Administration Of Human Menopausal Gonadotropin Research Articles

P-695 Optimizing oocyte donor stimulation: A revelation from 2,666 cases emphasizing the sole efficacy of exogenous FSH

Abstract Study question Does the administration of human menopausal gonadotrophin in controlled ovarian stimulation improve clinical outcomes in the oocyte donation program? Summary answer The addition of hMG (human menopausal gonadotropin) reduces the number of retrieved oocytes without improving embryo development or clinical outcomes in oocyte donation program. What is known already In controlled ovarian stimulation for assisted reproduction treatments, follicle stimulating hormone(FSH) is essential, but the importance of LH supplementation from menopausal origin is controversial. It is a common practice to use hMG to provide the LH effect. The standard preparation contains FSH and LH effects in a 1:1 ratio.The FSH component would recruit ovarian follicles and stimulate their growth, while the LH component would facilitate their maturation. Our aim was to compare the outcomes of intracytoplasmic sperm injection (ICSI) treatments using a gonadotropin-releasing hormone GnRH) antagonist protocol with recombinant FSH(FSHr) alone and supplemented with hMG in the oocyte donation program. Study design, size, duration This is a retrospective cohort study of 2,666 patients enrolled in the oocyte donation program at a single center over four consecutive years. Donor stimulation commenced with daily FSHr injections. The FSHr group (n = 2,078) continued FSHr, while the FSHr+hMG group (n = 588) received hMG. Participants/materials, setting, methods Donors received GnRH agonist via i.m. injection until a mean diameter >18 mm in at least eight follicles. Transvaginal oocyte retrieval was scheduled 36h later, followed by ICSI for all retrieved oocytes. Embryos were cultured in time-lapse systems and evaluated using an artificial intelligence-based model (iDAScore v2). Recipients underwent hormone replacement therapy for endometrial preparation. Our comparative study examined oocytes retrieved, embryo score, implantation, and live birth outcomes in fresh and frozen embryo transfers (ETs). Main results and the role of chance The number of retrieved oocytes was higher in the FSHr group than in the FSHr+hMG group: 24.9±10.6 vs. 18.2±8.8 (p < 0.001). In addition, embryos from the FSHr+hMG group exhibited slower early development, with significantly lower division times to two, three, four and five cells in the FSHr group (p < 0.005). However, late parameters of embryo development showed no differences. Automatic scoring by the deep learning algorithm was identical for blastocysts in the FSHr (4.8±2.8) and FSHr+hMG groups (4.8±2.8); p = 1. Implantation rates showed no significant differences for fresh ET (FSHr: 58.6% vs. FSHr+hMG: 61.9%; n = 2,073; p = 1) or frozen ET (FSHr: 49.3% vs. FSHr+hMG: 46%; n = 2,687; p = 1). Similarly, there were no differences in live birth rates for fresh ET (FSHr: 45.6% vs. FSHr+hMG: 50.3%; n = 1,993; p = 1) or frozen ET (FSHr: 31.8% vs. FSHr+hMG: 33.8%; n = 2,508; p = 1). Limitations, reasons for caution The retrospective and single-center nature of the study would be its main limitations. It is essential to emphasize that these results are only applicable within the oocyte donation program. Wider implications of the findings Based on our findings, the use of exogenous FSHr alone is likely adequate in the GnRH antagonist protocol for optimal ovarian stimulation of donors, leading to the production of high-quality embryos and successful clinical outcomes. Trial registration number Not Applicable

Agonist long protocol improves outcomes of vitrified-warmed embryo transfer in repeatedly thin endometrium

Research questionDoes follicular stimulation using human menopausal gonadotrophin (HMG) after pituitary down-regulation by a GnRH agonist improve endometrial thickness (EMT) and clinical outcomes of frozen-thawed embryo transfer (FET; using vitrified-warmed embryos) in women with thin endometrium after intensified oestrogen administration (IOA)? DesignThis was a retrospective study. A total of 627 patients attempted 683 FET cycles with at least one previous history of thin endometrium. None of the cycles reached over 7 mm EMT after using oral and vaginal oestradiol for more than 21 days (IOA protocol). A total of 129 cycles proceeded with FET, 305 cycles were cancelled, and 249 cycles involved administration of HMG following GnRH agonist pituitary down-regulation (GnRH agonist + HMG protocol) for further endometrial preparation. ResultsEMT became significantly greater (7.18 ± 1.14 mm versus 6.13 ± 0.63 mm, P < 0.001) using GnRH agonist + HMG compared with previous IOA cycles, but this was not related to serum oestrogen concentrations. A total of 213 cycles after the GnRH agonist + HMG protocol proceeded with FET, showing a significantly increased clinical pregnancy rate, implantation rate and live birth rate compared with those after IOA. ConclusionsThe GnRH agonist + HMG protocol for endometrial preparation in FET cycles improves EMT in women with a thin endometrium after IOA and showed significantly better clinical outcomes than IOA. The authors suggest that the GnRH agonist + HMG protocol should be used for EMT that is less than 7 mm after there has been no optimal response to IOA.

The non-preventive effects of human menopausal gonadotropins on ovarian tissues in Nandrolone decanoate-treated female rats: A histochemical and ultra-structural study

The follicular growth and development may be affected by abused drugs. Nandrolone decanoate (ND) as an anabolic androgenic steroid can damage the morphological and functional features of the ovary and may lead to reproductive failure. This study was designed to evaluate the effects of synchronized and non-synchronized administration of Human Menopausal Gonadotropins (hMG) with ND on ovarian tissue and level of sex hormones in the adult female rat. Forty adult female Sprague Dawley rats were divided into eight groups. The five experimental groups received 3 and/or 10 mg/kg of ND synchronized and non-synchronized with 10 IU of hMG and hMG alone. The two shams and control groups received solvents of ND and hMG. The animals' serum levels of Follicle-stimulating hormone, Luteinizing hormone, progesterone and estrogen and the weight, volume and dimensions of the ovaries were measured. The ovaries were prepared for apoptosis assessment and morphological study. The ovarian volume and sex hormones in the experimental groups were decreased, but ovarian weight and dimensions didn't change. The rate of apoptosis was increased in the experimental groups as follows; a low and high dose of ND synchronized with hMG 48.80±18.70 and 65.20±14.20 respectively vs. Sham 1, 33.20±17.80, a low and high dose of ND non-synchronized with hMD 55.80±17.20 and 75.20±14.30 respectively vs. Sham 2, 31.60±32.40 groups, p˂0.01. Follicular and stromal cells were damaged in the experimental groups except for the hMG group. Administration of ND decreased the serum level of Luteinizing hormone, Follicle-stimulating hormone, progesterone and estrogen and damaged ovarian tissue irreversibly and irreparably and hMG cannot prevent the destruction of the follicles in the adult female rats. This can be a serious warning to women who abuse ND.

The Effects of Administrated Sildenafil Citrate on Uterine Luminal Epithelium Height Associated with Ovarian Angiogenesis: An Experimental Animal Study.

Background:Ovarian angiogenesis (OA) remains in lifetime and normal ovarian function depends to this continual remodeling of a complex vascular system. Endometrial thickness (ET) is one of the strongest predictors of successful implantation and pregnancy. Appropriate OA effects on ET by facilitating of ovarian hormone delivery.Materials and Methods:Thirty adult female mice and twenty adult male mice were purchased. The female mice were divided into three groups: (1) control group without any intervention (n = 10), (2) gonadotropin group: receiving human menopausal gonadotropin (HMG) and human chorionic gonadotropin (n = 10), and (3) gonadotropin and sildenafil citrate (SC) group: receiving HMG and SC administration (n = 10). After mating, animals were deeply anesthetized, and the ovary and uterus was rapidly removed for histology and immunohistochemistry process.Results:Four days after ovarian induction, all three layers of the uterus with specified thickness can be clearly seen. The heights of endometrial epithelial cells in gonadotropin group were not significantly different than those in control group. In gonadotropin and SC group, heights of the cells were significantly (P < 0.05) shorter than control and gonadotropin groups. ETs in all groups were not significantly deferent from each other (P > 0.05 each). Our results of immunohistochemistry survey for ovarian CD31 demonstrated that administrated SC increased OA but not significantly (P > 0.05 each).Conclusion:It may finally conclude that administration of SC does not cause notable alterations in OA and ET; although for realistic decision about the SC effects on aforementioned parameters, more molecular investigations and longer drug consumption period are necessary.

Clomiphene citrate versus letrozole with gonadotropins in intrauterine insemination cycles: A prospective randomized trial

Clomiphene citrate is one of the effective drugs for infertility treatment due to oligo-ovulation or anovulation. Intrauterine insemination (IUI) is one of more adherent methods for treatment of infertile cases which is followed by controlled ovarian hyperstimulation (COH). the aim of this study was to evaluate Clomiphene citrate versus letrozole with gonadotropins in IUI cycles. In this prospective randomized trial, 180 infertile women who were referred to Milad Hospital were selected. The first group received 5 mg/day letrozole on day 3-7 of menstrual cycle. The second group received 100 mg/day Clomiphene in the same way as letrozole. In both groups, human menopausal gonadotropin was administered every day starting on day between 6-8 of cycle. Ovulation was triggered with urinary Human Chorionic Gonadotropin (5000 IU) when have two follicles of ≥16 mm. IUI was performed 36 hr later. The number of matured follicles, cycle cancellation, and abortion were the same in both groups. Endometrial thickness was higher at the time of human menopausal gonadotropin administration in letrozole group. Chemical and clinical pregnancy rates were much higher in letrozole group. Ovarian hyperstimulation was significantly higher in clomiphene group. Letrozole appears to be a good alternative to clomiphene citrate with fewer side effects.

The Effect of Insulin Resistance on &amp;lt;i&amp;gt;In-Vitro&amp;lt;/i&amp;gt; Fertilization-Embryo Transfer in Women without Polycystic Ovary Syndrome

Purpose: Insulin resistance (IR) plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS); therefore, insulin-sensitizing agents are widely used to improve IR in women with PCOS. However, whether IR in patients without PCOS should be treated remains uncertain. This study aims to clarify whether IR in patients without PCOS affects the outcomes of in-vitro fertilization-embryo transfer (IVF-ET) and pregnancy. Methods: Between January 2011 and December 2013, we retrospectively reviewed the medical records of 116 non-PCOS patients who underwent the first IVF–ET cycle. IR was calculated using the homeostasis model assessment (HOMA) index [HOMA-IR = (insulin × glucose)/405]. A HOMA index of >2.5 was used to indicate IR. Based on the HOMA index calculation, 28 patients were IR(+) and 88 patients had normal insulin sensitivity. We retrospectively compared the response with controlled ovarian hyperstimulation, retrieved oocytes number, fertilization rates, pregnancy rate, live birth rates, and gestational diabetes mellitus (GDM) incidence. Results: There were no significant differences in human menopausal gonadotropin administration, peak estradiol, retrieved oocyte number, fertilized embryo number, good quality embryo number, implantation rate, clinical pregnancy rate, miscarriage rate, delivery rate, or ovarian hyperstimulation syndrome and GDM incidences between the groups. Conclusion: IR in non-PCOS patients has no effect on IVF-ET outcomes or perinatal prognosis.

Immunohistochemical (Ki-67) study of endometrial maturation in mice after use of phosphodiesterase type 5 inhibitor.

Background:Uterine receptivity for the implantation is a complicated process, that ovarian factors (hormonal), endometrium and embryo simultaneously are involved in this phenomenon. A successful implantation needs appropriate development of the endometrium. Furthermore, embryo must be capable of reacting with the endometrium and producing suitable adhesion molecules. This study aimed to examine one of endometrial maturation indices in mice before implantation, i.e., proliferation of stromal cells.Materials and Methods:A total of 40 adult female mice were divided into four groups: Control, gonadotropin, gonadotropin + progesterone, and gonadotropin + sildenafil citrate. The three experimental groups were first injected 7.5 IU of human chorionic gonadotropin (HCG) and then 7.5 IU of human menopausal gonadotropin (HMG). Then, every two female mice were placed in a cage with a male mouse for mating. Two groups were injected 1 mg of progesterone and 3 mg/kg of sildenafil citrate at intervals of 24, 48, and 72 h after injection of HMG. After 96 h, all the mice were killed, and their uterine samples subjected to tissue passage and prepared for analysis. Immunohistochemical method, Ki-67, and stromal mitotic cell count were used in this study.Results:Our observations in all groups showed changes in the luminal epithelium. ANOVA analysis Ki-67-positive stromal cells among all groups were not statistically significant.Conclusion:The results showed that administration of HMG and HCG following that of progesterone and sildenafil citrate could change the indices of endometrial maturation, and they were not involved in the phase immediately before implantation in stromal mitotic index.

Ovarian follicular development stimulated by leuprorelin acetate plus human menopausal gonadotropin in chimpanzees

We attempted ovarian stimulation using gonadotropins in 14 chimpanzees. Subjects were given a single administration of leuprorelin acetate, followed by repeated administration of human menopausal gonadotropin (hMG) for 16-21 days. During the dosing period, the ovarian follicle diameter and count were measured by transvaginal ultrasonography. The hormone administration induced the development of multiple follicles, and multiple oocytes were subsequently retrieved. However, the follicle count was decreased, suggesting atresia, in some subjects. Statistically, the final follicle diameter was dependent on the dosing duration and the hMG dose in the late stage, while the maximum follicle count during hMG administration was dependent on age and the hMG dose in the early stage. Five subjects showed mild ovarian hyperstimulation syndrome (OHSS)-like symptoms with a high serum estradiol (E2) concentration. These results suggest that leuprorelin acetate plus hMG administration successfully stimulates the development of multiple ovarian follicles for oocyte retrieval and that the serum E2 concentration is predictive of OHSS-like symptoms in chimpanzees.

Intra-venous albumin for preventing severe ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition that occurs after the administration of human menopausal gonadotrophin (hMG) with or without gonadotrophin releasing hormone (GnRH) agonists. OHSS is a threat to every woman undergoing ovulation induction and is potentially lethal in its severest form. Severe OHSS is characterised by growth of multiple large follicles with massive extravascular protein rich fluid shift. This may lead to hypovolaemia, haemoconcentration, oliguria, and electrolyte disturbance. Human albumin solutions are now used in the management of shock and other conditions in which restoration of blood volume is urgent, the acute management of burns, and clinical situations associated with hypoproteinaemia. Recently, a number of clinical trials with conflicting results have been reported in which albumin has been tested as a possible way for preventing the severe form of OHSS. To review the effectiveness of human albumin administration in prevention of severe ovarian hyperstimulation syndrome. The Menstrual Disorders and Subfertility Group literature search strategy was used to identify randomised trials that had compared the use of human albumin with placebo or no treatment in the prevention of severe ovarian hyperstimulation syndrome. A diverse search strategy was employed, including handsearching of core journals from 1966 to the present, searching bibliographies of relevant trials, MEDLINE, EMBASE, PsychLIT and CINAHL databases, the MDSG specialised register, abstracts from North American and European meetings and contact with authors of relevant papers. Trials were included if they compared the effect of human albumin with placebo or no treatment on relevant outcomes. Only randomised controlled studies were included in this review. Trials under consideration were evaluated for methodological quality and appropriateness for inclusion without consideration of their results. Relevant data were extracted independently by two reviewers using the standardized data extraction sheet. Validity was assessed in terms of method of randomization, completeness of follow-up, presence or absence of crossover and co-intervention. 2x2 tables were generated for all relevant outcomes. Odds ratios were calculated using the Peto modified Mantel-Haenszel technique. Meta-analysis of the three included trials demonstrated significant reduction in severe ovarian hyperstimulation syndrome on administration of human albumin (common odds ratio 0.1, 95% confidence interval 0.03 to 0.39). There was no evidence of an increase in the pregnancy rate (common odds ratio 1.69, 95% confidence interval 0.7 to 4.07). This review shows a clear benefit from administration of intra-venous albumin at the time of oocyte retrieval in prevention of severe OHSS in high-risk cases. However, the results of this review can not be regarded as conclusive as they are based on only three small trials. Further trials are urgently needed.

Subcutaneous human menopausal gonadotropin administration for controlled ovarian hyperstimulation with intrauterine insemination cycles

Objective: This study was undertaken to determine the feasibility of administering human menopausal gonadotropin subcutaneously for controlled ovarian hyperstimulation with intrauterine insemination. Study Design: This was a prospective nonrandomized matched-group comparison. Study patients (n = 25) undergoing controlled ovarian hyperstimulation with intrauterine insemination infertility treatment between June 1998 and March 1999 self-administered human menopausal gonadotropin subcutaneously for ovulation induction. Cycles (n = 39) were analyzed for duration of human menopausal gonadotropin treatment, total number of ampules of human menopausal gonadotropin used, peak serum estradiol level, number of mature follicles (≥15 mm), cycle fecundity, and acceptability of the subcutaneous route of human menopausal gonadotropin administration. Age-matched historical control subjects who followed the same protocol except for the route of human menopausal gonadotropin administration, which was instead intramuscular, were used for comparison. Results: Study and control cycles did not differ with respect to duration of human menopausal gonadotropin treatment (7.49 vs 8.18 d), total number of ampules of human menopausal gonadotropin used (17.44 vs 19.55), peak serum estradiol level (881 vs 769 pg/mL), number of mature follicles (≥15 mm; 3.39 vs 2.92), or cycle fecundity rate (15.4% vs 17.9%). Two study patients were switched from subcutaneous to intramuscular administration because of minor local injection site reactions. Conclusion: Subcutaneous human menopausal gonadotropin administration for controlled ovarian hyperstimulation with intrauterine insemination treatment cycles was generally well tolerated and yielded stimulation parameters and pregnancy rates similar to those associated with the intramuscular route. Patients subjectively preferred subcutaneous human menopausal gonadotropin administration because of the ability to self-administer the injections, the use of a smaller injection needle, and reduced muscular pain at the injection site. (Am J Obstet Gynecol 2000;182:1421-6.)

Effects of aging on ovarian fecundity in terms of the incidence of apoptotic granulosa cells.

The objective was to determine the effects of women's age on the ovarian fecundity as assessed by the incidence of apoptotic granulosa cells. Twenty-eight normo-ovulatory women underwent ovulation induction for standard IVF. The husbands of these women showed severe male infertility factors. The women were divided into four groups according to their ages. Women underwent follicle aspiration after the administration of human menopausal gonadotropin plus human chorionic gonadotropin. The nuclei of granulosa cells were examined by using fluorescence microscopy, and the incidence of apoptotic granulosa cells was tabulated. Granulosa cells in the older women revealed a significant increase in the number of apoptotic cells. The number of total oocytes and the number of mature oocytes obtained significantly decreased with age. However, endometrial thickness and follicular estradiol, progesterone, and free testosterone levels were not significantly different among four different age groups. Age increases apoptotic changes in granulosa cells and consequently decreases the ovarian fecundity.

The relationship between ovarian vascularity and the duration of stimulation in in-vitro fertilization.

The role of transvaginal pulsed colour Doppler ultrasound in the assessment of ovarian vascularity was studied in 196 in-vitro fertilization (IVF) cycles. The changes in ovarian blood flow after gonadotrophin-releasing hormone agonist (GnRHa) down-regulation and human menopausal gonadotrophin (HMG) stimulation were determined. The data obtained showed that the ovarian blood flow was significantly improved by oestradiol secretion (P = 0.05) and human chorionic gonadotrophin (HCG) administration (P = 0.003). Folliculogenesis was affected by blood flow supply. The resistance index (RI) value was significantly different (P = 0.05) according to the duration of ovarian stimulation. Patients with a mean RI value >0.56 had a longer stimulation with a significantly lower mean number of oocytes retrieved (P = 0.01) despite the administration of a standard dose of HMG. The RI value is a good indicator of modifications in ovarian vascularization during stimulation. Doppler blood flow measurement could be used to determine the optimal timing for the beginning of HMG administration in patients undergoing ovarian stimulation after down-regulation for IVF treatment.

An improvement in the embryo quality and pregnancy rate by the pulsatile administration of human menopausal gonadotropin in patients with previous unsuccessful in vitro fertilization attempts

To examine whether the pulsatile administration of hMG improves IVF outcomes in patients with previous unsuccessful attempts using IM injections of hMG. A prospective randomized study. In vitro fertilization program at a university hospital. Eighty-eight endocrine-normal ovulatory women under 40 years of age, with normal male partners and a history of unsuccessful IVF treatment by the IM administration of hMG. Patients were assigned randomly to receive either IM (bolus group) or pulsatile administration of hMG (pulsatile group) after pituitary desensitization by a GnRH agonist. The proportion of retrieved oocytes with a polar body, the number of fertilized oocytes and embryos, the proportion of morphologically superior embryos, and the rate of pregnancy per initiated cycle were compared. The proportion of retrieved oocytes with a polar body and the number of fertilized oocytes and embryos were similar in both groups. Significantly more embryos had superior morphology in the pulsatile group (77%) than the bolus group (52%). The rates of overall and clinical pregnancy per initiated cycle were significantly higher in the pulsatile group (39% and 30%, respectively, n = 44) than in the bolus group (18% and 11%, respectively, n = 44). In women with failed IVF attempts using IM administration of hMG, the pulsatile administration of hMG produces superior embryos and, hence, a higher pregnancy rate.

Hormonal serum profiles and follicular development after intramuscular and pulsatile intravenous administration of human menopausal gonadotrophin

A study was performed to compare, in a randomized way, the effect of pulsatile intravenous (i.v.) and intramuscular (im) human menopausal gonadotrophin (hMG) administration on hormonal serum profiles and follicular development in in vitro fertilization (IVF). Fourteen IVF patients participated in the study, aged between 20 and 40 years, with a normal endocrine profile, no hormonal medication used for at least 3 months previously, no endometriosis, both ovaries present and a normal male factor. Seven patients were treated with im hMG at a daily dose of 150 IU and seven patients with pulsatile i.v. hMG at a daily dose of 112.5 IU, in both cases in combination with buserelin. Ultrasonography was performed every other day during the stimulation phase and blood samples were collected once daily up to five times a day during the entire IVF cycle. Serum concentrations of follicle-stimulating hormone, luteinizing hormone, 17 beta-oestradiol, progesterone and human chorionic gonadotrophin were determined. There were no differences in hormonal profiles between the two groups. The numbers of retrieved oocytes, fertilization rates and mean embryo quality were identical in this study, as was follicular growth. In conclusion, in the present randomized study no differences were observed in hormonal levels or follicular development after im and pulsatile i.v. hMG treatment.

Heterotopic pregnancy following administration of human menopausal gonadotropin and following in vitro fertilization and embryo transfer: two case reports and review of the literature

We report two cases of heterotopic (combined intra- and extra-uterine) pregnancy in women treated for infertility. In the first case the patient conceived following administration of human menopausal gonadotropin. In the seventh week of gestation she had a spontaneous abortion and in the eighth week required urgent laparotomy for acute abdomen due to the rupture of pregnant right tube. In the second case the patient conceived from IVF-ET; in the eighth week a salpingectomy was made. The intrauterine pregnancy continued regularly until term and the patient was delivered of a healthy baby by caesarean section. We reviewed the literature and we found that heterotopic pregnancy is an insidious disease with a constant increase of incidence, especially in infertile women submitted to therapy for ovulation induction or assisted reproductive techniques. All the patients who have risk factors should be submitted to careful controls in early pregnancy, including an ultrasound transvaginal scan.

Comparative study of hormonal dynamics in pregnant and nonpregnant cycles during pulsatile subcutaneous administration of human menopausal gonadotropin in anovulatory infertile women

To assess the clinical relevance of daily hormonal changes for achieving a successful pregnancy in anovulatory infertile women. A comparative study of hormonal dynamics in pregnant and nonpregnant cycles during the pulsatile subcutaneous administration of hMG. Subjects received subcutaneous injection of either 9.375 IU or 14.0625 IU of hMG diluted in 50-microL physiological saline (total daily dose, 150 or 225 IU) at 90-minute intervals by means of a portable peristaltic pump. Kyorin University Hospital and Ichikawa General Hospital. We analyzed 18 pregnant and 42 nonpregnant cycles in 17 patients with secondary hypothalamic/pituitary amenorrhea who conceived after receiving pulsatile hMG treatment. Another 14 women with normal spontaneous ovulation, including 14 pregnant and 15 nonpregnant cycles, served as controls. Serum concentrations of LH, FSH, E2, and P were measured, and the P:E2 ratio was determined. Serum concentrations of LH and FSH did not differ significantly between the pregnant and nonpregnant cycles. Serum levels of P and E2 were significantly higher during the hMG treatments than those of the spontaneous ovulatory cycles throughout the follicular and luteal phases. Up to the midluteal phase, the P and E2 values in the nonpregnant cycles during the hMG treatments did not differ significantly from those in the pregnant cycles. The P:E2 ratios were comparable between the pulsatile stimulatory cycles and the normal spontaneous ovulatory cycles. However, the P:E2 ratio in the early and midluteal phases was significantly greater in the pregnant cycles than in the nonpregnant cycles. The P:E2 ratio in the early and midluteal phases is a more important indicator of hormonal function for implantation than the absolute levels of either P or E2.

The long protocol of administration of gonadotropin-releasing hormone agonist is superior to the short protocol for ovarian stimulation for in vitro fertilization

To investigate whether pituitary desensitization with the gonadotropin-releasing hormone agonist (GnRH-a), buserelin acetate, before the administration of human menopausal gonadotropin (hMG) for ovarian stimulation in in vitro fertilization (IVF) is superior to the simultaneous administration of both hormones at the beginning of the treatment cycle. Prospective randomized study. Ninety-one patients having their first attempt at IVF. Patients in group 1 (long protocol) were administered subcutaneous (SC) buserelin acetate 200 micrograms/d from day 1 of the menstrual cycle, and hMG was started only after pituitary desensitization had been achieved at least 14 days later. Patients in group 2 (short protocol) were administered SC buserelin acetate 200 micrograms/d from day 2 and the same dose of hMG used in the long protocol from day 3 of the menstrual cycle. The median total amount of hMG required in both groups was comparable. There were significantly more follicles (P = 0.0001), oocytes (P = 0.0008), fertilized oocytes (P = 0.0001), and cleaved embryos (P = 0.0001), and a higher fertilization rate (P = 0.0047) in patients in group 1. The pregnancy rates per initiated cycle and per embryo transfer were 19.57% and 25.71% in group 1 compared with 8.89% and 16.67% in group 2. The long protocol is superior in terms of significantly greater follicular recruitment, oocyte recovery and fertilization rates, and significantly greater number of embryos available for transfer. In general, it is the preferred method when GnRH-a are used for ovarian stimulation in IVF.

Outcome of Ovarian Response after Suppression with a Gonadotropin Releasing Hormone Agonist in Different Chronological Periods prior to Gonadotropin Stimulation for in vitro Fertilization

Gonadotropin-releasing hormone analogues (GnRH-a) are currently used in combination with gonadotropins in ovarian stimulation for in vitro fertilization programs (IVF). The present study aims at evaluating the treatment cycles for IVF for which human menopausal gonadotropin (HMG) was initiated only when pituitary desensitization was confirmed regardless of the time of GnRH-a administration. Two groups of patients were examined. Patients in group A (n = 46) were commenced with HMG treatment on day 15 when E2 level was less than 40 pg/ml. Group B patients (n = 27) comprised the cycle treatments in which E2 levels were greater than 40 pg/ml on day 15. In these cases HMG was first given when E2 levels declined to less than 40 pg/ml. The fertilization rate was similar in both A and B groups, 71.6 and 67.7% respectively. The pregnancy rate per transfer was 27.5 and 34.6% in group A and B respectively. Multiple pregnancies were found at 18.1% in group A versus 44.4% in group B. It is concluded that postponement of HMG administration in patients with high levels of E2 on day 15 after GnRH-a administration seems to offer an improvement in embryo cleavage speed, pregnancy rate and multiple pregnancies.

Ovarian response in repetitive cycles induced by menotrophin alone or combined with gonadotrophin releasing hormone analogue

The number of oocytes retrieved for in-vitro fertilization (IVF) has a major influence on the number of embryos developed and pregnancy success. This study was designed to investigate the ovarian response in the same patient under the same and different stimulation protocols. In group A, 19 patients underwent two consecutive cycles, both stimulated with human menopausal gonadotrophin (HMG). Group B comprised 27 patients who experienced two successive cycles treated with the combination of long-acting gonadotrophin releasing hormone analogue (GnRHa) and HMG. Group C included 27 patients whose first cycle was stimulated with HMG alone, and their second with a GnRHa/HMG combination. The mean number of HMG ampoules administered and the duration of treatment were similar in both cycles of group A and B patients while in group C, both the amount and duration of HMG administration were significantly higher and longer in the combined protocol compared to HMG alone. This study demonstrates an identical ovarian response using the same mode of stimulation in repeated cycles, and a significantly improved response with the GnRHa/HMG combination compared with HMG alone in the same patient.

Ovulation and successful pregnancy in a woman with ovarian failure after hypophysectomy and gonadotropin therapy

A 38-year-old woman ovulated and conceived after administration of human menopausal gonadotropins despite a previous diagnosis of ovarian failure at age 18. Possible explanations include restoration of down-regulated gonadotropin receptors by development of a prolactinoma, spontaneous remission of autoimmune oophoritis, or prior tumor secretion of biologically inert gonadotropins.