Exogenous Human Chorionic Gonadotropin Research Articles

Bilateral testicular Leydig cell hyperplasia presented incidentally: A case report.

IntroductionLeydig cell hyperplasia or tumor represents less than 3% of all testicular tumors. It can be defined as an increase in the size and number of Leydig cell within the testicles. These cells are responsible for the production of testosterone in human males.Case presentationOur patient is a forty-eight-year-old male presented with erectile dysfunction and decreased libido for the past six months. Ultrasound of the scrotum show bilateral hypoechoic testicular masses larger on the left size thus left orchidectomy was performed. Histopathology confirmed our diagnosis.DiscussionLeydig cell hyperplasia (LCH) is a rare and mostly benign entity that affects both children and adults. In adults, it might be associated with variety of condition including Klinefelter's syndrome, exogenous human chorionic gonadotropin (hCG) therapy, and many others but it mostly occurs idiopathically. Scrotal ultrasound and tumor markers can be used to diagnose most of the patients with LCH.ConclusionLCH should be differentiated from Leydig cell tumor to avoid unnecessary and sometimes harmful intervention in the future.

Clinical Pregnancy and Incidence of Ovarian Hyperstimulation Syndrome in High Ovarian Responders Receiving Different Doses of hCG Supplementation in a GnRH-Agonist Trigger Protocol.

Objective Ovarian hyperstimulation syndrome (OHSS) is a side effect of the exogenous human chorionic gonadotropin (hCG) hormones used to trigger oocyte maturation. High ovarian responders represent a population with a higher risk of OHSS and are characterized by an exaggerated response to gonadotropin administration. In this study, we compared clinical pregnancy and incidence of OHSS in high ovarian responders receiving different doses of hCG supplementation in a GnRH-agonist trigger protocol. Methods A total of 205 high ovarian responders who were to undergo in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were recruited and randomly assigned to receive different doses of hCG supplementation in a GnRH-agonist trigger protocol: GnRH-a (n = 42), GnRH-a + 1000 IU hCG (n = 49), GnRH-a + 2000 IU hCG (n = 54), and GnRH-a + 3000 IU hCG (n = 60) groups. Results The GnRH-a + 1000 IU hCG, GnRH-a + 2000 IU hCG, and GnRH-a + 3000 IU hCG groups had more oocytes retrieved, embryos, high-quality embryos, and a higher rate of high-quality embryos than the GnRH-a group (p < 0.05). The GnRH-a + 1000 IU hCG group demonstrated more oocytes retrieved, embryos, high-quality embryos, and a higher rate of high-quality embryos than the GnRH-a + 2000 IU hCG and GnRH-a + 3000 IU hCG groups (p < 0.05). No moderate and severe OHSS cases occurred in the GnRH-a and GnRH-a + 1000 IU hCG groups. The incidence rate of moderate and severe OHSS was remarkably lower in the GnRH-a group and GnRH-a + 1000 IU hCG groups than in the GnRH-a + 2000 IU hCG and GnRH-a + 3000 IU hCG groups (p < 0.05). The GnRH-a + 1000 IU hCG, GnRH-a + 2000 IU hCG, and GnRH-a + 3000 IU hCG groups had a higher clinical pregnancy rate than the GnRH-a group, showing no significant difference (p > 0.05). The GnRH-a + 1000 IU hCG, GnRH-a + 2000 IU hCG, and GnRH-a + 3000 IU hCG groups had a lower abortion rate than the GnRH-a group (p < 0.05). Conclusion Based on the data obtained from this prospective study, we recommend 1000 IU hCG supplementation in a GnRH-agonist trigger protocol for high ovarian responders during IVF/ICSI cycles considering a higher rate of high-quality embryos, a lower incidence rate of moderate and severe OHSS, and a lower abortion rate.

Measuring the Effects of a Single Dose of Human Chorionic Gonadotropin (hCG) on Plasma Testosterone Concentrations in Leopard Geckos (Eublepharis macularius)

Current estimates suggest that one-fifth of all reptiles are currently threatened with extinction because of anthropogenic activity, and that if nothing is done to mitigate these impacts, massive extinctions will occur over the coming decades. Assisted reproductive technologies (ART) can be used to develop ex vivo conservation programs to ensure species survival until environmental deficiencies can be corrected. Geckos represent one of the most diverse groups of reptiles on earth and need protection; however, to date, no ART have been developed for these animals. Exogenous human chorionic gonadotropin (hCG) is routinely used to alter reproductive hormones of vertebrates and are integrated in ART. The purpose of this study was to determine if a single dose of hCG could increase plasma testosterone concentrations in the leopard gecko (Eublepharis macularius) within 24 h of administration. The study was performed in September, which is considered the nonbreeding season for this species in the northern hemisphere. Twelve captive-bred, adult, male leopard geckos were randomly divided into three treatment groups and administered an intramuscular injection of hCG (50 or 100 IU) or saline. Whole blood was collected prior to injection (baseline) and 12 and 24 h after injection. Plasma testosterone concentrations were measured using an enzyme immunoassay kit. There was no significant difference (P = 0.195) in testosterone concentrations between treatment groups. Because there was no difference, an observed testosterone range (61.0 ± 42.5, 5.5–149.0) for September was calculated. These results suggest that captive leopard geckos may be in a recrudescence phase in September in the northern hemisphere.

Endocrine and molecular milieus of ovarian follicles are diversely affected by human chorionic gonadotropin and gonadotropin-releasing hormone in prepubertal and mature gilts

Different strategies are used to meet optimal reproductive performance or manage reproductive health. Although exogenous human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone (GnRH) agonists (A) are commonly used to trigger ovulation in estrous cycle synchronization, little is known about their effect on the ovarian follicle. Here, we explored whether hCG- and GnRH-A-induced native luteinizing hormone (LH) can affect the endocrine and molecular milieus of ovarian preovulatory follicles in pigs at different stages of sexual development. We collected ovaries 30 h after hCG/GnRH-A administration from altrenogest and pregnant mare serum gonadotropin (eCG)-primed prepubertal and sexually mature gilts. Several endocrine and molecular alternations were indicated, including broad hormonal trigger-induced changes in follicular fluid steroid hormones and prostaglandin levels. However, sexual maturity affected only estradiol levels. Trigger- and/or maturity-dependent changes in the abundance of hormone receptors (FSHR and LHCGR) and proteins associated with lipid metabolism and steroidogenesis (e.g., STAR, HSD3B1, and CYP11A1), prostaglandin synthesis (PTGS2 and PTGFS), extracellular matrix remodeling (MMP1 and TIMP1), protein folding (HSPs), molecular transport (TF), and cell function and survival (e.g., VIM) were observed. These data revealed different endocrine properties of exogenous and endogenous gonadotropins, with a potent progestational/androgenic role of hCG and estrogenic/pro-developmental function of LH.

Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation

The future fertility of prepubertal boys with cancer may be irreversibly compromised by chemotherapy and/or radiotherapy. Successful spermatogenesis has not been achieved following the xenotransplantation of prepubertal human testis tissue, which is likely due to the failure of somatic cell maturation and function. We used a validated xenograft model to identify the factors required for Leydig and Sertoli cell development and function in immature human testis. Importantly, we compared the maturation status of Sertoli cells in xenografts with that of human testis tissues (n = 9, 1 year-adult). Human fetal testis (n = 6; 14–21 gestational weeks) tissue, which models many aspects of prepubertal testicular development, was transplanted subcutaneously into castrated immunocompromised mice for ~12 months. The mice received exogenous human chorionic gonadotropin (hCG; 20IU, 3×/week). In xenografts exposed continuously to hCG, we demonstrate the maintenance of Leydig cell steroidogenesis, the acquisition of features of Sertoli cell maturation (androgen receptor, lumen development), and the formation of the blood–testis barrier (connexin 43), none of which were present prior to the transplantation or in xenografts in which hCG was withdrawn after 7 months. These studies provide evidence that hCG plays a role in Sertoli cell maturation, which is relevant for future investigations, helping them generate functional gametes from immature testis tissue for clinical application.

Effect of exogenous human chorionic gonadotropin on ovulation in mice

The implementation of assisted reproductive technologies (ART), hormonal stimulation in particular, may change the quality of ovulated oocytes. The purpose of our work was to study ovulation in CD1 mice after their stimulation with human chorionic gonadotropin (hCG) and to investigate the effects of such hormonal stimulation on the pregnancy duration, fetal losses and the weight of the offspring. No significant differences were found in the total number of ovulated oocytes or in the number of immature (without a polar body) ovulated oocytes; nor were there differences between the groups in the number of oocytes with a developing polar body. However, the number of matured oocytes with a distinct polar body was significantly higher (p &lt; 0.05) in mice stimulated with hCG (experimental group) as compared with the controls (6.2 ± 0.86 and 2.2 ± 0.97, respectively). No significant differences were observed between the experimental and control mice in the duration of pregnancy or in the numbers of term offspring, including the percentage of live and stillborn pups. However, the body weight of the offspring in the experimental group was significantly lower (p &lt; 0.001) as compared with the controls on the fifth day after birth (3.16 ± 0.09 and 3.76 ± 0.07, respectively). Thus, exogenous hCG facilitates the development of mouse oocytes in vivo, which leads to the larger number of their mature forms at ovulation, however, the offspring born after hCG-stimulated pregnancy was characterized by a lower body weight on the fifth day after birth.

To Compare the Exogenous Human Chorionic Gonadotropin Trigger with Endogenous Leutinizing Hormone Surge in Ultrasound Monitored Cycles for Timing of Intrauterine Insemination in Women with Unexplained Infertility

To Compare the Exogenous Human Chorionic Gonadotropin Trigger with Endogenous Leutinizing Hormone Surge in Ultrasound Monitored Cycles for Timing of Intrauterine Insemination in Women with Unexplained Infertility

High level of C-type natriuretic peptide induced by hyperandrogen-mediated anovulation in polycystic ovary syndrome mice.

Polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, is a complex endocrinopathy that affects the fertility of 9-18% of reproductive-aged women. However, the exact mechanism of PCOS, especially hyperandrogen-induced anovulation, is largely unknown to date. Physiologically, the natriuretic peptide type C/natriuretic peptide receptor 2 (CNP/NPR2) system is essential for sustaining oocyte meiotic arrest until the preovulatory luteinizing hormone (LH) surge. We therefore hypothesized that the CNP/NPR2 system is also involved in PCOS and contributes to arresting oocyte meiosis and ovulation. Here, based on a dehydroepiandrosterone (DHEA)-induced PCOS-like mouse model, persistent high levels of CNP/NPR2 were detected in anovulation ovaries. Meanwhile, oocytes arrested at thegerminal vesicle stage correlated with persistent high levels of androgen and estrogen. We further showed that ovulation failure in these mice could be a result of elevated Nppc/Npr2 gene transcription that was directly increased by androgen (AR) and estrogen (ER) receptor signaling. Consistent with this, anovulation was alleviated by administration of either exogenous human chorionic gonadotropin (hCG) or inhibitors of AR or ER to reduce the level of CNP/NPR2. Additionally, the CNP/NPR2 expression pattern in the anovulated follicles was, to some extent, consistent with the clinical expression in PCOS patients. Therefore, our study highlights the important role an overactive CNP/NPR2 system caused by hyperandrogenism in preventing oocytes from maturation and ovulation in PCOS mice. Our findings provide insight into potential mechanisms responsible for infertility in women with PCOS.

Exogenous human chorionic gonadotropin exposure from the ovulatory trigger does not impair endometrial receptivity

It has been reported that exogenous hCG from a trigger injection impairs embryo implantation and endometrial receptivity. This study was performed to determine if a relationship exists between exogenous hCG exposure (dose, serum level) and clinical pregnancy in fresh autologous embryo transfer cycles, while controlling for confounding variables.

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

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 factorVIII 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.

Does a Reduced HCG Trigger Dose Compromise Outcomes in a Large Prospective Trial of Vaginal Progesterone for Luteal Phase Support?

Exogenous human chorionic gonadotrophin (hCG) is often used to trigger ovulation in controlled ovarian stimulation protocols. The most common hCG dose used in in vitro fertilization (IVF) cycles is 10,000 IU, although lower doses may benefit women predicted to be high responders and at risk for ovarian hyperstimulation syndrome (OHSS). The optimal hCG trigger dose that balances achieving successful IVF outcomes while minimizing the risk of OHSS has yet to be determined.

First manic episode associated with use of human chorionic gonadotropin for obesity: a case report

Although highly controversial, the treatment of obesity with exogenous human chorionic gonadotropin (HCG) remains popular in the USA. We report the case of a patient whose first manic episode was associated with the use of HCG for weight loss. A 32-year-old female patient was admitted to our psychiatric inpatient unit due to a two-week history of manic symptoms. She had no previous history of manic or hypomanic episodes and had completed a 45-day course of sublingual HCG for weight loss immediately prior to the onset of the manic episode. The patient was treated with lithium carbonate and aripiprazole, and progressed with improvement in the symptoms. While it is not possible to definitively link the HCG use to the development of mania, available evidence suggests that HCG may have a contributing role in triggering manic symptomatology.

Effects of steroid ablation and progestin replacement on the transcriptome of the primate corpus luteum during simulated early pregnancy

Previous microarray analyses indicated that a portion of the transcriptome in the macaque corpus luteum (CL) of the menstrual cycle was regulated indirectly by luteinizing hormone via the local actions of steroid hormones, notably progesterone (P). The current study was designed to investigate this concept in the CL of early pregnancy by analyzing chorionic gonadotrophin (CG)-regulated genes that are dependent versus independent of local steroid action. Exogenous human chorionic gonadotropin treatment simulating early pregnancy (SEP) began on Day 9 of the luteal phase in female rhesus monkeys with and without concurrent administration of the 3-β-hydroxysteroid dehydrogenase inhibitor trilostane (TRL) with or without the synthetic progestin R5020. Compared with SEP treatment alone, TRL altered 50 mRNA transcripts on Day 10, rising to 95 on Day 15 (P<0.05, ≥2-fold change in gene expression). Steroid-sensitive genes were validated; notably effects of steroid ablation and P replacement varied by day. Expression of some genes previously identified as P-regulated in the macaque CL during the menstrual cycle were not significantly altered by steroid ablation and P replacement during CG exposure in SEP. These data indicate that the majority of CG-regulated luteal transcripts are differentially expressed independently of local steroid actions. However, the steroid-regulated genes in the macaque CL may be essential during early pregnancy, based on previous reports that TRL treatment initiates premature structural regression of the CL during SEP. These data reinforce the concept that the structure, function and regulation of the rescued CL in early pregnancy differs from the CL of the menstrual cycle in primates.

Identification of the High-Risk Patient for Ovarian Hyperstimulation Syndrome

Ovarian hyperstimulation syndrome (OHSS), an iatrogenic complication of ovarian stimulation for assisted reproduction, is a potentially life-threatening condition. Exogenous human chorionic gonadotropin (hCG) administered for final oocyte maturation and endogenous hCG produced by a developing pregnancy are fundamental in the development of the disease. Vascular endothelial growth factor is the key molecule mediating the pathophysiology of the syndrome, and genetic predisposition might play a role. Because the most severe cases are usually the late OHSS cases that occur when a pregnancy is established, several predictive markers have been introduced to identify the high-risk patient profile and consequently develop preventive strategies. This article reviews the most recent evidence evaluating the accuracy of different OHSS prediction parameters. Stratification was attempted according to the phase of the ovarian stimulation that the patients undergo. Anti-Müllerian hormone and the number of follicles seen on ultrasound seem promising discriminating factors, whereas prediction models that include age, antral follicle count, and estrogen levels on the day of ovulation triggering provide variable sensitivity and specificity. Until reliable genetic tests are available, and considering that the occurrence of pregnancy is unpredictable, the use of prognostic factors will be mainly indicative of risk rather than preventive of OHSS.

A unique human chorionic gonadotropin antagonist suppresses ovarian hyperstimulation syndrome in rats.

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.

Expression and regulation of oestrogen receptors in the human corpus luteum

The molecular mechanisms underlying the control of corpus luteum lifespan in women are not fully understood. Oestradiol has various luteolytic, or luteotrophic, functions in some species, and as it is synthesised within the human corpus luteum, it is an excellent candidate molecule to be a paracrine regulator of luteal function. This study aimed to comprehensively investigate the expression, regulation and effects of oestrogen receptors (ER) in human luteal cells. Genomic oestrogen receptors ERalpha, ERbeta1 and ERbeta2 were immunolocalised in human corpora lutea from throughout the luteal phase. mRNA expression was investigated throughout the luteal phase and after luteal rescue with exogenous human chorionic gonadotrophin (hCG). The regulation of ER expression and oestradiol action was investigated in cultures of luteinised granulosa cells. ER subtypes ERbeta1 and ERbeta2 were localised throughout the luteal phase to steroidogenic cells in the human corpus luteum and cells of the surrounding stroma. Unlike follicular granulosa cells, steroidogenic cells in the corpus luteum showed minimal ERalpha immunostaining. The presence of endothelial cells in the granulosa cell layer with ERbeta1 and ERbeta2 positive nuclei was noted. ERbeta1 and ERbeta2 were differentially regulated across the luteal phase with ERbeta1 maximally expressed in the mid-luteal phase, while ERbeta2 expression was maximal in the early luteal phase. In vivo and in vitro, hCG had no long-term effect on ER expression, although in vitro hCG and oestradiol acutely down-regulated ERs. Treatment with oestradiol in vitro down-regulated 11beta-hydroxysteroid dehydrogenase type 1 and inhibin betaA subunit confirming a functional oestradiol response. These data highlight functional and differentially regulated oestradiol reception in human luteal cells.

P-129: Leuprolide acetate 0.2 cc with human chorionic gonadotropin to trigger ovulation as an effective method to decrease ovarian hyperstimulation syndrome pain without affecting the implantation rate in donor oocyte cycles

Ovarian Hyperstimulation (OHSS) is a significant complication of gonadotropin therapy. Ovulation induction cycles should be highly individualized and should use the minimum effective dosage of Human Chorionic Gonadotropin (HCG) to significantly reduce the risk of OHSS. However, it is unclear if pregnancy rates are compromised by Leuprolide Acetate (LA) trigger alone. Oocyte donors with OHSS will frequently have to take time off from work and will refuse to do another Donor Egg/IVF cycle. The use of LA alone has been shown in several studies to trigger ovulation through an endogenous LH surge. This effect is more physiological than an exogenous HCG trigger, thus reducing the risk of pain and OHSS. This is a retrospective study of donor oocyte patients: Leuprolide Acetate (LA) 1 mg (o.2cc) subcutaneously was given synchronously with 1.25 - 5K HCG. Patients were evaluated for OHSS symptoms (pain 1 to 2 days after the oocyte retrieval), number of oocytes retrieved, peak estradiol levels, number of cryopreserved embryos, and implantation rate. Retrospective review of 33 donor oocyte retrievals from 1/2004 - 1/2006 were evaluated in patients who received LA 0.2cc trigger with HCG. These patients were categorized according to if they had pain versus no pain 1 to 2 days after the retrieval. Ages of the egg donors ranged from 20 to 34. Patients were selected to receive HCG plus LA if their estradiol level ranged from 1600-8800 and the number of follicles greater than 15 ranged from 5-12 A total of 33 donor oocyte patients received LA 0.2cc with HCG. There were 8 shared cycles for a total of 39 transfers. Patients who received LA 0.2cc with HCG had estradiol peak levels ranging from 1618 to 8806, total number of oocytes ranging from 13-68, implantation occurred in 29 recipients (16 singletons, 11 twins, and 2 triplets) with cryopreserved embryos ranging form 0-45. There were a total of 7 patients with complaints of mild to moderate pain and 2 OHSS patients. There was a low incidence of pain in the LA plus HCG donors even though their estradiol levels were high and high number of oocytes retrieved. Oocyte donor patients who receive LA with HCG may have a reduced risk of OHSS symptoms, however the amounts of HCG may be the significant factor. It is prudent for all oocyte donor patients to be assessed for OHSS. Lowering HCG dose and/or using LA may decrease the incidenceof OHSS in a donor oocyte program. Oocytes donors may have less morbidity and may be more likely to pursue additional donation cycles if the incidence of OHSS were lower. Larger studies are needed to compare LA with HCG with donor oocyte patients, as well as regular IVF patients. Other factors to consider are evaluating whether it is the effect of the Gonadotropin Releasing Hormone (GnRH) agonist, LA 0.2cc with HCG or is it the lower dosage of HCG that decreases the incidence of OHSS. Also another question to explore would be if lower doses of HCG would be as effective without LA?

First trimester threatened miscarriage treatment with human chorionic gonadotrophins: a randomised controlled trial

To determine whether administration of exogenous human chorionic gonadotrophin (hCG) treatment improve the pregnancy outcome in first trimester threatened miscarriages. A prospective, double blind, randomised, placebo-controlled trial. The Early Pregnancy Assessment Unit, Royal Bolton Hospital, Bolton, United Kingdom. One hundred and eighty-three women with vaginal bleeding and a viable fetus seen on ultrasound scan (USS) in the first 12 weeks of pregnancy. The patients were randomised to receive either hCG or placebo treatment until 14 weeks of gestation. The primary objective of the trial was to determine the miscarriage rate in the hCG arm compared from the placebo arm. Of the 183 cases, 87 were randomised to treatment with hCG while 96 were randomised to receive a placebo. Forty-seven (25%) did not comply with the study protocol. The mean [SD] gestational age at presentation was 7 [1.33] weeks. The mean [SD] age of women in study was 27 [5] years in the placebo and 28 [5] in the hCG group. The mean body mass index (kg/m(2)) was 25 [5] in the study. The number of patients actively bleeding per vaginum at presentation was 85 (93%) in placebo group and 79 (96%) in the hCG group. The median number of hCG or placebo injections for both groups was 7. Ten women (11%) in the placebo group proceeded to have a complete miscarriage, as did 10 women (12%) in the hCG group, relative risk (RR) [95% confidence interval (CI)] of 1.1 (0.63-1.6). Our study showed no evidence of a difference in the outcome of threatened miscarriages when treated with hCG in the first trimester, this may be because our study sample size was small and follow up was suboptimal. A large, randomised, multicentre trial is still needed to establish the usefulness of hCG treatment in cases of threatened miscarriage.

Prevention of Endometrial Apoptosis: Randomized Prospective Comparison of Human Chorionic GonadotropinVersusProgesterone Treatment in the Luteal Phase

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.

Upregulation of mRNA expression of vascular endothelial growth factor and its receptors by exogenous human chorionic gonadotropin in cultured oviduct mucosal cells

The mucosal cells were isolated from the ampullary regions of 20 human oviducts and cultured with or without hCG in five different concentrations (1-100 ng/mL). As analyzed by the semiquantitative reverse-transcriptase polymerase chain reaction, hCG treatment significantly increased mRNA expression of vascular endothelial growth factor and its receptor flt-1 in the cultured mucosal cells in a dose-dependent manner but had no effect on the expression of another receptor, KDR.