiomyomas during initial pregnancy. Fibroid growth during initial pregnancy seems to correlate to the similar increase of serum hCG levels until 12 weeks of gestation. The presence of functional Luteinizing Hormone/human Chorionic Gonadotropin (LH/hCG) receptors was demonstrated on leiomyomas. In vitro treatment of leiomyoma cells with hCG determines an up to 500% increase in cell number after three days. Expression of cyclin E and cyclin-dependent kinase 1 was significantly increased in leiomyoma cells by hCG treatment. Moreover, upon binding to the receptor, hCG stimulates prolactin secretion in leiomyoma cells, promoting cell proliferation via the mitogen-activated protein kinase cascade. Fibroid enlargement during initial pregnancy may be regulated by serum hCG.

Human Chorionic Gonadotrophin as a Possible Mediator of Leiomyoma Growth during Pregnancy: Molecular Mechanisms

PubMed Central

Sarais, Veronica; Cermisoni, Greta Chiara; Schimberni, Matteo; Alteri, Alessandra; Papaleo, Enrico; Somigliana, Edgardo; Vigano’, Paola

2017-01-01

Uterine fibroids are the most common gynecologic benign tumors. Studies supporting a strong pregnancy-related growth of leiomyomas generally claimed a crucial role of sex steroid hormones. However, sex steroids are unlikely the unique actors involved as estrogen and progesterone achieve a pick serum concentration in the last trimester while leiomyomas show a typical increase during the first trimester. Given the rapid exponential raise in serum human Chorionic Gonadotrophin (hCG) at the beginning of gestation, we conducted a review to assess the potential role of hCG in the striking growth of leiomyomas during initial pregnancy. Fibroid growth during initial pregnancy seems to correlate to the similar increase of serum hCG levels until 12 weeks of gestation. The presence of functional Luteinizing Hormone/human Chorionic Gonadotropin (LH/hCG) receptors was demonstrated on leiomyomas. In vitro treatment of leiomyoma cells with hCG determines an up to 500% increase in cell number after three days. Expression of cyclin E and cyclin-dependent kinase 1 was significantly increased in leiomyoma cells by hCG treatment. Moreover, upon binding to the receptor, hCG stimulates prolactin secretion in leiomyoma cells, promoting cell proliferation via the mitogen-activated protein kinase cascade. Fibroid enlargement during initial pregnancy may be regulated by serum hCG. PMID:28930160

Using a simulation model to assess risk of false negative point-of-care urinary human chorionic gonadotropin device results due to high-dose hook interference.

PubMed

Milhorn, Denise; Korpi-Steiner, Nichole

2015-02-01

It is unclear if the point-of-care (POC) Clinitest hCG device is subject to high-dose hook interference from physiological concentrations of intact human chorionic gonadotropin (hCG), β-core fragment of hCG (hCGβcf), and hCG free β-subunit (hCGβ) found in urine during pregnancy. We used a simulation model to address this question and related our findings to our institution's pregnant population in order to assess risk for potential false-negative hCG results. The expected distribution of days relative to ovulation during routine POC hCG testing was estimated from 182 patients. Clinitest-Clinitek Status hCG device susceptibility to high-dose hook interference from hCG variants and potential risk of false-negative results as it relates to this population were evaluated by testing increasing concentrations of hCG, hCGβcf, hCGβ as well as urine simulating physiological hCG, hCGβcf and hCGβ concentrations expected during early pregnancy (≤44 days post-ovulation). The Clinitest-Clinitek Status hCG device exhibited high-dose hook interference from hCGβcf alone, but not from hCG, hCGβ, or simulated physiological urinary concentrations of combined hCG, hCGβcf and hCGβ expected during early pregnancy. The majority of our patient population had urinary hCG testing conducted during early pregnancy. The Clinitest-Clinitek Status hCG device is unlikely to exhibit false-negative urinary hCG results due to high-dose hook interference for women in early healthy pregnancy, although additional studies are necessary to determine potential risk in other patient populations. Visual interpretation of POC urinary hCG device results is an important failure mode to consider in risk analyses for erroneous urinary hCG device results. Published by Elsevier Inc.

Immunochemical mapping of gonadotropins.

PubMed

Berger, P; Bidart, J M; Delves, P S; Dirnhofer, S; Hoermann, R; Isaacs, N; Jackson, A; Klonisch, T; Lapthorn, A; Lund, T; Mann, K; Roitt, I; Schwarz, S; Wick, G

1996-12-20

As a glycoprotein hormone, human chorionic gonadotropic (hCG) is not a single molecular entity but this term rather comprises an array of molecular variants such as hCG, hCG beta, hCGn, hCG beta n, hCG beta cf, -CTPhCG, hCG beta CTP, deglyhCG, asialohCG, hCGav and the closely related molecules hLH, hLH beta and hLH beta ef. The advent of monoclonal antibodies (MCA), the availability of ultrasensitive detection systems and the recent determination of the crystal structure of hCG, made it possible to design special purpose diagnostic and clinical research immunoassays for hCG-like molecules. For more than a decade we and others have tried to refine epitope maps for hCG and related molecules by means of a large panel of MCA, naturally occurring metabolic variants of hCG (hCGn, hCG beta, hCG alpha, hCG beta cf, hCG beta CTP), homologous hormones and subunits of various species (e.g. hLH, hLH beta, hFSH, hTSH, oLH, rLH beta), chemically modified molecules (deglyhCG, asialohCG, tryptic and chymotryptic hCG beta and hCG alpha fragments) and synthetic peptides (octapeptides and longer). It appeared that all epitopes on molecular hCG-variants recognized by our MCA are determined by the protein backbone. Except for the two major epitopes on hCG beta CTP and parts of two antigenic domains on hCG alpha, epitopes on hCG-derived molecules are determined by the tertiary and quarternary structure. Operationally useful descriptive epitope maps were designed including information on assay suitability of antigenic determinants. On this basis we established ultrasensitive time-resolved fluoroimmuno-assays for hCG, hCG and hCGn, hCG beta and hCG beta n and hCG beta cf, hCG alpha and additional assays recognizing different spectra of hCG-variants. Such assay have been applied by us and others to the detection of pregnancy, early pregnancy loss, choriocarcinoma, testicular cancer, other cancers and prenatal diagnosis. However, as the molecular structure of many epitopes utilized in immunoassays of different laboratories was not resolved, comparability of results was not satisfactory. Consequently, attempts were made to compare schematic epitope maps from different research institutions. The situation has been much improved by solving the three-dimensional (3D) structure of hCG. It has been shown that hCG is a member of the structural superfamily of cystine knot growth factors like NGF, PDGF-B and TGF-beta. Each of its subunits is stabilized in its topology by three disulfide bonds forming a cystine knot. Moreover, it turned out that the disulfide bridges in their majority have previously been wrongly assigned. Computer molecular modeling of crystallographic coordinates of hCG and subsequent selective combined--PCR-based and immunological--mutational analyses of hCG beta expressed via the transmembrane region of a MHC molecule made it possible to more precisely localize epitopes on hCG-derived molecules. Although the entire surface of hCG has to be regarded as potentially immunogenic there seems to be hot spots where epitopes are clustered in antigenic domains. These are located on the first and third loops protuding from the cystine knots of both subunits and are possibly centered around the knot itself. Ultimate answers on epitope localizations will be given by the crystal structure determination of hCG complexed with different Fabs.

Hyperglycosylated human chorionic gonadotropin does not increase progesterone production by luteinized granulosa cells.

PubMed

Crochet, John R; Shah, Anish A; Schomberg, David W; Price, Thomas M

2012-09-01

Trophoblast-derived human chorionic gonadotropin (hCG) promotes corpus luteum progesterone (P4) production, and wide ranges of serum P4 levels are noted in various pregnancy outcomes, despite similar hCG concentrations. There are five unique biologically active hCG variants in human pregnancy urine, and previous studies of P4 production in response to hCG have used only preparations containing all isoforms. Understanding exactly which hCG variant is primarily responsible for stimulating corpus luteum steroidogenesis may have great clinical and diagnostic implications, including in the setting of ectopic pregnancy. Our objective was to delineate the role of the standard and hyperglycosylated (H)-hCG isoforms in stimulating P4 production by luteinized granulosa cells. Cell culture, ELISA, and fluorometric-based protein assays were done at Duke University Medical Center. Patients were anonymous oocyte donors. Cultured luteinized granulosa cells were treated with 0.25, 0.5, and 1.0 ng/ml total hCG, which contains all isoforms, purified standard hCG (37.1 kDa), and purified H-hCG (42.8 kDa). P4 produced per total cellular protein (nanograms per microgram) was measured via ELISA and fluorometric protein determination kits. Both total hCG (P = 0.0003) and purified standard hCG (P < 0.0001) stimulated a dose-dependent increase in P4 production. Purified H-hCG did not change the P4 produced per total cellular protein response (P value not significant). Standard hCG stimulated P4 production by cultured granulosa cells and likely supports corpus luteum function via interactions with the LH/hCG receptor. In contrast, H-hCG did not increase P4 production, which indicates a nonsteroidogenic role for this protein during early gestation.

A Unique Human Chorionic Gonadotropin Antagonist Suppresses Ovarian Hyperstimulation Syndrome in Rats

PubMed Central

Vardhana, Pratibhasri A.; Julius, Martin A.; Pollak, Susan V.; Lustbader, Evan G.; Trousdale, Rhonda K.; Lustbader, Joyce W.

2009-01-01

Ovarian hyperstimulation syndrome (OHSS) is a complication of in vitro fertilization associated with physiological changes after hCG administration to induce final oocyte maturation. It presents as widespread increases in vascular permeability and, in rare cases, results in cycle cancellation, multi-organ dysfunction, and pregnancy termination. These physiological changes are due primarily to activation of the vascular endothelial growth factor (VEGF) system in response to exogenous human chorionic gonadotropin (hCG). An hCG antagonist (hCG-Ant) could attenuate these effects by competitively binding to the LH/CG receptor, thereby blocking LH activity in vivo. We expressed a form of hCG that lacks three of its four N-linked glycosylation sites and tested its efficacy as an antagonist. The hCG-Ant binds the LH receptor with an affinity similar to native hCG and inhibits cAMP response in vitro. In a rat model for ovarian stimulation, hCG-Ant dramatically reduces ovulation and steroid hormone production. In a well-established rat OHSS model, vascular permeability and vascular endothelial growth factor (VEGF) expression are dramatically reduced after hCG-Ant treatment. Finally, hCG-Ant does not appear to alter blastocyst development when given after hCG in mice. These studies demonstrate that removing specific glycosylation sites on native hCG can produce an hCG-Ant that is capable of binding without activating the LH receptor and blocking the actions of hCG. Thus hCG-Ant will be investigated as a potential therapy for OHSS. PMID:19443574

Recognition of N-Glycoforms in Human Chorionic Gonadotropin by Monoclonal Antibodies and Their Interaction Motifs*

PubMed Central

Li, Daoyuan; Zhang, Ping; Li, Fei; Chi, Lequan; Zhu, Deyu; Zhang, Qunye; Chi, Lianli

2015-01-01

The glycosylation of human chorionic gonadotropin (hCG) plays an important role in reproductive tumors. Detecting hCG N-glycosylation alteration may significantly improve the diagnostic accuracy and sensitivity of related cancers. However, developing an immunoassay directly against the N-linked oligosaccharides is unlikely because of the heterogeneity and low immunogenicity of carbohydrates. Here, we report a hydrogen/deuterium exchange and MS approach to investigate the effect of N-glycosylation on the binding of antibodies against different hCG glycoforms. Hyperglycosylated hCG was purified from the urine of invasive mole patients, and the structure of its N-linked oligosaccharides was confirmed to be more branched by MS. The binding kinetics of the anti-hCG antibodies MCA329 and MCA1024 against hCG and hyperglycosylated hCG were compared using biolayer interferometry. The binding affinity of MCA1024 changed significantly in response to the alteration of hCG N-linked oligosaccharides. Hydrogen/deuterium exchange-MS reveals that the peptide β65–83 of the hCG β subunit is the epitope for MCA1024. Site-specific N-glycosylation analysis suggests that N-linked oligosaccharides at Asn-13 and Asn-30 on the β subunit affect the binding affinity of MCA1024. These results prove that some antibodies are sensitive to the structural change of N-linked oligosaccharides, whereas others are not affected by N-glycosylation. It is promising to improve glycoprotein biomarker-based cancer diagnostics by developing combined immunoassays that can determine the level of protein and measure the degree of N-glycosylation simultaneously. PMID:26240146

Effect of intrauterine injection of human chorionic gonadotropin before embryo transfer on clinical pregnancy rates from in vitro fertilisation cycles: a prospective study.

PubMed

Santibañez, Alvaro; García, Jorge; Pashkova, Olga; Colín, Omar; Castellanos, Guillermo; Sánchez, Ana P; De la Jara, Julio F

2014-01-29

The implantation process after embryo transfer depends on the embryo quality and endometrial receptivity. It is estimated that fifty to seventy-five per cent of pregnancies are lost due to a failure of implantation. There is evidence that there is an early secretion of human chorionic gonadotrophin before embryo implantation, and this secretion has been linked to an important function in angiogenesis and the inflammatory response that promotes the implantation process. Our objective was to determine the effects of intrauterine injection of human chorionic gonadotropin (hCG) before the embryo transfer in an in vitro fertilisation cycle. A prospective randomised study was conducted in Reproductive Medicine Centre PROCREA in Mexico City. Infertile patients who had a medical indication for in vitro fertilisation were studied. Two groups were included (n 210); the intervention group received an intrauterine injection of 500 IU of hCG before the embryo transfer (n 101). The control group (n 109) did not receive hCG. Comparisons were performed using a chi-square test. The clinical pregnancy rate (CPR) was our principal outcome. The implantation rate was a secondary outcome. The implantation rate was significantly higher in the hCG group compared to the control group (52.4% vs 35.7%, p 0.014). The clinical pregnancy rate was also significantly higher (50.4 vs 33.0%, p 0.010). No adverse effects were observed. The intrauterine injection of hCG before embryo transfer showed a significant increase in the clinical pregnancy rate. More clinical trials are needed to reproduce these results on this promising intervention. The live birth rate must be included in subsequent studies.

Layer-by-layer assembly of gold nanoparticles and cysteamine on gold electrode for immunosensing of human chorionic gonadotropin at picogram levels.

PubMed

Roushani, Mahmoud; Valipour, Akram; Valipour, Mehdi

2016-04-01

The development of an electrochemical immunosensor for the detection of human chorionic gonadotropin (hCG) is described with a limit of detection as low as 0.3 pg mL(-1) in phosphate buffer. In this immunosensor, cysteamine (Cys) and gold nanoparticles (AuNPs) were used to immobilize an anti-hCG monoclonal antibody onto a gold electrode (GE). The structure of AuNPs has been confirmed by EDS, SEM, and TEM analysis. Due to the large specific surface area and excellent electrical conductivity of AuNPs, electron transfer was promoted and the amount of hCG antibody was enhanced significantly. A systematic study on the effects of experimental parameters such as pH, incubation time in the hCG solution and urea solution used for experiments on the binding between the immobilized antibody and hCG has been carried out. Under optimal experimental parameters, differential pulse voltammetry (DPV) signal changes of the [Fe(CN)6](3-/4-) are used to detect hCG with two broad linear ranges: 0.001 to 0.2 and 0.2 to 60.7 ng mL(-1). The LOD value proves more sensitive in comparison with previously reported methods. The prepared immunosensor showed high sensitivity and stability. In addition, the immunosensor was successfully used for the determination of hCG in human serum. Copyright © 2015 Elsevier B.V. All rights reserved.

Hyperglycosylated human chorionic gonadotropin as an early predictor of pregnancy outcomes after in vitro fertilization.

PubMed

Chuan, Sandy; Homer, Michael; Pandian, Raj; Conway, Deirdre; Garzo, Gabriel; Yeo, Lisa; Su, H Irene

2014-02-01

To determine whether serum hyperglycosylated human chorionic gonadotropin (hhCG) measured as early as 9 days after egg retrieval can predict ongoing pregnancies after in vitro fertilization and fresh embryo transfer (IVF-ET). Cohort Academic assisted reproduction center. Consecutive patients undergoing IVF-ET INTERVENTION(S): Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Ongoing pregnancy beyond 9 weeks of gestation. Ongoing pregnancy (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG. However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. A D9 hhCG level of >110 pg/mL was 96% specific for an ongoing pregnancy, yielding a positive predictive value of 94%. Compared with the D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67, respectively). The diagnostic test characteristics were similar between the D16 hhCG and hCG levels. In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable, and hhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. In this early assessment, hhCG was superior to traditional hCG and highly predictive of ongoing pregnancies. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Human chorionic gonadotropin radioantibodies in the radioimmunodetection of cancer and for disclosure of occult metastases.

PubMed Central

Goldenberg, D M; Kim, E E; DeLand, F H

1981-01-01

Radioimmunodetection (RaID) of tumors containing human chorionic gonadotropin (hCG; choriogonadotropin) was evaluated in 25 patients by injecting 131I-labeled goat antibody IgG against hCG and performing total-body photoscans with a gamma scintillation camera 24 and 48 hr later. All 10 testicular cancer patients with proven tumor sites had positive RaID results, whereas three cases without known tumor were negative. Four patients with hydatidiform mole and one with degenerative products of conception showed positive RaID results consistent with elevated serum hCG titers. Two putatively false-positive results were obtained in patients with lung or ovarian cancer, whereas a false-negative metastasis to the liver of a patient with lung cancer and an elevated serum hCG titer was observed. Of 14 tumor sites found by RaID in 10 testicular cancer patients, 4 were revealed by RaID prior to any other detection method used and provided a lead time to definitive diagnosis by other measures of a few days to greater than 1 yr. Although a number of patients had high serum hCG levels, even exceeding 3 microgram/ml, the xenogeneic antibody was capable of localizing in tumor. No adverse effects were noted in any of the patients studied. Thus, hCG RaID appears to be a safe and effective method of detecting and locating hCG-producing tumors and has been found to disclose occult testicular cancers. Images PMID:6278487

Effect of the human chorionic gonadotropin diet on patient outcomes.

PubMed

Goodbar, Nancy H; Foushee, Jaime A; Eagerton, David H; Haynes, Katie B; Johnson, Amanda A

2013-05-01

To report a case of left lower extremity deep vein thrombosis (DVT) and bilateral pulmonary embolisms in a patient who initiated the human chorionic gonadotropin (HCG) diet 2 weeks prior to presentation. A 64-year-old white female presented with leg swelling and shortness of breath. Lower extremity ultrasound revealed left leg DVT, and a computed tomography angiogram revealed bilateral pulmonary embolisms. A complete history and physical examination were unremarkable for any risk factors for acute thrombosis, with the exception of the initiation of the HCG diet approximately 2 weeks prior to presentation; the patient was taking 20 sublingual drops of HCG twice daily. Results of her hypercoagulable workup were negative. Upon admission, therapy was started with enoxaparin 120 mg subcutaneously twice daily and warfarin 5 mg orally once daily. According to the Naranjo probability scale, initiation of the HCG diet was a probable cause of our patient's adverse effects. The HCG diet has very few efficacy studies and no significant safety studies associated with its use. Six relevant studies were identified for assessment of efficacy, and only 1 was associated with a significant weight reduction in the HCG diet study population. All of these studies evaluated the use of the HCG diet via injections of the hormone and significant calorie restriction, which is known as the Simeons method. Currently marketed HCG products include sublingual drops, lozenges, and pellets, but none of these methods has an evidence-based efficacy and safety standard. As popularity of the HCG diet continues to increase, so do the potential adverse events associated with the management of weight loss via an unproven strategy. Patient safety information regarding this dieting strategy should be recognized by medical professionals.

Gestational trophoblastic neoplasia after spontaneous human chorionic gonadotropin normalization following molar pregnancy evacuation.

PubMed

Braga, Antonio; Maestá, Izildinha; Matos, Michelle; Elias, Kevin M; Rizzo, Julianna; Viggiano, Maurício Guilherme Campos

2015-11-01

To evaluate the risk of gestational trophoblastic neoplasia (GTN) after spontaneous human chorionic gonadotropin normalization in postmolar follow-up. Retrospective chart review of 2284 consecutive cases of hydatidiform mole with spontaneous normalization of hCG following uterine evacuation treated at one of five Brazilian reference centers from January 2002 to June 2013. After hCG normalization, GTN occurred in 10/2284 patients (0.4%; 95% CI 0.2%-0.8%). GTN developed in 9/1424 patients (0.6%; 95% CI 0.3%-1.2%) after a complete hydatidiform mole, in 1/849 patients (0.1%; 95% CI<0.01%-0.7%) after a partial hydatidiform mole, and in 0/13 patients (0%; 95% CI 0%-27%) after a twin molar pregnancy. The median time to GTN diagnosis after hCG normalization was 18months, and no diagnoses were made before six months of postmolar surveillance. Patients who required more than 56days to achieve a normal hCG value had a ten-fold increased risk of developing GTN after hCG normalization (9/1074; 0.8%; 95% CI 0.4%-1.6%) compared to those who reached a normal hCG level in fewer than 56days (1/1210;0.08%; 95% CI<0.01%-0.5%; p=0.008). All patients presented with symptoms at the time of GTN diagnosis. GTN after spontaneous hCG normalization following molar pregnancy is exceedingly rare, and the few patients who do develop GTN after achieving a normal hCG value are likely to be diagnosed after completing the commonly recommended six months of postmolar surveillance. Current recommendations for surveillance after hCG normalization should be revisited. Copyright © 2015 Elsevier Inc. All rights reserved.

Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant.

PubMed

Glueck, Charles J; Lee, Kevin; Prince, Marloe; Jetty, Vybhav; Shah, Parth; Wang, Ping

2016-01-01

When exogenous testosterone or treatments to elevate testosterone (human chorionic gonadotropin [HCG] or Clomid) are prescribed for men who have antecedent thrombophilia, deep venous thrombosis and pulmonary embolism often occur and may recur despite adequate anticoagulation if testosterone therapy is continued. A 55-year-old white male was referred to us because of 4 thrombotic events, 3 despite adequate anticoagulation over a 5-year period. We assessed interactions between thrombophilia, exogenous testosterone therapy, and recurrent thrombosis. In 2009, despite low-normal serum testosterone 334 ng/dL (lower normal limit [LNL] 300 ng/dL), he was given testosterone (TT) cypionate (50 mg/week) and human chorionic gonadotropin (HCG; 500 units/week) for presumed hypogonadism. Ten months later, with supranormal serum T (1385 ng/dL, upper normal limit [UNL] 827 ng/dL) and estradiol (E2) 45 pg/mL (UNL 41 pg/mL), he had a pulmonary embolus (PE) and was then anticoagulated for 2 years (enoxaparin, then warfarin). Four years later, on TT-HCG, he had his first deep venous thrombosis (DVT). TT was stopped and HCG continued; he was anticoagulated (enoxaparin, then warfarin, then apixaban, then fondaparinux). One year after his first DVT, on HCG, still on fondaparinux, he had a second DVT (5/315), was anticoagulated (enoxaparin + warfarin), with a Greenfield filter placed, but 8 days later had a second PE. Thrombophilia testing revealed the lupus anticoagulant. After stopping HCG, and maintained on warfarin, he has been free of further DVT-PE for 9 months. When DVT-PE occur on TT or HCG, in the presence of thrombophilia, TT-HCG should be stopped, lest DVT-PE reoccur despite concurrent anticoagulation.

Serum human chorionic gonadotropin levels and thyroid hormone levels in gestational transient thyrotoxicosis: Is the serum hCG level useful for differentiating between active Graves' disease and GTT?

PubMed

Yoshihara, Ai; Noh, Jaeduk Yoshimura; Mukasa, Koji; Suzuki, Miho; Ohye, Hidemi; Matsumoto, Masako; Kunii, Yo; Watanabe, Natsuko; Suzuki, Nami; Kameda, Toshiaki; Sugino, Kiminori; Ito, Koichi

2015-01-01

Gestational transient thyrotoxicosis (GTT) is defined as transient thyrotoxicosis caused by the stimulating effect of human chorionic gonadotropin (hCG) during pregnancy. We attempted to identify the serum hCG level that causes GTT, and we compared the serum hCG levels and thyroid hormone levels of GTT patients according to whether they had a background of thyroid disease. We also evaluated serum hCG as a parameter for differentiating between active Graves' disease (GD) and GTT. We reviewed the 135 cases of pregnant women who came to our hospital to be evaluated for thyrotoxicosis during their 7th to 14th week of pregnancy, and their serum hCG level was measured at that time. Among the 135 pregnant women with thyrotoxicosis; 103 of the women had GTT, and the other 32 women had active GD. There were no correlations between their serum hCG levels and free thyroid hormone levels. There were no significant differences in thyroid hormone levels or hCG levels among the GTT groups with different thyroid disease backgrounds; i.e., the GTT group without thyroid disease, GTT group with chronic thyroiditis, GTT group with non-functioning thyroid nodules, and GTT group with GD in remission. The serum hCG level of the GTT group was significantly higher than in the active GD group, but it was not a good parameter for differentiating between the two groups. The FT3/FT4 ratio of the active GD was significantly higher than in GTT group, and was a better parameter for differentiation.

The Endometrial Response to Chorionic Gonadotropin Is Blunted in a Baboon Model of Endometriosis

PubMed Central

Sherwin, J. R. A.; Hastings, J. M.; Jackson, K. S.; Mavrogianis, P. A.; Sharkey, A. M.; Fazleabas, A. T.

2010-01-01

Endometriosis-associated infertility has a multifactorial etiology. We tested the hypothesis that the endometrial response to the early embryonic signal, human chorionic gonadotropin (hCG), alters over time in a nonhuman primate model of endometriosis. Animals with experimental or spontaneous endometriosis were treated with hCG (30 IU/d), from d 6 after ovulation for 5 d, via an oviductal cannula. Microarray analysis of endometrial transcripts from baboons treated with hCG at 3 and 6 months of disease (n = 6) identified 22 and 165 genes, respectively, whose levels differed more than 2-fold compared with disease-free (DF) animals treated with hCG (P < 0.01). Quantitative RT-PCR confirmed abnormal responses of known hCG-regulated genes. APOA1, SFRP4, and PAPPA, which are normally down-regulated by hCG were up-regulated by hCG in animals with endometriosis. In contrast, the ability of hCG to induce SERPINA3 was lost. Immunohistochemistry demonstrated dysregulation of C3 and superoxide dismutase 2 proteins. We demonstrate that this abnormal response to hCG persists for up to 15 months after disease induction and that the nature of the abnormal response changes as the disease progresses. Immunohistochemistry showed that this aberrant gene expression was not a consequence of altered LH/choriogonadotropin receptor distribution in the endometrium of animals with endometriosis. We have shown that endometriosis induces complex changes in the response of eutopic endometrium to hCG, which may prevent the acquisition of the full endometrial molecular repertoire necessary for decidualization and tolerance of the fetal allograft. This may in part explain endometriosis-associated implantation failure. PMID:20668030

Immunoextraction-Tandem Mass Spectrometry Method for Measuring Intact Human Chorionic Gonadotropin, Free β-Subunit, and β-Subunit Core Fragment in Urine

PubMed Central

Woldemariam, Getachew A.; Butch, Anthony W.

2015-01-01

BACKGROUND Human chorionic gonadotropin (hCG) stimulates testosterone production by the testicles. Because of the potential for abuse, hCG is banned (males only) in most sports and has been placed on the World Anti-Doping Agency list of prohibited substances. Intact hCG, free β-subunit (hCGβ), and β-subunit core fragment (hCGβcf) are the major variants or isoforms in urine. Immunoassays are used by antidoping laboratories to measure urinary hCG. Cross-reactivity with isoforms differs among immunoassays, resulting in widely varying results. We developed a sequential im-munoextraction method with LC-MS/MS detection for quantification of intact hCG, hCGβ, and hCGβcf in urine. METHODS hCG isoforms were immunoextracted with antibody-conjugated magnetic beads and digested with trypsin, and hCGβ and hCGβcf unique peptides were quantified by LC-MS/MS with the corresponding heavy peptides as internal standard. hCG isoform concentrations were determined in urine after administration of hCG, and the intact hCG results were compared to immunoassay results. RESULTS The method was linear to 20 IU/L. Total imprecision was 6.6%-13.7% (CV), recovery ranged from 91% to 109%, and the limit of quantification was 0.2 IU/L. Intact hCG predominated in the urine after administration of 2 hCG formulations. The window of detection ranged from 6 to 9 days. Mean immunoassay results were 12.4-15.5 IU/L higher than LC-MS/MS results. CONCLUSIONS The performance characteristics of the method are acceptable for measuring hCG isoforms, and the method can quantify intact hCG and hCGβ separately. The limit of quantification will allow LC-MS/MS hCG reference intervals to be established in nondoping male athletes for improved doping control. PMID:24899693

Features of natural and gonadotropin-releasing hormone antagonist-induced corpus luteum regression and effects of in vivo human chorionic gonadotropin.

PubMed

Del Canto, Felipe; Sierralta, Walter; Kohen, Paulina; Muñoz, Alex; Strauss, Jerome F; Devoto, Luigi

2007-11-01

The natural process of luteolysis and luteal regression is induced by withdrawal of gonadotropin support. The objectives of this study were: 1) to compare the functional changes and apoptotic features of natural human luteal regression and induced luteal regression; 2) to define the ultrastructural characteristics of the corpus luteum at the time of natural luteal regression and induced luteal regression; and 3) to examine the effect of human chorionic gonadotropin (hCG) on the steroidogenic response and apoptotic markers within the regressing corpus luteum. Twenty-three women with normal menstrual cycles undergoing tubal ligation donated corpus luteum at specific stages in the luteal phase. Some women received a GnRH antagonist prior to collection of corpus luteum, others received an injection of hCG with or without prior treatment with a GnRH antagonist. Main outcome measures were plasma hormone levels and analysis of excised luteal tissue for markers of apoptosis, histology, and ultrastructure. The progesterone and estradiol levels, corpus luteum DNA, and protein contents in induced luteal regression resembled those of natural luteal regression. hCG treatment raised progesterone and estradiol in both natural luteal regression and induced luteal regression. The increase in apoptosis detected in induced luteal regression by cytochrome c in the cytosol, activated caspase-3, and nuclear DNA fragmentation, was similar to that observed in natural luteal regression. The antiapoptotic protein Bcl-2 was significantly lower during natural luteal regression. The proapoptotic proteins Bax and Bak were at a constant level. Apoptotic and nonapoptotic death of luteal cells was observed in natural luteal regression and induced luteal regression at the ultrastructural level. hCG prevented apoptotic cell death, but not autophagy. The low number of apoptotic cells disclosed and the frequent autophagocytic suggest that multiple mechanisms are involved in cell death at luteal regression. hCG restores steroidogenic function and restrains the apoptotic process, but not autophagy.

Second-trimester maternal serum marker screening: maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, estriol, and their various combinations as predictors of pregnancy outcome.

PubMed

Yaron, Y; Cherry, M; Kramer, R L; O'Brien, J E; Hallak, M; Johnson, M P; Evans, M I

1999-10-01

We evaluated the value of all 3 common biochemical serum markers, maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, and unconjugated estriol, and combinations thereof as predictors of pregnancy outcome. A total of 60,040 patients underwent maternal serum screening. All patients had maternal serum alpha-fetoprotein measurements; beta-human chorionic gonadotropin was measured in 45,565 patients, and 24,504 patients had determination of all 3 markers, including unconjugated estriol. The incidences of various pregnancy outcomes were evaluated according to the serum marker levels by using clinically applied cutoff points. In confirmation of previous observations, increased maternal serum alpha-fetoprotein levels (>2.5 multiples of the median) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, intrauterine growth restriction, intrauterine fetal death, oligohydramnios, and abruptio placentae. Increased beta-human chorionic gonadotropin levels (>2.5 multiples of the median [MoM]) were significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, and intrauterine fetal death. Finally, decreased unconjugated estriol levels (<0.5 MoM) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, intrauterine growth restriction, and intrauterine fetal death. As with increased second-trimester maternal serum alpha-fetoprotein levels, increased serum beta-human chorionic gonadotropin and low unconjugated estriol levels are significantly associated with adverse pregnancy outcomes. These are most likely attributed to placental dysfunction. Multiple-marker screening can be used not only for the detection of fetal anomalies and aneu-ploidy but also for detection of high-risk pregnancies.

Conversion of human choriogonadotropin into a follitropin by protein engineering

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

Campbell, R.K.; Dean-Emig, D.M.; Moyle, W.R.

1991-02-01

Human reproduction is dependent upon the action of follicle-stimulating hormone (hFSH), luteinizing hormone (hLH), and chorionic gonadotropin (hCG). While the {alpha} subunits of these heterodimeric proteins can be interchanged without effect on receptor-binding specificity, their {beta} subunits differ and direct hormone binding to either LH/CG or FSH receptors. Previous studies employing chemical modifications of the hormones, monoclonal antibodies, or synthetic peptides have implicated hCG {beta}-subunit residues between Cys-38 and Cys-57 and corresponding regions of hLH{beta} and hFSH{beta} in receptor recognition and activation. Since the {beta} subunits of hCG or hLH and hFSH exhibit very little sequence similarity in this region,more » the authors postulated that these residues might contribute to hormone specificity. To test this hypothesis the authors constructed chimeric hCG/hFSH {beta} subunits, coexpressed them with the human {alpha} subunit, and examined their ability to interact with LH and FSH receptors and hormone-specific monoclonal antibodies. Surprisingly, substitution of hFSH{beta} residues 33-52 for hCG{beta} residues 39-58 had no effect on receptor binding or stimulation. However, substitution of hFSH{beta} residues 88-108 in place of the carboxyl terminus of hCG{beta} (residues 94-145) resulted in a hormone analog identical to hFSH in its ability to bind and stimulate FSH receptors. The altered binding specificity displayed by this analog is not attributable solely to the replacement of hCG{beta} residues 108-145 or substitution of residues in the determinant loop located between hCD{beta} residues 93 and 100.« less

Central hypogonadism due to a giant, "silent" FSH-secreting, atypical pituitary adenoma: effects of adenoma dissection and short-term Leydig cell stimulation by luteinizing hormone (LH) and human chorionic gonadotropin (hCG).

PubMed

Santi, Daniele; Spaggiari, Giorgia; Casarini, Livio; Fanelli, Flaminia; Mezzullo, Marco; Pagotto, Uberto; Granata, Antonio R M; Carani, Cesare; Simoni, Manuela

2017-06-01

We present a case report of an atypical giant pituitary adenoma secreting follicle-stimulating hormone (FSH). A 55-year-old patient presented for erectile dysfunction, loss of libido and fatigue. The biochemical evaluation showed very high FSH serum levels in the presence of central hypogonadism. Neither testicular enlargement nor increased sperm count was observed, thus a secretion of FSH with reduced biological activity was supposed. The histological examination after neuro-surgery showed an atypical pituitary adenoma with FSH-positive cells. Hypogonadism persisted and semen analyses impaired until azoospermia in conjunction with the reduction in FSH levels suggesting that, at least in part, this gonadotropin should be biologically active. Thus, we hypothesized a concomitant primary testicular insufficiency. The patient underwent short-term treatment trials with low doses of either recombinant luteinizing hormone (LH) or human chorionic gonadotropin (hCG) in three consecutive treatment schemes, showing an equal efficacy in stimulating testosterone (T) increase. This is the first case of atypical, giant FSH-secreting pituitary adenoma with high FSH serum levels without signs of testicular hyperstimulation, in presence of hypogonadism with plausible combined primary and secondary etiology. Hypophysectomized patients may represent a good model to assess both pharmacodynamics and effective dose of LH and hCG in the male.

Fetal sex differences in human chorionic gonadotropin fluctuate by maternal race, age, weight and by gestational age

PubMed Central

Adibi, J. J.; Lee, M. K.; Saha, S.; Boscardin, W. J.; Apfel, A.; Currier, R. J.

2015-01-01

Circulating levels of the placental glycoprotein hormone human chorionic gonadotropin (hCG) are higher in women carrying female v. male fetuses; yet, the significance of this difference with respect to maternal factors, environmental exposures and neonatal outcomes is unknown. As a first step in evaluating the biologic and clinical significance of sex differences in hCG, we conducted a population-level analysis to assess its stability across subgroups. Subjects were women carrying singleton pregnancies who participated in prenatal and newborn screening programs in CA from 2009 to 2012 (1.1 million serum samples). hCG was measured in the first and second trimesters and fetal sex was determined from the neonatal record. Multivariate linear models were used to estimate hCG means in women carrying female and male fetuses. We report fluctuations in the ratios of female to male hCG by maternal factors and by gestational age. hCG was higher in the case of a female fetus by 11 and 8% in the first and second trimesters, respectively (P <0.0001). There were small (1–5%) fluctuations in the sex difference by maternal race, weight and age. The female-to-male ratio in hCG decreased from 17 to 2% in the first trimester, and then increased from 2 to 19% in the second trimester (P <0.0001). We demonstrate within a well enumerated, diverse US population that the sex difference in hCG overall is stable. Small fluctuations within population subgroups may be relevant to environmental and physiologic effects on the placenta and can be probed further using these types of data. PMID:26242396

Human chorionic gonadotropin, fetal sex and risk of hypertensive disorders of pregnancy: A nested case-control study.

PubMed

Zheng, Qizhen; Deng, Yuqing; Zhong, Shilin; Shi, Yu

2016-01-01

To assess whether human chorionic gonadotropin (HCG) and fetal sex are two independent risk factors for hypertensive pregnancy in the early second-trimester of pregnancy. This was a retrospective nested case-control study based on a cohort of 2521 singleton pregnancies, among whom we recruited 98 hypertensive pregnancies (subdivided into severe preeclampsia, n=34; mild preeclampsia, n=29 and gestational hypertension, n=35) and 196 normotensive pregnancies. Maternal serum HCG levels were measured at 15-20 weeks of gestation and fetal sex was determined from the neonatal record. Mann-Whitney U and chi-square tests were performed to assess differences of HCG levels and fetal sex between groups. Logistic regressions were performed to evaluate the effect of HCG and fetal sex on hypertensive pregnancy. There were 35 male and 63 female fetuses in the hypertensive group, and 102 male and 94 female fetuses in the normotensive group (p=0.008). HCG (MoM) levels were significantly higher in only severe preeclamptic pregnancies (n=34) (p=0.013). There were no significant differences of the HCG (MoM) levels between male and female fetuses in each sub-group. aOR for increased maternal HCG levels and female fetus were 2.4 (95% CI: 1.434-3.954) and 2.9 (95% CI: 1.227-6.661) respectively in severe preeclamptic pregnancies compared with normotensive pregnancies. There is a female preponderance in hypertensive pregnancies. Increased HCG levels and female fetus are two independent risk factors for severe preeclampsia in the early second-trimester of pregnancy. Copyright © 2016 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Influence of multiple injections of human chorionic gonadotropin (hCG) on urine and serum endogenous steroids concentrations.

PubMed

Strahm, Emmanuel; Marques-Vidal, Pedro; Pralong, François; Dvorak, Jiri; Saugy, Martial; Baume, Norbert

2011-12-10

Since it is established that human chorionic gonadotropin (hCG) affects testosterone production and release in the human body, the use of this hormone as a performance enhancing drug has been prohibited by the World Anti-Doping Agency. Nowadays, the only validated biomarker of a hCG doping is its direct quantification in urine. However, this specific parameter is subjected to large inter-individual variability and its determination is directly dependent on the reliability of hCG immunoassays used. In order to counteract these weaknesses, new biomarkers need to be evidenced. To address this issue, a pilot clinical study was performed on 10 volunteers submitted to 3 subsequent hCG injections. Blood and urine samples were collected during two weeks in order to follow the physiological effects on related compounds such as the steroid profile or hormones involved in the hypothalamo-pituitary axis. The hCG pharmacokinetic observed in all subjects was, as expected, prone to important inter-individual variations. Using ROC plots, level of testosterone and testosterone on luteinizing hormone ratio in both blood and urine were found to be the most relevant biomarker of a hCG abuse, regardless of inter-individual variations. In conclusion, this study showed the crucial importance of reliable quantification methods to assess low differences in hormonal patterns. In regard to these results and to anti-doping requirements and constraints, blood together with urine matrix should be included in the anti-doping testing program. Together with a longitudinal follow-up approach it could constitute a new strategy to detect a hCG abuse, applicable to further forms of steroid or other forbidden drug manipulation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Is human chorionic gonadotropin supplementation beneficial for frozen and thawed embryo transfer in estrogen/progesterone replacement cycles?: A randomized clinical trial.

PubMed

Shiotani, Masahide; Matsumoto, Yukiko; Okamoto, Eri; Yamada, Satoshi; Mizusawa, Yuri; Furuhashi, Kohyu; Ogata, Hiromi; Ogata, Seiji; Kokeguchi, Shoji

2017-04-01

Human chorionic gonadotropin (hCG) is used frequently for luteal support in fresh in vitro fertilization cycles as it induces progesterone secretion from the ovaries after oocyte retrieval and modulates the endometrium for implantation in fresh cycles. In contrast, hCG is not usually used for the transfer of cryopreserved-thawed embryos in estrogen/progesterone replacement cycles because ovulation is suppressed. However, several studies have shown that luteinizing hormone and hCG receptors are present in the human endometrium and that hCG can directly induce the decidualization of endometrial stromal cells in vitro. Thus, this study evaluated whether hCG supplementation can be beneficial for cryopreserved-thawed embryo transfer in estrogen/progesterone replacement cycles. One-hundred-and seventy-three cryopreserved-thawed embryo transfer cycles with estrogen/progesterone replacement were divided randomly into two groups. Transdermal oestradiol was used in combination with vaginal progesterone suppositories for HR. The embryo transfer was performed on day 17 and/or day 20 of the HR therapy cycle in both groups. In Group A, 3000 IU of hCG was administered on days 17, 20, and 23. In Group B, hCG was not used. There was no significant difference in the average age of the patients, the average number of previous assisted reproductive technology cycles, or the average number of embryo transfers between the two groups. The rates of pregnancy and implantation per embryo were 37.2% and 25.3%, respectively, in Group A and 35.6% and 21.7%, respectively, in Group B. The pregnancy and implantation rates were similar in both groups. Supplementation with hCG is not beneficial for cryopreserved-thawed embryo transfer in estrogen/progesterone replacement cycles.

Expression of potential target antigens for immunotherapy on primary and metastatic prostate cancers.

PubMed

Zhang, S; Zhang, H S; Reuter, V E; Slovin, S F; Scher, H I; Livingston, P O

1998-02-01

Defining the expression of tumor-associated antigens on primary and metastatic prostate cancer is the crucial first step in selecting appropriate targets for immune attack. In this study, the distribution of the tumor-associated antigens GM2, Tn, sTn, Thompson-Friedenreich antigen (TF), Globo H, Le(y), MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC7, carcinoembryonic antigen, beta chain of human chorionic gonadotropin (hCG beta), HER2/neu, PSMA, and KSA on primary and metastatic prostate cancer and 16 types of normal tissues was compared by immunohistochemistry, using a panel of well-characterized monoclonal antibodies. Our results show that GM2, KSA, and MUC2 were strongly expressed on 8 or 9 of 9 metastatic prostate cancer biopsy specimens and, with PSMA, hCG beta, TF, Tn, and sTn, on 8 or more of 11 primary prostate cancer specimens. Tn, MUC1, and PSMA were expressed on 4-6 of 9 metastatic specimens. The remaining antigens were expressed on no more than three of nine metastatic specimens. Normal tissues were also tested with all antibodies. With regard to the eight antigens most widely expressed on prostate cancers, PSMA was not expressed significantly on any of the normal tissues except prostate epithelium. Tn, sTn, hCG beta, and MUC2 were detected on up to 3 of 10 types of normal epithelia. GM2, TF, MUC1, and KSA were more broadly distributed on normal epithelia, all primarily at the secretory borders. STn, KSA, and hCG beta were also detected in the testis, and GM2 was expressed on gray matter of brain. From the 30 antigens that we have screened, this study provides the basis for selecting GM2, TF, Tn, sTn, hCG beta, MUC1, MUC2, KSA, and PSMA as target antigens for specific immunotherapy of prostate cancer.

Effect of human gonadotropins on spermiation and androgen biosynthesis in the testis of the toad Bufo arenarum (Amphibia, Anura).

PubMed

Pozzi, Andrea Gabriela; Rosemblit, Cinthia; Ceballos, Nora Raquel

2006-01-01

This paper analyzes, in the toad Bufo arenarum, the effect on spermiation and androgen secretion of two human recombinant gonadotropins, human recombinant LH (hrLH) and human recombinant FSH (hrFSH) as well as the well-known spermiation-inducing hormone, human chorionic gonadotropin (hCG). For this purpose, testes were incubated with different concentrations of hrLH (0.01-2.5 microg/ml) and hrFSH (0.05-5 microg/ml), and results were compared with those obtained with 2.5 microg/ml hCG. Spermiation was most efficiently stimulated by hrFSH, which elicited a higher response than either hrLH or hCG. Both hrFSH and hrLH produced a bell-shaped dose-response curve, with a 50% inhibition on spermiation at a concentration twice higher than that necessary to get the highest response. However, none of the gonadotropins yielded a biphasic response on androgen secretion, hrLH producing the highest response at a concentration that evoked a 70% inhibition in the spermiation test. Regarding steroidogenesis, hrLH and hrFSH were more active than hCG. Taken together, the results described in this paper suggest that, in B. arenarum, spermiation and androgen secretion are mediated by different receptors. After comparing the effects of recombinant hormones, we conclude that hrFSH has a greater effect on spermiation than hCG or hrLH.

Human Chorionic Gonadotropin Mediated Generation of Reactive Oxygen Species Is Sufficient to Induce Meiotic Exit but Not Apoptosis in Rat Oocytes

PubMed Central

Tiwari, Meenakshi; Chaube, Shail K.

2017-01-01

Abstract Generation of reactive oxygen species (ROS) is associated with final stages of follicular development and ovulation in mammals. The human chorionic gonadotropin (hCG) mimics the action of luteinizing hormone and triggers follicular development and ovulation. However, it remains unclear whether hCG induces generation of ROS, if yes, whether hCG-mediated increased level of ROS could induce meiotic exit and/or apoptosis in rat oocytes. For this purpose, cumulus–oocyte complexes (COCs) were collected from ovary of experimental rats injected with 20 IU pregnant mare's serum gonadotropin for 48 h followed by 20 IU hCG for 0, 7, 14, and 21 h. The morphological changes in COCs, meiotic status of oocyte, total ROS, hydrogen peroxide (H2O2), inducible nitric oxide synthase (iNOS), nitric oxide (NO), Bax, Bcl-2, cytochrome c, telomerase reverse transcriptase (TERT) expression levels, and DNA fragmentation were analyzed in COCs. Our data suggest that hCG surge increased total ROS as well as H2O2 levels but decreased iNOS expression and total NO level in oocytes. The hCG-mediated increased level of ROS was sufficient to induce meiotic cell cycle resumption in majority of oocytes as evidenced by meiotic exit from diplotene as well as metaphase-II (M-II) arrest and their meiotic status. However, increase of ROS level due to hCG surge was not sufficient to trigger Bax and cytochrome c expression levels and DNA fragmentation in COCs. In addition, increased TERT activity was observed in oocytes collected 21 h post-hCG surge showing onset of oocyte aging. Taken together, these results suggest that hCG induces generation of ROS sufficient to trigger meiotic exit from diplotene, as well as M-II arrest, but not good enough to induce apoptosis in rat oocytes. PMID:29098117

Highly sensitive radioimmunoassay for chorionic gonadotropin in human urine. [/sup 125/I tracer technique

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

Ayala, A.R.; Nisula, B.C.; Chen, H.C.

1978-10-01

The value of RIAs that measure hCG levels in human urine has been limited principally because of cross-reactivity with human LH. Recently, antisera generated to antigenic determinants on the intact hCG..beta.. subunit and its carboxyl-terminal peptide have been shown to exhibit substantially reduced human LH cross-reactivity. To take maximal advantage of these antisera and to minimize interference by nonspecific substances in urine, a procedure for extracting and concentrating hCG from 24-h urine samples was developed. The procedure involves preparation of a standard kaolin-acetone urine concentrate and adsorption of the hCG in the concentrate to Concanavalin A covalently linked to agarosemore » for purification and subsequent RIA. In urine samples obtained from patients with gestational trophoblastic disease, there was a direct correlation between hCG levels measured by RIA and those estimated by mouse uterine weight bioassy. In individual subjects, hCG levels were determined in serum and urine obtained the same day. When hCG was clearly detectable in the serum at levels greater than 1 ng/ml, the quantity of hCG measured in the urine concentrate exceeded 500 ng/24 h. The concentrates prepared from the urine of normal persons contained an hCG-like glycoprotein substance with antigenic determinants similar to those of the carboxyl-terminal peptide of hCG..beta... As the range of hCG immunoreactivity measured in the urine concentrates of normal subjects was 6 to 52 ng/24 h, specific and sensitive detection of urinary hCG could be accomplished in patients whose sera contained hCG undetectable by conventional RIA. Partial purification and concentration of urinary hCG by this procedure with subsequent RIA provides a sensitive and reliable method for detecting hCG in urine.« less

Effect of human chorionic gonadotropin on luteal function and reproductive performance of high-producing lactating Holstein dairy cows.

PubMed

Santos, J E; Thatcher, W W; Pool, L; Overton, M W

2001-11-01

The objectives were to evaluate effects of human chorionic gonadotropin (hCG) (3,300 IU i.m.) administered on d 5 after AI on CL number, plasma progesterone concentration, conception rate, and pregnancy loss in high-producing dairy cows. Following the synchronization of estrus and AI, 406 cows were injected with either hCG or saline on d 5 after AI in a randomized complete block design. Blood sampling and ovarian ultrasonography were conducted once between d 11 and 16 after AI. Pregnancy diagnoses were performed on d 28 by ultrasonography and on d 45 and 90 after AI by rectal palpation. Treatment with hCG on d 5 resulted in 86.2% of the cows with more than one CL compared with 23.2% in controls. Plasma progesterone concentrations were increased by 5.0 ng/mL in hCG-treated cows. The presence of more than one CL increased progesterone concentration in hCG-treated cows but not in controls. Conception rates were higher for hCG-treated cows on d 28 (45.8 > 38.7%), 45 (40.4 > 36.3%), and 90 (38.4 > 31.9%) after AI. Treatment with hCG improved conception rate in cows losing body condition between AI and d 28 after Al. Pregnancy losses were similar between treatment groups. Treatment with hCG on d 5 after AI induces accessory CL, enhances plasma progesterone concentration, and improves conception rate of high-producing dairy cows.

Pharmacokinetics and pharmacodynamics of human chorionic gonadotropin (hCG) after rectal administration of hollow-type suppositories containing hCG.

PubMed

Kowari, Kouji; Hirosawa, Iori; Kurai, Hirono; Utoguchi, Naoki; Fujii, Makiko; Watanabe, Yoshiteru

2002-05-01

To determine the effectiveness of human chorionic gonadotropin (hCG) administered rectally, we studied the pharmacokinetics and pharmacodynamics of hCG using a hollow-type suppository. HCG was not detected in plasma when only hCG was administered rectally, even at a higher dose (4,000 IU/kg body weight) than intravenous injection, because of its low bioavailability due to high molecular weight or degradation by proteolytic activity. To enhance the rectal absorption of hCG, the effectiveness of its coadministration with alpha-cyclodextrin (alpha-CyD), an absorption-enhancing agent, was investigated in male rabbits. HCG was detected in plasma following coadministration of hCG and alpha-CyD (10 mg/kg body weight) into the rectum. The plasma hCG concentration increased with increasing dose of alpha-CyD. The AUC(0-48) observed after coadministration of hCG and alpha-CyD at 30 mg/kg body weight was approximately four times higher than that of hCG and alpha-CyD at 10mg/kg body weight. HCG at a high concentration induced a rapid increase in the plasma testosterone concentration (74.2 +/- 3.4 ng/ml) 2 h after intravenous administration. However, the testosterone concentration 24 h after intravenous administration decreased to the physiological level (approximately 20 ng/ml) which had been observed before such administration. On the other hand, the maximum level of testosterone concentration (40.0 +/- 12.6 ng/ml) was observed 24 h after rectal administration of hCG (400 IU/kg body weight) in combination with alpha-CyD (30 mg/kg body weight). Moreover, the plasma testosterone concentration (31.0 +/- 11.4 ng/ml) obtained 72 h after rectal administration tended to be maintained at a higher level than that (14.4 +/- 0.9ng/ml) observed before the administration. These results suggest that the hollow-type suppository as a rectal delivery system of hCG is promising as a new mode of hCG therapy.

Preliminary evidence for associations between second-trimester human chorionic gonadotropin and unconjugated oestriol levels with pregnancy outcome in Down syndrome pregnancies.

PubMed

Benn, P A

1998-04-01

Fifty-six cases of Down syndrome were identified in a population of women who had undergone maternal serum triple marker screening [alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated oestriol (uE3) analyses]. These affected pregnancies represented all known cases present in the population of 34,368 women screened. Using a 1:270 mid-trimester Down syndrome risk to define the screen-positive group, 42 affected pregnancies were screen-positive (medians: AFP = 0.79 MOM, hCG = 2.13 MOM, uE3 = 0.62 MOM, age 34.6 years) and 14 pregnancies were screen-negative (medians: AFP = 0.82 MOM, hCG = 1.57 MOM, uE3 = 0.92 MOM, age 24.2 years). Four affected pregnancies were associated with in utero death and each of these cases was associated with relatively extreme values of AFP, hCG, and uE3, including the three highest levels of hCG in the entire series of Down syndrome pregnancies. Twenty-nine (15 screen-positive and 14 screen-negative) affected pregnancies resulted in liveborns. Down syndrome pregnancies had a significantly shorter gestational term than controls, and Down syndrome babies were also lighter than controls, even after adjustment for sex and gestational age. In affected pregnancies, a low uE3 level appeared to be associated with a greater chance of a small-for-gestational age baby. No correlations could be demonstrated between AFP or hCG levels and gestational age-adjusted term weight. Based on this small series, it would appear that uE3 may be particularly useful in detecting those Down syndrome cases associated with small-for-gestational age fetuses. A very high hCG value may indicate a higher probability of fetal death.

Treatment preferences and outcome in male hypogonadotropic hypogonadism: an Indian perspective.

PubMed

Sanyal, D; Chatterjee, S

2016-06-01

This retrospective study assessed treatment preferences and outcome with testosterone or HCG / HCG-FSH combination in Indian male idiopathic hypogonadotropic hypogonadism (IHH) subjects (n = 31) above 18 years of age. 38.7% of IHH study subjects had no fertility plans and chose 3 monthly intramuscular testosterone undecanoate. 73.7% of subjects with fertility plans chose human chorionic gonadotropin (HCG) alone due to cost considerations. Spermatogenesis occurred in 21.4% on HCG alone and 60% of subjects on HCG with follicle-stimulating hormone (FSH) combination. Treatment failure is higher than published Western rates. FSH and HCG combination regimen is costly but superior to HCG alone. However, treatment failure still persists, suggesting unknown testicular defect in IHH. © 2015 Blackwell Verlag GmbH.

A unique case of growth hormone and human chorionic gonadotropin treatment in a 45,X male with Y: autosome translocation and literature review.

PubMed

Mareri, Arianna; Iezzi, MariaLaura; Salvatore, Alessia; Ligas, Claudio; D'Alessandro, Elvira

2016-07-01

Maleness associated with a 45,X karyotype is a rare condition in childhood. It is usually diagnosed in adult age because of infertility. We report a unique case of an unbalanced translocation t(Y;21) in a 14-year-old boy with 45,X karyotype referred because of short stature, thin habitus and puberty delay. Hormone analysis showed low serum levels of basal testosterone, insulin-like growth factor (IGF-I) and gonadotrophins. Diagnosis of GH deficiency and puberty delay were made. He was treated with human chorionic gonadotropin (hCG) and GH therapy, respectively, for 6 and 24 months.

Evaluation of four slide test kits for the detection of human chorionic gonadotropin in urine

PubMed Central

Dietrich, Michael; French, J. A.

1974-01-01

Three “indirect-type” slide tests utilizing the principle of hemagglutination inhibition and one new “direct-type” slide test employing direct agglutination were evaluated for their sensitivity in detecting human chorionic gonadotropin (HCG) in urine. The results of positive tests in a group of woman in very early pregnancy were correlated with the “days after last menses”. In this series the direct slide test was the most accurate. A control must be used with each direct test to indicate interfering substances and when such are present a different test must be used. All tests were found to be of the relative sensitivity stated by the manufacturer. PMID:4851924

Effects of ethanol on superovulation in the immature rat following pregnant mare's serum gonadotropin (PMSG) or PMSG and human chorionic gonadotropin treatment.

PubMed

Bo, W J; Krueger, W A; Rudeen, P K

1983-05-01

We sought to determine whether superovulation could occur in immature rats on a 5% ethanol diet and treated with pregnant mare's serum gonadotropin (PMSG) alone or with human chorionic gonadotropin (hCG). Holtzman female rats were divided into five groups at 20 days of age. Six rats (Group I) were killed at that age. Ten rats (Group II) were placed on an ad libitum laboratory chow diet and killed on Day 33. Twenty-four rats (Group III) were placed on an ad libitum laboratory chow diet. Twenty-four rats (Group IV) were placed on 5% ethanol liquid diet, while 24 rats in Group V were pair-fed with the animals in Group IV. At 30 days of age, 12 rats from each Group, III, IV, and V, received 25 IU of PMSG s.c. and were killed 74-76 h later. The remaining 12 rats from each Group, III, IV and V, received 25 IU of PMSG and 54-56 h later received 10 IU of hCG and were killed 20 h later. Ovulation occurred in all the rats of Groups III and V that received PMSG alone or with hCG. In the ethanol-treated rats that received PMSG alone, 75% ovulated, while 92% ovulated that received PMSG and hCG. The number of ova shed in the ethanol-PMSG-treated rats was significantly less than in the ethanol-PMSG-hCG-treated animals and in the controls. The uterine weights and morphology of the animals in Group IV were similar to those in Groups III and V. The study indicates that ethanol does not have a direct gonadotoxic effect on the ovary but indicates that ethanol has an effect on the hypothalamus and/or the pituitary, thereby disrupting the synthesis and/or release of luteinizing hormone releasing hormone (LHRH) or luteinizing hormone (LH).

Dual trigger of triptorelin and HCG optimizes clinical outcome for high ovarian responder in GnRH-antagonist protocols.

PubMed

Li, Saijiao; Zhou, Danni; Yin, Tailang; Xu, Wangming; Xie, Qingzhen; Cheng, Dan; Yang, Jing

2018-01-12

In this paper, a retrospective cohort study was conducted to the high ovarian responders in GnRH-antagonist protocols of IVF/ICSI cycles. The purpose of the study is to investigate whether dual triggering of final oocyte maturation with a combination of gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (HCG) can improve the clinical outcome compared with traditional dose (10000IU) HCG trigger and low-dose (8000IU) HCG trigger for high ovarian responders in GnRH-antagonist in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) cycles. Our study included 226 couples with high ovarian responders in GnRH-antagonist protocols of IVF/ICSI cycles. Standard dosage of HCG trigger (10000 IU of recombinant HCG) versus dual trigger (0.2 mg of triptorelin and 2000 IU of recombinant HCG) and low-dose HCG trigger (8000IU of recombinant HCG) were used for final oocyte maturation. Our main outcome measures were high quality embryo rate, the number of usable embryos, the risk of OHSS, duration of hospitalization and incidence rate of complications. Our evidence demonstrated that dual trigger is capable of preventing severe OHSS while still maintaining excellent high quality embryo rate in in high ovarian responders of GnRH-antagonist protocols.

Rapid and transient upregulation of CCL11 (eotaxin-1) in mouse ovary during terminal stages of follicular development.

PubMed

Kuwabara, Yoshimitsu; Katayama, Akira; Igarashi, Tsutomu; Tomiyama, Ryoko; Piao, Hua; Kaneko, Reika; Abe, Takashi; Mine, Katsuya; Akira, Shigeo; Orimo, Hideo; Takeshita, Toshiyuki

2012-05-01

This study aimed to investigate the regulation of expression, localization and physiological role of the CCL11/CCR3 axis in mouse ovary during the periovulatory period. CCL11/CCR3 expression in the mouse ovary after treatment with pregnant mare serum gonadotropin (PMSG) followed by human chorionic gonadotropin (hCG) 48 hr later was assessed in vivo and in 3-dimensional cultures in vitro. Real-time RT-PCR analyses revealed transient CCL11 mRNA upregulation 6 hr after hCG treatment. Immunohistochemical staining of serial ovarian sections demonstrated overlapping expression of CCL11, CCR3 and CD31 endothelial cell marker in the theca-interstitial layer at 10 hr after hCG treatment. In vitro 3-dimensional cultures of periovulatory ovarian tissues demonstrated that treatment with anti-CCL11 neutralizing antibody significantly decreased CD31 transcript. Gonadotropin surge leads to transient CCL11/CCR3 axis upregulation in the ovarian theca-interstitial layer, suggesting that it is involved in periovulatory physiological processes by affecting follicular vessels. © 2012 John Wiley & Sons A/S.

Early serum human chorionic gonadotropin (hCG) trends after medication abortion.

PubMed

Pocius, Katherine D; Maurer, Rie; Fortin, Jennifer; Goldberg, Alisa B; Bartz, Deborah

2015-06-01

Despite increased reliance on human chorionic gonadotropin (hCG) for early pregnancy monitoring, there is limited information about hCG trends soon after medication abortion. The purpose of this study was to determine if there is a predictable decline in serum hCG values shortly after medication abortion. This is a retrospective study of women with early intrauterine pregnancies who underwent medication abortion with mifepristone and misoprostol and had a serum hCG level on Day 1 (day of mifepristone) and a repeat value on Day 2 to 6. The percent hCG decline was calculated from baseline to repeat measure, with repeat values from the same patient accounted for through repeated measure analysis of variance. Eighty-eight women with a mean gestational age of 5.5 weeks and median baseline hCG of 5220 IU met study criteria over a 3-year period. The mean decline (±SD) in hCG from the Day 1 baseline value was 56.9%±29.5% on Day 3, 73.5%±38.6% on Day 4, 86.1%±8.8% on Day 5, and 92.9%±3.4% on Day 6. Eighty-two women (93% of the cohort) had a complete abortion without further intervention. The least square means hCG decline among these women was 57.6% [95% confidence interval (CI): 50.3-64.9%] on Day 3, 78.9% (95% CI: 75.0-82.8%) on Day 4 and 86.2% (95% CI: 81.3-91.1%) on Day 5. There is a rapid decline in serum hCG within the first few days after early medication abortion. Further research is needed to delineate how soon after medication abortion this decline may be specific enough to confirm abortion completion. This study provides the largest cohort of patients followed with serial hCG values in the first few days after medication abortion. Our findings demonstrate the trend in hCG decline in this population, which may be predictable by Day 5. Copyright © 2015 Elsevier Inc. All rights reserved.

Label-Free Sensors Based on Graphene Field-Effect Transistors for the Detection of Human Chorionic Gonadotropin Cancer Risk Biomarker

PubMed Central

Haslam, Carrie; Damiati, Samar; Whitley, Toby; Ifeachor, Emmanuel

2018-01-01

We report on the development of label-free chemical vapour deposition (CVD) graphene field effect transistor (GFET) immunosensors for the sensitive detection of Human Chorionic Gonadotropin (hCG), a glycoprotein risk biomarker of certain cancers. The GFET sensors were fabricated on Si/SiO2 substrate using photolithography with evaporated chromium and sputtered gold contacts. GFET channels were functionalised with a linker molecule to an immobile anti-hCG antibody on the surface of graphene. The binding reaction of the antibody with varying concentration levels of hCG antigen demonstrated the limit of detection of the GFET sensors to be below 1 pg/mL using four-probe electrical measurements. We also show that annealing can significantly improve the carrier transport properties of GFETs and shift the Dirac point (Fermi level) with reduced p-doping in back-gated measurements. The developed GFET biosensors are generic and could find applications in a broad range of medical diagnostics in addition to cancer, such as neurodegenerative (Alzheimer’s and Parkinson’s) and cardiovascular disorders. PMID:29316718

Glycoprotein hormone receptors: determinants in leucine-rich repeats responsible for ligand specificity

PubMed Central

Smits, Guillaume; Campillo, Mercedes; Govaerts, Cédric; Janssens, Véronique; Richter, Christine; Vassart, Gilbert; Pardo, Leonardo; Costagliola, Sabine

2003-01-01

Glycoprotein hormone receptors [thyrotropin (TSHr), luteinizing hormone/chorionic gonadotropin (LH/CGr), follicle stimulating hormone (FSHr)] are rhodopsin-like G protein-coupled receptors with a large extracellular N-terminal portion responsible for hormone recognition and binding. In structural models, this ectodomain is composed of two cysteine clusters flanking nine leucine-rich repeats (LRRs). The LRRs form a succession of β-strands and α-helices organized into a horseshoe-shaped structure. It has been proposed that glycoprotein hormones interact with residues of the β-strands making the concave surface of the horseshoe. Gain-of-function homology scanning of the β-strands of glycoprotein hormone receptors allowed identification of the critical residues responsible for the specificity towards human chorionic gonadotropin (hCG). Substitution of eight or two residues of the LH/CGr into the TSHr or FSHr, respectively, resulted in constructs displaying almost the same affinity and sensitivity for hCG as wild-type LH/CGr. Molecular dynamics simulations and additional site-directed mutagenesis provided a structural rationale for the evolution of binding specificity in this duplicated gene family. PMID:12773385

Determination of serum hCG levels by radioreactor assay in the clinical laboratory

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

Boyko, W.L.

1979-09-01

The radioreceptorassay (RRA) has been used for measuring human chorionic gonadotropin (hCG) in sera from 751 individuals. The RRA is shown to be sensitive (98%) and specific (99.8%) in detecting hCG in a wide variety of conditions, including normal pregnancy and threatened or missed abortions. As a rapid qualitative or semiquantitative assay for hCG, the RRA is a valuable adjunct in the laboratory to less sensitive tests for hCG. Variation among different quantitative assays for hCG is examined, and it is concluded that the same assay system should be used for monitoring hCG levels in a single individual over amore » period of time in order to avoid inconsistent results. Application of the quantitative RRA for hCG in detecting the midcycle luteinizing hormone surge in infertillity is also presented.« less

hCG - related molecules and their measurement.

PubMed

Szczerba, Anna; Białas, Piotr; Pięta, Paweł Piotr; Jankowska, Anna

2016-01-01

Measurements of human chorionic gonadotropin (hCG) synthesized by trophoblast cells is a powerful tool of pregnancy monitoring. It was showed that similarly to pregnancy also trophoblastic and nontrophoblastic malignancies produce variety of hCG molecules. In urine and serum of both pregnant women and tumors patients a fifteen various forms of hCG, such as: regular hCG, hyperglycosylated hCG and predominant hyperglycosylated hCG free β, were identified. These forms might be useful in order to recognize between physiological and pathological pregnancies as well as cancers. Even the presence of these different hormone variants is well documented the commercially available biochemical tests detecting hCG failed to identified and distinguish among these forms. Especially hard is to identify glycan chains linked to heterodimer. Thus, a detailed analysis of hCG-related molecules produced during physiological and pathological condition, together with a new tests development are needed.

Ovarian FAM110C (Family with Sequence Similarity 110C): Induction During the Periovulatory Period and Regulation of Granulosa Cell Cycle Kinetics in Rats1

PubMed Central

Li, Feixue; Jang, Hyein; Puttabyatappa, Muraly; Jo, Misung; Curry,, Thomas E.

2012-01-01

ABSTRACT FAM110C belongs to a family of proteins that regulates cell proliferation. In the present study, the spatiotemporal expression pattern of FAM110C and its potential role were examined during the periovulatory period. Immature female rats were injected with equine chorionic gonadotropin (eCG) followed by human chorionic gonadotropin (hCG) and ovaries or granulosa cells were collected at various times after hCG administration (n = 3/time point). Expression levels of Fam110c mRNA and protein were highly induced both in intact ovaries and granulosa cells at 8 to 12 h after hCG treatment. In situ hybridization analysis demonstrated Fam110c mRNA expression was induced in theca and granulosa cells at 4 h after hCG, primarily localized to granulosa cells at 8 h and 12 h, and decreased at 24 h after hCG. There was negligible Fam110c mRNA detected in newly forming corpora lutea. In rat granulosa cell cultures, hCG induced expression of Fam110c mRNA was inhibited by RU486, whereas NS398 and AG1478 had no effect, suggesting that Fam110c expression is regulated in part by the progesterone receptor pathway. Promoter activity analysis revealed that an Sp1 site was important for the induction of Fam110c expression by hCG. Overexpression of FAM110C promoted granulosa cells to arrest at the G1 phase of the cell cycle but did not change progesterone levels. In summary, hCG induces Fam110c mRNA expression in granulosa cells by activation of an Sp1-binding site and the actions of progesterone. Our findings suggest that FAM110C may control granulosa cell differentiation into luteal cells by arresting cell cycle progression. PMID:22460667

Progestin Exposure Before Gonadotropin Stimulation Improves Embryo Development after In Vitro Fertilization in the Domestic Cat1

PubMed Central

Pelican, Katharine M.; Spindler, Rebecca E.; Pukazhenthi, Budhan S.; Wildt, David E.; Ottinger, Mary A.; Howard, JoGayle

2010-01-01

This study investigated the influence of progestin priming and ovarian quiescence on response to exogenous gonadotropin stimulation in the cat. Because a subpopulation of cats routinely ovulated spontaneously, there also was the opportunity to examine the ovary's reaction to the added impact of endogenously secreted progestagen. Queens were given 1) equine chorionic gonadotropin (eCG) plus human chorionic gonadotropin (hCG) only (control; n = 9 cats), 2) GnRH antagonist (antide) injections followed by eCG and hCG (n = 9), and 3) a progestin implant (levonorgestrel) followed by eCG and hCG (n = 9). Laparoscopy was used to assess ovarian activity and aspirate follicular oocytes that were graded on the basis of morphology. In five cats per treatment, half of the high-quality oocytes were assessed for glucose, pyruvate, and lactate metabolism as well as nuclear maturation. Remaining oocytes were inseminated in vitro, cultured, and examined at 72 h after insemination for cleavage. In the remaining four cats per treatment, all oocytes were inseminated in vitro and assessed at 72, 120, and 168 h after insemination for embryo developmental stage. Cats pretreated with progestin had more follicles and produced more embryos per donor (including at the combined morula/blastocyst stage) than controls or females treated with GnRH antagonist (P < 0.05). There were no differences among groups (P > 0.05) in oocyte carbohydrate metabolism, nuclear maturation metrics, or fertilization success, although there was a tendency toward improvements in all three (P < 0.2) in progestin-treated females. Interestingly, cats that spontaneously ovulated within 60 days of treatment onset also produced more embryos per cat than induced-ovulation counterparts (P < 0.05). Results indicate that prior exposure to exogenous progestin (via implant) or endogenous progestagen (via spontaneous ovulation) improves ovarian responsiveness to gonadotropins in the cat through a mechanism that is independent of the induction of ovarian quiescence. PMID:20463355

Single-dose pharmacokinetic study comparing the pharmacokinetics of recombinant human chorionic gonadotropin in healthy Japanese and Caucasian women and recombinant human chorionic gonadotropin and urinary human chorionic gonadotropin in healthy Japanese women.

PubMed

Bagchus, Wilhelmina; Wolna, Peter; Uhl, Wolfgang

2018-01-01

Recombinant hCG (r-hCG) was approved in Japan in 2016. As a prerequisite for a Phase III study in Japan related to this approval, the pharmacokinetic (PK) profile of r-hCG was investigated. An open-label, partly randomized, single-center, single-dose, group-comparison, Phase I PK-bridging study was done that compared a single 250 μg dose of r-hCG with a single 5000 IU dose of urinary hCG (u-hCG) in healthy Japanese women, as well as comparing a single 250 μg dose of r-hCG in Japanese and Caucasian women. The Japanese participants were randomized 1:1 to receive either r-hCG or u-hCG, while the Caucasian participants were weight-matched to the Japanese participants who were receiving r-hCG in a 1:1 fashion. The primary PK parameters were the area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC 0-∞ ) and the maximum serum concentration (C max ). The mean serum hCG concentration-time profiles of r-hCG in the Japanese and Caucasian participants were a similar shape, but the level of overall exposure was ~20% lower in the Japanese participants. For the Japanese participants, r-hCG resulted in an 11% lower C max but a 19% higher AUC 0-∞ compared with u-hCG. No new safety signal was identified. This study cannot exclude a potential difference in the PK profile of r-hCG between Japanese and Caucasian participants. However, this study does not indicate that there are clinically relevant differences in the serum PK of r-hCG and u-hCG in the Japanese participants.

Serum human chorionic gonadotropin (hCG) trend within the first few days after medical abortion: a prospective study.

PubMed

Pocius, Katherine D; Bartz, Deborah; Maurer, Rie; Stenquist, Asha; Fortin, Jennifer; Goldberg, Alisa B

2017-03-01

To prospectively describe the decline in serum human chorionic gonadotropin (hCG) in the first 5 days after complete medical abortion and evaluate the influence of initial hCG and gestational duration. We conducted a prospective, physiologic study of women ≤63 days gestation who underwent medical abortion with 200 mg mifepristone and 800 mcg buccal misoprostol. We stratified enrollment into two gestational cohorts, <49 days and 49-63 days, to ensure gestational variability. We collected serum quantitative hCG values on Day 1 (day of mifepristone), Day 3, Day 5 and a routine follow up hCG on Days 7-14. We calculated the percent hCG decline from Day 1 to each repeat measure and evaluated trends based on initial serum hCG level and gestation. We enrolled 66 women; 59 were protocol-adherent and included in our analysis. Mean gestation on Day 1 was 49 days and mean baseline hCG was 72,332 IU. Fifty-seven subjects (97%) had a complete medical abortion without further intervention. The mean serum hCG decline among subjects with complete medical abortion was 70.0±10.6% [range 36.9-98.6%] on Day 3 and 91.4±4.4% [range 68.4-97.7%] on Day 5. The mean serum hCG decline from Day 1 to routine follow-up on Days 7-9 was 97.1±1.7% [range 92.4-99.2%], from Day 1 to Day 10-11 was 98.5±1.4% [range 94.7-99.6%] and from Day 1 to Day 12-14 was 98.7±2.8% [range 86.7-99.9%]. There was no difference in percent hCG decline stratified by initial hCG or gestation. There is a rapid and predictable decline in serum hCG as early as Day 5 after complete medical abortion through 63 days gestation. Rate of hCG decline is not affected by initial hCG or gestational duration. For women who require confirmation of complete abortion sooner than 1 week after mifepristone, due to patient preference, logistical constraints or in the setting of pregnancy of unconfirmed location, a single repeat hCG on Day 5 may be clinically useful. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Standardization of Epitopes for Human Chorionic Gonadotropin (hCG) Immunoassays.

PubMed

Berger, Peter; Lapthorn, Adrian J

2016-01-01

hCG and its variants are markers for pregnancy tests, pregnancyrelated complications, trophoblastic diseases, pre-natal screening of Down's syndrome and doping controls. Strong demands are imposed on diagnostic methods by the dynamic changes in the absolute and relative levels of hCG protein backbone variants and glycosylation isoforms in serum and urine during development of pregnancy or the progression/remission of tumors. Observed differences in the results between commercial diagnostic immunoassays reflect the unequal molar recognition of the different metabolic hCG variants, in particular the hCG beta core fragment (hCGβcf), by the diagnostic antibodies (Abs), as their epitopes are not standardized, and the fact that suboptimal hCG standards are used. To rapidly characterize Abs by their epitope recognition and specificity to evaluate their suitability for diagnostic immunoassays a procedure of comparative epitope mapping has been developed using epitope-defined reference Abs. Comparative epitope mapping of diagnostic Abs will provide the basis for the standardization of diagnostic antigenic domains/epitopes and consequently for improved reliability of hCG measurements. Diagnostic first line assays likely consist of pairs of Abs that recognize specific epitopes at the top of the neighboring peptide loops 1 and 3 (Ł1+3) and the cystine knot (ck) of hCGβ, respectively. In future, significant improvements of reliability, robustness and comparability of the results of immunoassays for complex glycoproteins such as hCG will be achieved by the use (i) of standardized diagnostic Abs against welldefined epitopes and (ii) of the new International Standards for hCG and for five hCG variants established by WHO, that are calibrated in molar (SI) units.

Small GTPases are involved in sprout formation in human granulosa lutein cells.

PubMed

Franz, Maximilian B; Daube, Stefanie; Keck, Christoph; Sator, Michael; Pietrowski, Detlef

2013-04-01

The corpus luteum (CL), develops from the ruptured follicle after gonadotropin stimulation. Based on intracellular reorganization of the cytoskeleton an human chorionic gonadotropin (hCG) dependent sprouting and migration of luteinizing granulosa cells (LGCs) and endothelial cells is observed. Rho-GTPases are shown to be key regulators of cytoskeletal restructuring. In the present study we analyzed the role of Rho-GTPases in the sprouting activity of LGCs. We used the Rho-GTPase-inhibitors Toxin A and -B and the Cdc42-activator Bradykinin in a LGC-spheroid sprouting assay to determine the effect of these modulators in LGCs. Toxin A and Toxin B reduces sprout formation in LGC spheroids. However, the reduction is less than in hCG treated cells. The usage of Bradykinin demonstrates both, a reduction of sprouts in untreated spheroids and an increase of sprouting in previous hCG treated spheroids. The presented results let us suggest that small Rho-GTPases may regulate the sprouting activity of LGCs after stimulation by hCG and that this mechanism may play a role in CL formation.

Combined human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) treatment in gonadotropin-deficient males with pituitary dwarfism.

PubMed

Tanaka, T; Hibi, I; Tanae, A

1992-04-01

The effects of hCG-hMG treatment in 13 boys with pituitary dwarfism associated with gonadotropin deficiency, were assessed. No patients except one showed signs of puberty at a bone age of 13 years or above. The one patient with some signs of puberty did not become fully mature. The hCG-hMG was started at a mean age of 20.4 years. The hCG at a dose of 5,000 IU was injected intramuscularly twice a week and the hMG at a dose of 75 IU was given once a week at first. During treatment, the frequency of hMG injections was increased to twice a week in six patients who still had not produced normal sperm counts. After a mean duration of 19.23 months, spermatozoa appeared in eight patients, of whom four showed more than 20 x 10(6) sperm/ml. Among six patients who did not have normal sperm counts and had increased hMG injections, one produced a pregnancy and four achieved sperm counts of more than 35 x 10(6)/ml. One patient had refractory azoospermia. In 13 boys with growth hormone and gonadotropin deficiency, hCG-hMG treatment produced normal spermatogenesis in nine patients, one of whom fathered a girl. Thus, hCG-hMG treatment, especially twice-a-week injections of both hCG and hMG, appears to be effective for gonadotropin deficiency in males.

A Positive Feedback Loop between Glial Cells Missing 1 and Human Chorionic Gonadotropin (hCG) Regulates Placental hCGβ Expression and Cell Differentiation

PubMed Central

Cheong, Mei-Leng; Wang, Liang-Jie; Chuang, Pei-Yun; Chang, Ching-Wen; Lee, Yun-Shien; Lo, Hsiao-Fan; Tsai, Ming-Song

2015-01-01

Human chorionic gonadotropin (hCG) is composed of a common α subunit and a placenta-specific β subunit. Importantly, hCG is highly expressed in the differentiated and multinucleated syncytiotrophoblast, which is formed via trophoblast cell fusion and stimulated by cyclic AMP (cAMP). Although the ubiquitous activating protein 2 (AP2) transcription factors TFAP2A and TFAP2C may regulate hCGβ expression, it remains unclear how cAMP stimulates placenta-specific hCGβ gene expression and trophoblastic differentiation. Here we demonstrated that the placental transcription factor glial cells missing 1 (GCM1) binds to a highly conserved promoter region in all six hCGβ paralogues by chromatin immunoprecipitation-on-chip (ChIP-chip) analyses. We further showed that cAMP stimulates GCM1 and the CBP coactivator to activate the hCGβ promoter through a GCM1-binding site (GBS1), which also constitutes a previously identified AP2 site. Given that TFAP2C may compete with GCM1 for GBS1, cAMP enhances the association between the hCGβ promoter and GCM1 but not TFAP2C. Indeed, the hCG-cAMP-protein kinase A (PKA) signaling pathway also stimulates Ser269 and Ser275 phosphorylation of GCM1, which recruits CBP to mediate GCM1 acetylation and stabilization. Consequently, hCG stimulates the expression of GCM1 target genes, including the fusogenic protein syncytin-1, to promote placental cell fusion. Our study reveals a positive feedback loop between GCM1 and hCG regulating placental hCGβ expression and cell differentiation. PMID:26503785

Differential responsiveness of luteinized human granulosa cells to gonadotropins and insulin-like growth factor I for induction of aromatase activity

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

Christman, G.M.; Randolph, J.F. Jr.; Peegel, H.

1991-06-01

The objective of this study was to examine the in vitro responsiveness of cultured luteinized human granulosa cells over time to insulin-like growth factor 1 (IGF-1), human follicle-stimulating hormone (FSH), and human chorionic gonadotropin (hCG) for the induction of aromatase activity. Granulosa cells were retrieved from preovulatory follicles in patients undergoing in vitro fertilization. Cells were cultured for a period of 72 hours or 10 days. The ability of hCG, human FSH, and/or IGF-I to induce aromatase activity was assayed by the stereospecific release of tritium from (1B-3H)androstenedione. Short-term cultures (72 hours) demonstrated a marked rise in aromatase activity inmore » response to human FSH and IGF-I, whereas a smaller response to hCG was observed. In contrast, 10-day cultures demonstrated responsiveness predominantly to hCG rather than human FSH for the induction of aromatase activity with no remarkable effect of IGF-I. Luteinized human granulosa cells undergo a transformation from an initial human FSH and IGF-I responsive state to an hCG responsive state in long-term cultures.« less

Chorionic gonadotropin regulates the transcript level of VHL, p53, and HIF-2alpha in human granulosa lutein cells.

PubMed

Herr, D; Keck, C; Tempfer, C; Pietrowski, Detlef

2004-12-01

The ovarian corpus luteum plays a critical role in reproduction being the primary source of circulating progesterone. After ovulation the corpus luteum is build by avascular granulosa lutein cells through rapid vascularization regulated by gonadotropic hormones. The present study was performed to investigate whether this process might be influenced by the human chorionic gonadotropin (hCG)-dependent expression of different tumor suppressor genes and hypoxia dependent transcription factors. RNA was isolated from cultured granulosa lutein cells, transcribed into cDNA, and the transcript level of following genes were determined: RB-1, VHL, NF-1, NF-2, Wt-1, p53, APC, and hypoxia inducible factor-1 (HIF-1), -2, and -3alpha. Additionally, the influence of hCG on the expression of VHL, p53, and HIf2alpha were investigated. We demonstrate that in human granulosa lutein cells the tumor suppressor genes RB-1, VHL, NF-1, NF-2, Wt-1, p53, and APC and the hypoxia dependent transcription factors HIF-1alpha, -2alpha, and -3alpha are expressed. In addition, we showed that hCG regulates the expression of p53, VHL, and HIF-2alpha. Our results indicate that hCG may determine the growth and development of the corpus luteum by mediating hypoxic and apoptotic pathways in human granulosa lutein cells. Copyright 2004 Wiley-Liss, Inc.

Postmenopausal pregnancy? Evaluation of elevated hCG in a 59-year-old woman.

PubMed

Basham, Mary Margaret; Bryan, Teresa

2017-06-05

Slightly elevated serum human chorionic gonadotropin (hCG) can be a normal finding in postmenopausal women. We report a case of a 59-year-old woman with a history of abnormal uterine bleeding who presented with a concern for pregnancy after developing nausea and vomiting a few weeks after unprotected intercourse. Although pregnancy was extremely unlikely, hCG was obtained in order to reassure the patient since she reported that her mother conceived at the age of 60. Serum hCG was positive, prompting concern for malignancy versus pregnancy. Stable serum hCG levels, elevated follicle-stimulating hormone and negative transvaginal ultrasound ruled out both malignancy and pregnancy. Positive serum pregnancy test and hCG elevation was attributed to normal postmenopausal state. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[The application of gonadotropin in treatment of male central hypogonadism].

PubMed

Di, Fu-song; Cui, Yu-gui; Jia, Yue

2005-11-01

To observe the efficacy of human chorionic gonadotrophin (hCG) and hCG plus human menopausal gonadotropin (HMG) for central hypogonadism in male patients. 64 men with central hypogonadism were recruited in this study, including 19 patients with Kallmann syndrome, 41 patients with idiopathic hypogonadotrophic hypogonadism (IHH) and 4 patients with hypogonadism after brain surgery. 33 patients were treated with hCG 1500 IU intramuscularly twice a week, whereas 31 patients were treated with intramuscular hCG 1500 IU plus HMG 75 IU twice a week, for at least 6 months. After treatment, all patients felt stronger physically and 42/64 patients developed beard, pubes or armpit hair. The testis volume enlarged significantly [(3.08 +/- 2.44) ml vs (8.92 +/- 5.37) ml, P < 0.001], and serum follicle-stimulating hormone, luteinizing hormone and testosterone concentrations were higher significantly than those before treatment (P < 0.05). 6/64 patients underwent spermatorrhea and 2 patient were found to have spermatogenesis. If judged by the testis volume, 52 patients (81.2%) were effective and 12 patients were ineffective. For male patients with the central hypogonadism, hCG and hCG plus HMG can promote the pubertal development and maturation of second sex characteristics, as well as enhance the physical strength; in some patients both androgen production and spermatogenesis can be achieved.

Luteal phase support for in vitro fertilization-embryo transfer--present and future methods to improve successful implantation.

PubMed

Check, J H

2012-01-01

To present reasons for luteal phase deficiency when taking controlled ovarian hyperstimulation (COH) for purposes of inducing multiple oocytes for in vitro fertilization (IVF), and to suggest strategies to overcome the defect. Treatment options presented include luteal phase support with human chorionic gonadotropin (hCG) injection, progesterone, estradiol, gonadotropin releasing hormone agonists, cytokines, e.g., granulocyte colony stimulating factor, and lymphocyte immunotherapy. hCG and progesterone produce the best results and are comparable or at best a slight edge to hCG but the latter is associated with too high a risk for ovarian hyperstimulation syndrome. Vaginal progesterone is the most efficacious with the least side-effects. Better methods are needed to adequately assess full correction of the luteal phase defect. In some cases the luteal phase defect associated with COH is not correctable and FSH stimulation should be reduced or all embryos frozen and defer transfer to an artificial estrogen progesterone or natural cycle.

Gonadotropin-releasing hormone for infertility in women with primary hypothalamic amenorrhea. Toward a more-interventional approach.

PubMed

Kesrouani, A; Abdallah, M A; Attieh, E; Abboud, J; Atallah, D; Makhoul, C

2001-01-01

To assess the effectiveness of a protocol of pulsatile gonadotropin releasing-hormone (GnRH) in treating infertility in women with primary hypothalamic amenorrhea. Retrospective analysis of 44 cycles treated at an infertility center. Twenty-four patients with primary hypothalamic amenorrhea were treated intravenously with pulsatile GnRH using 5 micrograms per bolus every 90 minutes. Ultrasound monitoring and cervical assessment by Insler's scoring system allowed timed injection of human chorionic gonadotropin (hCG) and intrauterine insemination if needed. Luteal support was provided with hCG. The ovulation rate was 95% with the 5-microgram dose. A single follicle was produced in 91% of cycles. The overall pregnancy rate per ovulatory cycle was 45%, and the pregnancy rate per patient was 83%. In patients treated previously with exogenous gonadotropins, poor results were observed. Only one case of mild overstimulation was reported. Pulsatile GnRH is an effective and safe method of treating infertility in women with primary hypothalamic amenorrhea, thus simulating normal ovulation; however, more-interventional management, including the qualitative estrogenic response, may lead to optimal results and increase the pregnancy rate.

Efficacy of a single injection of human chorionic gonadotropin at peak follicular maturation in natural cycles on pregnancy rate and mid-luteal hormonal and sonographic parameters.

PubMed

Check, J H; Liss, J R; DiAntonio, G; Summers, D

2016-01-01

To discover if infertile women with presumed luteal phase deficiency would improve pregnancy rates, mid-luteal sera estradiol (E2) and progesterone (P), and increase the percentage of women achieving a mid-luteal sonographic homogeneous hyperechogenic endometrial texture by the addition of a single injection of human chorionic gonadotropin (hCG). Women with over one year of infertility with regular menses and with no other known infertility factor were presumed to have the need for extra P in the luteal phase based on previous studies. Women aged ≥ 30 years were selected along with women < 30 years who had pelvic pain or dysmenorrhea. Women aged 40-45 were evaluated separately. They were treated with either vaginal micronized P 8% twice daily alone or 10,000 units of hCG at the time of peak follicular maturation was also given. Women were eliminated if they did not achieve an 18-24 average diameter follicle with a serum E2 of > 200 pg/ml. Seven days after ovulation, sera E2 and P were measured along with endometrial thickness and echo patterns. The only significant difference between groups was an increased mid-luteal serum E2 in the group receiving additional hCG. However, this did not result in an increased pregnancy rate. In general, adding a single injection of hCG to P luteal support does not improve pregnancy rates in natural cycles where women were treated with supplemental P.

Late-onset hypogonadism: the advantages of treatment with human chorionic gonadotropin rather than testosterone.

PubMed

La Vignera, Sandro; Condorelli, Rosita Angela; Cimino, Laura; Russo, Giorgio Ivan; Morgia, Giuseppe; Calogero, Aldo E

2016-01-01

The traditional pharmacological treatment of patients with late onset hypogonadism (LOH) is represented by different formulations of testosterone (T) or alternatively by the extractive human chorionic gonadotropin (HCG). The hormone replacement treatment (HRT) is associated with the potential increase of hematocrit, serum concentrations of prostate-specific antigen (PSA) and prostate volume. Moreover, the gynecomastia represent a condition frequently associated with HRT. Recent evidences showed the role of leydig cells in the 25-hydroxylation of vitamin D and the elevated frequency of hypovitaminosis D among LOH patients. Finally, another important aspect of LOH is represented by the frequency of secondary infertility due to age or to traditional HRT. This study evaluated 40 LOH patients treated for 6 months with extractive HCG (n = 10 patients) and three different formulations of T: transdermal (n = 10 patients), undecaonate (n = 10 patients) and enantate (n = 10 patients). Hormonal, anthropometric, metabolic and sperm parameters were evaluated and compared. Moreover, the main safety parameters and the results of the main questionnaires were evaluated. After treatment, HCG group showed serum concentrations of 25-OH-vitamin D significantly higher (p < 0.05) and serum concentrations of oestrogens significantly lower (p < 0.05) compared with other groups. Moreover, they showed a mean value of hematocrit, PSA and prostate volume significantly lower (p < 0.05) compared with other groups. Finally, all the groups treated with T showed a significant reduction (p < 0.05) of sperm density and of percentage of spermatozoa with progressive motility compared with HCG group.

HCG variants, the growth factors which drive human malignancies

PubMed Central

Cole, Laurence A

2012-01-01

The term human chorionic gonadotropin (hCG) refers to a group of 5 molecules, each sharing the common amino acid sequence but each differing in meric structure and carbohydrate side chain structure. The 5 molecules are each produced by separate cells and each having separate biological functions. hCG and sulfated hCG are hormones produced by placental syncytiotrophoblast cells and pituitary gonadotrope cells. Hyperglycosylated hCG is an autocrine produced by placental cytotrophoblast cells. Hyperglycosylated hCG drives malignancy in placental cancers, and in testicular and ovarian germ cell malignancies. hCGβ and hyperglycosylated hCGβ are autocrines produce by most advanced malignancies. These molecules, particularly the malignancy promoters are presented in this review on hCG and cancer. hCGβ and hyperglycosylated hCGβ are critical to the growth and invasion, or malignancy of most advanced cancers. In many ways, while hCG may appear like a nothing, a hormone associated with pregnancy, it is not, and may be at the center of cancer research. PMID:22206043

Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California

ERIC Educational Resources Information Center

Windham, Gayle C.; Lyall, Kristen; Anderson, Meredith; Kharrazi, Martin

2016-01-01

We examined prenatal screening markers and offspring autism spectrum disorder (ASD) using California statewide data on singleton births in 1996 and 2002. Second trimester levels of unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and maternal serum alpha-fetoprotein (MSAFP) were compared between mothers of children with ASD…

The aryl hydrocarbon receptor is required for normal gonadotropin responsiveness in the mouse ovary.

PubMed

Barnett, Kimberly R; Tomic, Dragana; Gupta, Rupesh K; Babus, Janice K; Roby, Katherine F; Terranova, Paul F; Flaws, Jodi A

2007-08-15

The aryl hydrocarbon receptor (AHR) mediates the toxicity of a variety of environmental chemicals. Although little is known about the physiological role of the AHR, studies suggest that it plays an important role in regulating ovulation because Ahr deficient (AhRKO) mice have a reduced number of ovulations compared to wild-type (WT) mice. The reasons for the reduced ability of AhRKO mice to ovulate are unknown. Normal ovulation, however, requires estrous cyclicity, appropriate luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and LH and FSH responsiveness. Thus, the purpose of this study was to test the hypothesis that Ahr deletion regulates ovulation by altering cyclicity, FSH and LH levels, follicle-stimulating hormone receptor (Fshr) and luteinizing hormone receptor (Lhcgr) levels and/or gonadotropin responsiveness. The data indicate that AhRKO and WT mice have similar levels of FSH and LH, but AhRKO mice have reduced Fshr and Lhcgr mRNA levels compared to WT mice. Furthermore, AhRKO ovaries contain fewer corpora lutea compared to WT ovaries after 5 IU equine chorionic gonadotropin (eCG) treatment. Lastly, both AhRKO and WT mice ovulate a similar number of eggs in response to 5 IU human chorionic gonadotropin (hCG), but AhRKO mice ovulate fewer eggs than WT mice in response to 2.5 IU and 1.25 IU hCG. Collectively, these data indicate that AhRKO follicles have a reduced capacity to ovulate compared to WT follicles and that this is due to reduced responsiveness to gonadotropins. Thus, in addition to mediating toxicity of environmental chemicals, the Ahr is required for normal ovulation.

The aryl hydrocarbon receptor is required for normal gonadotropin responsiveness in the mouse ovary

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

Barnett, Kimberly R.; Tomic, Dragana; Gupta, Rupesh K.

2007-08-15

The aryl hydrocarbon receptor (AHR) mediates the toxicity of a variety of environmental chemicals. Although little is known about the physiological role of the AHR, studies suggest that it plays an important role in regulating ovulation because Ahr deficient (AhRKO) mice have a reduced number of ovulations compared to wild-type (WT) mice. The reasons for the reduced ability of AhRKO mice to ovulate are unknown. Normal ovulation, however, requires estrous cyclicity, appropriate luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and LH and FSH responsiveness. Thus, the purpose of this study was to test the hypothesis that Ahr deletion regulatesmore » ovulation by altering cyclicity, FSH and LH levels, follicle-stimulating hormone receptor (Fshr) and luteinizing hormone receptor (Lhcgr) levels and/or gonadotropin responsiveness. The data indicate that AhRKO and WT mice have similar levels of FSH and LH, but AhRKO mice have reduced Fshr and Lhcgr mRNA levels compared to WT mice. Furthermore, AhRKO ovaries contain fewer corpora lutea compared to WT ovaries after 5 IU equine chorionic gonadotropin (eCG) treatment. Lastly, both AhRKO and WT mice ovulate a similar number of eggs in response to 5 IU human chorionic gonadotropin (hCG), but AhRKO mice ovulate fewer eggs than WT mice in response to 2.5 IU and 1.25 IU hCG. Collectively, these data indicate that AhRKO follicles have a reduced capacity to ovulate compared to WT follicles and that this is due to reduced responsiveness to gonadotropins. Thus, in addition to mediating toxicity of environmental chemicals, the Ahr is required for normal ovulation.« less

Superovulation induction in the house musk shrew (Suncus murinus).

PubMed

Matsuzaki, T; Matsuzaki, K; Yokoyama, M; Yamada, S; Saito, M

1997-07-01

The number of ovulated oocytes in the adult house musk shrews was examined by natural mating. The positive rate of ovulation was 83.3%, and the mean number of ovulated oocytes was 4.4 +/- 1.9 (Mean +/- SD). The induction of superovulation was examined by administering either pregnant mare's serum gonadotropin (PMSG) or human chorionic gonadotropin (hCG), exogenous gonadotropin, to house musk shrews. As a result, the number of ovulated oocytes were within the number of oocytes ovulated spontaneously. The method of superovulation induction by administering both PMSG and hCG to house musk shrews was investigated. In the group intraperitoneally with 7.5 i.u. of PMSG followed by 7.5 i.u. of hCG 48 hr later, the positive rate of ovulation was as high as 94.6% and the mean number of ovulated oocytes was 11.7 +/- 13.4. Moreover, in 15 out of these 35 animals positive for ovulation, 10 oocytes or more were observed and the mean number of ovulated oocytes was 21.0 +/- 16.5, showing the superovulatory response. In the group of 5.0 i.u. PMSG and 5.0 i.u. hCG injected at an interval of 72 hr, every animal was induced to ovulate and the mean number of ovulated oocytes was 41.3 +/- 19.9. Thus, the injection of PMSG and hCG at a longer interval increased the number of superovulated oocytes. Furthermore, 97.5% of eggs recovered from superovulating animals contained cumulus cells.

Gonadotropin stimulation of cyclic adenosine monophosphate and testosterone production without detectable high-affinity binding sites in purified Leydig cells from rat testis

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

Browne, E.S.; Bhalla, V.K.

1991-02-01

Rat testicular interstitial cells were separated by three different gradient-density procedures and, with each, two biochemically and morphologically distinct cell fractions were isolated. The lighter density cells in fraction-I bound iodine 125-labeled human chorionic gonadotropin (hCG) with high-affinity (apparent equilibrium dissociation constant, Kd, approximately 10{sup {minus} 10} M) without producing either cyclic adenosine monophosphate or testosterone in response to hormone action. The heavier-density cells displayed morphologic features typical of Leydig cells and produced cyclic adenosine monophosphate and testosterone in the presence of hCG without detectable {sup 125}I-labeled hCG high-affinity binding. These cell fractions were further characterized by studies using deglycosylatedmore » hCG, a known antagonist to hCG action. Cell concentration-dependent studies with purified Leydig cells revealed that maximal testosterone production was achieved when lower cell concentrations (0.5 x 10(6) cells/250 microliters) were used for in vitro hCG stimulation assays. Under these conditions, the {sup 125}I-labeled hCG binding was barely detectable (2.24 fmol; 2,698 sites/cell). Furthermore, these studies revealed that the hCG-specific binding in Leydig cells is overestimated by the classic method for nonspecific binding correction using excess unlabeled hormone. An alternate method is presented.« less

Gonadotropin-releasing hormone agonist triggering with concomitant administration of low doses of human chorionic gonadotropin or a freeze-all strategy in high responders.

PubMed

Karacan, Meric; Erdem, Erkan; Usta, Akin; Arvas, Ayse; Cebi, Ziya; Camlibel, Teksen

2017-06-01

To compare the live birth rates and moderate/severe ovarian hyperstimulation syndrome (OHSS) rates of 2 different approaches using gonadotropin-releasing hormone (GnRH) agonist triggering in high responder women. Methods: A retrospective cohort study was performed to evaluate intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) outcomes in high responder women who underwent ovulation induction with a GnRH antagonist protocol between April 2011 and March 2015. In group 1 (n=74), GnRH agonist was used for ovulation triggering with the concomitant use of 1500 IU of urinary human chorionic gonadotropin (hCG) immediately after oocyte retrieval followed by fresh ET and standard luteal support. In group 2 (n=48), GnRH agonist was used for triggering after freezing all embryos and subsequent frozen/thawed embryo transfer (FET); this approach is considered the "freeze-all" approach. Results: Baseline characteristics were similar between the groups. The clinical pregnancy rates for group 1 was 45.9% and group 2 was 43.8% (p=0.812, chi-squared test) and live birth rates for group 1 was 40.5% and for group 2 41.7% (p=0.902, chi-squared test) were comparable between groups. In group 1, late-onset OHSS was observed (one severe case and one moderate case) in 2 patients (2.7%). In group 2, none of the patients experienced moderate/severe OHSS. Conclusion: The live birth rate with GnRH agonist triggering and concomitant use of 1500 IU of hCG immediately after oocyte retrieval was similar to that obtained with the freeze-all approach and FET in a subsequent cycle. The administration of a low dose of hCG in GnRH agonist trigger cycles caused moderate/severe OHSS in 2.7% of the patients.

Proportion hyperglycosylated hCG: a new test for discriminating gestational trophoblastic diseases.

PubMed

Cole, Laurence A

2014-11-01

Hyperglycosylated human chorionic gonadotropin (hCG) is a variant of hCG with large oligosaccharide side chains. Although hCG is produced by syncytiotrophoblast cells, hyperglycosylated hCG marks cytotrophoblast cell. Hyperglycosylated hCG signals placental implantation. Total hCG in serum and urine is measured by the Siemens Immulite hCG pregnancy test; the result is in milli-international unit per milliliter. Hyperglycosylated hCG is determined by the B152 microtiter plate assay; the result is in nanogram per milliliter. Hyperglycosylated hCG results can be converted to milli-international unit per milliliter equivalents by multiplying by 11. The test measures proportion hyperglycosylated hCG, hyperglycosylated hCG / total hCG. Proportion hyperglycosylated hCG marks cases intent on developing persistent hydatidiform mole (68% detection at 17% false detection). Proportion hyperglycosylated hCG also marks persistent hydatidiform mole (100% detection at 5.1% false detection). Proportion hyperglycosylated hCG distinguishes choriocarcinoma and gestational trophoblastic neoplasm cases, absolutely discriminating aggressive cases and minimally aggressive cases. Proportion hyperglycosylated hCG identifies quiescent gestational trophoblastic disease cases. It recognizes quiescent cases that become persistent disease (100% detection at 0% false positive). Proportion hyperglycosylated hCG is an invaluable test for discriminating gestational trophoblastic diseases.

The steroid response to human chorionic gonadotropin (hCG) stimulation in men with Klinefelter syndrome does not change using immunoassay or mass spectrometry.

PubMed

Roli, L; Santi, D; Belli, S; Tagliavini, S; Cavalieri, S; De Santis, M C; Baraldi, E; Fanelli, F; Mezzullo, M; Granata, A R; Pagotto, U; Pasquali, R; Rochira, V; Carani, C; Simoni, M; Trenti, T

2017-08-01

Liquid-chromatography tandem mass-spectrometry (LC-MS/MS) was developed in parallel to Immunoassays (IAs) and today is proposed as the "gold standard" for steroid assays. Leydig cells of men with Klinefelter syndrome (KS) are able to respond to human chorionic gonadotropin (hCG) stimulation, even if testosterone (T) production was impaired. The aim was to evaluate how results obtained by IAs and LC-MS/MS can differently impact on the outcome of a clinical research on gonadal steroidogenesis after hCG stimulation. A longitudinal, prospective, case-control clinical trial. (clinicaltrial.gov NCT02788136) was carried out, enrolling KS men and healthy age-matched controls, stimulated by hCG administration. Serum steroids were evaluated at baseline and for 5 days after intramuscular injection of 5000 IU hCG using both IAs and LC-MS/MS. 13 KS patients (36 ± 9 years) not receiving T replacement therapy and 14 controls (32 ± 8 years) were enrolled. T, progesterone, cortisol, 17-hydroxy-progesterone (17OHP) and androstenedione, were significantly higher using IAs than LC-MS/MS. IAs and LC-MS/MS showed direct correlation for all five steroids, although the constant overestimation detected by IAs. Either methodology found the same 17OHP and T increasing profile after hCG stimulation, with equal areas under the curves (AUCs). Although a linearity between IA and LC-MS/MS is demonstrated, LC-MS/MS is more sensitive and accurate, whereas IA shows a constant overestimation of sex steroid levels. This result suggests the need of reference intervals built on the specific assay. This fundamental difference between these two methodologies opens a deep reconsideration of what is needed to improve the accuracy of steroid hormone assays.

Effects of a single administration of different gonadotropins on day 7 post-insemination on pregnancy outcomes of rabbit does.

PubMed

Hashem, N M; Aboul-Ezz, Z R

2018-01-01

This study aimed to investigate the effects of a single administration of one of three different gonadotropins on Day 7 post-insemination on ovarian activity, progesterone (P 4 ) concentration and pregnancy outcomes of rabbit does. Multiparous, non-lactating, V-line does were artificially inseminated after synchronization and ovulation induction with equine chorionic gonadotropin (eCG; 25 IU im) and gonadotropin releasing hormone (GnRH; 0.8  μg buserelin im) 48 h later. On Day 7 post-inseminarion, does were randomly allocated into four groups (n = 40/group). Does of each group were intramuscularly injected with a single dose of one of physiological saline (placebo; control), GnRH (0.8  μg buserelin), human chorionic gonadotropin (hCG; 25 IU) or eCG (25 IU). Concentration of serum P 4 was determined on Days 6, 9, 11 and 18 post-insemination. On Day 14 post-insemination, the ovaries and reproductive tracts of pregnant does were removed and weighed. Also, numbers of visible follicles, hemorrhagic follicles, corpora lutea of pregnancy (pCLs), new CLs (nCLs; formed after Day 7 post-insemination) and implantation sites were recorded. Conception rate, parturition rate, abortion rate, litter size/weight and litter viability were recorded. The highest (P < 0.05) reproductive tract and ovary weights were for eCG. The highest (P < 0.05) number of visible ovarian follicles was for eCG, whereas the lowest (P < 0.05) was for GnRH. Treatment with eCG increased (P < 0.05) numbers of pCLs and total implantation sites compared to the other groups. Treatment with GnRH or hCG increased (P < 0.05) number of nCLs compared to control and eCG. The highest rate of fetal loss was in does treated with GnRH. The concentration of serum P 4 decreased (P < 0.05) following the treatment with GnRH and continued low until Day 18. However, it remained in line for control, hCG and eCG groups up to Day 11, then decreased (P < 0.05) for control and hCG on Day 18, being lower for hCG than control, while continued to increase for eCG up to Day 18. Compared to control, treatment with eCG improved (P < 0.05) conception and parturition rates by 24 and 22%; respectively, while GnRH and hCG treatments decreased (P < 0.05) them by 57 and 47.6%; respectively. Litter size and litter weight at birth were improved by eCG, but were adversely affectd by GnRH and hCG. In conclusion, a single administration of eCG 7 Days post-insemination could be recommended for improving pregnancy outcomes in rabbits. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of beta-carotene on fertility in rabbits when using embryo transfer programs.

PubMed

Besenfelder, U; Solti, L; Seregi, J; Brem, G

1993-05-01

The effect of beta-carotene on reproduction traits in rabbits was studied in 509 (superovulated and normally ovulated) donors and 239 recipients by using embryo/gene transfer performed at 2 different locations. All of the bucks and the half of the females were fed a diet supplemented with 40 mg synthetic beta-carotene (Rovimix((R)))/kg feed. Embryos at the pronucleus stage were collected 19 to 21 hours after induction of ovulation with human chorionic gonadotropin (hCG); they were then microinjected into the male pronucleus and transferred to synchronized recipients. Data were obtained from the time when the donors and recipients were caged, until the pups resulting from the embryo transfers were weaned. Supplemented beta-carotene did not affect most of the 30 traits that were analyzed. However superovulated donors in Project 2 that received the beta-carotene enriched diet had a 14% lighter ovary weight (P<0.05) and less than half of the oocytes were unfertilized (P<0.05). In Project 1 (beta-carotene group) there was a greater number of pups born (36%, P<0.05) and more of these pups were born alive (53%, P<0.05).

The use of human chorionic gonadotropin (HCG) for penile reconstruction in bladder exstrophy and total epispadias patients.

PubMed

Makedonsky, I A

2006-12-01

The effect of intramuscular human chorionic gonadotropin (HCG) administration on penile enlargement before genital surgery, its influence on penile skin histology and testicular descent were investigated. We examined 45 male patients (median age, 8 months; range 3-28) with total epispadias and classic bladder exstrophy, combined with cryptorchidism. 30 patients were administered 250-500 IU HCG intramuscularly 2 times per week for 3 weeks before reconstructive surgery. Skin biopsies were obtained for human epidermal growth factor (EGF) and human epidermal growth factor receptor (Her2/neu) determination. Skin specimens of the prepuce of 18 circumcised patients were used as controls. Post treatment testicle position was evaluated. HCG caused a mean increase in penile length of 1.8 cm (p < 0.01) and in circumference of 1.2 cm (p < 0.05) as well as improved local vascularity in all patients. Compared to the controls, the penile skin of exstrophy/epispadias patients showed a significant decrease in the average amount per field of EGF and Her2/neu positive material (controls 81% [mean 79, SE 2.3] vs. 31% [mean 28, SE 3.6; p < 0.001]). Treatment with HCG led to an increase in average EGF and Her2/neu positive material by 10% (mean 8, SE 2; p < 0.05). The potential side effects of HCG treatment were monitored 3 to 6 months postoperatively. Basal testosterone and LH levels were obtained in patients before and during therapy and postoperatively. Testicular descent was achieved in 21 patients (70%). No significant side effects or complications were encountered in any of our patients. Mean EGF and Her2/neu values are decreased in the penile skin of exstrophy/epispadias patients. The use of preoperative HCG administration leads to an increase in EGF and Her2/neu values and significantly contributes to successful reconstruction in these patients, especially in cases with a paucity of penile skin and in patients who have undergone previous repairs. Temporary penile stimulation by HCG in patients with bladder exstrophy combined with cryptorchidism allows the penile operation to be carried out earlier and contributes to testicular descent while demonstrating negligible side effects.

Preparation and characterization of magnetic nanoparticles containing Fe(3)O(4)-dextran-anti-β-human chorionic gonadotropin, a new generation choriocarcinoma-specific gene vector.

PubMed

Jingting, Cai; Huining, Liu; Yi, Zhang

2011-01-01

To evaluate the feasibility of using magnetic iron oxide (Fe(3)O(4))-dextran-anti-β-human chorionic gonadotropin (HCG) nanoparticles as a gene vector for cellular transfections. Fe(3)O(4)-dextran-anti-β-HCG nanoparticles were synthesized by chemical coprecipitation. The configuration, diameter, and iron content of the nanoparticles were detected by transmission electron microscopy (TEM), light scatter, and atomic absorption spectrophotometry. A3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide assay was used to evaluate the cytotoxicity of Fe(3)O(4)-dextran-anti-β-HCG nanoparticles. Enzyme-linked immunosorbent assay and indirect immunofluorescence were used to evaluate immunoreactivity. The efficiency of absorbing DNA and resisting deoxyribonuclease I (DNase I) digestion when bound to Fe(3)O(4)-dextran-anti-β-HCG nanoparticles was examined by agarose gel electrophoresis. The ability of Fe(3)O(4)-dextran-anti-β-HCG nanoparticles to absorb heparanase antisense oligodeoxynucleotides (AS-ODN) nanoparticles in different cell lines was evaluated by flow cytometry. The tissue distribution of heparanase AS-ODN magnetic nanoparticles in choriocarcinoma tumors transplanted in nude mice was detected by atomic absorption spectrophotometry. TEM demonstrated that the shape of nanoparticles is irregular. Light scatter revealed nanoparticles with a mean diameter of 75.5 nm and an iron content of 37.5 μg/mL. No cytotoxicity was observed when the concentration of Fe(3)O(4)-dextran-anti-β-HCG nanoparticles was <37.5 μg/mL. Fe(3)O(4)-dextran nanoparticles have a satisfactory potential to combine with β-HCG antibody. Agarose gel electrophoresis analysis of binding experiments showed that after treatment with sodium periodate, Fe(3)O(4)-dextran-anti-β-HCG nanoparticles have a satisfactory potential to absorb DNA, and the protection experiment showed that nanoparticles can effectively protect DNA from DNase I digestion. Aldehyde Fe(3)O(4)-dextran-anti-β-HCG nanoparticles can transfect reporter genes, and the transfection efficiency of these nanoparticles is greater than that of liposomes (P < 0.05). Fe(3)O(4)-dextran-anti-β-HCG nanoparticles can concentrate in choriocarcinoma cells and in transplanted choriocarcinoma tumors. The results confirm that Fe(3)O(4)-dextran-anti-β-HCG nanoparticles have potential as a secure, effective, and choriocarcinoma-specific targeting gene vector.

The benefit of individualized low-dose hCG support for high responders in GnRHa-triggered IVF/ICSI cycles.

PubMed

Huang, Chen-Yu; Shieh, Miawh-Lirng; Li, Hsin-Yang

2016-07-01

To assess the pregnancy outcome and ovarian hyperstimulation syndrome (OHSS) incidence in high responders receiving gonadotropin-releasing hormone agonist (GnRHa) trigger plus individualized support of low-dose human chorionic gonadotropin (hCG). Such support includes 500-1000 IU hCG given at trigger and, if serum estradiol (E2) dropped to below 800 pg/mL before the 6(th) day after oocyte retrieval, an additional rescue dose of 300 IU hCG. This was a retrospective study of potential high responders aged from 28 years to 40 years at a tertiary fertility center in Taiwan. By means of chart review, we assessed the pregnancy outcome and OHSS incidence in high responders receiving GnRHa trigger plus individualized low-dose hCG support. The main outcomes were measured by ongoing pregnancy rate and OHSS incidence (SPSS), in which statistical significance was determined by Chi-square test. Moderate to severe OHSS did not develop in any patient receiving GnRHa trigger plus individualized low-dose hCG support. In fact, a satisfactory ongoing pregnancy rate (46.9%) was noted in patients receiving GnRHa trigger plus individualized low-dose hCG support. Our study suggested that GnRHa trigger combined with individualized low-dose hCG support appears to be a safe approach with a satisfactory pregnancy outcome. Copyright © 2016. Published by Elsevier Taiwan LLC.

[Spermatogenesis of pulsatile gonadotropin-releasing hormone infusion versus gonadotropin therapy in male idiopathic hypogonadotropic hypogonadism].

PubMed

Huang, Bingkun; Mao, Jiangfeng; Xu, Hongli; Wang, Xi; Liu, Zhaoxiang; Nie, Min; Wu, Xueyan

2015-05-26

To compare the efficacies of pulsatile gonadotropin-releasing hormone (GnRH) versus human chorionic gonadotropin/human menopausal gonadotropin (HCG/HMG) for spermatogenesis in male idiopathic hypogonadotropic hypogonadism (IHH). For this retrospective study, a total of 92 male IHH outpatients from May 2010 to October 2014 were recruited and categorized into GnRH (n = 40) and HCG/HMG (n = 52) groups. Each subject selected one specific therapy voluntarily. The gonadotropin levels were measured in the first week and monthly post-treatment in GnRH group. And serum total testosterone (TT), testicular volume (TV) and rate of spermatogenesis were observed monthly post-treatment in two groups. Spermatogenesis, TT and TV were compared between two groups. All IHH patients were treated for over 3 months. The median follow-up periods in GnRH and HCG/HMG groups was 8.2 (3.0-18.4) and 9.2 (3.0-18.6) months respectively (P = 0.413). In GnRH group, LH ((0.5 ± 0.6) vs (3.4 ± 2.4) U/L, P < 0.01) and FSH ((1.3 ± 1.1) vs (5.8 ± 3.8) U/L, P < 0.01) increased after 1-week treatment. In GnRH group, at the end of follow-up, TT ((1.0 ± 1.0) vs (7.4 ± 5.2) nmol/L, P < 0.01) and TV ((2.3 ± 1.5) vs (8.1 ± 4.0) ml, P < 0.01) significantly increased compared to baseline. In HCG/HMG group, TT ((0.8 ± 0.6) vs (14.4 ± 8.0) nmol/L, P < 0.01) and TV ((2.3 ± 2.1) vs (7.6 ± 4.2) ml, P < 0.01) significantly increased after therapy. The success rate of spermatogenesis was 50.0% (20/40) in GnRH group versus 28.8% (15/52) in HCG/HMG group (P = 0.038). GnRH group required a shorter treatment time for initial sperm appearance than HCG/HMG group ((6.5 ± 3.1) vs (10.8 ± 3.7) months, P = 0.001). Pulsatile GnRH requires a shorter time for initiation of spermatogenesis than gonadotropin therapy in IHH male patients.

Human chorionic gonadotropin but not the calcitonin gene-related peptide induces postnatal testicular descent in mice.

PubMed

Houle, A M; Gagné, D

1995-01-01

The androgen-regulated paracrine factor, calcitonin gene-related peptide (CGRP), has been proposed as a possible mediator of testicular descent. This peptide has been found to increase rhythmic contractions of gubernaculae and is known to be released by the genitofemoral nerve. We have investigated the ability of CGRP to induce premature testicular descent. CGRP was administered alone, or in combination with human chorionic gonadotropin (hCG) to C57BL/6 male mice postnatally. The extent of testicular descent at 18 days postpartum was then ascertained. The potential relationship between testicular weight and descent was also examined. Our results show that testes of mice treated with either hCG alone, or in combination with 500 ng CGRP, were at a significantly lower position than those of controls by 16% and 17%, respectively. In contrast, mice treated with 500 ng of CGRP alone had testes at a higher position when compared to those of controls, by 19%. In mice treated with 50 ng of CGRP alone or in combination with hCG, testes were at a position similar to those in controls. Furthermore, testicular descent was analyzed in relation to testicular weight, and we found that significantly smaller testes per gram of body weight than those of controls were at a significantly lower position compared to those of controls. Our data demonstrate that CGRP had no effect on postnatal testicular descent and that there is no relationship between postnatal descent and testicular weight.

[Changes in levels of chorionic gonadotrophin (hCG) and its subunit alpha and beta in pregnancy complicated by diabetes (GDM)].

PubMed

Olszewski, J; Szczurowicz, A; Wójcikowski, C

1995-02-01

The aim of the study was estimation of endocrinological function of placenta in pregnancy complicated by GDM. The study were performed on a group 13 women with GDM and 14 women in normal pregnancy. All women with GDM were treat by diet and intensive insulinotherapy with self monitoring levels of glucose. In women with GDM level of fructosamine and HbAlc were significant higher but in normal range. In 28 and 36 week of pregnancy were determined levels of hCG, alpha hCG, beta hCG, in serum. Level of hCG in control group and in women with GDM were respectively 97.29 U/ml vs. 29.29 U/ml, p < 0.01 in 28 week of pregnancy and 77.23 U/ml vs. 37.93 U/ml, p < 0.05 in 36 week. Level of alpha hCG was lower and beta hCG was higher in group with GDM.

Gestational Trophoblastic Disease Diagnosis Delayed by the Hook Effect.

PubMed

Cormano, Julia; Mackay, Gillian; Holschneider, Christine

2015-10-01

A "hook effect" resulting from saturation of antibodies used in pregnancy tests can occur at human chorionic gonadotropin (hCG) levels above 500,000 milliinternational units/mL, resulting in falsely negative values. A 34-year-old woman, gravida 5 para 3, presented to the emergency department after heavy bleeding. Ultrasonogram revealed a uterine mass, urine pregnancy test result was negative, and endometrial biopsy inconclusive. The patient was discharged and presented 10 days later with recurrent bleeding. Urine pregnancy test result was again negative, but serum hCG was 581 milliinternational units/mL. Serial dilution revealed an actual hCG higher than 5 million milliinternational units/mL. She was diagnosed with gestational trophoblastic disease. Awareness of the risk of a false-negative pregnancy test result when hCG levels are extremely high may prevent delayed diagnosis of gestational trophoblastic disease.

Enhanced urothelial expression of human chorionic gonadotropin beta (hCGβ) in bladder pain syndrome/interstitial cystitis (BPS/IC).

PubMed

Schwalenberg, Thilo; Stolzenburg, Jens-Uwe; Ho, Thi Phuc; Mallock, Tobias; Hartenstein, Siegurd; Alexander, Henry; Zimmermann, Gerolf; Hohenfellner, Rudolf; Denzinger, Stefan; Burger, Maximilian; Horn, Lars-Christian; Neuhaus, Jochen

2012-06-01

Bladder pain syndrome/interstitial cystitis (BPS/IC) is associated with urothelial lesions. Pathomechanisms of urothelial damage and factors for urothelial restoration are unknown. hCG is a factor for cellular differentiation, angiogenesis and immune competence of the endometrium during pregnancy. Clinical observations demonstrate improvement of BPS/IC symptoms during pregnancy or during infertility treatment with hCG. Our research aims were to examine the expression of hCG and luteinizing hormone receptor (LHR) in the urothelium of BPS/IC patients and compare the levels of hCGβ with healthy controls. Bladder biopsies of BPS/IC (CLSM: n = 10; qPCR: n = 15); Tumour-free control tissue from cystectomies (n = 12). hCGα, hCGβ and LHR expression were examined by confocal laser scanning microscopy (CLSM), and hCGβ expression was quantified. hCGβ5 and hCGβ7 mRNA splice variants were quantified in real-time polymerase chain reaction. We found constitutive expression of hCGα, hCGβ and LHR in healthy controls. HCGβ was significantly upregulated in BPS/IC patients in CLSM. PCR analysis revealed higher levels of hCGβ7 than hCGβ5 in controls and BPS/IC patients. The constitutive expression of hCG and LHR speaks in favour for a functional signalling in urothelial cells without any association with either pregnancy or tumour. We show for the first time that hCGβ is upregulated in BPS/IC urothelium and that hCGβ7 is the dominant splice variant in those cells. Our findings imply a major role of hCG for urothelial integrity and a disturbance of hCG signalling in case of BPS/IC. We conclude that hCG could gain therapeutical relevance in the future.

Embryo survival from gossypol-fed heifers after transfer to lactating cows treated with human chorionic gonadotropin.

PubMed

Galvão, K N; Santos, J E P; Coscioni, A C; Juchem, S O; Chebel, R C; Sischo, W M; Villaseñor, M

2006-06-01

Objectives were to determine the effects of gossypol exposure during early embryo development on embryonic survival after transfer of frozen and thawed embryos to lactating dairy cows treated with human chorionic gonadotropin (hCG). Holstein cows (n = 269) were either treated or not treated with 3,300 IU of hCG on d 5 of the estrous cycle and received an embryo collected from heifers fed or not fed gossypol. Embryo donor heifers consumed either 0 or 12 g/d of free gossypol for 76 d prior to embryo collection, resulting in mean plasma gossypol concentrations of 0 and 7.38 microg/mL, respectively. Embryos were transferred on d 7 of the estrous cycle and pregnancy diagnosed 21 and 35 d later. Progesterone was analyzed in plasma collected on d 5 and 12 of the estrous cycle. Treatment with hCG increased the total luteal area on d 12 (818.0 vs. 461.1 mm2) because of increased number of corpora lutea (2.0 vs. 1.0) and increased area of the original corpora lutea (522.7 vs. 443.5 mm2). Plasma progesterone concentrations were similar between treatments on d 5, but increased by d 12 in hCG-treated cows (6.46 vs. 4.78 ng/ mL). Pregnancy rates on d 28 and 42 were not affected by hCG. However, after transfer into lactating cows, embryos collected from heifers not fed gossypol resulted in higher pregnancy rates at 28 d (33.3 vs. 23.1%) and 42 d (29.6 vs. 20.2%) of gestation compared with embryos collected from heifers fed gossypol. Our data suggest that the negative effects of gossypol on fertility are mediated by changes in embryo viability in spite of similar grade quality at transfer.

Human Chorionic Gonadotropin Stimulation Test in Prepubertal Children with Micropenis Can Accurately Predict Leydig Cell Function in Pubertal or Postpubertal Adolescents.

PubMed

Ishii, Tomohiro; Matsuo, Nobutake; Sato, Seiji; Ogata, Tsutomu; Tamai, Shinya; Anzo, Makoto; Kamimaki, Tsutomu; Sasaki, Goro; Inokuchi, Mikako; Hori, Naoaki; Amano, Naoko; Narumi, Satoshi; Shibata, Hironori; Hasegawa, Tomonobu

2015-01-01

To evaluate the accuracy of the human chorionic gonadotropin (hCG) stimulation test in children with micropenis in predicting later Leydig cell function. We conducted a retrospective investigation of testosterone response to a 3-day hCG test (3,000 IU/m2/day) in prepuberty to indicate the need for hormone replacement therapy (HRT) in adolescence. Fifty Japanese boys (range, 0.8-15.4 years of age; median, 8.9) with micropenis were enrolled. Thirty-four spontaneously developed puberty and preserved the ability of testosterone production (group 1), while 16 did not develop any pubertal signs without HRT (group 2). Serum testosterone levels after the hCG test (post-hCG T) in group 2 (range, <0.05-1.1 ng/ml; median, 0.24) were significantly lower than in group 1 (range, 0.5-8.7 ng/ml; median, 2.4; p < 0.0001). Based on true positives who required continuous HRT, the area under the receiver-operating characteristics curve for post-hCG T was 0.983 [95% confidence interval (CI), 0.90-1.00]. The post-hCG T cut-off level corresponding to the Youden index was 1.1 ng/ml (95% CI, 1.0-1.1), with a sensitivity of 100.0% (95% CI, 79.4-100.0) and a specificity of 94.1% (95% CI, 80.3-99.3). The hCG test in prepubertal children with micropenis can be useful for predicting Leydig cell function in pubertal or postpubertal adolescents. The post-hCG T cut-off level of 1.1 ng/ml is recommended to screen for those who will likely require HRT for pubertal development. © 2015 S. Karger AG, Basel.

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.

The steroidogenic response and corpus luteum expression of the steroidogenic acute regulatory protein after human chorionic gonadotropin administration at different times in the human luteal phase.

PubMed

Kohen, Paulina; Castro, Olga; Palomino, Alberto; Muñoz, Alex; Christenson, Lane K; Sierralta, Walter; Carvallo, Pilar; Strauss, Jerome F; Devoto, Luigi

2003-07-01

This study was designed 1) to assess corpus luteum (CL) steroidogenesis in response to exogenous human chorionic gonadotropin (hCG) at different times during the luteal phase, 2) to examine the effect of hCG on steroidogenic acute regulatory protein (StAR) expression within the CL, 3) to correlate StAR expression and luteal steroidogenic responses to hCG, and 4) to determine whether endogenous LH regulates ovarian steroidogenesis in the early luteal phase. Blood was collected before and after hCG treatment for steroid and hCGbeta determinations. CL were obtained at the time of surgery to assess StAR gene and protein expression. During the early luteal phase various women received the GnRH antagonist for 24-48 h; some of them also received hCG 24 h after the GnRH antagonist. A slight steroidogenic response to hCG was observed in early luteal phase; 17alpha-hydroxyprogesterone, but not progesterone (P4), levels were significantly increased 8 h post-hCG, indicating a differential response by the granulosa and theca-lutein cells. The 1.6- and 4.4-kb StAR transcripts and the 37-kDa preprotein and 30-kDa mature StAR protein did not change post-hCG administration in early luteal phase CL. In contrast, the StAR 4.4- and 1.6-kb transcripts diminished significantly (P < 0.05) after the antagonist treatment. Immunohistochemical staining for StAR protein was weak, particularly in granulosa-lutein cells. Treatment with hCG restored StAR mRNA and protein and plasma P4 levels within 24 h in antagonist-treated women. hCG stimulated the highest plasma concentrations of P4 and estradiol in the midluteal phase, indicating its greatest steroidogenic capacity. Midluteal tissue StAR gene and protein expression increased by 1.6- and 1.4-fold after 24 h of hCG treatment, respectively. Administration of hCG resulted in the greatest increment in plasma P4 (4-fold) and 17alpha-hydroxyprogesterone (3-fold) levels over baseline in the late luteal phase. This was associated with an increase in StAR mRNA (3.5-fold) and protein (1.8-fold). Collectively, these data indicate that 1) the hCG-stimulated steroidogenic response is dependent on the age of the CL; 2) the early luteal phase CL is relatively insensitive to exogenous hCG in the presence of normal pituitary gonadotropin support, but becomes responsive when the latter is withdrawn; 3) the hCG-stimulated steroidogenic response in the mid- and late luteal phase is correlated with increased StAR mRNA and protein abundance; and 4) there are differential responses of small and large luteal cells to hCG stimulation that depend upon the age of the CL.

Oral Progestin Priming Increases Ovarian Sensitivity to Gonadotropin Stimulation and Improves Luteal Function in the Cat1

PubMed Central

Stewart, Rosemary A.; Pelican, Katharine M.; Crosier, Adrienne E.; Pukazhenthi, Budhan S.; Wildt, David E.; Ottinger, Mary Ann; Howard, JoGayle

2012-01-01

ABSTRACT As the only domesticated species known to exhibit both induced and spontaneous ovulation, the cat is a model for understanding the nuances of ovarian control. To explore ovarian sensitivity to exogenous gonadotropins and the influence of progestin priming, we conducted a study of queens that were down-regulated with oral progestin or allowed to cycle normally, followed by low or high doses of equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG). Our metrics included 1) fecal steroid metabolite profiles before and after ovulation induction, 2) laparoscopic examination of ovarian follicles and corpora lutea (CL) on Days 2 and 17 (Day 0 = hCG administration), and 3) ovariohysterectomy (Day 17) to assess CL progesterone concentrations, morphometrics, and histology. Reproductive tracts from time-matched, naturally mated queens (n = 6) served as controls. Every progestin-primed cat (n = 12) produced the desired response of morphologically similar, fresh CL (regardless of eCG/hCG dose) by Day 2, whereas 41.7% of unprimed counterparts (n = 12) failed to ovulate or had variable-aged CL suggestive of prior spontaneous ovulation (P < 0.05). The ovarian response to low, but not high, eCG/hCG was improved (P < 0.05) in primed compared to unprimed cats, indicating increased sensitivity to gonadotropin in the progestin-primed ovary. Progestin priming prevented hyperelevated fecal steroid metabolites and normalized CL progesterone capacity, but only when combined with low eCG/hCG. However, priming failed to prevent ancillary CL formation, smaller CL mass, or abnormal luteal cell density, which were common to all eCG/hCG-treated cats. Thus, the domestic cat exposed to eCG/hCG produces CL with structural and functional aberrations. These anomalies can be partially mitigated by progestin priming, possibly due to a protective effect of progestin associated with enhanced ovarian sensitivity to gonadotropins. PMID:23100619

Human LH and hCG stimulate differently the early signalling pathways but result in equal testosterone synthesis in mouse Leydig cells in vitro.

PubMed

Riccetti, Laura; De Pascali, Francesco; Gilioli, Lisa; Potì, Francesco; Giva, Lavinia Beatrice; Marino, Marco; Tagliavini, Simonetta; Trenti, Tommaso; Fanelli, Flaminia; Mezzullo, Marco; Pagotto, Uberto; Simoni, Manuela; Casarini, Livio

2017-01-05

Human luteinizing hormone (LH) and chorionic gonadotropin (hCG) are glycoprotein hormones regulating development and reproductive functions by acting on the same receptor (LHCGR). We compared the LH and hCG activity in gonadal cells from male mouse in vitro, i.e. primary Leydig cells, which is a common tool used for gonadotropin bioassay. Murine Leydig cells are naturally expressing the murine LH receptor (mLhr), which binds human LH/hCG. Cultured Leydig cells were treated by increasing doses of recombinant LH and hCG, and cell signaling, gene expression and steroid synthesis were evaluated. We found that hCG is about 10-fold more potent than LH in cAMP recruitment, and slightly but significantly more potent on cAMP-dependent Erk1/2 phosphorylation. However, no significant differences occur between LH and hCG treatments, measured as activation of downstream signals, such as Creb phosphorylation, Stard1 gene expression and testosterone synthesis. These data demonstrate that the responses to human LH/hCG are only quantitatively and not qualitatively different in murine cells, at least in terms of cAMP and Erk1/2 activation, and equal in activating downstream steroidogenic events. This is at odds with what we previously described in human primary granulosa cells, where LHCGR mediates a different pattern of signaling cascades, depending on the natural ligand. This finding is relevant for gonadotropin quantification used in the official pharmacopoeia, which are based on murine, in vivo bioassay and rely on the evaluation of long-term, testosterone-dependent effects mediated by rodent receptor.

Gestational Trophoblastic Disease - Clinicopathological Study at Tertiary Care Hospital

PubMed Central

Aher, Vidhya; Gadhiya, Suchi; Jagtap, Swati Sunil

2017-01-01

Introduction Gestational Trophoblastic Disease (GTD) is a term used for a group of pregnancy-related tumours. These consist of various tumours and tumour like lesions characterized by proliferation of trophoblastic tissue. Amongst GTD, hydatidiform moles are the most common form. These lesions sometimes may develop into invasive moles, or, in rare cases, into choriocarcinoma. Aim To study the clinicopathologic characteristics and prevalence of different forms of gestational trophoblastic disease in a tertiary care hospital. Materials and Methods The present study was descriptive, observational, analytical type done in Department of Pathology at tertiary care hospital from May 2012 to April 2016. All cases clinically suspected of GTD were included and confirmation was done by histopathological study on H&E stained slides. The cases of GTD were classified according to WHO classification. Detailed histomorphological features and beta human Chorionic Gonadotropin (hCG) levels were correlated. Results During study period, 18345 deliveries were reported; out of which 77 cases were diagnosed as GTD. Almost 97.40% cases were of hydatidiform moles, 1.30% cases of choriocarcinoma and 1.30% cases of Placental Site Trophoblastic Tumour (PSTT). Among the cases of hydatidiform mole 57.34% were complete mole and 41.33% cases were of partial mole. The common clinical presentation was per vaginal bleeding and amenorrhea. The blood group A was most commonly observed in patient (49.35%). In majority of cases beta hCG levels were between 50,000 to 100000 mIU/ml. The correlation between beta hCG level and GTD were done. Conclusion Pregnant females clinically presenting with abnormal vaginal bleeding must be evaluated for GTD. Histopathological examination is helpful for confirmatory diagnosis. Follow up of such patients is essential for early detection of malignant trophoblastic tumours. PMID:28969138

Dedifferentiated Liposarcoma With Rhabdomyosarcomatous Differentiation Producing HCG: A Case Report of a Diagnostic Pitfall.

PubMed

Maryamchik, Elena; Lyapichev, Kirill A; Halliday, Bradford; Rosenberg, Andrew E

2018-03-01

We report a first case of paraneoplastic human chorionic gonadotropin (HCG) production in a dedifferentiated liposarcoma with rhabdosarcomatous differentiation in an 83-year-old man with a retroperitoneal mass, unilateral scrotal enlargement, and a serum HCG level of 843 IU/L. Core biopsy of the retroperitoneal mass revealed rhabdomyosarcoma. Orchiectomy revealed a paratesticular dedifferentiated liposarcoma with rhabdosarcomatous differentiation. Fluorescence in situ hybridization analysis performed on both the retroperitoneal and paratesticular masses revealed amplification of MDM2. The retroperitoneal tumor was interpreted as metastatic dedifferentiated liposarcoma with the dedifferentiated component represented by rhabdomyosarcoma. HCG production is a common feature of testicular germ cell tumors, less common in carcinomas, and extremely rare in sarcomas. Accordingly, sarcomas secreting HCG are a potential diagnostic pitfall, and raise the differential diagnosis of germ cell tumors and a variety of carcinomas. HCG production by carcinomas is a known poor prognostic finding, however the significance of its production in sarcomas is unknown.

Antibody Recognition of a Human Chorionic Gonadotropin Epitope (hCGβ66–80) Depends on Local Structure Retained in the Free Peptide*

PubMed Central

Gregor, Craig R.; Cerasoli, Eleonora; Schouten, James; Ravi, Jascindra; Slootstra, Jerry; Horgan, Adrian; Martyna, Glenn J.; Ryadnov, Maxim G.; Davis, Paul; Crain, Jason

2011-01-01

Human chorionic gonadotropin (hCG) is an important biomarker in pregnancy and oncology, where it is routinely detected and quantified by specific immunoassays. Intelligent epitope selection is essential to achieving the required assay performance. We present binding affinity measurements demonstrating that a typical β3-loop-specific monoclonal antibody (8G5) is highly selective in competitive immunoassays and distinguishes between hCGβ66–80 and the closely related luteinizing hormone (LH) fragment LHβ86–100, which differ only by a single amino acid residue. A combination of optical spectroscopic measurements and atomistic computer simulations on these free peptides reveals differences in turn type stabilized by specific hydrogen bonding motifs. We propose that these structural differences are the basis for the observed selectivity in the full protein. PMID:21592960

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.

Reconstituted normal human breast in nude mice: effect of host pregnancy environment and human chorionic gonadotropin on proliferation.

PubMed

Popnikolov, N; Yang, J; Liu, A; Guzman, R; Nandi, S

2001-03-01

The proliferation of normal human breast epithelial cells in women is highest during the first trimester of pregnancy. In an attempt to analyze this hormonal environment in a model system, the effect of host mouse pregnancy and the administration of human chorionic gonadotropin (hCG) were assessed in normal human breast epithelial cells transplanted into athymic nude mice. Human breast epithelial cells, dissociated from reduction mammoplasty specimens and embedded inside the extracellular matrices comprised of collagen gel and Matrigel, were transplanted into nude mice. Proliferation was measured in vivo by BrdU labeling followed by immunostaining of sections from recovered gels in response to an altered hormonal environment of the host animal. The host animal was mated to undergo pregnancy and the complex hormonal environment of the host animal pregnancy stimulated growth of transplanted human cells. This effect increased with progression of pregnancy and reached the maximum during late pregnancy prior to parturition. In order to determine whether additional stimulation could be achieved, the transplanted human cells were exposed to a second cycle of host mouse pregnancy by immediately mating the animal after parturition. This additional exposure of host mouse pregnancy did not result in further increase of proliferation. The effect of hCG administration on transplanted human cells was also tested, since hCG level is highest during the first trimester of human pregnancy and coincides with the maximal breast cell proliferation. Administration of hCG alone stimulated proliferation of human cells in a dose-dependent manner, and could further enhance stimulation achieved with estrogen. The host mouse mammary gland also responded to hCG treatment resulting in increased branching and lobulo-alveolar development. However, the hCG effect on both human and mouse cells was dependent on intact ovary since the stimulation did not occur in ovariectomized animals. Although hCG receptor transcripts were detected in human breast epithelial cells, raising the possibility of a direct mitogenic action, the hCG effect observed in this study may have been mediated via the ovary by increased secretion of ovarian steroids. In summary, using our in vivo nude mice system, the proliferation of normal human breast epithelial cells could be stimulated by host mouse pregnancy and by administration of hCG.

Human chorionic gonadotropin triggers angiogenesis via the modulation of endometrial stromal cell responsiveness to interleukin 1: a new possible mechanism underlying embryo implantation.

PubMed

Bourdiec, Amélie; Shao, Rong; Rao, C V; Akoum, Ali

2012-09-01

Deep functional changes occurring within the endometrium during implantation are orchestrated by embryonic and maternal signals. Human chorionic gonadotropin (hCG), a major embryonic signal, plays a critical role in the initiation and maintenance of pregnancy. Interleukin (IL) 1, one of the earliest embryonic signals, appears to exert a direct impact on the receptive endometrium and to induce major molecular changes that are essential for embryo implantation. Herein we investigate whether hCG can modulate endometrial stromal cell (ESC) receptivity to IL1 during the implantation window and assess the impact on angiogenesis in vitro. Primary cultures of ESCs from normal fertile women during the implantation window were treated for 24 h with different concentrations of hCG (0-100 ng/ml) and stimulated for 24 h with IL1B (0-0.1 ng/ml). IL1 receptors (IL1Rs), IL1R antagonist (IL1RA), and monocyte chemotactic protein (MCP) 1 were analyzed by real-time PCR, ELISA, and Western blotting. The angiogenic activity in vitro was studied using human microvascular endothelial cell line, scratch wound assay, and cell proliferation via BrdU incorporation into DNA. Human CG induced a dose-dependent imbalance in ESC receptivity to IL1 by significantly upregulating the functional signaling IL1R1 and concomitantly downregulating the decoy inhibitory IL1R2 and IL1RA upon subsequent exposure to IL1B. Prior exposure to hCG amplified MCP1 secretion by ESCs in response to IL1B and triggered the release of angiogenic activity in vitro in which MCP1 appeared to play a significant role. Overexpression of IL1R2 using cell transfection inhibited IL1 and hCG/IL1B-mediated MCP1 secretion. These findings suggest that hCG coordinates embryonic signal interaction with the maternal endometrium, and point to a new possible pathway by which it may promote embryonic growth.

Prevention of endometrial apoptosis: randomized prospective comparison of human chorionic gonadotropin versus progesterone treatment in the luteal phase.

PubMed

Lovely, Laurie P; Fazleabas, Asgerally T; Fritz, Marc A; McAdams, Devin G; Lessey, Bruce A

2005-04-01

To study control of apoptosis in human endometrium, we examined late luteal-phase endometrial biopsies obtained in the late luteal phase for evidence of apoptosis and compared the effects of exogenous human chorionic gonadotropin (hCG) and progesterone on this process. Using a controlled, prospective, and randomized study design, 12 healthy, fertile, reproductive-age women (ages 20-34 yr) with regular menstrual cycles (range, 26-32 d) were recruited. Each underwent an endometrial biopsy 12 d after a urinary LH surge in a control and treatment cycle. After biopsy in a natural cycle, subjects were randomized to receive luteal doses of either 200 mg intravaginal progesterone (d 18-27) or a single im injection of 10,000 IU of hCG (d 19) followed by repeat endometrial biopsy and collection of serum on d 26. Apoptosis was assessed by DNA laddering, localizing apoptotic bodies using immunofluorescent labeling of DNA fragments (the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method), and immunohistochemical assessment of apoptosis markers bcl-2, bcl-x, and bax. Serum progesterone levels were compared between treatment groups. Evidence of apoptosis in control cycles was significantly reduced in endometrium after both luteal-phase treatments. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling results demonstrated significantly less apoptosis in the hCG treatment group compared with controls. Immunostaining for bcl-2 was higher in hCG- and progesterone-treated cycles, whereas bax expression was decreased and bcl-x immunostaining was not different between treatments. Serum progesterone levels were highest in the hCG-treated group, although statistical significance was not reached (P = 0.08). These results demonstrate that signs of apoptosis, already apparent by d 26 of the menstrual cycle can be reduced with either hCG or progesterone treatment. The clinical utility of these findings includes a rational use of luteal-phase support for treatment of women with infertility and/or recurrent pregnancy loss.

Induction of ovulation with subcutaneous pulsatile gonadotropin-releasing hormone: correlation with body weight and other parameters.

PubMed

Thomas, A K; Mander, J; Hale, J; Walstab, J; Forrest, M S

1989-05-01

We treated 21 anovulatory infertile patients with subcutaneous pulsatile gonadotropin-releasing hormone (GnRH) administered via a syringe pump. Response to treatment was assessed by urinary estrogen excretion and ultrasound measurement of follicular growth. Ten patients ovulated and 8 subsequently conceived, for a total of 10 pregnancies. Human chorionic gonadotropin (hCG) was not administered routinely, but two patients required hCG to induce follicular rupture. The majority of the patients who conceived had a body mass index (BMI) of less than 21 and a luteinizing hormone (LH)/follicle-stimulating hormone ratio of less than 1. Conversely, those patients with either elevated BMI or LH or both generally failed to respond satisfactorily to this treatment. It is suggested that pulsatile GnRH is most likely to succeed in inducing ovulation if the BMI is less than 21 and the LH is normal, but is unlikely to be successful if there is both an elevated LH and a BMI of greater than 25. Between these two extremes, the response is variable and a therapeutic trial may be appropriate.

Lunar synchronization of testicular development and steroidogenesis in rabbitfish.

PubMed

Rahman, M S; Takemura, A; Takano, K

2001-06-01

Lunar synchronization of testicular development in the golden rabbitfish, Siganus guttatus, was assessed by measuring changes in sperm motility and conditions in the seminal plasma, and by in vitro production of steroid hormones in testicular fragments and sperm preparations. The duration and percentage of sperm motility was low 1 week before spawning (the new moon), but increased significantly on the day of spawning (the first lunar quarter). During the first lunar quarter, the osmolality decreased, but Ca(2+) concentration increased in the seminal plasma. These results suggest that spermiation occurs rapidly towards the specific lunar phase. Testicular fragments and sperm preparations were incubated with human chorionic gonadotropin (hCG) and two precursor steroid hormones, 17alpha-hydroxyprogesterone (17alpha-OHP) and testosterone (T), during the two lunar phases. The production of 11-ketotestosterone (11-KT) increased significantly when the testicular fragments were incubated with hCG at the first lunar quarter, while incubation of sperm preparations with 17alpha-OHP during the same moon phase resulted in a significant increase in 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP) production in the medium. These results suggest that 11-KT is produced in the somatic cells of the testis under the influence of gonadotropin, and that sperm can convert 17alpha-OHP to DHP. Additionally, steroidogenic activity was considered to increase toward the specific lunar phase. The synchronous increase in testicular activity supports the hypothesis that lunar periodicity is a major factor for the testicular development of S. guttatus.

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.

Complication of cesarean section: pregnancy on the cicatrix of a previous cesarean section.

PubMed

Wang, Weimin; Long, Wenqing; Yu, Qunhuan

2002-02-01

To probe into the clinical manifestation, diagnosis, as well as treatment of pregnancy on the cicatrix of a previous cesarean section at the uterine isthmus in the first trimester. Analysis of 14 patients with pregnancy on the cicatrix of a previous cesarean section at the uterine isthmus in the first trimester was made after conservative treatment by drugs from January 1996 to December 1999. The 14 patients with a pregnancy on the cicatrix of a previous cesarean section at the uterine isthmus in the first trimester were painless, had slight vaginal bleeding, and concurrently had increased serum beta-subunit human chorionic gonadotropin (beta-HCG). Doppler ultrasonic examination revealed an obvious enlargement of the previous cesarean section cicatrix in the uterine isthmus, and found a gestational sac or mixed mass attached to the cicatrice, with a very thin myometrium between the gestational sac and bladder walls. Among the 14 patients, 12 patients had crystalline trichosanthes injected into the cervix, mifepristone taken orally, or methotrexate in the form of intramuscular injection. Following this procedure, their serum beta-HCG dropped to normal. The other 2 patients had a total hysterectomy. Pregnancy on the cicatrix of a previous cesarean section at the uterine isthmus in the first trimester is a complication of cesarean section. Early diagnosis and effective conservative treatment by drugs are instrumental in decreasing the potential occurrence of uterine rupture, which is also conducive to preserving the patient's future fertility.

SDS-PAGE Electrophoretic Property of Human Chorionic Gonadotropin (hCG) and its β-subunit

PubMed Central

2005-01-01

The microheterogeneity property of hCG with regards to its sialic acid contents resulted in variable mobility of the glycoprotein in SDS-PAGE. The intact hCG molecule is composed of two dissimilar subunits, namely α- and β-subunits. The identification of hCG bands in SDS-PAGE was accomplished by the immunoblotting experiment, whereby the antibody directed toward the specific region of β-subunit of hCG was used. The data shows that the different mobility of intact hCG was attributed to the different degree of desialylation of the glycoprotein. Nevertheless, unlike the intact hCG, the mobility of its β-subunit was not affected by its variety sialic acid content. This characteristic of β-hCG is beneficial when semi-quantification of total hCG is required. Quantification of hCG using the HPLC-reversed phase C18 analytical column is not possible as the glycoprotein was eluted in multiple fractions at different retention times. The identification of denatured hCG (HPLC eluted fractions) was carried out by immunoblotting experiment whilst immunoassay technique failed to detect its presence in any fraction. PMID:16094462

Ultrastructure of the human preovulatory oocyte.

PubMed

Szöllösi, D; Mandelbaum, J; Plachot, M; Salat-Baroux, J; Cohen, J

1986-08-01

The ultrastructure of preovulatory human oocyte-cumulus complexes was described after inducing maturation by clomiphene, human menopausal gonadotropin (hMG), human chorionic gonadotropin (hCG) treatment. The majority of the oocytes was at metaphase II of meiosis, with a radially orientated spindle. The oocyte surface was covered by a multitude of microvilli. Cortical granules were nonuniformly distributed along the cortex. A cytoplasmic polarization was observed. The cytoplasmic organelles were in general uniformly dispersed, with the exception of a narrow segment within which cytoplasmic membranes and mitochondria formed clusters. The spindle was usually found at the borderline between the two regions of the cytoplasm. The functional significance of this polarization is not yet known.

Serum human chorionic gonadotropin levels on the day before oocyte retrieval do not correlate with oocyte maturity.

PubMed

Levy, Gary; Hill, Micah J; Ramirez, Christina; Plowden, Torrie; Pilgrim, Justin; Howard, Robin S; Segars, James H; Csokmay, John

2013-05-01

To evaluate the correlation of preretrieval quantitative serum hCG level with oocyte maturity. Retrospective cohort study. Military assisted reproductive technology (ART) program. Fresh autologous ART cycles. Serum hCG level the day before oocyte retrieval. Linear regression was used to correlate serum hCG levels and oocyte maturity rates. Normal oocyte maturity was defined as ≥75% and the Wilcoxon rank sum test was used to compare serum hCG levels in patients with normal and low oocyte maturity. Threshold analysis was performed to determine hCG levels that could predict oocyte maturity. A total of 468 ART cycles were analyzed. Serum hCG level was not correlated with hCG dose; however, it was negatively correlated with body mass index (BMI). Serum hCG levels did not differ between patients with oocyte maturity of <75% and ≥75%. Serum hCG levels did not correlate with oocyte maturity rates. Receiver operator characteristic and less than efficiency curves failed to demonstrate thresholds at which hCG could predict oocyte maturity. Serum hCG levels were not correlated with oocyte maturity. Although a positive hCG was reassuring that mature oocytes would be retrieved for most patients, the specific value was not helpful. Copyright © 2013. Published by Elsevier Inc.

Predictive value of some hematological parameters for non-invasive and invasive mole pregnancies.

PubMed

Abide Yayla, Cigdem; Özkaya, Enis; Yenidede, Ilter; Eser, Ahmet; Ergen, Evrim Bostancı; Tayyar, Ahter Tanay; Şentürk, Mehmet Baki; Karateke, Ates

2018-02-01

The aim of this study was to discriminate mole pregnancies and invasive forms among cases with first trimester vaginal bleeding by the utilization of some complete blood count parameters conjunct to sonographic findings and beta human chorionic gonadotropin concentration. Consecutive 257 cases with histopathologically confirmed mole pregnancies and 199 women without mole pregnancy presented with first trimester vaginal bleeding who admitted to Zeynep Kamil Women and Children's Health Training Hospital between January 2012 and January 2016 were included in this cross-sectional study. The serum beta HCG level at presentation, and beta hCG levels at 1st, 2nd and 3rd weeks of postevacuation with some parameters of complete blood count were utilized to discriminate cases with molar pregnancy and cases with invasive mole among first trimester pregnants presented with vaginal bleeding and abnormal sonographic findings. Levels of beta hCG at baseline (AUC = 0.700, p < 0.05) and 1st (AUC = 0.704, p < 0.05), 2nd (AUC = 0.870, p < 0.001) and 3rd (AUC = 0.916, p < 0.001) weeks of postevacuation period were significant predictors for the cases with persistent disease. While area under curve for mean platelet volume is 0.715, it means that mean platelet volume has 21.5% additional diagnostic value for predicting persistency in molar patients. For 8.55 cut-off point for mean platelet volume, sensitivity is 84.6% and specificity is 51.6%. Area under curve for platelet/lymphocyte ratio is 0.683 means that platelet/lymphocyte ratio has additional 18.3% diagnostic value. For 102.25 cut-off point sensitivity is 86.6% and specificity is 46.2. Simple, widely available complete blood count parameters may be used as an adjunct to other risk factors to diagnose molar pregnancies and predict postevacuation trophoblastic disease.

Demonstration of postovulatory sphincter action by the isthmus of the rabbit oviduct.

PubMed

Blair, W D; Beck, L R

1976-04-01

Doughnut-shaped, carbon-impregnated rubber microtransducers calibrated to measure changes in diameter are used to demonstrate the occurrence of a sphincter action in the isthmus of the rabbit oviduct following human chorionic gonadotropin (HCG)-induced ovulation. The postovulatory constricture of the isthmus is temporal and coincides with the period when ova are retained in the oviduct. The mean change in diameter of transducers positioned within the lumen of the isthmus in rabbits treated with HCG are significantly different from mean changes observed in nontreated control rabbits when tested at 8-hour intervals over a 104-hour period. The difference is due to a statistically significant decrease in transducer diameter which occurs between 16 and 56 hours post-HCG injection. Treatment with exogenous estrogen in combination with HCG enhances both the magnitude and duration of this constricture. Significant differences occur between 8 and 104 hours. Pretreatment with progesterone prior to HCG-induced ovulation completely blocks the constricture of the isthmus. Both oviducts exhibit identical responses following HCG-induced ovulation. Sphincter action is not confirmed to a small localized segment of the isthmus but occurs over a wide area.

Absence of luteal phase defect and spontaneous pregnancy in IVF patients despite GnRH-agonist trigger and "freeze all policy" without luteal phase support: a report of four cases.

PubMed

Gurbuz, Ali Sami; Deveer, Ruya; Ozcimen, Necati; Ozcimen, Emel Ebru; Lawrenz, Barbara; Banker, Manish; Garcia-Velasco, Juan Antonio; Fatemi, Human Mousavi

2016-01-01

Human chorionic gonadotropin (hCG) is commonly used for final oocyte maturation in "in vitro fertilization" (IVF)-treatment cycles, however, the main important risk is development of severe ovarian hyperstimulation syndrome (OHSS). OHSS can almost be avoided by using gonadotrophin-releasing-hormone agonist for final oocyte maturation in an antagonist protocol. However, primarily this approach lead to a very poor reproductive outcome, despite the use of a standard luteal phase support. The reason seems to be severe luteolysis. Obviously, luteolysis post-gonadotropin-releasing-hormone-agonist (post-GnRH-a) trigger is individual specific, and not all patients will develop a complete luteolysis, as expected previously. Luteolysis can been reverted by the administration of hCG. Unprotected intercourse around the time of ovulation induction and oocyte retrieval can lead to a spontaneous conception in IVF treatment and, endogenous hCG, produced by the trophoblast, will rescue the corpora lutea. Therefore, one should not rely on complete luteolysis after GnRH-a triggering and, especially patients for egg donation and pre-implantation-genetic diagnosis for single gene disorder, have to be counselled to avoid unprotected intercourse.

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.

Effect of rejuvenation hormones on spermatogenesis.

PubMed

Moss, Jared L; Crosnoe, Lindsey E; Kim, Edward D

2013-06-01

To review the current literature for the effect of hormones used in rejuvenation clinics on the maintenance of spermatogenesis. Review of published literature. Not applicable. Men who have undergone exogenous testosterone (T) and/or anabolic androgenic steroid (AAS) therapies. None. Semen analysis, pregnancy outcomes, and time to recovery of spermatogenesis. Exogenous testosterone and anabolic androgenic steroids suppress intratesticular testosterone production, which may lead to azoospermia or severe oligozoospermia. Therapies that protect spermatogenesis involve human chorionic gonadotropin (hCG) therapy and selective estrogen receptor modulators (SERMs). The studies examining the effect of human growth hormone (HGH) on infertile men are uncontrolled and unconvincing, but they do not appear to negatively impact spermatogenesis. At present, routine use of aromatase inhibitors is not recommended based on a lack of long-term data. The use of hormones for rejuvenation is increasing with the aging of the Baby Boomer population. Men desiring children at a later age may be unaware of the side-effect profile of hormones used at rejuvenation centers. Testosterone and anabolic androgenic steroids have well-established detrimental effects on spermatogenesis, but recovery may be possible with cessation. Clomiphene citrate, human growth hormone (HGH)/insulin-like growth factor-1 (IGF-1), human chorionic gonadotropin (hCG), and aromatase inhibitors do not appear to have significant negative effects on sperm production, but quality data are lacking. Copyright © 2013 American Society for Reproductive Medicine. 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.

Partial hydatidiform mole with false-negative urine human chorionic gonadatropin test in the emergency department.

PubMed

Mundangepfupfu, Tichaendepi; Waseem, Muhammad

2014-03-01

Hydatidiform mole (molar pregnancy) is a benign tumor of placental trophoblastic cells, which release human chorionic gonadotropin (hCG). Several case reports have described complete hydatidiform moles with false-negative urine qualitative hCG tests. These negative pregnancy tests have been attributed to the hook effect. We report an unusual presentation of a partial mole and review an alternative explanation for the negative hCG test. As partial moles are usually not associated with a large proliferation of trophoblastic cells, levels of hCG are commonly < 100,000 mIU/mL. The most common presentation of a hydatidiform mole is vaginal bleeding. Hydatidiform mole is associated with a risk of malignant transformation and disseminated disease. In a pregnant patient, vaginal bleeding and abdominal pain are common presentations. Molar pregnancy is an uncommon cause of abdominal pain and vaginal bleeding that should be considered. A 47-year-old female presented to the emergency department with abdominal pain and vaginal bleeding. Urine qualitative hCG was negative and serum quantitative hCG was 1,094,950 mIU/mL. Pelvic ultrasonography showed a uterine cavity containing a soft-tissue mass with multiple cystic lesions and the hydatidiform mole was extracted with suction curettage. Tissue pathology confirmed partial hydatidiform mole. In addition to the hook effect, we present another possible explanation for the false-negative test; namely the inability of some assays to detect hCG-degradation products, which may be higher in clinical samples from patients with hydatidiform mole. This case underscores the importance of knowing the limitations of the commonly used hCG assays. Copyright © 2014 Elsevier Inc. All rights reserved.

Urinary hCG patterns during the week following implantation

PubMed Central

Nepomnaschy, PA; Weinberg, CR; Wilcox, AJ; Baird, DD

2013-01-01

BACKGROUND Human chorionic gonadotropin (hCG) is used to monitor pregnancy status. Yet the pattern of hCG excretion in the first week following implantation has not been adequately described. OBJECTIVE To describe hCG's average profile and its variability during the 7 days following estimated implantation in a population of naturally-conceived pregnancies. METHODS We measured daily hCG concentrations in first-morning urine for 142 clinical pregnancies from women with no known fertility problems. Mixed-effects regression models were used to estimate the hCG trajectory and its variability in relation to pregnancy outcomes. RESULTS HCG rose three-fold between the day of detection and the next day (95% CI = 2.7–3.4). The relative rate of rise decreased thereafter, reaching 1.6-fold (95% CI = 1.5–1.8) between days 6 and 7. HCG levels followed a log-quadratic trajectory, and the patterns of rise were unrelated to number of fetuses, risk of miscarriage, or sex of the baby. Later implantations (after 10 luteal days) produced slower rates of increase. CONCLUSIONS While mean hCG follows a log-quadratic trajectory during the first week of detectability, there is high variability across pregnancies. Later implantation may reflect characteristics of the uterus or conceptus that slow hCG production. PMID:18083748

Insulin has a biphasic effect on the ability of human chorionic gonadotropin to induce ovarian cysts in the rat.

PubMed

Bogovich, K; Clemons, J; Poretsky, L

1999-08-01

Hyperinsulinemia enhances the ability of subovulatory doses of human chorionic gonadotropin (hCG) to induce ovarian follicular cysts in the rat. To determine the relative contribution of these hormones to the development of ovarian cysts, adult female rats were treated with either (1) vehicle alone (controls), (2) a high-fat diet (HFD) to control for the effects of weight gain, (3) 1.5 to 6 IU hCG twice daily plus 6 U insulin (Ins)/d, or (4) 1.5 to 9 U Ins/d plus 3 IU hCG twice daily. On day 23 of the in vivo treatments, all groups that received at least 6 U Ins/d displayed increased body weight compared with control and HFD rats (P < or = .05). No control rats and only one HFD rat displayed ovarian cysts on this day. Plasma estrone (E1) and androstenedione (A4) were elevated in HFD rats with noncystic follicles compared with control rats (P < or = .05). Between 64% and 80% of rats on 6 U Ins/d plus twice-daily injections of 1.5 to 6 IU hCG displayed ovarian cysts on day 23. Plasma estradiol (E2) concentrations for these treatment groups were similar to those of control rats. Of the hormonally treated animals, only those that had ovarian cysts in response to twice-daily injections of 4.5 or 6 IU hCG plus 6 U Ins/d displayed elevated plasma A4 and/or testosterone compared with controls. In contrast, plasma E1 concentrations were elevated on day 23 for animals bearing ovarian cysts in response to increasing doses of hCG plus the fixed dose of 6 U Ins/d. Between 70% and 80% of rats treated twice daily with 3 IU hCG plus a daily dose of 1.5 to 6 U Ins displayed ovarian cysts on day 23. In marked contrast, only 25% of rats treated with this dose of hCG plus 9 U Ins/d developed cystic follicles. Of the plasma steroids tested, only E1 and A4 were elevated in these treatment groups compared with controls. However, these increases in plasma steroid concentrations did not correlate with the dose of insulin. We conclude from these data that, although the mechanisms remain to be elucidated, extreme hyperinsulinemia has the paradoxical ability to attenuate the induction of ovarian cysts by hCG in some animals.

Comparison of dual trigger with combination GnRH agonist and hCG versus hCG alone trigger of oocyte maturation for normal ovarian responders.

PubMed

Zhou, Xingyu; Guo, Pingping; Chen, Xin; Ye, Desheng; Liu, Yudong; Chen, Shiling

2018-06-01

To investigate whether dual triggering of oocyte maturation with a gonadotropin-releasing hormone (GnRH) agonist and standard dose of human chorionic gonadotropin (hCG) can improve clinical outcomes for normal ovarian responders in GnRH antagonist cycles. The present retrospective cohort study included women aged up to 40 years with normal ovarian response who underwent in vitro fertilization and/or intracytoplasmic sperm injection under the GnRH antagonist protocol at Nanfang Hospital, China, between January 1 and December 31, 2015. Patients were grouped by whether oocyte maturation was triggered with GnRH agonist plus 5000-10 000 IU of hCG (dual trigger) or hCG alone. The primary outcome was live delivery rate. There were 325 women included; 224 in the dual trigger group and 101 in the hCG alone group. The live delivery rate did not differ significantly between the groups (P=0.083). The mean number of retrieved oocytes was similar in the two groups (P=0.719), but the mean number of two-pronuclear embryos (P=0.004), the mean number of embryos available (P=0.001), and the mean number of high-quality embryos (P=0.011) was higher in the dual trigger group. Dual trigger of oocyte maturation was not associated with any change in the live delivery rate but was associated with improvements in the quantity and quality of embryos; it could optimize pregnancy outcomes for normal ovarian responders. © 2018 International Federation of Gynecology and Obstetrics.

Prospective assessment of early fetal loss using an immunoenzymometric screening assay for detection of urinary human chorionic gonadotropin.

PubMed

Taylor, C A; Overstreet, J W; Samuels, S J; Boyers, S P; Canfield, R E; O'Connor, J F; Hanson, F W; Lasley, B L

1992-06-01

To develop an economical, nonradiometric immunoenzymometric assay (IEMA) for the detection of urinary human chorionic gonadotropin (hCG) in studies of early fetal loss. To be effective, the IEMA must have a sensitivity equal to the standard immunoradiometric assay (IRMA) and sufficient specificity to eliminate the need for screening most nonconceptive cycles with the expensive and labor-intensive IRMA. Two different assays were used to measure hCG in daily early morning urine samples from potential conceptive cycles. Women undergoing donor artificial insemination (AI) were evaluated in a prospective study. Ninety-two women volunteers were selected on the basis of apparent normal reproductive health. Artificial insemination with nonfrozen donor semen was performed by cervical cup twice each menstrual cycle at 48-hour intervals, and daily urine samples were self-collected throughout the menstrual cycle. An IEMA was developed to detect urinary hCG using the same antibodies as in the standard IRMA; a study was designed to determine whether this nonradiometric assay could successfully detect the early fetal loss that was detected by the IRMA. Of 224 menstrual cycles analyzed by both assays, a total of six early fetal losses were detected by the IRMA. When the tentative screening rule was set to allow all six of these losses and 95% of future losses to be detected by the IEMA, an additional 34 false-positive results were detected by the IEMA. The specificity of the IEMA with this rule was calculated to be 84%. An IEMA based on the same antibodies used for the standard IRMA can serve as an efficient screening assay for the detection of early fetal loss. When the IEMA is used in this manner, nearly 80% of screened menstrual cycles can be eliminated without further testing by the IRMA.

Effect of semen extenders on frozen-thawed boar sperm characteristics and distribution in the female genital tract after deep intrauterine insemination in sows.

PubMed

Noguchi, Michiko; Yoshioka, Koji; Hikono, Hirokazu; Suzuki, Chie; Kikuchi, Kazuhiro

2015-12-01

We compared the effects of extenders of frozen-thawed semen on post-thaw sperm characteristics and the distribution of frozen-thawed spermatozoa in the female genital tract after fixed-timed deep intrauterine insemination (DIUI) in sows. Frozen semen samples were thawed and diluted in either modified Modena solution (mMS) or porcine fertilization medium (PFM) containing theophylline, adenosine and cysteine. Sperm quality, assessed in vitro based on motility using a computer-assisted sperm analyzer and the integrity of the plasma and acrosomal membranes using flow cytometry, was evaluated at 0.5, 1.5, 3 and 6h after thawing. Progressive motility and the percentage of spermatozoa with damaged acrosomal membranes in PFM were significantly better than in mMS throughout the 6h. Sows with estrus synchronized using prostaglandin F2 alpha, equine chorionic gonadotropin and human chorionic gonadotropin (hCG) were inseminated once with mMS- or PFM-diluted 5 × 10(8) frozen-thawed spermatozoa by DIUI at 34 h after the hCG injection. At 4h after DIUI, reproductive tracts were recovered from 30 sows. There were significantly fewer polymorphonuclear leukocytes (PMNs) and more spermatozoa outside PMNs in the uterine horn after PFM treatment than with mMS. When 22 sows were administered DIUI with 10 × 10(8) frozen-thawed spermatozoa at 36 h after hCG, the pregnancy rates did not differ significantly between the mMS- (36%) and PFM- (64%) treated groups. Thus, PFM enhanced progressive sperm motility but increased sperm membrane damage compared with mMS; it also suppressed the migration of PMNs into the uterine lumen. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparative effects of sub-stimulating concentrations of non-human versus human Luteinizing Hormones (LH) or chorionic gonadotropins (CG) on adenylate cyclase activation by forskolin in MLTC cells.

PubMed

Nguyen, Thi-Mong Diep; Filliatreau, Laura; Klett, Danièle; Combarnous, Yves

2018-05-15

We have compared various Luteinizing Hormone (LH) and Chorionic Gonadotropin (CG) preparations from non-human and human species in their ability to synergize with 10 µM forskolin (FSK) for cyclic AMP intracellular accumulation, in MLTC cells. LH from rat pituitary as well as various isoforms of pituitary ovine, bovine, porcine, equine and human LHs and equine and human CG were studied. In addition, recombinant human LH and CG were also compared with the natural human and non-human hormones. Sub-stimulating concentrations of all LHs and CGs (2-100 pM) were found to stimulate cyclic AMP accumulation in MLTC cells in the presence of an also non-stimulating FSK concentration (10 µM). Like rat LH, the most homologous available hormone for mouse MLTC cells, all non-human LHs and CG exhibit a strong potentiating effect on FSK response. The human, natural and recombinant hLH and hCG also do so but in addition, they were found to elicit a permissive effect on FSK stimulation. Indeed, when incubated alone with MLTC cells at non-stimulating concentrations (2-70 pM) hLH and hCG permit, after being removed, a dose-dependent cyclic AMP accumulation with 10 µM FSK. Our data show a clearcut difference between human LH and CG compared to their non-human counterparts on MLTC cells adenylate cyclase activity control. This points out the risk of using hCG as a reference ligand for LHR in studies using non-human cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Reproductive performance of lactating dairy cows after inducing ovulation using hCG in a five-day progesterone-based fixed-time AI protocol.

PubMed

Garcia-Ispierto, I; De Rensis, F; Casas, X; Caballero, F; Mur-Novales, R; López-Gatius, F

2018-02-01

This study compares the effects of inducing ovulation using human chorionic gonadotropin (hCG) or gonadotropin releasing hormone (GnRH) at the end of a 5-day progesterone(P4)-based protocol for fixed-time artificial insemination (FTAI) in lactating dairy cows on ovarian dynamics and fertility. A P4 intravaginal device (PRID) was fitted for five days and GnRH administered upon PRID insertion and a double dose (24 h apart) of prostaglandin F 2α upon PRID removal. Cows received either GnRH (GnRH group; n = 98), 1000 IU hCG (hCG-1 group; n = 97), or 3000 IU hCG (hCG-2 group; n = 104) 36 h after PRID removal and were inseminated 50-56 h after PRID removal. Based on Tukey-Kramer tests, cows in hCG-1 and hCG-2 showed a larger follicle diameter at AI than cows in GnRH (P < 0.05). HCG-2 treatment increased corpus luteum (CL) size on Day 7 post-AI compared with the GnRH and hCG-1 treatments (P < 0.05). Based on odds ratios, the likelihood of ovulation failure decreased with increasing follicle diameter at AI (P = 0.002). Cows in hCG-1 or hCG-2 that did not become pregnant were more likely to return to estrus than cows in GnRH (P < 0.01). A larger CL size post-AI was related to an increased conception rate at FTAI (P = 0.003). Cows given hCG-2 treatment showed a 1.9-fold cumulative pregnancy rate after two rounds of AI compared to cows receiving GnRH. Our results indicate that hCG treatment hCG treatment used to induce ovulation at the end of a short protocol for FTAI improves follicular/luteal dynamics compared to GnRH treatment. Of the two hCG treatments tested, better results were obtained with the 3000 IU dose. Copyright © 2017 Elsevier Inc. All rights reserved.

Heterophile antibody interference in qualitative urine/serum hCG devices: Case report.

PubMed

Patel, Khushbu K; Gronowski, Ann M

2016-06-01

This case report investigates the origin of a false positive result on a serum qualitative human chorionic gonadotropin (hCG) device. A 46-year-old woman diagnosed with chronic myeloid leukemia presented with nausea and vomiting. A qualitative serum hCG test was interpreted as positive; however, a quantitative serum hCG test was negative (<5IU/L). To further investigate this discrepancy, the sample was pretreated with heterophilic blocking reagent (HBR). Additionally, the sample was tested on other qualitative hCG devices composed of antibodies from different animal sources. Blocking reagent from an automated quantitative immunoassay was also tested for its ability to inhibit the heterophile antibody interference. The qualitative test result was negative after pretreatment with heterophilic blocking reagent. Other devices composed of antibodies from different animal sources also demonstrated mixed results with the patient's sample. Blocking reagent obtained from the automated quantitative assay inhibited the heterophile antibody interference in the patient's sample. This case demonstrates that positive serum point-of-care hCG results should be interpreted with caution and confirmed with a quantitative serum hCG immunoassay when clinical suspicion is raised. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Galactose inhibition of ovulation in mice.

PubMed

Swartz, W J; Mattison, D R

1988-03-01

Clinical evidence suggests an association between galactosemia and premature ovarian failure. In the present study, adult female mice were fed a diet consisting of 50% galactose for either 2, 4, or 6 weeks. At all times there was a decrease in the normal ovulatory response, as evidenced by a reduction in the number of corpora lutea when compared with controls. Additionally, the exposure of galactose-treated mice to a superovulatory regimen of pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) failed to induce an increased ovulatory response. Morphologic alterations, such as the increase in interstitial tissue and the appearance of lipofuscin, coupled with the failure to respond to exogenous gonadotropins, suggest that the reduced ovulatory response may be occurring at the level of the ovary. This effect, however, is reversible with cessation of galactose treatment.

Serum human chorionic gonadotropin levels on the day before oocyte retrieval do not correlate with oocyte maturity

PubMed Central

Levy, Gary; Hill, Micah J.; Ramirez, Christina; Plowden, Torrie; Pilgrim, Justin; Howard, Robin S.; Segars, James H.; Csokmay, John

2014-01-01

Objective To evaluate the correlation of preretrieval quantitative serum hCG level with oocyte maturity. Design Retrospective cohort study. Setting Military assisted reproductive technology (ART) program. Patient(s) Fresh autologous ART cycles. Intervention(s) Serum hCG level the day before oocyte retrieval. Main Outcome Measure(s) Linear regression was used to correlate serum hCG levels and oocyte maturity rates. Normal oocyte maturity was defined as ≥ 75% and the Wilcoxon rank sum test was used to compare serum hCG levels in patients with normal and low oocyte maturity. Threshold analysis was performed to determine hCG levels that could predict oocyte maturity. Result(s) A total of 468 ART cycles were analyzed. Serum hCG level was not correlated with hCG dose; however, it was negatively correlated with body mass index (BMI). Serum hCG levels did not differ between patients with oocyte maturity of <75% and ≥ 75%. Serum hCG levels did not correlate with oocyte maturity rates. Receiver operator characteristic and less than efficiency curves failed to demonstrate thresholds at which hCG could predict oocyte maturity. Conclusion(s) Serum hCG levels were not correlated with oocyte maturity. Although a positive hCG was reassuring that mature oocytes would be retrieved for most patients, the specific value was not helpful. PMID:23375205

Absence of TGF-β Receptor Activation by Highly Purified hCG Preparations.

PubMed

Koistinen, Hannu; Hautala, Laura; Koli, Katri; Stenman, Ulf-Håkan

2015-12-01

Recently, several LH/human chorionic gonadotropin (hCG) receptor-independent activities for hCG have been described, including activation of the TGF-β receptor (TGFβR) by hyperglycosylated hCG and stimulation of trophoblast invasion. Because the hCG concentrations used in these studies have been rather high, reflecting physiological hCG levels in pregnancy, even a minor contamination with growth factors, which act at very low concentrations, may be significant. Several commercial hCG preparations have been found to contain significant amounts of epidermal growth factor (EGF), which we also confirmed here. Furthermore, we found that some hCG preparations also contain significant amounts of TGF-β1. These hCG preparations were able to activate ERK1/2 in JEG-3 choriocarcinoma cells or TGFβR in mink lung epithelial cells transfected with a reporter gene for TGFβR activation. No such activation was found with highly purified hCG or its free β-subunit (hCGβ), irrespective of whether they were hyperglycosylated or not. Taken together, our results suggest that the growth factor contaminations in the hCG preparations can cause activation of TGFβR and, at least in JEG-3 cells, MAPK signaling. This highlights the importance to carefully control for potential contaminations and that highly purified hCG preparations have to be used for biological studies.

Absence of TGF-β Receptor Activation by Highly Purified hCG Preparations

PubMed Central

Hautala, Laura; Koli, Katri; Stenman, Ulf-Håkan

2015-01-01

Recently, several LH/human chorionic gonadotropin (hCG) receptor-independent activities for hCG have been described, including activation of the TGF-β receptor (TGFβR) by hyperglycosylated hCG and stimulation of trophoblast invasion. Because the hCG concentrations used in these studies have been rather high, reflecting physiological hCG levels in pregnancy, even a minor contamination with growth factors, which act at very low concentrations, may be significant. Several commercial hCG preparations have been found to contain significant amounts of epidermal growth factor (EGF), which we also confirmed here. Furthermore, we found that some hCG preparations also contain significant amounts of TGF-β1. These hCG preparations were able to activate ERK1/2 in JEG-3 choriocarcinoma cells or TGFβR in mink lung epithelial cells transfected with a reporter gene for TGFβR activation. No such activation was found with highly purified hCG or its free β-subunit (hCGβ), irrespective of whether they were hyperglycosylated or not. Taken together, our results suggest that the growth factor contaminations in the hCG preparations can cause activation of TGFβR and, at least in JEG-3 cells, MAPK signaling. This highlights the importance to carefully control for potential contaminations and that highly purified hCG preparations have to be used for biological studies. PMID:26495869

Peripheral Precocious Puberty Caused by Human Chorionic Gonadotropin Producing Pineal Gland Tumor.

PubMed

Hammadur Rahaman, S K; Khandelwal, Deepak; Khadgawat, Rajesh; Kandasamy, Devasenathipathy; Bakhshi, Sameer

2018-03-15

Pineal gland lesions usually present with central precocious puberty. A 3½-yr-old boy presented with precocious puberty. Clinically and biochemically, it was gonadotropin releasing hormone (GnRH) independent. Serum and CSF beta-hCG levels were increased. Thin section magnetic resonance imaging of brain revealed a pineal gland tumor. He received chemotherapy followed by radiotherapy and responded well. CSF beta-hCG should be measured in all cases of peripheral precocity, and if CSF beta-hCG is elevated, thin section magnetic resonance imaging of brain should be considered.

Atypical postcesarean epithelioid trophoblastic lesion with cyst formation: a case report and literature review.

PubMed

Zhou, Feng; Lin, Kaiqing; Shi, Haiyan; Qin, Jiale; Lu, Bingjian; Huang, Lili

2015-07-01

We report an extremely rare case of atypical postcesarean epithelioid trophoblastic lesion with cyst formation. A 41-year-old Chinese woman presented with lower abdominal pain and menstrual disorder. Her serum human chorionic gonadotropin (hCG) was low (0.373 IU/L), and her urine hCG was negative. Ultrasound images showed a 3.7×2.8×2.5 cm(3) mass on the surface of the lower uterine segment, and a laparoscopy indicated a cystic mass in the serosal surface of the lower uterine segment. Histology indicated a cystic lesion consisting of epithelioid trophoblastic cells with an intermediate pattern between a classical placental site nodule and an epithelioid trophoblastic tumor; thus, the term atypical postcesarean epithelioid trophoblastic lesion with cyst formation was appropriate. As in atypical placental site nodule, serum hCG monitoring after treatment is necessary. Copyright © 2015. Published by Elsevier Inc.

Binding of /sup 125/I-hCG to rainbow trout (Salmo gairdneri) testis in vitro. [Human Chorionic Gonadotropin

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

Schlaghecke, R.

1983-02-01

Homogenates of maturing rainbow trout testes show specific binding sites for /sup 125/I-labeled hCG (. /sup 125/I-labeled hCG). The binding is competitively inhibited by unlabeled hCG and by a hypophyseal extract of rainbow trout. It could be demonstrated that the tissue /sup 125/I-hCG binding specificity is restricted to the gonadal preparation. The trout testis was characterized by determining affinity and capacity from Scatchard plot analysis giving a high constant of dissociation Kd 3.65 x 10(-10)/M and a low binding capacity of 0.88 x 10(-15) M/mg tissue. The test system is markedly dependent on temperature, incubation-time, and pH. The maximum bindingmore » was found at 37 degrees during 2 hr of incubation in a buffer of pH 7.5.« less

Maternal hyperthyroidism after intrauterine insemination due to hypertrophic action of human chorionic gonadotropin: a case report.

PubMed

Bakas, P; Tzouma, C; Creatsa, M; Boutas, I; Hassiakos, D

2016-01-01

To report a rare case of maternal hyperthyroidism after intrauterine insemination due to hypertrophic action of hCG. A 36-year-old woman after successful intrauterine insemination and triplet pregnancy, developed hyperthyroidism with resistance to medical treatment. All signs of hyperthyroidism resolved and the results of thyroid function tests returned to normal without any medication after embryo meiosis. De novo maternal hyperthyroidism may develop during pregnancy as a result of pathological stimulation of the thyroid gland from the high levels of hCG hormone that can be seen in multiple pregnancies. The risk of hyperthyroidism is related to the number of fetuses. Reversibility of symptomatology can be seen after fetal reduction of multiple pregnancies.

A comparison of human chorionic gonadotropin and luteinizing hormone releasing hormone on the induction of spermiation and amplexus in the American toad (Anaxyrus americanus).

PubMed

Kouba, Andrew J; delBarco-Trillo, Javier; Vance, Carrie K; Milam, Callie; Carr, Meghan

2012-08-20

Captive breeding programs for endangered amphibian species often utilize exogenous hormones for species that are difficult to breed. The purpose of our study was to compare the efficacy of two different hormones at various concentrations on sperm production, quantity and quality over time in order to optimize assisted breeding. Male American toads (Anaxyrus americanus) were divided into three separate treatment groups, with animals in each group rotated through different concentrations of luteinizing hormone releasing hormone analog (LHRH; 0.1, 1.0, 4.0 and 32 micrograms/toad), human chorionic gonadotropin (hCG; 50, 100, 200, and 300 IU), or the control over 24 hours. We evaluated the number of males that respond by producing spermic urine, the sperm concentration, percent motility, and quality of forward progression. We also evaluated the effects of hCG and LHRH on reproductive behavior as assessed by amplexus. Data were analyzed using the Generalized Estimating Equations incorporating repeated measures over time and including the main effects of treatment and time, and the treatment by time interaction. The hormone hCG was significantly more effective at stimulating spermiation in male Anaxyrus americanus than LHRH and showed a dose-dependent response in the number of animals producing sperm. At the most effective hCG dose (300 IU), 100% of the male toads produced sperm, compared to only 35% for the best LHRH dose tested (4.0 micrograms). In addition to having a greater number of responders (P < 0.05), the 300 IU hCG treatment group had a much higher average sperm concentration (P < 0.05) than the treatment group receiving 4.0 micrograms LHRH. In contrast, these two treatments did not result in significant differences in sperm motility or quality of forward progressive motility. However, more males went into amplexus when treated with LHRH vs. hCG (90% vs. 75%) by nine hours post-administration. There is a clear dichotomy between the two hormones' physiological responses on gamete production and stimulation of amplexus. Understanding how these two hormones influence physiology and reproductive behaviors in amphibians will have direct bearing on establishing similar breeding protocols for endangered species.

LH and hCG Action on the Same Receptor Results in Quantitatively and Qualitatively Different Intracellular Signalling

PubMed Central

Casarini, Livio; Lispi, Monica; Longobardi, Salvatore; Milosa, Fabiola; La Marca, Antonio; Tagliasacchi, Daniela; Pignatti, Elisa; Simoni, Manuela

2012-01-01

Human luteinizing hormone (hLH) and chorionic gonadotropin (hCG) act on the same receptor (LHCGR) but it is not known whether they elicit the same cellular and molecular response. This study compares for the first time the activation of cell-signalling pathways and gene expression in response to hLH and hCG. Using recombinant hLH and recombinant hCG we evaluated the kinetics of cAMP production in COS-7 and hGL5 cells permanently expressing LHCGR (COS-7/LHCGR, hGL5/LHCGR), as well as cAMP, ERK1/2, AKT activation and progesterone production in primary human granulosa cells (hGLC). The expression of selected target genes was measured in the presence or absence of ERK- or AKT-pathways inhibitors. In COS-7/LHCGR cells, hCG is 5-fold more potent than hLH (cAMP ED50: 107.1±14.3 pM and 530.0±51.2 pM, respectively). hLH maximal effect was significantly faster (10 minutes by hLH; 1 hour by hCG). In hGLC continuous exposure to equipotent doses of gonadotropins up to 36 hours revealed that intracellular cAMP production is oscillating and significantly higher by hCG versus hLH. Conversely, phospho-ERK1/2 and -AKT activation was more potent and sustained by hLH versus hCG. ERK1/2 and AKT inhibition removed the inhibitory effect on NRG1 (neuregulin) expression by hLH but not by hCG; ERK1/2 inhibition significantly increased hLH- but not hCG-stimulated CYP19A1 (aromatase) expression. We conclude that: i) hCG is more potent on cAMP production, while hLH is more potent on ERK and AKT activation; ii) hGLC respond to equipotent, constant hLH or hCG stimulation with a fluctuating cAMP production and progressive progesterone secretion; and iii) the expression of hLH and hCG target genes partly involves the activation of different pathways depending on the ligand. Therefore, the LHCGR is able to differentiate the activity of hLH and hCG. PMID:23071612

Immunohistochemical and ultrastructural changes in rat fat tissue related to the local hCG injection.

PubMed

Tunç, E; Erdogan, D; Calgüner, E; Göktas, G; Elmas, Ç; Gözil, R; Bahçelioglu, M; Öktem, H

2013-11-01

Recently, it has been observed that weight loss is accelerated by human chorionic gonadotropin (hCG) hormone preparation used for hypothalamic dysfunction in obesity treatment in both sexes. hCG is also used for in vitro fertilization and in treatment of hypogonadotropic hypogonadism. Our aim was to observe the ultrastructural changes caused by local injections of hCG made for purpose of weight loss and to present them to inform those receiving such therapy. In our study, 10 obese female, 10 male obese, 10 non-obese female and 10 non-obese male rats were used. In each group, single dose of subcutaneous hCG injection has been applied to 7 rats for 5 weeks in 5 days of the week, and placebo has been applied to the remaining 3 rats. Following the injection, the tissues were evaluated morphologically, immunohistochemically and ultrastructurally. Leptin immunoreactivity was similar in all groups. When the adipose tissue samples were examined under electron microscope, they were observed to exhibit normal structure with organelles located around the nuclei and nucleoli, and no distinctive features were found among the groups. Administering hCG in addition to diet had no advantage on weight reduction in rats.

Sex differences in the MB49 syngeneic, murine model of bladder cancer

PubMed Central

White-Gilbertson, Shai; Davis, Megan; Voelkel-Johnson, Christina; Kasman, Laura M.

2016-01-01

OBJECTIVE The MB49 syngeneic, murine model of bladder cancer has been widely used for more than 35 years. In humans, bladder cancer is one third as prevalent in women as in men, with a trend toward lower prevalence in parous compared to nulliparous women. Our objective was to determine if the MB49 bladder cancer model reproduces the sex differences observed in humans, and to determine its sensitivity to testosterone and the pregnancy hormone, human chorionic gonadotropin (hCG). METHODS Male and female C57BL/6 mice were implanted with MB49 murine bladder cancer cells, and observed for tumor growth. MB49 dose responses to hCG and dihydrotestosterone were determined in vitro. RESULTS MB49 tumor growth was significantly greater in male mice than female mice. Pregnancy did not affect MB49 tumor growth in female mice. MB49 cells did not proliferate in response to hCG in vitro and the functional receptor for gonadotropins was absent. Dihydrotestosterone strongly stimulated growth of MB49 cells in vitro. CONCLUSIONS The MB49 murine model of bladder cancer reproduced some aspects of the sex differences observed in humans. Our results suggest that testosterone may stimulate MB49 cell proliferation, which may explain the more rapid MB49 tumor growth observed in male mice. PMID:26998503

Sex differences in the MB49 syngeneic, murine model of bladder cancer.

PubMed

White-Gilbertson, Shai; Davis, Megan; Voelkel-Johnson, Christina; Kasman, Laura M

The MB49 syngeneic, murine model of bladder cancer has been widely used for more than 35 years. In humans, bladder cancer is one third as prevalent in women as in men, with a trend toward lower prevalence in parous compared to nulliparous women. Our objective was to determine if the MB49 bladder cancer model reproduces the sex differences observed in humans, and to determine its sensitivity to testosterone and the pregnancy hormone, human chorionic gonadotropin (hCG). Male and female C57BL/6 mice were implanted with MB49 murine bladder cancer cells, and observed for tumor growth. MB49 dose responses to hCG and dihydrotestosterone were determined in vitro . MB49 tumor growth was significantly greater in male mice than female mice. Pregnancy did not affect MB49 tumor growth in female mice. MB49 cells did not proliferate in response to hCG in vitro and the functional receptor for gonadotropins was absent. Dihydrotestosterone strongly stimulated growth of MB49 cells in vitro . The MB49 murine model of bladder cancer reproduced some aspects of the sex differences observed in humans. Our results suggest that testosterone may stimulate MB49 cell proliferation, which may explain the more rapid MB49 tumor growth observed in male mice.

Blastocyst transfer does not improve cycle outcome as compared to D3 transfer in antagonist cycles with an elevated progesterone level on the day of hCG.

PubMed

Demirel, Cem; Aydoğdu, Serkan; Özdemir, Arzu İlknur; Keskin, Gülşah; Baştu, Ercan; Buyru, Faruk

2017-09-01

To evaluate the association between progesterone elevation on the day of human chorionic gonadotropin (hCG) administration and clinical pregnancy rates of gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles with the transfer of embryos at different developmental stages (day-3 versus day-5 ETs). This is a retrospective analysis of fresh IVF/ICSI; 194 cycles out of 2676 conducted in a single center. A total of 2676 cycles were analyzed, of which 386 had no progesterone measurements available. Two hundred eighteen cycles had progesterone elevation (p>1.5 ng/mL) giving an overall incidence of 9.5%. Twenty-four cycles were excluded from further analysis. Of the remaining 194 cycles, 151 had day-3 transfers and 43 had blastocyst transfers. There was no statistically significant difference in pregnancy and clinical pregnancy rates per transfer between the D3-ET and D5-ET groups (46% vs. 49%, and 39% vs. 35%, respectively). The results of this study suggest that blastocyst transfer does not improve cycle outcomes compared with D3 transfer in GnRH antagonist cycles with an elevated progesterone level on the day of hCG.

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.

Gestational Trophoblastic Disease Treatment

MedlinePlus

... Z List of Cancer Drugs Complementary & Alternative Medicine (CAM) Questions to Ask about Your Treatment Research Coping ... years of age. A very high level of beta human chorionic gonadotropin (β-hCG), a hormone made ...

Fertilizability of Superovulated Eggs by Estrous Stage-independent PMSG/hCG Treatment in Adult Wistar-Imamichi Rats

PubMed Central

Kon, Hiroe; Hokao, Ryoji; Shinoda, Motoo

2014-01-01

We investigated the fertilization and developmental ability of superovulated eggs obtained from adult Wistar-Imamichi (WI) rats, by using pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) treatment. Female WI rats, 11–13 weeks of age, were divided into four groups by estrous stage (metestrus [ME], diestrus [DE], proestrus [PE], or estrus [E]). PMSG (150 IU/kg) and hCG (75 IU/kg) were injected at an interval of 48 or 55 h and the female rats were mated with mature male rats. The ovulated eggs were collected 20, 24, and 27 h after hCG injection. Regardless of the estrous stage at the time of PMSG injection, the treated rats mated and ovulated similar to the untreated spontaneously ovulated rats (S group). Although the proportion of fertilized eggs in the E- and PE-treated groups was less than the S group 20 h after hCG injection, the proportion was not different among all treated and S groups 24 h after hCG injection. The proportion of fertilized eggs using in vitro fertilization and the proportion of offspring obtained from 2-cell stage embryo transfer did not differ among the treated and S groups. In comparison with PMSG/hCG-treated immature rats, mating and ovulation rate of adult rats were significantly higher. The proportion of fertilized eggs obtained from mated rats did not differ between immature and adult rats. These results demonstrate that adult WI rats are good egg donors for reproductive biotechnological studies using unfertilized or fertilized eggs. PMID:24770643

Serum oestradiol and beta-HCG measurements after day 3 or 5 embryo transfers in interpreting pregnancy outcome.

PubMed

Kumbak, Banu; Oral, Engin; Karlikaya, Guvenc; Lacin, Selman; Kahraman, Semra

2006-10-01

The aim of this study was to assess the clinical value of serum oestradiol concentration 8 days after embryo transfer (D8E2) and beta-human chorionic gonadotrophin (HCG-beta) concentration 12 days after embryo transfer (D12HCG-beta) in the prediction of pregnancy and the outcome of pregnancy following assisted reproduction, taking into account the day of transfer, which was either day 3 (D3) or day 5 (D5). The objective was to improve patient counselling by giving quantitative and reliable predictive information instead of non-specific uncertainties. A total of 2035 embryo transfer cycles performed between January 2003 and June 2005 were analysed retrospectively. Biochemical pregnancy, ectopic pregnancy and first-trimester abortions were classified as non-viable pregnancies; pregnancies beyond 12 weeks gestation were classified as ongoing pregnancies (OP). Significantly higher D8E2 and D12HCG-beta were obtained in D5 transfers compared with D3 transfers with regard to pregnancy and OP (P

Pituitary origin of persistently elevated human chorionic gonadotropin in a patient with gonadal failure.

PubMed

Merhi, Zaher; Pollack, Staci E

2013-01-01

To report a case of persistently elevated low levels of hCG to increase awareness of pituitary origin of persistently elevated hCG in patients with gonadal failure. Case report and literature review. Large university-affiliated infertility practice. A 16-year-old patient with primary amenorrhea, normal secondary sex characteristics, ovarian failure, and a 46,XY karyotype. Her past medical history was significant for focal segmental glomerulosclerosis, leading to a diagnosis of Frasier syndrome. At age 31 years, she desired pregnancy by oocyte donation and was found to have persistently elevated low levels of hCG (>35 mIU/mL). Pituitary hCG. Both serum free β-hCG and hyperglycosylated hCG were undetectable. Total serum hCG diluted appropriately was not blocked by blocking agent and was detected in the urine. Subsequent treatment with exogenous E(2), in preparation of a donor oocyte cycle, suppressed her hCG levels (down to 8 mIU/mL). These results indicated a pituitary source of the serum hCG. This report reinforces the need to consider pituitary hCG as the origin of persistently elevated hCG levels in patients with gonadal failure. Although levels of hCG <14 mIU/mL have been considered normal in postmenopausal women, our case suggests that patients with gonadal failure at younger ages might have a higher pituitary output of hCG. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Lowered reference limits for hCG improve follow-up of patients with hCG-producing tumors.

PubMed

Nome, Ragnhild V; Bjøro, Trine; Paus, Elisabeth; Bjerner, Johan; Fosså, Sophie D; Steen, Rita; Nustad, Kjell; Bolstad, Nils

2018-02-01

Human Chorionic Gonadotropin (hCG) is produced by germ cell tumors, but can also be elevated in benign conditions such as primary hypogonadism, where hCG is produced by the pituitary gland. In our experience, the reference limits for hCG (Elecsys hCG+β-assay, Roche Diagnostics), were unnecessarily high and did not reflect levels encountered in clinical practice. We wanted to establish new reference limits to increase the clinical utility of the hCG-assay. We analysed hCG in serum samples from a healthy adult population and in a cohort of testicular cancer survivors. The gonadotropins LH and FSH were measured in the cohort and in a selection of the reference population to assess gonadal function. We found low hCG levels for all men and women <45years (97.5 percentiles 0.1 and 0.2IU/L, respectively) from the healthy population (n=795) having normal FSH and LH. Due to assay limitations, we suggest a common reference limit of <0.3IU/L. For the age group ≥45, the 97.5 percentiles in the healthy population were 0.5IU/L for men and 6.0IU/L for women. In all subjects from both the reference population and the cohort (n=732), hCG levels exceeding the reference limit could be fully explained by reduced gonadal function indicated by elevated LH and FSH levels. The Elecsys hCG+β-assay should have lower reference limits than recommended by the manufacturer, with important implications for tumor follow-up. Elevated hCG is rare with intact gonadal function, both in a normal population and among survivors of testicular cancer, and should lead to further investigations when encountered in clinical practice. Copyright © 2017 Oslo University Hospital. Published by Elsevier Inc. All rights reserved.

Primary Intracranial Choriocarcinoma Located in the Suprasellar Region

PubMed Central

Li, Xiuli; Murayama, Kazuhiro; Watanabe, Ayumi; Abe, Masato; Toyama, Hiroshi

2016-01-01

A 10 year old girl was admitted to our hospital due to headache, nausea, and weight loss for about half a year. She also had visual field disorders. Suprasellar tumor was found by X-ray computed tomography, and magnetic resonance imaging showed a ring-like lobulated enhanced mass with hemorrhage and necrosis. Biopsy of this lesion showed primary intracranial choriocarcinoma on histopathological examination. The serum human chorionic gonadotropin (hCG) level was measured after the biopsy and was elevated at 71,298.2 IU/L. The patient died due to hydrocephalus caused by an increase in the size of the tumor with a larger amount of hemorrhage than the preoperative features. If young patients present with a suprasellar lobulated mass with hemorrhage, the serum hCG level should be measured before operation. PMID:27499824

[Complete Resection of Non-seminomatous Germ Cell Tumor with Plastron Approach].

PubMed

Suzuki, Jun; Oizumi, Hiroyuki; Kato, Hirohisa; Endoh, Makoto; Watarai, Hikaru; Hamada, Akira; Suzuki, Katsuyuki; Nakahashi, Kenta; Sasage, Takayuki; Sadahiro, Mitsuaki

2016-07-01

A 17-year-old man was admitted to our hospital for the abnormal chest shadow. Chest computed tomography(CT) demonstrated mediastinal tumor, measuring 13 cm in diameter with high serum level of alpha fetoprotein (AFP) and human chorionic gonadotropin (hCG). The lesions were diagnosed as mixed germ cell tumors including a non-seminomatous malignant component by CT guided needle biopsy. After 5 courses of chemotherapy, the serum AFP and hCG were decreased almost normal level but the tumor size was not changed. Because it seemed to be difficult to get sufficient operating field with standard median sternotomy and patient wanted to treat funnel chest, we selected tumor resection with plastron approach. The tumor was completely resected with a good operation field by this procedure.

Prediction of first-trimester preeclampsia: Relevance of the oxidative stress marker MDA in a combination model with PP-13, PAPP-A and beta-HCG.

PubMed

Asiltas, Burak; Surmen-Gur, Esma; Uncu, Gurkan

2018-02-27

Early diagnosis of preeclampsia (PE) is very important and various parameters, individually or in combined models, are reported useful for prediction of PE. The objective of this study is to investigate the predictive value of pregnancy-associated plasma protein-A (PAPP-A), placental protein-13 (PP-13), human Chorionic Gonadotropin (B-HCG), and oxidative stress marker malondialdehyde (MDA), individually and in combination. Maternal sera of 38 cases with PE and 122 controls were collected for first trimester screening and tested for PAPP-A and B-HCG by chemiluminescence, for PP-13 by using ELISA, and for MDA by high-performance liquid chromatography. Combined models of parameters were constituted as "MDA + PP-13", "PP-13 + PAPP-A + B-HCG" and "MDA + PP-13 + PAPP-A + B-HCG". The diagnostic performances of serum markers of preeclampsia were examined by nonparametric receiver-operator characteristics (ROC) analysis. PP-13 levels were significantly lower (p < 0.001) and MDA levels were significantly higher (p < 0.001) in PE. The area under the ROC curve (AUC) for MDA and PP-13 were greater than those for PAPP-A and B-HCG (p < 0.001). The AUCs of the combined models were significantly larger than those of individual parameters. The combined model "MDA + PP-13 + PAPP-A + B-HCG" exhibited the best predictive outcome with an AUC of 0.91 [95% CI 0.86-0.95], 97% [95% CI 86.2-99.9] sensitivity and 75% [95% CI 66.5-82.6] specificity, and was significantly different from that of "PAPP-A + PP-13 + B-HCG" model, but similar to that of "MDA + PP-13" model. Combined models consisting of various parameters of different origin, may provide better predictive outcomes, and oxidative markers should be considered in combination with other placental biomarkers in prediction of PE. Copyright © 2018 Elsevier B.V. All rights reserved.

Stages of Gestational Trophoblastic Tumors and Neoplasia

MedlinePlus

... Z List of Cancer Drugs Complementary & Alternative Medicine (CAM) Questions to Ask about Your Treatment Research Coping ... years of age. A very high level of beta human chorionic gonadotropin (β-hCG), a hormone made ...

hCG and Its Disruption by Environmental Contaminants during Human Pregnancy

PubMed Central

Paulesu, Luana; Rao, Ch.V.; Ietta, Francesca; Pietropolli, Adalgisa; Ticconi, Carlo

2018-01-01

Human chorionic gonadotropin (hCG) is a hormone of considerable importance in the establishment, promotion and maintenance of human pregnancy. It has been clearly demonstrated that hCG exerts multiple endocrine, paracrine and autocrine actions on a variety of gestational and non-gestational cells and tissues. These actions are directed to promote trophoblast invasiveness and differentiation, placental growth, angiogenesis in uterine vasculature, hormone production, modulation of the immune system at the maternal-fetal interface, inhibition of myometrial contractility as well as fetal growth and differentiation. In recent years, considerable interest has been raised towards the biological effects of environmental contaminants, particularly endocrine disrupting chemicals (EDCs). Emerging evidence suggests that prenatal exposure to selected EDCs can have a deleterious impact on the fetus and long-lasting consequences also in adult life. The results of the in vitro effects of commonly found EDCs, particularly Bisphenol A (BPA) and para-Nonylphenol (p-NP), indicate that these substances can alter hCG production and through this action could exert their fetal damage, suggesting that hCG could represent and become a potentially useful clinical biomarker of an inappropriate prenatal exposure to these substances. PMID:29558393

hCG and Its Disruption by Environmental Contaminants during Human Pregnancy.

PubMed

Paulesu, Luana; Rao, Ch V; Ietta, Francesca; Pietropolli, Adalgisa; Ticconi, Carlo

2018-03-20

Human chorionic gonadotropin (hCG) is a hormone of considerable importance in the establishment, promotion and maintenance of human pregnancy. It has been clearly demonstrated that hCG exerts multiple endocrine, paracrine and autocrine actions on a variety of gestational and non-gestational cells and tissues. These actions are directed to promote trophoblast invasiveness and differentiation, placental growth, angiogenesis in uterine vasculature, hormone production, modulation of the immune system at the maternal-fetal interface, inhibition of myometrial contractility as well as fetal growth and differentiation. In recent years, considerable interest has been raised towards the biological effects of environmental contaminants, particularly endocrine disrupting chemicals (EDCs). Emerging evidence suggests that prenatal exposure to selected EDCs can have a deleterious impact on the fetus and long-lasting consequences also in adult life. The results of the in vitro effects of commonly found EDCs, particularly Bisphenol A (BPA) and para -Nonylphenol ( p -NP), indicate that these substances can alter hCG production and through this action could exert their fetal damage, suggesting that hCG could represent and become a potentially useful clinical biomarker of an inappropriate prenatal exposure to these substances.

Response to luteinizing releasing hormone, thyrotrophic releasing hormone, and human chorionic gonadotropin administration in healthy men at different risks for prostatic cancer and in prostatic cancer patients.

PubMed

Hill, P; Wynder, E L; Garbaczewski, L; Garnes, H; Walker, A R

1982-05-01

A comparative study of the pituitary and testicular response to luteinizing releasing hormone (LHRH), thyrotrophic releasing hormone (TRH), and human chorionic gonadotrophin (HCG) administration was carried out in (a) low-risk young South African black men and high-risk North American black men for prostatic cancer and (b) healthy elderly South African men and South African black men with prostatic cancer. A comparable HCG response occurred in young South African and North American black men, while a greater release of prolactin, but a lesser release of luteinizing hormone in response to LHRH:TRH occurred in South African black men. The response to HCG was comparable in elderly and young South African black men, although the prolactin release in response to TRH was greater in elderly men. A more prolonged release of luteinizing hormone was evident in men with prostatic cancer. Higher estradiol and estrone but lower androstenedione levels occurred in men with prostatic cancer. Data suggest that, in the elderly South African black men with prostatic cancer, estrogen metabolism is modified and that either the estrogen level or the higher estrogen:androgen levels modify the pituitary response to LHRH:TRH. A Western diet enhanced the changes in hormone profiles evident in black South African men with prostatic cancer.

Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience.

PubMed

Andersen, C Yding; Fischer, R; Giorgione, V; Kelsey, Thomas W

2016-10-01

For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential advances and disadvantages. Based on the pharmacokinetic characteristics of hCG, the mathematical modelling of the concentration profiles of hCG during the luteal phase has been evaluated in connection with several different approaches for hCG administration as LPS. It is suggested that the currently employed LPS provided in connection with the GnRHa trigger (i.e. 1.500 IU) is too strong, and that daily micro-dose hCG administration is likely to provide an optimised LPS with the current available drugs. Initial clinical results with the micro-dose hCG approach are presented.

Distinct responses of human granulosa lutein cells after hCG or LH stimulation in a spheroidal cell culture system.

PubMed

Becker, Julia; Walz, Andrea; Daube, Stefanie; Keck, Christoph; Pietrowski, Detlef

2007-10-01

The growth and development of the corpus luteum (CL) is regulated by gonadotropic hormones. It is formed by granulosa cells (GCs), theca cells, and endothelial cells, and is the primary source of circulating progesterone. During early pregnancy only human chorionic gonadotropin (hCG) but not luteinizing hormone (LH) extends the life span of the CL, although hCG and LH interact with the same receptor and have similar actions on the CL. In this study a recently by our group established spheroidal GC culture assay served as a model of CL development on which we compared the actions of the gonadotropic hormones LH and hCG. To find out which signal pathways take part in the hormonal regulation of GC we stimulated GC-spheroids with modulators of protein kinases A and C dependent signaling cascades and determined their impact on sprout forming activity in GC. Our results indicate that PKA-dependent signaling pathways play a major role in mediating the hormonal-induced signaling cascades leading to sprouting in GC. Furthermore, this study strongly indicates that the different effects of hCG and LH in the maintenance of the CL may be reasoned in different signal transduction pathways triggered by hCG or LH. (c) 2007 Wiley-Liss, Inc.

Effect of Antiprogesterone RU486 on VEGF Expression and Blood Vessel Remodeling on Ovarian Follicles before Ovulation

PubMed Central

Berardinelli, Paolo; Russo, Valentina; Bernabò, Nicola; Di Giacinto, Oriana; Mattioli, Mauro; Barboni, Barbara

2014-01-01

Background The success of ovarian follicle growth and ovulation is strictly related to the development of an adequate blood vessel network required to sustain the proliferative and endocrine functions of the follicular cells. Even if the Vascular Endothelial Growth Factor (VEGF) drives angiogenesis before ovulation, the local role exerted by Progesterone (P4) remains to be clarified, in particular when its concentration rapidly increases before ovulation. Aim This in vivo study was designed to clarify the effect promoted by a P4 receptor antagonist, RU486, on VEGF expression and follicular angiogenesis before ovulation, in particular, during the transition from pre to periovulatory follicles induced by human Chorionic Gonadotropins (hCG) administration. Material and Methods Preovulatory follicle growth and ovulation were pharmacologically induced in prepubertal gilts by combining equine Chorionic Gonadotropins (eCG) and hCG used in the presence or absence of RU486. The effects on VEGF expression were analyzed using biochemical and immunohistochemical studies, either on granulosa or on theca layers of follicles isolated few hours before ovulation. This angiogenic factor was also correlated to follicular morphology and to blood vessels architecture. Results and Conclusions VEGF production, blood vessel network and follicle remodeling were impaired by RU486 treatment, even if the cause-effect correlation remains to be clarified. The P4 antagonist strongly down-regulated theca VEGF expression, thus, preventing most of the angiogenic follicle response induced by hCG. RU486-treated follicles displayed a reduced vascular area, a lower rate of endothelial cell proliferation and a reduced recruitment of perivascular mural cells. These data provide important insights on the biological role of RU486 and, indirectly, on steroid hormones during periovulatory follicular phase. In addition, an in vivo model is proposed to evaluate how periovulatory follicular angiogenesis may affect the functionality of the corpus luteum (CL) and the success of pregnancy. PMID:24756033

[Preparation of polyacrylamide gel electrophoresis for human chorionic gonadotropin chimeric peptide 12 expressed in E. coli].

PubMed

Zou, Yong-Shui; Xu, Wan-Xiang; He, Yuan; Sun, Zhi-Da; Xue, Xiao-Lin

2002-09-01

In recent years, development of chimeric peptide (CP) immunogens is a trend in the vaccinological field. The CPs contain a B cell epitope(s) of target antigen and a promiscuous self - or foreign- T cell epitope(s). However, such constructed CPs were all expressed in prokaryotic or eukaryotic systems at lower levels. To purify the human chorionic gonadotropin (hCG) CP12 expressed in E. coli at the level of about 1% of the total cell proteins, an improved method of preparative gel polyacrylamide gel electrophoresis (PAGE) was developed. The important improvement to routine preparative PAGE involves: (1) running reversed electrophoresis by rearranging the gel- carrying plate when the bromophenol blue band arrived at 1-1.5 centimeter from the bottom of the gel; (2) making a collecting trough between the gel and a dialytic membrane that was used to isolate the upper tank buffer. About 8 fractions were collected at regular intervals of 15 minutes after bromophenol blue running out of gel. And then 0.2 ml was taken from each fraction and the protein was precipitated by sequentially adding trichloroacetic acid and acetone. Each sample was dissolved in 20 microL sample buffer and analyzed and identified by SDS-PAGE and Western blotting. As a result, the hCG CP12 expression product with 95% relative homogeneity was harvested at a 50-100 microgram level after a single-step purification of this preparative PAGE, with respect to the sample which contained 3-4 mg of cell proteins.

HYPERGLYCOSYLATED HUMAN CHORIONIC GONADOTROPIN AS AN EARLY PREDICTOR OF PREGNANCY OUTCOMES AFTER IN VITRO FERTILIZATION

PubMed Central

Chuan, Sandy; Homer, Michael; Pandian, Raj; Conway, Deirdre; Garzo, Gabriel; Yeo, Lisa; Su, H. Irene

2014-01-01

Objective To determine if hyperglycosylated hCG (hhCG), produced by invasive trophoblasts, measured as early as 9 days after egg retrieval can predict ongoing pregnancies (OP) after in vitro fertilization and fresh embryo transfer (IVF-ET). Design Cohort Setting Academic ART center Patients Consecutive patients undergoing IVF-ET Interventions Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Outcome Ongoing pregnancy (OP) beyond 9 weeks of gestation Results OP (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. D9 hhCG levels >110 pg/mL was 96% specific for OP, yielding a positive predictive value of 95%. Compared to D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67). Diagnostic test characteristics were similar between D16 hhCG and hCG levels. Conclusions In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable. HhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. At this early assessment, hhCG is superior to traditional hCG and highly predictive of ongoing pregnancies. PMID:24355054

hCG stimulates angiogenic signals in lymphatic endothelial and circulating angiogenic cells.

PubMed

Schanz, Andrea; Lukosz, Margarete; Hess, Alexandra P; Baston-Büst, Dunja M; Krüssel, Jan S; Heiss, Christian

2015-08-01

Human chorionic gonadotropin (hCG) has long been associated with the initiation and maintenance of pregnancy, where angiogenesis plays an important role. However, the function of hCG in angiogenesis and the recruitment of vascular active cells are not fully understood. In this study, the role of hCG and its receptor in circulating angiogenic and human endothelial cells, including lymphatic, uterine microvascular, and umbilical vein endothelial cells, was examined. Immunohistochemistry and immunoblot analysis were used to detect LH/hCG receptor expression and the expression of hCG-induced angiogenic molecules. HIF-1α was determined via ELISA and downstream molecules, such as CXCL12 and CXCR4, via real-time PCR. Chemotaxis was analyzed using Boyden chambers. Our results show that the LH/hCG receptor was present in all tested cells. Furthermore, hCG was able to stimulate LH/hCG-receptor-specific migration in a dose-dependent fashion and induce key angiogenic molecules, including HIF-1α, CXCL12, and CXCR4. In conclusion, our findings underscore the importance of hCG as one of the first angiogenic molecules produced by the conceptus. hCG itself alters endothelial motility, recruitment, and expression of pro-angiogenic molecules and may therefore play an important role in vascular adaption during implantation and early placental formation. Copyright © 2015. Published by Elsevier Ireland Ltd.

Oligopeptides of Chorionic Gonadotropin β-Subunit in Induction of T Cell Differentiation into Treg and Th17.

PubMed

Zamorina, S A; Shirshev, S V

2015-11-01

The role of oligopeptides of chorionic gonadotropin β-subunit (LQGV, AQGV, and VLPALP) in induction of differentiation into T-regulatory lymphocytes (Treg) and IL-17-producing lymphocytes (Th17) was studied in an in vitro system. Chorionic gonadotropin and oligopeptides promoted CD4(+) cell differentiation into functionally active Treg (FOXP3(+)GITR(+) and FOXP3(+)CTLA-4(+)), while chorionic gonadotropin and AQGV additionally stimulated IL-10 production by these cells. In parallel, chorionic gonadotropin and oligopeptides prevented CD4(+) cell differentiation into Th17 lymphocytes (ROR-gt(+)IL-17A(+)) and suppressed IL-17A secretion. Hence, oligopeptides of chorionic gonadotropin β-subunit promoted differentiation of CD4(+) cells into Treg and, in parallel, suppress Th17 induction, thus virtually completely reproducing the effects of the hormone, which opens new vista for their use in clinical practice.

Gonadotropin-dependent oocyte maturational competence requires activation of the protein kinase A pathway and synthesis of RNA and protein in ovarian follicles of Nibe, Nibea mitsukurii (Teleostei, Sciaenidae)

USGS Publications Warehouse

Yoshizaki, G.; Shusa, M.; Takeuchi, T.; Patino, R.

2002-01-01

Luteinizing hormone- (LH)-dependent ovarian follicle maturation has been recently described in two stages for teleost fishes. The oocyte's ability to respond to the steroidal maturation-inducing hormone (MIH), also known as oocyte maturational competence (OMC), is acquired during the first stage; whereas the MIH-dependent resumption of meiosis occurs during the second stage. However, studies directly addressing OMC have been performed with a limited number of species and therefore the general relevance of the two-stage model and its mechanisms remain uncertain. In this study, we examined the hormonal regulation of OMC and its basic transduction mechanisms in ovarian follicles of the sciaenid teleost, Nibe (Nibea mitsukurii). Exposure to MIH [17,20??-dihydroxy-4-pregnen-3-one or 17,20??,21-trihydroxy-4-pregnen-3-one] stimulated germinal vesicle breakdown (index of meiotic resumption) in full-grown follicles primed with human chorionic gonadotropin (HCG, an LH-like gonadotropin) but not in those pre-cultured in plain incubation medium. The induction of OMC by HCG was mimicked by protein kinase A (PKA) activators (forskolin and dibutyryl cyclic AMP), and blocked by specific inhibitors of PKA (H89 and H8) as well as inhibitors of RNA (actinomycin D) and protein (cycloheximide) synthesis. Forskolin-induced OMC was also inhibited by actinomycin D and cycloheximide. A strong activator of protein kinase C, PMA, inhibited HCG-dependent OMC. In conclusion, OMC in Nibe ovarian follicles is gonadotropin-dependent and requires activation of the PKA pathway followed by gene transcription and translation events. These observations are consistent with the two-stage model of ovarian follicle maturation proposed for other teleosts, and suggest that Nibe can be used as new model species for mechanistic studies of ovarian follicle differentiation and maturation in fishes.

Serum Human Chorionic Gonadotropin (β- hCG) Clearance Curves in Women with Successfully Expectantly Managed Tubal Ectopic Pregnancies: A Retrospective Cohort Study

PubMed Central

Helmy, Samir; Mavrelos, Dimitrios; Sawyer, Elinor; Ben-Nagi, Jara; Koch, Marianne; Day, Andrea; Jurkovic, Davor

2015-01-01

Objective To establish clearance curves for serum β -hCG in women with successfully expectantly managed tubal ectopic pregnancies. Design Retrospective cohort study. Non- viable tubal ectopic pregnancy was diagnosed on transvaginal ultrasound. If initial serum β hCG was less than 5000 IU/L and patients were asymptomatic, expectant management was offered. Patients underwent serial β hCG measurements until serum β hCG was less than 20 IU/l, or the urine pregnancy test was negative. Setting Early Pregnancy and Gynaecology Assessment Unit, Kings College Hospital, London (December 1998 to July 2006). Patients We included 161 women with diagnosed non-viable tubal ectopic pregnancy who underwent successful expectant management. Main outcome measure Serum β hCG level. Results Mean initial serum β- hCG was 488 IU/L (41 - 4883) and median serum β hCG clearance time was 19 days (5 - 82). The average half-life of β hCG clearance was 82.5 hours (±SD 50.2) in patients with steadily declining serum β- hCG levels compared to 106.7 hours (±SD 72.0) in patients with primarily plateauing β-hCG levels in the declining phase. However, these differences were not significant (p>0.05). Conclusion We identified a median follow-up of 19 days until serum β hCG clearance in women with tubal ectopic pregnancy and successful expectant management. Although non- significant, women with initially plateauing serum β hCG showed a longer follow-up time until clearance compared to women with steadily declining β hCG levels. This information may serve as a guideline enabling clinicians to predict the length of follow-up for women with tubal ectopic pregnancy and expectant management. PMID:26135923

Thyroid Function and Premature Delivery in TPO Antibody-Negative Women: The Added Value of hCG.

PubMed

Korevaar, Tim I M; Steegers, Eric A P; Chaker, Layal; Medici, Marco; Jaddoe, Vincent W V; Visser, Theo J; de Rijke, Yolanda B; Peeters, Robin P

2017-09-01

Human chorionic gonadotropin (hCG) stimulates thyroid function during pregnancy. We recently showed that thyroid autoimmunity severely attenuated the thyroidal response to hCG stimulation and that this may underlie the higher risk of premature delivery in thyroperoxidase antibody (TPOAb)-positive women. We hypothesized that a lower thyroidal response to hCG stimulation in TPOAb-negative women is also associated with a higher risk of premature delivery and preterm premature rupture of membranes (pPROM). Thyrotropin (TSH), free thyroxine (FT4), and hCG concentrations were available in 5644 TPOAb-negative women from a prospective cohort. We tested for interaction between TSH or FT4 and hCG in linear regression models for duration of pregnancy and logistic regression models for premature delivery/pPROM. Accordingly, analyses were stratified per TSH percentile (TSH ≥ 85th percentile) and hCG per 10,000 IU/L. Women with high TSH and low hCG concentrations did not have a higher risk of premature delivery or pPROM, with protective effect estimates. In contrast, women with a high TSH concentration despite a high hCG concentration had twofold to 10-fold higher risk of premature delivery (Pdifference = 0.022) and an up to fourfold higher risk of pPROM (Pdifference = 0.079). hCG concentrations were not associated with premature delivery or pPROM. In TPOAb-negative women with high-normal TSH concentrations, only women with high hCG concentrations had a higher risk of premature delivery or pPROM. These results suggest a lower thyroidal response to hCG stimulation is also associated with premature delivery in TPOAb-negative women and that an additional measurement of hCG may improve thyroid-related risk assessments during pregnancy. Copyright © 2017 Endocrine Society

An HCG-rich microenvironment contributes to ovarian cancer cell differentiation into endothelioid cells in a three-dimensional culture system.

PubMed

Su, Min; Fan, Chao; Gao, Sainan; Shen, Aiguo; Wang, Xiaoying; Zhang, Yuquan

2015-11-01

We investigated the expression of human chorionic gonadotropin (HCG) and its effects on vasculogenic mimicry (VM) formation in ovarian cancer cells under normoxic and hypoxic conditions in three-dimensional matrices preconditioned by an endothelial-trophoblast cell co-culture system. The co-culture model was established using human umbilical vein endothelial cells (HUVECs) and HTR-8 trophoblast cells in a three-dimensional culture system. The co-cultured cells were removed with NH4OH, and ovarian cancer cells were implanted into the preconditioned matrix. VM was identified morphologically and by detecting vascular markers expressed by cancer cells. The specificity of the effects of exogenous HCG in the microenvironment was assessed by inhibition with a neutralizing anti-HCG antibody. HCG siRNA was used to knock down endogenous HCG expression in OVCAR-3 ovarian cancer cells. HTR-8 cells 'fingerprinted' HUVECs to form capillary-like tube structures in co-cultures. In the preconditioned HCG-rich microenvironment, the number of vessel-like network structures formed by HCG receptor-positive OVCAR-3 cells and the expression levels of CD31, VEGF and factor VIII were significantly increased. The preconditioned HCG-rich microenvironment significantly increased the expression of hypoxia inducible factor-1α (HIF‑1α) and VM formation in OVCAR-3 cells under hypoxic conditions. Treatment with a neutralizing anti-HCG antibody but not HCG siRNA significantly inhibited the formation of vessel-like network structures. HCG in the microenvironment contributes to OVCAR-3 differentiation into endothelioid cells in three-dimensional matrices preconditioned with an endothelial-trophoblast cell co-culture system. HCG may synergistically enhance hypoxia-induced vascular markers and HIF-1α expression. These findings would provide perspectives on new therapeutic targets for ovarian cancer.

Reference ranges and determinants of total hCG levels during pregnancy: the Generation R Study.

PubMed

Korevaar, Tim I M; Steegers, Eric A P; de Rijke, Yolanda B; Schalekamp-Timmermans, Sarah; Visser, W Edward; Hofman, Albert; Jaddoe, Vincent W V; Tiemeier, Henning; Visser, Theo J; Medici, Marco; Peeters, Robin P

2015-09-01

Human chorionic gonadotropin (hCG) is a pregnancy hormone secreted by the placental synctiotrophoblast cell layer that has been linked to fetal growth and various placental, uterine and fetal functions. In order to investigate the effects of hCG on clinical endpoints, knowledge on reference range (RR) methodology and determinants of gestational hCG levels is crucial. Moreover, a better understanding of gestational hCG physiology can improve current screening programs and future clinical management. Serum total hCG levels were determined in 8195 women participating in the Generation R Study. Gestational age specific RRs using 'ultrasound derived gestational age' (US RRs) were calculated and compared with 'last menstrual period derived gestational age' (LMP RRs) and a model-based RR. We also investigated which pregnancy characteristics were associated with hCG levels. Compared to the US RRs, the LMP RRs were lower, most notably for the median and lower limit levels. No considerable differences were found between RRs calculated in the general population or in uncomplicated pregnancies only. Maternal smoking, BMI, parity, ethnicity, fetal gender, placental weight and hyperemesis gravidarum symptoms were associated with total hCG. We provide gestational RRs for total hCG and show that total hCG values and RR cut-offs during pregnancy vary depending on pregnancy dating methodology. This is likely due to the influence of hCG on embryonic growth, suggesting that ultrasound based pregnancy dating might be less reliable in women with high/low hCG levels. Furthermore, we identify different pregnancy characteristics that influence total hCG levels considerably and should therefore be accounted for in clinical studies.

How and when human chorionic gonadotropin curves in women with an ectopic pregnancy mimic other outcomes: differences by race and ethnicity.

PubMed

Dillon, Katherine E; Sioulas, Vasileios D; Sammel, Mary D; Chung, Karine; Takacs, Peter; Shaunik, Alka; Barnhart, Kurt T

2012-10-01

To investigate the hCG profiles in a diverse patient group with ectopic pregnancy (EP) and to understand when they may mimic the curves of an intrauterine pregnancy (IUP) or spontaneous abortion (SAB). Retrospective cohort study. Three university hospitals. One hundred seventy-nine women with symptomatic pregnancy of unknown location. None. Slope of log hCG; days and visits to final diagnosis. Of women with an EP, 60% initially exhibited an increase in hCG values, with a median slope of 32% increase in 2 days; 40% of subjects initially had an hCG decrease, with the median slope calculated as a 15% decline in 2 days. In total, the hCG curves in 27% of women diagnosed with EP resembled that of a growing IUP or SAB. Of the EP hCG curves, 16% demonstrated a change in the direction of the slope of the curve. This was more common in African Americans and less evident in Hispanics. Furthermore, it was associated with more clinical visits and days until final diagnosis. The rate of change in serial hCG values can be used to distinguish EP from an IUP or SAB in only 73% of cases. The number of women who had a change in direction of serial hCG values was associated with race and ethnicity. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

[Influence of human chorionic gonadotropin (hCG) in combination with a 500 calorie diet on clinical and laboratory parameters in premenopausal women with and without hormonal contraception].

PubMed

Rabe, T; Richter, S; Kiesel, L; Zaloumis, M; Runnebaum, B

1987-07-01

82 premenopausal, healthy, nonpregnant volunteers were treated with a 500 kcal reduction diet for 28 days. They were randomized into 2 groups--OC and non-OC users. In addition, 1 of the subgroups in each main group was treated with hCG injections (250 IU/day im for 21 days. The non-OC users (both with and without hCG injections) consisted of 24 subjects each. In the groups of OC users, 13 patients were treated with hCG, 16 were not treated; 5 volunteers discontinued their diet. All groups experienced strong sensations of hunger during the 1st week of the diet (9-16%) which decreased slowly thereafter. No differences between the individual groups could be found. Diet adjustment improved more greatly in those groups who had not received hCG (15-20%) than in the groups with hCG (2-12%). No change was found during the dieting among the subgroups. Serum electrolytes, urea, uric acid, creatinine, and liver enzymes did not change during the dieting. Slight changes were observed in serum cholesterol and triglycerides. Side effects were seen in 2 volunteers from the hCG group, 1 of whom suffered from severe headache and the other who suffered from ovarian cysts which were punctured by laparoscopy. The success of the diet was based on motivation and good information, rather than on the hCG administration. (author's modified)

Predicting success of methotrexate treatment by pretreatment HCG level and 24-hour HCG increment.

PubMed

Levin, Gabriel; Saleh, Narjes A; Haj-Yahya, Rani; Matan, Liat S; Avi, Benshushan

2018-04-01

To evaluate β-human chorionic gonadotropin (β-HCG) level and its 24-hour increment as predictors of successful methotrexate treatment for ectopic pregnancy. Data were retrospectively reviewed from women with ectopic pregnancy who were treated by single-dose methotrexate (50 mg/m 2 ) at a university hospital in Jerusalem, Israel, between January 1, 2000, and June 30, 2015. Serum β-HCG before treatment and its percentage increment in the 24 hours before treatment were compared between treatment success and failure groups. Sixty-nine women were included in the study. Single-dose methotrexate treatment was successful for 44 (63.8%) women. Both mean β-HCG level and its 24-hour increment were lower for women with successful treatment than for those with failed treatment (respectively, 1224 IU\\L vs 2362 IU\\L, P=0.018; and 13.5% vs 29.6%, P=0.009). Receiver operator characteristic curve analysis yielded cutoff values of 1600 IU\\L and 14% increment with a positive predictive value of 75% and 82%, respectively, for treatment success. β-HCG level and its 24-hour increment were independent predictors of treatment outcome by logistic regression (both P<0.01). A β-HCG increment of less than 14% in the 24 hours before single-dose methotrexate and serum β-HCG of less than 1600 IU\\L were found to be good predictors of treatment success. © 2017 International Federation of Gynecology and Obstetrics.

Progesterone concentration, pregnancy and calving rate in Simmental dairy cows after oestrus synchronisation and hCG treatment during the early luteal phase.

PubMed

Šuluburić, Adam; Milanović, Svetlana; Vranješ-Đurić, Sanja; Jovanović, Ivan B; Barna, Tomislav; Stojić, Milica; Fratrić, Natalija; Szenci, Ottó; Gvozdić, Dragan

2017-09-01

Early embryonic development may be negatively affected by insufficient progesterone (P4) production. Therefore, the aim of our study was to increase P4 by gonadotropin-releasing hormone (GnRH) and/or human chorionic gonadotropin (hCG) treatments after inducing oestrus by prostaglandin (PG) treatment. Lactating Simmental dairy cows (n = 110), between 1 to 5 lactations, with an average milk production of 6,500 1/305 days, at 40-80 days postpartum were used and grouped as follows: (1) PG + GnRH treatment at AI (GnRH group), (2) PG + hCG treatment at day 7 after AI (hCG group), (3) PG + GnRH at AI + hCG treatment at day 7 after AI (GnRH/hCG group), and (4) spontaneous oestrus (C: control group). All animals were double inseminated (at the time of oestrus detection and 12 ± 2 h thereafter). Blood serum and milk samples were collected at the day of observed oestrus (day 0), and 14, 21 and 28 days after AI. Serum P4 was determined using a commercial radioimmunoassay (RIA) test (INEP, Zemun), and milk P4 was determined using enzyme-linked immunoassay (ELISA) test (NIV Novi Sad). Pregnancy status was confirmed by ultrasonography between days 28 and 35 after AI. Differences of serum or milk P4 medians, pregnancy (and calving) rate were determined using Dunn's Multiple Comparison Tests and Z test, respectively. Serum P4 medians were significantly higher at days 14, 21 and 28 after AI in the hCG-treated animals, indicating increased luteal activity, with a similar tendency in whole milk P4 values. Treatment with hCG during the early luteal phase significantly contributed to the maintenance of gestation at days 28-35 after AI, and also increased the calving rate in Simmental dairy cows.

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).

Atypical presentation of Wilson disease.

PubMed

Wadera, Sheetal; Magid, Margret S; McOmber, Mark; Carpentieri, David; Miloh, Tamir

2011-08-01

A 15-year-old Caucasian female on human chorionic gonadotropin (HCG) diet presented with fever, cholestasis, coagulopathy, hemolytic anemia, and acute renal dysfunction. Imaging of the biliary system and liver were normal. She responded to intravenous antibiotics, vitamin K and blood transfusions but experienced relapse upon discontinuation of antibiotics. She had remission with reinstitution of antibiotics. Liver biopsy revealed pronounced bile ductular reaction, bridging fibrosis, and hepatocytic anisocytosis and anisonucleosis with degenerative enlarged eosinophilic hepatocytes, suggestive of Wilson disease. Diagnosis of Wilson disease was further established based on the low serum ceruloplasmin, increased urinary and hepatic copper and presence of Kayser-Fleischer rings. The multisystem involvement of the liver, kidney, blood, and brain are consistent with Wilson disease; however, the clinical presentation of cholangitis and reversible coagulopathy is uncommon, and may result from concurrent acute cholangitis and/or the HCG diet regimen the patient was on. © Thieme Medical Publishers.

The effect of a rise or fall of serum estradiol the day before oocyte retrieval in women aged 40-42 with diminished egg reserve.

PubMed

Check, J H; Amui, J; Choe, J K; Cohen, R

2015-01-01

To determine the effect of a drop in serum estradiol the day after injection of human chorionic gonadotropin (hCG) in in vitro fertilization-embryo transfer (IVF-ET) cycles in women aged 40-42 with diminished oocyte reserve. Retrospective study with further requirement that the female partner had a day 3 serum follicle stimulating hormone (FSH) of ≥ 12 miU/mL and ≥ five antral follicles. A drop in serum estradiol the day after hCG injection is not associated with a lower chance of pregnancy compared to those women whose serum estradiol increases. However, their chances of releasing the oocyte before retrieval is significantly higher. A drop in serum estradiol in women of advanced reproductive age with diminished oocyte reserve should not signal the need to cancel the retrieval.

Identification of Hepsin and Protein Disulfide Isomerase A3 as Targets of Gelatinolytic Action in Rat Ovarian Granulosa Cells During the Periovulatory Period1

PubMed Central

Rosewell, Katherine; Al-Alem, Linah; Li, Feixue; Kelty, Brian; Curry, Thomas E.

2011-01-01

The matrix metalloproteinase (MMP) family is believed to play a role in the ovulatory process because MMP inhibitors block oocyte release. However, little is known about the mechanisms by which the MMPs affect ovulation. The present study investigated the degradomic actions of the gelatinases, MMP2 and MMP9, by identifying gelatinolytic targets in periovulatory granulosa cells. Granulosa cells were collected from immature rats 48 h after equine chorionic gonadotropin treatment and were cultured with human chorionic gonadotropin (hCG) in the absence or presence of a specific MMP2/9 inhibitor ((2R)-2-[(4-biphenylylsulfonyl)amino]-3-phenylpropionic acid) for an additional 24 h. The conditioned media was analyzed for gelatinolytic activity, progesterone, and peptide profiles. Gelatinolytic activity and progesterone were induced in response to hCG; however, there was no difference in progesterone between cells treated with or without the inhibitor. Peptide fragments of proteins altered in the presence of the gelatinase inhibitor were identified by two-dimensional gel electrophoresis and mass spectrometry. Protein disulfide isomerase A3 (PDIA3), which plays a role in protein folding, was identified as a peptide that decreased in the presence of inhibitor while the serine protease hepsin, was found to increase with inhibitor treatment. Subsequent experiments established that PDIA3 and hepsin were targets of MMP2/9 action by cleavage with MMP2 and Western blot analysis, respectively. Additionally, hepsin was identified as a gelatinolytic target in ovarian cancer cells. In the present study, proteomics has identified proteins that may be involved in novel ways in the complex cascades that are mediated by gelatinolytic MMPs during the periovulatory period. PMID:21734266

Identification of hepsin and protein disulfide isomerase A3 as targets of gelatinolytic action in rat ovarian granulosa cells during the periovulatory period.

PubMed

Rosewell, Katherine; Al-Alem, Linah; Li, Feixue; Kelty, Brian; Curry, Thomas E

2011-10-01

The matrix metalloproteinase (MMP) family is believed to play a role in the ovulatory process because MMP inhibitors block oocyte release. However, little is known about the mechanisms by which the MMPs affect ovulation. The present study investigated the degradomic actions of the gelatinases, MMP2 and MMP9, by identifying gelatinolytic targets in periovulatory granulosa cells. Granulosa cells were collected from immature rats 48 h after equine chorionic gonadotropin treatment and were cultured with human chorionic gonadotropin (hCG) in the absence or presence of a specific MMP2/9 inhibitor ((2R)-2-[(4-biphenylylsulfonyl)amino]-3-phenylpropionic acid) for an additional 24 h. The conditioned media was analyzed for gelatinolytic activity, progesterone, and peptide profiles. Gelatinolytic activity and progesterone were induced in response to hCG; however, there was no difference in progesterone between cells treated with or without the inhibitor. Peptide fragments of proteins altered in the presence of the gelatinase inhibitor were identified by two-dimensional gel electrophoresis and mass spectrometry. Protein disulfide isomerase A3 (PDIA3), which plays a role in protein folding, was identified as a peptide that decreased in the presence of inhibitor while the serine protease hepsin, was found to increase with inhibitor treatment. Subsequent experiments established that PDIA3 and hepsin were targets of MMP2/9 action by cleavage with MMP2 and Western blot analysis, respectively. Additionally, hepsin was identified as a gelatinolytic target in ovarian cancer cells. In the present study, proteomics has identified proteins that may be involved in novel ways in the complex cascades that are mediated by gelatinolytic MMPs during the periovulatory period.

Effects of diets supplemented by fish oil on sex ratio of pups in bitch.

PubMed

Gharagozlou, Faramarz; Youssefi, Reza; Akbarinejad, Vahid

2016-01-01

The present study was conducted to evaluate the effect of fish oil supplementation prior to mating on secondary sex ratio of pups (the proportion of males at birth) in bitches. Sixty five bitches (German Shepherd, n = 35; Husky, n = 30) were enrolled in the study. Bitches (140-150 days post-estrus) were given 2% per dry matter intake palm oil and fish oil in the control (n = 33) and treatment (n = 32) groups, respectively. To induce estrus, bitches were received equine chorionic gonadotropin (eCG) administration (50 IU kg(-1)) 30 days after nutritional supplementation followed by human chorionic gonadotropin (hCG) administration (500 IU per dog) seven days later. Bitches were introduced to dogs of the same breed after hCG administration. The weight of bitches was increased over time (p < 0.05), but their weight change was not different between two groups (p > 0.05). The mating rate, pregnancy rate and litter size were not influenced by treatment and breed. Secondary sex ratio was higher in the treatment (105/164; 64.00%) than in the control (68/147; 46.30%) group (p < 0.05; adjusted odds ratio = 2.068). Moreover, secondary sex ratio was higher in Husky bitches (88/141; 62.40%) compared to German Shepherd (85/170; 50.00%; p < 0.05; adjusted odds ratio = 1.661). In conclusion, the present study showed that inclusion of fish oil in the diet of bitches prior to mating could increase the proportion of male pups at birth. In addition, it appears that there might be variation among dog breeds with regard to the sex ratio of offspring.

Effects of diets supplemented by fish oil on sex ratio of pups in bitch

PubMed Central

Gharagozlou, Faramarz; Youssefi, Reza; Akbarinejad, Vahid

2016-01-01

The present study was conducted to evaluate the effect of fish oil supplementation prior to mating on secondary sex ratio of pups (the proportion of males at birth) in bitches. Sixty five bitches (German Shepherd, n = 35; Husky, n = 30) were enrolled in the study. Bitches (140-150 days post-estrus) were given 2% per dry matter intake palm oil and fish oil in the control (n = 33) and treatment (n = 32) groups, respectively. To induce estrus, bitches were received equine chorionic gonadotropin (eCG) administration (50 IU kg-1) 30 days after nutritional supplementation followed by human chorionic gonadotropin (hCG) administration (500 IU per dog) seven days later. Bitches were introduced to dogs of the same breed after hCG administration. The weight of bitches was increased over time (p < 0.05), but their weight change was not different between two groups (p > 0.05). The mating rate, pregnancy rate and litter size were not influenced by treatment and breed. Secondary sex ratio was higher in the treatment (105/164; 64.00%) than in the control (68/147; 46.30%) group (p < 0.05; adjusted odds ratio = 2.068). Moreover, secondary sex ratio was higher in Husky bitches (88/141; 62.40%) compared to German Shepherd (85/170; 50.00%; p < 0.05; adjusted odds ratio = 1.661). In conclusion, the present study showed that inclusion of fish oil in the diet of bitches prior to mating could increase the proportion of male pups at birth. In addition, it appears that there might be variation among dog breeds with regard to the sex ratio of offspring. PMID:27482354

Is maternal serum triple screening a better predictor of Down syndrome in female than in male fetuses?

PubMed

Ghidini, A; Spong, C Y; Grier, R E; Walker, C N; Pezzullo, J C

1998-02-01

Among euploid gestations, female fetuses have been reported to have significantly lower maternal serum alpha-fetoprotein (MSAFP) and higher human chorionic gonadotropin (hCG) levels than male fetuses. Since in maternal serum triple screening, low MSAFP and high hCG MOM independently confer greater risk of a Down syndrome fetus, we investigated the hypothesis that maternal serum triple screening is more efficacious at detecting female than male Down syndrome fetuses. A database containing all karyotypes from amniocentesis performed between August 1994 and August 1996 was accessed. All trisomy 21 cases were identified. The male-to-female ratio among trisomy 21 fetuses detected at amniocentesis after abnormal maternal serum triple screening was compared with that among trisomy 21 fetuses detected at amniocentesis for advanced maternal age (AMA), which served as the control group. Statistical analysis utilized chi-square, Fisher's exact test, and Student's t-test. A P value of less than 0.05 was considered statistically significant. Forty-nine trisomy 21 fetuses were detected in the women who underwent amniocentesis because of abnormal triple screening and 311 were detected in the control group. The proportion of male fetuses among the triple screening group was not significantly different from that of the AMA group (55 per cent vs. 57 per cent; P=0.9). Our study had a power of 80 per cent to detect a difference of 25 per cent in the male-to-female ratio (alpha=0.05, beta=0.20). The reported differences in MSAFP and hCG levels between male and female euploid fetuses do not appear to affect the sex ratio among Down syndrome fetuses detected because of an abnormal maternal serum triple screening.

Expression analysis of sox3 during testicular development, recrudescence, and after hCG induction in catfish, Clarias batrachus.

PubMed

Rajakumar, Anbazhagan; Senthilkumaran, Balasubramanian

2014-01-01

In teleosts, the expression of steroidogenic enzymes and related transcription factor genes occurs in a stage- and tissue-specific manner causing sexual development. The role of sox3, an evolutionary ancestor of SRY, has not been studied in detail. Therefore, the full-length cDNA of sox3 (1,197 kb) was cloned from catfish testis, and mRNA expression was analyzed during gonadal development, during the seasonal reproductive cycle, and after human chorionic gonadotropin (hCG) induction. Tissue distribution analysis showed that sox3 expression was higher in testis, ovary, and brain compared to other tissues analyzed. Developing and mature testis showed higher sox3 expression than ovary of corresponding stages, and more sox3 transcripts were found during the spawning phase of the seasonal reproductive cycle. Expression of sox3 was upregulated by hCG after in vivo and in vitro induction, suggesting that gonadotropins might stimulate it. In situ hybridization and immunohistochemistry showed the presence of sox3 mRNA and protein in somatic and interstitial cell layers of the testis. Sox3 could also be found in the zona radiata of developing and mature oocytes. Exposure of methyltestosterone (1 µg/l) and ethinylestradiol (1 µg/l) for 21 days during testicular development showed lower sox3 expression levels in the testis and brain, indicating a certain feedback intervention. These results suggest a possible role for Sox3 in the regulation of testicular development and function. © 2014 S. Karger AG, Basel.

Change of maternal thyroid function in twin-twin transfusion syndrome.

PubMed

Hanaoka, Masachi; Arata, Naoko; Sago, Haruhiko

2015-01-01

Human chorionic gonadotropin (hCG) has weak thyroid-stimulating activity because of its homology with thyroid stimulating hormone (TSH). In twin-twin transfusion syndrome (TTTS), which is a severe complication of monochorionic twin pregnancies, a close association between maternal serum hCG concentration and TTTS has been reported. And, TTTS can be treated by fetoscopic laser coagulation of the communicating vessels. To clarify the relationship between maternal serum hCG and maternal thyroid function in TTTS, the present study investigated the change in thyroid hormone and hCG levels after laser therapy. The protocol included collection of serial maternal blood samples in TTTS before laser therapy, and at two and four weeks after laser therapy. For 131 cases of TTTS, the following parameters were determined at each point: hCG, TSH, free triiodothyronine (fT3), and free thyroxine (fT4). The multiple of the median (MoM) of pre-operative hCG concentration in TTTS was 5.39 MoM (interquartile range, 2.83 - 8.64). There was a moderate positive correlation between hCG and fT3 in TTTS pre-operatively (R = 0.22, P = 0.030). fT4 was also positively correlated with hCG (R = 0.33, P < 0.001). Some cases showed very high concentration in fT3. When laser therapy for TTTS was effective, the hCG concentration significantly decreased, and fT3 and fT4 decreased progressively in concert with the decrease in hCG. The relationship between hCG and thyroid function in TTTS supports the finding of TTTS as a novel etiology of hCG-mediated hyperthyroidism during pregnancy.

[Pregnancy-associated hormones and fetal-maternal relations].

PubMed

Gailly-Fabre, E; Kerlan, V; Christin-Maitre, S

2015-10-01

Pregnancy is an immunological paradox that implies that a semi-allogeneic fetus is not rejected by the maternal immune system, from implantation of the embryo to delivery. Progesterone (P4), estradiol (E2) and human chorionic gonadotropin (hCG), contribute to the transformation of immune cells in a transient tolerance state, necessary to the maintenance of pregnancy. The effects of pregnancy hormones depend probably of their maternal plasma level. hCG is dangerous at high concentrations because it can stimulate autoantibodies production, whereas in physiological concentrations, hCG, P4 and E2 upregulate immune response expanding regulatory T and B cells, allowing the fetus to grow within the maternal uterus in a protective environment. A second example of fetal-maternal relation found recently is the role of maternal nutrition on development of the fetal hypothalamic neurons. Experiments in mice fed on a high fat diet reveal a critical timing when altered maternal metabolism affect formation of hypothalamic neurocircuits of the offspring and predispose him to long-term metabolic disorders. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Water-Soluble Dried Blood Spot in Protein Analysis: A Proof-of-Concept Study.

PubMed

Rosting, Cecilie; Gjelstad, Astrid; Halvorsen, Trine Grønhaug

2015-08-04

In the present work human chorionic gonadotropin (hCG) was used as a model protein in a proof-of-concept study combining water-soluble dried blood spot (DBS) material in liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based protein analysis. A water-soluble material consisting of commercially available carboxymethyl cellulose (CMC) was evaluated as sampling material for this purpose. The material dissolved readily at physiological pH. Different sample preparation methods were evaluated, and in the final method, 15 μL of whole blood was deposited and dried on CMC before the whole spot was dissolved prior to cleanup by immunoaffinity extraction, tryptic digest, and preconcentration by solid-phase extraction (SPE). The results indicated complete dissolution of hCG from the spots, acceptable limit of detection (LOD) (0.1 IU/mL), linearity (R(2) = 0.959), accuracy (16%), and precision (≤22%). Long-term stability (45 days) of hCG in dried spots at reduced temperatures (≤8 °C) was also demonstrated. The analyte recovery was comparable to the commercially available nonsolvable cellulose material (FTA DMPK-C card).

Hormonal therapy (hCG and rhFSH) for infertile men with adult-onset idiopathic hypogonadotropic hypogonadism.

PubMed

Kobori, Yoshitomo; Suzuki, Keisuke; Iwahata, Toshiyuki; Shin, Takeshi; Sato, Ryo; Nishio, Kojiro; Yagi, Hiroshi; Arai, Gaku; Soh, Shigehiro; Okada, Hiroshi

2015-04-01

Adult-onset idiopathic male hypogonadotropic hypogonadism (IMHH) is a very rare but treatable disease. This study was conducted to examine the efficacy and safety of a combination of human chorionic gonadotropin (hCG) and recombinant human follicle-stimulating hormone (rhFSH) for inducing spermatogenesis in men with adult-onset IMHH. Seven men (34-45 years of age) with azoospermia and/or sexual dysfunction, with a low serum testosterone concentration, and apulsatile secretion of luteinizing hormone, were referred to our hospital for infertility. All had normal secondary sexual characteristics. Thorough endocrinologic examination and magnetic resonance imaging revealed no identifiable cause of hypogonadotropic hypogonadism. Adult-onset IMHH was diagnosed in all cases and treatment was started with 150 IU rhFSH and 5,000 IU hCG, both administered two times per week. Spermatogenesis was restored in five of the seven patients. During treatment one patient achieved spontaneous pregnancy with his wife, and spermatozoa recovered from the other four patients were frozen for future use in intracytoplasmic sperm injection.

Angiogenesis in the Primate Ovulatory Follicle Is Stimulated by Luteinizing Hormone via Prostaglandin E21

PubMed Central

Trau, Heidi A.; Davis, John S.; Duffy, Diane M.

2014-01-01

ABSTRACT Rapid angiogenesis occurs as the ovulatory follicle is transformed into the corpus luteum. To determine if luteinizing hormone (LH)-stimulated prostaglandin E2 (PGE2) regulates angiogenesis in the ovulatory follicle, cynomolgus macaques received gonadotropins to stimulate multiple follicular development and chorionic gonadotropin (hCG) substituted for the LH surge to initiate ovulatory events. Before hCG, vascular endothelial cells were present in the perifollicular stroma but not amongst granulosa cells. Endothelial cells entered the granulosa cell layer 24–36 h after hCG, concomitant with the rise in follicular PGE2 and prior to ovulation, which occurs about 40 h after hCG. Intrafollicular administration of the PG synthesis inhibitor indomethacin was coupled with PGE2 replacement to demonstrate that indomethacin blocked and PGE2 restored follicular angiogenesis in a single, naturally developed monkey follicle in vivo. Intrafollicular administration of indomethacin plus an agonist selective for a single PGE2 receptor showed that PTGER1 and PTGER2 agonists most effectively stimulated angiogenesis within the granulosa cell layer. Endothelial cell tracing and three-dimensional reconstruction indicated that these capillary networks form via branching angiogenesis. To further explore how PGE2 mediates follicular angiogenesis, monkey ovarian microvascular endothelial cells (mOMECs) were isolated from ovulatory follicles. The mOMECs expressed all four PGE2 receptors in vitro. PGE2 and all PTGER agonists increased mOMEC migration. PTGER1 and PTGER2 agonists promoted sprout formation while the PTGER3 agonist inhibited sprouting in vitro. While PTGER1 and PTGER2 likely promote the formation of new capillaries, each PGE2 receptor may mediate aspects of PGE2's actions and, therefore, LH's ability to regulate angiogenesis in the primate ovulatory follicle. PMID:25376231

Characterization of rat leydig cell gonadotropin receptor structure by affinity cross-linking

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

Zhang, Q.Y.; Hwang, J.; Menon, K.M.J.

1986-05-01

The gonadotropin receptor from rat leydig cell has been characterized with respect to binding kinetics and physiological regulation. The present study was intended to examine the structure of the receptor. Leydig cell suspension was prepared by either collagenase digestion or by mechanical disruption of the testis. The cells were incubated with /sup 125/I-hCG and the unreacted hCG was removed by centrifugation. The /sup 125/I-hCG was then covalently linked to the cell surface receptor using cleavable (dithiobis (succinimidyl propionate)) and non-cleavable (disuccinimidyl suberate) cross-linking reagents. The extracted cross-linked membrane proteins were resolved on SDS-polyacrylamide gels under reducing and non-reducing conditions andmore » subjected to autoradiographic analysis. Under non-reducing conditions, two labeled species with M/sub r/ = 87,000 and 120,000 were detected. However, only one labeled band was detected under reducing conditions with M/sub r/ = 64,000. The binding of /sup 125/I-hCG to the receptor was inhibited by hCG and LH, but not by a number of peptides and proteins. The data suggest that hCG receptor in leydig cell is an oligomeric complex consisting of four subunits, ..cap alpha cap alpha beta gamma... The ..beta.. and ..gamma.. subunits are each linked to an ..cap alpha.. subunit through disulfide linkage and the hormone binds to each ..cap alpha.. subunit. The two dimers formed (..cap alpha beta cap alpha gamma..) are associated by noncovalent interactions.« less

Effect of additional human chorionic gonadotrophin (hCG) on follicular growth and ovulation in gonadotrophin-treated gilts

PubMed Central

Manjarín, Rodrigo; Cassar, Glen; Friendship, Robert M.; Garcia, José C.; Dominguez, J. Carlos; Kirkwood, Roy N.

2015-01-01

The objective of this study was to determine the effect of additional human chorionic gonadotrophin (hCG) on the ovarian response of gilts previously treated with 200 IU hCG combined with 400 IU equine chorionic gonadotrophin (eCG) (eCG/hCG). Seventy-one prepuberal gilts (105 ± 7.5 kg) were assigned to groups: i) eCG/hCG (hCG-0; n = 25); ii) eCG/hCG followed by 100 IU of hCG at 24 h (hCG-100; n = 24); iii) eCG/hCG followed by 200 IU hCG at 24 h (hCG-200; n = 10); and iv) controls (CON; n = 12). Ovulation response was assessed by ovarian dissection or real-time ultrasonography. Additional hCG did not significantly improve numbers of gilts ovulating. Numbers of corpora lutea increased with hCG, and was higher in hCG-200 (P < 0.01). Compared to hCG-0, the frequency of cysts in gilts was higher in hCG-100 (P < 0.05) and further increased in hCG-200 (P < 0.01). The number of cysts per gilt was dose-dependently increased by additional hCG. We conclude that supplemental hCG will increase the number of corpora lutea but will be associated with follicular cyst development in a dose dependent manner. PMID:26130853

Hyperglycosylated hCG: a Unique Human Implantation and Invasion Factor.

PubMed

Evans, Jemma

2016-03-01

Human chorionic gonadotropin (hCG), as one of the first embryonic products, has been extensively investigated for its role in implantation and placental development. Discovery of an over-glycosylated form of this hormone, hyperglycosylated hCG (hCG-H), has provided an additional level of complexity in our understanding of the implantation and placentation process; the structure, activity and functional implications of alterations in hCG isoforms throughout pregnancy are still being characterized. HCG-H comprises up to 90% of total hCG measurable in serum and urine during the first 2-3 weeks of pregnancy when invasive trophoblast activity is high, dropping to negligible proportions, less than 5%, of total hCG at the end of the first trimester. Functionally, hCG-H promotes trophoblast invasion during early pregnancy and has potential roles in immune cell modulation and endothelial function within the uterus at the time of pregnancy initiation. Altered levels of hCG-H are characteristics of pregnancy complications of altered trophoblast function and inadequate placentation, such as pre-eclampsia, and also over-abundance of invasive cytotrophoblasts, such as Down's syndrome. Improving our basic knowledge of the functional role-specific hCG isoforms plays in the complex cascade of events involved in implantation and placental development, and determining dynamic changes in the structure and activity of hCG isoforms throughout gestation will facilitate evidence-based decisions in assisted reproduction/in vitro fertilization based on the potential of embryos to implant, provide biomarkers for diagnosis of pregnancy complications associated with altered placental development and enhance understanding of how hCG isoforms may influence receptivity of the endometrium. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Application of hormonal treatment in hypogonadotropic hypogonadism: more than ten years experience.

PubMed

Yang, Luo; Zhang, Si Xiao; Dong, Qiang; Xiong, Zi Bing; Li, Xiang

2012-04-01

To demonstrate the efficacy of hormone treatment on the patients with hypogonadotropic hypogonadism (HH), we summarized our more than 10 years experience. A total of 242 male patients (age range 15-52 years old) with HH including two Kallmann syndrome treated at the andrology outpatient clinics of university hospital in the past 10 years were reviewed retrospectively. The patients were divided into three groups based on the different treatment strategy. There were 84 patients treated with human chorionic gonadotropin (hCG) (group 1, hCG treatment group), 74 patients treated with hCG plus human menopause gonadotropin (hMG) (group 2, hCG + hMG treatment group), and 84 patients treated with testosterone (group 3, T treatment group). Sex characteristics, testicular volume, and sperm production were determined before and after the treatments. The therapeutic effects in the three groups were analyzed statistically. In total, 42 patients of group 1 (50.0%) and 56 of group 2 (75.7%) had their testicular volumes increased after 6-18 months treatment, from 2.0 ± 1.1 to 6.8 ± 3.2 mL and 2.1 ± 1.1 to 8.8 ± 3.9 mL, respectively. Only six patients of group 3 had their testicular volumes increased but no statistically significant. Among the patients with testes growth, 34 patients of group 1 and 48 patients of group 2 achieved spermatogenesis, and three of them made their wives pregnant naturally. During the follow-up after treatment, there were 36 patients finally defined as delayed puberty, and 204 patients defined as idiopathic hypogonadotropic hypogonadism. For the hormonal treatment of HH, testosterone therapy could not stimulate testes growth and spermatogenesis, but HCG therapy and hCG/hMG combination therapy both are effective, while hCG/hMG combination therapy could achieve better therapeutic effects.

Gonadotropin-binding sites in the rhesus monkey ovary: role of the vasculature in the selective distribution of human chorionic gonadotropin to the preovulatory follicle

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

Zeleznik, A.J.; Schuler, H.M.; Reichert, L.E. Jr.

These experiments were initiated to determine if differences exist in the vasculature of individual follicles in the rhesus monkey ovary during the late follicular phase of the menstrual cycle and to determine whether differences in vascularity result in differential exposure of certain follicles to gonadotropic hormones. The density of blood vessels within the thecal layer of the dominant follicle and other antral follicles was determined in ovaries from four animals removed on day 9 or 10 of the menstrual cycle. Blood vessels were identified using a histochemical stain for hemoglobin. Morphometric analysis indicated that the percentage of the thecal layermore » occupied by blood vessels in the dominant follicles (48%) was significantly greater (P less than 0.005) than that of other smaller antral follicles either within the same ovary as the dominant follicle (24%) or in the contralateral ovary (26%). To determine if differences in vascularity result in a differential supply of gonadotropins to the dominant follicle, we studied, by autoradiography, the in vivo and in vitro binding of (125I)hCG in four rhesus monkeys on day 9 of the menstrual cycle. Results of in vitro binding studies indicated that the thecal layer of virtually every antral follicle possessed hCG-binding sites. However, when (125I)hcg was injected iv into animals and allowed to distribute via the vasculature, the dominant follicle was heavily labeled while other smaller antral follicles accumulated little, if any, radioiodinated hCG. These observations indicate that increased vascularization of individual follicles results in preferential delivery of gonadotropins, and suggest that blood flow to individual follicles may play an instrumental role in the selective maturation of the preovulatory follicle in the rhesus monkey.« less

Gonadotropin-dependent regulation of the prostaglandin E2 receptor in equine preovulatory follicles during the ovulatory process in mares.

PubMed

Sayasith, Khampoune; Bouchard, Nadine; Doré, Monique; Sirois, Jean

2009-02-01

The objectives of the study were to clone the primary structure of the prostaglandin E2 receptor subtype 2 (PTGER2) cDNA and to characterize its regulation in equine follicles during gonadotropin-induced ovulation. Results from DNA isolation indicated that the equine PTGER2 cDNA encodes a predicted 353-amino acid protein, which is highly similar (76-85%) to known mammalian homologues. The regulation of PTGER2 was studied by semi-quantitative RT-PCR/Southern blot using preparations of theca interna and mural granulosa cells isolated from equine follicles 0-39 hr post-treatment with human chorionic gonadotropin (hCG). Results indicated that a significant increase of PTGER2 mRNA occurred at 24 and 39 hr post-hCG in granulosa cells, and 30 and 33 hr post-hCG in theca cells (P < 0.05). Immunohistochemical staining and immunoblotting performed on equine follicular samples showed a corresponding increase of PTGER2 protein in both cell types after treatment with hCG. Levels of PTGER2 mRNA were also high in uterus, thymus and spleen, but moderate to low in other tested tissues. In the ovary, the expression of PTGER4 mRNA was observed and predominantly occurred in granulosa cells, with highest abundance of transcripts observed at 12 and 39 hr post-hCG. Thus, this study reports for the first time in mares that the ovulatory process is accompanied by the gonadotropin-dependent up-regulation of PTGER2 and PTGER4, which may in turn regulate PGE2-mediated preovulatory effects. (c) 2008 Wiley-Liss, Inc.

In vitro effect of 4-nonylphenol on human chorionic gonadotropin (hCG) stimulated hormone secretion, cell viability and reactive oxygen species generation in mice Leydig cells.

PubMed

Jambor, Tomáš; Tvrdá, Eva; Tušimová, Eva; Kováčik, Anton; Bistáková, Jana; Forgács, Zsolt; Lukáč, Norbert

2017-03-01

Nonylphenol is considered an endocrine disruptor and has been reported to affect male reproductive functions. In our in vitro study, we evaluated the effects of 4-nonylphenol (4-NP) on cholesterol levels, hormone formation and viability in cultured Leydig cells from adult ICR male mice. We also determined the potential impact of 4-NP on generation of reactive oxygen species (ROS) after 44 h of cultivation. The cells were cultured with addition of 0.04; 0.2; 1.0; 2.5 and 5.0 μg/mL of 4-NP in the present of 1 IU/mL human chorionic gonadotropin (hCG) and compared to the control. The quantity of cholesterol was determined from culture medium using photometry. Determination of hormone production was performed by enzyme-linked immunosorbent assay. Metabolic activity assay was used for quantification of cell viability. The chemiluminescence technique, which uses a luminometer to measure reactive oxygen species, was employed. Applied doses of 4-NP (0.04-5.0 μg/mL) slight increase cholesterol levels and decrease production of dehydroepiandrosterone after 44 h of cultivation, but not significantly. Incubation of 4-NP treated cells with hCG significantly (P < 0.001) inhibited androstenedione, but not testosterone, formation at the highest concentration (5.0 μg/mL). The viability was significantly (P < 0.05); (P < 0.001) increased at 1.0; 2.5 and 5.0 μg/mL of 4-NP after 44 h treatment. Furthermore, 44 h treatment of 4-NP (0.04-5.0 μg/mL) caused significant (P < 0.001) intracellular accumulation of ROS in exposed cells. Taken together, the results of our in vitro study reported herein is consistent with the conclusion that 4-nonylphenol is able to influence hormonal profile, cell viability and generate ROS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular cloning of pituitary glycoprotein alpha-subunit and follicle stimulating hormone and chorionic gonadotropin beta-subunits from New World squirrel monkey and owl monkey.

PubMed

Scammell, Jonathan G; Funkhouser, Jane D; Moyer, Felricia S; Gibson, Susan V; Willis, Donna L

2008-02-01

The goal of this study was to characterize the gonadotropins expressed in pituitary glands of the New World squirrel monkey (Saimiri sp.) and owl monkey (Aotus sp.). The various subunits were amplified from total RNA from squirrel monkey and owl monkey pituitary glands by reverse transcription-polymerase chain reaction and the deduced amino acid sequences compared to those of other species. Mature squirrel monkey and owl monkey glycoprotein hormone alpha-polypeptides (96 amino acids in length) were determined to be 80% homologous to the human sequence. The sequences of mature beta subunits of follicle stimulating hormone (FSHbeta) from squirrel monkey and owl monkey (111 amino acids in length) are 92% homologous to human FSHbeta. New World primate glycoprotein hormone alpha-polypeptides and FSHbeta subunits showed conservation of all cysteine residues and consensus N-linked glycosylation sites. Attempts to amplify the beta-subunit of luteinizing hormone from squirrel monkey and owl monkey pituitary glands were unsuccessful. Rather, the beta-subunit of chorionic gonadotropin (CG) was amplified from pituitaries of both New World primates. Squirrel monkey and owl monkey CGbeta are 143 and 144 amino acids in length and 77% homologous with human CGbeta. The greatest divergence is in the C terminus, where all four sites for O-linked glycosylation in human CGbeta, responsible for delayed metabolic clearance, are predicted to be absent in New World primate CGbetas. It is likely that CG secreted from pituitary of New World primates exhibits a relatively short half-life compared to human CG.

Successful treatment algorithm for evaluation of early pregnancy after in vitro fertilization.

PubMed

Cookingham, Lisa Marii; Goossen, Rachel P; Sparks, Amy E T; Van Voorhis, Bradley J; Duran, Eyup Hakan

2015-10-01

To evaluate a prospectively implemented clinical algorithm for early identification of ectopic pregnancy (EP) and heterotopic pregnancy (HP) after assisted reproductive technology (ART). Analysis of prospectively collected data. Academic medical center. All ART-conceived pregnancies between January 1995 and June 2013. Early pregnancy monitoring via clinical algorithm with all pregnancies screened using human chorionic gonadotropin (hCG) levels and reported symptoms, with subsequent early ultrasound evaluation if hCG levels were abnormal or if the patient reported pain or vaginal bleeding. Algorithmic efficiency for diagnosis of EP and HP and their subsequent clinical outcomes using a binary forward stepwise logistic regression model built to determine predictors of early pregnancy failure. Of the 3,904 pregnancies included, the incidence of EP and HP was 0.77% and 0.46%, respectively. The algorithm selected 96.7% and 83.3% of pregnancies diagnosed with EP and HP, respectively, for early ultrasound evaluation, leading to earlier treatment and resolution. Logistic regression revealed that first hCG, second hCG, hCG slope, age, pain, and vaginal bleeding were all independent predictors of early pregnancy failure after ART. Our clinical algorithm for early pregnancy evaluation after ART is effective for identification and prompt intervention of EP and HP without significant over- or misdiagnosis, and avoids the potential catastrophic morbidity associated with delayed diagnosis. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Hormonal Evidence Supports the Theory of Selection in Utero

PubMed Central

Catalano, RA; Saxton, KB; Bruckner, TA; Pearl, M; Anderson, E; Goldman-Mellor, S; Margerison-Zilko, C; Subbaraman, M; Currier, RJ; Kharrazi, M

2012-01-01

Objectives Antagonists in the debate over whether the maternal stress response during pregnancy damages or culls fetuses have invoked the theory of selection in utero to support opposing positions. We describe how these opposing arguments arise from the same theory and offer a novel test to discriminate between them. Our test, rooted in reports from population endocrinology that human chorionic gonadotropin (hCG) signals fetal fitness, contributes not only to the debate over the fetal origins of illness, but also to the more basic literature concerned with whether and how natural selection in utero affects contemporary human populations. Methods We linked maternal serum hCG measurements from prenatal screening tests with data from the California Department of Public Health birth registry for the years 2001–2007. We used time series analysis to test the association between the number of live born male singletons and median hCG concentration among males in monthly gestational cohorts. Results Among the 1.56 million gestations in our analysis, we find that median hCG levels among male survivors of monthly conception cohorts rise as the number of male survivors falls. Conclusions Elevated median hCG among relatively small male birth cohorts supports the theory of selection in utero and suggests that the maternal stress response culls cohorts in gestation by raising the fitness criterion for survival to birth. PMID:22411168

False-positive pregnancy test after transfusion of solvent/detergent-treated plasma.

PubMed

Jilma-Stohlawetz, Petra; Wreford-Bush, Tim; Mills, Francesca; Davidson, Fiona; Kursten, Friedrich W; Jilma, Bernd; Birchall, Janet

2017-12-01

The transmission of pathogens, antibodies, and proteins is a possible consequence of blood product transfusion. A female patient had an unexpected positive serum β-human chorionic gonadotropin result, indicative of pregnancy, after she had received a transfusion with 1 unit of platelet concentrate, 4 units of red blood cells, and 4 units of pooled solvent/detergent-treated plasma (Octaplas). To investigate the possibility of passive transfusion of β-human chorionic gonadotropin from the plasma transfusion, one additional unit from the same batch was thawed and analyzed. To validate the β-human chorionic gonadotropin assay for use in solvent/detergent-treated plasma and to investigate any interference in the assay, dilution experiments were performed using the implicated plasma batch diluted with male and non-pregnant female sera. Also, plasma from a known pregnant woman was diluted with Octaplas (tested negative for β-human chorionic gonadotropin) and with a male serum to validate the assay for use in solvent/detergent-treated plasma. The implicated solvent/detergent-treated plasma had a mean β-human chorionic gonadotropin level of 91.5 mIU/mL. Results from the dilution experiments revealed an excellent correlation (r > 0.99) between β-human chorionic gonadotropin measurement in solvent/detergent-treated plasma and male serum and no over or under recovery of the expected results. Further measurements of β-human chorionic gonadotropin levels in the female recipient revealed an estimated half-life of 6 hours. This case demonstrates the importance of considering the possibility of passive transmission of analytes to a patient from the transfusion of blood products. Furthermore, the measurement of β-human chorionic gonadotropin is valid in solvent/detergent-treated plasma using a Roche Cobas analyzer. © 2017 AABB.

Abnormal human chorionic gonadotropin (hCG) trends after transfer of multiple embryos resulting in viable singleton pregnancies.

PubMed

Brady, Paula C; Farland, Leslie V; Missmer, Stacey A; Racowsky, Catherine; Fox, Janis H

2018-03-01

The purpose of this study is to investigate whether abnormal hCG trends occur at a higher incidence among women conceiving singleton pregnancies following transfer of multiple (two or more) embryos (MET), as compared to those having a single embryo transfer (SET). Retrospective cohort study was performed of women who conceived singleton pregnancies following fresh or frozen autologous IVF/ICSI cycles with day 3 or day 5 embryo transfers between 2007 and 2014 at a single academic medical center. Cycles resulting in one gestational sac on ultrasound followed by singleton live birth beyond 24 weeks of gestation were included. Logistic regression models adjusted a priori for patient age at oocyte retrieval and day of embryo transfer were used to estimate the Odds Ratio of having an abnormal hCG rise (defined as a rise or < 66% in 2 days) following SET as compared to MET. Among patients receiving two or more embryos, 6.1% (n = 84) had abnormal hCG rises between the first and second measurements, compared to 2.7% (n = 17) of patients undergoing SET (OR 2.16, 95% CI 1.26-3.71). Among patients with initially abnormal hCG rises who had a third level checked (89%), three-quarters had normal hCG rises between the second and third measurements. Patients who deliver singletons following MET were more likely to have suboptimal initial hCG rises, potentially due to transient implantation of other non-viable embryo(s). While useful for counseling, these findings should not change standard management of abnormal hCG rises following IVF. The third hCG measurements may clarify pregnancy prognosis.

Screening method to evaluate point-of-care human chorionic gonadotropin (hCG) devices for susceptibility to the hook effect by hCG β core fragment: evaluation of 11 devices.

PubMed

Nerenz, Robert D; Song, Haowei; Gronowski, Ann M

2014-04-01

The predominant hCG variant in urine, hCG β core fragment (hCGβcf), has been demonstrated to cause false-negative results in qualitative point-of-care (POC) hCG devices. This is a major concern for healthcare professionals using POC pregnancy tests. We developed a screening method to evaluate qualitative POC hCG devices for their susceptibility to inhibition by hCGβcf. Using this method, we evaluated the performance of 11 commonly used devices. A wide range of purified hCG and hCGβcf concentrations were mixed and tested on 2 POC devices. By use of those results, a screening method was defined and 9 additional POC devices were evaluated. Two solutions containing (a) 500 pmol/L (171 IU/L) intact hCG with 0 pmol/L hCGβcf and (b) 500 pmol/L intact hCG with 500 000 pmol/L hCGβcf were used to screen all POC devices. The OSOM and Cen-Med Elite devices were found to be most susceptible to false-negative results due to hCGβcf. The BC Icon 20 and the Alere were the least susceptible. The remaining 7 were moderately affected. Devices that gave the strongest signal with hCGβcf alone were those that were least likely to show a hook effect. The screening method put forth here can be used by device users and manufacturers to evaluate POC devices for inhibition by hCGβcf. Of 11 devices evaluated, only 2 have been identified that exhibit minimal to no susceptibility to hCGβcf.

Human chorionic gonadotrophin in early gestation induces growth of estrogenic ovarian follicles and improves primiparous sow fertility during summer.

PubMed

Seyfang, Jemma; Langendijk, P; Chen, T Y; Bouwman, E; Kirkwood, R N

2016-09-01

Reduced summer farrowing rates may be due to inadequate corpora luteal (CL) support. Porcine CL become dependent on LH from 12 d of pregnancy and the embryonic estrogen signal for maternal recognition of pregnancy (MRP) is initiated at about 11-12 d after insemination. We hypothesised that injection of the LH analogue human chorionic gonadotropin (hCG) would induce growth of estrogenic follicles and, by mimicking the signal for MRP and stimulating progesterone secretion, increase primiparous sow fertility. In Experiment 1, during a 28 d lactation 53 mixed parity sows were full-fed either throughout lactation (n=16) or until 18 d and then feed restricted during the last 10 d of lactation (n=36). At 12 d after mating restrict-fed sows were injected with 1000IU hCG (n=17) or were not injected (n=19); the full-fed sows acted as non-treated positive controls. Transrectal ovarian ultrasound exams were performed on days 12, 16, 20, 24, and 28; blood samples were obtained on days 12, 14, and 15 for estradiol and progesterone assay. For Experiment 2, during the summer months primiparous sows received 1000IU hCG 12 d after mating (n=28) or were non-injected controls (n=27). Pregnancy status was determined at 28 d and sows allowed to go to term to determine farrowing rates and litter sizes. In Experiment 1, injection of hCG increased (P<0.001) follicle diameter and serum concentrations of estradiol (P<0.01) and progesterone (P<0.05). There were no effects of lactation feeding level on wean-estrus interval, farrowing rate or subsequent litter size. In Experiment 2, hCG injection was associated with a higher pregnancy rate (P<0.05) and farrowing rate (P<0.08). There was no effect on litter size. These data confirm that hCG stimulates growth of estrogenic follicles and CL function, and improves primiparous sow fertility during the summer months. Copyright © 2016 Elsevier B.V. All rights reserved.

The carboxyl-terminal region is a determinant for the intracellular behavior of the chorionic gonadotropin beta subunit: effects on the processing of the Asn-linked oligosaccharides.

PubMed

Muyan, M; Boime, I

1998-05-01

The placental hormone human CG (hCG) consists of two noncovalently linked alpha- and beta-subunits similar to the other glycoprotein hormones LH, FSH, and TSH. These heterodimers share a common alpha subunit but differ in their structurally distinct beta subunits. The CGbeta subunit is distinguished among the beta subunits by the presence of a C-terminal extension with four serine-linked oligosaccharides (carboxyl terminal peptide or CTP). In previous studies we observed that deleting this sequence decreased assembly of the truncated CGbeta subunit (CGbeta114) with the alpha-subunit and increased the heterogeneity of the secreted forms of the uncombined subunit synthesized in transfected Chinese hamster ovary (CHO) cells. The latter result was attributed to alterations in the processing of the two N-linked oligosaccharides. To examine at what step this heterogeneity occurs, the CGbeta and CGbeta114 genes were transfected into wild-type and mutant CHO cell lines that are defective in the late steps of the N-linked carbohydrate-processing pathway. We show here that removal of the CTP alters the processing of the core mannosyl unit of the subunit to complex forms at both glycosylation sites and that the oligosaccharides contain polylactosamine. Although it has been presumed that there is little intramolecular interaction between the CTP and the proximal domains of the subunit, our data suggest that the CTP sequence participates in the folding of the newly synthesized subunit, which is manifest by the posttranslational changes observed here.

Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial.

PubMed

Strug, Michael R; Su, Renwei; Young, James E; Dodds, William G; Shavell, Valerie I; Díaz-Gimeno, Patricia; Ruíz-Alonso, Maria; Simón, Carlos; Lessey, Bruce A; Leach, Richard E; Fazleabas, Asgerally T

2016-07-01

Does a single intrauterine infusion of human chorionic gonadotropin (hCG) at the time corresponding to a Day 3 embryo transfer in oocyte donors induce favorable molecular changes in the endometrium for embryo implantation? Intrauterine hCG was associated with endometrial synchronization between endometrial glands and stroma following ovarian stimulation and the induction of early decidual markers associated with stromal cell survival. The clinical potential for increasing IVF success rates using an intrauterine hCG infusion prior to embryo transfer remains unclear based on previously reported positive and non-significant findings. However, infusion of CG in the non-human primate increases the expression of pro-survival early decidual markers important for endometrial receptivity, including α-smooth muscle actin (α-SMA) and NOTCH1. Oocyte donors (n=15) were randomly assigned to receive an intrauterine infusion of 500 IU hCG (n=7) or embryo culture media vehicle (n=8) 3 days following oocyte retrieval during their donor stimulation cycle. Endometrial biopsies were performed 2 days later, followed by either RNA isolation or tissue fixation in formalin and paraffin embedding. Reverse transcription of total RNA from endometrial biopsies generated cDNA, which was used for analysis in the endometrial receptivity array (ERA; n = 5/group) or quantitative RT-PCR to determine relative expression of ESR1, PGR, C3 and NOTCH1. Tissue sections were stained with hematoxylin and eosin followed by blinded staging analysis for dating of endometrial glands and stroma. Immunostaining for ESR1, PGR, α-SMA, C3 and NOTCH1 was performed to determine their tissue localization. Intrauterine hCG infusion was associated with endometrial synchrony and reprograming of stromal development following ovarian stimulation. ESR1 and PGR were significantly elevated in the endometrium of hCG-treated patients, consistent with earlier staging. The ERA did not predict an overall positive impact of intrauterine hCG on endometrial receptivity. However, ACTA2, encoding α-SMA was significantly increased in response to intrauterine hCG. Similar to the hCG-treated non-human primate, sub-epithelial and peri-vascular α-SMA expression was induced in women following hCG infusion. Other known targets of hCG in the baboon were also found to be increased, including C3 and NOTCH1, which have known roles in endometrial receptivity. This study differs from our previous work in the hCG-treated non-human primate along with clinical studies in infertile patients. Specifically, we performed a single intrauterine infusion in oocyte donors instead of either continuous hCG via an osmotic mini-pump in the baboon or infusion followed by blastocyst-derived hCG in infertile women undergoing embryo transfer. Therefore, the full impact of intrauterine hCG in promoting endometrial receptivity may not have been evident. Our findings suggest a potential clinical benefit for intrauterine hCG prior to embryo transfer on Day 3 in counteracting endometrial dyssynchrony from ovarian stimulation and promoting expression of markers important for stromal survival. Finally, there were no obvious negative effects of intrauterine hCG treatment. Funding for this work was provided by NICHD R01 HD042280 (A.T.F.) and NICHD F30 HD082951 (M.R.S.). C.S. and P.D.-G are co-inventors of the patented ERA, which is owned by IGENOMIX SL and was used in this study, and C.S. is a shareholder in IGENOMIX SL. M.R.-A. is employed by IGENOMIX SL. No other authors have any conflicts of interest to report. This study was registered with ClinicalTrials.gov (NCT01786252). 5 February 2013. 10 May 2013. © 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.

Intravenous infusion of PAF affects ovulation, fertilization and preimplantation embryonic development in NZB x NZW F1 hybrid mice.

PubMed

Sakellariou, Maria; Drakakis, Peter; Antonopoulou, Smaragdi; Anagnostou, Elli; Loutradis, Dimitris; Patargias, Theoxaris

2008-03-01

Platelet Activating Factor (PAF) is a bioactive phospholipid, which exhibits a variety of biological activities and plays a significant role in all aspects of reproduction. In this work, a single intravenous injection of various concentrations of PAF shortly after Human Chorionic Gonadotropin (HCG) administration as well as 24 and 48 h before HCG administration was studied in NZB x NZW F1 hybrid mice. Optimum results were observed when PAF was injected just after the administration of HCG. In this protocol, the concentrations of PAF exhibited bell-shaped response to every stage of development. Any concentration of PAF between 5.5 x 10(-11) and 5.5 x 10(-15)g/g b.w., caused an improved ovulation rate, an increased fertilization rate, an increased rate of cell cycle and an enhanced hatching blastocyst rate (P<0.05 for all stages). Injection of lyso-PAF had no effect in any stage. Our data show that the effect of PAF on early stages of embryo development in vitro is dependent on its way of administration, on the concentrations used as well as on the time PAF is injected.

Bisphenol A alters β-hCG and MIF release by human placenta: an in vitro study to understand the role of endometrial cells.

PubMed

Mannelli, C; Ietta, F; Carotenuto, C; Romagnoli, R; Szostek, A Z; Wasniewski, T; Skarzynski, D J; Paulesu, Luana

2014-01-01

A proper fetomaternal immune-endocrine cross-talk in pregnancy is fundamental for reproductive success. This might be unbalanced by exposure to environmental chemicals, such as bisphenol A (BPA). As fetoplacental contamination with BPA originates from the maternal compartment, this study investigated the role of the endometrium in BPA effects on the placenta. To this end, in vitro decidualized stromal cells were exposed to BPA 1 nM, and their conditioned medium (diluted 1 : 2) was used on chorionic villous explants from human placenta. Parallel cultures of placental explants were directly exposed to 0.5 nM BPA while, control cultures were exposed to the vehicle (EtOH 0.1%). After 24-48 h, culture medium from BPA-treated and control cultures was assayed for concentration of hormone human Chorionic Gonadotropin ( β -hCG) and cytokine Macrophage Migration Inhibitory Factor (MIF). The results showed that direct exposure to BPA stimulated the release of both MIF and β -hCG. These effects were abolished/diminished in placental cultures exposed to endometrial cell-conditioned medium. GM-MS analysis revealed that endometrial cells retain BPA, thus reducing the availability of this chemical for the placenta. The data obtained highlight the importance of in vitro models including the maternal component in reproducing the effects of environmental chemicals on human fetus/placenta.

[Risk-benefit analysis of a hCG-500 kcal reducing diet (cura romana) in females].

PubMed

Rabe, T; Richter, S; Kiesel, L; Runnebaum, B

1987-05-01

The British physician A.T.W. Simeons described in 1954 a new method for dieting. He combined a reduction diet (500 kcal per day) with daily injections of the pregnancy hormone human chorionic gonadotropin (hCG) (125 IU i.m.). According to Simeons the patient should not lose more weight during a 4-to-6 weeks' diet than without hCG, but the injections should facilitate to maintain the diet and to lose body weight at specific parts of the body (e.g. hip, belly, thigh). After the first publication various studies conducted with male and female patients analysed the efficacy of the "Cura romana". 10 of these studies showed positive and another 10 studies negative results with regard to hCG-related weight reduction. Two of these studies with positive results were double-blind studies (hCG vs. placebo). Most of them were reports on therapeutical experiences and were not controlled studies. According to these reports the body proportions normalized and the feeling of hunger was tolerable. Four out of 10 studies with negative results were controlled studies (hCG vs. control without hCG), whereas 6 were double-blind studies. These studies showed a significant weight reduction during dieting, but no differences between treatment groups in respect of body weight, body proportions and feeling of hunger. One of them is the only German study conducted by Rabe et al. in 1981 in which 82 randomised premenopausal volunteers had been dieting either with hCG or without hCG injections. In recent publications describing mostly well-documented double-blind studies authors largely reject hCG administration in dieting. Supporters of the hCG diet must prove the efficacy of this method in controlled studies according to the German Drug Law. Until then the opinion of the German steroid toxicology panel is still valid, that hCG is ineffective in dieting and should not be used (Bolt 1982 a, 1982 b).

Human Chorionic Gonadotropine in Cul-de-sac Fluid in Tubal Ectopic Pregnacy; A New Diagnostic Approach.

PubMed

Karahasanoglu, Ayse; Uzun, Isil; Ozdemir, Mucize; Yazicioglu, Fehmi

2016-04-01

Although new diagnostic abilities are being utilised increasingly yet early detection of tubal pregnancy remains a challenge. The use of highly sensitive hCG kits has facilitated the early diagnosis of a pregnancy. But it takes time to determine the localisation of the pregnancy. Early diagnosis of ectopic pregnancy may reduce the morbidity of ectopic pregnancy. This study was conducted to analyse the cul-de-sac and serum βhCG ratio in tubal ectopic pregnancy cases which may be a new diagnostic approach for ectopic pregnancy. Between January 2004 and July 2011, 263 patients with ectopic pregnancy were included in the study. Risk factors of patients and treatment modalities were evaluated. hCG was measured in peripheral serum and peritoneal fluid, obtained by puncture of Douglas pouch in 52 patients with tubal ectopic pregnancy. hCG level was determined in the cul-de-sac fluid and in the maternal serum for comparison. Tubectomy (5.3%), history of abortion (9.5%), history of previous surgery (14.8%), previous cesarean section (8%) and pelvic infamatorry disease (15.9 %) were the important risk factors for ectopic pregnancy in our cases. In 51 of 52 patients with tubal pregnancy, the cul-de-sac hCG vaule and the serum hCG value ratio was >1. It is concluded that the ratio of hCG in cul-de -sac and serum can be used for the verification of tubal ectopic pregnancy in addition to other diagnostic methods. This may help rapid confirmation of the diagnosis of ectopic pregnancy.

[Clinical use of RU 486: control of the menstrual cycle and effect on the hypophyseal-adrenal axis].

PubMed

Gaillard, R C; Herrmann, W

1983-01-01

RU 486 is a synthetic 19 norsteroid with a great affinity for progesterone and glucocorticosteroid receptors. The antiprogesterone activity of RU 486 permits interruption of the luteal phase of the menstrual cycle and of early pregnancy, while the antiglucocorticosteroid activity interrupts the feedback mechanisms of cortisol at the hypothalamic-pituitary axis. 11 women aged 18-34 years who were 6-8 weeks pregnant were given daily doses of 200 mg of sensation of lipothymia. Blood pressure and laboratory test results remained normal. The daily increase of beta human chorionic gonadotropin (HCG) and progesterone was stopped by the antiprogesterone. It has been demonstrated in vitro that RU 486 inhibits secretion of beta HCG by cells of trophoblastic origin. 2 weeks after expulsion of the products of conception, the blood levels of beta HCG, progesterone, and estradiol had returned to nonpregnant values and ovarian activity was normal in women not using oral contraceptives. The reason for failure of expulsion in 2 cases was not known. RU 486 was also used to interrupt the luteal phase of normal menstrual cycles in 3 young women. 50 mg/day of RU 486 starting on the 22nd day was sufficient to induce bleeding within 48 hours. Studies using RU 486 50 mg/day beginning on the 10th cycle day indicate that progesterone plays a central and follicular role during the preovulatory period. The antiglucocorticosteroid activity of RU 486 was observed in pregnant women who received the abortifacient dose of 200 mg/day. The 8 a.m. plasma level of ACTH and beta-LPH cortisol remained elevated for thee 4 days of treatment. Nonpregnant women receiving 50 mg of RU 486 for 4 days beginning on the 22nd cycle day had no change in the level of hypophyseal-adrenal hormones.dd Tests in young male volunteers showed that RU 486 amplified circadian rhythms of the hypophysealadrenal axis, affecting specifically the morning hormonal levels without influencing afternoon levels. A test in which RU 486 was used to antagonize the inhibition producedd by dexamethasone during a test of suppression of the hypophyseal-adrenal axis confirmed that the antiglucocorticosteroid effect of RU 486 is produced at the level of the glucocorticosteroid receptors. The antiglucocorticosteroid effect is independent of the antiprogesterone effect. RU 486 may be utilizable in fertility control, to control undesirable effects of steroids in cases of hypercorticism, and perhaps eventually to test the hypophyseal-adrenal axis.

Molecular cloning, expression analysis and transcript localization of testicular orphan nuclear receptor 2 in the male catfish, Clarias batrachus.

PubMed

Murugananthkumar, R; Akhila, M V; Rajakumar, A; Mamta, S K; Sudhakumari, C C; Senthilkumaran, B

2016-12-01

Testicular receptor 2 (TR2; also known as Nr2c1) is one of the first orphan nuclear receptors identified and known to regulate various physiological process with or without any ligand. In this study, we report the cloning of full length nr2c1 and its expression analysis during gonadal development, seasonal testicular cycle and after human chorionic gonadotropin (hCG) induction. In addition, in situ hybridization (ISH) was performed to localize nr2c1 transcripts in adult testis and whole catfish (1day post hatch). Tissue distribution and gonadal ontogeny studies revealed high expression of nr2c1 in developing and adult testis. Early embryonic stage-wise expression of nr2c1 seems to emphasize its importance in cellular differentiation and development. Substantial expression of nr2c1 during pre-spawning phase and localization of nr2c1 transcripts in sperm/spermatids were observed. Significant upregulation after hCG induction indicate that nr2c1 is under the regulation of gonadotropins. Whole mount ISH analysis displayed nr2c1 expression in notochord indicating its role in normal vertebrate development. Taken together, our findings suggest that nr2c1 may have a plausible role in the testicular and embryonic development of catfish. Copyright © 2015. Published by Elsevier Inc.

The Alternative Epac/cAMP Pathway and the MAPK Pathway Mediate hCG Induction of Leptin in Placental Cells

PubMed Central

Maymó, Julieta Lorena; Pérez Pérez, Antonio; Maskin, Bernardo; Dueñas, José Luis; Calvo, Juan Carlos; Sánchez Margalet, Víctor; Varone, Cecilia Laura

2012-01-01

Pleiotropic effects of leptin have been identified in reproduction and pregnancy, particularly in the placenta, where it works as an autocrine hormone. In this work, we demonstrated that human chorionic gonadotropin (hCG) added to JEG-3 cell line or to placental explants induces endogenous leptin expression. We also found that hCG increased cAMP intracellular levels in BeWo cells in a dose-dependent manner, stimulated cAMP response element (CRE) activity and the cotransfection with an expression plasmid of a dominant negative mutant of CREB caused a significant inhibition of hCG stimulation of leptin promoter activity. These results demonstrate that hCG indeed activates cAMP/PKA pathway, and that this pathway is involved in leptin expression. Nevertheless, we found leptin induction by hCG is dependent on cAMP levels. Treatment with (Bu)2cAMP in combination with low and non stimulatory hCG concentrations led to an increase in leptin expression, whereas stimulatory concentrations showed the opposite effect. We found that specific PKA inhibition by H89 caused a significant increase of hCG leptin induction, suggesting that probably high cAMP levels might inhibit hCG effect. It was found that hCG enhancement of leptin mRNA expression involved the MAPK pathway. In this work, we demonstrated that hCG leptin induction through the MAPK signaling pathway is inhibited by PKA. We observed that ERK1/2 phosphorylation increased when hCG treatment was combined with H89. In view of these results, the involvement of the alternative cAMP/Epac signaling pathway was studied. We observed that a cAMP analogue that specifically activates Epac (CPT-OMe) stimulated leptin expression by hCG. In addition, the overexpression of Epac and Rap1 proteins increased leptin promoter activity and enhanced hCG. In conclusion, we provide evidence suggesting that hCG induction of leptin gene expression in placenta is mediated not only by activation of the MAPK signaling pathway but also by the alternative cAMP/Epac signaling pathway. PMID:23056265

The Risk of Preeclampsia According to High Thyroid Function in Pregnancy Differs by hCG Concentration.

PubMed

Korevaar, Tim I M; Steegers, Eric A P; Chaker, Layal; Medici, Marco; Jaddoe, Vincent W V; Visser, Theo J; de Rijke, Yolanda B; Peeters, Robin P

2016-12-01

During pregnancy, there is an increased demand for thyroid hormone. The pregnancy hormone human chorionic gonadotropin (hCG) is an important physiological stimulator of thyroid function. Already high-normal maternal free T 4 concentrations are associated with a higher risk of preeclampsia. The objective of the investigation was to study our hypothesis that hCG concentrations can distinguish a physiological form of high thyroid function from a more pathological form of high thyroid function and that the risk of preeclampsia would differ accordingly. TSH, free T 4 , hCG, or thyroperoxidase antibody concentrations were determined in pregnant women participating in a population-based prospective cohort study. The study was conducted in the general community. A nonselected sample of 5146 pregnant women participated in the study. There were no interventions. Preeclampsia was measured. Women with high hCG-associated high thyroid function did not have a higher risk of preeclampsia than women with normal thyroid function. In contrast, women with low hCG and high thyroid function had a 3.4- to 11.1-fold higher risk of preeclampsia. These risk estimates were amplified in women with a high body mass index. Women with a low hCG and suppressed TSH (<0.10 mU/L) had a 3.2- to 8.9-fold higher risk of preeclampsia. hCG was not associated with preeclampsia, and results remained similar after exclusion of thyroperoxidase antibody-positive women. This study suggests that, in contrast to women with a high hCG associated high thyroid function, women with low hCG and high thyroid function during pregnancy are at a higher risk of developing preeclampsia. The additional measurement of hCG may therefore help to distinguish a more pathological form of high thyroid function and women at a high risk of preeclampsia.

HCG-Activated Human Peripheral Blood Mononuclear Cells (PBMC) Promote Trophoblast Cell Invasion

PubMed Central

Wang, Yaqin; Guo, Yue; Zhou, Danni; Xu, Mei; Ding, Jinli; Yang, Jing

2015-01-01

Successful embryo implantation and placentation depend on appropriate trophoblast invasion into the maternal endometrial stroma. Human chorionic gonadotropin (hCG) is one of the earliest embryo-derived secreted signals in the peripheral blood mononuclear cells (PBMC) that abundantly expresses hCG receptors. The aims of this study were to estimate the effect of human embryo–secreted hCG on PBMC function and investigate the role and underlying mechanisms of activated PBMC in trophoblast invasion. Blood samples were collected from women undergoing benign gynecological surgery during the mid-secretory phase. PBMC were isolated and stimulated with or without hCG for 0 or 24 h. Interleukin-1β (IL-1β) and leukemia inhibitory factor (LIF) expressions in PBMC were detected by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (PCR). The JAR cell line served as a model for trophoblast cells and was divided into four groups: control, hCG only, PBMC only, and PBMC with hCG. JAR cell invasive and proliferative abilities were detected by trans-well and CCK8 assays and matrix metalloproteinase (MMP)-2 (MMP-2), MMP-9, vascular endothelial growth factor (VEGF), tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 expressions in JAR cells were detected by western blotting and real-time PCR analysis. We found that hCG can remarkably promote IL-1β and LIF promotion in PBMC after 24-h culture. PBMC activated by hCG significantly increased the number of invasive JAR cells in an invasion assay without affecting proliferation, and hCG-activated PBMC significantly increased MMP-2, MMP-9, and VEGF and decreased TIMP-1 and TIMP-2 expressions in JAR cells in a dose-dependent manner. This study demonstrated that hCG stimulates cytokine secretion in human PBMC and could stimulate trophoblast invasion. PMID:26087261

Intrauterine administration of recombinant human chorionic gonadotropin before embryo transfer on outcome of in vitro fertilization/ intracytoplasmic sperm injection: A randomized clinical trial

PubMed Central

Zarei, Afsoon; Parsanezhad, Mohammad Ebrahim; Younesi, Masoumeh; Alborzi, Saeed; Zolghadri, Jaleh; Samsami, Alamtaj; Amooee, Sedigheh; Aramesh, Shahintaj

2014-01-01

Background: The direct effect of hCG on the human endometrium was studied several times. Objective: The objectives of this study were to evaluate the effectiveness of intrauterine injection of recombinant human chorionic gonadotropin (rhCG) before embryo transfer (ET). Materials and Methods: In this randomized placebo-controlled clinical trial, a total number of 182 infertile patients undergoing their first in vitro fertilization/ intracytoplasmic sperm injection (IVF-ICSI) cycles were randomly assigned to receive 250μg intrauterine rhCG (n=84) or placebo (n=98) before ET. The implantation and pregnancy rates were compared between groups. Results: Patients who received intrauterine rhCG before ET had significantly higher implantation (36.9% vs. 22.4%; p=0.035), clinical pregnancy rates (34.5% vs. 20.4%; p=0.044) and ongoing pregnancy rate (32.1% vs. 18.4%; p=0.032) when compared to those who received placebo. The abortion (2.4% vs. 2.0%; p=0.929) and ectopic pregnancy rates (1.2% vs. 1.0%; p=0.976) were comparable between groups of rhCG and placebo, respectively. Conclusion: Intrauterine injection of 250μg of rhCG before ET significantly improves the implantation and pregnancy rates in IVF/ICSI cycles. Registration ID in IRCT: IRCT2012121711790N1 This article extracted from fellowship course thesis. (Masoumeh Younesi) PMID:24799855

Relevance of Wnt10b and activation of β-catenin/GCMa/syncytin-1 pathway in BeWo cell fusion.

PubMed

Malhotra, Sudha Saryu; Banerjee, Priyanka; Chaudhary, Piyush; Pal, Rahul; Gupta, Satish Kumar

2017-10-01

To study the involvement of specific Wnt(s) ligand during trophoblastic BeWo cell differentiation. BeWo cells on treatment with forskolin/human chorionic gonadotropin (hCG) were studied for cell fusion by desmoplakin I+II staining and/or hCG secretion by ELISA. Levels of Wnt10b/β-catenin/glial cell missing a (GCMa)/syncytin-1 were studied by qPCR/Western blotting in forskolin-/hCG-treated control siRNA and Wnt10b silenced BeWo cells. BeWo cells on treatment with hCG (5 IU/mL) led to a 94-fold increase in Wnt10b transcript. Wnt10b silencing showed significant decrease in forskolin-/hCG-mediated BeWo cell fusion and/or hCG secretion. It led to down-regulation of β-catenin (nuclear and cytoplasmic), GCMa and syncytin-1 expression. Treatment of BeWo cells with H89, protein kinase A (PKA) signaling inhibitor, significantly reduced forskolin-/hCG-induced Wnt10b, β-catenin, and syncytin-1 expression, which also resulted in reduced cell fusion. Wnt10b is involved in forskolin/hCG-mediated BeWo cell fusion via β-catenin/GCMa/syncytin pathway, which may also involve activation of PKA. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The application of hCG, CPH and Ovopel in successful artificial reproduction of goldfish (Carassius auratus auratus) under controlled conditions.

PubMed

Targońska, K; Kucharczyk, D

2011-08-01

Artificial reproduction of fish is one of the main goals of aquaculture production. The aim of this study is to optimize the method of goldfish reproduction under controlled conditions by comparing the effectiveness of carp pituitary homogenate (CPH), Ovopel and human chorionic gonadotropin (hCG), administered as a one-off dose and inducing two spawns in the same fish within a short time period. Goldfish spawners were stimulated with hCG, CPH and Ovopel, and the results were compared to the fish from the control group, comprised of unstimulated fish. In another experiment, spawn were induced twice within an interval of 21 days with the same group of fish. The best results in the first experiment in terms of the percentage of ovulating females and survival to the eyed-egg stage were achieved after administering hCG (100% and 88.7%, respectively). However, the highest fecundity was observed in fish stimulated with Ovopel (89,960 eggs/kg). It was shown in the second experiment that female goldfish produce higher weight of eggs during the first spawning, but the number of eggs/BW ratio was higher during the next reproduction process. Survival, both that of embryos to the eyed-egg stage and that of spawners, is higher during the first reproduction act. © 2010 Blackwell Verlag GmbH.

Establishing reference intervals for hCG in postmenopausal women.

PubMed

Patel, Khushbu K; Qavi, Abraham J; Hock, Karl G; Gronowski, Ann M

2017-03-01

Plasma concentrations of human chorionic gonadotropin (hCG) have been shown to increase with age due to pituitary secretion. We previously recommended that an hCG cutoff of 14.0IU/L be used for women ≥55years of age. However, it remains unknown whether concentrations >14.0IU/L can be expected in women with advanced age. Our objectives were to establish plasma hCG reference intervals and correlate follicle stimulating hormone (FSH) and hCG concentrations in postmenopausal females ≥55years. Residual plasma samples from 798 women ≥55years were utilized with 303, 269, and 226 samples belonging to the age groups 55-69, 70-84, and ≥85years, respectively. FSH and hCG were measured using the Abbott ARCHITECT. All positive hCG samples (hCG ≥5IU/L) were analyzed for potential heterophile antibody interference and 3 were excluded. Electronic medical records were reviewed and patients with malignancy were excluded. 8% (56/666) of women age≥55years had plasma hCG ≥5IU/L. There were 19, 16, and 21 patients with hCG ≥5IU/L in the age groups 55-69, 70-84, and ≥85years, respectively. The highest hCG concentrations observed in each age group were: 55-69years maximum=11.7IU/L and 97.5th percentile=9.6IU/L; 70-84years maximum=18.09IU/L, 97.5th percentile=6.2IU/L; ≥85years maximum=11.1IU/L and 97.5th percentile=10.0IU/L, and the overall 97.5th percentile=8.5IU/L for all women ≥55years of age. Neither hCG nor FSH concentrations continued to increase with age in women ≥55years. The prevalence of positive hCG in women ≥55years is 8%. This study confirms our previously recommended cutoff of 14IU/L for women ≥55years of age. In women ≥55years of age, FSH concentrations do not predict hCG concentrations. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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

Expression and regulation of the tumor suppressor, SEF, during folliculogenesis in humans and mice.

PubMed

Lutwak, Ela; Price, Christopher A; Abramovich, Sagit-Sela; Rabinovitz, Shiri; Granot, Irit; Dekel, Nava; Ron, Dina

2014-11-01

Similar expression to FGF (Sef or IL17-RD), is a tumor suppressor and an inhibitor of growth factors as well as of pro-inflammatory cytokine signaling. In this study, we examined the regulation of Sef expression by gonadotropins during ovarian folliculogenesis. In sexually immature mice, in situ hybridization (ISH) localized Sef gene expression to early developing oocytes and granulosa cells (GC) but not to theca cells. Sef was also expressed in mouse ovarian endothelial cells, in the fallopian tube epithelium as well as in adipose tissue venules. SEF protein expression, determined by immunohistochemistry (IHC), correlated well with Sef mRNA expression in GC, while differential expression was noticed in oocytes. High Sef mRNA but undetectable SEF protein levels were observed in the oocytes of primary/secondary follicles, while an inverse correlation was found in the oocytes of preantral and small antral follicles. Sef mRNA expression dropped after pregnant mare's serum gonadotropin (PMSG) administration, peaked at 6-8 h after human chorionic gonadotropin (hCG) treatment, and declined by 12 h after this treatment. ISH and IHC localized the changes to oocytes and mural GC following PMSG treatment, whereas Sef expression increased in mural GC and declined in granulosa-lutein cells upon hCG treatment. The ovarian expression of SEF was confirmed using human samples. ISH localized SEF transcripts to human GC of antral follicles but not to corpora lutea. Furthermore, SEF mRNA was detected in human GC recovered from preovulatory follicles. These results are the first to demonstrate SEF expression in a healthy ovary during folliculogenesis. Hormonal regulation of its expression suggests that SEF may be an important factor involved in intra-ovarian control mechanisms. © 2014 Society for Reproduction and Fertility.

High exposure to progesterone between the end of menstruation and the day of triggering final oocyte maturation is associated with a decreased probability of pregnancy in patients treated by in vitro fertilization and intracytoplasmic sperm injection.

PubMed

Kyrou, Dimitra; Kolibianakis, Efstratios M; Fatemi, Human M; Camus, Michel; Tournaye, Herman; Tarlatzis, Basil C; Devroey, Paul

2011-10-01

To investigate the association between the probability of pregnancy and hormone exposure between the end of menstruation and the day of triggering final oocyte maturation (menstruation-free interval). Prospective study. University. One hundred women (aged ≤ 39 years) stimulated with a fixed dose of recombinant follicle-stimulating hormone (200 IU). Daily gonadotropin-releasing hormone antagonist (GnRH, 0.25 mg) used from day 6 of stimulation onward, final oocyte maturation triggered by administration of 10,000 IU of human chorionic gonadotropin (hCG) as soon as ≥ 3 follicles ≥ 17 mm were present, and hormone assessment performed at initiation of stimulation, on the first day after menstruation had stopped, on the day of antagonist initiation, and on the day of hCG administration. The association between hormone exposure during the menstruation-free interval and the probability of ongoing pregnancy. The exposure to progesterone during the menstruation-free interval was statistically significantly higher in patients who did not become pregnant compared with those who did (4.20 ± 2.54 vs. 3.13 ± 1.14, respectively). Binary logistic regression confirmed the adverse effect of the increased exposure to progesterone for the achievement of pregnancy. In recombinant follicle-stimulating hormone/gonadotropin-releasing hormone antagonist in vitro fertilization/intracytoplasmic sperm injection cycles, a lower probability of pregnancy is associated with a higher exposure to progesterone during the menstruation-free interval. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Prader-Willi syndrome with elevated follicle stimulating hormone levels and diabetes mellitus.

PubMed

Nagai, T; Mimura, N; Tomizawa, T; Monden, T; Mori, M

1998-12-01

A 21 -year-old man with Prader-Willi syndrome (PWS) was hospitalized due to hyperglycemia. After diet therapy and transient insulin administration, his blood glucose levels improved. Based on the fact that his urinary C-peptide levels increased, the diabetes mellitus may have been due to insulin resistance with obesity. In addition, his testes had become atrophied. Testosterone levels remained low even after human chorionic gonadotropin (HCG) administration. Luteinizing hormone (LH) levels were also low after LH releasing hormone (LHRH) administration. The LH response increased slightly after daily LHRH administration, indicating hypothalamic hypogonadism. Follicle stimulating hormone (FSH) levels were, however, high and increased after LHRH administration. The selective FSH elevation may have been due to the accompanying idiopathic oligospermia.

Pulsatile GnRH Is Superior to hCG in Therapeutic Efficacy in Adolescent Boys With Hypogonadotropic Hypogonadodism.

PubMed

Gong, Chunxiu; Liu, Ying; Qin, Miao; Wu, Di; Wang, Xiaoling

2015-07-01

We investigated the efficacy and safety of two different treatments that have not been evaluated in peripuberty boys with hypogonadotropic hypogonadism (HH). The objective of the study was to assess the effectiveness and safety of GnRH or human chorionic gonadotropin (hCG) treatment in adolescent boys with HH. Twelve patients received 8-10 μg of GnRH, sc injected every 90 minutes using a pump. Another 22 patients received hCG, injected im as follows: for the first 3 months, 1000 IU of hCG was injected two times per week and then once every other day for the next 3 months. The dose of hCG was increased to 2000 IU after a 6-month treatment and the above cycle was repeated for another 6 months. All patients were treated for 12-14 months and followed up every 3 months. Thirty-five participants were chosen from Beijing Children's Hospital from 2008 to 2014. Twenty-three patients with Kallmann syndrome and 12 with normosmic idiopathic hypogonadotropic hypogonadism. The age ranged from 10 to 16 years. Twelve patients were treated with pulsatile pump GnRH (group 1), and 22 patients were treated with im hCG (group 2). One patient was treated successively with hCG and GnRH, which was removed in data analysis. Testicular volume was measured by an orchidometer. The levels of T, LH, and FSH serum were measured with a chemiluminesent immunoassay. Bone age was measured by x-ray. Patients treated with GnRH showed larger testes than those treated with hCG. Patients in both groups showed a significantly increased length of penis and T levels. But the difference of the two groups was not statistically significant. There was no significant difference in side effects in both groups. Boys with HH may be effectively treated with GnRH. We suggested that GnRH exhibits higher efficacy in treating adolescent boys with HH than hCG.

Contributions of arginines-43 and -94 of human choriogonadotropin. beta. to receptor binding and activation as determined by oligonucleotide-based mutagenesis

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

Fang Chen; Puett, D.

1991-10-22

Members of the glycoprotein hormone family contain a common {alpha} subunit and a hormone-specific {beta} subunit. Human choriogonadotropin (hCG) {beta} is a 145 amino acid residue protein glycosylated at 6 positions (2 N-linked and 4 O-linked oligosaccharides). In an effort to elucidate receptor determinants on hCG{beta}, the authors have used site-directed mutagenesis to prepare and express several mutant cDNAs with replacements at arginines-43 and -94. Arg-43 is invariant in all known mammalian CG/lutropin {beta} amino acid sequences, and Arg-94 is conserved in 10 of the 12 sequences. Moreover, various studies involving synthetic peptides and enzymatic digestions of intact {beta} chainsmore » suggest that these residues may be important in hCG receptor binding. Point mutants were made in which these two arginines were replaced with the corresponding residues in human follitropin {beta}, Leu-43 and Asp-94. The wild-type and mutant {beta} chains were expressed in CHO cells containing a stably integrated gene for bovine {alpha}, and heterodimer formation occurred. These heterologous gonadotropins were active in assays using transformed Leydig cells, competitive binding with standard {sup 125}I-hCG, and cAMP and progesterone production, but the potency was considerably less than that associated with the hCG{beta} wild-type-containing gonadotropin. The double-mutant protein Arg-43 to Leu/Arg-94 to Asp also associated with bovine {alpha}, but the resultant heterodimer exhibited only low activity. Replacement but the Lys-43-containing {beta} chain appeared to exhibit a low degree of subunit association or reduced stability relative to the expressed hCG{beta} wild type. These results demonstrate that arginines-43 and -94 contribute to receptor binding through a positive charge.« less

Direct analysis of hCGβcf glycosylation in normal and aberrant pregnancy by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

PubMed

Iles, Ray K; Cole, Laurence A; Butler, Stephen A

2014-06-05

The analysis of human chorionic gonadotropin (hCG) in clinical chemistry laboratories by specific immunoassay is well established. However, changes in glycosylation are not as easily assayed and yet alterations in hCG glycosylation is associated with abnormal pregnancy. hCGβ-core fragment (hCGβcf) was isolated from the urine of women, pregnant with normal, molar and hyperemesis gravidarum pregnancies. Each sample was subjected to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) analysis following dithiothreitol (DTT) reduction and fingerprint spectra of peptide hCGβ 6-40 were analyzed. Samples were variably glycosylated, where most structures were small, core and largely mono-antennary. Larger single bi-antennary and mixtures of larger mono-antennary and bi-antennary moieties were also observed in some samples. Larger glycoforms were more abundant in the abnormal pregnancies and tri-antennary carbohydrate moieties were only observed in the samples from molar and hyperemesis gravidarum pregnancies. Given that such spectral profiling differences may be characteristic, development of small sample preparation for mass spectral analysis of hCG may lead to a simpler and faster approach to glycostructural analysis and potentially a novel clinical diagnostic test.

[Difficulties in adressing purging behaviour in the treatment of a patient with anorexia nervosa].

PubMed

Keifenheim, Katharina Eva; Giel, Katrin Elisabeth; Leehr, Elisabeth Johanna; Becker, Sandra; Mörike, Klaus; Zipfel, Stephan; Teufel, Martin

2013-08-01

We report on a 24-year-old patient with secondary amenorrhoea, underweight (BMI 15,0 kg/m²), and a fear of weight gain, who used laxatives, diuretics, excessive sport and human chorionic gonadotropin (hCG) for weight regulation. On physical examination, cachexia, bradycardia, lanugo hair on face and back, and cyanosis of hands and feet were observed. In the laboratory findings, leukopenia, recurrent low potassium and an elevated mean corpuscular volume (MCV) were remarkable. We diagnosed anorexia nervosa, binge/purging type (AN-BP). We treated the patient for seven weeks in a multimodal setting specific for patients with eating disorders. She gained 3.9 kg (11% of her initial weight). Special challenges included the complications of her laxative abuse as well as her distinct body image disturbance. With knowledge of her background, we understood this misuse of hCG. Purging behaviour should be questioned in detail in patients with eating disorders, because purging methods are not always reported right away and are accompanied with great shame. However, purging behaviour can be very dangerous to one's health. Using a hCG diet (Hollywood diet) is a rare purging method in patients with anorexia nervosa. © Georg Thieme Verlag KG Stuttgart · New York.

Human Chorionic Gonadotropine in Cul-de-sac Fluid in Tubal Ectopic Pregnacy; A New Diagnostic Approach

PubMed Central

Karahasanoglu, Ayse; Ozdemir, Mucize; Yazicioglu, Fehmi

2016-01-01

Introduction Although new diagnostic abilities are being utilised increasingly yet early detection of tubal pregnancy remains a challenge. The use of highly sensitive hCG kits has facilitated the early diagnosis of a pregnancy. But it takes time to determine the localisation of the pregnancy. Early diagnosis of ectopic pregnancy may reduce the morbidity of ectopic pregnancy. Aim This study was conducted to analyse the cul-de-sac and serum βhCG ratio in tubal ectopic pregnancy cases which may be a new diagnostic approach for ectopic pregnancy. Materials and Methods Between January 2004 and July 2011, 263 patients with ectopic pregnancy were included in the study. Risk factors of patients and treatment modalities were evaluated. hCG was measured in peripheral serum and peritoneal fluid, obtained by puncture of Douglas pouch in 52 patients with tubal ectopic pregnancy. hCG level was determined in the cul-de-sac fluid and in the maternal serum for comparison. Results Tubectomy (5.3%), history of abortion (9.5%), history of previous surgery (14.8%), previous cesarean section (8%) and pelvic infamatorry disease (15.9 %) were the important risk factors for ectopic pregnancy in our cases. In 51 of 52 patients with tubal pregnancy, the cul-de-sac hCG vaule and the serum hCG value ratio was >1. Conclusion It is concluded that the ratio of hCG in cul-de –sac and serum can be used for the verification of tubal ectopic pregnancy in addition to other diagnostic methods. This may help rapid confirmation of the diagnosis of ectopic pregnancy. PMID:27190895

Cervical poorly differentiated adenocarcinoma with dominant choriocarcinomatous pattern--A case report.

PubMed

Nikolić, Branka; Ćurković, Aleksandar; Dikić, Svetlana Dragojević; Mitrović, Ana; Kuzmanović, Igor; Arandjelović, Aleksandra; Stanković, Goran

2015-07-01

Gestational trophoblastic neoplasm (GTN), choriocarcinoma in coexistence with primary cervical adenocarcinoma, is a rare event not easy to diagnose. Choriocarcinoma is a malignant form of GTN but curable if metastases do not appear early and spread fast. We presented choriocarcinoma in coexistence with primary cervical adenocarcinoma in a 48-year-old patient who had radical hysterectomy because of confirmed cervical carcinoma (Dg: Carcinomaporo vaginalis uteri FIGO st I B1). Histological findings confirmed cervical choriocarcinoma with extensive vascular invasion and apoptosis but GTN choriocarcinoma was finally confirmed after immunohystochemical examinations. Preoperative serum human gonadotropine (beta hCG) level stayed unknown. This patient did not have any pregnancy-like symptoms before the operation. The first beta hCG monitoring was done two months after the operation and found negative. According to the final diagnosis the decision of Consilium for Malignant Diseases was that this patient needed serum hCG monitoring as well as treatment with chemotherapy for high-risk GTN and consequent irradiation for adenocarcinoma. The early and proper diagnosis of nonmetastatic choriocarcinoma of nongestational origine in coexistence with cervical carcinoma is curable and can have good prognosis.

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.

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.

The function of the corpus luteum of pregnancy in ovulatory dysfunction and luteal phase deficiency.

PubMed

Soules, M R; Hughes, C L; Aksel, S; Tyrey, L; Hammond, C B

1981-07-01

Relatively little knowledge exists of corpus luteum function in early pregnancy after the successful treatment of ovulatory dysfunction or luteal phase deficiency. To assess the activity of the corpus luteum of such patients, human chorionic gonadotropin (hCG) and 17-hydroxyprogesterone (17-OH-P) levels were determined in serum samples obtained from normal women (44 patients), women with ovulatory dysfunction (10 patients), and women with luteal phase deficiency (7 patients); all determinations were made during conceptive cycles, and sampling continued into the first trimester of pregnancy. There were no statistically significant abnormalities of hCG levels when infertility patients were compared with control patients. According to the premise that 17-OH-P levels reflect corpus luteal function, there appeared to be adequate function in pregnancies after progesterone treatment of luteal phase deficiency. In pregnancies following ovulation induction with clomiphene, the corpus luteum function, on the basis of 17-OH-P levels, was significantly increased in magnitude and duration. These results have clinical implications with regard to supplemental hormone therapy in early pregnancy.

Effect of kisspeptin-10, LH and hCG on serum testosterone concentrations in stallions, donkeys and mules.

PubMed

Akhtar, Rana Waseem; Shah, Syed Aftab Hussain; Qureshi, Irfan Zia

2017-10-15

This study was conducted to determine the response of serum testosterone (T) in male equines (stallions, donkeys and mules) after administering intravenous doses of kisspeptin-10 (KP-10), human chorionic gonadotropin (hCG) and luteinizing hormone (LH) and saline as a control. The animals were divided into four groups of three each: Group I, 3 ml of 0.95% saline; Group II, 50 μg KP-10; Group III, 2500 IU hCG and group IV, 400 μg LH. The administration of KP-10 and hCG to stallions resulted in a significant increase in serum T concentration at 240 min; whereas it was significantly higher at 30, 60, 120, and 240 min with LH treatment as compared to pre-dose concentrations. Both KP-10 and hCG significantly elevated the T concentrations in donkeys at 120 and 240 min, respectively; whereas it was significantly higher at 60, 120, and 240 min with LH treatment as compared to pre-dose concentration. Both KP-10 and LH elevated T in donkeys at 240 min as compared to the control and hCG concentrations. After 120 and 240 min, T concentrations in mules were higher (p < 0.05) with administration of KP-10, hCG and LH as compared to the control. In conclusion, the administration of KP-10, hCG and LH elevate the serum T concentration in normal male equines. It is suggested that KP-10 may be useful in situations where an increase in T is desired. Further work is required to determine the effect of KP-10 on T in male equids with reproductive abnormalities before it can be used in clinical situations. Copyright © 2017 Elsevier Inc. All rights reserved.

Insulin stimulates synthesis and release of human chorionic gonadotropin by choriocarcinoma cell lines

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

Ren, S.G.; Braunstein, G.D.

1991-03-01

Recent studies have shown that insulin regulates placental lactogen, progesterone, and estrogen production from human trophoblast cells. This study was performed to examine whether insulin also regulates the production of hCG by this type of cell. After 24-36 h of preincubation, JEG-3 and JAR cells (2-3 x 10(5) cells/ml.well) or human term trophoblast cells (1 x 10(6) cells/ml.well) were exposed to the test hormone in serum-free Dulbecco's Modified Eagle's Medium for 24-96 h. Secretion of hCG from JEG-3 cells was stimulated by human insulin, human proinsulin, or porcine insulin in a dose-dependent manner, with lowest effective doses of 6.7, 96,more » and 53 mg/L, respectively. Time-course studies showed that hCG secretion peaked at 72-96 h with insulin exposure; in contrast, no decernable peak was seen without insulin in serum-free media. Exposure of JEG-3 cells for 24 h to 209 mg/liter insulin stimulated hCG synthesis, with 40 +/- 3% more immunoreactive intracellular hCG (P less than 0.05). Cells grown in the presence of insulin and (35S)methionine had 47 +/- 21% more labeled intracellular hCG and 56 +/- 13% more immunoprecipitable (35S)methionine-hCG secreted into the medium than the control cultures (P less than 0.05). During this time period, human placental lactogen release and total trichloroacetice acid-precipitable (35S)methionine protein were not increased. The insulin-induced stimulation of hCG synthesis was inhibited by cycloheximide. Additionally, insulin did not significantly affect total intracellular protein during 24-96 h of incubation. Insulin also increased hCG release from JAR cells, but not from human term trophoblast cells. A mouse monoclonal antibody to the IGF-I receptor inhibited the stimulation of insulin in JEG-3 cells.« less

Increasing age influences uterine integrity, but not ovarian function or oocyte quality, in the cheetah (Acinonyx jubatus).

PubMed

Crosier, Adrienne E; Comizzoli, Pierre; Baker, Tom; Davidson, Autumn; Munson, Linda; Howard, JoGayle; Marker, Laurie L; Wildt, David E

2011-08-01

Although the cheetah (Acinonyx jubatus) routinely lives for more than 12 yr in ex situ collections, females older than 8 yr reproduce infrequently. We tested the hypothesis that reproduction is compromised in older female cheetahs due to a combination of disrupted gonadal, oocyte, and uterine function/integrity. Specifically, we assessed 1) ovarian response to gonadotropins; 2) oocyte meiotic, fertilization, and developmental competence; and 3) uterine morphology in three age classes of cheetahs (young, 2-5 yr, n = 17; prime, 6-8 yr, n = 8; older, 9-15 yr, n = 9). Ovarian activity was stimulated with a combination of equine chorionic gonadotropin and human chorionic gonadotropin (hCG), and fecal samples were collected for 45 days before gonadotropin treatment and for 30 days after oocyte recovery by laparoscopy. Twenty-six to thirty hours post-hCG, uterine morphology was examined by ultrasound, ovarian follicular size determined by laparoscopy, and aspirated oocytes assessed for nuclear status or inseminated in vitro. Although no influence of age on fecal hormone concentrations or gross uterine morphology was found (P > 0.05), older females produced fewer (P < 0.05) total antral follicles and oocytes compared to younger counterparts. Regardless of donor age, oocytes had equivalent (P > 0.05) nuclear status and ability to reach metaphase II and fertilize in vitro. A histological assessment of voucher specimens revealed an age-related influence on uterine tissue integrity, with more than 87% and more than 56% of older females experiencing endometrial hyperplasia and severe pathologies, respectively. Our collective findings reveal that lower reproductive success in older cheetahs appears to be minimally influenced by ovarian and gamete aging and subsequent dysfunction. Rather, ovaries from older females are responsive to gonadotropins, produce normative estradiol/progestogen concentrations, and develop follicles containing oocytes with the capacity to mature and be fertilized. A more likely cause of reduced fertility may be the high prevalence of uterine endometrial hyperplasia and related pathologies. The discovery that a significant proportion of oocytes from older females have developmental capacity in vitro suggests that in vitro fertilization and embryo transfer may be useful for "rescuing" the genome of older, nonreproductive cheetahs.

Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial

PubMed Central

Strug, Michael R.; Su, Renwei; Young, James E.; Dodds, William G.; Shavell, Valerie I.; Díaz-Gimeno, Patricia; Ruíz-Alonso, Maria; Simón, Carlos; Lessey, Bruce A.; Leach, Richard E.; Fazleabas, Asgerally T.

2016-01-01

STUDY QUESTION Does a single intrauterine infusion of human chorionic gonadotropin (hCG) at the time corresponding to a Day 3 embryo transfer in oocyte donors induce favorable molecular changes in the endometrium for embryo implantation? SUMMARY ANSWER Intrauterine hCG was associated with endometrial synchronization between endometrial glands and stroma following ovarian stimulation and the induction of early decidual markers associated with stromal cell survival. WHAT IS KNOWN ALREADY The clinical potential for increasing IVF success rates using an intrauterine hCG infusion prior to embryo transfer remains unclear based on previously reported positive and non-significant findings. However, infusion of CG in the non-human primate increases the expression of pro-survival early decidual markers important for endometrial receptivity, including α-smooth muscle actin (α-SMA) and NOTCH1. STUDY DESIGN, SIZE, DURATION Oocyte donors (n=15) were randomly assigned to receive an intrauterine infusion of 500 IU hCG (n=7) or embryo culture media vehicle (n=8) 3 days following oocyte retrieval during their donor stimulation cycle. Endometrial biopsies were performed 2 days later, followed by either RNA isolation or tissue fixation in formalin and paraffin embedding. PARTICIPANTS/MATERIALS, SETTING, METHODS Reverse transcription of total RNA from endometrial biopsies generated cDNA, which was used for analysis in the endometrial receptivity array (ERA; n = 5/group) or quantitative RT–PCR to determine relative expression of ESR1, PGR, C3 and NOTCH1. Tissue sections were stained with hematoxylin and eosin followed by blinded staging analysis for dating of endometrial glands and stroma. Immunostaining for ESR1, PGR, α-SMA, C3 and NOTCH1 was performed to determine their tissue localization. MAIN RESULTS AND THE ROLE OF CHANCE Intrauterine hCG infusion was associated with endometrial synchrony and reprograming of stromal development following ovarian stimulation. ESR1 and PGR were significantly elevated in the endometrium of hCG-treated patients, consistent with earlier staging. The ERA did not predict an overall positive impact of intrauterine hCG on endometrial receptivity. However, ACTA2, encoding α-SMA was significantly increased in response to intrauterine hCG. Similar to the hCG-treated non-human primate, sub-epithelial and peri-vascular α-SMA expression was induced in women following hCG infusion. Other known targets of hCG in the baboon were also found to be increased, including C3 and NOTCH1, which have known roles in endometrial receptivity. LIMITATIONS, REASONS FOR CAUTION This study differs from our previous work in the hCG-treated non-human primate along with clinical studies in infertile patients. Specifically, we performed a single intrauterine infusion in oocyte donors instead of either continuous hCG via an osmotic mini-pump in the baboon or infusion followed by blastocyst-derived hCG in infertile women undergoing embryo transfer. Therefore, the full impact of intrauterine hCG in promoting endometrial receptivity may not have been evident. WIDER IMPLICATIONS OF THE FINDINGS Our findings suggest a potential clinical benefit for intrauterine hCG prior to embryo transfer on Day 3 in counteracting endometrial dyssynchrony from ovarian stimulation and promoting expression of markers important for stromal survival. Finally, there were no obvious negative effects of intrauterine hCG treatment. STUDY FUNDING/COMPETING INTEREST(S) Funding for this work was provided by NICHD R01 HD042280 (A.T.F.) and NICHD F30 HD082951 (M.R.S.). C.S. and P.D.-G are co-inventors of the patented ERA, which is owned by IGENOMIX SL and was used in this study, and C.S. is a shareholder in IGENOMIX SL. M.R.-A. is employed by IGENOMIX SL. No other authors have any conflicts of interest to report. TRIAL REGISTRATION NUMBER This study was registered with ClinicalTrials.gov (NCT01786252). TRIAL REGISTRATION DATE 5 February 2013. DATE OF FIRST PATIENT'S ENROLLMENT 10 May 2013. PMID:27122490

Medical management of ectopic pregnancy with single-dose and 2-dose methotrexate protocols: human chorionic gonadotropin trends and patient outcomes.

PubMed

Mergenthal, Michelle C; Senapati, Suneeta; Zee, Jarcy; Allen-Taylor, Lynne; Whittaker, Paul G; Takacs, Peter; Sammel, Mary D; Barnhart, Kurt T

2016-11-01

Ectopic pregnancy, although rare, is an important cause of female morbidity and mortality and early, effective treatment is critical. Systemic methotrexate has become widely accepted as a safe and effective alternative to surgery in the stable patient. As the number and timing of methotrexate doses differ in the 3 main medical treatment regimens, one might expect trends in serum human chorionic gonadotropin and time to resolution to vary depending on protocol. Furthermore, human chorionic gonadotropin trends and time to resolution may predict ultimate treatment success. This study hypothesized that the 2-dose methotrexate protocol would be associated with a faster initial decline in serum human chorionic gonadotropin levels and a shorter time to resolution compared to the single-dose protocol. A prospective multicenter cohort study included clinical data from women who received medical management for ectopic pregnancy. Rates of human chorionic gonadotropin change and successful pregnancy resolution were assessed. Propensity score modeling addressed confounding by indication, the potential for differential assignment of patients with better prognosis to the single-dose methotrexate protocol. In all, 162 ectopic pregnancies were in the final analysis; 114 (70%) were treated with the single-dose methotrexate and 48 (30%) with the 2-dose protocol. Site, race, ethnicity, and reported pain level were associated with differential protocol allocation (P < .001, P = .011, P < .001, and P = .035, respectively). Women had similar initial human chorionic gonadotropin levels in either protocol but the mean rate of decline of human chorionic gonadotropin from day 0 (day of administration of first dose of methotrexate) to day 7 was significantly more rapid in women who received the single-dose protocol compared to those treated with the 2-dose protocol (mean change -31.3% vs -10.4%, P = .037, adjusted for propensity score and site). The 2 protocols had no significant differences in success rate or time to resolution. In a racially and geographically diverse group of women, the single- and double-dose methotrexate protocols had comparable outcomes. The more rapid human chorionic gonadotropin initial decline in the single-dose group suggested these patients were probably at lower risk for ectopic rupture than those getting the 2-dose protocol. A prospective randomized controlled design is needed to remove confounding by indication. Copyright © 2016 Elsevier Inc. All rights reserved.

Prognostic value of total testosterone for pregnancy during treatment in patients with clomiphene-citrate-resistant polycystic ovary syndrome: a pilot study.

PubMed

Li, Chunyang; Cheng, Jing; Wang, Jianguang; Xue, Yamei; Huang, Zhaoxia; Zhang, Shengkun; Lv, Jieqiang

2011-09-01

Reduction of serum total testosterone (TT) is associated with pregnancy rate in polycystic ovary syndrome (PCOS) women receiving metformin, but most of the studies focus on the changes of basal levels of TT. The aim of this study was to evaluate whether the TT level around the ovulation period is related to the outcome of pregnancy in women with PCOS. In total, 30 non-obese PCOS women with clomiphene citrate (CC) resistance from the Medical College's Reproductive Health Center were enrolled and randomly assigned to be treated with placebo (Group 1) or metformin (850 mg) (Group 2) twice daily for 3 months as the pre-treatment. Then, metformin alone was administered with CC, human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG) to induce ovulation for 3 months in Group 1. In Group 2, CC/HMG/HCG was used to induce ovulation for 3 months without metformin. Follicle-stimulating hormone, luteinizing hormone, estradiol and TT levels before and after ovulation in pregnant cycles and non-pregnant cycles were evaluated over the course of treatment. A total of 26 subjects completed 65 cycles. The TT levels after ovulation in the pregnant cycles were significantly lower than in the non-pregnant cycles in both groups (P = 0.001 and P < 0.001, respectively). The level of TT after ovulation may be of prognostic value for pregnancy in non-obese women with PCOS and CC resistance during treatment.

Hormonal control of spermatogenesis in men: therapeutic aspects in hypogonadotropic hypogonadism.

PubMed

Pitteloud, Nelly; Dwyer, Andrew

2014-05-01

During the first two trimesters of intrauterine life, fetal sex steroid production is driven by maternal human chorionic gonadotropin (hCG). The HPG axis is activated around the third trimester and remains active for the first 6-months of neonatal life. This so-called mini-puberty is a developmental window that has profound effects on future potential for fertility. In early puberty, GnRH secretion is reactivated first at night and then night and day. Pulsatile GnRH stimulates both LH and FSH, which induce maturation of the seminiferous tubules and Leydig cells. Congenital hypogonadotropic hypogonadism (CHH) results from GnRH deficiency. Men with CHH lack the mini-pubertal and pubertal periods of Sertoli Cell proliferation and thus present with prepubertal testes (<4mL) and low inhibin serum levels --reflecting diminished SC numbers. To induce full maturation of the testes, GnRH-deficient patients can be treated with either pulsatile GnRH, hCG or combined gonadotropin therapy (FSH+hCG). Fertility outcomes with each of these regimens are highly variable. Recently, a randomized, open label treatment study (n=13) addressed the question of whether a sequential treatment with FSH alone prior to LH and FSH (via GnRH pump) could enhance fertility outcomes. All men receiving the sequential treatment developed sperm in the ejaculate, whereas 2/6 men in the other group remained azoospermic. A large, multicenter clinical trial is needed to definitively prove the optimal treatment approach for severe CHH. Copyright © 2014. Published by Elsevier Masson SAS.

A case report of a patient with high β-hCG levels after operation because of primary broad ligament pregnancy.

PubMed

Zu, M; Zhao, G Q; Liu, Z Q; Zhang, H T; Chen, L; Zhao, D H

2017-01-01

A broad ligament pregnancy is an extremely rare condition and diagnosis is frequently missed and finally made during laparotomy. This is a case of a young patient with high serum beta-human chorionic gonadotropin (β-hCG) levels after operation because of broad ligament pregnancy. A 31-year-old multipara complained of intermittent lower abdominal pain with vaginal bleeding for four months. A color ultrasonography revealed a cystic mass in the left attachment area, indicating an interstitial tubal pregnancy. However, trophoblastic disease could not be excluded. She accepted conservative treatment with methotrexate (MTX) at first, but observation showed that conservative treatment was slow and accompanied with liver function damage. Therefore, exploratory laparotomy was performed. Intraoperative situations and postoperative pathology confirmed broad ligament pregnancy. Her serum p- hCG was sustained at a high level for three months after operation. Her examinations of serum, CT, and ultrasonography could explain this situation. Primary broad ligament pregnancy refers to pregnancy where implantation of the fertilized ovum occurs directly between the two leaves of the broad ligament. The gravid substance was removed, however serum β-hCG could not gradually re- turn to normal levels. This case should be followed-up closely to prevent adverse outcomes.

Expression of anti-Müllerian hormone in two rat models of polycystic ovary syndrome.

PubMed

Du, Dan-Feng; Li, Xue-Lian; Zheng, Sai-Hua

2016-12-01

Anti-Müllerian hormone (AMH) levels are two to three times higher in patients with polycystic ovary syndrome (PCOS), but the mechanism of increased AMH levels in PCOS remains unclear. The purpose of our experiment was to investigate a change in AMH levels in two kinds of commonly used rat models and to determine an ideal model for future research of AMH in the pathogenesis of PCOS. Thirty female Sprague Dawley rats were treated using two modeling methods: implantation of a levonorgestrel silastic implant or injection with sodium prasterone sulfate plus human chorionic gonadotropin (hCG). Rats in the control group were implanted with a blank silastic stick. Serum steroid concentrations, ovarian morphology and ovarian expression of AMH and AMH-receptor II (RII) proteins were determined and their correlations were studied. The results from the levonorgestrel and hCG group were closer to those displayed by human PCOS patients than the sodium prasterone sulfate and hCG group. Ovarian local expression of AMH and AMH-RII was increased in these both models compared with the control group; however, an elevation of serum AMH concentration was not observed (12.53 ± 0.99 ng/ml and 13.22 ± 1.09 ng/ml vs 16.30 ± 0.98 ng/ml). The levonorgestrel and hCG model is more suitable for the study of PCOS in puberty. © 2016 Japan Society of Obstetrics and Gynecology.

Early serum interleukin-8 evaluation may prove useful in localizing abnormally implanted human gestations after in vitro fertilization.

PubMed

Morelli, Sara S; Keegan, Debbra A; Krey, Lewis C; Katz, Joseph; Liu, Mengling; Noyes, Nicole

2008-12-01

To determine whether early measurement of the serum cytokines interleukin-2 receptor (IL-2R), IL-6, and IL-8 along with human chorionic gonadotropin (hCG) and progesterone (P(4)) can differentiate an ectopic from an intrauterine gestation. Retrospective analysis. University-based fertility center. 75 women who underwent treatment with in vitro fertilization (IVF) and subsequently had an ectopic gestation (n = 15), spontaneous abortion (SAB) (n = 30), or term delivery (TD) (n = 30). Serum samples were obtained 14 (day 28) and 21 (day 35) days after oocyte retrieval. Serum concentrations of IL-2R, IL-6, IL-8, P(4), and hCG. Median hCG readings on day 28 and day 35 were statistically significantly lower in the ectopic gestation group than in those with spontaneous abortion or term delivery. On day 28, median IL-8 levels were lower in the ectopic gestation group when compared with all intrauterine gestations combined. No statistically significant differences in IL-2R or IL-6 levels were noted between groups. Despite P(4) supplementation, median day-35 P(4) levels were lower in ectopic gestation than in the spontaneous abortion and term delivery cycles. In the setting of a rise or plateau in hCG levels, low day-28 IL-8 and day-35 P(4) levels suggested an extrauterine implantation. This assay combination may facilitate earlier diagnosis of an ectopic gestation when pregnancy location is unclear.

Superovulation Using the Combined Administration of Inhibin Antiserum and Equine Chorionic Gonadotropin Increases the Number of Ovulated Oocytes in C57BL/6 Female Mice

PubMed Central

Takeo, Toru; Nakagata, Naomi

2015-01-01

Superovulation is a reproductive technique generally used to produce genetically engineered mice. Superovulation in mice involves the administration of equine chorionic gonadotropin (eCG) to promote follicle growth and then that of human chorionic gonadotropin (hCG) to induce ovulation. Previously, some published studies reported that inhibin antiserum (IAS) increased the number of ovulated oocytes in ddY and wild-derived strains of mice. However, the effect of IAS on the C57BL/6 strain, which is the most widely used inbred strain for the production of genetically engineered mice, has not been investigated. In addition, the combined effect of IAS and eCG (IASe) on the number of ovulated oocytes in superovulation treatment has not been examined. In this study, we examined the effect of IAS and eCG on the number of ovulated oocytes in immature female mice of the C57BL/6 strain in superovulation treatment. Furthermore, we evaluated the quality of obtained oocytes produced by superovulation using IASe by in vitro fertilization (IVF) with sperm from C57BL/6 or genetically engineered mice. The developmental ability of fresh or cryopreserved embryos was examined by embryo transfer. The administration of IAS or eCG had a similar effect on the number of ovulated oocytes in C57BL/6 female mice. The number of ovulated oocytes increased to about 3-fold by the administration of IASe than by the administration of IAS or eCG alone. Oocytes derived from superovulation using IASe normally developed into 2-cell embryos by IVF using sperm from C57BL/6 mice. Fresh or cryopreserved 2-cell embryos produced by IVF between oocytes of C57BL/6 mice and sperm from genetically engineered mice normally developed into live pups following embryo transfer. In summary, a novel technique of superovulation using IASe is extremely useful for producing a great number of oocytes and offspring from genetically engineered mice. PMID:26024317

The laparoscopic ovarian electrocautery versus gonadotropin therapy in infertile women with clomiphene citrate-resistant polycystic ovary syndrome; a randomized controlled trial.

PubMed

Mehrabian, Ferdous; Eessaei, Fatemeh

2012-03-01

This study aimed to compare two methods of treatment of infertility with gonadotropin with laparoscopic ovarian electrocauterization in patients with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). A number of 104 nulipara patients with polycystic ovary syndrome, who were resistant to clomiphene citrate were randomly assigned to two groups. One group received gonadotropin; after the bleeding withdrawal and from the third day of the cycle, the injection of human menopausal gonadotropin (HMG) was started with 10 mg medroxy progesterone. The patients were followed with serial trans-vaginal sonographies. When the diameter of follicles reached to 18 mm, human chorionic gonadotropin (HCG) was prescribed. The other group was treated with laparoscopic ovarian electrocauterization under general anesthesia. If after 3 cycles, the anovulation was established with progesterone measurement, the clomiphene citrate was prescribed. Gonadotropin was administered, if the lack of ovulation persisted. No significant difference was documented between the two groups in terms of the obesity indexes, duration of infertility, age, sonographic and laboratory findings. In the gonadotropin group, 37 cases (71%) of pregnancy occurred. The rate of pregnancy was the same in the other group consisting of 18 cases treated by electrocautery, 9 cases with cautery + clomiphene, and 10 cases with clomiphene + cautery + gonadotropin. In the group treated with gonadotropin, there were 1 triple and 4 twins pregnancies. In the group treated with ovarian electrocautery, one twin pregnancy was observed. In the group treated with gonadotropin, 2 cases of ovarian hyperstimulation syndrome, 1 case of ectopic pregnancy and 6 cases of miscarriage occurred; the corresponding figure in the ovarian electrocautery group consisted of 5 cases of miscarriage. Our findings suggest that ovarian electrocauterization is an appropriate method with good efficacy and low complication rate for infertility treatment of women with clomiphene citrate-resistant polycystic ovary syndrome.

Case report of a pituitary thyrotropin-secreting macroadenoma with Hashimoto thyroiditis and infertility.

PubMed

Li, Jiaqi; Li, Jianwei; Jiang, Shu; Yu, Ruichao; Yu, Yerong

2018-01-01

Thyrotropin-secreting adenoma (TSHoma) is rare, diagnosis and treatment are often delayed if the condition coexists with Hashimoto thyroiditis. The enlarged pituitary adenoma may eventually induce panhypopituitarism, infertility, or the compression of optic nerves and optic chiasma. This patient was a 36-year-old man who had been referred to the pituitary disease multidisciplinary team (MDT) of the West China Hospital, due to infertility. Examinations revealed pituitary thyrotropin-secreting macroadenoma. We conducted trans-sphenoidal surgery. Human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) were used for reproductive reconstruction after surgery. This patient successfully fathered a child. To date, the multidisciplinary team treatment of TSHoma was rare, TSHomas are often misdiagnosed as macroadenomas, because the clinical features are varied and it often takes a long time to be diagnosed. So the purpose of this case report is to attract attention to the manifestation of increased thyroid stimulating hormone (TSH) concentration and discuss MDT treatment for TSH-secreting adenoma. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

The characteristics of vasa gene from Japanese sea bass ( Lateolabrax japonicas) and its response to the external hormones

NASA Astrophysics Data System (ADS)

Chi, Meili; Wen, Haishen; Ni, Meng; Qian, Kun; Zhang, Pei; Chai, Senhao

2015-08-01

The RNA helicase Vasa is an important regulator of primordial germ cell development. Its function in mature fish, especially the hormone-related differences in maturing male fish has seldom been documented. In this study, a full length cDNA sequence of the vasa gene was cloned from Japanese sea bass, Lateolabrax japonicas, and it was named jsb-vasa. Homology analysis showed that jsb-vasa was closely related to its teleost homologs. The spatial distribution of jsb-vasa indicated that it was only highly expressed in testis, showing its germ cell-specific expression pattern. During the testicular development cycle, jsb-vasa was highly expressed during early period of spermatogenesis, and reduced when spermatogenesis advanced. In addition, the jsb-vasa gene expression was significantly inhibited at 6 h, 12 h and 24 h after injecting hCG (human chorionic gonadotropin) and GnRHa (Gonadotropin-releasing hormone analogue), indicating that jsb-vasa gene may play an important role in spermatogenesis of Japanese sea bass, and be under the regulation of external sex hormones.

Application of gonadotropin releasing hormone in hypogonadotropic hypogonadism--diagnostic and therapeutic aspects.

PubMed

Delemarre-van de Waal, Henriette A

2004-11-01

Puberty is the result of reactivation of the gonadotropin releasing hormone (GnRH) pulse generator resulting in an increasing release of GnRH by the hypothalamus, which stimulates the gonadotropic cells of the pituitary to synthesize and secrete LH and FSH. Hypogonadotropic hypogonadism (HH) is often the result of GnRH deficiency. The clinical picture is characterized by the absence of pubertal development and infertility. It is difficult to differentiate HH from delayed puberty since low gonadotropin and low testosterone levels are found in both conditions. We hypothesized that long-term GnRH administration may differentiate between the two conditions by a difference in the increase of gonadotropins, the idea being that in normal delayed puberty the pituitary of the patient has been primed with GnRH during the fetal and early postnatal period. Seventeen adolescents suspected of having hypogonadotropic hypogonadism were treated with pulsatile GnRH for 7 days. At the present time, the diagnosis of these patients is known and the results of the long-term GnRH stimulation have been evaluated according to the present diagnosis. The results show that the increase in gonadotropins following GnRH treatment is similar in both conditions. Therefore, at a prepubertal age a normal delayed puberty cannot be distinguished from hypogonadotropic hypogonadism using long-term GnRH stimulation. Long-term pulsatile GnRH treatment is a physiological therapy for the induction of puberty. Unlike testosterone it has the advantage of stimulation of testicular growth and fertility, as well as virilization, in males. We have treated 68 male patients with HH with pulsatile GnRH. The results show testicular growth and virilization in all the patients and spermatogenesis in 58 patients. Wearing a portable pump is cumbersome. However, the patients were very motivated and adapted very easily to this inconvenience. When spermatogenesis had developed, GnRH treatment was changed to human chorionic gonadotropin (hCG) administration 1-2 times per week intramuscularly or subcutaneously. During hCG therapy spermatogenesis was maintained or even improved. At least ten patients fathered children. Pulsatile GnRH cannot distinguish between a normal delayed puberty and a hypothalamic defect in still prepubertal patients. Pulsatile GnRH offers an appropriate way to initiate testicular growth including virilization and fertility in males with hypogonadotropic hypogonadism.

Maternal plasma levels of cell-free β-HCG mRNA as a prenatal diagnostic indicator of placenta accrete.

PubMed

Zhou, J; Li, J; Yan, P; Ye, Y H; Peng, W; Wang, S; Wang, X Tong

2014-09-01

Several biomarkers, including maternal serum creatinine kinase and α-fetoprotein, have been described as potential tools for the diagnosis of placental abnormalities. This study aimed to determine whether maternal plasma mRNA levels of the β subunit of human chorionic gonadotropin (β-HCG) could predict placenta accreta prenatally. Sixty-eight singleton pregnant women with prior cesarean deliveries (CDs) were classified into three groups: normal placentation (35 women, control group); placenta previa alone (21 women, placenta previa group); and both placenta previa and placenta accreta (12 women, placenta previa/accreta group). Maternal plasma concentrations of cell-free β-HCG mRNA were measured by real-time reverse-transcription polymerase chain reaction and were expressed as multiples of the median (MoM). Cell-free β-HCG mRNA concentrations (MoM, range) were significantly higher in women with placenta accreta (3.65, 2.78-7.19) than in women with placenta previa (0.94, 0.00-2.97) or normal placentation (1.00, 0.00-2.69) (Steel-Dwass test, P < 0.01 and P < 0.01, respectively). In the placenta previa/accreta group, the concentration of cell-free β-HCG mRNA was significantly higher among women who underwent CDs with hysterectomy (4.41, 3.49-7.19) than among women whose CDs did not result in hysterectomy (3.20, 2.78-3.70) (Mann-Whitney U test, P = 0.012). An increased level of cell-free β-HCG mRNA in the maternal plasma of women with placenta accreta may arise from direct uteroplacental transfer of cell-free placental mRNA molecules. The concentration of cell-free β-HCG mRNA in maternal plasma may be applicable to the prenatal diagnosis of placenta accreta, especially to identify women with placenta accreta likely to require hysterectomy. Copyright © 2014 Elsevier Ltd. All rights reserved.

76 FR 17927 - Withdrawal of Approval of New Animal Drug Applications; Chorionic Gonadotropin; Cuprimyxin...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0151] Withdrawal of Approval of New Animal Drug Applications; Chorionic Gonadotropin; Cuprimyxin... wholly owned TRAMISOL-10% Pig Wormer....... (000856) subsidiary of Pfizer, Inc., 235 East (levamisole...

Adverse effects of 4-tert-octylphenol on the production of oxytocin and hCG in pregnant rats

PubMed Central

Kim, Jun; Kang, Eun-Jin; Park, Mee-Na; Lee, Jae-Eon; Hong, So-Hye; An, Sung-Min; Kim, Seung-Chul; Hwang, Dae-Youn

2014-01-01

Endocrine-disrupting chemicals (EDCs) are exogenous substances that alter the structure or function of the endocrine system. 4-Tert-octylphenol (OP) is one of the most representative EDCs and has estrogenic effects. In this study, we examined the effects of ethinyl estradiol (EE) and OP on the pituitary gland, placenta, and uterus of pregnant rats. Expression levels of human chorionic gonadotropin (hCG), oxytocin (OT), and contraction-associated proteins (CAPs) were determined, and uterine contractile activity was measured by uterine contraction assay. EE and OP both increased mRNA expression of OT and hCG in the pituitary gland but not the placenta. Since OT and hCG control uterine contraction, we next examined CAP expression in the uterus. Expression of 15-hydroxyprostaglandin-dehydrogenase (PGDH) was upregulated by OP, whereas expression of other CAPs was unaffected. To clarify the effect of OP on uterine contraction in pregnant rats, uterine contraction assay was performed. The 17β-Estradiol (E2) did not affect contraction of primary uterine cells harvested from pregnant rats in a 3D collagen gel model. However, OP showed different effects from E2 by significantly reducing contraction activity. In summary, we demonstrated that OP interferes with regulation of OT and hCG in the pituitary gland as well as PGDH in the uterus, thereby reducing uterine contraction activity. This result differs from the action of endogenous E2. Collectively, these findings suggest that exposure to EDCs such as OP during pregnancycan reduce uterine contractile ability, which may result in contraction-associated adverse effects such as metratonia, bradytocia, and uterine leiomyomata. PMID:25324873

Estrogen Modulates Specific Life and Death Signals Induced by LH and hCG in Human Primary Granulosa Cells In Vitro.

PubMed

Casarini, Livio; Riccetti, Laura; De Pascali, Francesco; Gilioli, Lisa; Marino, Marco; Vecchi, Eugenia; Morini, Daria; Nicoli, Alessia; La Sala, Giovanni Battista; Simoni, Manuela

2017-04-28

Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are glycoprotein hormones used for assisted reproduction acting on the same receptor (LHCGR) and mediating different intracellular signaling. We evaluated the pro- and anti-apoptotic effect of 100 pM LH or hCG, in the presence or in the absence of 200 pg/mL 17β-estradiol, in long-term, serum-starved human primary granulosa cells (hGLC) and a transfected granulosa cell line overexpressing LHCGR (hGL5/LHCGR). To this purpose, phospho-extracellular-regulated kinase 1/2 (pERK1/2), protein kinase B (pAKT), cAMP-responsive element binding protein (pCREB) activation and procaspase 3 cleavage were evaluated over three days by Western blotting, along with the expression of target genes by real-time PCR and cell viability by colorimetric assay. We found that LH induced predominant pERK1/2 and pAKT activation STARD1 , CCND2 and anti-apoptotic XIAP gene expression, while hCG mediated more potent CREB phosphorylation, expression of CYP19A1 and procaspase 3 cleavage than LH. Cell treatment by LH is accompanied by increased (serum-starved) cell viability, while hCG decreased the number of viable cells. The hCG-specific, pro-apoptotic effect was blocked by a physiological dose of 17β-estradiol, resulting in pAKT activation, lack of procaspase 3 cleavage and increased cell viability. These results confirm that relatively high levels of steroidogenic pathway activation are linked to pro-apoptotic signals in vitro, which may be counteracted by other factors, i.e., estrogens.

Testicular growth and spermatogenesis: new goals for pubertal hormone replacement in boys with hypogonadotropic hypogonadism? -a multicentre prospective study of hCG/rFSH treatment outcomes during adolescence.

PubMed

Rohayem, Julia; Hauffa, Berthold P; Zacharin, Margaret; Kliesch, Sabine; Zitzmann, Michael

2017-01-01

Testosterone treatment for pubertal induction in boys with hypogonadotropic hypogonadism (HH) provides virilization, but does not induce testicular growth or fertility. Larger studies evaluating the outcomes of gonadotropin replacement during adolescence have not been reported to date; whether previous testosterone substitution affects testicular responses is unresolved. We aimed to assess the effects of human chorionic gonadotropin (hCG) and recombinant FSH (rFSH) in boys and adolescents with HH with respect to a) testicular growth, b) spermatogenesis, c) quality of life (QoL) and to identify factors influencing therapeutic success. A prospective case study was conducted in 26 paediatric endocrine centres PATIENTS/INTERVENTIONS: HCG and rFSH were administered until cessation of testicular growth and plateauing of spermatogenesis to (1) prepubertal HH boys with absent or early arrested puberty (group A) and to (2) HH adolescents who had previously received full testosterone replacement (group B). Bi-testicular volumes (BTVs), sperm concentrations and QoL. Sixty (34 A/26 B) HH patients aged 14-22 years were enrolled. BTVs rose from 5 ± 5 to 34 ± 3 ml in group A vs 5 ± 3 to 32 ± 3 ml in group B, with normal final BTVs (≥24 ml) attained in 74%/70% after 25/23 months in A/B, respectively. Sperm in the ejaculate were found in 21/23(91%)/18/19(95%), with plateauing concentrations after 31/30 months of hCG and 25/25 months of combined treatment in A/B. Sperm concentrations were normal (≥15 mill/ml) in 61%/32%, with mean concentrations of 40 ± 73 vs 19 ± 38 mill/ml in A/B (n.s.). Outcomes were better in patients without bilateral cryptorchidism, with non-congenital HH causes, higher baseline BTVs, and higher baseline inhibin B and AMH levels. QoL increased in both groups. HCG/rFSH replacement during adolescence successfully induces testicular growth and spermatogenesis, irrespective of previous testosterone replacement, and enhances QoL. © 2016 John Wiley & Sons Ltd.

An Investigation of the Single and Combined Phthalate Metabolite Effects on Human Chorionic Gonadotropin Expression in Placental Cells

PubMed Central

Zhao, Yaqi; Zhan, Lei V.; Kapidzic, Mirhan; Larocque, Nicholas; Koistinen, Hannu; Huhtaniemi, Ilpo T.; Stenman, Ulf-Håkan

2017-01-01

Background: Observational studies have reported associations between maternal phthalate levels and adverse outcomes at birth and in the health of the child. Effects on placental function have been suggested as a biologic basis for these findings. Objective: We evaluated the effects of phthalates on placental function in vitro by measuring relevant candidate genes and proteins. Materials and Methods: Human trophoblast progenitor cells were isolated at 7–14 wk of pregnancy (two female and three male concepti), and villous cytotrophoblast cells (vCTBs) were isolated at 15–20 wk (three female and four male concepti). Cells were cultured in vitro with four phthalate metabolites and their combination at concentrations based on levels found previously in the urine of pregnant women: mono-n-butyl (MnBP, 200 nM), monobenzyl (MBzP, 3μM), mono-2-ethylhexyl (MEHP, 700 nM), and monoethyl (MEP, 1.5μM) phthalates. mRNA levels of CGA, CGB, PPARG, CYP19A1, CYP11A1, PTGS2, EREG, and the intracellular β subunit of human chorionic gonadotropin (hCGβ) and peroxisome proliferator activated receptor γ (PPARγ) were measured in the cellular extracts, and protein levels for four forms of secreted hCG were measured in the conditioned media. Results: Previously reported associations between maternal phthalates and placental gene expression were reproduced experimentally: MnBP with CGA, MBzP with CYP11A1, and MEHP with PTGS2. CGB and hCGβ were up-regulated by MBzP. In some cases, there were marked, even opposite, differences in response by sex of the cells. There was evidence of agonism in female cells and antagonism in male cells of PPARγ by simultaneous exposure to multiple phthalates. Conclusions: Concentrations of MnBP, MBzP and MEHP similar to those found in the urine of pregnant women consistently altered hCG and PPARγ expression in primary placental cells. These findings provide evidence for the molecular basis by which phthalates may alter placental function, and they provide a preliminary mechanistic hypothesis for opposite responses by sex. https://doi.org/10.1289/EHP1539 PMID:29089286

Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman.

PubMed

Yu, Xiu-Jie; Zhang, Lin; Liu, Zai-Ping; Shi, Yi-Quan; Liu, Yi-Xin

2014-01-01

Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels.

Treatment of hypogonadotropic male hypogonadism: Case-based scenarios

PubMed Central

Crosnoe-Shipley, Lindsey E; Elkelany, Osama O; Rahnema, Cyrus D; Kim, Edward D

2015-01-01

The aim of this study is to review four case-based scenarios regarding the treatment of symptomatic hypogonadism in men. The article is designed as a review of published literature. We conducted a PubMed literature search for the time period of 1989-2014, concentrating on 26 studies investigating the efficacy of various therapeutic options on semen analysis, pregnancy outcomes, time to recovery of spermatogenesis, as well as serum and intratesticular testosterone levels. Our results demonstrated that exogenous testosterone suppresses intratesticular testosterone production, which is an absolute prerequisite for normal spermatogenesis. Cessation of exogenous testosterone should be recommended for men desiring to maintain their fertility. Therapies that protect the testis involve human chorionic gonadotropin (hCG) therapy or selective estrogen receptor modulators (SERMs), but may also include low dose hCG with exogenous testosterone. Off-label use of SERMs, such as clomiphene citrate, are effective for maintaining testosterone production long-term and offer the convenience of representing a safe, oral therapy. At present, routine use of aromatase inhibitors is not recommended based on a lack of long-term data. We concluded that exogenous testosterone supplementation decreases sperm production. It was determined that clomiphene citrate is a safe and effective therapy for men who desire to maintain fertility. Although less frequently used in the general population, hCG therapy with or without testosterone supplementation represents an alternative treatment. PMID:25949938

hCG-dependent regulation of angiogenic factors in human granulosa lutein cells.

PubMed

Phan, B; Rakenius, A; Pietrowski, D; Bettendorf, H; Keck, C; Herr, D

2006-07-01

As prerequisite for development and maintenance of many diseases angiogenesis is of particular interest in medicine. Pathologic angiogenesis takes place in chronic arthritis, collagen diseases, arteriosclerosis, retinopathy associated with diabetes, and particularly in cancers. However, angiogenesis as a physiological process regularly occurs in the ovary. After ovulation the corpus luteum is formed by rapid vascularization of initially avascular granulosa lutein cell tissue. This process is regulated by gonadotropic hormones. In order to gain further insights in the regulatory mechanisms of angiogenesis in the ovary, we investigated these mechanisms in cell culture of human granulosa lutein cells. In particular, we determined the expression and production of several angiogenic factors including tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), Leptin, connective tissue growth factor (CTGF), meningioma-associated complimentary DNA (Mac25), basic fibroblast growth factor (bFGF), and Midkine. In addition, we showed that human chorionic gonadotropin (hCG) has distinct effects on their expression and production. hCG enhances the expression and production of TIMP-1, whereas it downregulates the expression of CTGF and Mac25. Furthermore it decreases the expression of Leptin. Our results provide evidence that hCG determines growth and development of the corpus luteum by mediating angiogenic pathways in human granulosa lutein cells. Hence we describe a further approach to understand the regulation of angiogenesis in the ovary.

High Serum FSH is Associated with Brown Oocyte Formation and a Lower Pregnacy Rate in Human IVF Parctice.

PubMed

Xu, Hongyi; Deng, Kai; Luo, Qingbing; Chen, Juan; Zhang, Xin; Wang, Xiaoyan; Diao, Honglu; Zhang, Changjun

2016-01-01

To investigate whether brown zona pellucida (ZP) of oocytes affects the outcome of fertilization, embryo quality and pregnancy rate in in vitro fertilization-embryo transfer (IVF-ET). Based on the ZP color of their oocytes, a total number of 703 patients dated from 2012 to 2014 were divided into a normal egg group (group A) and a brown oocyte group (group B), with 629 and 74 cases, respectively. Clinical characteristics, gonadotropin (Gn) days, Gn dosage, serum hormone levels on the day of human chorionic gonadotropin (HCG) injection, ZP thickness (ZPT) of the eggs, fertilization rate, rescue intracytoplasmic sperm injection (rICSI) rate, good-quality embryo rate and pregnancy rate were compared between the two groups. No significant differences were found in the duration and the causes of infertility, and their basal level of endocrine hormone before IVF-ET between normal egg group and brown egg group. The level of serum hormone including estradiol, progesterone and luteinizing hormone on the day of HCG injection were again similar. Moreover, there were no differences in number of mature oocytes, oocyte fertilization rates and rICSI rates after IVF between the two groups. However, we observed that the ZPT of brown oocytes (group B) was higher than that of normal oocytes (group A). Moreover, the Gn dosage and FSH levels on the day of HCG injection were significantly higher in group B than in group A and the good-quality embryo rate and pregnancy rate in group B were lower than those in group A. Compared with normal eggs, oocytes with a brown ZP were found to have a higher ZPT, lower embryo quality and lower pregnancy rate, which might be due to a high Gn dosage injection and high serum FSH levels during IVT-ET cycles. © 2016 The Author(s) Published by S. Karger AG, Basel.

Expression analysis of cyp11a1 during gonadal development, recrudescence and after hCG induction and sex steroid analog treatment in the catfish, Clarias batrachus.

PubMed

Rajakumar, Anbazhagan; Senthilkumaran, Balasubramanian

2014-10-01

In teleosts, the levels of steroids are critical for sexual development and hence, expression of steroidogenic enzyme genes and specific substrate availability are indispensable for gonadal steroidogenesis. Early stages of steroidogenesis specifically cholesterol to pregnenolone conversion by Cyp11a1 is crucial for estradiol and testosterone biosynthesis. Based on this, in this study, full length cDNA of cyp11a1 (2581bp) was cloned from catfish testis to investigate the importance of Cyp11a1 by analyzing the expression of cyp11a1 during gonadal development, seasonal reproductive cycle, after human chorionic gonadotropin (hCG) induction and sex steroid analog treatment. Phylogenetic analysis revealed that the Cyp11a1 is more conserved across teleosts. Tissue distribution analysis showed that the cyp11a1 expression was higher in the testis followed by the brain, head kidney, muscle and ovary compared to other tissues analyzed. High expression of cyp11a1 in the head kidney and muscle revealed that Cyp11a1 could potentially regulate the extra-gonadal and/or circulating steroid levels in teleosts. Developing and mature testes showed higher expression of cyp11a1 than the ovary of corresponding age group. Further, cyp11a1 expression was found to be higher during pre-spawning and spawning phases of testicular cycle and was upregulated by hCG, in vivo and in vitro, which indicates the possible regulation by gonadotropin. Exposure of methyltestosterone (1μg/L) and ethinylestradiol (1μg/L) for 21days during catfish testicular development showed lower cyp11a1 expression levels in the testis and brain indicating a certain feedback intervention. These results suggest possible role for Cyp11a1 in the testis development and recrudescence. Copyright © 2014 Elsevier Inc. All rights reserved.

Insulin-like peptide 3 (INSL3) in men with congenital hypogonadotropic hypogonadism/Kallmann syndrome and effects of different modalities of hormonal treatment: a single-center study of 281 patients.

PubMed

Trabado, Séverine; Maione, Luigi; Bry-Gauillard, Hélène; Affres, Hélène; Salenave, Sylvie; Sarfati, Julie; Bouvattier, Claire; Delemer, Brigitte; Chanson, Philippe; Le Bouc, Yves; Brailly-Tabard, Sylvie; Young, Jacques

2014-02-01

Insulin-like factor 3 (INSL3) is a testicular hormone secreted during fetal life, the neonatal period, and after puberty. To measure INSL3 levels in a large series of men with congenital hypogonadotropic hypogonadism (CHH)/ Kallmann syndrome (KS), in order to assess its diagnostic value and to investigate its regulation. We studied 281 CHH/KS patients (91 untreated, 96 receiving T, and 94 receiving combined gonadotropin therapy [human chorionic gonadotropin, hCG, and FSH]) and 72 age-matched healthy men. Serum INSL3 was immunoassayed with a validated RIA. Mean (±SD) INSL3 levels (pg/mL) were 659 ± 279 in controls and lower (60 ± 43; P < .001) in untreated CHH/KS patients, with no overlap between the two groups, when the threshold of 250 pg/mL was used. Basal INSL3 levels were lower in both untreated CHH/KS men with cryptorchidism than in those with intrascrotal testes and in patients with testicular volumes below 4 mL. Significant positive correlations between INSL3 and both serum total T and LH levels were observed in untreated CHH/KS. Mean INSL3 levels remained low in T-treated CHH/KS patients and were significantly higher in men receiving combined hCG-FSH therapy (P < .001), but the increase was lower cryptorchid patients. FSH-hCG combination therapy or hCG monotherapy, contrary to T and FSH monotherapies, significantly increased INSL3 levels in CHH/KS. INSL3 is as sensitive a marker as T for the evaluation of altered Leydig cell function in CHH/KS patients. INSL3 levels correlate with LH levels in CHH/KS men showing, together with the rise in INSL3 levels during hCG therapy, that INSL3 secretion seems not constitutively secreted during adulthood but is dependence on pituitary LH.

The utility of six over-the-counter (home) pregnancy tests.

PubMed

Cole, Laurence A

2011-08-01

The home pregnancy market is rapidly evolving. It has moved from detection of pregnancy on the day of missed menstrual bleeding, to detection claims 4 days prior. It is moving from all manual tests to digital tests, with a monitor reading the bands and informing women they are pregnant. A thorough study is needed to investigate the validity of claims and evolving usefulness of devices. Studies were proposed to examine the sensitivity and specificity of home tests and their abilities to detect pregnancy. Methods examined the abilities of tests to detect human chorionic gonadotropin (hCG), hyperglycosylated hCG, free β-subunit, a mixture of these antigens in 40 individual early pregnancy urines. Using a mixture of hCG, hyperglycosylated hCG and free β-subunit typical for early pregnancy, the sensitivity of the First Response manual and digital tests was 5.5 mIU/mL, while the sensitivities of the EPT and ClearBlue brand manual and digital tests was 22 mIU/mL. On further evaluation, the First Response manual and digital tests both detected 97% of 120 pregnancies on the day of missed menstrual bleeding. The EPT manual and digital devices detected 54% and 67% of pregnancies, respectively, and the ClearBlue manual and digital devices detected 64% and 54% of pregnancies, respectively. First Response manual and digital claim >99% detection on the day of missed menses. The results here suggest similar sensitivity for these two tests. The EPT and ClearBlue manual and digital test make similar >99% claims, the data presented here disputes their elevated claim.

Early pregnancy assessment with transvaginal ultrasound scanning.

PubMed Central

Daya, S; Woods, S; Ward, S; Lappalainen, R; Caco, C

1991-01-01

OBJECTIVE: To establish normal parameters in early pregnancy through transvaginal ultrasonography so that gestational age can be determined and to correlate the sonographic findings with serum human chorionic gonadotropin (hCG) levels calibrated against the first international reference preparation standard. SETTING: Infertility clinic. PATIENTS: Thirty-five women with normal intrauterine pregnancy. INTERVENTIONS: Serial measurement of the serum hCG level and the diameter of the gestational sac through transvaginal ultrasonography. MAIN RESULTS: The gestational sac could not be visualized when the hCG level was less than 1100 IU/L. The average growth rate of the sac was 0.9 mm/d. The threshold values for sac diameter, serum hCG level and gestational age below which the yolk sac was not visible were 3.7 mm, 1900 IU/L and 36 days respectively; the corresponding values above which the yolk sac was always visible were 6.7 mm, 5800 IU/L and 40 days. The threshold values below which cardiac activity was not visible were 8.3 mm, 9200 IU/L and 41 days respectively, and the corresponding values above which cardiac activity was always visible were 14.0 mm, 24,000 IU/L and 46 days. The mean gestational ages and the 95% confidence and prediction intervals were tabulated so that measurement of the gestational sac diameter could be used to estimate gestational age early in normal pregnancy. CONCLUSIONS: Transvaginal ultrasonography enables detection of an intrauterine sac and reliable estimation of gestational age on the basis of sac dimensions before an embryo can be seen. PMID:1993291

hCGbeta core fragment is a metabolite of hCG: evidence from infusion of recombinant hCG.

PubMed

Norman, R J; Buchholz, M M; Somogyi, A A; Amato, F

2000-03-01

The availability of recombinant human chorionic gonadotrophin (r-hCG) has allowed us to measure its metabolic and renal clearance rates and to study the origin of the beta core fragment of hCG (hCGbetacf). Serum and urine samples were collected from six subjects, after an intravenous injection of 2 mg (equivalent to 44 000 IU Urinary hCG) r-hCG, and assayed for hCG and the beta subunit (hCGbeta). Urine from four of the subjects was also subjected to gel chromatography and assayed for hCGbetacf and hCG. r-hCG, administered as an intravenous dose, was distributed, initially in a volume of 3.4+/-0.7 l (mean+/-s.d.) and then in 6.5+/-1.15 l at steady-state. The disappearance of r-hCG from serum was bi-exponential, with an initial half-life of 4.5+/-0.7 h and a terminal half-life of 29.0+/-4.6 h. The mean residence time was 28. 6+/- 3.6 h and the total systemic clearance rate of r-hCG was 226+/-18 ml/h. The renal clearance rate was 28.75+/-6.2 ml/h (mean+/-s.d). hCGbetacf was detected in all urine samples collected at 6 h intervals. Over the 138 h period of urine collection, 12.9% (range 10.1-17.3% ) of r-hCG injected was recovered as the intact molecule and 1.7% (range 0.8-2.9%) was recovered as the hCGbetacf, in 4 subjects. The molar ratio of hCGbetacf to hCG in urine increased from 3.1+/-1.7%, on day 1, to 76+/-34.3% (mean+/-s.e.m.) on day 5, after r-hCG infusion, suggesting that hCGbetacf is a metabolic product of the infused r-hCG.

Quality of common marmoset (Callithrix jacchus) oocytes collected after ovarian stimulation.

PubMed

Kanda, Akifumi; Nobukiyo, Asako; Yoshioka, Miyuki; Hatakeyama, Teruhiko; Sotomaru, Yusuke

2018-01-15

The common marmoset (Callithrix jacchus) is an experimental animal that is considered suitable for the creation of next-generation human disease models. It has recently been used in the reproductive technology field. Oocytes can be effectively collected from female marmosets via ovarian stimulation with injections of follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG). The oocytes, collected about 28 h after the hCG injection, include both premature oocytes and postmature (in vivo matured; IVO) oocytes, and the premature oocytes can be matured by in vitro culture (in vitro matured; IVM). Although IVM and IVO oocytes are equivalent in appearance at the MII stage, it remains unclear whether there are differences in their properties. Therefore, we investigated their in vitro fertilization and developmental capacities and cytoskeletal statuses. Our findings revealed that the IVM and IVO oocytes had similar fertilization rates but that no IVO oocytes could develop to the blastocyst stage. Additionally, IVO oocytes showed abnormal cytoskeletal formation. It is concluded that IVM oocytes maintain normal function, whereas IVO oocytes would be affected by aging and other factors when they remain for a long time in the ovary. Copyright © 2017 Elsevier Inc. All rights reserved.

Computerized optimization of radioimmunoassays for hCG and estradiol: an experimental evaluation

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

Yanagishita, M.; Rodbard, D.

1978-07-15

The mathematical and statistical theory of radioimmunoassays (RIAs) has been used to develop a series of computer programs to optimize sensitivity or precision at any desired dose level for either equilibrium or nonequilibrium assays. These computer programs provide for the calculation of the equilibrium constants of association and binding capacities for antisera (parameters of Scatchard plots), the association and dissociation rate constants, and prediction of optimum concentration of labeled ligand and antibody and optimum incubation times for the assay. This paper presents an experimental evaluation of the use of these computer programs applied to RIAs for human chorionic gonadotropin (hCG)more » and estradiol. The experimental results are in reasonable semiquantitative agreement with the predictions of the computer simulations (usually within a factor of two) and thus partially validate the use of computer techniques to optimize RIAs that are reasonably well behaved, as in the case of the hCG and estradiol RIAs. Further, these programs can provide insights into the nature of the RIA system, e.g., the general nature of the sensitivity and precision surfaces. This facilitates empirical optimization of conditions.« less

Monitoring stimulated cycles during in vitro fertilization treatment with ultrasound only--preliminary results.

PubMed

Wiser, Amir; Gonen, Ofer; Ghetler, Yehudit; Shavit, Tal; Berkovitz, Arie; Shulman, Adrian

2012-06-01

To evaluate if monitoring patients by ultrasound (US) only during in vitro fertilization (IVF) treatment is safe. Randomized prospective study. Patients undergoing their first IVF treatment were randomized into two groups. The ultrasound only group (study group) was monitored by US for follicle size and endometrial thickness without blood tests. In this group, only one blood test was taken before human chorionic gonadotropin (hCG) injection, to ensure a safe level of estradiol (E(2)) regarding ovarian hyperstimulation syndrome (OHSS) risk. The control group was monitored by ultrasound plus serum estradiol and progesterone concentration at each visit. Clinical pregnancy rate. No differences were found between the groups in the parameters of IVF treatment, induction days, number of ampoules, E(2) level of hCG, as well as embryo quality. The clinical pregnancy rate was not statistically different between the groups, 57.5% vs. 40.0%, respectively (p = 0.25). No OHSS cases were found among the study or control groups. Ultrasound as a single monitoring tool for IVF cycles is reliable, safe, patient friendly, and reduces treatment expenses. In an era of cost effectiveness awareness, this regimen should be considered for routine management in IVF programs.

Factors for consideration in the interpretation of the adverse effects of elevated environmental temperatures on reproduction in the male rat

NASA Astrophysics Data System (ADS)

Bedrak, E.; Chap, Z.; Fried, K.

1980-06-01

Continuous exposure of male rats to an elevated environmental temperature (33 35° C) for 3 weeks led to heat-acclimatized (HA) rats whose serum testosterone concentratrion was significantly lower (P<0.01) than that of control (C) rats (20 22° C). The decrease in the androgen level was independent of major changes in serum FSH and LH concentrations, as well as hypothalamic content of thyrotropin-releasing hormone (THR), gonadotropin-releasing hormone (GnRH) and prostaglandin E2 (PGE2). However, the prostaglandin F2α(PGF2α) content of the hypothalamus of HA rats was significantly lower (P < 0.05) than that of C. The number of receptors for human chorionic gonadotropin (hCG) was significantly lower in testicular tissue of HA rats as compared to C males. Histological examination of the testis disclosed that exposure to heat adversely affected the sperm production and integrity of the Sertoli cells. Activity of enzymes associated with testosterone biosynthesis in testicular tissue of rats incubated at temperatures similar to those prevailing in the scrotum of HA rats resembled the activity of these enzymes observed in HA animals. Catabolism of testosterone was enhanced when kidney and liver of C rats were incubated at temperatures similar to the deep-body temperatures of HA rats, supporting the thesis that acclimatization to heat is coupled, inter alin, with increase androgen catabolism and excretion. It is suggested that the lower reproductive performance of HA rats is associated with several phenomena: a low number of receptors for hCG in the testes, decreased testoster one production rate by the Leydig cells, increased cata bolism and excretion of androgen, and partial atrophy of seminiferous tubules and Sertoli cells. These changes appear to be independent of either alteration in serum gonadotropin concentration or hypothalamic contents of TRH, GnR H and PGE2. The physiological significance in the response of PGF2α awaits further clarification.

Beta Human Chorionic Gonadotropin - Induction of Apoptosis in Breast Cancer

DTIC Science & Technology

2006-01-01

R., Sturzl, M ., Albini, A., Tschachler, E., Zangerle, R., Donini , S., Feichtinger, H., Schwarz, S., 1997. Induction of apoptosis in Kaposi’s...Roth, B., Bock, G., Recheis, H., Sgonc, R., Sturzl, M ., Albini, A., 18 Tschachler, E., Zangerle, R., Donini , S., Feichtinger, H., Schwarz, S., 1997...Biol. Anim. 30A, 4-8. Bièche, I., Lazar, V., Noguès, C., Poynard, T., Giovangrandi, Y., Bellet, D., Lidereau, R., Vidaud, M ., 1998. Prognostic value

microRNA-371a-3p as informative biomarker for the follow-up of testicular germ cell cancer patients.

PubMed

van Agthoven, Ton; Eijkenboom, Wil M H; Looijenga, Leendert H J

2017-08-01

α-fetoprotein (AFP) and human chorionic gonadotropin subunit beta (B-HCG) are informative serum biomarkers for the primary diagnosis and follow-up of testicular germ cell cancer (TGCC) patients. About 20% of TGCC patients with a non-seminoma (NS) and about 80% with a seminoma (SE) are, however, negative for these biomarkers. Embryonic stem cell microRNAs (miRs) may serve as promising alternative serum biomarkers. Here we investigated a retrospective series of serum samples from selected TGCC patients who developed a relapse in time to test the possible additional value of the serum-based ampTSmiR test compared to the conventional serum-based protein biomarkers for follow-up. We investigated 261 retrospective serum samples of six selected fully evaluated TGCC patients with a proven relapse using the ampTSmiR test for miR-371a-3p, miR-373-3p, and miR-367-3p and compared the results to those of the conventional protein biomarkers. At primary diagnosis, elevated serum B-HCG, AFP and LDH levels were found to be informative in 4/6, 3/6 and 3/6 patients, respectively. At primary diagnosis the levels of miR-371a-3p and miR-373-3p were elevated in 4/4, and miR-367-3p in 3/4 patients. For two cases no starting serum sample was available for retrospective miR analysis. Residual disease (overlooked by histopathological examination) was detected in one case by miR-371a-3p only. The miR-371a-3p level was increased in one patient two months before detection of an intracranial metastasis. B-HCG was informative in 3/4 and the ampTSmiR test in 4/4 patients with a relapse or residual disease. None of the biomarkers were informative for the detection of residual mature teratoma. The ampTSmiR test is more sensitive than the conventional TGCC protein biomarkers for the detection of residual disease and relapse, excluding mature teratoma.

Ovarian membrane-type matrix metalloproteinases: induction of MMP14 and MMP16 during the periovulatory period in the rat, macaque, and human.

PubMed

Puttabyatappa, Muraly; Jacot, Terry A; Al-Alem, Linah F; Rosewell, Katherine L; Duffy, Diane M; Brännström, Mats; Curry, Thomas E

2014-08-01

An intrafollicular increase in proteolytic activity drives ovulatory events. Surprisingly, the periovulatory expression profile of the membrane-type matrix metalloproteinases (MT-MMPs), unique proteases anchored to the cell surface, has not been extensively examined. Expression profiles of the MT-MMPs were investigated in ovarian tissue from well-characterized rat and macaque periovulatory models and naturally cycling women across the periovulatory period. Among the six known MT-MMPs, mRNA expression of Mmp14, Mmp16, and Mmp25 was increased after human chorionic gonadotropin (hCG) administration in rats. In human granulosa cells, mRNA expression of MMP14 and MMP16 increased following hCG treatment. In contrast, mRNA levels of MMP16 and MMP25 in human theca cells were unchanged before ovulation but declined by the postovulatory stage. In macaque granulosa cells, hCG increased mRNA for MMP16 but not MMP14. Immunoblotting showed that protein levels of MMP14 and MMP16 in rats increased, similar to their mRNA expression. In macaque granulosa cells, only the active form of the MMP14 protein increased after hCG, unlike its mRNA or the proprotein. By immunohistochemistry, both MMP14 and MMP16 localized to the different ovarian cell types in rats and humans. Treatment with hCG resulted in intense immunoreactivity of MMP14 and MMP16 proteins in the granulosa and theca cells. The present study shows that MMP14 and MMP16 are increased by hCG administration in the ovulating follicle, demonstrating that these MMPs are conserved among rats, macaques, and humans. These findings suggest that MT-MMPs could have an important role in promoting ovulation and remodeling of the ovulated follicle into the corpus luteum. © 2014 by the Society for the Study of Reproduction, Inc.

Ovarian Membrane-Type Matrix Metalloproteinases: Induction of MMP14 and MMP16 During the Periovulatory Period in the Rat, Macaque, and Human1

PubMed Central

Puttabyatappa, Muraly; Jacot, Terry A.; Al-Alem, Linah F.; Rosewell, Katherine L.; Duffy, Diane M.; Brännström, Mats; Curry, Thomas E.

2014-01-01

ABSTRACT An intrafollicular increase in proteolytic activity drives ovulatory events. Surprisingly, the periovulatory expression profile of the membrane-type matrix metalloproteinases (MT-MMPs), unique proteases anchored to the cell surface, has not been extensively examined. Expression profiles of the MT-MMPs were investigated in ovarian tissue from well-characterized rat and macaque periovulatory models and naturally cycling women across the periovulatory period. Among the six known MT-MMPs, mRNA expression of Mmp14, Mmp16, and Mmp25 was increased after human chorionic gonadotropin (hCG) administration in rats. In human granulosa cells, mRNA expression of MMP14 and MMP16 increased following hCG treatment. In contrast, mRNA levels of MMP16 and MMP25 in human theca cells were unchanged before ovulation but declined by the postovulatory stage. In macaque granulosa cells, hCG increased mRNA for MMP16 but not MMP14. Immunoblotting showed that protein levels of MMP14 and MMP16 in rats increased, similar to their mRNA expression. In macaque granulosa cells, only the active form of the MMP14 protein increased after hCG, unlike its mRNA or the proprotein. By immunohistochemistry, both MMP14 and MMP16 localized to the different ovarian cell types in rats and humans. Treatment with hCG resulted in intense immunoreactivity of MMP14 and MMP16 proteins in the granulosa and theca cells. The present study shows that MMP14 and MMP16 are increased by hCG administration in the ovulating follicle, demonstrating that these MMPs are conserved among rats, macaques, and humans. These findings suggest that MT-MMPs could have an important role in promoting ovulation and remodeling of the ovulated follicle into the corpus luteum. PMID:24920038

Circulating miR-323-3p as a Biomarker of Ectopic Pregnancy

PubMed Central

Zhao, Zhen; Zhao, Qiuhong; Warrick, Joshua; Lockwood, Christina M.; Woodworth, Alison; Moley, Kelle H.; Gronowski, Ann M.

2013-01-01

BACKGROUND The use of serum human chorionic gonadotropin (hCG) and progesterone to identify patients with ectopic pregnancy (EP) has been shown to have poor clinical utility. Pregnancy-associated circulating microRNAs (miRNAs) have been proposed as potential biomarkers for the diagnosis of pregnancy-associated complications. This proof-of concept study examined the diagnostic accuracy of various miRNAs to detect EP in an emergency department (ED) setting. METHODS This was a retrospective case-control analysis of 89 women who presented to the ED with vaginal bleeding and/or abdominal pain/cramping, and were diagnosed with viable intrauterine pregnancy (VIP), spontaneous abortion (SA), or EP. Serum hCG and progesterone concentrations were determined by immunoassays. Serum miR-323-3p, miR-517a, miR-519d, and miR-525-3p concentrations were measured using TaqMan real-time PCR. Statistical analysis was performed to determine the clinical utility of these biomarkers as single markers and as multimarker panels for EP. RESULTS Concentrations of serum hCG, progesterone, miR-517a, miR-519d, and miR-525-3p were significantly lower in EP and SA than in VIP. In contrast, the concentration of miR-323-3p was significantly elevated in EP as compared to SA and VIP. As a single marker, miR-323-3p had the highest sensitivity of 37.0% (at a fixed-specificity of 90%). Comparatively, combined hCG, progesterone, and miR-323-3p panel yielded the highest sensitivity of 77.8% (at a fixed-specificity of 90%). A stepwise analysis using hCG, then progesterone, and then miR-323-3p resulted in 96.3% sensitivity and 72.6% specificity. CONCLUSIONS Pregnancy-associated miRNAs, especially miR-323-3p, added significant diagnostic accuracy to a panel including hCG and progesterone for the diagnosis of EP. PMID:22395025

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

Calcitriol affects hCG gene transcription in cultured human syncytiotrophoblasts

PubMed Central

Barrera, David; Avila, Euclides; Hernández, Guillermo; Méndez, Isabel; González, Leticia; Halhali, Ali; Larrea, Fernando; Morales, Angélica; Díaz, Lorenza

2008-01-01

Background In pregnancy, maternal serum concentrations of calcitriol significantly rise as a result of increased renal and placental contribution in order to assure calcium supply for the developing fetus. Considering that placenta is a site for vitamin D activation, and the versatility and potency of calcitriol, it is feasible that this hormone participates in fetal/placental development and physiology. In the present work we studied calcitriol actions upon human chorionic gonadotropin (hCG) secretion and expression in cultured trophoblasts, as well as vitamin D receptor (VDR) and CYP27B1 immunolocalization in placental villi. Methods Quantification of hCG in culture media was performed by immunoassay. Expression studies were carried out by real time PCR. Analysis of CYP27B1 and VDR localization in placental slides were performed by immunohistochemistry. Statistical significance was established by one way ANOVA using Tukey test for comparisons. Results Calcitriol regulated hCG in a time-dependent manner: at 6 h the secosteroid stimulated hCG, whereas longer incubations (24 h) showed opposite effects. Interestingly, calcitriol stimulatory effects on hCG were accompanied by an increase in intracellular cAMP content and were abolished by pre-incubation of the cells with a selective protein kinase A inhibitor. Immunohistochemical techniques showed differential VDR localization in the syncytiotrophoblast layer or in the vascular smooth muscle cells depending on the epitope to which the antibodies were raised (specific for the carboxy- or amino-terminal regions, respectively). CYP27B1 was immunolocalized in the syncytiotrophoblast layer of placental villi. Conclusion The presence and location of the vitamin D activating enzyme CYP27B1 as well as the specific receptor for vitamin D were shown in placental sections. The latter, together with findings demonstrating specific effects of calcitriol acting through the VDR and the cAMP/PKA signaling pathway upon hCG expression and secretion, indicate that there is a functional vitamin D endocrine system in the placenta, and recognize calcitriol as an autocrine regulator of hCG. PMID:18211694

[Two Cases of Germ Cell Tumors with Hyperthyroidism Due to High Serum hCGLevels].

PubMed

Chihara, Ichiro; Nitta, Satoshi; Kimura, Tomokazu; Kandori, Shuya; Kawahara, Takashi; Waku, Natsui; Kojima, Takahiro; Joraku, Akira; Miyazaki, Jun; Iwasaki, Hitoshi; Suzuki, Hiroaki; Kawai, Koji; Nishiyama, Hiroyuki

2016-09-01

We reported two cases of hyperthyroidism that developed during induction chemotherapy for advanced germ cell tumors with high serum human chorionic gonadotropin (hCG) levels. Case 1 : An 18-year-old man with mediastinal choriocarcinoma complained of tachycardia and tremor. His pretreatment serum hCG level was 1.37 million mIU/ml. The free thyroxine (fT4) level measured on day 2 of the first course of bleomycin, etoposide and cisplatin (BEP) was elevated to 7.8 ng/dl (＜1.7 ng/dl), whereasthe thyroidstimulating hormone (TSH) level was undetectable. We diagnosed the patient with hyperthyroidism and started oral propranolol and thiamazole. Subsequently, his tachycardia and tremor disappeared. On day 12 of the first course of BEP, his hCG level decreased to less than 50,000 mIU/ml. Also, his fT4 level returned to the normal range. Case 2 : A 29-year-old man presented with a left scrotal mass. He was diagnosed with non-seminoma testicular cancer (embryonal carcinoma and choriocarcinoma) with multiple lung, liver and lymph node metastases. On the admission day, his serum hCG and fT4 levels were high ; 3.23 million mIU/ml and 2.2 ng/dl, respectively. The TSH level was low at 0.011 mIU/ml. On day 3 of the first course of BEP, his hCG and fT4 levels increased to 4.5 million mIU/ml and 3.0 ng/dl, respectively. He complained of tachycardia, tremor and hyperhydrosis. He was started on propranolol and potassium iodide. After the treatment, histachycardia, tremor and hyperhidrosisdis appeared. HisfT4 level normalized on day 17 of the first course of BEP. The TSH-like activity of hCG is considered to be responsible for paraneoplastic hyperthyroidism among germ cell cancer patients with high hCG levels. To our knowledge, thisisthe first report of such a case in Japan. However, thisphenomenon isnot rare among patients with extremely high hCG levels. Therefore, we should be careful of these patients.

Human chorionic gonadotrophin and weight loss. A double-blind, placebo-controlled trial.

PubMed

Bosch, B; Venter, I; Stewart, R I; Bertram, S R

1990-02-17

Low-dose human chorionic gonadotrophin (HCG) combined with a severe diet remains a popular treatment for obesity, despite equivocal evidence of its effectiveness. In a double-blind, placebo-controlled study, the effects of HCG on weight loss were compared with placebo injections. Forty obese women (body mass index greater than 30 kg/m2) were placed on the same diet supplying 5,000 kJ per day and received daily intramuscular injections of saline or HCG, 6 days a week for 6 weeks. A psychological profile, hunger level, body circumferences, a fasting blood sample and food records were obtained at the start and end of the study, while body weight was measured weekly. Subjects receiving HCG injections showed no advantages over those on placebo in respect of any of the variables recorded. Furthermore, weight loss on our diet was similar to that on severely restricted intake. We conclude that there is no rationale for the use of HCG injections in the treatment of obesity.

Luteal estrogen supplementation in pregnancies associated with low serum estradiol concentrations.

PubMed

Kaider, A S; Coulam, C B

2000-07-01

The role of luteal phase estrogen in pregnancy outcome has been a matter of considerable debate. In order to evaluate the effectiveness of estrogen supplementation in gonadotropin releasing hormone agonist (GnRHa)/human menopausal gonadotropin (hMG)-stimulated cycles associated with low luteal estrogen concentration, a study was performed comparing the ongoing pregnancy rates in cycles with serum concentrations of estradiol (E2) <100 pg/ml 11 days post embryo transfer (p-ET), treated with luteal phase progesterone (P4) vs. E2 and P4 supplementation. Among 1106 serum samples studied, 951 were from women receiving GnRHa and follicle stimulating hormone (FSH) prior to oocyte retrieval and P4 (50 mg-100 mg IM daily) as luteal phase supplementation beginning day 11 after retrieval. The remaining 155 were from women receiving both E2 (2 mg-6 mg estrace orally each day) and P4 during the luteal phase. Significantly greater frequencies of preclinical losses were observed among women with human chorionic gonadotropin (hCG) concentrations>5 mIU/ml and concurrent E2 concentrations <100 pg/ml compared with E2 >100 pg/ml (p<0.00001). Among the 128 women who had hCG concentrations >5 mIU/ml and E2 concentrations <100 pg/ml, 102 received P4 only during the luteal phase and 26 were treated with estrace 2 mg-6 mg daily, as well as P4 during the luteal phase. The frequency of preclinical pregnancy losses among the 102 women with hCG >5 mIU/ml and E2 <100 pg/ml who did not receive luteal E2 supplementation was 72%, compared with 50% who received luteal E2 supplementation (p=0.04) The increase in preclinical pregnancy loss rates among women not receiving luteal E2 resulted in a decrease in ongoing pregnancy rate (8%), compared to those receiving luteal E2 supplementation (31%) (p=0.002). Our results indicated that a subset of women losing pregnancies preclinically after GnRHa and FSH stimulation due to low luteal phase serum E2 level may benefit from luteal estrogen supplementation. More sensitive and specific markers are needed to identify prospectively women in this risk group.

HCG administration after endogenous LH rise negatively influences pregnancy rate in modified natural cycle for frozen-thawed euploid blastocyst transfer: a pilot study.

PubMed

Litwicka, Katarzyna; Mencacci, Cecilia; Arrivi, Cristiana; Varricchio, Maria Teresa; Caragia, Alina; Minasi, Maria Giulia; Greco, Ermanno

2018-03-01

The aim of the present study was to evaluate whether in a modified natural cycle (modified-NC) for a frozen-thawed single euploid blastocyst transfer, a critical LH value, above which human chorionic gonadotropin (hCG) administration should be avoided, may be defined. One hundred and sixty-seven patients underwent modified natural cycle in order to transfer a single frozen-thawed euploid blastocyst. All embryos were obtained by intracytoplasmic sperm injection and were biopsied at the blastocyst stage and analyzed by means of array comparative genomic hybridization (aCGH). Ovulation was induced using 10.000 IU hCG when the mean follicle diameter was at least of 17 mm, independently from LH values. The primary end points were the hCG-positive test and clinical pregnancy. The interim analysis showed that LH value ≥ 13 mIU/ml on the day of hCG injection may negatively influence the clinical results, suggesting that in this condition, it should be advisable waiting for spontaneous ovulation. Among patients who received hCG for ovulation induction, the hCG-positive test and clinical pregnancy rates in modified-NC were significantly lower in cycles with LH ≥ 13 mIU/ml in respect to those with LH < 13 mIU/ml (45.4 vs 73.3 and 36.4 vs 65.9%, in LH ≥ 13 and LH < 13 groups, respectively). In patients with LH value ≥ 13 mIU/ml, hCG administration led to significantly lower rates of hCG-positive test (45.4 vs 74.5% in hCG administration and spontaneous ovulation groups, respectively) and clinical pregnancy (36.4 vs 64.7% in hCG administration and spontaneous ovulation groups, respectively). The baseline patient characteristics were comparable in all groups. The findings of this study highlight that LH elevation ≥ 13 mIU/ml prior to hCG administration may negatively affect clinical pregnancy rates in modified-NC for single euploid blastocyst transfer. The LH determination should be routinely performed during follicular monitoring. In the presence of LH level ≥ 13 mIU/ml, hCG administration should be avoided, and the embryo transfer should be planned only after spontaneous follicular rupture.

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.

Efficacy and Outcome Predictors of Gonadotropin Treatment for Male Congenital Hypogonadotropic Hypogonadism: A Retrospective Study of 223 Patients.

PubMed

Liu, Zhaoxiang; Mao, Jangfeng; Wu, Xueyan; Xu, Hongli; Wang, Xi; Huang, Bingkun; Zheng, Junjie; Nie, Min; Zhang, Hongbing

2016-03-01

Gonadotropin induces masculinization and spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). However, large cohort studies for the efficacy and reliable predictors of this therapy need to be conducted. The aim of this study was to investigate the efficacy of gonadotropin treatment in a large cohort of male CHH patients and analyze putative predictors for successful spermatogenesis. This retrospective study included 223 CHH azoospermic patients without puberty development treated between 2005 and 2014. All patients received combined human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) and were followed up for >6 months (5109 person-months). Serum total testosterone level, testicular size, spermatogenesis, and pregnancy outcome were recorded at each visit. After gonadotropin therapy, testicular size was enlarged from 2.1 ± 1.6 to 8.1 ± 4.6 mL (P < 0.001) and serum total testosterone was elevated from 0.9 ± 0.5 to 15.1 ± 8.2 nmol/L (P < 0.001). Spermatogenesis (>0/mL) occurred at a median period of 15 months (95% confidence interval 13.5-16.5). Larger basal testicular volume (P = 0.012) and noncryptorchidism history (P = 0.028) are independent predictors for earlier sperm appearance. Sixty four percent (143/223) of patients succeeded in producing sperms and the average time for initial sperm detection was 14 ± 8 months. However, their sperm concentrations (11.7 [2.1, 24.4] million/mL) and sperm progressive motility (A + B 36.9% ± 20.2%) are significantly lower than World Health Organization standards. Of the 34 patients who desired for fathering children, 19 patients impregnanted their partners during the treatment. Gonadotropin therapy induces spermatogenesis in male CHH patients. A larger basal testicular size and noncryptorchidism history are favorable indicators for earlier spermatogenesis.

Efficacy and Outcome Predictors of Gonadotropin Treatment for Male Congenital Hypogonadotropic Hypogonadism

PubMed Central

Liu, Zhaoxiang; Mao, Jangfeng; Wu, Xueyan; Xu, Hongli; Wang, Xi; Huang, Bingkun; Zheng, Junjie; Nie, Min; Zhang, Hongbing

2016-01-01

Abstract Gonadotropin induces masculinization and spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). However, large cohort studies for the efficacy and reliable predictors of this therapy need to be conducted. The aim of this study was to investigate the efficacy of gonadotropin treatment in a large cohort of male CHH patients and analyze putative predictors for successful spermatogenesis. This retrospective study included 223 CHH azoospermic patients without puberty development treated between 2005 and 2014. All patients received combined human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) and were followed up for >6 months (5109 person-months). Serum total testosterone level, testicular size, spermatogenesis, and pregnancy outcome were recorded at each visit. After gonadotropin therapy, testicular size was enlarged from 2.1 ± 1.6 to 8.1 ± 4.6 mL (P < 0.001) and serum total testosterone was elevated from 0.9 ± 0.5 to 15.1 ± 8.2 nmol/L (P < 0.001). Spermatogenesis (>0/mL) occurred at a median period of 15 months (95% confidence interval 13.5–16.5). Larger basal testicular volume (P = 0.012) and noncryptorchidism history (P = 0.028) are independent predictors for earlier sperm appearance. Sixty four percent (143/223) of patients succeeded in producing sperms and the average time for initial sperm detection was 14 ± 8 months. However, their sperm concentrations (11.7 [2.1, 24.4] million/mL) and sperm progressive motility (A + B 36.9% ± 20.2%) are significantly lower than World Health Organization standards. Of the 34 patients who desired for fathering children, 19 patients impregnanted their partners during the treatment. Gonadotropin therapy induces spermatogenesis in male CHH patients. A larger basal testicular size and noncryptorchidism history are favorable indicators for earlier spermatogenesis. PMID:26945370

Immunogenicity and Safety of an Inactivated Rift Valley Fever Vaccine in a 19-Year Study

DTIC Science & Technology

2011-02-26

in general good health. Women of childbearing potential were required to have a negative beta subunit human chorionic gonadotropin (BhCG) pregnancy ...3 of the primary series (Fig. 1). 3.3.1.1. Serological analysis primary series of most prevalent lots uti - lized. When immune response analysis was...reported in one study with sheep that received MP-12 in the first trimester of pregnancy , other studies in ewes and in cattle showed no evidence of

Retroperitoneal ectopic pregnancy: a case report and review of the literature.

PubMed

Yang, Man; Cidan, Lamu; Zhang, Dan

2017-10-16

Retroperitoneal ectopic pregnancy (REP) is an extremely rare type of ectopic pregnancy, with a total of less than 20 cases reported in the English literature. However, failure to recognize REP may result in severe consequences. We report a case of 32-year-old woman with REP. She had amenorrhea, left lower abdominal pain, but no vaginal bleeding. Her urine human chorionic gonadotropin (HCG) test was positive and blood HCG level was 1880 m-international units per milliliter (mIU/mL). Transvaginal ultrasound sonography showed a left adnexal mass. Laparoscopy found an enlarged uterus, normal right uterine tube and ovary, and normal left uterine tube. The left ovary was partly covered by a blood clot, but appeared normal after removing the clot. There was a 10-mm circular peritoneal defect located lateral to the left sacrocervical ligament, anterior to the left ovarian fossa, and next to the lower edge of the left broad ligament. The patient was diagnosed of having REP with the gestational tissues covered by the peritoneum. The REP was removed by laparoscopic surgery. Bleeding was stopped by bipolar coagulation and absorbable hemostatic cellulose. The patient recovered smoothly and was discharged on the next day after surgery. Her blood HCG returned to normal range 29 days after surgery. REP is very rare, but in any suspected case of ectopic pregnancy, caution must be paid to find signs of REP when the common sites of ectopic pregnancy do not have any positive findings.

Induction of proteinases in the human preovulatory follicle of the menstrual cycle by human chorionic gonadotropin.

PubMed

Rosewell, Katherine L; Al-Alem, Linah; Zakerkish, Farnosh; McCord, Lauren; Akin, James W; Chaffin, Charles L; Brännström, Mats; Curry, Thomas E

2015-03-01

To explore the temporal expression in granulosa and theca cells of key members of the MMP and ADAMTS families across the periovulatory period in women to gain insight into their possible roles during ovulation and early luteinization. Experimental prospective clinical study and laboratory-based investigation. University medical center and private IVF center. Thirty-eight premenopausal women undergoing surgery for tubal ligation and six premenopausal women undergoing assisted reproductive techniques. Administration of hCG and harvesting of follicles by laparoscopy and collection of granulosa-lutein cells at oocyte retrieval. Expression of mRNA for matrix metalloproteinase (MMPs) and the A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) in human granulosa cells and theca cells collected across the periovulatory period of the menstrual cycle and in cultured granulosa-lutein cells after hCG. Localization of MMPs and ADAMTSs by immunohistochemistry. Expression of MMP1 and MMP19 mRNA increased in both granulosa and theca cells after hCG administration. ADAMTS1 and ADAMTS9 mRNA increased in granulosa cells after hCG treatment, however, thecal cell expression for ADAMTS1 was unchanged, while ADAMTS9 expression was decreased. Expression of MMP8 and MMP13 mRNA was unchanged. Immunohistochemistry confirmed the localization of MMP1, MMP19, ADAMTS1, and ADAMTS9 to the granulosa and thecal cell layers. The collection of the dominant follicle throughout the periovulatory period has allowed the identification of proteolytic remodeling enzymes in the granulosa and theca compartments that may be critically involved in human ovulation. These proteinases may work in concert to regulate breakdown of the follicular wall and release of the oocyte. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Chemokine Ligand 20: A Signal for Leukocyte Recruitment During Human Ovulation?

PubMed

Al-Alem, Linah; Puttabyatappa, Muraly; Rosewell, Kathy; Brännström, Mats; Akin, James; Boldt, Jeffrey; Muse, Ken; Curry, Thomas E

2015-09-01

Ovulation is one of the cornerstones of female fertility. Disruption of the ovulatory process results in infertility, which affects approximately 10% of couples. Using a unique model in which the dominant follicle is collected across the periovulatory period in women, we have identified a leukocyte chemoattractant, chemokine ligand 20 (CCL20), in the human ovary. CCL20 mRNA is massively induced after an in vivo human chorionic gonadotropin (hCG) stimulus in granulosa (>10 000-fold) and theca (>4000-fold) cells collected during the early ovulatory (12-18 h) and late ovulatory (18-34 h) periods after hCG administration. Because the LH surge sets in motion an inflammatory reaction characterized by an influx of leukocytes and CCL20 is known to recruit leukocytes in other systems, the composition of ovarian leukocytes (CD45+) containing the CCL20 receptor CCR6 was determined immediately prior to ovulation. CD45+/CCR6+ cells were primarily natural killer cells (41%) along with B cells (12%), T cells (11%), neutrophils (10%), and monocytes (9%). Importantly, exogenous CCL20 stimulated ovarian leukocyte migration 59% within 90 minutes. Due to the difficulties in obtaining human follicles, an in vitro model was developed using granulosa-lutein cells to explore CCL20 regulation. CCL20 expression increased 40-fold within 6 hours after hCG, was regulated partially by the epithelial growth factor pathway, and was positively correlated with progesterone production. These results demonstrate that hCG dramatically increases CCL20 expression in the human ovary, that ovarian leukocytes contain the CCL20 receptor, and that CCL20 stimulates leukocyte migration. Our findings raise the prospect that CCL20 may aid in the final ovulatory events and contribute to fertility in women.

Chemokine Ligand 20: A Signal for Leukocyte Recruitment During Human Ovulation?

PubMed Central

Al-Alem, Linah; Puttabyatappa, Muraly; Rosewell, Kathy; Brännström, Mats; Akin, James; Boldt, Jeffrey; Muse, Ken

2015-01-01

Ovulation is one of the cornerstones of female fertility. Disruption of the ovulatory process results in infertility, which affects approximately 10% of couples. Using a unique model in which the dominant follicle is collected across the periovulatory period in women, we have identified a leukocyte chemoattractant, chemokine ligand 20 (CCL20), in the human ovary. CCL20 mRNA is massively induced after an in vivo human chorionic gonadotropin (hCG) stimulus in granulosa (>10 000-fold) and theca (>4000-fold) cells collected during the early ovulatory (12–18 h) and late ovulatory (18–34 h) periods after hCG administration. Because the LH surge sets in motion an inflammatory reaction characterized by an influx of leukocytes and CCL20 is known to recruit leukocytes in other systems, the composition of ovarian leukocytes (CD45+) containing the CCL20 receptor CCR6 was determined immediately prior to ovulation. CD45+/CCR6+ cells were primarily natural killer cells (41%) along with B cells (12%), T cells (11%), neutrophils (10%), and monocytes (9%). Importantly, exogenous CCL20 stimulated ovarian leukocyte migration 59% within 90 minutes. Due to the difficulties in obtaining human follicles, an in vitro model was developed using granulosa-lutein cells to explore CCL20 regulation. CCL20 expression increased 40-fold within 6 hours after hCG, was regulated partially by the epithelial growth factor pathway, and was positively correlated with progesterone production. These results demonstrate that hCG dramatically increases CCL20 expression in the human ovary, that ovarian leukocytes contain the CCL20 receptor, and that CCL20 stimulates leukocyte migration. Our findings raise the prospect that CCL20 may aid in the final ovulatory events and contribute to fertility in women. PMID:26125463

Optimization of an Optical Inspection System Based on the Taguchi Method for Quantitative Analysis of Point-of-Care Testing

PubMed Central

Yeh, Chia-Hsien; Zhao, Zi-Qi; Shen, Pi-Lan; Lin, Yu-Cheng

2014-01-01

This study presents an optical inspection system for detecting a commercial point-of-care testing product and a new detection model covering from qualitative to quantitative analysis. Human chorionic gonadotropin (hCG) strips (cut-off value of the hCG commercial product is 25 mIU/mL) were the detection target in our study. We used a complementary metal-oxide semiconductor (CMOS) sensor to detect the colors of the test line and control line in the specific strips and to reduce the observation errors by the naked eye. To achieve better linearity between the grayscale and the concentration, and to decrease the standard deviation (increase the signal to noise ratio, S/N), the Taguchi method was used to find the optimal parameters for the optical inspection system. The pregnancy test used the principles of the lateral flow immunoassay, and the colors of the test and control line were caused by the gold nanoparticles. Because of the sandwich immunoassay model, the color of the gold nanoparticles in the test line was darkened by increasing the hCG concentration. As the results reveal, the S/N increased from 43.48 dB to 53.38 dB, and the hCG concentration detection increased from 6.25 to 50 mIU/mL with a standard deviation of less than 10%. With the optimal parameters to decrease the detection limit and to increase the linearity determined by the Taguchi method, the optical inspection system can be applied to various commercial rapid tests for the detection of ketamine, troponin I, and fatty acid binding protein (FABP). PMID:25256108

Atrazine activates multiple signaling pathways enhancing the rapid hCG-induced androgenesis in rat Leydig cells.

PubMed

Pogrmic-Majkic, Kristina; Fa, Svetlana; Samardzija, Dragana; Hrubik, Jelena; Kaisarevic, Sonja; Andric, Nebojsa

2016-08-10

Atrazine (ATR) is an endocrine disruptor that affects steroidogenic process, resulting in disruption of reproductive function of the male and female gonads. In this study, we used the primary culture of peripubertal Leydig cells to investigate the effect of ATR on the rapid androgen production stimulated by human chorionic gonadotropin (hCG). We demonstrated that ATR activated multiple signaling pathways enhancing the rapid hCG-stimulated androgen biosynthesis in Leydig cells. Low hCG concentration (0.25ng/mL) caused cAMP-independent, but ERK1/2-dependent increase in androgen production after 60min of incubation. Co-treatment with ATR for 60min enhanced the cAMP production in hCG-stimulated cells. Accumulation of androgens was prevented by addition of U0126, N-acetyl-l-cysteine and AG1478. Co-treatment with hCG and ATR for 60min did not alter steroidogenic acute regulatory protein (Star) mRNA level in Leydig cells. After 120min, hCG further increased androgenesis in Leydig cells that was sensitive to inhibition of the cAMP/PKA, ERK1/2 and ROS signaling pathways. Co-treatment with ATR for 120min further enhanced the hCG-induced androgen production, which was prevented by inhibition of the calcium, PKC and EGFR signaling cascades. After 120min, ATR enhanced the expression of Star mRNA in hCG-stimulated Leydig cells through activation of the PKA and PKC pathway. Collectively, these data suggest that exposure to ATR caused perturbations in multiple signaling pathways, thus enhancing the rapid hCG-dependent androgen biosynthesis in peripubertal Leydig cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Placenta percreta: methotrexate treatment and MRI findings.

PubMed

Heiskanen, Nonna; Kröger, Jaana; Kainulainen, Sakari; Heinonen, Seppo

2008-02-01

Our patient was a 24-year-old gravida 2 para 0 woman. After delivery, placenta percreta was noticed. There was no postpartum hemorrhage, and the patient desired future pregnancies. Although placenta percreta is rare, its sequelae include potentially lethal hemorrhage and loss of reproduction function. Placenta percreta was confirmed histologically and with ultrasonography and magnetic resonance imaging (MRI). Placenta percreta was treated conservatively with methotrexate. On follow-up, MRI showed a small calcified transmural extension of the placenta throughout the uterus in the right fundal area. Color Doppler ultrasonography showed no blood flow in the corresponding area, and maternal serum human chorionic gonadotropin (hCG) was undetectable. Use of MRI is a new method to detect abnormal placentation, and it could be used on follow-up in selective cases with other follow-up modalities. However, it seems likely that conservative management to preserve future fertility remains a secured and reasonable alternative when a patient has no active bleeding.

Effects of prolonged physical exercise and fasting upon plasma testosterone level in rats.

PubMed

Guezennec, C Y; Ferre, P; Serrurier, B; Merino, D; Pesquies, P C

1982-01-01

Prolonged physical exercise and fasting in male rats were studied to determine the effect of these two treatments on plasma testosterone level. Blood and tissue samples were drawn after 1 h, 3 h, 5 h, and 7 h treadmill running, and after 24 h, 48 h, and 72 h of fasting. Both treatments resulted in a significant fall in plasma testosterone, plasma luteinizing hormone (LH), plasma Insulin (IRI) and in liver and muscle glycogen stores. In the course of these two treatments the injection of a supra maximal dose of Human Chorionic Gonadotropin (HCG) produced a rise in plasma testosterone similar to that in control rats. This indicates that the decrease of plasma LH may be responsible for the decrease in plasma testosterone, which is time-related with the decrease in glycogen stores. The possible metabolic role of the decrease in plasma testosterone is discussed.

Cyclic estrous-like behavior in a spayed cat associated with excessive sex-hormone production by an adrenocortical carcinoma.

PubMed

Meler, Erika N; Scott-Moncrieff, J Catharine; Peter, Augustine T; Bennett, Sara; Ramos-Vara, Jose; Salisbury, S Kathleen; Naughton, James F

2011-06-01

A 15-year-old, spayed female domestic shorthair cat was evaluated for 1-year duration of cyclic intermittent estrous behavior. Diagnostic testing performed before referral, including baseline progesterone concentration, human chorionic gonadotropin (hCG) hormone stimulation test and surgical exploratory laparotomy, had remained inconclusive for a remnant ovary. Evaluation of sex hormones before and after adrenocorticotropic hormone (ACTH) administration revealed increased basal concentrations of androstenedione, estradiol, progesterone, and 17α-hydroxyprogesterone and normal ACTH-stimulated hormone concentrations. Enlargement of the right adrenal gland was identified by abdominal ultrasound. The cat underwent an adrenalectomy and histopathology of the excised adrenal gland was consistent with an adrenocortical carcinoma. Clinical signs resolved immediately following surgery, and most hormone concentrations declined to within or below the reference interval (RI) by 2 months after surgery. Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Managing pregnancy of unknown location based on initial serum progesterone and serial serum hCG levels: development and validation of a two-step triage protocol.

PubMed

Van Calster, B; Bobdiwala, S; Guha, S; Van Hoorde, K; Al-Memar, M; Harvey, R; Farren, J; Kirk, E; Condous, G; Sur, S; Stalder, C; Timmerman, D; Bourne, T

2016-11-01

A uniform rationalized management protocol for pregnancies of unknown location (PUL) is lacking. We developed a two-step triage protocol to select PUL at high risk of ectopic pregnancy (EP), based on serum progesterone level at presentation (step 1) and the serum human chorionic gonadotropin (hCG) ratio, defined as the ratio of hCG at 48 h to hCG at presentation (step 2). This was a cohort study of 2753 PUL (301 EP), involving a secondary analysis of prospectively and consecutively collected PUL data from two London-based university teaching hospitals. Using a chronological split we used 1449 PUL for development and 1304 for validation. We aimed to assign PUL as low risk with high confidence (high negative predictive value (NPV)) while classifying most EP as high risk (high sensitivity). The first triage step assigned PUL as low risk using a threshold of serum progesterone at presentation. The remaining PUL were triaged using a novel logistic regression risk model based on hCG ratio and initial serum progesterone (second step), defining low risk as an estimated EP risk of < 5%. On validation, initial serum progesterone ≤ 2 nmol/L (step 1) classified 16.1% PUL as low risk. Second-step classification with the risk model selected an additional 46.0% of all PUL as low risk. Overall, the two-step protocol classified 62.1% of PUL as low risk, with an NPV of 98.6% and a sensitivity of 92.0%. When the risk model was used in isolation (i.e. without the first step), 60.5% of PUL were classified as low risk with 99.1% NPV and 94.9% sensitivity. PUL can be classified efficiently into being either high or low risk for complications using a two-step protocol involving initial progesterone and hCG levels and the hCG ratio. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism.

PubMed

Nieschlag, Eberhard; Bouloux, Pierre-Marc G; Stegmann, Barbara J; Shankar, R Ravi; Guan, Yanfen; Tzontcheva, Anjela; McCrary Sisk, Christine; Behre, Hermann M

2017-03-07

Hypogonadotropic hypogonadism (HH) in men results in insufficient testicular function and deficiencies in testosterone and spermatogenesis. Combinations of human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (recFSH) have been successful in the treatment of HH. Corifollitropin alfa is a long-acting FSH-analog with demonstrated action in women seeking infertility care. The aim of this study was to investigate the efficacy and safety of corifollitropin alfa combined with hCG to increase testicular volume and induce spermatogenesis in men with HH. This was a Phase III, multi-center, open-label, single-arm trial of corifollitropin alfa in azoospermic men aged 18 to 50 years with HH. After 16 weeks of pretreatment of 23 subjects with hCG alone, 18 subjects with normalized testosterone (T) levels who remained azoospermic entered the 52-week combined treatment phase with hCG twice-weekly and 150 μg corifollitropin alfa every other week. The increase in testicular volume (primary efficacy endpoint) and induction of spermatogenesis resulting in a sperm count ≥1 × 10 6 /mL (key secondary efficacy endpoint) during 52 weeks of combined treatment were assessed. Safety was evaluated by the presence of anti-corifollitropin alfa antibodies and the occurrence of adverse events (AEs). Mean (±SD) testicular volume increased from 8.6 (±6.09) mL to 17.8 (±8.93) mL (geometric mean fold increase, 2.30 [95% CI: 2.03, 2.62]); 14 (77.8%) subjects reached a sperm count ≥1 × 10 6 /mL. No subject developed confirmed anti-corifollitropin alfa antibodies during the trial. Treatment was generally well tolerated. Corifollitropin alfa 150 μg administrated every other week combined with twice-weekly hCG for 52 weeks increased testicular volume significantly, and induced spermatogenesis in >75% of men with HH who had remained azoospermic after hCG treatment alone. ClinicalTrials.gov: NCT01709331 .

Induction of Tissue Factor Pathway Inhibitor 2 by hCG Regulates Periovulatory Gene Expression and Plasmin Activity.

PubMed

Puttabyatappa, Muraly; Al-Alem, Linah F; Zakerkish, Farnosh; Rosewell, Katherine L; Brännström, Mats; Curry, Thomas E

2017-01-01

Increased proteolytic activity is a key event that aids in breakdown of the follicular wall to permit oocyte release. How the protease activity is regulated is still unknown. We hypothesize that tissue factor pathway inhibitor 2 (TFPI2), a Kunitz-type serine protease inhibitor, plays a role in regulating periovulatory proteolytic activity as in other tissues. TFPI2 is secreted into the extracellular matrix (ECM) where it is postulated to regulate physiological ECM remodeling. The expression profile of TFPI2 during the periovulatory period was assessed utilizing a well-characterized human menstrual cycle model and a gonadotropin-primed rat model. Administration of an ovulatory dose of human chorionic gonadotropin (hCG) increased TFPI2 expression dramatically in human and rat granulosa and theca cells. This increase in Tfpi2 expression in rat granulosa cells required hCG-mediated epidermal growth factor, protein kinase A, mitogen-activated protein kinase (MAPK) 1/2, p38 MAPK and protease activated receptor 1-dependent cell signaling. A small interferingRNA-mediated knockdown of TFPI2 in rat granulosa cells resulted in increased plasmin activity in the granulosa cell conditioned media. Knockdown of TFPI2 also reduced expression of multiple genes including interleukin 6 (Il6) and amphiregulin (Areg). Overexpression of TFPI2 using an adenoviral vector partially restored the expression of Il6 and Areg in TFPI2 siRNA treated rat granulosa cells. These data support the hypothesis that TFPI2 is important for moderating plasmin activity and regulating granulosa cell gene expression during the periovulatory period. We, therefore, propose that through these actions, TFPI2 aids in the tissue remodeling taking place during follicular rupture and corpus luteum formation. Copyright © 2017 by the Endocrine Society.

Induction of Tissue Factor Pathway Inhibitor 2 by hCG Regulates Periovulatory Gene Expression and Plasmin Activity

PubMed Central

Puttabyatappa, Muraly; Al-Alem, Linah F.; Zakerkish, Farnosh; Rosewell, Katherine L.; Brännström, Mats

2017-01-01

Increased proteolytic activity is a key event that aids in breakdown of the follicular wall to permit oocyte release. How the protease activity is regulated is still unknown. We hypothesize that tissue factor pathway inhibitor 2 (TFPI2), a Kunitz-type serine protease inhibitor, plays a role in regulating periovulatory proteolytic activity as in other tissues. TFPI2 is secreted into the extracellular matrix (ECM) where it is postulated to regulate physiological ECM remodeling. The expression profile of TFPI2 during the periovulatory period was assessed utilizing a well-characterized human menstrual cycle model and a gonadotropin-primed rat model. Administration of an ovulatory dose of human chorionic gonadotropin (hCG) increased TFPI2 expression dramatically in human and rat granulosa and theca cells. This increase in Tfpi2 expression in rat granulosa cells required hCG-mediated epidermal growth factor, protein kinase A, mitogen-activated protein kinase (MAPK) 1/2, p38 MAPK and protease activated receptor 1-dependent cell signaling. A small interferingRNA-mediated knockdown of TFPI2 in rat granulosa cells resulted in increased plasmin activity in the granulosa cell conditioned media. Knockdown of TFPI2 also reduced expression of multiple genes including interleukin 6 (Il6) and amphiregulin (Areg). Overexpression of TFPI2 using an adenoviral vector partially restored the expression of Il6 and Areg in TFPI2 siRNA treated rat granulosa cells. These data support the hypothesis that TFPI2 is important for moderating plasmin activity and regulating granulosa cell gene expression during the periovulatory period. We, therefore, propose that through these actions, TFPI2 aids in the tissue remodeling taking place during follicular rupture and corpus luteum formation. PMID:27813674

High-dose hook effect in six automated human chorionic gonadotrophin assays.

PubMed

Al-Mahdili, Huda A; Jones, Graham R D

2010-07-01

The high-dose hook effect is a well-known phenomenon of two-site immunoassays including those for human chorionic gonadotrophin (hCG). We investigated the occurrence of a high-dose hook effect in six routinely available hCG assays using a sample with a total hCG concentration of approximately 3,600,000 IU/L. Dilutions of a sample with high hCG concentration were analysed using six common methods: Advia Centaur, Immulite 2000, Dimension RxL, Unicel DxI 800, Roche E170 and Abbott Architect. The measured concentrations and corresponding assay signals were obtained for each method. Performance was compared with manufacturer claims. Four of the tested platforms demonstrated a clear high-dose hook effect, while the other methods showed no hook effect at the highest level tested. Our results indicate that the hook effect may occur in some hCG assays, although the risk of reporting falsely low results was in most cases at higher concentrations than those indicated in manufacturers' product information. Assay design plays a major role in its occurrence. Laboratories should be aware of the assay limitations in this regard.

Adjuvant gonadotrophin-releasing hormone agonist trigger with human chorionic gonadotrophin to enhance ooplasmic maturity.

PubMed

Pereira, Nigel; Elias, Rony T; Neri, Queenie V; Gerber, Rachel S; Lekovich, Jovana P; Palermo, Gianpiero D; Rosenwaks, Zev

2016-11-01

This study investigates whether an adjuvant gonadotrophin-releasing hormone agonist (GnRHa) trigger with human chorionic gonadotrophin (HCG) improves fresh intracytoplasmic sperm injection (ICSI) cycle outcomes in patients with poor fertilization history after standard HCG trigger alone. This study compared 156 patients with <40% fertilization rate in a prior ICSI cycle with standard HCG trigger who underwent another ICSI cycle with a combined 2 mg GnRHa and 1500 IU HCG ovulatory trigger. There was no difference in the baseline demographics, ovarian stimulation outcomes or sperm parameters of the groups. More mature oocytes were retrieved in the combined trigger group compared with the HCG trigger group: 12 (9-14) versus 10 (7-12); P = 0.01. The fertilization rate in the combined trigger group (59.2%) was higher than the HCG group (35.3%); P = 0.01. The odds of clinical pregnancy and live birth were 1.8 and 1.7 times higher, respectively, when comparing the former group to the latter; P = 0.03. The results suggest that combined GnRHa and HCG trigger in ICSI cycles is a reasonable approach to increase oocyte maturity, specifically ooplasmic maturity, thereby increasing fertilization and improving ICSI cycle outcomes in patients with a history of poor fertilization after standard HCG trigger alone. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Elevated second-trimester maternal serum β-human chorionic gonadotropin and amniotic fluid alpha-fetoprotein as indicators of adverse obstetric outcomes in fetal Turner syndrome.

PubMed

Alvarez-Nava, Francisco; Soto, Marisol; Lanes, Roberto; Pons, Hector; Morales-Machin, Alisandra; Bracho, Ana

2015-12-01

The objective of this study was to determine the ability of biochemical analytes to identify adverse outcomes in pregnancies with Turner syndrome. Maternal serum and amniotic fluid (AF) marker concentrations were measured in 73 singleton pregnancies with Turner syndrome (10-22 weeks of gestation). Fetal Turner syndrome was definitively established by cytogenetic analysis. Two subgroups, fetuses with hydrops fetalis versus fetuses with cystic hygroma, were compared. Receiver operating characteristic curves and relative risk were established for a cut-off multiples of the median ≥3.5 for β-subunit of human chorionic gonadotropin (hCG) or AF alpha-fetoprotein (AFP). Forty-nine (67%) of 73 pregnant women had an abnormal maternal serum. While levels of pregnancy-associated plasma protein-A and free β-subunit (fβ)-hCG were not different to those of the control group, AFP, unconjugated estriol and β-hCG concentrations were significantly different in the study group (P < 0.05), when compared to those of unaffected pregnancies. Levels of β-hCG in pregnancies with hydrops fetalis were significantly higher than in those with cystic hygroma (P <0.0001), as were AF-AFP concentrations (P <0.0015). In addition, abnormalities in both maternal serum β-hCG and AF-AFP predicted fetal death. The relative risk of adverse obstetric outcome was 10.667 (P = 0.0004; 95% confidence interval [CI]: 1.554-73.203) for β-hCG and 2.19 (P = 0.0256; 95% CI: 1.001 to 4.779), for AF-AFP. Maternal serum β-hCG and AF-AFP levels may preferentially identify those Turner syndrome pregnancies with the highest risk of fetal death. © 2015 Japan Society of Obstetrics and Gynecology.

[No effect of digitalis on sex and adrenal hormones in healthy subjects and in patients with congestive heart failure].

PubMed

Kley, H K; Abendroth, H; Hehrmann, R; Müller, A; Keck, E; Schneitler, H; Elsässer, H; Krüskemper, H L

1984-01-16

Digoxin was studied to see whether it impairs adrenal function and feminizes male subjects by changing plasma sexual hormones; both have been reported on previously. In eight healthy male subjects neither estrone (38.7 +/- 7.7 vs 35.4 +/- 3.2 pg/ml) nor estradiol (35.8 +/- 6.4 vs 32.2 +/- 3.9 pg/ml) nor testosterone (6.32 +/- 0.74 vs 6.45 +/- 0.73 ng/ml) were found to be altered by digoxin administration (plasma levels 1.55 +/0- 0.27 ng/ml) lasting 35 days. The same was true of free testosterone (147 +/- 24 vs 142 +/- 19 pg/ml) and free estradiol (657 +/- 77 vs 615 +/- 78 fg/ml). Even maximal stimulation of the adrenal and gonadal glands by adrenocorticotropic hormone (ACTH) and human chorionic gonadotropin (hCG) did not exhibit any digoxin-induced alterations in the synthesizing capacity of steroid hormones, as shown by plasma cortisol (increase from 128 +/- 18 to 389 +/- 18 ng/ml) and testosterone (from 5.96 +/- 0.90 to 10.33 +/- 1.19 ng/ml). Furthermore, seven subjects on digoxin were observed over a period of 150-210 days; they did not show any increase of estrogens. This was also found in three subjects when estrogen levels were elevated initially due to extreme obesity. Also, 35 patients who took beta-methyldigoxin (n = 8), beta-acetyldigoxin (n = 20) and digitoxin (n = 7) from 1 to 9 (mean: 1.9) years demonstrated normal plasma concentrations of gonadal and adrenal steroids, irrespective of duration of application or the digitalis compound.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of an inducible platform for intercellular protein delivery.

PubMed

Siller, Richard; Dufour, Eric; Lycke, Max; Wilmut, Ian; Jung, Yong-Wook; Park, In Hyun; Sullivan, Gareth J

2017-04-30

A challenge to protein based therapies is the ability to produce biologically active proteins and their ensured delivery. Various approaches have been utilised including fusion of protein transduction domains with a protein or biomolecule of interest. A compounding issue is lack of specificity, efficiency and indeed whether the protein fusions are actually translocated into the cell and not merely an artefact of the fixation process. Here we present a novel platform, allowing the inducible export and uptake of a protein of interest. The system utilises a combination of the Tetracyline repressor system, combined with a fusion protein containing the N-terminal signal peptide from human chorionic gonadotropin beta-subunit, and a C-terminal poly-arginine domain for efficient uptake by target cells. This novel platform was validated using enhanced green fluorescent protein as the gene of interest. Doxycycline efficiently induced expression of the fusion protein. The human chorionic gonadotropin beta-subunit facilitated the export of the fusion protein into the cell culture media. Finally, the fusion protein was able to efficiently enter into neighbouring cells (target cells), mediated by the poly-arginine cell penetrating peptide. Importantly we have addressed the issue of whether the observed uptake is an artefact of the fixation process or indeed genuine translocation. In addition this platform provides a number of potential applications in diverse areas such as stem cell biology, immune therapy and cancer targeting therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

The human leukocyte antigen G promotes trophoblast fusion and β-hCG production through the Erk1/2 pathway in human choriocarcinoma cell lines

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

Wang, Ji-meng; State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101; Zhao, Hong-xi

2013-05-10

Highlights: •HLA-G expression promotes BeWo cells fusion and fusogenic gene expression. •HLA-G is capable of inducing β-hCG production in human choriocarcinoma cell lines. •Up-regulation of β-hCG production by HLA-G is mediated via the Erk1/2 pathway. -- Abstract: The human leukocyte antigen G (HLA-G) is expressed on the fetal–maternal interface and plays a role in protecting fetal-derived trophoblasts from the maternal immune response, allowing trophoblasts to invade the uterus. However, HLA-G also possesses immune suppressing-independent functions. We found that HLA-G expressing BeWo choriocarcinoma cells increased cell–cell fusion compared to control BeWo cells under forskolin treatment. Regardless of forskolin treatment, the expressionmore » of fusogenic gene mRNAs, including syncytin-1, the transcription factor glial cell missing 1 (Gcm1), and beta human chorionic gonadotropin (β-hCG) were elevated. HLA-G up-regulates β-hCG production in human choriocarcinoma cells because HLA-G knockdown in JEG-3 cells induces a dramatic decrease in β-hCG compared with control cells. The defect in β-hCG production in HLA-G knocked-down cells could not be completely overcome by stimulating hCG production through increasing intracellular cAMP levels. HLA-G expressing cells have increased phosphorylation levels for extracellular signal-regulated kinase1/2 (Erk1/2) in BeWo cells. The Erk1/2 pathway is inactivated after the inhibition of HLA-G expression in JEG-3 cells. Finally, Erk1/2 inhibition was able to suppress the increased hCG production induced by HLA-G expression. Together, these data suggest novel roles for HLA-G in regulating β-hCG production via the modulation of the Erk1/2 pathway and by inducing trophoblast cell fusion.« less

Molecular characterization of insulin resistance and glycolytic metabolism in the rat uterus

PubMed Central

Zhang, Yuehui; Sun, Xue; Sun, Xiaoyan; Meng, Fanci; Hu, Min; Li, Xin; Li, Wei; Wu, Xiao-Ke; Brännström, Mats; Shao, Ruijin; Billig, Håkan

2016-01-01

Peripheral insulin resistance and hyperandrogenism are the primary features of polycystic ovary syndrome (PCOS). However, how insulin resistance and hyperandrogenism affect uterine function and contribute to the pathogenesis of PCOS are open questions. We treated rats with insulin alone or in combination with human chorionic gonadotropin (hCG) and showed that peripheral insulin resistance and hyperandrogenism alter uterine morphology, cell phenotype, and cell function, especially in glandular epithelial cells. These defects are associated with an aberration in the PI3K/Akt signaling pathway that is used as an indicator for the onset of insulin resistance in classical metabolic tissues. Concomitantly, increased GSK3β (Ser-9) phosphorylation and decreased ERK1/2 phosphorylation in rats treated with insulin and hCG were also observed. We also profiled the expression of glucose transporter (Glut) isoform genes in the uterus under conditions of insulin resistance and/or hyperandrogenism. Finally, we determined the expression pattern of glycolytic enzymes and intermediates during insulin resistance and hyperandrogenism in the uterus. These findings suggest that the PI3K/Akt and MAPK/ERK signaling pathways play a role in the onset of uterine insulin resistance, and they also suggest that changes in specific Glut isoform expression and alterations to glycolytic metabolism contribute to the endometrial dysfunction observed in PCOS patients. PMID:27461373

Seasonal effects on ovarian responsiveness to exogenous gonadotrophins and successful artificial insemination in the snow leopard (Uncia uncia).

PubMed

Roth, T L; Armstrong, D L; Barrie, M T; Wildt, D E

1997-01-01

Ovaries of the seasonally-breeding snow leopard (Uncia uncia) were examined to determine whether they were responsive to exogenous gonadotrophins throughout the year. The potential of laparoscopic artificial insemination (AI) also was assessed for producing offspring. During the non-breeding, pre-breeding, breeding and post-breeding seasons, females (n = 20) were treated with a standardized, dual-hormone regimen given intramuscularly (600 I.U. of equine chorionic gonadotrophin followed 80-84 h later with 300 I.U. of human chorionic gonadotrophin (hCG)). Laparoscopy was performed 45-50 h after administration of hCG, and all ovarian structures were described. Females with fresh corpora lutea (CL) were inseminated, and anovulatory females were subjected to follicular aspiration to examine oocyte quality. Snow leopards responded to exogenous gonadotrophins throughout the year. Mean number of total ovarian structures (distinct follicles mature in appearance plus CL) did not differ (P > or = 0.05) with season, but the proportion of CL: total ovarian structures was greater (P < 0.01) for the breeding season compared with all other seasons. The proportion of females ovulating was greater (P < 0.05) during the breeding and post-breeding seasons than during the pre-breeding and non-breeding seasons respectively. No Grade-1 quality oocytes were recovered from follicles of anovulatory females. Serum concentrations of oestradiol-17 beta appeared elevated in all females, and neither oestradiol-17 beta concentrations nor progesterone concentrations differed (P > or = 0.05) among seasons. Of 15 females artificially inseminated, the only one that was inseminated in the non-breeding season became pregnant and delivered a single cub. This is the first successful pregnancy resulting from AI in this endangered species.

[Comparison of human chorionic gonadotropin (Pregnyl 10 000 IU i.m.) versus GnRH agonist (triptorelin 0,2 mg s.c.) for final oocytes maturation in the same egg donors--clinical and embryological characteristics].

PubMed

Streda, R; Mardesic, T; Sobotka, V; Koryntová, D; Hybnerová, L; Jindra, M; Paseková, V; Slámová, J; Stevíková, M; Voboril, J; Jelínková, L; Vilímová, S; Ichová, J; Mádrová, J; Tersová, H; Masata, M; Sobotková, J

2011-04-01

To compare clinical and embryological characteristics in donor cycles triggered for final oocytes maturation with Pregnyl 10 000 IU i.m. versus triptorelin 0.2 mg s.c. in the same patients in two sequential stimulation cycles. The aim of the study is to decrease the risk of the development of ovarian hyperstimulation syndrome (OHSS) at high response donors by the replacement of Pregnyl 10 000 IU i.m. vs. triptorelin 0.2 mg s.c. The administration of a single dose of gonadotropin-releasing hormone agonist (triptorelin 0.2 mg s.c.) induces release of LH from the pituitary gland similarly to a spontaneous LH surge. Prospective cross-over trial. Sanatorium Pronatal, Praha. From August 2009 to July 2010 we analysed 24 stimulation cycles in 12 egg donors treated with GnRH antagonist protocol with recombinant FSH (follitropin beta). We identified patients with more than 15 follicles during examination by transvaginal ultrasound. When at least 3 leading follicles reached 17 mm in diameter we administrated Pregnyl 10 000 IU i.m. for final oocytes maturation and triptorelin 0.2 mg s.c in the subsequent treatment cycle. The primary outcome measure was number of oocytes, proportion mature oocytes and fertilized oocytes. The secondary outcome were duration of FSH stimulation, total dose of gonadotropins and mean daily dose of gonadotropins. Data was analysed by paired t-test. We retrieved 17.2 +/- 8.6 vs. 15.8 +/- 5.3 (ns) oocytes, 12.6 +/- 7.3 vs. 13.0 +/- 5.4 (ns) metaphase II oocytes, proportion of metaphase II oocytes (%) was 73 vs. 83 (ns), number of fertilized oocytes 11.5 +/- 6.7 vs. 11.7 +/- 4.5 (ns), fertilization rate (%) 91 vs. 90 (ns) in Pregnyl's vs. triptorelin's group, resp. Duration of FSH stimulation (days) 12.2 +/- 0.8 vs. 12.4 +/- 0.7 (ns), total dose of gonadotropins (IU) 1744 +/- 277 vs. 1740 +/- 276 (ns), mean daily dose of gonadotropins (IU) 238 +/- 43 vs. 221 +/- 36 (ns), were not statistically different in both groups. Number of mature oocytes and subsequent embryonic cleavage is comparable to standard hCG treatment. There are no differences in clinical and embryological characteristics in both groups. Only one patient with administration of Pregnyl 10 000 IU i.m. was treated for OHSS grade II by vaginal paracentesis. Administration of triptorelin 0.2 mg s.c. is a safe and effective approach to achieve mature oocytes in egg donation programme, where we do not take care of implantation, which has got some limitations based on several studies.

False Negative Urine Pregnancy Testing with Complete Molar Pregnancy: An Example of the Hook Effect.

PubMed

Anderson, Zachary; Larson, Eric; Khan, Muhammad; Bell, Maria

2016-02-01

Gestational trophoblastic disease (GTD) encompasses a group of tumors derived from trophoblasts, which normally form the placenta during pregnancy. Human chorionic gonadotropin (hCG) is a glycoprotein composed of an alpha subunit identical to that of thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Detection of beta-hCG is achievable in both urine and serum samples, proving useful for the detection of normal pregnancy and GTD. However, in the presence of very high levels of beta-hCG, a false negative result may be obtained due to a phenomenon called the "hook effect" or "prozone phenomenon." In certain circumstances, trophoblastic tumors can produce very high levels of beta-hCG, causing misleading results on urine pregnancy testing. A 49-year-old Caucasian female with past medical history pertinent for deep vein thrombosis, ovarian cysts, and osteopenia presented to her internist with report of irregular uterine bleeding for the preceding three months, accompanied by complaints of abdominal bloating, night sweats, and constipation. The patient stated she had completed two negative qualitative urine pregnancy tests and had been seen by both gynecology and gastroenterology, with recommendations to start supplemental estrogen for her symptoms and begin additional fiber intake for irritable bowel syndrome, respectively. Despite negative urine beta-hCG, a quantitative serum beta-hCG was obtained and revealed a level greater than 200,000 international units (IU). The patient was referred to gynecologic oncology and an open abdominal hysterectomy with preservation of her ovaries was performed. Histopathologic examination showed a complete hydatiform mole with no evidence of invasion. The case highlights the importance of clinical judgment in modern medicine, where biochemical methods and imaging modalities have become main stays in diagnosis. As mentioned, there are ways to reduce the incidence of the hook effect, but with added time and cost. Clinicians need to consider the possibility of the hook effect for instances where the clinical picture points to a disease entity despite negative test results. Delaying diagnoses, as illustrated with GTD, has the potential to cause significant morbidity and mortality.

Evaluation of treatments with hCG and carprofen at embryo transfer in a demi-embryo and recipient virgin heifer model.

PubMed

Torres, A; Chagas E Silva, J; Diniz, P; Lopes-da-Costa, L

2013-08-01

An in vivo model, combining a low developmental competence embryo (demi-embryo) and a high-fertility recipient (virgin dairy heifer) was used to evaluate the effects of treatment with human chorionic gonadotropin (hCG) and carprofen at embryo transfer (ET) on plasma progesterone (P₄) concentrations of recipients and on embryonic growth and survival. Embryos were bisected and each demi-embryo was transferred to a recipient on Day 7 of the estrous cycle. At ET, heifers (n = 163) were randomly allocated to treatment with hCG (2500 IU im), carprofen (500 mg iv), hCG plus carprofen or to untreated controls. Plasma P₄ concentrations were measured on Days 0, 7, 14 and 21 of all recipients plus on Days 28, 42 and 63 of pregnant recipients. Pregnancy was presumed to be present in recipients with luteal plasma P4 concentrations until Day 21 and confirmed by using transrectal ultrasonography on Days 28, 42 and 63. Embryonic measurements (crown-rump length and width) were obtained on Day 42. Treatment with hCG induced formation of secondary corpora lutea (CL) in 97% of heifers and increased (P < 0.01) mean plasma P₄ concentrations of non-pregnant recipients on Day 14 and of pregnant heifers on Days 14 to 63. This was associated to a significant decrease in early embryonic mortality. In contrast, subsequent embryonic losses resulted in a non-significant numerical increase by 8% of pregnancies maintained to Day 63. Therefore, treatment with hCG significantly rescued embryos through the maternal recognition of pregnancy window but was not able to support development thereafter. Treatment with carprofen at ET had no significant effects on plasma P₄ concentrations and rate of embryo mortality. Treatment with hCG plus carprofen at ET induced formation of secondary CL in 90% of heifers but decreased the luteotrophic effect of hCG, resulting in no effect on embryo survival. Low developmental competence embryos showed an intrinsic deficiency in overcoming the maternal recognition of pregnancy challenge and in proceeding to further development until Day 28 of pregnancy, whereas mortality beyond this point was residual. Results on pregnancy rates should be confirmed in further experiments involving a larger sample size.

Second Trimester Maternal Serum Screening for Fetal Down Syndrome: as a Screening Test for Hemoglobin Bart's Disease: A Prospective Population-based Study.

PubMed

Wanapirak, Chanane; Piyamomgkol, Wirawit; Sirichotiyakul, Supatra; Tongprasert, Fuanglada; Srisupundit, Kasemsri; Luewan, Suchaya; Traisrisilp, Kuntharee; Jatavan, Phudit; Tongsong, Theera

2018-06-21

To determine the effectiveness of second-trimester maternal serum screening (MSS) for Down syndrome as a screening test for fetal hemoglobin (Hb) Bart's disease among an unselected population. A secondary analysis of a large prospective database (20,254 pregnancies) was conducted to compare the levels of MSS, alpha-fetoprotein (AFP), free beta-human chorionic gonadotropin (hCG) and unconjugated estriol (uE3) between pregnancies with Hb Bart's disease and unaffected pregnancies. The median AFP levels were much higher among affected fetuses, (1.96 vs. 1.12 multiple of the median (MoM); p<0.001), yielding a sensitivity of 81.6% and specificity of 86.4%. Thus, AFP measurement is effective in predicting fetal Hb Bart's disease among an unselected population when using a cut-off value of 1.5 MoM. The serum free b-hCG levels were slightly, but significantly, higher in the affected pregnancies, while the serum uE3 levels were minimally, but significantly, lower among the affected pregnancies. Second trimester maternal serum AFP levels were significantly elevated in cases of fetal Hb Bart's disease. Pregnancies with unexplained elevated serum AFP levels in areas of high prevalence of Hb Bart's disease should always undergo a detailed ultrasound examination to detect any early signs of fetal anemia before development of hydrops fetalis. This article is protected by copyright. All rights reserved.

hCG-induced endoplasmic reticulum stress triggers apoptosis and reduces steroidogenic enzyme expression through activating transcription factor 6 in Leydig cells of the testis

PubMed Central

Park, Sun-Ji; Kim, Tae-Shin; Park, Choon-Keun; Lee, Sang-Hee; Kim, Jin-Man; Lee, Kyu-Sun; Lee, In-kyu; Park, Jeen-Woo; Lawson, Mark A; Lee, Dong-Seok

2014-01-01

Endoplasmic reticulum (ER) stress generally occurs in secretory cell types. It has been reported that Leydig cells, which produce testosterone in response to human chorionic gonadotropin (hCG), express key steroidogenic enzymes for the regulation of testosterone synthesis. In this study, we analyzed whether hCG induces ER stress via three unfolded protein response (UPR) pathways in mouse Leydig tumor (mLTC-1) cells and the testis. Treatment with hCG induced ER stress in mLTC-1 cells via the ATF6, IRE1a/XBP1, and eIF2α/GADD34/ATF4 UPR pathways, and transient expression of 50 kDa protein activating transcription factor 6 (p50ATF6) reduced the expression level of steroidogenic 3β-hydroxy-steroid dehydrogenase Δ5-Δ4-isomerase (3β-HSD) enzyme. In an in vivo model, high-level hCG treatment induced expression of p50ATF6 while that of steroidogenic enzymes, especially 3β-HSD, 17α-hydroxylase/C17–20 lyase (CYP17), and 17β-hydrozysteroid dehydrogenase (17β-HSD), was reduced. Expression levels of steroidogenic enzymes were restored by the ER stress inhibitor tauroursodeoxycholic acid (TUDCA). Furthermore, lentivirus-mediated transient expression of p50ATF6 reduced the expression level of 3β-HSD in the testis. Protein expression levels of phospho-JNK, CHOP, and cleaved caspases-12 and -3 as markers of ER stress-mediated apoptosis markedly increased in response to high-level hCG treatment in mLTC-1 cells and the testis. Based on transmission electron microscopy and H&E staining of the testis, it was shown that abnormal ER morphology and destruction of testicular histology induced by high-level hCG treatment were reversed by the addition of TUDCA. These findings suggest that hCG-induced ER stress plays important roles in steroidogenic enzyme expression via modulation of the ATF6 pathway as well as ER stress-mediated apoptosis in Leydig cells. PMID:23256993

Alteration of the lipid composition of rat testicular plasma membranes by dietary (n-3) fatty acids changes the responsiveness of Leydig cells and testosterone synthesis.

PubMed

Sebokova, E; Garg, M L; Wierzbicki, A; Thomson, A B; Clandinin, M T

1990-06-01

Experiments were conducted to assess whether changing dietary fat composition altered phospholipid composition of rat testicular plasma membranes in a manner that altered receptor-mediated action of luteinizing hormone (LH)/human chorionic gonadotropin (hCG). Weanling rats were fed diets that provided high or low cholesterol intakes and that were enriched with linseed oil, fish oil or beef tallow for 4 wk. Feeding diets high in (n-3) fatty acids decreased plasma and testicular plasma membrane 20:4(n-6) content. A marked reduction of the 22:5(n-6) content and an increase in the 22:6(n-3) content of testicular plasma membrane was found only in animals fed fish oil. A decrease in binding capacity of the gonadotropin (LH/hCG) receptor in the plasma membrane, with no change in receptor affinity, was observed for animals fed either linseed oil or fish oil diets. Dietary treatments that raised plasma membrane cholesterol content and the cholesterol to phospholipid ratio in the membrane were associated with increased binding capacity of the gonadotropin receptor. Feeding diets high in 18:3(n-3) vs. those high in fish oil altered receptor-mediated adenylate cyclase activity in a manner that depended on the level of dietary cholesterol. Feeding diets high in cholesterol or fish oil increased basal and LH-stimulated testosterone synthesis relative to that in animals fed the low cholesterol diet containing linseed oil. It is concluded that changing the fat composition of the diet alters the phospholipid composition of rat testicular plasma membranes and that this change in composition influences membrane-mediated unmasking of gonadotropin receptor-mediated action in testicular tissue.

Regulation of Iodide Uptake in Placental Primary Cultures

PubMed Central

Burns, R.; O'Herlihy, C.; Smyth, P.P.A.

2013-01-01

Background Maintenance of adequate iodide supply to the developing fetus is dependent not only on maternal dietary iodine intake but also on placental iodide transport. The objective of this study was to examine the effects of different pregnancy-associated hormones on the uptake of radioiodide by the placenta and to determine if iodide transporter expression is affected by hormone incubation. Methods Primary cultures of placental trophoblast cells were established from placentas obtained at term from pre-labor caesarean sections. They were pre-incubated with 17β-estradiol, prolactin, oxytocin, human chorionic gonadotropin (hCG) and progesterone either singly or in combination over 12 h with 125I uptake being measured after 6 h. RNA was isolated from placental trophoblasts and real-time RT-PCR performed using sodium iodide symporter (NIS) and pendrin (PDS) probes. Results Significant dose response increments in 125I uptake by trophoblast cells (p < 0.01) were observed following incubation with hCG (60% increase), oxytocin (45% increase) and prolactin (32% increase). Although progesterone (50-200 ng/ml) and 17β-estradiol (1,000-15,000 pg/ml) alone produced no significant differences in uptake, they facilitated increased uptake when combined with prolactin or oxytocin, with a combination of all four hormones producing the greatest increase (82%). Increased 125I uptake was accompanied by corresponding increments in NIS mRNA (ratio 1.52) compared to untreated control cells. No significantly increased expression levels of PDS were observed. Conclusions Pregnancy-associated hormones, particularly oxytocin and hCG, have a role in promoting placental iodide uptake which may protect the fetus against iodine deficiency. PMID:24783055

Regulation of the angiopoietin-2 gene by hCG in ovarian cancer cell line OVCAR-3.

PubMed

Pietrowski, D; Wiehle, P; Sator, M; Just, A; Keck, C

2010-05-01

Angiogenesis is a crucial step in growing tissues including many tumors. It is regulated by pro- and antiangiogenic factors including the family of angiopoietins and their corresponding receptors. In previous work we have shown that in human ovarian cells the expression of angiopoietin 2 (ANG2) is regulated by human chorionic gonadotropin (hCG). To better understand the mechanisms of hCG-dependent regulation of the ANG2-gene we have now investigated upstream regulatory active elements of the ANG2-promoter in the ovarian carcinoma cell line OVCAR-3. We cloned several ANG2-promoter-fragments of different lengths into a luciferase reporter-gene-vector and analyzed the corresponding ANG2 expression before and after hCG stimulation. We identified regions of the ANG2-promoter between 1 048 bp and 613 bp upstream of the transcriptional start site where hCG-dependent pathways promote a significant downregulation of gene expression. By sequence analysis of this area we found several potential binding sites for transcription factors that are involved in regulation of ANG2-expression, vascular development and ovarian function. These encompass the forkhead family transcription factors FOXC2 and FOXO1 as well as the CCAAT/enhancer binding protein family (C/EBP). In conclusion, we have demonstrated that the regulation of ANG2-expression in ovarian cancer cells is hCG-dependent and we suggest that forkhead transcription factor and C/EBP-dependent pathways are involved in the regulation of ANG2-expression in ovarian cancer cells. Georg Thieme Verlag KG Stuttgart-New York.

Restoration and maintenance of spermatogenesis by HCG therapy in patients with hypothalamo-hypophyseal damage.

PubMed

Levalle, O; Bokser, L; Pacenza, N; Aszenmil, G; Fiszlejder, L; Chervin, A; Guitelman, A

1984-01-01

Both gonadotropins are necessary to induce spermatogenesis in man and to recover hypophysectomized males. The patients who suffer from tumoral or traumatic hypothalamo-hypophyseal lesion use to have low endogenous gonadotropins (opposite to hypophysectomized patients), which can produce a minor involution of spermatogenesis. Three patients with postpubertal hypogonadotropic hypogonadism and oligozoospermia were studied. Two of them were operated on for chromophobous adenoma of pituitary, and the other patient had traumatic hypothalamo-hypophyseal lesion. The three patients were treated with 5000 IU HCG/week, associated with testosterone enanthate, in two cases and with bromocryptine in the remaining one. All the patients had normalized spermiogram, but when HCG was interrupted, the sperm count regressed to pretreatment levels in spite of the maintenance of treatment with testosterone or bromocryptine. Minimal amounts of FSH together the testosterone supplied by Leydig cell under the HCG stimulus, are able to recover and maintain the spermatogenesis in these patients.

Associations between maternal serum free beta human chorionic gonadotropin (β-hCG) levels and adverse pregnancy outcomes.

PubMed

Sirikunalai, P; Wanapirak, C; Sirichotiyakul, S; Tongprasert, F; Srisupundit, K; Luewan, S; Traisrisilp, K; Tongsong, T

2016-01-01

The objective was to determine the strength of relationship between maternal free beta human chorionic gonadotropin (β-hCG) concentrations and rates of adverse pregnancy outcomes. Consecutive records of the database of our Down screening project were assessed for free β-hCG levels and pregnancy outcomes. Pregnancies with foetal chromosomal or structural anomalies and those with underlying disease were excluded. Free β-hCG levels of < 0.5, > 0.5 and < 2.0, and ≥ 2.0 MoM were categorised as low, normal and high, respectively. Of 17,082 screened women, 13,620 were available for analysis. In the first trimester (n = 8150), low β-hCG levels significantly increased risk for intrauterine growth restriction (IUGR), preterm birth, low birth weight (LBW) and low Apgar score with relative risk of 1.66, 1.43, 1.83 and 2.89; whereas high β-hCG group had a significant decreased risk of preterm birth and GDM with relative risk of 0.73 and 0.62. In the second trimester (n = 5470), both low and high β-hCG groups had significant increased risks of the most common adverse outcomes, i.e. spontaneous abortion, IUGR and preterm birth. In conclusion, abnormally low (< 0.5MoM) or high (> 2.0 MoM) free β-hCG levels are generally associated with an increased risk of adverse pregnancy outcomes. Nevertheless, high free β-hCG levels in the first trimester may possibly decrease risk of preterm delivery and GDM.

hCG Test (Pregnancy Test)

MedlinePlus

... Time and International Normalized Ratio (PT/INR) PSEN1 Quantitative Immunoglobulins Red Blood Cell (RBC) Antibody Identification Red ... Us Also Known As Pregnancy Test Qualitative hCG Quantitative hCG Beta hCG Total hCG Total beta hCG ...

[Clinical observation on effect of Chinese herbal medicine plus human chorionic gonadotropin and progesterone in treating anticardiolipin antibody-positive early recurrent spontaneous abortion].

PubMed

Shu, Jing; Miao, Pin; Wang, Ruo-jie

2002-06-01

To find a method without corticosteroids, aspirin or heparin for treatment of anticardiolipin antibody-positive early recurrent spontaneous abortion (AARSA). Twenty-three patients of AARSA in the treated group were treated with Chinese herbal medicine (CHM) plus human chorionic gonadotropin and progesterone, and 18 patiens in the control group were treated with multi-vitamin only. The change of anticardiolipin antibody was determined by enzyme linked immunoabsorbent assay (ELISA). After treatment, anticardiolipin antibody negative converted in 20 cases (86.9%) of the treated group. The cure rate of abortion in the treated group was 82.6% (19/23), which was raised to 95% (19/20) in those patients with antibody negative conversion, while in the control group, it was 16.7% (3/18) merely, comparison between the two groups in cure rate showed significant difference (P < 0.01). CHM plus human chorionic gonadotropin and progesterone could cure AARSA effectively.

A model system for the evaluation of radioimmunoimaging of tumors

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

Koizumi, M.; Endo, K.; Sakahara, H.

1985-05-01

The authors have developed a simple model system that can be used to evaluate methods of radioimmunoimaging of tumors, using human chorionic gonadropin (hCG) as a model antigen, and a monoclonal antibody against hCG ..beta..-subunit as a model antibody. HCG was coated on a polystylene spherical bead with a quarter inch in diameter, and coated beads were washed extensively with phosphate buffered saline, and glycine acid buffer to remove the easily dissociable antigen. HCG-coated beads were put into the subcutaneous tissue on the back of mice. At 24 hr after the transplantation, when serum hCG was not detectable by themore » conventional RIA, radiolabeled antibodies were injected and its bio-distribution monitored. The %ID/g for the hCG coated beads increased to a maximum of 48 hr after the injection of radioiodinad antibody, whereas the %ID/g for most organs decreased with time. As a nonspecific antigen, beads coated with bovine serum albumin were transplanted and its uptake was as low as about one 50th of hCG-coated ones. The %ID/g of radioiodinated monoclonal antibody against human thyroglobulin (a nonspecific antibody) for hCG-coated beads was also negligible. Thus, the localization index (%ID of specific antibody / %ID of nonspecific antibody) reached to 15.0 at 24 hr, 35.5 at 48 hr and 57.8 at 96 hr after the injection. The biodistribution of In-111 labeled specific monoclonal antibody, prepared through the chelation with DTPA, demonstrated similar results with radioiodinated ones. This mouse model system that did not involve the use of tumors, yielded high localization index and reproducibilities and could be used to evaluate different methods for radiolabelng monoclonal antibodies.« less

Immunomodulation of the mother during pregnancy.

PubMed

Hegde, U C

1991-06-01

The concept that the immune responsiveness of the mother is reduced during pregnancy arose from studies which appeared to show that immune response to certain antigens is reduced during pregnancy (1, 2). Various substances claimed to have immunosuppressive or immunomodulating effect include alpha fetoprotein, placental proteins, early pregnancy factor (EPF), human chorionic gonadotropin (HCG), corticosteroids, estrogens, androgens and progesterone (2). To summarise a body of literature, there is very little change in the immune competence of the mother during pregnancy. This makes sense, as generalized immunosuppression would be a risky way to ensure the survival of the fetus. Immune enhancement and subsequent immunomodulation of the mother is likely to be the mechanism operative during pregnancy. It is conceivable that the overall immune response in pregnancy could be the net result of an interplay of various interactions that may be operating to ensure non-rejection of the antigenically alien fetus while at the same time preventing a state of excessive immunosuppression. Such a dynamic homeostatic mechanism appears to be important for the successful completion of pregnancy.

Hyperthyroidism as a clinical manifestation of a embryonal carcinoma of the testis.

PubMed

Arrabal-Polo, M A; Jimenez-Pacheco, A; Arrabal-Martin, M; Moreno-Jimenez, J; Gutierrez-Tejero, F; Galisteo-Moya, R; Zuluaga-Gomez, A

2012-01-01

This case report describes a case of hyperthyroidism as manifestation of an embryonal carcinoma, and illustrates the causes that led to it. The case describes a 33-year-old male patient who complained of chest pain, palpitations, mild dyspnoea, and weight loss. Blood analysis reveals high levels of human chorionic gonadotropin (833818 mlU/ml), T3 (16.90 pg/ml), and T4 (7.77 ng/dl), as well as a fall of TSH (0.01 ulU/ml). Physical examination and imaging procedures confirm the occurrence of a left testicular tumour associated with numerous lung, hepatic and retroperitoneal metastases. Treatment with carbimazol and propanolol is established to manage hyperthyroidism, and an urgent orchiectomy is performed; the histologic diagnosis confirms an embryonal carcinoma (organoid type), but the patient died unexpectedly 24 hours later after having suffered sudden dyspnoea, tachypnoea, and tachyarrhythmia. Hyperthyroidism is a rare manifestation of a testicular tumour that should be borne in mind with regard to the patient's symptomatology and HCG levels.

Enhancement of lateral flow assay performance by electromagnetic relocation of reporter particles

PubMed Central

Jacinto, Maria João; Trabuco, João R. C.; Vu, Binh V.; Garvey, Gavin; Khodadady, Mohammad; Azevedo, Ana M.; Aires-Barros, Maria Raquel; Chang, Long; Kourentzi, Katerina; Litvinov, Dmitri

2018-01-01

Lateral flow assays (LFAs) are a widely-used point-of care diagnostic format, but suffer from limited analytical sensitivity, especially when read by eye. It has recently been reported that LFA performance can be improved by using magnetic reporter particles and an external magnetic field applied at the test line. The mechanism of sensitivity/performance enhancement was suggested to be concentration/retardation of reporter particles at the test line. Here we demonstrate an additional mechanism of particle relocation where reporter particles from the lower depths of the translucent LFA strip relocate to more-visible locations nearer to the top surface, producing a more visible signal. With a magnetic field we observed an improvement in sensitivity of human chorionic gonadotropin (hCG) detection from 1.25 ng/mL to 0.31 ng/mL. We also observed an increase of the color intensity per particle in test lines when the magnetic field was present. PMID:29309424

Solid-phase receptor binding assay for /sup 125/I-hCG

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

Bortolussi, M.; Selmin, O.; Colombatti, A.

1987-01-01

A solid-phase radioligand-receptor assay (RRA) to measure the binding of /sup 125/I-labelled human chorionic gonadotropin (/sup 125/I-hCG) to target cell membranes has been developed. The binding of /sup 125/I-hCG to membranes immobilized on the wells of microtitration plates reached a maximum at about 3 hours at 37 degrees C, was saturable, displayed a high affinity (Ka = 2.4 X 10(9) M-1) and was specifically inhibited by unlabelled hCG. In comparison with RRAs carried out with membranes in suspension, the solid-phase RRA is significantly simpler and much faster to perform as it avoids centrifugation or filtration procedures. The solid-phase RRA wasmore » adapted profitably to process large numbers of samples at the same time. It proved particularly useful as a screening assay to detect anti-hCG monoclonal antibodies with high inhibitory activity for binding of /sup 125/I-hCG to its receptors.« less

White blood cell counts and neutrophil to lymphocyte ratio in the diagnosis of testicular cancer: a simple secondary serum tumor marker.

PubMed

Yuksel, Ozgur Haki; Verit, Ayhan; Sahin, Aytac; Urkmez, Ahmet; Uruc, Fatih

2016-01-01

The aim of the study was to investigate white blood cell counts and neutrophil to lymphocyte ratio (NLR) as markers of systemic inflammation in the diagnosis of localized testicular cancer as a malignancy with initially low volume. Thirty-six patients with localized testicular cancer with a mean age of 34.22±14.89 years and 36 healthy controls with a mean age of 26.67±2.89 years were enrolled in the study. White blood cell counts and NLR were calculated from complete blood cell counts. White blood cell counts and NLR were statistically significantly higher in patients with testicular cancer compared with the control group (p<0.0001 for all). Both white blood cell counts and NLR can be used as a simple test in the diagnosis of testicular cancer besides the well-known accurate serum tumor markers as AFP (alpha fetoprotein), hCG (human chorionic gonadotropin) and LDH (lactate dehydrogenase).

Effects of progesterone and its metabolites on human granulosa cells.

PubMed

Pietrowski, D; Gong, Y; Mairhofer, M; Gessele, R; Sator, M

2014-02-01

The corpus luteum (CL) is under control of gonadotrophic hormones and produces progesterone, which is necessary for endometrial receptivity. Recent studies have shown that progesterone and its metabolites are involved in cell proliferation and apoptosis of cancer cells. Here weanalyzed the role of progesterone and its meta-bolites on luteinized granulosa cells (LGC) by FACS analysis and quantitative Real-Time PCR. We detected the mRNA of the progesterone metabolizing genes SRD5A1, AKR1C1, and AKR1C2 in LGC. The stimulation of LGC with progesterone or progesterone metabolites did not show any effect on the mRNA expression of these genes. However, a downregulation of Fas expression was found to be accomplished by progesterone and human chorionic gonadotropin. Our findings do not support the concept of an effect of progesterone metabolites on LGCs. However, it suggests an antiapoptotic effect of hCG and progesterone during corpus luteum development by downregulation of Fas. © Georg Thieme Verlag KG Stuttgart · New York.

Artificial reproduction of wild and cultured barbel (Barbus barbus, Cyprinidae) under controlled conditions.

PubMed

Targońska, Katarzyna; Kucharczyk, Dariusz; Zarski, Daniel; Cejko, Beata Irena; Krejszeff, Sławomir; Kupren, Krzysztof; Król, Radosław; Dryl, Katarzyna; Kowalski, Radosław Kajetan; Glogowski, Jan

2011-09-01

The aim of this work was to compare the effects of controlled reproduction of cultured and wild common barbel, Barbus barbus (L.). Preparations containing different GnRH analogues and dopamine receptor antagonists (Ovopel, Ovaprim) as well as human chorionic gonadotropin (hCG) (in the case of cultured fish) were applied and their influence on ovulation, spermiation and quality of gametes obtained was determined. No differences in the qualitative or quantitative parameters of semen were found between fish stimulated with different hormonal preparations and those not receiving hormonal stimulation. The high suitability of Ovaprim for ovulation induction in (cultured and wild) barbel was confirmed. The highest synchronisation of ovulation was obtained after the application of Ovopel (18 ± 3 h), but the best results of controlled reproduction (expressed as the percentage of ovulations and survival of embryos) were obtained by applying Ovaprim (83.2 ± 4.1). A significantly higher percentage of ovulation was obtained in cultured fish (80-90%) than in wild fish (< 25%).

[The treatment of hypogonadism and maintenance of fertility in men].

PubMed

Rabijewski, Michał

2016-03-01

In past few years we observed the increasing of population of men, who are treated with testosterone due to hypogonadism associated with aging but the most of them have no indications to testosterone replacement therapy. The classical symptoms of hypogonadism including depression, loss of libido, erectile dysfunction, and fatigue may be related to any others diseases. The increase in prevalence of androgenic anabolic steroids specifically among younger athletes is also observed. Exogenous testosterone and anabolic androgenic steroids can inhibit the hypothalamic-pituitary-gonadal axis leading to decreasing of endogenous testosterone synthesis and impaired spermatogenesis. In hypogonadal men who are in reproduction age the goal of therapy should be not only replacement therapy but also achiving and/or maintaining of spermatogenesis. Human chorionic gonadotropin (hCG) and selective estrogens receptor modulators (SERM) are efficacy in treatment of clinical signs and symptoms of hypoigonadism, has been shown to reverse spermatogenesis disturbances and can to maintain elevated intratesticular testosterone levels necessary to optimal spermatogenesis. © 2016 MEDPRESS.

In utero virilization secondary to a maternal Krukenberg tumor: case report and review of literature.

PubMed

Bustamante, Carmen; Hoyos-Martínez, Alfonso; Pirela, Daniela; Díaz, Alejandro

2017-07-26

Krukenberg tumors are ovarian metastatic adenocarcinomas with a primary origin usually located in the stomach, colon, gallbladder, pancreas, or breast. Occasionally, these tumors produce virilization in the affected individual due to androgen production by luteinization of the tumoral stroma. It is believed that during pregnancy these tumors are more likely to increase androgen production due to the elevated levels of human chorionic gonadotropin (hCG). High maternal androgens can cross the placenta producing virilization of the female fetus. A 46,XX newborn female, whose mother was diagnosed with a metastatic ovarian tumor during her second trimester of gestation associated with worsening hirsutism and acne, was found to have ambiguous genitalia at birth. Testosterone levels in both the mother and infant were elevated. Follow-up laboratory tests showed progressive normalization of circulating androgens after delivery. Krukenberg tumors are rare and may produce virilization of the mother and the female fetus when present during pregnancy.

De Novo-Synthesized Retinoic Acid in Ovarian Antral Follicles Enhances FSH-Mediated Ovarian Follicular Cell Differentiation and Female Fertility

PubMed Central

Kawai, Tomoko; Yanaka, Noriyuki; Richards, JoAnne S.

2016-01-01

Retinoic acid (RA) is the active form of vitamin A and is synthesized from retinol by two key enzymes, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH). As the physiological precursor of RA, retinol impacts female reproductive functions and fertility. The expression of Adh1 and Adh5 as well as Aldh1a1 and Aldh1a7 are significantly increased in the ovaries of mice treated with equine chorionic gonadotropin/FSH. The RA receptor is expressed and localized in granulosa cells and is activated by endogenous RA as indicated by LacZ expression in granulosa cells of RA-responsive transgene-LacZ transgenic mice (RA reporter mice). Coinjection of the ADH inhibitor, 4-methylpyrazole, with equine chorionic gonadotropin significantly decreases the number and developmental competence of oocytes ovulated in response to human chorionic gonadotropin/LH as compared with controls. Injections of RA completely reverse the effects of the inhibitor of ovulation and oocyte development. When mice were fed a retinol-free, vitamin A-deficient diet that significantly reduced the serum levels of retinol, the expression of the LH receptor (Lhcgr) was significantly lower in the ovaries of the vitamin A-deficient mice, and injections of human chorionic gonadotropin failed to induce genes controlling ovulation. These results indicate that ovarian de novo biosynthesis of RA is required for the follicular expression of Lhcgr in granulosa cells and their ability to respond to the ovulatory LH surge. PMID:27022678

Epiregulin-dependent amphiregulin expression and ERBB2 signaling are involved in luteinizing hormone-induced paracrine signaling pathways in mouse ovary.

PubMed

Kim, Kyoungmi; Lee, Hyunji; Threadgill, David W; Lee, Daekee

2011-02-11

Sustained EGF receptor (EGFR) phosphorylation by de novo synthesis of EGFR ligands plays an essential role in mediating luteinizing hormone (LH)-induced ovulation process in the preovulatory follicles (POFs). In the present study, the effect of epiregulin (EREG) on oocyte maturation and ovulation was investigated using Ereg knockout (Ereg-/-) mice congenic on a C57BL/6 background. Rate of spontaneous oocyte meiotic resumption of denuded oocytes (DOs) or cumulus cell-oocyte complexes (COCs) in vitro is similar between wild-type and Ereg-/- mice. However, gonadotropin-induced meiotic resumption in vivo is attenuated, and the number of COCs with expanded cumulus matrix and superovulated eggs dramatically decrease in Ereg-/- mice. Nonetheless, the number of eggs ovulated during normal estrus cycles and litter sizes in Ereg-/- mice are comparable to those of wild-type littermates. In contrast to other EGFR ligands, induction of amphiregulin (Areg) mRNA is severely reduced in ovaries collected from Ereg-/- mice either after human chorionic gonadotropin (hCG) treatment in immature mice or LH surge in adults. Gonadotropin-induced EGFR and ERBB2 phosphorylation in ovaries is attenuated in immature Ereg-/- mice, and MAPK3/1 phosphorylation and prostaglandin synthase 2 (PTGS2) protein levels are reduced. This attenuation, however, is no longer detectable in adult Ereg-/- mice after LH surge. This study implicates that EREG mediates signals downstream of Areg mRNA expression and that EGFR-ERBB2 signals contributes to regulation of ovulation process. Copyright © 2011 Elsevier Inc. All rights reserved.

Transient expression of progesterone receptor and cathepsin-l in human granulosa cells during the periovulatory period.

PubMed

García, Víctor; Kohen, Paulina; Maldonado, Carola; Sierralta, Walter; Muñoz, Alex; Villarroel, Claudio; Strauss, Jerome F; Devoto, Luigi

2012-03-01

To study in vivo the progesterone receptor (PR) expression levels in human granulosa cells (GCs) during the periovulatory period and the affect of the protein kinase A (PKA) pathway on PR expression and cathepsin-L expression-activation. Experimental study. University research unit. Twenty-five women of reproductive age. Follicular fluid and GCs obtained from spontaneous cycles before and during the normal luteinizing hormone surge, and samples obtained 36 hours after human chorionic gonadotropin (hCG) administration in patients undergoing in vitro fertilization. To determine PR, cathepsin-L messenger RNA (mRNA) analysis via real-time polymerase chain reaction, and protein of PR, cathepsin-L, and PKA in human GCs. The Western blot analysis revealed that bands of PR (isoform A) were the most abundant and that mRNA (PR-A and PR-B) have a temporal pattern of expression throughout the periovulatory period. The protein levels of PR and cathepsin-L were up-regulated by hCG. The abundance of PR was diminished in the presence of PKA inhibitor, and cathepsin-L with PR receptor antagonist. The transient expression of PR in human GCs of the preovulatory follicle suggests that PR and its ligand play a role in the activation of cathepsin-L, which is presumably involved in the degradation of the follicular extracellular matrix during human ovulation. Copyright © 2012 American Society for Reproductive Medicine. All rights reserved.

Effect of Increased Endometrial Thickness and Implantation Rate by Granulocyte Colony-Stimulating Factor on Unresponsive Thin Endometrium in Fresh In Vitro Fertilization Cycles: A Randomized Clinical Trial

PubMed Central

Sarvi, Fatemeh; Arabahmadi, Marjan; Alleyassin, Ashraf; Aghahosseini, Marzieh

2017-01-01

Background The correlation between endometrial thickness and receptivity has been mentioned in various studies. This study investigated the effect of granulocyte colony-stimulating factor in treating thin endometrium of infertile women who were chosen for in vitro fertilization in our infertility clinic in 2014 and 2015. Methods In this randomized clinical trial, 28 women who were chosen for in vitro fertilization and had endometrial thickness of less than 6 mm on the day of human chorionic gonadotropin (hCG) injection were included in the study. They were randomly divided into two groups: investigation and control groups. In investigation group (n = 13) one granulocyte colony-stimulating factor vial (300 micrograms in 1 mL) was infused into the uterus within five minutes by embryo transfer catheter. In control group (n = 15) 1 mL of saline was injected into the uterus with the same catheter. Results There were significant differences between the two groups in terms of means of endometrial thickness on oocyte retrieval day (P = 0.001), embryo transfer day (P = 0.001), hCG injections (P = 0.001), and implantation rates (P = 0.001). Conclusion Granulocyte colony-stimulating factor can increase endometrial thickness in women treated with in vitro fertilization. RCT Code is 201406046063N2. PMID:28791050

Clinical characteristics of mirror syndrome: a comparison of 10 cases of mirror syndrome with non-mirror syndrome fetal hydrops cases.

PubMed

Hirata, Go; Aoki, Shigeru; Sakamaki, Kentaro; Takahashi, Tsuneo; Hirahara, Fumiki; Ishikawa, Hiroshi

2016-01-01

To investigate clinical features of mirror syndrome. We retrospectively reviewed 71 cases of fetal hydrops with or without mirror syndrome, and compared with respect to maternal age, the body mass index, the primipara rate, the gestational age at delivery, the timing of fetal hydrops onset, the severity of fetal edema, placental swelling, the laboratory data and the fetal mortality. The data are expressed as the medians. Mirror syndrome developed in 29% (10/35) of the cases with fetal hydrops. In mirror group, the onset time of fetal hydrops was significantly earlier (29 weeks versus 31 weeks, p = 0.011), and the severity of fetal hydrops (fetal edema/biparietal diameter) was significantly higher than non-mirror group (0.23 versus 0.16, p < 0.001). There was significantly higher serum human chorionic gonadotropin (hCG) (453,000 IU/L versus 80,000 IU/L, p < 0.001) and lower hemoglobin (8.9 g/dL versus 10.1 g/dL, p =0.002), hypoalbuminemia (2.3 mg/dL versus 2.7 mg/dL, p = 0.007), hyperuricemia (6.4 mg/dL versus 5.0 mg/dL, p = 0.043) in mirror group. Mirror syndrome is occurred frequently in early and severe fetal hydrops and cause hemodilution and elevation of serum hCG.

Effects of vitamin C, vitamin E, and molecular hydrogen on the placental function in trophoblast cells.

PubMed

Guan, Zhong; Li, Huai-Fang; Guo, Li-Li; Yang, Xiang

2015-08-01

This study aimed to investigate the effects of three different antioxidants, namely vitamin C, vitamin E, and molecular hydrogen, on cytotrophoblasts in vitro. Two trophoblast cell lines, JAR and JEG-3, were exposed to different concentrations of vitamin C (0, 25, 50, 100, 500, 1,000, 5,000 μmol/L), vitamin E (0, 25, 50, 100, 500, 1,000, 5,000 μmol/L), and molecular hydrogen (0, 25, 50, 100, 500 μmol/L) for 48 h. The cell viability was detected using the MTS assay. The secretion of human chorionic gonadotropin (hCG) and the tumor necrosis factor-α (TNF-α) were assessed and the expression of TNF-α mRNA was observed by real-time RT-PCR. Cell viability was significantly suppressed by 500 μmol/L vitamins C and E (P < 0.05), but not by 500 μmol/L molecular hydrogen (P > 0.05). The expression of TNF-α was increased by 100 μmol/L vitamin C and 50 μmol/L vitamins E, separately or combined (P < 0.05), but not by molecular hydrogen (0-500 μmol/L), as validated by real-time RT-PCR. But the secretion of hCG was both inhibited by 50-500 μmol/L molecular hydrogen and high levels of vitamin C and E, separately or combined. High levels of antioxidant vitamins C and E may have significant detrimental effects on placental function, as reflected by decreased cell viability and secretion of hCG; and placental immunity, as reflected by increased production of TNF-a. Meanwhile hydrogen showed no such effects on cell proliferation and TNF-α expression, but it could affect the level of hCG, indicating hydrogen as a potential candidate of antioxidant in the management of preeclampsia (PE) should be further studied.

Knockdown of Progesterone Receptor (PGR) in Macaque Granulosa Cells Disrupts Ovulation and Progesterone Production.

PubMed

Bishop, Cecily V; Hennebold, Jon D; Kahl, Christoph A; Stouffer, Richard L

2016-05-01

Adenoviral vectors (vectors) expressing short-hairpin RNAs complementary to macaque nuclear progesterone (P) receptor PGR mRNA (shPGR) or a nontargeting scrambled control (shScram) were used to determine the role PGR plays in ovulation/luteinization in rhesus monkeys. Nonluteinized granulosa cells collected from monkeys (n = 4) undergoing controlled ovarian stimulation protocols were exposed to either shPGR, shScram, or no virus for 24 h; human chorionic gonadotropin (hCG) was then added to half of the wells to induce luteinization (luteinized granulosa cells [LGCs]; n = 4-6 wells/treatment/monkey). Cells/media were collected 48, 72, and 120 h postvector for evaluation of PGR mRNA and P levels. Addition of hCG increased (P < 0.05) PGR mRNA and medium P levels in controls. However, a time-dependent decline (P < 0.05) in PGR mRNA and P occurred in shPGR vector groups. Injection of shPGR, but not shScram, vector into the preovulatory follicle 20 h before hCG administration during controlled ovulation protocols prevented follicle rupture in five of six monkeys as determined by laparoscopic evaluation, with a trapped oocyte confirmed in three of four follicles of excised ovaries. Injection of shPGR also prevented the rise in serum P levels following the hCG bolus compared to shScram (P < 0.05). Nuclear PGR immunostaining was undetectable in granulosa cells from shPGR-injected follicles, compared to intense staining in shScram controls. Thus, the nuclear PGR appears to mediate P action in the dominant follicle promoting ovulation in primates. In vitro and in vivo effects of PGR knockdown in LGCs also support the hypothesis that P enhances its own synthesis in the primate corpus luteum by promoting luteinization. © 2016 by the Society for the Study of Reproduction, Inc.

[Effect of chorionic gonadotropin on thymocyte differentiation in the presence of thymus epithelial cells].

PubMed

Kuklina, E M; Shirshev, S V; Sharova, N I; Iarilin, A A

2003-01-01

We studied the effects of the main placental hormone, chorionic gonadotropin, on differentiation of human thymocytes in vitro in the presence of thymic epithelial cells. It was shown that the hormone at a high dose (100 IU/ml) enhanced the epithelium-induced phenotypic maturation of thymocytes, which is registered by an increased expression of the membrane marker CD3 and transition of CD4+8+ thymocytes in the cells with CD4+8- and CD4-8+ phenotypes. In addition, gonadotropin enhanced the proliferative response of thymocytes to the mitogen during their cultivation with the epithelium. The stimulating effect of the hormone on the epithelium-induced differentiation of thymocytes is mediated by the humoral factors of epithelial cells. In addition, gonadotropin at this dose exerts its own differentiating activity with respect to thymocytes and stimulates their phenotypic and functional maturation in a monoculture.

MTA3 regulates CGB5 and Snail genes in trophoblast

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

Chen, Ying; Miyazaki, Jun; Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake

Highlights: •Impaired MTA3, raised CGB5 and Snail expression are associated with preeclampsia. •Knock-down of MTA3 causes up-regulation of CGB5 and Snail genes in BeWo cells. •MTA3 occupies CGB5 and Snail gene promoters in BeWo cells. -- Abstract: Secreted by the placental trophoblast, human chorionic gonadotropin (hCG) is an important hormone during pregnancy and is required for the maintenance of pregnancy. Previous studies have shown that dys-regulation of hCG expression is associated with preeclampsia. However, the exact relationship between altered hCG levels and development of preeclampsia is unknown. Metastasis associated protein 3 (MTA3), a chromatin remodeling protein, is abundantly expressed inmore » the placental trophoblasts, but its function is unknown. In breast cancer, MTA3 has been shown to repress the expression of Snail and cell migration. However, whether MTA3 acts similarly in the trophoblast has not been investigated. In the present study, we examined the role of MTA3 in regulating the hCG β-subunit gene (gene name: CGB5) and Snail expression in the trophoblast cell line, BeWo, as well as its relevance to the high hCG expression levels seen in preeclampsia. First, we investigated MTA3 expression in preeclamptic placenta as compared to normal control placenta via gene expression microarray and qRT-PCR and found that MTA3 was significantly down-regulated, whereas both CGB5 and Snail were up-regulated in preeclamptic placenta. Secondly, we knocked down MTA3 gene in trophoblast cell line BeWo and found Snail and hCG were both up-regulated, suggesting that MTA3 represses Snail and hCG gene expression in trophoblasts. Next, we cloned the CGB5 and Snail promoters into the pGL3-basic vector individually and found that silencing of MTA3 by siRNA resulted in an increase of both CGB5 and Snail promoter activities. To confirm that this MTA3 inhibition is a direct effect, we performed a chromatin immune-precipitation (ChIP) assay and found that MTA3 occupied the proximal promoter regions of both Snail and hCG within BeWo cells. Furthermore, we examined MTA3 expression in placental trophoblast by immunohistochemistry and found that MTA3 expression was higher in villous cytotrophoblasts versus syncytiotrophoblasts, which supports an inverse association of MTA3 with hCG expression. Lastly, using the well-characterized trophoblast fusion model, we examined MTA3 and hCG levels in forskolin-treated BeWo cells and found that MTA3 down-regulation was accompanied by an up-regulation of hCG. These data further suggest that MTA3 is repressing placental hCG expression. In summary, MTA3 plays a critical role in repressing hCG and Snail in placenta trophoblast and its deregulation is associated with preeclampsia.« less

Ovulatory Induction of SCG2 in Human, Nonhuman Primate, and Rodent Granulosa Cells Stimulates Ovarian Angiogenesis.

PubMed

Hannon, Patrick R; Duffy, Diane M; Rosewell, Katherine L; Brännström, Mats; Akin, James W; Curry, Thomas E

2018-06-01

The luteinizing hormone (LH) surge is essential for ovulation, but the intrafollicular factors induced by LH that mediate ovulatory processes (e.g., angiogenesis) are poorly understood, especially in women. The role of secretogranin II (SCG2) and its cleaved bioactive peptide, secretoneurin (SN), were investigated as potential mediators of ovulation by testing the hypothesis that SCG2/SN is induced in granulosa cells by human chorionic gonadotropin (hCG), via a downstream LH receptor signaling mechanism, and stimulates ovarian angiogenesis. Humans, nonhuman primates, and rodents were treated with hCG in vivo resulting in a significant increase in the messenger RNA and protein levels of SCG2 in granulosa cells collected early during the periovulatory period and just prior to ovulation (humans: 12 to 34 hours; monkeys: 12 to 36 hours; rodents: 4 to 12 hours post-hCG). This induction by hCG was recapitulated in an in vitro culture system utilizing granulosa-lutein cells from in vitro fertilization patients. Using this system, inhibition of downstream LH receptor signaling pathways revealed that the initial induction of SCG2 is regulated, in part, by epidermal growth factor receptor signaling. Further, human ovarian microvascular endothelial cells were treated with SN (1 to 100 ng/mL) and subjected to angiogenesis assays. SN significantly increased endothelial cell migration and new sprout formation, suggesting induction of ovarian angiogenesis. These results establish that SCG2 is increased in granulosa cells across species during the periovulatory period and that SN may mediate ovulatory angiogenesis in the human ovary. These findings provide insight into the regulation of human ovulation and fertility.

Different processing of LH/hCG receptors in cultured rat luteal cells and murine Leydig tumor cells (MLTC-1)

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

Kellokumpu, S.

1987-02-01

The metabolic fate of LH/hCG receptors after exposure to human chorionic gonadotropin (hCG) was examined in cultured rat luteal cells and murine Leydig tumor cells (MLTC-1). Kinetic studies performed after pulse-labelling of the cells with (/sup 125/I)hCG indicated that the bound hormone was lost much more rapidly from the tumor cells than from the luteal cells. The tumor cells were also found to internalize and degrade the hormone more effectively than the luteal cells. Chemical cross-linking and analyses by SDS-PAGE of this material revealed that both cell types also released, in addition to intact hCG, two previously characterized receptor fragment-(/supmore » 125/I)hCG complexes (M/sub r/ 96,000 and 74,000) into the medium, although their amount was negligible in MLTC-1 cells. Possibly due to rapid discharge of the ligand from its receptor, no similar complexes could be detected inside the MLTC-1 cells, suggesting that they were released directly from the cell surface. However, the M/sub r/ 74,000 complex was observed inside MLTC-1 cells if chloroquine, a lysosomotropic agent, was present during the incubations. This suggests that the internalized receptor also becomes degraded, at least when complexed to hCG. The results thus provide evidence that there exist two different mechanisms for proteolytic processing of LH/hCG receptors in these target cells. In tumor cells, the degradation seems to occur almost exclusively intracellularly, whereas in luteal cells a substantial portion of the receptors is also degraded at the cell surface.« less

Replacing Alpha-Fetoprotein With Alpha-Fetoprotein-L3 Increases the Sensitivity of Prenatal Screening for Trisomy 21.

PubMed

Huai, Lei; Leng, Jianhang; Ma, Shenglin; Huang, Fang; Shen, Junya; Ding, Yu

This study aimed to investigate the serum concentration of alpha-fetoprotein (AFP)-L3 in midterm pregnancies and its potential application in prenatal trisomy screening. The serum samples from 27 women with trisomy 21 fetuses and 800 women with normal fetuses were examined to measure the concentrations of AFP, AFP-L3, human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and inhibin-A. The screening results of various tests consisting of these markers were analyzed. In normal pregnancies within 15-20 weeks of gestation, the medians of serum AFP-L3 were 4.63, 5.70, 5.78, 6.58, 7.03, and 7.25 pg/mL. The median of AFP-L3 MoM in the trisomy 21 group was 0.46, which was significantly lower than the value of 1 in the normal group (P < 0.05). When using a cutoff value of 1/270, the sensitivity of the triple marker test (AFP, hCG, uE3) was improved from 74% to 81% by replacing AFP with AFP-L3, with the false-positive rate slightly increased from 5.4% to 6.8%. Similarly, the sensitivity of the quad marker test (AFP, hCG, uE3, inhibin-A) was improved from 81% to 89% by replacing AFP with AFP-L3, with the false-positive rate slightly increased from 4.6% to 5.6%. Serum AFP-L3 concentration increases along with more weeks of gestation in the midterm pregnancies. Trisomy 21 screening tests with AFP replaced by AFP-L3 have higher sensitivities at the expense of slightly increased false-positive rates. This improvement in screening may help to better prepare the parents and caregivers for the special needs of newborns with trisomy 21.

Induced reproduction and early development histology of Oscar Astronotus ocellatus (Agassiz, 1831).

PubMed

Paes, Maria do Carmo Faria; Makino, Lilian Cristina; Vasquez, Leonardo Avendaño; Fernandes, João Batista Kochenborger; Valentin, Fernanda Nogueira; Nakaghi, Laura Satiko Okada

2015-04-01

Oscar (Astronotus ocellatus) is an important fish from the Amazon Basin that has great potential for fish farming, human consumption, sport fishing and fish keeping. This study aimed to evaluate the effect of two hormonal treatments on the induction of artificial reproduction in broodstock and to describe the histological development of embryos and larvae. Broodstocks were selected and induced using two different hormones: (i) extract of carp pituitary (ECP); and (ii) synthetic human chorionic gonadotropin (hCG). Spawnings were transferred to hatcheries, collected at pre-established times, processed and analysed by histology. Astronotus ocellatus did not respond well to induced reproduction. From 16 couples of breeding fish, only five out of the eight females released oocytes after the hormonal action time, three with hCG and two with ECP; just one male responded positively to hCG. Oscar eggs were oval, and semi-adhesive, the yolk contained granules, and egg diameter was approximately 1.65 ± 0.057 to 1.98 ± 0.038 mm. Development from the initial collection (IC) point until the total absorption of the yolk lasted 315 h, at an average temperature of 27.45 ± 2.13°C. Several events marked embryonic and larval development, including the formation of the optic cup, forebrain, otic vesicle and cephalic divisions. The newly hatched larvae had non-pigmented eyes, and a closed mouth and anus, as well as the presence of adhesive glands on the head. Larval development was characterized by formation of the heart, liver, gaseous bladder, gills, pronephros, brain, fins and also the digestive tract. These results provide important information for the rearing and reproduction of A. ocellatus.

Docking and free energy simulations to predict conformational domains involved in hCG-LH receptor interactions using recombinant antibodies.

PubMed

Majumdar, Ritankar; Railkar, Reema; Dighe, Rajan R

2011-11-01

Single chain fragment variables (ScFvs) have been extensively employed in studying the protein-protein interactions. ScFvs derived from phage display libraries have an additional advantage of being generated against a native antigen, circumventing loss of information on conformational epitopes. In the present study, an attempt has been made to elucidate human chorionic gonadotropin (hCG)-luteinizing hormone (LH) receptor interactions by using a neutral and two inhibitory ScFvs against hCG. The objective was to dock a computationally derived model of these ScFvs onto the crystal structure of hCG and understand the differential roles of the mapped epitopes in hCG-LH receptor interactions. An anti-hCG ScFv, whose epitope was mapped previously using biochemical tools, served as the positive control for assessing the quality of docking analysis. To evaluate the role of specific side chains at the hCG-ScFv interface, binding free energy as well as residue interaction energies of complexes in solution were calculated using molecular mechanics Poisson-Boltzmann/surface area method after performing the molecular dynamic simulations on the selected hCG-ScFv models and validated using biochemical and SPR analysis. The robustness of these calculations was demonstrated by comparing the theoretically determined binding energies with the experimentally obtained kinetic parameters for hCG-ScFv complexes. Superimposition of hCG-ScFv model onto a model of hCG complexed with the 51-266 residues of LH receptor revealed importance of the residues previously thought to be unimportant for hormone binding and response. This analysis provides an alternate tool for understanding the structure-function analysis of ligand-receptor interactions. Copyright © 2011 Wiley-Liss, Inc.

Pregnancy testing with hCG--future prospects.

PubMed

Berger, Peter; Sturgeon, Catharine

2014-12-01

Pregnancy tests for human chorionic gonadotrophin (hCG) are used widely in hospital and home settings. Assays measuring hCG also have uses in prenatal screening and oncology. The output from three recent international workshops provides a framework for reliable measurement of hCG. Requirements for future hCG assays include use of clear descriptive nomenclature, informed selection of antibodies of well-defined epitope specificities, and design of robust methods. Tests will be precisely characterized and calibrated in SI units using six International Reference Reagents (IRR) for hCG and variants, and the Fifth International Standard for hCG 07/364, making it possible to report clinical results in molar units. These measures will help to increase patient safety by reducing the risk of erroneous or misleading hCG results. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intermediate Conductance Ca2+-Activated K+ Channels Modulate Human Placental Trophoblast Syncytialization

PubMed Central

Díaz, Paula; Wood, Amber M.; Sibley, Colin P.; Greenwood, Susan L.

2014-01-01

Regulation of human placental syncytiotrophoblast renewal by cytotrophoblast migration, aggregation/fusion and differentiation is essential for successful pregnancy. In several tissues, these events are regulated by intermediate conductance Ca2+-activated K+ channels (IKCa), in part through their ability to regulate cell volume. We used cytotrophoblasts in primary culture to test the hypotheses that IKCa participate in the formation of multinucleated syncytiotrophoblast and in syncytiotrophoblast volume homeostasis. Cytotrophoblasts were isolated from normal term placentas and cultured for 66 h. This preparation recreates syncytiotrophoblast formation in vivo, as mononucleate cells (15 h) fuse into multinucleate syncytia (66 h) concomitant with elevated secretion of human chorionic gonadotropin (hCG). Cells were treated with the IKCa inhibitor TRAM-34 (10 µM) or activator DCEBIO (100 µM). Culture medium was collected to measure hCG secretion and cells fixed for immunofluorescence with anti-IKCa and anti-desmoplakin antibodies to assess IKCa expression and multinucleation respectively. K+ channel activity was assessed by measuring 86Rb efflux at 66 h. IKCa immunostaining was evident in nucleus, cytoplasm and surface of mono- and multinucleate cells. DCEBIO increased 86Rb efflux 8.3-fold above control and this was inhibited by TRAM-34 (85%; p<0.0001). Cytotrophoblast multinucleation increased 12-fold (p<0.05) and hCG secretion 20-fold (p<0.05), between 15 and 66 h. Compared to controls, DCEBIO reduced multinucleation by 42% (p<0.05) and hCG secretion by 80% (p<0.05). TRAM-34 alone did not affect cytotrophoblast multinucleation or hCG secretion. Hyposmotic solution increased 86Rb efflux 3.8-fold (p<0.0001). This effect was dependent on extracellular Ca2+, inhibited by TRAM-34 and 100 nM charybdotoxin (85% (p<0.0001) and 43% respectively) but unaffected by 100 nM apamin. In conclusion, IKCa are expressed in cytotrophoblasts and their activation inhibits the formation of multinucleated cells in vitro. IKCa are stimulated by syncytiotrophoblast swelling implicating a role in syncytiotrophoblast volume homeostasis. Inappropriate activation of IKCa in pathophysiological conditions could compromise syncytiotrophoblast turnover and volume homeostasis in pregnancy disease. PMID:24595308

Efficacy of the Levonorgestrel-Releasing Intrauterine System on IVF-ET Outcomes in PCOS With Simple Endometrial Hyperplasia.

PubMed

Bian, Jiang; Shao, Hongfang; Liu, Hua; Li, Hui; Fang, Lu; Xing, Changying; Wang, Lihong; Tao, Minfang

2015-06-01

This study investigated the in vitro fertilization (IVF) outcome of levonorgestrel-releasing intrauterine system (LNG-IUS) pretreatment for simple endometrial hyperplasia (EH) in patients with polycystic ovary syndrome (PCOS) undergoing IVF embryo transfer (IVF-ET). One hundred ninety patients with PCOS and simple EH without cytologic atypia were allocated randomly to 2 independent arms, that is, the LNG-IUS group (90 patients) and the non-LNG-IUS group (100 patients). Four hundred fourteen patients with PCOS without endometrial disease comprised the control group. Each patient was reevaluated by transvaginal ultrasonography (TVS) and endometrial biopsy after 6 months. For each patient, IVF outcome measures, such as number of recombinant follicle-stimulating hormone, endometrial thickness on human chorionic gonadotropin (HCG) day, hormone levels (progesterone, luetinizing hormone, and serum estradiol) on HCG day, number of oocytes, fertilization rate, clinical pregnancy rate, and miscarriage rate were compared among the 3 groups. In general, the 3 groups did not differ with respect to the main clinical and biochemical data. After 6 months, patients in LNG-IUS group had an EH resolution rate of 87.77%. In the non-LNG-IUS group, the resolution rate was 15.00%, and 3% of these patients showed progression of EH. The clinical pregnancy rates in the non-LNG-IUS group were significantly lower (28.04%) than that in the LNG-IUS group (46.06%) and the control group (44.65%). The miscarriage rate was highest in the non-LNG-IUS group, but no significant difference in miscarriage rate existed among the 3 groups. The study illustrates that the LNG-IUS can be safely used for 6 months as a treatment for patients with PCOS and simple EH. Additionally, use of the LNG-IUS can increase the clinical pregnancy rates and implantation rates of patients with PCOS and simple EH who undergo gonadotropin-releasing hormone agonist IVF-ET protocols. © The Author(s) 2014.

Near-infrared laser irradiation improves the development of mouse pre-implantation embryos.

PubMed

Yokoo, Masaki; Mori, Miho

2017-05-27

The aim of the present study was to assess the effects of near-infrared laser irradiation on the in vitro development of mouse embryos. Female ICR mice were superovulated with pregnant mare serum gonadotropin and human chorionic gonadotropin (hCG), and mated with male mice. Two-cell stage embryos were collected 40 h after administering hCG and cultured in M16 medium. Two-cell embryos (0 h after culture), 8-cell embryos (approx. 30 h after culture), morula (approx. 48 h after culture), and blastocysts (approx. 73 h after culture) were irradiated at 904 nm for 60 s. These embryos were cultured in a time-lapse monitoring system and the timing of blastocyst hatching was evaluated. Some of the irradiated blastocysts were transferred to the uterine horns of pseudopregnant recipients immediately after irradiation. Pregnancy rates, and offspring growth and fertility, were evaluated. Near-infrared laser irradiation increased the speed of in vitro mouse embryo development. In irradiated blastocysts, hatching was faster than in control (non-irradiated) blastocysts (18.4 vs. 28.2 h, P < 0.05). When 195 irradiated blastocysts were transferred to 18 pseudopregnant mice, all became pregnant and 92 (47.2%) normal-looking pups were born alive. When 182 control blastocysts were transferred to 17 pseudopregnant mice, 14 (82.4%) became pregnant and 54 (29.7%) normal-looking pups were born alive. The growth trajectories (up to 5 weeks) of offspring from irradiated blastocysts were similar to those from control blastocysts. Second generation offspring from transplanted animals were all fertile. These results indicate that near-infrared laser irradiation improves the quality of mouse embryo development in vitro, and increases the live birth rate without affecting the normality of the offspring. Thus, the near-infrared laser method may enhance the quality of embryos and contribute to improvements in reproductive technologies in mammals. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

17 beta-hydroxysteroid dehydrogenase 3 deficiency in the Mediterranean population.

PubMed

Rosler, Ariel

2006-08-01

Eighty-five males with 17 beta-HSD3 were identified among a highly inbred Arab population in Israel and 57 studied over a period of 25 years. The founders of this defect originated in the mountainous regions of present Lebanon and Syria, but most of the families now live in Jerusalem, Hebron, the Tel-Aviv area and, in particular, in Gaza, where the frequency of affected males is estimated at 1 in 100 to 150. Affected individuals are born with ambiguity of the external genitalia and reared as females until puberty. Thereafter marked virilization occurs, leading in many cases to the spontaneous adoption of a male gender identity and role. Adults develop a male habitus with abundant body hair and beard and the phallus and testes enlarge to adult proportions. Gender reassignment in infancy was only possible when enough erectile tissue was present at birth and developed into a normal size penis with testosterone. 17 beta-HSD3 deficiency can be reliably diagnosed by endocrine evaluation and mutation analysis. In adults the defect is characterized by markedly increased concentrations of androstenedione (A) with borderline low to normal testosterone (T) levels and a high A/T ratio. 5a-dihydrotestosterone (DHT) concentrations are moderately decreased, normal or high and dehydroepiandrosterone (DHEA) levels are high. The estrogen pathway is also impaired, even though both estrone (E-1) and estradiol-17 beta (E-2) levels are high. Children have low basal levels of all androgens, but the defect may be demonstrated after prolonged stimulation with human chorionic gonadotropin (HCG). LH and FSH levels are very high after puberty and normal in childhood. 17 beta-HSD3 isozyme is encoded by the chromosome 9q22 17 beta-HSD3 gene and expressed exclusively in testes. A point mutation in exon 3, codon 80 of the 17 beta-HSD3 gene, R80Q, caused by a single base substitution from CGG ( arginine) to CAG ( glutamine) was identified in both alleles of 24 individuals from 9 extended Arab families from Gaza, Jerusalem and Lod-Ramle. Twenty-one homozygote males (46,XY) were MPH with testicular 17 beta-HSD3 deficiency whereas the three homozygote females (46,XX) were asymptomatic, had normal internal and external genitalia, normal sexual development and revealed no biochemical evidence of 17 beta-HSD3 deficiency. The molecular pattern is compatible with an autosomal recessive mode of inheritance, sex dependent.

Expression of Eph receptor tyrosine kinases and their ligands in human Granulosa lutein cells and human umbilical vein endothelial cells.

PubMed

Xu, Y; Zagoura, D; Keck, C; Pietrowski, D

2006-11-01

Corpus luteum development is regulated by gonadotropins and accompanied by extremely rapid vascularization of the avascular granulosa cell compartiment by endothelial cells (EC). The proliferation of Granulosa cells (GC) and EC is a complex interplay and takes place in a spatially and temporarily coordinated manner. The erythropoietin-producing hepatoma amplified sequence (Eph) receptors and their ligands-the ephrins- are a recently detected family of membrane located protein tyrosine kinases which play a crucial role in the growth and development of nerve and blood vessel network. We report about the mRNA expression pattern of Ephs and their ligands in human GC, in human EC, and in carcinoma cell lines OvCar-3 and Hela. The mRNA of EphA4, EphA7, ephrinA4, ephrinB1 and ephrinB2 was detected in GC and EC, while EphA2 was expressed only in GC. The expression of various Ephs and ephrins did not change in GC after stimulation with human chorion gonadotropin. Our study analyzes for the first time the expression of the complete human Eph/ephriny-system in GC and in EC. The remarkable similarity between these two cell types supports the theory of a functional relationship of EC and GC. In addition, it was shown that hCG is not a major determinant of Eph/ephrin regulation in GC.

Amenorative effects of exogenous gonadotropins on reproductive profiles of replacement gilts with delayed puberty in a farm in Thailand.

PubMed

Am-In, Nutthee; Roongsitthichai, Atthaporn

2017-02-01

This study was to investigate the effect of gonadotropins on reproductive profiles of replacement gilts with delayed puberty. Totally, 136 Landrace X Yorkshire crossbred gilts, were categorized into control (n = 58) and treatment (n = 78) groups. Gonadotropins (400 U eCG plus 200 IU hCG) were administered in treatment group only. The results revealed that gilts in treatment group had higher number of gilts with estrus (92.3 vs 25.9%, P < 0.001), shorter onset to estrus (4.7 ± 0.3 vs 9.0 ± 0.8 d, P < 0.001), higher number of dominant follicles (18.0 ± 0.2 vs 13.2 ± 0.3 follicles, P < 0.001), and higher farrowing rate (87.5 vs 53.3%, P = 0.002) than those in control group. In conclusion, gonadotropins containing 400 IU eCG plus 200 IU hCG could improve reproductive profiles in replacement gilts with delayed puberty.

Maternal serum alpha-fetoprotein and human chorionic gonadotropin levels in women with human immunodeficiency virus.

PubMed

Gross, Susan; Castillo, Wilfrido; Crane, Marilyn; Espinosa, Bialines; Carter, Suzanne; DeVeaux, Richard; Salafia, Carolyn

2003-04-01

The purpose of this study was to establish whether there is a correlation between maternal serum genetic screen analyte results in pregnant women with human immunodeficiency virus and corresponding human immunodeficiency virus index values. Medical records of all pregnant women with human immunodeficiency virus who were delivered at Bronx Lebanon Hospital Center from January 2000 through December 2001 were reviewed for maternal serum screen results, viral load, CD4 counts and percent, antiretroviral therapy, opportunistic infections, substance abuse, and other demographic data. Statistical analysis was accomplished with the chi(2) test, Mann-Whitney U test, and Spearman rank correlation test, with a probability value of <.05 considered significant. Of the 98 women with human immunodeficiency virus who were delivered, 49 women (50%) had a maternal serum genetic screen available. Screened and unscreened women had similar severity of human immunodeficiency virus disease, CD4 count and percentage, and viral loads. Serum screen results showed elevations in maternal serum human chorionic gonadotropin (1.43 +/- 1.04 multiples of the median [MoM]; range, 0.2-5.2 MoM) and maternal serum alpha-fetoprotein (1.29 +/- 0.9 MoM; range, 0.5-3.3 MoM) compared with expected values in the general obstetric population. Maternal serum human chorionic gonadotropin was correlated inversely with CD4 count (P =.002) and CD4 percent (P <.0001). Maternal serum alpha-fetoprotein varied directly with viral load (P <.0001). Increasing maternal serum human chorionic gonadotropin and maternal serum alpha-fetoprotein levels in patients with human immunodeficiency virus are correlated with increasing viral load and decreasing CD4 counts.

Uterine, ovarian, and production responses of lactating dairy cows to increasing dietary concentrations of menhaden fish meal.

PubMed

Mattos, R; Staples, C R; Williams, J; Amorocho, A; McGuire, M A; Thatcher, W W

2002-04-01

The primary objective was to determine whether the dietary polyunsaturated fatty acids, eicosapentaenoic (EPA, C20:5, n-3) and docosahexaenoic (DHA, C22:6, n-3), present in fish meal (FM) can attenuate uterine secretion of PGF2alpha in response to a challenge with estradiol and oxytocin in lactating dairy cows. Cycling multiparous cows (n = 32) were fed diets containing 0 (OFM), 2.6 (2.6FM), 5.2 (5.2FM), or 7.8% menhaden FM (7.8FM). The diet consisting of 7.8FM also contained fish oil (0.28% of dietary dry matter) to increase intake of EPA and DHA. Average dry matter intake was 24.9 kg/d and unaffected by diet. Combined intakes of EPA and DHA averaged 0, 12.8, 24.1, and 54.0 g/d from the OFM, 2.6FM, 5.2FM, and 7.8FM diets, respectively. At 30 to 34 d after initiation of dietary treatments, cows received an i.m. injection of 100 microg of GnRH followed by i.m. administration of 25 and 15 mg of PGF2alpha after 7 and 8 d, respectively. Synchronous ovulation was induced by an injection of 3000 IU of human chorionic gonadotropin (hCG) given 24 h later on d 9. Subsequent luteal phase increases in plasma progesterone concentrations did not differ (0.88 ng/ml per day). At 15 d after hCG injection, cows were injected with estradiol-17beta (3 mg, i.v.) at 0900 h and oxytocin (100 IU, i.v.) at 1300 h. Plasma PGF2alpha metabolite concentrations after oxytocin injection were reduced in cows fed diets containing FM compared with those fed OFM. Milk production (39.1 kg/d) and concentrations of fat, protein, or urea nitrogen in milk were not affected by diet. Feeding fish meal and fish oil containing eicosapentaenoic acid and docosahexaenoic acid reduced the proportion of n-6 fatty acids and increased that of n-3 fatty acids in milk in a dose-responsive manner.

Correlations between serum assays of human chorionic gonadotrophin (hCG) and human placental lactogen (hPL) and pre-eclampsia or intrauterine growth restriction (IUGR) among nulliparas younger than 38 years.

PubMed

Merviel, P; Müller, F; Guibourdenche, J; Berkane, N; Gaudet, R; Bréart, G; Uzan, S

2001-03-01

To study the relation between serum human chorionic gonadotrophin (hCG) levels measured at 15-18 weeks and gestational disorders, assess their correlation with the artery uteroplacental Doppler (AUD) at 24 weeks among nulliparas, and assess the predictivity of the hCG/hPL (human placental lactogen) ratio for pre-eclampsia. Retrospective study of two groups of women younger than 38 years old: one with an elevated serum hCG level (2 MoM (multiples of the median) or more) and a normal fetal karyotype (group A), and the other with a lower hCG level (group B). Within each group, we studied the nulliparas separately (respectively groups AO and BO). We analyzed the double screening, elevated hCG levels with abnormal AUD, for the predicting of hypertensive disorders. Elevated hCG levels were significantly (p<0.05) more prevalent among women who developed gestational diabetes (groups A and AO) and among nulliparas with pregnancy-induced hypertension and pre-eclampsia (AO). Among nulliparas, the combination of the hCG assay and a subsequent Doppler increased the positive predictive value (PPV) of the assay from 19 to 75%, without reducing its negative predictive value (NPV) for gestational vascular disorders. The hCG/hPL ratio did not improve the predictivity of the hCG assay alone for pre-eclampsia. An hCG level of 2 MoM or more at 15-18 weeks identifies a group of women at risk of gestational vascular disorders; it therefore ought to lead to an AUD at 24 weeks. This double screening should be able to define a population of women at risk of developing a hypertensive disorder, who could thus benefit from a preventive treatment, as aspirin.

HCG-. beta. -subunit radioimmunoassay: potential error in HCG measurement related to choice of labeled antigen. [/sup 125/I

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

Tyrey, L.; Hammond, C.B.

1976-05-15

Antiserum generated against the hormone-specific ..beta..-subunit of hCG was used with different labeled antigens to measure circulating hCG in patients having trophoblastic disease. When /sup 125/I-hCG..beta.. served as the labeled antigen, a small number of patient sera failed to show parallelism with the second IS-hCG reference and erroneous estimates of hormone concentrations were obtained. Replacement of the /sup 125/I-hCG..beta.. with labeled hCG corrected the nonparallelism exhibited by these samples. Inhibition curves obtained with purified hCG and hCG..beta.. suggested that both the nonparallelism and its correction with the change in labeled antigen would be consistent with the possibility that this assaymore » aberration may result from the presence of free hCG..beta.. in these sera. (auth)« less

Gender impact on first trimester markers in Down syndrome screening.

PubMed

Larsen, Severin Olesen; Wøjdemann, Karen R; Shalmi, Anne-Cathrine; Sundberg, Karin; Christiansen, Michael; Tabor, Ann

2002-12-01

The influence of fetal gender on the level in the first trimester of the serological markers alpha-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (betahCG) and on nuchal translucency is described for 2637 singleton pregnancies with normal outcome. Mean log MoM values for pregnancies with female and male fetuses were calculated using regression of log marker values on gestational age expressed as crown rump length and on maternal weight. A pronounced gender impact was found for free betahCG, being 16% higher for female than for male fetuses. Copyright 2002 John Wiley & Sons, Ltd.

Regulation of gonadotropin receptors, gonadotropin responsiveness, and cell multiplication by somatomedin-C and insulin in cultured pig Leydig cells

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

Bernier, M.; Chatelain, P.; Mather, J.P.

1986-11-01

The author have investigated the effects of insulin and somatomedin-C/insulin like growth factor I(Sm-C) in purified porcine Leydig cells in vitro on gonadotrophins (hCG) receptor number, hCG responsiveness (cAMP and testosterone production), and thymidine incorporation into DNA. Leydig cells cultured in a serum-free medium containing transferrin, vitamin E, and insulin (5 ..mu..g/ml) maintained fairly constant both hCG receptors and hCG responsiveness. When they were cultured for 3 days in the same medium without insulin, there was a dramatic decline (more than 80%) in both hCG receptor number and hCG responsiveness. However the cAMP but not the testosterone response to forskolinmore » was normal. Both insulin and Sm-C at nanomolar concentrations prevent the decline of both hCG receptors and hCG-induced cAMP production. At nanomolar concentrations, Sm-C and insulin enhanced hCG-induced testosterone production but the effect of Sm-C was significantly higher than that of insulin. However, the effect of insulin at higher concentrations (5 ..mu..g/ml) was significantly higher than that of Sm-C at 50 ng/ml. In contrast, at nanomolar concentrations only Sm-C stimulated (/sup 3/H)-thymidine incorporation into DNA and cell multiplication, the stimulatory effect of insulin on these parameters, was seen only at micromolar concentrations. These results indicate that both Sm-C and insulin acting through the receptors increase Leydig cell steroidogenic responsiveness to hCG by increasing hCG receptor number and improving some step beyond cAMP formation. In contrast, the mitogenic effects of insulin are mediated only through Sm-C receptors.« less

Structures of the SER/THR linked variant oligosaccharides present in equine chorionic gonadotropin (eCG). beta. -subunit

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

Bahl, O.P.; Anumula, K.R.

1986-05-01

eCG ..beta..-subunit contains more than 50% carbohydrate and constitutes about 72% of the hormone. O-linked carbohydrate (85%) was separated from the N-linked (15%) by gel filtration of the endoproteinase Lys-C digest. Six O-linked carbohydrate units were released by NaOH/NaB/sup 3/H/sub 4/ treatment. Oligosaccharides were fractionated by gel filtration and paper chromatography. Several oligosaccharides were obtained ranging in size from a sialyl di-saccharide to megalosaccharide with about 50 sugar residues. Methylation analyses and tlc examination of the oligosaccharides after endo- and exoglycosidase digestions and nitrous acid deamination and Smith degradation revealed a core structure of Gal..beta..1-4 GlcNAc..beta..1-6 (Gal ..beta..1-3) GalNAcH/sub 2/more » with poly-N-acetyllactosamine peripheral extensions. Nearly 50% of the oligosaccharides were large and were preferentially extended on 1,6 arm of the GalNAcH/sub 2/ by repeating N-acetyllactosamine units. Furthermore, these oligosaccharides contained branching 1,3,6-linked galactoses giving rise to tri, penta and multiantennary structures.« less

Reproducibility of risk figures in 2nd-trimester maternal serum screening for down syndrome: comparison of 2 laboratories.

PubMed

Benn, Peter A; Makowski, Gregory S; Egan, James F X; Wright, Dave

2006-11-01

Analytical error affects 2nd-trimester maternal serum screening for Down syndrome risk estimation. We analyzed the between-laboratory reproducibility of risk estimates from 2 laboratories. Laboratory 1 used Bayer ACS180 immunoassays for alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG), Diagnostic Systems Laboratories (DSL) RIA for unconjugated estriol (uE3), and DSL enzyme immunoassay for inhibin-A (INH-A). Laboratory 2 used Beckman immunoassays for AFP, hCG, and uE3, and DSL enzyme immunoassay for INH-A. Analyte medians were separately established for each laboratory. We used the same computational algorithm for all risk calculations, and we used Monte Carlo methods for computer modeling. For 462 samples tested, risk figures from the 2 laboratories differed >2-fold for 44.7%, >5-fold for 7.1%, and >10-fold for 1.7%. Between-laboratory differences in analytes were greatest for uE3 and INH-A. The screen-positive rates were 9.3% for laboratory 1 and 11.5% for laboratory 2, with a significant difference in the patients identified as screen-positive vs screen-negative (McNemar test, P<0.001). Computer modeling confirmed the large between-laboratory risk differences. Differences in performance of assays and laboratory procedures can have a large effect on patient-specific risks. Screening laboratories should minimize test imprecision and ensure that each assay performs in a manner similar to that assumed in the risk computational algorithm.

Dual-functional biomimetic materials: nonfouling poly(carboxybetaine) with active functional groups for protein immobilization.

PubMed

Zhang, Zheng; Chen, Shengfu; Jiang, Shaoyi

2006-12-01

We introduce a dual-functional biocompatible material based on zwitterionic poly(carboxybetaine methacrylate) (polyCBMA), which not only highly resists protein adsorption/cell adhesion, but also has abundant functional groups convenient for the immobilization of biological ligands, such as proteins. The dual-functional properties are unique to carboxybetaine moieties and are not found in other nonfouling moieties such as ethylene glycol, phosphobetaine, and sulfobetaine. The unique properties are demonstrated in this work by grafting a polyCBMA polymer onto a surface or by preparing a polyCBMA-based hydrogel. PolyCBMA brushes with a thickness of 10-15 nm were grafted on a gold surface using the surface-initiated atom transfer radical polymerization method. Protein adsorption was analyzed using a surface plasmon resonance sensor. The surface grafted with polyCBMA very largely prevented the nonspecific adsorption of three test proteins, that is, fibrinogen, lysozyme, and human chorionic gonadotropin (hCG). The immobilization of anti-hCG on the surface resulted in the specific binding of hCG while maintaining a high resistance to nonspecific protein adsorption. Transparent polyCBMA-based hydrogel disks were decorated with immobilized fibronectin. Aortic endothelial cells did not bind to the polyCBMA controls, but appeared to adhere well and spread on the fibronectin-modified surface. With their dual functionality and biomimetic nature, polyCBMA-based materials are very promising for their applications in medical diagnostics, biomaterials/tissue engineering, and drug delivery.

Hyperglycosylated hCG and Placenta Accreta Spectrum.

PubMed

Einerson, Brett D; Straubhar, Alli; Soisson, Sean; Szczotka, Kathryn; Dodson, Mark K; Silver, Robert M; Soisson, Andrew P

2018-02-28

 We aimed to evaluate the relationship between hyperglycosylated human chorionic gonadotropin (hCG-H) and placenta accreta spectrum (PAS) in the second and third trimesters of pregnancy.  This was a case-control study of PAS and controls. hCG-H was measured in the second and third trimesters of pregnancy in women with pathologically confirmed cases of PAS and in gestational age-matched controls without PAS. We compared serum hCG-H levels in cases and controls, calculated summary statistics for diagnostic accuracy, and used receiver operating characteristic (ROC) curves to define an optimal cut-point for diagnosis of PAS using hCG-H.  Thirty case samples and 30 control samples were evaluated for hCG-H. Mean hCG-H was lower in the case compared with control group (7.8 ± 5.9 μg/L vs. 11.8 ± 8.8 μg/L, p  = 0.03). At an optimal cut-point for hCG-H of ≤7.6 μg/L, the sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and area under the ROC curve were 66.7%, 69.7%, 2.20%, 0.48%, and 0.68%, respectively.  Hyperglycosylated hCG levels in the second and third trimesters of pregnancy were lower in patients with PAS than in controls, but hCG-H showed only modest capability as a diagnostic test for PAS. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Evaluation of the chemiluminescent enzyme immunoassay system for the measurement of testosterone in the serum and whole blood of stallions

PubMed Central

TOISHI, Yuko; TSUNODA, Nobuo; NAGATA, Shun-ichi; KIRISAWA, Rikio; NAGAOKA, Kentaro; WATANABE, Gen; YANAGAWA, Yojiro; KATAGIRI, Seiji; TAYA, Kazuyoshi

2017-01-01

Testosterone (T) concentration is a useful indicator of reproductive function in male animals. However, T concentration is not usually measured in veterinary clinics, partly due to the unavailability of reliable and rapid assays for animal samples. In this study, a rapid chemiluminescent enzyme immunoassay system (CLEIA system) that was developed for the measurement of T concentration in humans use was validated for stallion blood samples. First, serum T concentrations were measured using the CLEIA system and compared with those measured by a fluoroimmunoassay that has been validated for use in stallions. The serum T concentrations measured by the two methods were highly correlated (r = 0.9865, n = 56). Second, to validate the use of whole blood as assay samples, T concentrations in whole blood and in the serum were measured by the CLEIA system. T concentrations in both samples were highly correlated (r = 0.9665, n = 64). Finally, to evaluate the practical value of the CLEIA system in clinical settings, T concentrations were measured in three stallions with reproductive abnormalities after the administration of human chorionic gonadotropin (hCG). Two stallions with small or absent testes in the scrotum showed an increase in T production in response to hCG administration and one stallion with seminoma did not. In conclusion, the CLEIA system was found to be a rapid and reliable tool for measuring T concentrations in stallions and may improve reproductive management in clinical settings and in breeding studs. PMID:29129877

Low reversibility of intracellular cAMP accumulation in mouse Leydig tumor cells (MLTC-1) stimulated by human Luteinizing Hormone (hLH) and Chorionic Gonadotropin (hCG).

PubMed

Klett, Danièle; Meslin, Philippine; Relav, Lauriane; Nguyen, Thi Mong Diep; Mariot, Julie; Jégot, Gwenhaël; Cahoreau, Claire; Combarnous, Yves

2016-10-15

In order to study the intracellular cAMP response kinetics of Leydig cells to hormones with LH activity, we used MLTC-1 cells transiently expressing a chimeric cAMP-responsive luciferase so that real-time variations of intracellular cAMP concentration could be followed using oxiluciferin luminescence produced from catalyzed luciferin oxidation. The potencies of the different LHs and CGs were evaluated using areas under the curves (AUC) of their kinetics over 60 min stimulation. All mammalian LHs and CGs tested were found to stimulate cAMP accumulation in these cells. The reversibility of this stimulation was studied by removing the hormone from the culture medium after 10 min of incubation. The ratios of kinetics AUC after removing or not the hormone were used to evaluate the stimulation reversibility of each hormone. Natural and recombinant hLHs and hCGs were found to exhibit slowly reversible activation compared to pituitary rat, ovine, porcine, camel and equine LHs, serum-derived eCG (PMSG) and recombinant eLH/CGs. Carbohydrate side chains are not involved in this phenomenon since natural and recombinant homologous hormones exhibit the same reversibility rates. It is still unknown whether only one human subunit, α or β, is responsible for this behaviour or whether it is due to a particular feature of the hLH and hCG quaternary structure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

Apolipoprotein B is regulated by gonadotropins and constitutes a predictive biomarker of IVF outcomes.

PubMed

Scalici, Elodie; Bechoua, Shaliha; Astruc, Karine; Duvillard, Laurence; Gautier, Thomas; Drouineaud, Véronique; Jimenez, Clément; Hamamah, Samir

2016-05-21

Follicular fluid (FF) is an important micro-environment influencing oocyte growth, its development competence, and embryo viability. The FF content analysis allows to identify new relevant biomarkers, which could be predictive of in vitro fertilization (IVF) outcomes. Inside ovarian follicle, the amount of FF components from granulosa cells (GC) secretion, could be regulated by gonadotropins, which play a major role in follicle development. This prospective study included 61 female undergoing IVF or Intra-cytoplasmic sperm injection (ICSI) procedure. Apolipoprotein B (APOB) concentrations in follicular fluid and APOB gene and protein expression in granulosa cells from reproductively aged women undergoing an in vitro fertilization program were measured. The statistical analyses were performed according to a quartile model based on the amount of APOB level found in FF. Amounts of APOB were detected in human FF samples (mean ± SD: 244.6 ± 185.9 ng/ml). The odds of obtaining an oocyte in the follicle and a fertilized oocyte increased significantly when APOB level in FF was higher than 112 ng/ml [i.e., including in Quartile Q 2, Q3 and Q4] (p = 0.001; p < 0.001, respectively). The probabilities of obtaining an embryo and a top quality embryo on day 2, were significantly higher if APOB levels were within the ranges of 112 and 330 ng/ml (i.e. in Q2 and Q3) or 112 and 230 ng/ml (i.e. in Q2), respectively (p < 0.001; p = 0.047, respectively). In addition, our experiments in vitro indicated that APOB gene and protein expression, along with APOB content into culture were significantly under-expressed in GC upon stimulation with gonadotropins (follicular stimulating hormone: FSH and/or human chorionic gonadotropin: hCG). We are reporting a positive and statistically significant associations between APOB and oocyte retrieval, oocyte fertilization, and embryo quality. Using an experimental study component, the authors report significant reduced APOB expression and content for luteinized granulosa cells cultured in the presence of gonadotropins.

Single point biochemical measurement algorithm for early diagnosis of ectopic pregnancy.

PubMed

Butler, Stephen A; Abban, Thomas K A; Borrelli, Paola T A; Luttoo, Jameel M; Kemp, Bryn; Iles, Ray K

2013-09-01

Tubal rupture as a result of an ectopic pregnancy is the leading cause of first trimester maternal mortality. Currently, the diagnosis of ectopic pregnancy depends on transvaginal ultrasound and serial serum measurements of human chorionic gonadotrophin (hCG), which requires follow up. The objective of this study was to examine whether single point measurements at presentation could distinguish between women with ectopic pregnancy, viable pregnancy, and spontaneous miscarriage. Serum total hCG (hCGt), hyperglycosylated hCG (hCGh), free beta subunit of hCG (hCGβ), progesterone (P), and CA-125 were measured by chemiluminescence immunoassay over a 3 month period in 441 women presenting at the emergency room with abdominal pain and a positive pregnancy test. Patient outcomes were followed and confirmed by histology. 65 samples were excluded due to poor sample storage, or lost to follow up. The pregnancy outcomes were 175 viable pregnancies, 175 spontaneous miscarriages, and 26 ectopic pregnancies. A serum hCGt <3736 mIU/mL cut off was 100% sensitive, with 76% specificity, for distinguishing ectopic pregnancy from viable pregnancy; but did not differentiate spontaneous miscarriage. Serum CA125 <41.98 U/mL produced 100% sensitivity and 43% specificity in distinguishing ectopic pregnancy from spontaneous miscarriage. Sequential application of hCGt and CA-125 cut off followed by ultrasound could detect 100% of ectopic pregnancies with 87% specificity for all intrauterine pregnancies. The combination of serum hCGt <3736 mIU/mL, followed by CA125 <41.98 U/mL is a promising algorithm for detecting all ectopic pregnancy at initial presentation. © 2013.

Tumour-marker levels and prognosis in malignant teratoma of the testis.

PubMed Central

Germa-Lluch, J. R.; Begent, R. H.; Bagshawe, K. D.

1980-01-01

The effect of 6 putative prognostic factors on survival was studied in patients with Stages III and IV malignant teratoma of the testis. Differences between survival curves were tested for statistical significance. A diameter greater than 5 cm in the largest tumour mass, and greater than 8 pulmonary metastases were adverse prognostic factors (P = 0.004 and 0.008 respectively). Patients with malignant teratoma, trophoblastic, fared worse than those with malignant teratoma, undifferentiated, and malignant teratoma, intermediate (P = 0.011 and 0.023 respectively). Previous chemotherapy or radiotherapy had no significant effect. Serum alpha-foetoprotein (AFP) above 10(3) MRC u/ml and serum beta subunit of human chorionic gonadotrophin (hCG) above 10(5) miu/ml, were found to predict a poor prognosis (P = 0.010 and 0.001 respectively). A combination of measurements of the tumour markers gave the most consistent indication of prognosis, in that patients with either AFP greater than 10(3) MRC u/ml or hCG greater than 10(5) miu/ml, or both, fared much worse than those with neither factor (P = 0.001). Serum concentrations of AFP and hCG should be stated in reports of treatment of testicular teratoma in order to provide a basis for comparison with other series. Regular and frequent measurements of these markers are appropriate throughout the clinical management of patients with malignant teratoma. PMID:6161630

Two-marker combinations for preoperative discrimination of benign and malignant ovarian masses.

PubMed

Freydanck, Maj Kristin; Laubender, Ruediger Paul; Rack, Brigitte; Schuhmacher, Lan; Jeschke, Udo; Scholz, Christoph

2012-05-01

When caring for patients with ovarian neoplasms, correct preoperative discrimination of benign and malignant disease is deemed vital. In this study, we tested serum biomarkers' alone and in combination, to achieve this aim. We measured the concentrations of Cancer Antigen (CA)-125, CA15-3, CA27-29, Carcinoembryonic Antigen (CEA), CA19-9, human chorionic gonadotropin (hCG), Placental Protein (PP)1490, CA72-4, galectin-3, galectin-1 and Human epididymis protein (HE)4 in sera of 133 patients with pelvic masses by ELISA and correlated the results to subsequent histology. We used the area under the curve (AUC) of biomarkers and their combinations and calculated the 95% confidence intervals by using casewise resampling. The best single biomarkers were CA-125 (sensitivity and AUC) and HE4 (specificity). Combinations with HE4 and CA19-9 improved the predictive power of CA-125. The best discrimination was achieved by the combination of CA-125 and HE4, with an AUC of 0.961. A combination of CA-125 with HE4 could facilitate the identification of women at risk for ovarian cancer.

Quantitative detection of the colloidal gold immunochromatographic strip in HSV color space

NASA Astrophysics Data System (ADS)

Wu, Yuanshu; Gao, Yueming; Du, Min

2014-09-01

In this paper, a fast, reliable and accurate quantitative detection method for the colloidal gold immunochromatographic strip(GICA) is presented. An image acquisition device which is mainly composed of annular LED source, zoom ratio lens, and 10bit CMOS image sensors with 54.5dB SNR is designed for the detection. Firstly, the test line is extracted from the strip window through using the H component peak points of the HSV space as the clustering centers via the Fuzzy C-Means(FCM) clustering method. Then, a two dimensional eigenvalue composed with the hue(H) and saturation(S) of HSV space was proposed to improve the accuracy of the quantitative detection. At last, the experiment of human chorionic gonadotropin(HCG) with the concentration range 0-500mIU/mL is carried out. The results show that the linear correlation coefficient between this method and optical density(OD) values measured by the fiber optical sensor reach 96.74%. Meanwhile, the linearity of fitting curve constructed with concentration was greater than 95.00%.

Biochemical markers of trisomy 21 in amniotic fluid.

PubMed

Spencer, K; Muller, F; Aitken, D A

1997-01-01

In a study of amniotic fluid from 91 Down's syndrome cases and 240 controls, we have shown that the median values of four biochemical markers (AFP, total hCG, free beta hCG, and unconjugated oestriol) in the amniotic fluid of pregnancies affected by Down's syndrome on the whole reflect those observed in the maternal serum of affected cases. The median MOM for AFP was lower than average (0.56), as was that for unconjugated oestriol (0.55), whilst those for total hCG (1.82) and free beta hCG (2.10) were increased on average. The width of the distribution of marker levels in amniotic fluid is similar to that in serum for free beta hCG and total hCG but between 1.5 and 2 times wider for unconjugated oestriol and AFP. Analysis of data by fetal sex showed a significantly higher median MOM in female control cases compared with male controls for the analytes free beta hCG, total hCG, and unconjugated oestriol, but not for AFP. Amongst the Down's syndrome cases, this trend was not statistically significant and we cannot confirm a previous study which reported that elevated levels of amniotic fluid total and free beta hCG were associated only with female fetuses.

hCG, the wonder of today's science

PubMed Central

2012-01-01

Background hCG is a wonder. Firstly, because hCG is such an extreme molecule. hCG is the most acidic glycoprotein containing the highest proportion of sugars. Secondly, hCG exists in 5 common forms. Finally, it has so many functions ranging from control of human pregnancy to human cancer. This review examines these molecules in detail. Content These 5 molecules, hCG, sulfated hCG, hyperglycosylated hCG, hCG free beta and hyperglycosylated free beta are produced by placental syncytiotrophoblast cells and pituitary gonadotrope cells (group 1), and by placental cytotrophoblast cells and human malignancies (group 2). Group 1 molecules are both hormones that act on the hCG/LH receptor. These molecules are central to human menstrual cycle and human pregnancy. Group 2 molecules are autocrines, that act by antagonizing a TGF beta receptor. These molecules are critical to all advanced malignancies. Conclusions The hCG groups are molecules critical to both the molecules of pregnancy or human life, and to the advancement of cancer, or human death. PMID:22455390

Serum oxidizability and antioxidant status in patients undergoing in vitro fertilization.

PubMed

Aurrekoetxea, Igor; Ruiz-Sanz, José Ignacio; del Agua, Ainhoa Ruiz; Navarro, Rosaura; Hernández, M Luisa; Matorras, Roberto; Prieto, Begoña; Ruiz-Larrea, M Begoña

2010-09-01

To evaluate the serum oxidizability and antioxidant status in women undergoing an in vitro fertilization (IVF) cycle and to assess the possible relationship of the oxidizability indexes with the pregnancy rate. Prospective, longitudinal study. Public university and public university hospital. Systematically recruited cohort of 125 women undergoing either IVF or intracytoplasmic sperm injection (ICSI). Serum samples were collected before the beginning of the use of gonadotropins (basal) and the day of human chorionic gonadotropin (hCG) administration (final) during an IVF cycle. The Cu2+-induced serum oxidation in terms of the oxidation rate in the lag (Vlag) and propagation (Vmax) phases and the time at which the oxidation rate is maximal (tmax), and measurements of serum total antioxidant activity (TAA), tocopherol, hydrophilic antioxidants, malondialdehyde, and nitric oxide. Albumin, urate, bilirubin, alpha-tocopherol and gamma-tocopherol, TAA, and tmax statistically significantly decreased after the IVF cycle. Conception cycles were associated with a serum more prone to oxidation compared with nonconception cycles. In multivariate logistic regression analysis, the difference (final-basal) of the oxidation index Vlag (OR 1.394) and the body mass index (OR 0.785) were independent predictors of pregnancy. Treatment with IVF induces the production of reactive oxygen species (ROS), which is reflected in a serum less protected against oxidation. The results also suggest a role for ROS in the occurrence of conception in IVF. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Could aspiration of the Graafian follicle cause luteal phase deficiency?

PubMed

Feichtinger, W; Kemeter, P; Szalay, S; Beck, A; Janisch, H

1982-02-01

Luteal phase quality was evaluated in 32 patients wih nonstimulated cycles after laparoscopic oocyte recovery for in vitro fertilization. A luteal phase deficiency occurred in two cases (6.2%), the mean duration of the luteal phase was 13.5 +/- 1.3 days in 30 patients, and two patients developed amenorrhea of 23 and 43 days respectively after laparoscopy in spite of normal progesterone values 7 and 9 days after oocyte recovery. Six embryo transfers were performed after fertilization and regular cleavage of the obtained oocytes. No pregnancy resulted from the embryo transfers, although the patients had apparently normal luteal phases. In one patient there was a transient beta-subunit human chorionic gonadotropin (beta-hCG) elevation in serum. Luteal phase deficiency should not be main cause of a nonsuccessful embryo transfer. However, a prophylactic luteal phase support after oocyte recovery and embryo transfer in nonstimulated cycles is proposed.

HBCDD-induced sustained reduction in mitochondrial membrane potential, ATP and steroidogenesis in peripubertal rat Leydig cells

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

Fa, Svetlana; Pogrmic-Majkic, Kristina; Samardzija, Dragana

Hexabromocyclododecane (HBCDD), a brominated flame retardant added to various consumer products, is a ubiquitous environmental contaminant. We have previously shown that 6-hour exposure to HBCDD disturbs basal and human chorionic gonadotropin (hCG)-induced steroidogenesis in rat Leydig cells. Reduction in mitochondrial membrane potential (ΔΨm) and cAMP production was also observed. Here, we further expanded research on the effect of HBCDD on Leydig cells by using a prolonged exposure scenario. Cells were incubated in the presence of HBCDD during 24 h and then treated with HBCDD + hCG for additional 2 h. Results showed that HBCDD caused a sustained reduction in ATPmore » level after 24 h of exposure, which persisted after additional 2-hour treatment with HBCDD + hCG. cAMP and androgen accumulations measured after 2 h of HBCDD + hCG treatment were also inhibited. Real-time PCR analysis showed significant inhibition in the expression of genes for steroidogenic enzymes, luteinizing hormone receptor, regulatory and transport proteins, and several transcription factors under both treatment conditions. Western blot analysis revealed a decreased level of 30 kDa steroidogenic acute regulatory protein (StAR) after HBCDD + hCG treatment. In addition, HBCDD decreased the conversion of 22-OH cholesterol to pregnenolone and androstenedione to testosterone, indicating loss of the activity of cytochrome P450C11A1 (CYP11A1) and 17β-hydroxysteroid dehydrogenase (HSD17β). Cell survival was not affected, as confirmed by cytotoxicity and trypan blue tests or DNA fragmentation analysis. In summary, our data showed that HBCDD inhibits ATP supply, most likely through a decrease in ΔΨm, and targets multiple sites in the steroidogenic pathway in Leydig cells. - Highlights: • HBCDD causes a sustained reduction in ΔΨm and ATP level in Leydig cells. • Prolonged HBCDD exposure decreases hCG-supported steroidogenesis in Leydig cells. • HBCDD targets StAR, HSD17β and CYP11A1 in Leydig cells.« less

Urinary nandrolone metabolites of endogenous origin in man: a confirmation by output regulation under human chorionic gonadotropin stimulation.

PubMed

Reznik, Y; Dehennin, L; Coffin, C; Mahoudeau, J; Leymarie, P

2001-01-01

19-Nortestosterone (nandrolone) is an anabolic steroid compound widely used as a doping agent by athletes. The analysis of its urinary metabolites, 19-norandrosterone (NA) and 19-noretiocholanolone (NE) glucuronides, allows the detection of surreptitious administration of nandrolone in sport. A threshold concentration at 2 microgram/L urinary nandrolone metabolites is advocated by the International Olympic Committee for the detection of doping, but some controversy concerning the validity of this threshold arose from the demonstration of endogenous production of nandrolone in mammals, including humans. The regulation of human nandrolone production and its contribution in vivo to the process of aromatization remain unknown. In the present study 10 healthy men were successively submitted to insulinic stress and gonadal stimulation by hCG administration. Urinary NA and NE concentrations were quantified by gas chromatography-mass spectrometry. NA was detected in basal urine samples from all subjects, with a mean urinary excretion rate (UER) of 3.17 +/- 0.35 ng/h, whereas NE was detected in 4 of 10 (UER range, 0.8-4.7 ng/h). Insulinic hypoglycemia did not significantly modify mean NA UER despite random intraindividual variations between timed urine collections. After hCG administration, NA UER increased by 250% (P < 0.01) and estradiol (E(2)) UER by 260% (P < 0.001). The maximum NA concentration obtained after stimulation was 0.43 microgram/L. NA UER, plasma E(2), and E(2)/T ratio peaked on day 1 after hCG administration, whereas plasma T peaked later on day 3. NA UER correlated with plasma E(2) (r = 0.61; P < 0.001) and E(2)/T (r = 0.51; P < 0.001), but not with plasma T. In conclusion, insulinic stress did not significantly alter nandrolone metabolism, whereas the effect of hCG was a stimulation of NA excretion in all subjects, which constitutes strong support for the endogenous origin of low basal NA excretion. The comparative kinetics of NA UER, plasma E(2), and E(2)/T ratio suggest a contribution of the aromatase process to nandrolone biosynthesis in man.

Use of fertility drugs and risk of uterine cancer: results from a large Danish population-based cohort study.

PubMed

Jensen, Allan; Sharif, Heidi; Kjaer, Susanne K

2009-12-01

Some epidemiologic studies have indicated that uterine cancer risk may be increased after use of fertility drugs. To further assess this association, the authors used data from a large cohort of 54,362 women diagnosed with infertility who were referred to Danish fertility clinics between 1965 and 1998. In a case-cohort study, rate ratios and 95% confidence intervals were used to assess the effects of 4 groups of fertility drugs on overall risk of uterine cancer after adjustment for potentially confounding factors. Through mid-2006, 83 uterine cancers were identified. Ever use of any fertility drug was not associated with uterine cancer risk (rate ratio (RR) = 1.10, 95% confidence interval (CI): 0.69, 1.76). However, ever use of gonadotropins (follicle-stimulating hormone and human menopausal gonadotropin) increased uterine cancer risk (RR = 2.21, 95% CI: 1.08, 4.50); the risk was primarily observed after 10 years of follow-up. Furthermore, uterine cancer risk increased with number of cycles of use for clomiphene (for > or =6 cycles, RR = 1.96, 95% CI: 1.03, 3.72) and human chorionic gonadotropin (for > or =6 cycles, RR = 2.18, 95% CI: 1.16, 4.08) but not for other gonadotropins. Use of gonadotropin-releasing hormone analogs was not associated with risk. Gonadotropins, and possibly clomiphene and human chorionic gonadotropin, may increase the risk of uterine cancer, with higher doses and longer follow-up leading to greater risk.

Validation of the Predictive Value of Modeled Human Chorionic Gonadotrophin Residual Production in Low-Risk Gestational Trophoblastic Neoplasia Patients Treated in NRG Oncology/Gynecologic Oncology Group-174 Phase III Trial.

PubMed

You, Benoit; Deng, Wei; Hénin, Emilie; Oza, Amit; Osborne, Raymond

2016-01-01

In low-risk gestational trophoblastic neoplasia, chemotherapy effect is monitored and adjusted with serum human chorionic gonadotrophin (hCG) levels. Mathematical modeling of hCG kinetics may allow prediction of methotrexate (MTX) resistance, with production parameter "hCGres." This approach was evaluated using the GOG-174 (NRG Oncology/Gynecologic Oncology Group-174) trial database, in which weekly MTX (arm 1) was compared with dactinomycin (arm 2). Database (210 patients, including 78 with resistance) was split into 2 sets. A 126-patient training set was initially used to estimate model parameters. Patient hCG kinetics from days 7 to 45 were fit to: [hCG(time)] = hCG7 * exp(-k * time) + hCGres, where hCGres is residual hCG tumor production, hCG7 is the initial hCG level, and k is the elimination rate constant. Receiver operating characteristic (ROC) analyses defined putative hCGRes predictor of resistance. An 84-patient test set was used to assess prediction validity. The hCGres was predictive of outcome in both arms, with no impact of treatment arm on unexplained variability of kinetic parameter estimates. The best hCGres cutoffs to discriminate resistant versus sensitive patients were 7.7 and 74.0 IU/L in arms 1 and 2, respectively. By combining them, 2 predictive groups were defined (ROC area under the curve, 0.82; sensitivity, 93.8%; specificity, 70.5%). The predictive value of hCGres-based groups regarding resistance was reproducible in test set (ROC area under the curve, 0.81; sensitivity, 88.9%; specificity, 73.1%). Both hCGres and treatment arm were associated with resistance by logistic regression analysis. The early predictive value of the modeled kinetic parameter hCGres regarding resistance seems promising in the GOG-174 study. This is the second positive evaluation of this approach. Prospective validation is warranted.

Effect of recombinant human follicle-stimulating hormone and luteinizing hormone on in vitro maturation of porcine oocytes evaluated by the subsequent in vitro development of embryos obtained by in vitro fertilization, intracytoplasmic sperm injection, or parthenogenetic activation.

PubMed

Silvestre, M A; Alfonso, J; García-Mengual, E; Salvador, I; Duque, C C; Molina, I

2007-05-01

The aim of this work was to study the effect of recombinant human (rh) FSH and LH on in vitro maturation of pig oocytes compared with a conventional hormonal supplement based on equine (PMSG) and human chorionic gonadotropins (hCG), as evaluated by the developmental ability of 3 types of pig embryos obtained by in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), or artificial activation (ATA). In Exp. 1, one cumulus-oocyte complex group (A group) was supplemented with rh-FSH and rh-LH (0.1 IU/mL each), and the other group (B group) was supplemented with PMSG and hCG (10 IU/mL each). No differences in nuclear maturation between the A and B groups were observed (68.5 vs. 71.4%, respectively). No differences were detected between hormonal treatments in the rates of cleavage or blastocyst formation of ATA, IVF, and ICSI embryos. Total cell number of the embryos was not significantly different in any experimental group (A: 31.1, 28.5, and 19.8 vs. B: 25.2, 25.5, and 20.6 for ATA, IVF, and ICSI embryos, respectively). In Exp. 2, the effects of different concentrations of rh-FSH and rh-LH (0.5, 0.1, or 0.05 IU/mL) in maturation medium on nuclear maturation and in vitro development of embryos obtained by IVF were studied. No effect of different hormonal concentrations on blastocyst formation rates was observed (8.5, 13.0, and 5.7%, respectively). Blastocyst cell number was not different in any experimental group. In conclusion, the results obtained here permit us to substitute PMSG and hCG with rh-FSH and rh-LH and to produce pig embryos obtained by IVF, ICSI, or ATA.

Hormone-induced 14-3-3γ Adaptor Protein Regulates Steroidogenic Acute Regulatory Protein Activity and Steroid Biosynthesis in MA-10 Leydig Cells*

PubMed Central

Aghazadeh, Yasaman; Rone, Malena B.; Blonder, Josip; Ye, Xiaoying; Veenstra, Timothy D.; Hales, D. Buck; Culty, Martine; Papadopoulos, Vassilios

2012-01-01

Cholesterol is the sole precursor of steroid hormones in the body. The import of cholesterol to the inner mitochondrial membrane, the rate-limiting step in steroid biosynthesis, relies on the formation of a protein complex that assembles at the outer mitochondrial membrane called the transduceosome. The transduceosome contains several mitochondrial and cytosolic components, including the steroidogenic acute regulatory protein (STAR). Human chorionic gonadotropin (hCG) induces de novo synthesis of STAR, a process shown to parallel maximal steroid production. In the hCG-dependent steroidogenic MA-10 mouse Leydig cell line, the 14-3-3γ protein was identified in native mitochondrial complexes by mass spectrometry and immunoblotting, and its levels increased in response to hCG treatment. The 14-3-3 proteins bind and regulate the activity of many proteins, acting via target protein activation, modification and localization. In MA-10 cells, cAMP induces 14-3-3γ expression parallel to STAR expression. Silencing of 14-3-3γ expression potentiates hormone-induced steroidogenesis. Binding motifs of 14-3-3γ were identified in components of the transduceosome, including STAR. Immunoprecipitation studies demonstrate a hormone-dependent interaction between 14-3-3γ and STAR that coincides with reduced 14-3-3γ homodimerization. The binding site of 14-3-3γ on STAR was identified to be Ser-194 in the STAR-related sterol binding lipid transfer (START) domain, the site phosphorylated in response to hCG. Taken together, these results demonstrate that 14-3-3γ negatively regulates steroidogenesis by binding to Ser-194 of STAR, thus keeping STAR in an unfolded state, unable to induce maximal steroidogenesis. Over time 14-3-3γ homodimerizes and dissociates from STAR, allowing this protein to induce maximal mitochondrial steroid formation. PMID:22427666

Purification and characterization of the glycoprotein hormone. cap alpha. -subunit-like material secreted by HeLa cells

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

Cox, G.S.; Rimerman, R.A.

1988-08-23

The protein secreted by HeLa cells that cross-reacts with antiserum developed against the ..cap alpha..-subunit of human chorionic gonadotropin (hCG) has been purified approximately 30,000-fold from concentrated culture medium by organic solvent fractionation followed by ion exchange, gel filtration, and lectin affinity chromatography. The final preparation had a specific activity (by RIA) of 6.8 x 10/sup 5/ ng of ..cap alpha../mg of protein and appeared homogeneous by electrophoresis on reducing/denaturing polyacrylamide gels (SDS-PAGE). Amino acid analysis indicated that HeLa-..cap alpha.. had a composition very similar to that of the urinary hCG ..cap alpha..-subunit. However, comparison of hCG-..cap alpha.. and HeLa-..capmore » alpha.. demonstrated that the tumor-associated subunit was not identical with its normal counterpart. The purified tumor protein had an apparent molecular weight greater than that of the urinary ..cap alpha..-subunit when analyzed by SDS-PAGE, and this difference was even greater when a partially purified preparation was examined by an immunoblot technique (Western). Isoelectric focusing of the HeLa and hCG subunits demonstrated that the tumor protein had a lower pI. Immunoprecipitation and electrophoresis of ..cap alpha..-subunit from HeLa cultures labeled with (/sup 3/H)fucose indicated that the tumor subunit was fucosylated, whereas analysis of hCG-..cap alpha.. hydrosylates by HPLC confirmed previous reports that the placental subunit does not contain fucose. The results indicate that, regardless of whether or not a single ..cap alpha..-subunit gene is being expressed in both normal and neoplastic tissues, posttranslational modifications lead to a highly altered subunit in the tumor. The differences observed may be useful in diagnosing neoplastic vs hyperplastic conditions and may lend insight into the mechanism of ectopic hormone production by tumors.« less

Predictive value of modeled AUC(AFP-hCG), a dynamic kinetic parameter characterizing serum tumor marker decline in patients with nonseminomatous germ cell tumor.

PubMed

You, Benoit; Fronton, Ludivine; Boyle, Helen; Droz, Jean-Pierre; Girard, Pascal; Tranchand, Brigitte; Ribba, Benjamin; Tod, Michel; Chabaud, Sylvie; Coquelin, Henri; Fléchon, Aude

2010-08-01

The early decline profile of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) in patients with nonseminomatous germ cell tumors (NSGCT) treated with chemotherapy may be related to the risk of relapse. We assessed the predictive values of areas under the curve of hCG (AUC(hCG)) and AFP (AUC(AFP)) of modeled concentration-time equations on progression-free survival (PFS). Single-center retrospective analysis of hCG and AFP time-points from 65 patients with IGCCCG intermediate-poor risk NSGCT treated with 4 cycles of bleomycin-etoposide-cisplatin (BEP). To determine AUC(hCG) and AUC(AFP) for D0-D42, AUCs for D0-D7 were calculated using the trapezoid rule and AUCs for D7-D42 were calculated using the mathematic integrals of equations modeled with NONMEM. Combining AUC(AFP) and AUC(hCG) enabled us to define 2 predictive groups: namely, patients with favorable and unfavorable AUC(AFP-hCG). Survival analyses and ROC curves assessed the predictive values of AUC(AFP-hCG) groups regarding progression-free survival (PFS) and compared them with those of half-life (HL) and time-to-normalization (TTN). Mono-exponential models best fit the patterns of marker decreases. Patients with a favorable AUC(AFP-hCG) had a significantly better PFS (100% vs 71.5%, P = .014). ROC curves confirmed the encouraging predictive accuracy of AUC(AFP-hCG) against HL or TTN regarding progression risk (ROC AUCs = 79.6 vs 71.9 and 70.2 respectively). Because of the large number of patients with missing data, multivariate analysis could not be performed. AUC(AFP-hCG) is a dynamic parameter characterizing tumor marker decline in patients with NSGCT during BEP treatment. Its value as a promising predictive factor should be validated. Copyright 2010 Elsevier Inc. All rights reserved.

"Hook-like effect" causes false-negative point-of-care urine pregnancy testing in emergency patients.

PubMed

Griffey, Richard T; Trent, Caleb J; Bavolek, Rebecca A; Keeperman, Jacob B; Sampson, Christopher; Poirier, Robert F

2013-01-01

Failure to detect pregnancy in the emergency department (ED) can have important consequences. Urine human chorionic gonadotropin (uhCG) point-of-care (POC) assays are valued for rapidly detecting early pregnancy with high sensitivity. However, under certain conditions, POC uhCG tests can fail to detect pregnancy. In investigating a series of late first-trimester false-negative pregnancy tests in our ED, a novel and distinct causative phenomenon was recently elucidated in our institution. We discuss uhCG POC tests, review our false-negative rate, and describe mechanisms for false negatives and potential remedies. The false-negative POC uhCG rate is very low, but in the setting of a large volume of tests, the numbers are worth consideration. In positive uhCG POC tests, free and fixed antibodies bind hCG to form a "sandwich"; hCG is present in several variant forms that change in their concentrations at different stages of pregnancy. When in excess, intact hCG can saturate the antibodies, preventing sandwich formation (hook effect phenomenon). Some assays may include an antibody that does not recognize certain variants present in later stages of pregnancy. When this variant is in excess, it can bind one antibody avidly and the other not at all, resulting in a false-negative test (hook-like phenomenon). In both situations, dilution is key to an accurate test. Manufacturers should consider that uhCG tests are routinely used at many stages of pregnancy. Characterizing uhCG variants recognized by their tests and eliminating lot-to-lot variability may help improve uhCG test performance. Clinicians need to be aware of and familiarize themselves with the limitations of the specific type of uhCG POC tests used in their practice, recognizing that under certain circumstances, false-negative tests can occur. Copyright © 2013 Elsevier Inc. All rights reserved.

Selection of tumor antigens as targets for immune attack using immunohistochemistry: protein antigens.

PubMed

Zhang, S; Zhang, H S; Cordon-Cardo, C; Ragupathi, G; Livingston, P O

1998-11-01

The relative expression of mucin antigens MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC7 and glycoprotein antigens KSA, carcinoembryonic antigen, prostate-specific membrane antigen (PSMA), HER-2/neu, and human chorionic gonadotropin-beta on different cancers and normal tissues is difficult to determine from available reports. We have compared the distribution of these antigens by immunohistology on a broad range of malignant and normal tissues. MUC1 expression was most intense in cancers of breast, lung, ovarian, and endometrial origin; MUC2 was most intense in cancers of colon and prostate origin; and MUC5AC was most intense in cancers of breast and gastric origin. MUC4 was intensely expressed in 50% of cancers of colon and pancreas origin, and MUC3, MUC5B, and MUC7 were expressed in a variety of epithelial cancers, but not so intensely. KSA was intensely and uniformly expressed on all epithelial cancers; carcinoembryonic antigen was expressed in most cancers of breast, lung, colon, pancreas, and gastric origin; and PSMA was expressed only in cancers of prostate origin. Human chorionic gonadotropin-beta was expressed on the majority of sarcomas and cancers of breast, lung, and pancreas origin, although intense staining was not seen. Staining on normal tissues was restricted to one or many normal epithelial tissues ranging from MUC3, MUC4, and PSMA, which were expressed only on epithelia of pancreas, stomach, and prostate origin, respectively, to MUC1 and KSA, which were expressed on most normal epithelia. Expression was restricted to the secretory borders of these epithelia while stroma and other normal tissues were completely negative. These results plus the results of the two previous papers (S. Zhang et al, Int. J. Cancer, 73: 42-49, 1997; S. Zhang et al., Int. J. Cancer, 73: 50-56, 1997) in this series provide the basis for selection of multiple cell surface antigens as targets for antibody-mediated attack against these cancers.

Methotrexate-treated ectopic pregnancy: beta human chorionic gonadotropin serum changes as a success predictor using a mathematical model validation.

PubMed

Kovaleva, Aleksandra; Irishina, Natalia; Pereira, Augusto; Cuesta-Guardiola, Tatiana; Ortiz-Quintana, Luis

2017-03-01

Surgical rescue of methotrexate-treated ectopic pregnancy is necessary when tubal rupture or medical therapy failure is detected during post-therapeutic monitoring. It is known that an increased beta human chorionic gonadotropin (β-hCG) concentration is the most important factor associated with treatment failure. Therefore, we suggested that relative changes in serum β-hCG could predict a successful result of medical treatment, leading to facilitation of the decision to forgo the prospect of possible surgical rescue. A retrospective observational study of 115 patients with an ectopic pregnancy who were treated with a single dosage protocol of 50mg/m 2 of methotrexate injected intramuscularly was performed at Puerta de Hierro University Hospital and Gregorio Marañón University General Hospital. Standard statistical tests were applied in order to evaluate the relative changes in β-hCG concentration between the 1st and the 4th days following methotrexate injection. Methotrexate treatment has a 95% probability to be successful if the relative change of β-hCG from the 1st to the 4th day of monitoring is within the following interval: [-1.02; 0.15]. Moreover, if the values of β-hCG-relative change from 1st to 4th day of monitoring are within [0.54; 1.2], it assures a negative result of treatment with 95% probability. Therefore, the value 0.15 (15%) of β-hCG relative change can be considered a cut-off value for a positive result to treatment. Our data support that negative β-hCG relative changes on the 4th day of treatment likely predict a successful result of methotrexate therapy, with a cut-off point of 0.15. Expectant management should be carried out in these cases if no clinical indications of surgery are presented. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sex steroid levels, oocyte maturation and spawning performance in Waigieu seaperch (Psammoperca waigiensis) exposed to thyroxin, human chorionic gonadotropin, luteinizing hormone releasing hormone and carp pituitary extract.

PubMed

Pham, Hung Quoc; Nguyen, Anh Tuong; Nguyen, Mao Dinh; Arukwe, Augustine

2010-02-01

In the present study, we have investigated the sex steroid hormone levels, oocyte maturation and spawning performance in Waigieu seaperch (Psammoperca waigiensis) exposed to different doses (0, (control), 0.05, 0.25 and 0.5 mg/kg fish) of thyroxin (T(4)) both through diet (continuously) and injection (single injection). In addition, we also studied plasma steroid hormone levels and spawning performances in female fish injected with a single dose of D-Ala(6), Pro(9)-Net-mGnRH (LHRHa: 50 microg/kg), human chronic gonadotropin (HCG: 1,500 IU/kg) and carp pituitary extract (CPE: 10 mg/kg). In all experiments, samples were collected at 0, 6, 12, 24 and 48 h after exposure. T4 exposure via dietary route produced differential and enhanced effects, compared with when the compound was injected to the broodstock. A significant association between exposure to dietary T4, elevated plasma steroid hormone levels, maturation-, spawning-, fertilization- and hatching rate, egg diameter, embryogenesis and larval growth were observed. Interestingly, we observed that broodstock groups fed with T4 doses spawned 20 days earlier than the control group. Thus, we propose that these differences may be attributed to higher systemic availability of T4 due to dietary exposure that is easily transferable to eggs and embryos, as opposed to injection that require absorption to increase bioavailability. Furthermore, our results show that LHRHa, CPE and HCG produced significant increase in spawning rate, but significantly reduced fertilization- and hatching rates. Waigieu seaperch is a new candidate for marine aquaculture in Vietnam and relatively little is known about the reproductive biology and endocrinology of this species. Therefore, the present study forms an integral basis for understanding the reproductive endocrinology of a tropical marine finfish with increasing aquaculture prospects and may also contribute in the development of sustainable aquaculture of this species in a developing country such as Vietnam. 2009 Elsevier Inc. All rights reserved.

Impact of preoperative hormonal stimulation on postoperative complication rates after hypospadias repair: a meta-analysis.

PubMed

Chao, Min; Zhang, Yin; Liang, Chaozhao

2017-06-01

To improve the surgical outcome of hypospadias repair surgery, preoperative hormonal stimulation (PHS) has been proposed. We conducted a meta-analysis to evaluate the impact of preoperative hormonal stimulation (PHS) treatment on complication rates following hypospadias repair surgery. A comprehensive literature search up to June 1st, 2015 was carried out for relevant studies. After literature identification and data extraction, relative ratio (RR) was calculated to compare postoperative complication rates. Heterogeneity among individual studies was tested using the Cochran χ2 Q test and quantified by calculating the I2 index. Meta-regression was applied to find potential affective factors. Overall, 428 patients from 6 studies had undergone primary hypospadias repair, of which 171 (39.95%) received some form of PHS with human chorionic gonadotropin (HCG), dihydrotestosterone (DHT) or testosterone (T). They underwent three different types of surgical techniques, including onlay island flap (N.=277), tubularized incised plate (N.=99) and Koyanagi urethroplasty (N.=52). These 6 studies classified the complication rates based on PHS. The relative ratio (RR) for a complication occurring following PHS use was 1.18 (95% CI: 0.70-2.00, Z=0.91, P=0.539). Significant heterogeneity (I2=47.1%, P=0.092) among various research literature was found and meta-regression was undertaken for the heterogeneity, but surgical technique, mean age of patients at time of surgery, types of PHS and the quality of studies were not the cause of heterogeneity. Use of T, DHT and HCG prior to hypospadias repair does not appear to increase the incidence of postoperative complications, but further investigation is needed.

Endometrial thickness affects the outcome of in vitro fertilization and embryo transfer in normal responders after GnRH antagonist administration.

PubMed

Wu, Yu; Gao, Xiaohong; Lu, Xiang; Xi, Ji; Jiang, Shan; Sun, Yin; Xi, Xiaowei

2014-10-09

The goal of this study was to assess the association between endometrial thickness on the chorionic gonadotropin (hCG) day and in vitro fertilization and embryo transfer (IVF-ET) outcome in normal responders after GnRH antagonist administration. A retrospective cohort study was performed in normal responders with GnRH antagonist administration from January 2011-December 2013. Patients were divided into four groups according to endometrial thickness, as follows: <7 mm (group 1), > = 7- < 8 mm (group 2), > = 8- < 14 mm (group 3), and > =14 mm (group 4). A total of 2106 embryo transfer cycles were analyzed. The pregnancy rate (PR) was 44.87%.The clinical pregnancy rate, ongoing pregnancy rate and the implantation rate (17.28%, 13.79%, 10.17%, respectively) were significantly lower in group 1 compared to the other three groups (p < 0.05). The miscarriage rate was higher in patients with endometrial thickness less than 7 mm. The clinical pregnancy rate, ongoing pregnancy rate and implantation rate were highest in patients with endometrial thickness higher than 14 mm, but showed no difference in patients with those of endometrial thickness between 8-14 mm. There is a correlation between endometrial thickness measured on hCG day and clinical outcome in normal responders with GnRH antagonist administration. The pregnancy rate was lower in patients with endometrial thickness less than 7 mm compared with patients with endometrial thickness more than 7 mm.

Effect of triptolide on progesterone production from cultured rat granulosa cells.

PubMed

Zhang, J; Jiang, Z; Mu, X; Wen, J; Su, Y; Zhang, L

2012-06-01

Triptolide(CAS 38748-32-2), a major active component of Tripterygium wilfordii Hook F (TWHF), is known to have multiple pharmacological activities. However, studies have also shown that triptolide is highly disrupt to the reproductive system by disrupting normal steroid hormone signaling. In the present study, we investigated the effect of triptolide (5, 10, or 20 nM for 24 h) on progesterone production by rat granulosa cells. Triptolide inhibited both basal and human chorionic gonadotropin (HCG)- and 8-bromo-cAMP-stimulated progesterone production as revealed by RIA assay. Furthermore, the HCG-evoked increase in cellular cAMP content was also inhibited by triptolide, indicating that disruption of the cAMP/PKA signaling pathway may mediate the deleterious effects of triptolide on progesterone regulation. In addition, triptolide inhibited 25-OH-cholesterol-stimulated progesterone production, suggesting that activity of the P450 side chain cleavage (P450scc) enzyme was also be inhibited by triptolide. Western blot and quantitative real-time PCR (qRT-PCR) assays further revealed that triptolide decreased mRNA and protein expression of P450scc and the steroidogenic regulatory (StAR) protein in granulosa cells. In contrast, cell viability tests using 3-(4,5-dimethyl-thiazol-2-yl)-2,5- diphenyl-tetrazolium bromide (MTT) indicated that triptolide did not cause measurable cell death at doses that suppressed steroidogenesis. The reproductive toxicity of triptolide may be caused by disruption of cAMP/PKA-mediated expression of a number of progesterone synthesis enzymes or regulatory proteins, leading to reduced progesterone synthesis and reproductive dysfunction. © Georg Thieme Verlag KG Stuttgart · New York.

Effects of human chorionic gonadotropin combined with clomiphene on Serum E2, FSH, LH and PRL levels in patients with polycystic ovarian syndrome.

PubMed

Yonggang, Huang; Xiaosheng, Lu; Zhaoxia, Huang; Yilu, Chen; Jiqiang, Lv; Huina, Zhang

2017-02-01

Effects of human chorionic gonadotropin combined with clomiphene on serum E 2 , FSH, LH and PRL levels in patients with polycystic ovarian syndrome were analyzed. 90 patients with polycystic ovarian syndrome treated from January 2015 to March 2016 were randomly and evenly divided into control group and observation group. Patients in the control group were only treated with clomiphene. On the basis of the treatment in control group, human chorionic gonadotropin was added in the treatment of observation group. The changes of E 2 , FSH, LH, PRL levels were compared between two groups before and after the treatment. Clinical curative effects of patients in the two groups was evaluated. Adverse reactions during treatment in two groups were observed and recorded. The incidence of adverse reactions was calculated. Serum E 2 , FSH, LH and PRL levels in the two groups decreased significantly after treatment compared with that before treatment. The difference is statistical significant ( P  < 0.05). After the treatment, E 2 , FSH, LH and PRL levels in the observation group were lower than that in the control group and the difference is statistical significant ( P  < 0.05). Total effective rate was 64.44% in the control group and 93.33% in the observation group. There were statistically significant difference in clinical curative effects in the two groups ( P  < 0.05). Different degrees of adverse reactions were found in both groups during treatment, such as nausea, vomiting, anorexia, liver dysfunction. There were 2 cases of nausea, 2 cases of vomiting, 3 cases of anorexia and 1 case of liver dysfunction from the 45 patients in control group. The total incidence of adverse reactions was 17.78% (8/45). There were 1 case of nausea, 1 case of vomiting, 1 case of anorexia and no liver dysfunction from the 45 patients in observation group. The total incidence of adverse reactions was 6.67% (3/45). The total incidence of adverse reactions in the observation group was significantly higher than that in the control group and the difference was not statistically significant ( P  > 0.05). Combined use of human chorionic gonadotropin can significantly reduce serum E 2 , FSH, LH and PRL levels, improve clinical curative effects and reduce the incidence of adverse reactions. Human chorionic gonadotropin has high application value on the treatment of polycystic ovary syndrome.

Effects of melengestrol acetate and P.G. 600 on fertility in Rambouillet ewes outside the natural breeding season.

PubMed

Windorski, E J; Schauer, C S; Wurst, A K; Inskeep, E K; Luther, J S

2008-07-15

The effects of melengestrol acetate (MGA) and P.G. 600 on ewe fertility outside the natural breeding season were evaluated. Rambouillet ewes were assigned to one of four groups: (1) control (C; n=92); (2) PG600 (n=86); (3) MGA (n=99); and (4) MGA+PG600 (n=92). A pellet with or without MGA (0.3mg/ewe/d) was fed at 0.15kg/ewe/d for 7d. On the last day of pellet feeding, ewes were given either saline or 5mL of P.G. 600 i.m. (400IU equine chorionic gonadotropin (eCG) and 200IU human chorionic gonadotropin (hCG)). Ultrasonography was performed between Days 20 and 25 of gestation for ewes that were mated during the first 6 d of the breeding period from the MGA (n=15) and MGA+PG600 (n=8) groups, and the number of luteal structures and embryos were counted. During the first 6d of the breeding period, MGA increased (P<0.05) the percentage of ewes that mated and conceived when compared to C and PG600 (24.2% vs. 3.3% and 10.5%, respectively). Relative to MGA, the mean (+/-S.E.M.) number of luteal structures per ewe was enhanced (P<0.03) in MGA+PG600 (1.53+/-0.13 vs. 2.38+/-0.42, respectively), however as pregnancy progressed, the number of embryos (1.5+/-0.13 vs. 1.8+/-0.16, respectively) and lambs born (1.3+/-0.15 vs. 1.5+/-0.27, respectively) did not differ. Treatment with MGA reduced (P<0.01) the interval from ram introduction to lambing relative to groups that did not receive MGA (168+/-0.8d vs. 171+/-0.6d, respectively). In conclusion, treatment with MGA increased the percentage of ewes conceiving early in the breeding period. Although P.G. 600 increased the number of luteal structures present per ewe, it did not significantly enhance ewe prolificacy.

Elevated β-hCG associated with aggressive Osteoblastoma.

PubMed

Morris, Carol D; Hameed, Meera R; Agaram, Narasimhan P; Hwang, Sinchun

2017-09-01

We present a unique case of an aggressive scapular osteoblastoma that produced β-hCG as a paraneoplastic manifestation in a 20-year-old woman. Serum β-hCG was found to be elevated during presurgical workup and consequently delayed surgical resection of the increasingly painful tumor because of suspected pregnancy. The paraneoplastic production of β-hCG was later proven by positive immunohistochemical stain of β-hCG in a curettage specimen and normalization of β-hCG levels after surgical resection of the aggressive osteoblastoma. Production of beta-human chorionic gonadotropin (β-hCG) has been reported in several carcinomas and sarcomas but, to our knowledge, it has not been reported in osteoblastoma in the English-language literature.

High oestradiol concentration after ovarian stimulation is associated with lower maternal serum beta-HCG concentration and neonatal birth weight.

PubMed

Liu, Suying; Kuang, Yanping; Wu, Yu; Feng, Yun; Lyu, Qifeng; Wang, Li; Sun, Yijuan; Sun, Xiaoxi

2017-08-01

In this retrospective study, the relationship between maternal serum oestradiol and progesterone levels after fresh embryo transfer or frozen embryo transfer (FET), and serum beta-HCG levels in early pregnancy and neonatal birth weight was examined. Included for analysis were 5643 conceived singletons: 2610 after FET and 3033 after fresh embryo transfer. Outcome measures included maternal serum oestradiol, progesterone, beta-HCG levels during the peri-implantation period, birth weight and small-for-gestational-age (SGA). Results at 4, 5 and 6 weeks' gestation were as follows: serum oestradiol and progesterone levels were significantly higher in women who underwent fresh embryo transfer compared with FET (all P < 0.0001 except progesterone at 6 weeks; P = 0.009); for fresh embryo transfers, serum beta-HCG levels were significantly lower than in women who underwent FET (P < 0.0001); beta-HCG levels were negatively correlated with serum oestradiol; and birth weight was negatively correlated with serum oestradiol. Incidence of SGA in fresh embryo transfer was increased significantly compared with FET (P < 0.001). Higher maternal oestradiol levels after fresh embryo transfer was correlated with lower beta-HCG in early pregnancy, lower birth weight and higher incidence of SGA. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Biological functions of hCG and hCG-related molecules

PubMed Central

2010-01-01

Background hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary. Results and discussion hCG has numerous functions. hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle. PMID:20735820

Validation of Electrochemiluminiscence Immunoassay for Ovarian Steroid Determination in Rhinella arenarum.

PubMed

Arias Torres, Ana Josefina; Páez, José Bernardino; Zelarayán, Liliana Isabel

2016-04-01

In this work, we describe the validation of an electrochemiluminescence immunoassay (ECLIA) that allowed us for the first time to determine the levels of progesterone (P4 ) and testosterone (T) secreted by Rhinella arenarum follicles during the preovulatory (POP) and reproductive (RP) periods. We also verified the relation between P4 and T levels and oocyte maturation. Moreover, we demonstrated that the extraction protocol developed for the determinations of P4 and T by ECLIA proved to be efficient and reproducible since the efficacy of the extraction was above 95% in all assays conducted. The results indicate that in the validation process the variation coefficient (CV) between assays is compatible with the analytical procedures based on automated immunoassays (CV < 8%) and that the adaptation proposed for the samples allows the determination of T and P4 with the Cobas e-411 analyzer. Our results indicate that in basal conditions the levels of T released by R. arenarum follicles were higher than those of P4 during POP and RP. In these conditions, steroid secretion failed to induce germinal vesicle break down (GVBD) in the follicles. Under gonadotropin stimulation, steroidogenesis showed a remarkable increase in both periods, especially during POP. This increase was correlated with a high maturation percentage in the follicles incubated in vitro (GVBD = 72 ± 16%) during POP. During RP, human Chorionic Gonadotropin (hCG) induced 81.75 ± 9.1% GVBD. This study is the first report of the seasonal steroidogenic activity in the ovary of R. arenarum in situ using an ECLIA-modified protocol developed in our laboratory. © 2016 Wiley Periodicals, Inc.

Gonadotropin-Dependent Precocious Puberty: Neoplastic Causes and Endocrine Considerations

PubMed Central

2011-01-01

Premature activation of the hypothalamic-pituitary-gonadal (HPG) axis manifests as gonadotropin-dependent precocious puberty. The mechanisms behind HPG activation are complex and a clear etiology for early activation is often not elucidated. Though collectively uncommon, the neoplastic and developmental causes of gonadotropin-dependent precocious puberty are very important to consider, as a delay in diagnosis may lead to adverse patient outcomes. The intent of the current paper is to review the neoplastic and developmental causes of gonadotropin-dependent precocious puberty. We discuss the common CNS lesions and human chorionic gonadotropin-secreting tumors that cause sexual precocity, review the relationship between therapeutic radiation and gonadotropin-dependent precocious puberty, and finally, provide an overview of the therapies available for height preservation in this unique patient population. PMID:21603196

Microdevice for plasma separation from whole human blood using bio-physical and geometrical effects

NASA Astrophysics Data System (ADS)

Tripathi, Siddhartha; Kumar, Y. V. Balavarun; Agrawal, Amit; Prabhakar, Amit; Joshi, Suhas S.

2016-06-01

In this research work, we present a simple and efficient passive microfluidic device for plasma separation from pure blood. The microdevice has been fabricated using conventional photolithography technique on a single layer of polydimethylsiloxane, and has been extensively tested on whole blood and enhanced (upto 62%) hematocrit levels of human blood. The microdevice employs elevated dimensions of about 100 μm such elevated dimensions ensure clog-free operation of the microdevice and is relatively easy to fabricate. We show that our microdevice achieves almost 100% separation efficiency on undiluted blood in the flow rate range of 0.3 to 0.5 ml/min. Detailed biological characterization of the plasma obtained from the microdevice is carried out by testing: proteins by ultra-violet spectrophotometric method, hCG (human chorionic gonadotropin) hormone, and conducting random blood glucose test. Additionally, flow cytometry study has also been carried on the separated plasma. These tests attest to the high quality of plasma recovered. The microdevice developed in this work is an outcome of extensive experimental research on understanding the flow behavior and separation phenomenon of blood in microchannels. The microdevice is compact, economical and effective, and is particularly suited in continuous flow operations.

A longitudinal study of the control of renal and uterine hemodynamic changes of pregnancy.

PubMed

Ogueh, Onome; Clough, Angela; Hancock, Maggie; Johnson, Mark R

2011-01-01

We have determined the sequence and extent of maternal renal and uterine adaptation to pregnancy and examined the role of hormonal factors in their regulation. Renal bipolar diameter (RBD), renal artery resistance index (RARI), uterine artery pulsatility index (UAPI), and plasma relaxin, human chorionic gonadotropin (hCG), progesterone, estradiol, urea, and creatinine were measured longitudinally in women with normal spontaneous singleton pregnancies, in vitro fertilization (IVF) singleton pregnancies, ovum donation (OD) singleton pregnancies, and multiple pregnancies from prepregnancy to postpartum. There was a progressive increase in the RBD and the RARI and a decrease in the UAPI during pregnancy. These changes reversed toward prepregnancy levels by 6 weeks post delivery. There was no difference in the rate of change of RBD, RARI, and UAPI between spontaneous singleton, IVF singleton, OD singleton, and multiple pregnancies (p < 0.05), but relaxin was directly correlated to the RARI (r = 0.654, p = 0.015), and progesterone was inversely correlated to uterine artery PI (r = 0.554, p = 0.049). These data show that renal size and resistance to blood flow increase with advancing gestation, whereas the uterine artery resistance declined with gestation. These changes may be influenced by relaxin and progesterone.

Amphiregulin mediates hCG-induced StAR expression and progesterone production in human granulosa cells.

PubMed

Fang, Lanlan; Yu, Yiping; Zhang, Ruizhe; He, Jingyan; Sun, Ying-Pu

2016-04-26

Progesterone plays critical roles in maintaining a successful pregnancy at the early embryonic stage. Human chorionic gonadotropin (hCG) rapidly induces amphiregulin (AREG) expression. However, it remains unknown whether AREG mediates hCG-induced progesterone production. Thus, the objective of this study was to investigate the role of AREG in hCG-induced progesterone production and the underlying molecular mechanism in human granulosa cells; primary cells were used as the experimental model. We demonstrated that the inhibition of EGFR and the knockdown of AREG abolished hCG-induced steroidogenic acute regulatory protein (StAR) expression and progesterone production. Importantly, follicular fluid AREG levels were positively correlated with progesterone levels in the follicular fluid and serum. Treatment with AREG increased StAR expression and progesterone production, and these stimulatory effects were abolished by EGFR inhibition. Moreover, activation of ERK1/2, but not PI3K/Akt, signaling was required for the AREG-induced up-regulation of StAR expression and progesterone production. Our results demonstrate that AREG mediates hCG-induced StAR expression and progesterone production in human granulosa cells, providing novel evidence for the role of AREG in the regulation of steroidogenesis.

Differential sensitivity of mouse oocytes to colchicine-induced aneuploidy

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

Mailhes, J.B.; Yuan, Z.P.

1987-01-01

Unpublished results from our laboratory showed that colchicine increased the incidence of hyperploid mouse metaphase II (MII) oocytes when injected at the same time as human chorionic gonadotrophin (HCG). The objective of the present study was to determine whether the time of administering colchicine influenced the incidence of aneuploidy in MII oocytes. CD-1 mice were given pregnant mare's serum (PMS) and, 48 hr later, HCG. An intraperitoneal injection of 0.2 mg/kg colchicine was given at +4, +2, 0, -2, or -4 hr relative to HCG. Oocytes were collected 17 hr post-HCG and processed, and chromosomes were subsequently C-banded. The percentagemore » of hyperploid oocytes was 0.77, 2.56, 5.71, 7.79, 3.54, and 2.70 for control, +4, +2, 0, -2, or -4 hr pre/post-HCG, respectively. Chi-square analyses of these data demonstrated that colchicine significantly increases the proportion of aneuploid oocytes, and that the relative sensitivity of colchicine-induced aneuploidy depends upon the time that this drug is administered relative to HCG.« less

Convenient radioimmunoassay for urinary human choriogonadotropin without interference by urinary human lutropin

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

Wehmann, R.E.; Harman, S.M.; Birken, S.

1981-12-01

We have devised a radioimmunoassay (RIA) for human choriogonadotropin (hCG) in first morning-voided urine specimens. Concanavalin A, a lectin, is used to extract and concentrate the hCG from urine. A high-affinity antiserum is used, directed to the hCG..beta.. carboxy-terminal peptide, a unique immunological determinant not shared by the beta subunit of human lutropin. This ensures that urinary human lutropin-related molecules, which interfere with RIAs involving antisera to the intact hCG..beta.. subunit, will not cross react in this assay. A concentration of hCG as low as 0.4 ..mu..g/L can be detected in the first morning-voided urine. The effective sensitivity of thismore » assay for the unequivocal detection of hCG production is somewhat better than that achieved with the serum hCG RIA involving antisera to the hCG..beta.. subunit. The improved specificity and sensitivity of this assay, and the greater convenience of collecting samples of urine rather than blood, are clinically useful advantages of this approach to assessing hCG production in humans.« less

Topographic antigenic determinants recognized by monoclonal antibodies on human choriogonadotropin beta-subunit

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

Bidart, J.M.; Troalen, F.; Salesse, R.

1987-06-25

We describe a first attempt to study the antibody-combining sites recognized by monoclonal antibodies raised against the beta-subunit of human choriogonadotropin (hCG). Two groups of antibodies were first defined by their ability to recognize only the free beta-subunit or the free and combined subunit. Antibodies FBT-11 and FBT-11-L bind only to hCG beta-subunit but not to hCG, whereas antibodies FBT-10 and D1E8 bind to both the beta-subunit and the hormone. In both cases, the antigenic determinants were localized to the core of the protein (residues 1-112), indicating the weak immunogenicity of the specific carboxyl-terminal extension of hCG-beta. Nine synthetic peptidesmore » spanning different regions of hCG-beta and lutropin-beta were assessed for their capacity to inhibit antibody binding. A synthetic peptide inclusive of the NH2-terminal region (residues 1-7) of the hCG beta-subunit was found to inhibit binding to the radiolabeled subunit of a monoclonal antibody specific for free hCG-beta (FBT-11). Further delineation of the antigenic site recognized by this antibody provided evidence for the involvement of fragment 82-92. Moreover, monoclonal antibody FBT-11 inhibited the recombination of hCG-beta to hCG-alpha, indicating that its antigenic determinant might be located nearby or in the hCG-beta portion interacting with the alpha-subunit. Binding of monoclonal antibody FBT-10, corresponding to the second antigenic determinant, was weakly inhibited by fragment 82-105 and did not impair the recombination of the hCG beta-subunit to the hCG alpha-subunit. Its combining site appeared to be located in a region of the intact native choriogonadotropin present at the surface of the hormone-receptor complex.« less

Hyperthyroidism and human chorionic gonadotrophin production in gestational trophoblastic disease

PubMed Central

Walkington, L; Webster, J; Hancock, B W; Everard, J; Coleman, R E

2011-01-01

Background: Gestational trophoblastic disease (GTD) is a rare complication of pregnancy, ranging from molar pregnancy to choriocarcinoma. Patients with persistent disease require treatment with chemotherapy. For the vast majority, prognosis is excellent. Occasionally, GTD is complicated by hyperthyroidism, which may require treatment. This is thought to occur due to molecular mimicry between human chorionic gonadotrophin (HCG) and thyroid-stimulating hormone (TSH), and hence cross-reactivity with the TSH receptor. Hyperthyroidism usually resolves as the GTD is successfully treated and correspondingly HCG levels normalise. Methods: This paper reviews cases of GTD treated over a 5-year period at one of the three UK centres and identifies the prevalence of hyperthyroidism in this population. Four cases with clinical hyperthyroidism are discussed. Results: On review of the 196 patients with gestational trophoblastic neoplasia treated with chemotherapy in Sheffield since 2005, 14 (7%) had biochemical hyperthyroidism. Of these, four had evidence of clinical hyperthyroidism. Conclusion: Concomitant biochemical thyroid disease in patients with GTD is relatively common, and measurement of thyroid function in patients with persistent GTD is, therefore, important. The development of hyperthyroidism is largely influenced by the level of HCG and disease burden, and usually settles with treatment of the persistent GTD. However, rarely the thyroid stimulation can have potentially life-threatening consequences. PMID:21522146

A Case of Nongerminomatous Germ Cell Tumor of the Pineal Region: Risks and Advantages of Biopsy by Endoscopic Approach

PubMed Central

Mancini, Fabrizio; Gladi, Maurizio; Scerrati, Massimo

2018-01-01

A 21-year-old male was admitted to our department with headache and drowsiness. CT scan and MRI revealed acute obstructive hydrocephalus caused by a pineal region mass. The serum and CSF levels of beta-human chorionic gonadotropin (beta-hCG) were 215 IU/L and 447 IU/L, respectively, while levels of alpha-fetoprotein (AFP) were normal. A germ cell tumor (GCT) was suspected, and the patient underwent endoscopic third ventriculostomy (ETV) with biopsy. After four days from surgery, the tumor bled with mass expansion and ETV stoma occlusion; thus, a ventriculoperitoneal shunt was positioned. After ten months, the tumor metastasized to the thorax and abdomen with progression of intracerebral tumor mass. Despite the aggressive nature of this tumor, ETV remains a valid approach for a pineal region mass, but in case of GCT, the risk of bleeding should be taken into account, during and after the surgical procedure. PMID:29713348

A Case of Nongerminomatous Germ Cell Tumor of the Pineal Region: Risks and Advantages of Biopsy by Endoscopic Approach.

PubMed

Dobran, Mauro; Nasi, Davide; Mancini, Fabrizio; Gladi, Maurizio; Scerrati, Massimo

2018-01-01

A 21-year-old male was admitted to our department with headache and drowsiness. CT scan and MRI revealed acute obstructive hydrocephalus caused by a pineal region mass. The serum and CSF levels of beta-human chorionic gonadotropin (beta-hCG) were 215 IU/L and 447 IU/L, respectively, while levels of alpha-fetoprotein (AFP) were normal. A germ cell tumor (GCT) was suspected, and the patient underwent endoscopic third ventriculostomy (ETV) with biopsy. After four days from surgery, the tumor bled with mass expansion and ETV stoma occlusion; thus, a ventriculoperitoneal shunt was positioned. After ten months, the tumor metastasized to the thorax and abdomen with progression of intracerebral tumor mass. Despite the aggressive nature of this tumor, ETV remains a valid approach for a pineal region mass, but in case of GCT, the risk of bleeding should be taken into account, during and after the surgical procedure.

Risk factors for persistent gestational trophoblastic neoplasia.

PubMed

Kuyumcuoglu, Umur; Guzel, Ali Irfan; Erdemoglu, Mahmut; Celik, Yusuf

2011-01-01

This retrospective study evaluated the risk factors for persistent gestational trophoblastic disease (GTN) and determined their odds ratios. This study included 100 cases with GTN admitted to our clinic. Possible risk factors recorded were age, gravidity, parity, size of the neoplasia, and beta-human chorionic gonadotropin levels (beta-hCG) before and after the procedure. Statistical analyses consisted of the independent sample t-test and logistic regression using the statistical package SPSS ver. 15.0 for Windows (SPSS, Chicago, IL, USA). Twenty of the cases had persistent GTN, and the differences between these and the others cases were evaluated. The size of the neoplasia and histopathological type of GTN had no statistical relationship with persistence, whereas age, gravidity, and beta-hCG levels were significant risk factors for persistent GTN (p < 0.05). The odds ratios (95% confidence interval (CI)) for age, gravidity, and pre- and post-evacuation beta-hCG levels determined using logistic regression were 4.678 (0.97-22.44), 7.315 (1.16-46.16), 2.637 (1.41-4.94), and 2.339 (1.52-3.60), respectively. Patient age, gravidity, and beta-hCG levels were risk factors for persistent GTN, whereas the size of the neoplasia and histopathological type of GTN were not significant risk factors.

Adrenal hormones in human follicular fluid.

PubMed

Jimena, P; Castilla, J A; Peran, F; Ramirez, J P; Vergara, F; Molina, R; Vergara, F; Herruzo, A

1992-11-01

Considerable evidence indicates that adrenal hormones may affect gonadal function. To assess the role of some adrenal hormones in human follicular fluid and their relationship with the ability of the oocyte to be fertilized and then to cleave in vitro, cortisol and dehydroepiandrosterone sulfate were measured in follicular fluid obtained at the time of oocyte recovery for in vitro fertilization from cycles stimulated by clomiphene citrate, human menopausal gonadotropin and human chorionic gonadotropin. Thirty-six follicular fluid containing mature oocyte-corona-cumulus complexes and free of visible blood contamination were included in this study. There was no significant difference in follicular fluid dehydroepiandrosterone sulfate concentration between follicles with oocytes which did or did not fertilize (5.1 +/- 1.1 vs 5.8 +/- 2.0 mumol/l). However, follicular fluid from follicles whose oocytes were not fertilized had levels of cortisol significantly higher than those in follicular fluid from follicles containing successfully fertilized oocytes (406.0 +/- 75.9 vs 339.2 +/- 37.0 nmol/l; p < 0.005). No significant correlations were found between rates of embryo cleavage and cortisol and dehydroepiandrosterone levels in follicular fluid. We conclude that cortisol levels in follicular fluid may provide an index of fertilization outcome, at least in stimulated cycles by clomiphene citrate, human menopausal gonadotropin and human chorionic gonadotropin.

The effects of ethanol and strontium on growth and development of two-cell arrested mouse embryos.

PubMed

Darabi, Mohammad Reza; Shiravi, Abdolhossein; Hojati, Vida

2012-01-01

Arresting at a certain stage of development like the two-cell stage could be one of the causes of infertility. The aim of this study is to evaluate the effects of ethanol and strontium on growth and development of mice embryos arrested at the two-cell stage. In this experimental study, female mice were coupled with a male following superovulation. Positive vaginal plug mice were sacrificed 48 hours after human chorionic gonadotropin (hCG) injection. Two-cell embryos were transferred to M16 medium and divided to four groups. The first control group was incubated without any exposure to low temperatures. Groups 2, 3 and 4 were exposed to 4°C for 24 hours. The second control group was incubated immediately, while the third and fourth groups were exposed to 10 mM strontium for five minutes and 0.1% ethanol for a further five minutes. Growth rate and developmental parameters of embryos were analyzed by one- way ANOVA. The significant difference between the groups was determined by Post Hoc. The data shows that developmental rate is decreased significantly by 4°C exposure. The mean percentage of degenerated embryo was significantly different between groups but the mean cleavage rate was not significantly different. The mean percent of morula, blastocyst and hatched blastocyst formation were significantly different between groups during a 120 hours study post hCG injection. The effect of strontium and ethanol on arrested two-cell embryos had no significant effect on the mean percentage of morula, but ethanol treatment significantly increased the percentage of blastocyst and hatched blastocyst formation compared to strontium.

Ovarian Expression and Regulation of the Stromelysins During the Periovulatory Period in the Human and the Rat1

PubMed Central

McCord, Lauren A.; Li, Feixue; Rosewell, Katherine L.; Brännström, Mats; Curry, Thomas E.

2011-01-01

ABSTRACT The matrix metalloproteinases (MMPs) are postulated to facilitate follicular rupture. In the present study, expression of the stromelysins (MMP3, MMP10, MMP11) was analyzed in the periovulatory human and rat ovary. Human granulosa and theca cells were collected from the dominant follicle at various times after human chorionic gonadotropin (hCG). Intact rat ovaries, granulosa cells, and residual tissue (tissue remaining after granulosa cell collection) were isolated from equine CG (eCG)-hCG-primed animals. Mmp10 mRNA was highly induced in human granulosa and theca cells and intact rat ovaries, granulosa cells, and residual tissue. Localization of MMP10 to granulosa and theca cells in both human and rat ovarian follicles was confirmed by immunohistochemistry. Mmp3 mRNA was unchanged in human cells and rat granulosa cells, but increased in intact rat ovaries and residual tissue. Mmp11 mRNA decreased following hCG treatment in human granulosa and theca cells as well as rat granulosa cells. Regulation of Mmp10 in cultured rat granulosa cells revealed that the EGF inhibitor AG1478 and the progesterone receptor antagonist RU486 suppressed the induction of Mmp10 mRNA, whereas the prostaglandin inhibitor NS398 had no effect. Studies on the Mmp10 promoter demonstrated that forskolin plus PMA stimulated promoter activity, which was dependent upon a proximal AP1 site. In conclusion, there are divergent patterns of stromelysin expression associated with ovulation, with a marked induction of Mmp10 mRNA and a decrease in Mmp11 mRNA, yet a species-dependent pattern on Mmp3 mRNA expression. The induction of Mmp10 expression suggests an important role for this MMP in the follicular changes associated with ovulation and subsequent luteinization. PMID:22116802

The expression of CXCR4 is induced by the luteinizing hormone surge and mediated by progesterone receptors in human preovulatory granulosa cells.

PubMed

Choi, Yohan; Park, Ji Yeon; Wilson, Kalin; Rosewell, Katherine L; Brännström, Mats; Akin, James W; Curry, Thomas E; Jo, Misung

2017-06-01

The chemokine CXC motif ligand 12 (CXCL12) and its cognate receptor, CXCR4, have been implicated in the ovulatory process in various animal models. However, little is known about the expression and regulation of CXCL12 and CXCR4 and their functions during the ovulatory period in the human ovary. In this study, we characterized the expression patterns of CXCL12 and CXCR4 in preovulatory follicles collected before the luteinizing hormone (LH) surge and at defined hours after hCG administration in women with the regular menstrual cycle. The levels of mRNA and protein for CXCR4 were increased in granulosa cells of late ovulatory follicles, whereas CXCL12 expression was constant in follicles throughout the ovulatory period. Both CXCR4 and CXCL12 were localized to a subset of leukocytes around and inside the vasculature of human preovulatory follicles. Using a human granulosa cell culture model, the regulatory mechanisms and functions of CXCL12 and CXCR4 expression were investigated. Human chorionic gonadotropin (hCG) stimulated CXCR4 expression, whereas CXCL12 expression was not affected, mimicking in vivo expression patterns. Both RU486 (progesterone receptor antagonist) and CoCl2 (HIFs activator) blocked the hCG-induced increase in CXCR4 expression, whereas AG1478 (EGFR inhibitor) had no effect. The treatment with CXCL12 had no effect on granulosa cell viability but decreased hCG-stimulated CXCR4 expression. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Coordinated Regulation Among Progesterone, Prostaglandins, and EGF-Like Factors in Human Ovulatory Follicles.

PubMed

Choi, Yohan; Wilson, Kalin; Hannon, Patrick R; Rosewell, Katherine L; Brännström, Mats; Akin, James W; Curry, Thomas E; Jo, Misung

2017-06-01

In animal models, the luteinizing hormone surge increases progesterone (P4) and progesterone receptor (PGR), prostaglandins (PTGs), and epidermal growth factor (EGF)-like factors that play essential roles in ovulation. However, little is known about the expression, regulation, and function of these key ovulatory mediators in humans. To determine when and how these key ovulatory mediators are induced after the luteinizing hormone surge in human ovaries. Timed periovulatory follicles were obtained from cycling women. Granulosa/lutein cells were collected from in vitro fertilization patients. The in vivo and in vitro expression of PGR, PTG synthases and transporters, and EGF-like factors were examined at the level of messenger RNA and protein. PGR binding to specific genes was assessed. P4 and PTGs in conditioned media were measured. PGR, PTGS2, and AREG expressions dramatically increased in ovulatory follicles at 12 to 18 hours after human chorionic gonadotropin (hCG). In human granulosa/lutein cell cultures, hCG increased P4 and PTG production and the expression of PGR, specific PTG synthases and transporters, and EGF-like factors, mimicking in vivo expression patterns. Inhibitors for P4/PGR and EGF-signaling pathways reduced hCG-induced increases in PTG production and the expression of EGF-like factors. PGR bound to the PTGS2, PTGES, and SLCO2A1 genes. This report demonstrated the time-dependent induction of PGR, AREG, and PTGS2 in human periovulatory follicles. In vitro studies indicated that collaborative actions of P4/PGR and EGF signaling are required for hCG-induced increases in PTG production and potentiation of EGF signaling in human periovulatory granulosa cells. Copyright © 2017 Endocrine Society

Ovarian expression and regulation of the stromelysins during the periovulatory period in the human and the rat.

PubMed

McCord, Lauren A; Li, Feixue; Rosewell, Katherine L; Brännström, Mats; Curry, Thomas E

2012-03-01

The matrix metalloproteinases (MMPs) are postulated to facilitate follicular rupture. In the present study, expression of the stromelysins (MMP3, MMP10, MMP11) was analyzed in the periovulatory human and rat ovary. Human granulosa and theca cells were collected from the dominant follicle at various times after human chorionic gonadotropin (hCG). Intact rat ovaries, granulosa cells, and residual tissue (tissue remaining after granulosa cell collection) were isolated from equine CG (eCG)-hCG-primed animals. Mmp10 mRNA was highly induced in human granulosa and theca cells and intact rat ovaries, granulosa cells, and residual tissue. Localization of MMP10 to granulosa and theca cells in both human and rat ovarian follicles was confirmed by immunohistochemistry. Mmp3 mRNA was unchanged in human cells and rat granulosa cells, but increased in intact rat ovaries and residual tissue. Mmp11 mRNA decreased following hCG treatment in human granulosa and theca cells as well as rat granulosa cells. Regulation of Mmp10 in cultured rat granulosa cells revealed that the EGF inhibitor AG1478 and the progesterone receptor antagonist RU486 suppressed the induction of Mmp10 mRNA, whereas the prostaglandin inhibitor NS398 had no effect. Studies on the Mmp10 promoter demonstrated that forskolin plus PMA stimulated promoter activity, which was dependent upon a proximal AP1 site. In conclusion, there are divergent patterns of stromelysin expression associated with ovulation, with a marked induction of Mmp10 mRNA and a decrease in Mmp11 mRNA, yet a species-dependent pattern on Mmp3 mRNA expression. The induction of Mmp10 expression suggests an important role for this MMP in the follicular changes associated with ovulation and subsequent luteinization.

Coordinated Regulation Among Progesterone, Prostaglandins, and EGF-Like Factors in Human Ovulatory Follicles

PubMed Central

Choi, Yohan; Wilson, Kalin; Hannon, Patrick R.; Rosewell, Katherine L.; Brännström, Mats; Akin, James W.; Curry, Thomas E.

2017-01-01

Context: In animal models, the luteinizing hormone surge increases progesterone (P4) and progesterone receptor (PGR), prostaglandins (PTGs), and epidermal growth factor (EGF)–like factors that play essential roles in ovulation. However, little is known about the expression, regulation, and function of these key ovulatory mediators in humans. Objective: To determine when and how these key ovulatory mediators are induced after the luteinizing hormone surge in human ovaries. Design and Participants: Timed periovulatory follicles were obtained from cycling women. Granulosa/lutein cells were collected from in vitro fertilization patients. Main Outcome Measures: The in vivo and in vitro expression of PGR, PTG synthases and transporters, and EGF-like factors were examined at the level of messenger RNA and protein. PGR binding to specific genes was assessed. P4 and PTGs in conditioned media were measured. Results: PGR, PTGS2, and AREG expressions dramatically increased in ovulatory follicles at 12 to 18 hours after human chorionic gonadotropin (hCG). In human granulosa/lutein cell cultures, hCG increased P4 and PTG production and the expression of PGR, specific PTG synthases and transporters, and EGF-like factors, mimicking in vivo expression patterns. Inhibitors for P4/PGR and EGF-signaling pathways reduced hCG-induced increases in PTG production and the expression of EGF-like factors. PGR bound to the PTGS2, PTGES, and SLCO2A1 genes. Conclusions: This report demonstrated the time-dependent induction of PGR, AREG, and PTGS2 in human periovulatory follicles. In vitro studies indicated that collaborative actions of P4/PGR and EGF signaling are required for hCG-induced increases in PTG production and potentiation of EGF signaling in human periovulatory granulosa cells. PMID:28323945

Early predicted time to normalization of tumor markers predicts outcome in poor-prognosis nonseminomatous germ cell tumors.

PubMed

Fizazi, Karim; Culine, Stéphane; Kramar, Andrew; Amato, Robert J; Bouzy, Jeannine; Chen, Isan; Droz, Jean-Pierre; Logothetis, Christopher J

2004-10-01

The prognostic relevance of the rate of decline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) during the first 3 weeks of chemotherapy for nonseminomatous germ cell tumors (NSGCT) was studied in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) classification. Data from 653 patients prospectively recruited in clinical trials were studied. Tumor markers were obtained before chemotherapy and 3 weeks later. Decline rates were calculated using a logarithmic formula and expressed as a predicted time to normalization (TTN). A favorable TTN was defined when both AFP and HCG had a favorable decline rate, including cases with normal values. The median follow-up was 50 months (range, 2 to 151 months). Tumor decline rate expressed as a predicted TTN was associated with both progression-free survival (PFS; P <.0001) and overall survival (OS; P <.0001). The 4-year PFS rates were 64% and 38% in patients from the poor-prognosis group who had a favorable and an unfavorable TTN, respectively. The 4-year OS rates were 83% and 58%, respectively. This effect was independent from the initial tumor marker values, the primary tumor site, and the presence of nonpulmonary visceral metastases: tumor marker decline rate remained a strong predictor for both PFS (hazard ratio = 2.5; P =.01) and OS (hazard ratio = 4.6; P =.002) in patients from the IGCCCG poor-prognosis group in multivariate analysis. Early predicted time to tumor marker normalization is an independent prognostic factor in patients with poor-prognosis NSGCT and may be a useful tool in the therapeutic management of these patients.

ARF6 Activated by the LHCG Receptor through the Cytohesin Family of Guanine Nucleotide Exchange Factors Mediates the Receptor Internalization and Signaling*

PubMed Central

Kanamarlapudi, Venkateswarlu; Thompson, Aiysha; Kelly, Eamonn; López Bernal, Andrés

2012-01-01

The luteinizing hormone chorionic gonadotropin receptor (LHCGR) is a Gs-coupled GPCR that is essential for the maturation and function of the ovary and testis. LHCGR is internalized following its activation, which regulates the biological responsiveness of the receptor. Previous studies indicated that ADP-ribosylation factor (ARF)6 and its GTP-exchange factor (GEF) cytohesin 2 regulate LHCGR internalization in follicular membranes. However, the mechanisms by which ARF6 and cytohesin 2 regulate LHCGR internalization remain incompletely understood. Here we investigated the role of the ARF6 signaling pathway in the internalization of heterologously expressed human LHCGR (HLHCGR) in intact cells using a combination of pharmacological inhibitors, siRNA and the expression of mutant proteins. We found that human CG (HCG)-induced HLHCGR internalization, cAMP accumulation and ARF6 activation were inhibited by Gallein (βγ inhibitor), Wortmannin (PI 3-kinase inhibitor), SecinH3 (cytohesin ARF GEF inhibitor), QS11 (an ARF GAP inhibitor), an ARF6 inhibitory peptide and ARF6 siRNA. However, Dynasore (dynamin inhibitor), the dominant negative mutants of NM23-H1 (dynamin activator) and clathrin, and PBP10 (PtdIns 4,5-P2-binding peptide) inhibited agonist-induced HLHCGR and cAMP accumulation but not ARF6 activation. These results indicate that heterotrimeric G-protein, phosphatidylinositol (PI) 3-kinase (PI3K), cytohesin ARF GEF and ARF GAP function upstream of ARF6 whereas dynamin and clathrin act downstream of ARF6 in the regulation of HCG-induced HLHCGR internalization and signaling. In conclusion, we have identified the components and molecular details of the ARF6 signaling pathway required for agonist-induced HLHCGR internalization. PMID:22523074

Preorchiectomy Leydig Cell Dysfunction in Patients With Testicular Cancer.

PubMed

Bandak, Mikkel; Jørgensen, Niels; Juul, Anders; Lauritsen, Jakob; Gundgaard Kier, Maria Gry; Mortensen, Mette Saksø; Daugaard, Gedske

2017-02-01

Little is known about preorchiectomy Leydig cell function in patients with testicular germ cell cancer (TGCC). The aim was to estimate the prevalence of preorchiectomy Leydig cell dysfunction and evaluate factors associated with this condition in a cohort of patients with TGCC. We evaluated luteinizing hormone (LH), total testosterone (TT), calculated free T (cFT), estradiol, and sex hormone-binding globulin (SHBG) preorchiectomy in 561 patients with TGCC and compared with 561 healthy controls. We calculated TT/LH and cFT/LH ratios and constructed bivariate charts of TT/LH and cFT/LH from the controls. Logistic regression analysis with an abnormal cFT/LH ratio as outcome and clinical stage, tumor size, age, histology, presence of contralateral germ cell neoplasia in situ (GCNIS), and bilateral tumors as covariates was performed. In patients who were negative for human chorionic gonadotropin (hCG) (n = 374), TT (P = .004), cFT (P < .001), TT/LH ratio (P = .003), and cFT/LH ratio (P = .002) were lower than in controls. A total of 95 (25%) and 91 (24%) of hCG-negative patients had abnormal values when using combined evaluation of TT/LH and cFT/LH, respectively. Increasing tumor size, contralateral GCNIS, and increasing age were associated with Leydig cell dysfunction. In patients positive for hCG (n = 187), all reproductive hormones except SHBG were different from controls (P < .001). Patients with TGCC are at increased risk of Leydig cell dysfunction before orchiectomy. Contralateral GCNIS, increasing age, and increasing tumor size are associated with Leydig cell dysfunction. We hypothesize that patients with preexisting Leydig cell dysfunction are at increased risk of testosterone deficiency following treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Ratio of progesterone-to-number of follicles as a prognostic tool for in vitro fertilization cycles.

PubMed

Roque, Matheus; Valle, Marcello; Sampaio, Marcos; Geber, Selmo; Checa, Miguel Angel

2015-06-01

To establish a ratio of the P level to the number of follicles (P/F ratio) on the day of human chorionic gonadotropin (hCG) administration and to evaluate whether this ratio is associated with in vitro fertilization (IVF) outcome. This study was conducted between January 2012 and June 2013. A total of 337 patients with cleavage-stage day-3 fresh embryo transfer with P levels ≤1.5 ng/mL on the day of hCG administration were included in the study. The main outcome was ongoing pregnancy rate. The P/F ratio was calculated according to the equation (P[ng/mL]/number of follicles) on the day of final oocyte maturation. Using ROC, we established a cut-off level of 0.075 for the P/F ratio. The area under the curve (AUC) (0.756; 95 % confidence interval [CI]: 0.704-0.807) indicated that it was a good prognostic test. In group 1 (patients under 36 years old), the ongoing pregnancy rates were 57 and 30 % for patients with P/F ratios ≤ .075 and > .075, respectively, (p = 0.003). In group 2 (patients between 36 and 39 years old), the ongoing pregnancy rates were 58 % and 17 % (p = 0.001) for patients with P/F ratios ≤ .075 and > .075, respectively. In group 3 (patients ≥ 40 years old), the ongoing pregnancy rates were 41.7 and 10.9 % (p = 0.001) for patients with P/F ratios ≤ .075 and > .075, respectively. The P/F ratio is a good prognostic test for predicting IVF outcome that can correlate the P level with ovarian response.

Recurrent seminomas: Clinical features and biologic implications

PubMed Central

Som, Avik; Zhu, Rui; Guo, Charles C.; Efstathiou, Eleni; Xiao, Li; Pisters, Louis L.; Matin, Angabin; Tu, Shi-Ming

2013-01-01

Objectives Certain patients with seminoma and clinically atypical phenotypes—visceral metastases, elevated levels of βhuman chorionic gonadotropin (βHCG), and/or recurrent disease— have a poor prognosis. The primary goal of this pilot study was to characterize the clinical characteristics and treatment profile of these rare patients. We also wished to test whether these tumors expressed any specific biomarkers that might distinguish them as a unique subtype of seminoma. Materials and methods We retrospectively identified 25 patients with a history of seminoma plus visceral metastases, βHCG levels >200 mU/ml, and/or recurrent disease. We reviewed these patients’ histories for treatment efficacy and clinical outcome. Tissue samples were available from 6 of those patients, and we studied them for expression of the markers OCT 3/4, PLAP, CD30, TRA-1-60, c-kit, and gp200. We compared our results with the expression of those markers in tissue samples from mixed seminoma/embryonal carcinomas and classic seminomas. Results Our analysis suggested that certain chemotherapeutic regimens (such as ifosfamide, paclitaxel, and cisplatin) are efficacious for the treatment of patients with these atypical seminomas. Further, specimens from the atypical seminomas generally had staining profiles that resembled those of classic seminomas and the seminoma components in mixed germ-cell tumors, but the profiles differed from those of the embryonal carcinoma components in the same mixed germ-cell tumors. Conclusions Although these atypical seminomas tend to be resistant to chemotherapy, they may still respond to certain chemotherapeutic regimens. Our pilot immunohistochemical study also suggested that the unique phenotypes associated with these atypical seminomas do not result from any relationship with embryonal carcinomas. More study is needed to confirm these initial findings. PMID:20822932

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

Ketoconazole inhibition of testicular secretion of testosterone and displacement of steroid hormones from serum transport proteins.

PubMed Central

Grosso, D S; Boyden, T W; Pamenter, R W; Johnson, D G; Stevens, D A; Galgiani, J N

1983-01-01

In vivo perfusion of canine testes with ketoconazole inhibited the stimulation of testosterone production by human chorionic gonadotropin in a dose-dependent manner. Ketoconazole also selectively displaced steroids from serum-binding globulins. Dihydrotestosterone and estradiol binding to sex hormone-binding globulin were inhibited by ketoconazole. Cortisol binding to corticosteroid-binding globulin was unaffected. The concentrations of ketoconazole that inhibited human chorionic gonadotropin stimulation of testicular androgen production and displaced sex steroids from sex hormone-binding globulin were in the range of blood levels found in patients on higher therapeutic dosage regimens. Suppression of testicular testosterone synthesis and displacement of estrogens from sex hormone-binding globulin may decrease the androgen/estrogen ratio of the blood and contribute to the development of gynecomastia that has been reported in some ketoconazole-treated patients. PMID:6301363

Aggregation of luteinizing hormone receptors in granulosa cells: a possible mechanism of desensitization to the hormone.

PubMed Central

Amsterdam, A; Berkowitz, A; Nimrod, A; Kohen, F

1980-01-01

The temporal relationship between redistribution of receptors to lutropin (luteinizing hormone)/human chorionic gonadotropin in cultured rat ovarian granulosa cells and the cellular response to hormonal challenge were studied. Visualization of receptor-bound human chorionic gonadotropin by indirect immunofluorescence, with hormone-specific antibodies after fixation with 2% formaldehyde, revealed the existence of small clusters around the entire cell circumference 5--20 min after exposure to the hormone at 37 degrees C. Such small receptor aggregates were also evident if hormone incubation was at 4 degrees C or if cells were fixed with 2% formaldehyde before incubation. Larger clusters were evident after prolonged incubation with the hormone (2--4 hr) at 37 degrees C. The later change coincided with diminished cyclic AMP accumulation in respose to challenge with fresh hormone. When the fixation step was omitted and antibodies to human chorionic gonadotropin were applied after hormonal binding, acceleration of both receptor clustering and the desensitization process was observed. This maneuver also induced capping of the hormone receptors. In contrast, monovalent Fab' fragments of the antibodies were without effect. Internalization of the bound hormone in lysosomes, and subsequent degradation, was evident 8 hr after hormonal application and was not accelerated by the antibodies. It is suggested that clustering of the luteinizing hormone receptors may play a role in cellular responsiveness to the hormone. Massive aggregation of the receptors may desensitize the cell by interferring with coupling to adenylate cyclase. Images PMID:6251459

Successful pregnancy following low-dose hCG administration in addition to hMG in a patient with hypothalamic amenorrhea due to weight loss.

PubMed

Tsutsumi, Ryo; Fujimoto, Akihisa; Osuga, Yutaka; Harada, Miyuki; Takemura, Yuri; Koizumi, Minako; Yano, Tetsu; Taketani, Yuji

2012-06-01

We describe successful ovulation induction with low-dose hCG administration in addition to hMG in a patient with refractory hypothalamic amenorrhea. A 24-year-old woman with weight loss-related amenorrhea underwent ovulation induction and intracytoplasmic sperm injection (ICSI). Administration of exogenous gonadotropins was ineffective in ovulation induction. Supplementation with low-dose hCG in order to increase luteinizing hormone (LH) activity in the late follicular phase produced late folliculogenesis and steroidogenesis, and ovulation was then successfully induced. This report reacknowledges the critical role that LH plays cooperatively with follicle-stimulating hormone in both folliculogenesis and steroidogenesis.

Combined ovulation triggering with GnRH agonist and hCG in IVF patients.

PubMed

Kasum, Miro; Kurdija, Kristijan; Orešković, Slavko; Čehić, Ermin; Pavičić-Baldani, Dinka; Škrgatić, Lana

2016-11-01

The aim of the review is to analyse the combination of a gonadotrophin releasing hormone (GnRH) agonist with a human chorionic gonadotrophin (hCG) trigger, for final oocyte maturation in in vitro fertilisation (IVF) cycles. The concept being a ''dual trigger'' combines a single dose of the GnRH agonist with a reduced or standard dosage of hCG at the time of triggering. The use of a GnRH agonist with a reduced dose of hCG in high responders demonstrated luteal phase support with improved pregnancy rates, similar to those after conventional hCG and a low risk of ovarian hyperstimulation syndrome (OHSS). The administration of a GnRH agonist and a standard hCG in normal responders, demonstrated significantly improved live-birth rates and a higher number of embryos of excellent quality, or cryopreserved embryos. The concept of the ''double trigger" represents a combination of a GnRH agonist and a standard hCG, when used 40 and 34 h prior to ovum pick-up, respectively. The use of the ''double trigger" has been successfully offered in the treatment of empty follicle syndrome and in patients with a history of immature oocytes retrieved or with low/poor oocytes yield. Further prospective studies are required to confirm the aforementioned observations prior to clinical implementation.

Luteal phase HCG support for unexplained recurrent pregnancy loss - a low hanging fruit?

PubMed

Fox, Chelsea; Azores-Gococo, Denise; Swart, Linda; Holoch, Kristin; Savaris, Ricardo F; Likes, Creighton E; Miller, Paul B; Forstein, David A; Lessey, Bruce A

2017-03-01

Recurrent pregnancy loss (RPL) is defined by two or more failed pregnancies and accounts for only 1-5% of pregnancy failures. Treatment options for unexplained RPL (uRPL) are limited. Previous studies suggest a link between delayed implantation and pregnancy loss. Based on this, a timely signal for rescue of the corpus luteum (CL) using human chorionic gonadotrophin (HCG) could improve outcomes in women with uRPL. This retrospective cohort study included 98 subjects with uRPL: 45 underwent 135 monitored cycles without HCG support; and 53 underwent 142 cycles with a single mid-luteal HCG injection. Based on Log-rank Mantel-Cox survival curves, miscarriage rate and time to pregnancy decreased in the HCG group (P = 0.0005). Women receiving luteal HCG support had an increased chance of an ongoing pregnancy compared with those not receiving it (RR = 2.4; 95% CI 1.4-3.6; number need to treat (NNT) = 7; 95% CI 4-18). Subjects receiving HCG support had a significant absolute risk reduction (ARR) of miscarriage (P < 0.001; ARR = 11.5%; 95% CI 3.6-19.5; NNT = 9(5-27). These data suggest restoration of synchrony and CL support improves outcomes in women with RPL. Further randomized controlled trials of luteal-phase HCG in women with RPL appears warranted. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Polycystic ovarian disease.

PubMed

Raj, S G; Talbert, L M

1984-01-01

Polycystic ovarian disease (PCOD) was first described as a single disease by Stein and Leventhal in 1935, but now has been separated into several distinct entities, comprising a symptom complex. The most frequent presenting symptoms associated with PCOD are obesity, hirsutism, amenorrhea or anovulation, dysfunctional uterine bleeding, irregular menses, and infertility. The common finding of hirsutism in PCOD patients is a reflection of the hyperandrogenism resulting from elevation of all the androgens, including testosterone, androstenediol, dehydroepiandrostrone sulfate (DHEA-S), and androstenedione. Some patients with all the clinical features of PCOD can be shown, through appropriate testing, to have an attenuated form of classic congenital adrenal hyperplasia (CAH). Serum follicle stimulating hormone (FSH) levels are usually low or in the normal range, and serum luteinizing hormone (LH) levels are usually elevated in patients with PCOD, resulting in an altered LH/FSH ratio. Treatment for PCOD must be based on the needs and desires of the individual patient, and on the pathophysiology of the patient's particular abnormalities. When pregnancy is desired, ovulation induction with clomiphene is indicated. Clomiphene is a weak estrogen that induces a transient rise in serum LH and FSH, followed by a gonadotropic pattern similar to normal cycles. A 72% ovulation rate and a 41.8% conception rate have been reported after treatment with clomiphene. In patients who do not respond to clomiphene, or clomiphene with added human chorionic gonadotropin (hCG), human menopausal gonadotropin (hMG) can be used to induce ovulation, but the patient should be closely monitored for multiple ovulation, multiple pregnancy, or hyperstimulation syndrome. For patients not interested in conception, regular menstrual cyclicity can be restored and hyperandrogenism reduced with oral contraceptives (OCs).

Evaluating The Effect of Melatonin on HAS2, and PGR expression, as well as Cumulus Expansion, and Fertility Potential in Mice.

PubMed

Ezzati, Maryam; Roshangar, Leila; Soleimani Rad, Jafar; Karimian, Nahid

2018-04-01

Infertility is a worldwide health problem which affects approximately 15% of sexually active couples. One of the factors influencing the fertility is melatonin. Also, protection of oocytes and embryos from oxidative stress inducing chemicals in the culture medium is important. The aim of the present study was to investigate if melatonin could regulate hyaluronan synthase-2 (HAS2) and Progesterone receptor (PGR) expressions in the cumulus cells of mice oocytes and provide an in vitro fertilization (IVF) approach. In this experimental study, for this purpose, 30 adult female mice and 15 adult male mice were used. The female mice were superovulated using 10 U of pregnant mare serum gonadotropin (PMSG) and 24 hours later, 10 U of human chorionic gonadotropin (hCG) were injected. Next, cumulus oocyte complexes (COCs) were collected from the oviducts of the female mice by using a matrix-flushing method. The cumulus cells were cultured with melatonin 10 μM for 6 hours and for real-time reverse transcription-polymerase chain reaction (RT-PCR) was used for evaluation of HAS2 and PGR expression levels. The fertilization rate was evaluated through IVF. All the data were analyzed using a t test. The results of this study showed that HAS2 and PGR expressions in the cumulus cells of the mice receiving melatonin increased in comparison to the control groups. Also, IVF results revealed an enhancement in fertilization rate in the experimental groups compared to the control groups. To improve the oocyte quality and provide new approaches for infertility treatment, administration of melatonin as an antioxidant, showed promising results. Thus, it is concluded that fertility outcomes can be improved by melatonin it enhances PGR. Copyright© by Royan Institute. All rights reserved.

Effects of 3-methyl-4-nitrophenol in diesel exhaust particles on the regulation of testicular function in immature male rats.

PubMed

Li, Chunmei; Taneda, Shinji; Suzuki, Akira K; Furuta, Chie; Watanabe, Gen; Taya, Kazuyoshi

2007-01-01

We investigated the effects of 3-methyl-4-nitrophenol (4-nitro-m-cresol, PNMC) isolated from diesel exhaust particles (DEP) on the reproductive functions of male rats. Twenty-eight-day-old rats were injected subcutaneously with PNMC (1, 10, or 100 mg/kg) daily for 5 days. The weights of the epididymis, seminal vesicle, and Cowper gland were significantly decreased in rats treated with 10 mg/kg PNMC. The plasma concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were significantly increased by PNMC at 100 mg/kg. However, the plasma concentrations of testosterone and immunoreactive (ir)-inhibin were significantly decreased by PNMC at 100 mg/kg. The testosterone content of the testicles was significantly decreased in the group treated with 100 mg/kg PNMC compared with the control group. Furthermore, testicular concentration of ir-inhibin was significantly decreased by PNMC at 1 mg/kg or 100 mg/kg. To investigate the direct effects of PNMC on the secretion of LH and FSH from the anterior pituitary gland, and on the secretion of testosterone from the testes, we exposed cultured anterior pituitary and interstitial Leydig cells to PNMC (10(-6), 10(-5), 10(-4) M) with or without gonadotropin-releasing hormone (GnRH; 10 nM) (for the LH and FSH tests) and human chorionic gonadotropin (hCG; 0.1 IU/mL) (for the testosterone test) for 24 hours. PNMC did not change either the basal or GnRH-stimulated levels of FSH and LH secretion. However, PNMC significantly inhibited both basal and hCG-stimulated testosterone production. These findings suggest that PNMC has a direct effect on the testes of immature male rats, causing a reduction in testosterone secretion.

Pregnancy Rate Following Luteal Phase Support in Iranian Women with Polycystic Ovarian Syndrome

PubMed Central

Foroozanfard, Fatemeh; Saberi, Hamidreza; Moraveji, Seyed Alireza; Bazarganipour, Fatemeh

2014-01-01

Background To assess the efficacy of luteal phase support (LPS) using intravaginal progesterone (P) on pregnancy rate in Iranian women with polycystic ovarian syndrome (PCOS) who used a combination for ovulation induction consisting of letrozole or clomi- phene citrate (CC) and human menopausal gonadotropin (HMG). Materials and Methods This was a randomized clinical trial undertaken in a fertility clinic in Kashan, Isfahan Province, Iran. A total of 198 patients completed treatment and follow up. Base on chosen ovulation induction programs, they were divided into two following group: i. CC group (n=98) used a combination consisting of CC (100 mg×5 day) and HMG (150 IU×5 day) and ii. letrozole group (n=100) used a combination consisting of letrozole (5 mg×5 day) and HMG (150 IU×5 day). After human chorionic gonadotropin (hCG) administration (5000 IU), the patients (n=122) who randomly re- ceived intravaginal P (Cyclogest, 400 mg daily) were included in LPS group, while the rest (n=123) were included in non-P cycles group. The outcome was the comparison of chemical pregnancy rate between the groups. Results Our findings showed that LPS was associated with a 10% higher pregnancy rate than in non-P cycles, although this difference did not reach statistical significant (p=0.08). LPS improved pregnancy rate in both CC (4%) and letrozole (6%) groups. In addition, patients who used letrozole for ovulation induction along with intravaginal P showed higher pregnancy rates than CC group. Conclusion Administration of vaginal P for LPS may improve the pregnancy rate in women with PCOS using letrozole or CC in combination with HMG for ovulation induc- tion (Registration Number: IRCT201206072967N4). PMID:25379150

A Potential Role for Endoplasmic Reticulum Stress in Progesterone Deficiency in Obese Women.

PubMed

Takahashi, Nozomi; Harada, Miyuki; Hirota, Yasushi; Zhao, Lin; Azhary, Jerilee M K; Yoshino, Osamu; Izumi, Gentaro; Hirata, Tetsuya; Koga, Kaori; Wada-Hiraike, Osamu; Fujii, Tomoyuki; Osuga, Yutaka

2017-01-01

Obesity in reproductive-aged women is associated with a shorter luteal phase and lower progesterone levels. Lipid accumulation in follicles of obese women compromises endoplasmic reticulum (ER) function, activating ER stress in granulosa cells. We hypothesized that ER stress activation in granulosa-lutein cells (GLCs) would modulate progesterone production and contribute to obesity-associated progesterone deficiency. Pretreatment with an ER stress inducer, tunicamycin or thapsigargin, inhibited human chorionic gonadotropin (hCG)-stimulated progesterone production in cultured human GLCs. Pretreatment of human GLCs with tunicamycin inhibited hCG-stimulated expression of steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) messenger RNAs (mRNAs) without affecting expression of cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), as determined by real-time quantitative polymerase chain reaction. Pretreatment with tunicamycin also inhibited hCG-stimulated expression of StAR protein and 3β-HSD enzyme activity in cultured human GLCs, as determined by Western blot analysis and an enzyme immunoassay, respectively, but did not affect hCG-induced intracellular 3',5'-cyclic adenosine monophosphate accumulation. Furthermore, tunicamycin attenuated hCG-induced protein kinase A and extracellular signal-regulated kinase activation, as determined by Western blot analysis. In vivo administration of tunicamycin to pregnant mare serum gonadotropin-treated immature mice prior to hCG treatment inhibited the hCG-stimulated increase in serum progesterone levels and hCG-induced expression of StAR and 3β-HSD mRNA in the ovary without affecting serum estradiol levels or the number of corpora lutea. Our findings indicate that ER stress in the follicles of obese women contributes to progesterone deficiency by inhibiting hCG-induced progesterone production in granulosa cells. Copyright © 2017 by the Endocrine Society.

Luteinizing hormone/chorionic gonadotrophin receptor overexpressed in granulosa cells from polycystic ovary syndrome ovaries is functionally active.

PubMed

Kanamarlapudi, Venkateswarlu; Gordon, Uma D; López Bernal, Andrés

2016-06-01

Polycystic ovarian syndrome (PCOS) is associated with anovulatory infertility. Luteinizing hormone/chorionic gonadotrophin receptor (LHCGR), which is critical for ovulation, has been suggested to be expressed prematurely in the ovarian follicles of women with PCOS. This study aimed to analyse the expression and activity of LHCGR in ovarian granulosa cells from PCOS patients and the involvement of ARF6 small GTPase in LHCGR internalization. Granulosa cells (GC) isolated from follicular fluid collected during oocyte retrieval from normal women (n = 19) and women with PCOS (n = 17) were used to study differences in LHCGR protein expression and activity between normal and PCOS patients. LHCGR expression is up-regulated in GC from PCOS women. LHCGR in PCOS GC is functionally active, as shown by increased cAMP production upon human gonadotrophin (HCG)-stimulation. Moreover, ARF6 is highly expressed in GC from PCOS patients and HCG-stimulation increases the concentrations of active ARF6. The inhibition of ARF6 activation attenuates HCG-induced LHCGR internalization in both normal and PCOS GC, indicating that there are no alterations in LHCGR internalisation in GC from PCOS. In conclusion, the expression and activation of LHCGR and ARF6 are up-regulated in GC from PCOS women but the mechanism of agonist-induced LHCGR internalization is unaltered. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes.

PubMed

Glujovsky, Demián; Pesce, Romina; Fiszbajn, Gabriel; Sueldo, Carlos; Hart, Roger J; Ciapponi, Agustín

2010-01-20

If a fresh embryo, assisted reproductive technology procedure cycle is unsuccessful and there are frozen embryos available, a frozen-thawed embryo transfer is performed. In some specific cases women may undergo oocyte donation treatment. In both situations the endometrium is primed by the administration of estrogen and progesterone. To prevent the possibility of spontaneous ovulation, gonadotropin-releasing hormone (GnRH) agonists are frequently used. To evaluate the most effective endometrial preparation for women undergoing transfer with frozen embryos or embryos from donor oocytes with regard to the subsequent live birth rate. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, LILACS, and abstracts of reproductive societies' meetings (from inception). No language restrictions were applied. Experts in the field were contacted. Randomised controlled trials evaluating endometrial preparation in women undergoing fresh donor cycles and frozen embryo transfers. Two review authors independently applied the inclusion criteria, assessed trial risk of bias, and extracted data. Twenty two randomised controlled trials were included. Five studies analysed the use of a GnRH agonist versus control. No significant benefit was demonstrated when using GnRH agonists. No evidence of statistically significant benefit was found for one GnRH agonist over another, or vaginal over intramuscular progesterone administration. No difference in pregnancy rate was demonstrated when no treatment was compared to aspirin, steroids, ovarian stimulation, or human chorionic gonadotropin (hCG) prior to embryo transfer, although using hCG several times before the oocyte retrieval decreases the pregnancy rate. Finally, when oocyte recipients were studied further, starting progesterone on the day of oocyte pick-up (OPU) or the day after OPU produced a significantly higher pregnancy rate (OR 1.87, 95% CI 1.13 to 3.08) than when recipients started progesterone the day prior to OPU. There is insufficient evidence to recommend any one particular protocol for endometrial preparation over another with regard to pregnancy rates after embryo transfers. These were either frozen embryos or embryos derived from donor oocytes. However, there is evidence of a lower pregnancy rate and a higher cycle cancellation rate when the progesterone supplementation is commenced prior to oocyte retrieval in oocyte donation cycles. Adequately powered studies are needed to evaluate each treatment more accurately.

Effects of hormonal stimulation on the concentration and quality of excreted spermatozoa in the critically endangered Panamanian golden frog (Atelopus zeteki).

PubMed

Della Togna, Gina; Trudeau, Vance L; Gratwicke, Brian; Evans, Matthew; Augustine, Lauren; Chia, Han; Bronikowski, Edward J; Murphy, James B; Comizzoli, Pierre

2017-03-15

Knowledge of basic gamete biology is critical to better protect and propagate endangered amphibian species and also to develop reproductive technologies combined with germplasm cryopreservation. The objectives of the study were to test different hormonal stimulations and then characterize the quantity and quality of Panamanian golden frog (Atelopus zeteki) spermatozoa. Following intraperitoneal injection of the gonadotropin-releasing hormone agonist (des-Gly 10 , D-Ala 6 , Pro-NHEt 9- -GnRH 1, 2 or 4 μg/g of body weight), human chorionic gonadotropin (hCG; 5 or 10 IU/gbw), or Amphiplex™ (0.4 μg/gbw GnRH-A + 10 μg/gbw metoclopramide hydrochloride), spermic urine samples from 29 males were collected at different time points (from 0.5 to 24 h post-injection) to analyze the concentration, motility, and morphology of the spermatozoa. Peak of sperm concentration was observed at 3.5 h post injection for all hormonal treatments. Amphiplex™ led to the highest sperm concentrations (4.45 ± 0.07 × 10 6  cells/mL) followed by 4 μg/gbw GnRH-A (2.65 ± 0.21 × 10 6  cells/mL). Other stimulation protocols and doses induced sperm production, but at lower levels (ranging from 1.34 to 1.70 × 10 6  cells/mL). More than 60% of spermatozoa were motile following all treatments but the highest motility (>90%) was obtained from the 10 IU/gbw hCG treatment. Spermic urine samples obtained with all hormone treatments had higher pH (ranging from 7.1 to 7.8) than the urine alone (6.7-6.8). Spermatozoa were filiform and elongated with an apical acrosome, a mitochondrial sheath, a small midpiece and a long tail with an undulating membrane. More than 80% of cells were morphologically normal and 50-70% had intact DNA. These sperm characteristics were not influenced by hormonal treatments. This first comprehensive characterization of sperm samples following optimized hormonal stimulations in A. zeteki lays the foundation for more fundamental studies, reproductive technologies, and future preservation strategies. Copyright © 2016. Published by Elsevier Inc.

Near-infrared laser irradiation improves the development of mouse pre-implantation embryos

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

Yokoo, Masaki; Mori, Miho

The aim of the present study was to assess the effects of near-infrared laser irradiation on the in vitro development of mouse embryos. Female ICR mice were superovulated with pregnant mare serum gonadotropin and human chorionic gonadotropin (hCG), and mated with male mice. Two-cell stage embryos were collected 40 h after administering hCG and cultured in M16 medium. Two-cell embryos (0 h after culture), 8-cell embryos (approx. 30 h after culture), morula (approx. 48 h after culture), and blastocysts (approx. 73 h after culture) were irradiated at 904 nm for 60 s. These embryos were cultured in a time-lapse monitoring system and the timing ofmore » blastocyst hatching was evaluated. Some of the irradiated blastocysts were transferred to the uterine horns of pseudopregnant recipients immediately after irradiation. Pregnancy rates, and offspring growth and fertility, were evaluated. Near-infrared laser irradiation increased the speed of in vitro mouse embryo development. In irradiated blastocysts, hatching was faster than in control (non-irradiated) blastocysts (18.4 vs. 28.2 h, P < 0.05). When 195 irradiated blastocysts were transferred to 18 pseudopregnant mice, all became pregnant and 92 (47.2%) normal-looking pups were born alive. When 182 control blastocysts were transferred to 17 pseudopregnant mice, 14 (82.4%) became pregnant and 54 (29.7%) normal-looking pups were born alive. The growth trajectories (up to 5 weeks) of offspring from irradiated blastocysts were similar to those from control blastocysts. Second generation offspring from transplanted animals were all fertile. These results indicate that near-infrared laser irradiation improves the quality of mouse embryo development in vitro, and increases the live birth rate without affecting the normality of the offspring. Thus, the near-infrared laser method may enhance the quality of embryos and contribute to improvements in reproductive technologies in mammals. - Highlights: • Irradiation of blastocysts with a near-infrared laser improves embryo development. • Irradiation of blastocysts increases the live birth rate after embryo transfer. • Irradiation of blastocysts did not affect the normality of the pups. • Near-infrared laser irradiation may be useful to enhance the quality of embryos. • This study may contribute to improvements in reproductive technologies in mammals.« less

[Effects of body mass index and age on the treatment of in vitro fertilization-embryo transfer among patients with non-polycystic ovarian syndrome].

PubMed

Chen, Hong; Wang, Wen-jun; Chen, Yu-zhen; Mai, Mei-qi; Ouyang, Neng-yong; Chen, Jing-hua; Tuo, Ping

2010-05-01

To investigate the impacts of body mass index (BMI) and age on in vitro fertilization-embryo transfer (IVF) and intracytoplasmic sperm injection (ICSI) treatment in infertile patients without polycystic ovary syndrome (PCOS). A retrospective study of 1426 patients during Jun. 2001 - Nov. 2009 was carried out. Multiple regression was used to analyze the effects of BMI (low weight: BMI < 18.5 kg/m(2), normal weight: BMI 18.5 - 23.99 kg/m(2) and over weight-obesity: BMI ≥ 24 kg/m(2)) and age (young: 20 - 34 years old, eld: 35 - 45 years old) on controlled ovarian stimulation (COH) [including: dose and duration of Gn, E2 level on day of human chorionic gonadotropin (HCG) administration, number of oocytes collected and full-grown follicles], number of fertilization, cleavage, two-pronucleus, normal embryos and cryopreserved embryos and clinical pregnancy outcome. (1) Gn dose for the patients whose age were 35 and the above, had a positive correlation with age (P < 0.001), 12.70% of the total variation of Gn dose was related to age (standardized partial regression coefficient was 0.343). (2) Estradiol level on day of HCG administration had a negative correlation with BMI in overweight-obesity patients, and so were the patients whose age were 35 and above (P value respectively lower than 0.037 and 0.018). 0.80% of the total variation of estradiol (HCG day) is related to age and overweight-obesity while age took greater proportion (standardized partial regression coefficients were 0.066 and 0.058 respectively). (3) For older patients, age appeared to have negative relationships with duration of Gn and number of oocytes collected, full-grown follicles, fertilization, cleavage, two-pronucleus, normal embryos and cryopreserved embryos (P < 0.05). (4) Compared to young-normal weight patients, the odds ratio of pregnancy in eld-low weight and eld-overweight-obesity patients were 0.482 and 0.529 (P < 0.05) respectively. Age, but not the BMI, had significant effects on IVF/ICSI treatment. It seems that factors as losing weight before IVF or ICSI treatment effective in reducing the dose of Gn.

Hormonal induction of gamete release, and in-vitro fertilisation, in the critically endangered Southern Corroboree Frog, Pseudophryne corroboree

PubMed Central

2010-01-01

Background Conservation Breeding Programs (CBP's) are playing an important role in the protection of critically endangered anuran amphibians, but for many species recruitment is not successful enough to maintain captive populations, or provide individuals for release. In response, there has been an increasing focus on the use of Assisted Reproductive Technologies (ART), including the administration of reproductive hormones to induce gamete release followed by in vitro fertilisation. The objective of this study was to test the efficacy of two exogenous hormones to induce gamete release, for the purpose of conducting in vitro fertilisation (IVF), in one of Australia's most critically endangered frog species, Pseudophryne corroboree. Methods Male frogs were administered a single dose of either human chorionic gonadotropin (hCG) or luteinizing hormone-releasing hormone (LHRHa), while female frogs received both a priming and ovulatory dose of LHRHa. Spermiation responses were evaluated at 3, 7, 12, 24, 36, 48, 60 and 72 h post hormone administration (PA), and sperm number and viability were quantified using fluorescent microscopy. Ovulation responses were evaluated by stripping females every 12 h PA for 5 days. Once gametes were obtained, IVF was attempted by combining spermic urine with oocytes in a dilute solution of simplified amphibian ringer (SAR). Results Administration of both hCG and LHRHa induced approximately 80% of males to release sperm over 72 h. Peak sperm release occurred at 12 h PA for hCG treated males and 36 h PA for LHRHa treated males. On average, LHRHa treated males released a significantly higher total number of live sperm, and a higher concentration of sperm, over a longer period. In female frogs, administration of LHRHa induced approximately 30% of individuals to release eggs. On average, eggs were released between 24 and 48 h PA, with a peak in egg release at 36 h PA. IVF resulted in a moderate percentage (54.72%) of eggs being fertilised, however all resultant embryos failed prior to gastrulation. Conclusions Hormone treatment successfully induced spermiation and ovulation in P. corroboree, but refinement of gamete induction and IVF techniques will be required before ART protocols can be used to routinely propagate this species. PMID:21114857

The HAPPY study (Holistic Approach to Pregnancy and the first Postpartum Year): design of a large prospective cohort study.

PubMed

Truijens, Sophie E M; Meems, Margreet; Kuppens, Simone M I; Broeren, Maarten A C; Nabbe, Karin C A M; Wijnen, Hennie A; Oei, S Guid; van Son, Maarten J M; Pop, Victor J M

2014-09-08

The HAPPY study is a large prospective longitudinal cohort study in which pregnant women (N ≈ 2,500) are followed during the entire pregnancy and the whole first year postpartum. The study collects a substantial amount of psychological and physiological data investigating all kinds of determinants that might interfere with general well-being during pregnancy and postpartum, with special attention to the effect of maternal mood, pregnancy-related somatic symptoms (including nausea and vomiting (NVP) and carpal tunnel syndrome (CTS) symptoms), thyroid function, and human chorionic gonadotropin (HCG) on pregnancy outcome of mother and foetus. During pregnancy, participants receive questionnaires at 12, 22 and 32 weeks of gestation. Apart from a previous obstetric history, demographic features, distress symptoms, and pregnancy-related somatic symptoms are assessed. Furthermore, obstetrical data of the obstetric record form and ultrasound data are collected during pregnancy. At 12 and 30 weeks, thyroid function is assessed by blood analysis of thyroid stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase antibodies (TPO-Ab), as well as HCG. Also, depression is assessed with special focus on the two key symptoms: depressed mood and anhedonia. After childbirth, cord blood, neonatal heel screening results and all obstetrical data with regard to start of labour, mode of delivery and complications are collected. Moreover, mothers receive questionnaires at one week, six weeks, four, eight, and twelve months postpartum, to investigate recovery after pregnancy and delivery, including postpartum mood changes, emotional distress, feeding and development of the newborn. The key strength of this large prospective cohort study is the holistic (multifactorial) approach on perinatal well-being combined with a longitudinal design with measurements during all trimesters of pregnancy and the whole first year postpartum, taking into account two physiological possible markers of complaints and symptoms throughout gestation: thyroid function and HCG. The HAPPY study is among the first to investigate within one design physiological and psychological aspects of NVP and CTS symptoms during pregnancy. Finally, the concept of anhedonia and depressed mood as two distinct aspects of depression and its possible relation on obstetric outcome, breastfeeding, and postpartum well-being will be studied.

Endometrial cysteine-rich secretory protein 3 is inhibited by human chorionic gonadotrophin, and is increased in the decidua of tubal ectopic pregnancy.

PubMed

Horne, A W; Duncan, W C; King, A E; Burgess, S; Lourenco, P C; Cornes, P; Ghazal, P; Williams, A R; Udby, L; Critchley, H O D

2009-05-01

Ectopic pregnancy (EP) remains a considerable cause of morbidity and occasional mortality. Currently, there is no reliable test to differentiate ectopic from intrauterine gestation. We have previously used array technology to demonstrate that differences in gene expression in decidualized endometrium from women with ectopic and intrauterine gestations could be used to identify candidate diagnostic biomarkers for EP. The aim of this study was to further investigate the decidual gene with the highest fold increase in EP, cysteine-rich secretory protein-3 (CRISP-3). Decidualized endometrium from gestation-matched women undergoing surgical termination of pregnancy (n = 8), evacuation of uterus for miscarriage (n = 6) and surgery for EP (n = 11) was subjected to quantitative RT-PCR, morphological assessment, immunohistochemistry and western blot analysis. Sera were analysed for progesterone and human chorionic gonadotrophin (hCG) levels. Immortalized endometrial epithelial cells were cultured with physiological concentrations of hCG. CRISP-3 mRNA and protein expression were greater in endometrium from ectopic when compared with intrauterine pregnancies (P < 0.05). CRISP-3 protein was localized to epithelium and granulocytes of endometrium. CRISP-3 serum concentrations were not different in women with ectopic compared with intrauterine pregnancies. CRISP-3 expression in endometrium was not related to the degree of decidualization or to serum progesterone levels. Endometrial CRISP-3 expression was inversely proportional to serum hCG concentrations (P < 0.001). Stimulation of endometrial epithelial cells with hCG in vitro caused a reduction in CRISP-3 expression (P < 0.01). The measurement of CRISP-3 in endometrium could provide an additional tool in the diagnosis of failing early pregnancy of unknown location. The absence of a local reduction in expression of CRISP-3 in decidualized endometrium of women with EP may be due to reduced exposure to hCG due to the ectopic location of the trophoblast.

Assessment of uterine artery and arcuate artery blood flow by transvaginal color Doppler ultrasound on the day of human chorionic gonadotropin administration as predictors of pregnancy in an in vitro fertilization program.

PubMed

Ivanovski, M; Damcevski, N; Radevska, B; Doicev, G

2012-01-01

To investigate whether success rates of IVF/ICSI could be predicted by using the Color Doppler technique by measuring the uterine artery and arcuate artery pulsatility (PI), resistance (RI), and velocity (Vs) indices on the day of hCG injection. This was a prospective observational study at the St Lazar Hospital, Skopje; 106 patients with an indication for IVF or ICSI according to departmental protocol underwent controlled ovarian hyperstimulation followed by IVF/ICSI and embryo transfer. Using Color Doppler in the two-dimensional (2D) mode, flow velocity waveforms were obtained from the ascending main branch of the uterine artery on the right and left sides of the cervix in a longitudinal plane and arcuate arteries, before they entered the uterus. The PI, RI and peak systolic velocity (PSV) of the uterine arteries and arcuate arteries were calculated electronically when similar consecutive waveforms of good quality were obtained and results were compared between patients who conceived and those who did not. In total, 106 patients, aged 24-42 years were included in the study. The patients were divided into two groups according to successful outcome, defined as pregnancy and failure of implantation, where no pregnancy was detected. A total of 40 pregnancies resulted; a crude pregnancy rate was 40/106 (37.7%). There were no significant differences between either group in patients' age, type and duration of infertility; basal levels of FSH, LH and E2; number of gonadotropin ampoules used for ovulation induction; number of retrieved oocytes and number of transferred embryos. No cycle was canceled after initiation of gonadotropin stimulation. In our results, there were statistically significant lower mean uterine artery PI and RI in the pregnant group than in the non-pregnant group (P < 0.05). Arcuate artery PI value was lower in the pregnant group than in the non-pregnant group, but this did not reach statistical significance. Peak systolic velocity (Vs) values in both the mean uterine artery and arcuate artery were higher in the pregnant group than in the non-pregnant group; however, the difference was not statistically significant. Vascular impedance was calculated with PI, RI, and Vs values, among which PI was found to be the most important. Optimal uterine receptivity can be accomplished by reduced vascular resistance and increased blood flow, which will improve pregnancy success. We suggest the use of transvaginal color Doppler ultrasonography to measure the blood flow in uterine arteries and arcuate arteries before hCG in IVF cycles.

The value of HCG serum concentrations after trigger in predicting pregnancy and live birth rates in IVF-ICSI.

PubMed

Zhou, Jianjun; Wang, Shanshan; Wang, Bin; Wang, Junxia; Chen, Hua; Zhang, Ningyuan; Hu, Yali; Sun, Haixiang

2015-06-01

The aim of this study was to determine if an association existed between serum human chorionic gonadotrophin (HCG) level at 12 h after trigger and IVF and intracytoplasmic sperm (ICSI) treatment outcomes. Women undergoing initial IVF-ICSI and embryo transfer treatment using the long luteal phase gonadotrophin-releasing hormone agonist protocol between April 2012 and March 2013 for tubal factor were included (n = 699). In the clinical pregnancy group, HCG after trigger was significantly elevated (276.0 ± 5.1 versus 198.5 ± 6.1 mIU/mL; P < 0.001). The optimal cut-off value proposed by the receiver operating characteristic analysis (area under curve = 0.730) for HCG was 201.2 mIU/ml. Compared with the lower HCG group, the clinical pregnancy rate in the higher HCG group was increased in obese and non-obese patients (77.8% versus 57.3%, P < 0.05; 85.6% versus 53.0%, P < 0.01, respectively). Adjusted for age and body mass index, an increase of HCG was associated with a better IVF-ICSI treatment outcome (OR 4.39, 95% CI 2.99 to 6.45). Clinical pregnancy rate was significantly higher across increasing quartiles of HCG. An elevated level of serum HCG at 12 h after trigger was associated with a better IVF-ICSI outcome. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

An outcomes analysis of five prenatal screening strategies for trisomy 21 in women younger than 35 years.

PubMed

Biggio, Joseph R; Morris, T Christopher; Owen, John; Stringer, Jeffery S A

2004-03-01

This study was undertaken to examine the cost-effectiveness and procedural-related losses associated with 5 prenatal screening strategies for fetal aneuploidy in women under 35 years old. Five prenatal screening strategies were compared in a decision analysis model: triple screen: maternal age and midtrimester serum alpha-fetoprotein, human chorionic gonadotropin (hCG), and unconjugated estriol; quad screen: triple screen plus serum dimeric inhibin A; first-trimester screen: maternal age, serum pregnancy-associated plasma protein A and free beta-hCG and fetal nuchal translucency at 10 to 14 weeks' gestation; integrated screen: first-trimester screen plus quad screen, but first-trimester results are withheld until the quad screen is completed when a composite result is provided; sequential screen: first-trimester screen plus quad screen, but the first-trimester screen results are provided immediately and prenatal diagnosis offered if positive; later prenatal diagnosis is available if the quad screen is positive. Model estimates were literature derived, and cost estimates also included local sources. The 5 strategies were compared for cost, the numbers of Down syndrome fetuses detected and live births averted, and the number of procedure-related euploid losses. Sensitivity analyses were performed for parameters with imprecise point estimates. In the baseline analysis, sequential screening was the least expensive strategy ($455 million). It detected the most Down syndrome fetuses (n=1213), averted the most Down syndrome live births (n=678), but led to the highest number of procedure-related euploid losses (n=859). The integrated screen had the fewest euploid losses (n=62) and averted the second most Down syndrome live births (n=520). If fewer than 70% of women diagnosed with fetal Down syndrome elect to abort, the quad screen became the least expensive strategy. Although sequential screening was the most cost-effective prenatal screening strategy for fetal trisomy 21, it had the highest procedure-related euploid loss rate. The patient's perspective on detection versus fetal safety may help define the optimal screening strategy.

Intrauterine administration of human chorionic gonadotropin (hCG) for subfertile women undergoing assisted reproduction.

PubMed

Craciunas, Laurentiu; Tsampras, Nikolaos; Coomarasamy, Arri; Raine-Fenning, Nick

2016-05-20

Subfertility affects 15% of couples and represents the inability to conceive naturally following 12 months of regular unprotected sexual intercourse. Assisted reproduction refers to procedures involving the in vitro handling of both human gametes and represents a key option for many subfertile couples. Most women undergoing assisted reproduction treatment will reach the stage of embryo transfer (ET) but the proportion of embryos that successfully implant following ET has remained small since the mid-1990s. Human chorionic gonadotropin (hCG) is a hormone synthesised and released by the syncytiotrophoblast and has a fundamental role in embryo implantation and the early stages of pregnancy. Intrauterine administration of synthetic or natural hCG via an ET catheter during a mock procedure around the time of ET is a novel approach that has recently been suggested to improve the outcomes of assisted reproduction. To investigate whether the intrauterine administration of hCG around the time of ET improves the clinical outcomes in subfertile women undergoing assisted reproduction. We performed a comprehensive literature search of the Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, registers of ongoing trials andreference lists of all included studies and relevant reviews (from inception to 10 November 2015), in consultation with the Cochrane Gynaecology and Fertility Group Trials Search Co-ordinator. We included all randomised controlled trials (RCTs) evaluating intrauterine administration of hCG around the time of ET in this review irrespective of language and country of origin. Two authors independently selected studies, assessed risk of bias, extracted data from studies and attempted to contact the authors where data were missing. We performed statistical analysis using Review Manager 5 in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. We assessed evidence quality using GRADE methods. Twelve RCTs investigated the effect of intrauterine administration of hCG for 4038 subfertile women undergoing assisted reproduction. The intra-cavity hCG (IC-hCG) was administered in variable doses at different timings before the ET. The source of hCG was from the urine of pregnant women or from cell cultures using recombinant DNA technology.Most of the studies (9/12) were at high risk of bias in at least one of the seven domains assessed. Common problems were unclear reporting of study methods and lack of blinding. The main limitations in the overall quality of the evidence were high risk of bias and serious imprecision.For the analyses of live birth and clinical pregnancy, there was considerable heterogeneity (I(2) greater than 75%) and we did not undertake a meta-analysis. Exploration for the sources of heterogeneity identified two key pre-specified variables as important determinants: stage of ET (cleavage versus blastocyst stage) and dose of IC-hCG (less than 500 international units (IU) versus 500 IU or greater). We then performed meta-analysis for these analyses within the subgroups defined by stage of embryo and dose of IC-hCG.There was an increase in live birth rate in the subgroup of women having cleavage-stage ETs with an IC-hCG dose of 500 IU or greater compared to women having cleavage-stage ETs with no IC-hCG (risk ratio (RR) 1.57, 95% confidence interval (CI) 1.32 to 1.87, three RCTs, n = 914, I(2) = 0%, moderate quality evidence). In a clinic with a live birth rate of 25% per cycle then the use of IC-hCG -500 IU or greater would be associated with a live birth rate that varies from 33% to 46%. We did not observe a significant effect on live birth in any of the other subgroups.The was an increase in clinical pregnancy rate in the subgroup of women having cleavage-stage ETs with an IC-hCG dose of 500 IU or greater compared to women having cleavage-stage ETs with no IC-hCG (RR 1.41, 95% CI 1.25 to 1.58, seven RCTs, n = 1414, I(2) = 0%, moderate quality evidence). We did not observe a significant effect on clinical pregnancy in either of the other subgroups.There was no evidence that miscarriage was influenced by intrauterine hCG administration (RR 1.09, 95% CI 0.83 to 1.43, seven RCTs, n = 3395, I(2) = 0%, very low quality evidence).Other complications reported in the included studies were ectopic pregnancy (three RCTs, n = 915, three events overall), heterotopic pregnancy (one RCT, n = 495, one event), intrauterine death (two RCTs, n = 978, 21 events) and triplets (one RCT, n = 48, three events). There was no evidence of a difference between the groups, but there were too few events to allow any conclusions to be drawn and the evidence was very low quality. The pregnancy outcome for cleavage-stage ETs using an IC-hCG dose of 500 IU or greater is promising. However, given the small size and the variable quality of the trials and the fact that the positive finding was from a subgroup analysis, the current evidence for IC-hCG treatment does not support its use in assisted reproduction cycles. A definitive large clinical trial with live birth as the primary outcome is recommended. There was no evidence that miscarriage was influenced by intrauterine hCG administration, irrespective of embryo stage at transfer or dose of IC-hCG. There were too few events to allow any conclusions to be drawn with regard to other complications.

Birth after human chorionic gonadotropin-primed oocyte in vitro maturation and fertilization with testicular sperm in a normo-ovulatory patient.

PubMed

González-Ortega, Claudia; Piña-Aguilar, Raul Eduardo; Cancino-Villareal, Patricia; Gutiérrez-Gutiérrez, Antonio Martin

2016-01-01

In this report, we present a case of in vitro maturation (IVM) with surgical retrieved testicular sperm in a normo-ovulatory female. Human chorionic gonadotropin-primed IVM, testicular biopsy for sperm retrieval and intracytoplasmic sperm injection with fresh sperm were performed. Fourteen cumulus-oocyte complexes were obtained in germinal vesicle or metaphase I stage, eight oocytes reached metaphase II, seven presumptive zygotes were obtained, and three cleavage stages embryos in day 2 were transferred producing a singleton pregnancy. A single healthy newborn was obtained. Our results suggest that IVM may be an alternative for in vitro fertilization in normo-ovulatory women even if surgical retrieval of sperm is needed. Further research is required to depict contributing factors to the success of IVM in indications different from polycystic ovaries syndrome and the role of male gamete.

Receptor-binding region in human choriogonadotropin/lutropin. beta. subunit

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

Keutmann, H.T.; Charlesworth, M.C.; Mason, K.A.

1987-04-01

Synthetic fragments have not been widely used thus far to evaluate structure-activity relations in the glycoprotein hormones. The authors prepared a series of peptides representing the intercysteine loop sequence (residues 38-57) in human choriogonadotropin (hCG) and lutropin (hLH) ..beta.. subunits, anticipating that it might be oriented toward the surface and accessible to receptors. The peptides were characterized chemically and tested for bioactivity by binding to rat ovarian membrane receptor and stimulation of Leydig cell testosterone production. The hCG..beta..-(38-57) and hLH..beta..-(38-57) peptides inhibited binding of /sup 125/I-labeled hCG half-maximally at 1.51 x 10/sup -4/ and 2.03 x 10/sup -5/ M, respectively,more » while other peptide hormones and fragments from elsewhere in the ..beta.. subunit were inactive. Both peptides stimulated testosterone production, with half-maximal responses at 3.55 x 10/sup -5/ M (hCG) and 2.18 x 10/sup -5/ M (hLH). By radioimmunoassay with an antibody to thyroglobulin-conjugated hCG..beta..-(38-57) peptide, native hCG and ..beta.. subunit were highly reactive, as were the reduced and carboxymethylated subunit and peptide. These results indicate that the 38-57 region of ..beta.. subunit is exposed on the surface and constitutes a component in the receptor-binding domain for hCG and hLH. A region of amphipathic-helical structure in the 38-57 sequence may promote hormone-receptor interactions in a manner proposed for several other peptide hormones.« less

The Role of Serum Beta hCG in Early Diagnosis and Management Strategy of Ectopic Pregnancy.

PubMed

Surampudi, Kameswari; Gundabattula, Sirisha Rao

2016-07-01

The presentation of Ectopic Pregnancy (EP) can be highly variable and serum Beta hCG estimation plays an important role in early diagnosis. Aim of the study was to determine the trends of hCG levels in EP and to explore the role of hCG in decisions related to management and follow-up of EPs. A retrospective study of women who had EPs from January 2006 to December 2012 at an advanced tertiary care centre in southern India was carried out. These women had undergone treatment based on the hospital protocol. The study identified 337 women with EP. Thirty one surgically confirmed cases were diagnosed below the discriminatory zone of 1500 mIU/ml. Among women who had Beta hCG estimations 48 hours apart, plateauing was observed in 22.5% while decrease >15% was noted in 26.8%. Almost half (47.9%) of the cases had an increase >15% and a few (2.8%) demonstrated an initial fall followed by a rise in titres. In 23.9% of these women, there was a rise >53% similar to intrauterine pregnancy. The average pre-treatment Beta hCG was 429.8, 3866.2 and 12961.5 mIU/ml for those who received expectant, medical and direct surgical treatment respectively. 43 women with relative contraindications received medical management and 39 were lost to follow-up after medical and expectant management. Excluding them, the success rate of these two modalities was 76.6% and 85.0% respectively. No single level of Beta hCG is diagnostic of EP and serial levels can demonstrate atypical trends in some cases. Hence, interpretation of these results should be done in conjunction with clinical and sonographic findings to arrive at a correct diagnosis.

Mitigation of septic shock in mice and rhesus monkeys by human chorionic gonadotrophin-related oligopeptides

PubMed Central

Khan, N A; Vierboom, M P M; van Holten – Neelen, C; Breedveld, E; Zuiderwijk-Sick, E; Khan, A; Kondova, I; Braskamp, G; Savelkoul, H F J; Dik, W A; ‘t Hart, B A; Benner, R

2010-01-01

The marked improvement of several immune-mediated inflammatory diseases during pregnancy has drawn attention to pregnancy hormones as potential therapeutics for such disorders. Low molecular weight fractions derived from the pregnancy hormone human chorionic gonadotrophin (hCG) have remarkable potent immunosuppressive effects in mouse models of diabetes and septic shock. Based on these data we have designed a set of oligopeptides related to the primary structure of hCG and tested these in models of septic shock in mice and rhesus monkeys. We demonstrate that mice exposed to lipopolysaccharide (LPS) and treated subsequently with selected tri-, tetra-, penta- and hepta-meric oligopeptides (i.e. MTR, VVC, MTRV, LQGV, AQGV, VLPALP, VLPALPQ) are protected against fatal LPS-induced septic shock. Moreover, administration of a cocktail of three selected oligopeptides (LQGV, AQGV and VLPALP) improved the pathological features markedly and nearly improved haemodynamic parameters associated with intravenous Escherichia coli-induced septic shock in rhesus monkeys. These data indicate that the designed hCG-related oligopeptides may present a potential treatment for the initial hyperdynamic phase of septic shock in humans. PMID:20345979

Microdevice for plasma separation from whole human blood using bio-physical and geometrical effects

PubMed Central

Tripathi, Siddhartha; Kumar, Y. V. BalaVarun; Agrawal, Amit; Prabhakar, Amit; Joshi, Suhas S.

2016-01-01

In this research work, we present a simple and efficient passive microfluidic device for plasma separation from pure blood. The microdevice has been fabricated using conventional photolithography technique on a single layer of polydimethylsiloxane, and has been extensively tested on whole blood and enhanced (upto 62%) hematocrit levels of human blood. The microdevice employs elevated dimensions of about 100 μm; such elevated dimensions ensure clog-free operation of the microdevice and is relatively easy to fabricate. We show that our microdevice achieves almost 100% separation efficiency on undiluted blood in the flow rate range of 0.3 to 0.5 ml/min. Detailed biological characterization of the plasma obtained from the microdevice is carried out by testing: proteins by ultra-violet spectrophotometric method, hCG (human chorionic gonadotropin) hormone, and conducting random blood glucose test. Additionally, flow cytometry study has also been carried on the separated plasma. These tests attest to the high quality of plasma recovered. The microdevice developed in this work is an outcome of extensive experimental research on understanding the flow behavior and separation phenomenon of blood in microchannels. The microdevice is compact, economical and effective, and is particularly suited in continuous flow operations. PMID:27279146

Smartphone-Based Dual-Modality Imaging System for Quantitative Detection of Color or Fluorescent Lateral Flow Immunochromatographic Strips

NASA Astrophysics Data System (ADS)

Hou, Yafei; Wang, Kan; Xiao, Kun; Qin, Weijian; Lu, Wenting; Tao, Wei; Cui, Daxiang

2017-04-01

Nowadays, lateral flow immunochromatographic assays are increasingly popular as a diagnostic tool for point-of-care (POC) test based on their simplicity, specificity, and sensitivity. Hence, quantitative detection and pluralistic popular application are urgently needed in medical examination. In this study, a smartphone-based dual-modality imaging system was developed for quantitative detection of color or fluorescent lateral flow test strips, which can be operated anywhere at any time. In this system, the white and ultra-violet (UV) light of optical device was designed, which was tunable with different strips, and the Sobel operator algorithm was used in the software, which could enhance the identification ability to recognize the test area from the background boundary information. Moreover, this technology based on extraction of the components from RGB format (red, green, and blue) of color strips or only red format of the fluorescent strips can obviously improve the high-signal intensity and sensitivity. Fifty samples were used to evaluate the accuracy of this system, and the ideal detection limit was calculated separately from detection of human chorionic gonadotropin (HCG) and carcinoembryonic antigen (CEA). The results indicated that smartphone-controlled dual-modality imaging system could provide various POC diagnoses, which becomes a potential technology for developing the next-generation of portable system in the near future.

Malignant mixed germ cell tumour of ovary--an unusual combination and review of literature.

PubMed

Goyal, Lajya Devi; Kaur, Sharanjit; Kawatra, Kanwardeep

2014-11-04

Mixed germ cell tumours of the ovary are malignant neoplasms of the ovary comprising of two or more types of germ cell components. Most of the malignant mixed germ cell tumours consists of dysgerminoma accompanied by endodermal sinus tumours, immature teratoma or choriocarcinoma. There are only few case reports of mixed germ cell tumours with different combinations of malignant components. We report a very rare case of mixed germ cell tumours consisted of malignant components of endodermal sinus tumour, emryonal carcinoma, and benign component of teratomatuos and trophoblastic differentiation. This is the first case report in the literature with both benign and malignant component of type described to best of our knowledge. Patient was an 18 year old girl, who presented with pain abdomen, abdominal mass and irregular bleeding. Ultrasound and CT scan showed a huge mass with solid and cystic component. Tumour markers i.e alpha feto- protein (AFP), human chorionic gonadotropin (hCG), lactate dehydrogenate (LDH) and Ca-125 were raised. We performed fertility sparing surgery by preserving one ovary, tube and uterus. Conclusion: Malingnant mixed germ cell tumours of ovary are highly aggressive neoplasm and early intervention and fertility sparing surgery is required for any adolescent girl presenting with rapidly enlarging pelvic mass.