Follicle-stimulating hormone or human menopausal gonadotropin for ovarian stimulation in in vitro fertilization cycles: a meta-analysis

OBJECTIVE: To reanalyze the results of using FSH alone and hMG during IVF treatment, taking into account the different protocols of administration of superactive GnRH agonist analogs. DESIGN: Meta-analysis. SETTING: The London Women's Clinic. PATIENT(S): Women undergoing IVF treatment. INTERVENTION(S): A meta-analysis of published randomized controlled trials from 1985 to 1999 of the use of FSH versus hMG for ovarian stimulation during IVF treatment. The common Peto odds ratio was calculated with use of a fixed effect model. The overall log odds ratio was estimated after demonstrating the consistency or homogeneity of the study results. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate per cycle of IVF. RESULT(S): The results suggested that in the "long and short GnRH agonists protocol" of IVF, FSH, and hMG were equally effective in achieving ovarian stimulation, and there were no differences in the clinical pregnancy rates per cycle of IVF. However, in protocols where no pituitary desensitization was used, FSH alone was more efficacious. CONCLUSION(S): The optimum choice of gonadotropin preparation for ovarian stimulation during IVF treatment is influenced by the regimen of pituitary desensitization used. The optimum gonadotropin to be used when GnRH antagonists are used has yet to be determined.     

Use of gonadotrophin-releasing hormone agonists to trigger ovulation

The introduction of gonadotrophin-releasing hormone (GnRH) agonists combined with gonadotrophins is considered to be one of the most significant advances in the development of in vitro fertilization (IVF) treatment. However, ovarian hyperstimulation syndrome (OHSS) remains a significant complication of controlled ovarian hyperstimulation. One possible strategy to reduce the risk of this complication would be the use of GnRH agonists instead of human chorionic gonadotrophin (hCG) to trigger the final stages of oocyte maturation. GnRH agonists are able to induce an endogenous surge of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and the effect may be more physiological than that of exogenous hCG. Several uncontrolled and controlled clinical studies have confirmed the efficacy of GnRH agonists for triggering ovulation, and pregnancy rates are comparable to those achieved with hCG. The incidence of OHSS appears to be decreased, but larger controlled studies are required to confirm this observation. The recent introduction of GnRH antagonists has led to renewed interest in the use of GnRH agonists to induce final oocyte maturation. An international multicentre randomized controlled trial has been completed recently comparing the efficacy of GnRH agonist with hCG for triggering ovulation in women undergoing controlled ovarian hyperstimulation using the GnRH antagonist ganirelix for pituitary suppression. The aim of the study was to determine the efficacy of the novel protocol for ovarian stimulation before IVF, in terms of pregnancy outcomes and the prevention of OHSS.     

In Vitro Fertilization with Low-Dose Clomiphene Citrate Stimulation in Women Who Respond Poorly to Superovulation

Purpose: Our experience with IVF using low-dose clomiphene citrate for stimulation in non- and poor responders was reviewed and the treatment outcomes with the previous controlled ovarian stimulation cycles in which hMG and GnRH agonist were used were compared. Methods: The treatment outcome in 11 non- and 20 poor responders having 30 and 53 clomiphene citrate IVF treatment cycles, respectively, were compared with the treatment outcome in the previous long-protocol buserelin/hMG cycles. Results: The clinical pregnancy rates per oocyte collection achieved in the first clomiphene citrate cycle in non (9.1%)- and poor (10%) responders were comparable to those achieved by poor responders (11.9%) who had buserelin/hMG using the long protocol. Although the numbers were small, a similar pregnancy rate could still be achieved in poor responders up to the third attempt using clomiphene citrate. Conclusions: IVF using long-protocol buserelin/hMG is more successful than using clomiphene citrate stimulation. However, this advantage may not be significant in those women with a previous poor response to buserelin/hMG. It is suggested that for such poor responders, three attempts of IVF in a clomiphene citrate cycle may offer a viable therapeutic alternative before reverting to more stressful, expensive, and time-consuming treatment.     

Follow-up of 32 hypothalamo-hypopituitary patients treated with pulsatile gonadotropin-releasing hormone or human menopausal gonadotropin.

In a clinical retrospective study, a follow-up of hypothalamo-amenorrheic patients treated firstly with gonadotropin-releasing hormone (GnRH) pump stimulation and secondly with human menopausal gonadotropin (hMG) was performed. Thirty-two hypothalamo-amenorrheic patients, 24-38 years old, were submitted to 103 GnRH stimulation cycles. Seven, with polycystic ovaries (PCO) on ultrasound, were stimulated with hMG after one or several unsuccessful pump cycles. Ovulation was confirmed by a luteinizing hormone (LH) surge or triggered by human chorionic gonadotropin in 80 out of 103 cycles (77.7%/cycle) leading to 62 timed sexual intercourses and 17 intrauterine inseminations (IUI). Twenty-one pregnancies (26.3%/cycle) terminated in eight abortions (38.1%/pregnancy) and 13 deliveries (40.6%/patient). hMG stimulation, in the seven PCO patients (six IVF, one IUI), led to four additional deliveries in three patients. Five patients became pregnant spontaneously after pump failure (n = 2) or unsuccessful IVF (n = 3). Combining all cycles, 17 deliveries were obtained in 16 patients. No case of ovarian hyperstimulation syndrome (OHSS) was observed. GnRH is an efficient and safe treatment of hypothalamo-amenorrheic-induced anovulation. Following GnRH or hMG ovarian stimulation, spontaneous ovulation and conception may be restored in certain hypothalamo-amenorrheic patients.     

Results of in vitro fertilization and embryo transfer by combined long-acting gonadotropin-releasing hormone analog D-Trp-6-luteinizing hormone-releasing hormone and gonadotropins

To avoid cancellation of in vitro fertilization (IVF) because of early luteinization, pituitary suppression by gonadotropin-releasing hormone (GnRH) was carried out in 111 cycles. D-Trp-6-luteinizing hormone-releasing hormone (LH-RH) microcapsules were administered intramuscularly at menstruation and menotropin (hMG) stimulation was started 19 days (mean) later. In 3 cycles (2.7%), only early luteinization occurred. The mean number of oocytes per cycle was 6.7, with a fertilization and cleavage rate of 50 and 95%, respectively. A mean of 3.4 embryos were transferred per cycle. The 111 cycles resulted in 34 clinical pregnancies, 41% per cycle with embryo transfer. The early abortion, multiple pregnancy, and ovarian hyperstimulation rates were 24, 18, and 11%, respectively. It is concluded that D-Trp-6-LH-RH/hMG cycles are associated with a very low occurrence of early luteinization, high number of oocytes and embryos, and a substantial incidence of ovarian hyperstimulation syndrome.     

Induction of ovulation with D-Trp6-LHRH combined with purified FSH in patients with polycystic ovarian disease

Seventeen patients with polycystic ovarian disease (PCOD) and evidence of mild or severe ovarian hyperstimulation syndrome (OHSS) during therapy with CC/hCG, FSH/hCG or hMG/hCG were treated with D-Trp6-LHRH until medical gonadectomy was attained. Under the suppressive therapy with the GnRH agonist (GnRHa) ovulation was induced with FSH/hCG. In 15 out of 17 patients, ovulatory cycles were obtained with this new modality of treatment. Seven patients conceived (3 viable pregnancies and 4 early abortions) after the 1st treatment cycle. Fourteen of the 17 patients demonstrated symptoms of mild OHSS which did not require hospitalization. Only 1 patient developed severe OHSS after the combined treatment. Our results suggest that therapy with GnRHa, especially in its delayed release formulation, is effective for the prevention of severe ovarian hyperstimulation in PCOD patients undergoing treatment with menotropins for the induction of ovulation.     

Follicular stimulation for in vitro fertilization using pituitary suppression and human menopausal gonadotropins

Multiple follicular stimulation is a prerequisite to the efficient use of in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). For some individuals, however, this stimulation may be difficult using standard superovulation protocols because of dominant follicle formation, suboptimal estradiol response, or premature luteinizing hormone surge. A group of such individuals with several previous failed attempts at superovulation were studied. Follicular stimulation was accomplished using a long-acting agonist of gonadotropin-releasing hormone (GnRH) for pituitary suppression followed by human menopausal gonadotropin (hMG) for follicular stimulation. Fourteen cycles (12 IVF, 2 GIFT) were completed in 12 individuals. There were no cycle cancellations. Mean number of prior cycle cancellations per patient was 3.1 +/- 0.4. Mean number of mature oocytes recovered was 3.9 +/- 0.5. Two pregnancies resulted. Pituitary suppression with a long-acting agonist of GnRH followed by hMG appears to be an effective adjunct to current superovulation regimens.     

Kallmann syndrome: a case of twin pregnancy and review of the literature

In order to evaluate the possibilities for induction of ovulation, the functional competence of the pituitary gland of a woman with Kallmann syndrome was examined by two consecutive dynamic GnRH tests. The second test was conducted after 1 week's treatment by a GnRH pump. The results, which showed some rise of LH but no response of FSH, favored induction by hMG/hCG therapy. Three treatment cycles resulted in a twin pregnancy which was normal and was carried to term. Review of the literature shows only six previously reported pregnancies in women with Kallmann syndrome. Five of them were treated by hMG/hCG, and one by pulsatile GnRH. The two methods of induction are discussed in relation to the heterogeneity of the pituitary and ovarian function in Kallmann syndrome. We show that this heterogeneity dictates that the treatment for induction of ovulation should be individually adjusted according to the pituitary and ovarian competence.     

Prediction of ovarian reserve based on day-3 serum follicle stimulating hormone concentrations during the pituitary suppression cycle using a gonadotropin releasing hormone agonist in patients undergoing in vitro fertilization–embryo transfer

Satisfactory results following in vitro fertilization–embryo transfer (IVF-ET) treatments depend on retrieving an appropriate number of mature oocytes without causing the development of ovarian hyperstimulation syndrome (OHSS). The present study was carried out to investigate whether the ovarian reserve is predictable based on the day-3 serum concentration of follicle stimulating hormone (FSH) during the pituitary suppression cycle using a gonadotropin releasing hormone (GnRH) agonist (defined as day-3 FSH) in patients undergoing IVF-ET treatment. Day-3 FSH before the administration of gonadotropin was assessed in 72 IVF-ET cycles from 59 infertile women. The mean?±?SD of day-3 FSH, the total amount of FSH plus human menopausal gonadotropin (hMG) administered, and the total number of oocytes retrieved was 5.5?±?2.6 mIU/ml, 2834.2?±?1236.5?IU and 7.7?±?5.8, respectively. There were significant correlations between day-3 FSH and the total amount of FSH–hMG administered (p?<?0.001), and day-3 FSH and total number of oocytes retrieved (p?<?0.001). There was a significant difference of day-3 FSH between patients who subsequently conceived (4.4?±?1.3 mIU/ml) and those who did not conceive (6.1?±?2.9 mIU/ml) (p?= 0.001). There was also a significant difference of day-3 FSH between patients who developed moderate or severe OHSS (4.5?±?1.2 mIU/ml) and those who did not (5.9?±?2.8 mIU/ml) (p?=?0.003). Receiver-operator characteristic curve analysis showed that the significant cut-off point for day-3 FSH for predicting ovarian reserve was 5.25?mIU/ml. These findings indicate that day 3-FSH is useful for predicting ovarian reserve during the pituitary suppression cycle using a GnRH agonist in patients undergoing IVF-ET.     

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

OBJECTIVE: 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. DESIGN: Prospective randomized study. PATIENTS: Ninety-one patients having their first attempt at IVF. INTERVENTIONS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Pituitary down-regulation in IVF cycles: Is it necessary to use strict criteria?

Purpose In a retrospective study we have reviewed the data of 570 consecutive IVF cycles in which a GnRH agonist (GnRHa) was started in the early follicular phase (long protocol). Cycles were divided in groups according to estradiol levels before HMG administration: A, <20 pg/ml; B, 20 to 50pg/ml; C, 51 to 100pg/ml. Our objective was to determine if the degree of pituitary suppression had any effect on the ovarian response to stimulation by exogenous gonadotropins, and/or on the IVF outcome.Results There were no significant differences in cycle cancellation rates, no. of days of stimulation and ampoules of HMG, serum estradiol after HMG, no. of oocytes retrieved and fertilization rates between groups. Pregnancy rates (19.4%, 21% and 31.8%/cycle, and 24.1%, 27.5% and 37.8%/embryo transfer, respectively) and live-birth rates.(16.2%, 16.1% and 25.0%/cycle, 20.1%, 21.2% and 29.7%/embryo transfer, respectively) were also not significantly different.Conclusions The degree of pituitary suppression had no effects on either the ovarian response to gonadotropins (including HMG requirements) or the overall IVF results.Presented at the IXth World Congress on In Vitro Fertilization and Alternate Assisted Reproduction, April 3–7, 1995, Vienna, Austria.     

Clomiphene citrate and hMG: An alternative stimulation protocol for selected failed in vitro fertilization patients

Purpose This study was carried out to evaluate the potential role of the combination clomiphene citrate/human menopausal gonadotropin (CC/hMG) for patients who failed previous in vitrofertilization (IVF) attempts with gonadotropin-releasing hormone analogs (GnRH- a) and/ or exogenous gonadotropins.Methods Patients were stimulated with CC/hMG (n=93) after unsuccessfully undergoing 182 gonadotropin cycles with (n=106) or without (n=76) luteal-phase GnRH- a. Cancellation rate, length of stimulation, and peak estradiol levels did not differ significantly between the two regimens.Results Although fewer oocytes were retrieved when the CC/hMG combination was used, 16 patients were able to successfully achieve a pregnancy (26.2% delivery rate/ transfer). When daily follicle stimulating hormone (FSH) levels were measured in two successive cycles in those women who conceived with the CC/hMG stimulation, baseline levels did not differ when compared with a previous GnRH-a/hMG cycle. Nevertheless, serum FSH levels rose rapidly and remained higher in the GnRH- a/hMG cycle, reaching significantly higher levels on day of human chorionic gonadotropin (hCG) administration.Conclusion Selected patients who failed previous IVF attempts with gonadotropins with or without GnRH analogs may benefit from the addition of CC to their ovarian stimulation protocol.Presented at the 50th Annual Meeting of the American Fertility Society, San Antonio, Texas, November 5–10, 1994.     

The reproductive performance of women with hypogonadotropic hypogonadism in an in vitro fertilization and embryo transfer program

Purpose: To evaluate the outcome of women with hypogonadotropic hypogonadism undergoing in-vitro fertilization (IVF).Methods: We retrospectively assessed outcomes in 58 women with hypogonadotropic hypogonadism (HH) and, as matched controls, in 116 women with tubal factor (TF) infertility who underwent assisted reproduction treatment (ART). For ovulation induction, human menopausal gonadotropin (hMG) was used in HH patients and a combination of hMG and gonadotropin releasing hormone (GnRH) agonist was used in TF patients. Conception and implantation rates, as well as duration of stimulation and number of oocytes retrieved, were the main outcome measures.Results:Of the 58 HH patients, 53 (91.3%) responded adequately to ovulation induction and underwent ET. A larger amount of gonadotropins and a longer duration of ovarian stimulation were needed in HH patients than in TF patients. The mean number of retrieved oocytes and implantation rates did not differ between the groups. In addition, there were no differences between the HH and TF groups in pregnancy (53.8 vs. 48.6%) and multiple pregnancy (63.4 vs. 48.4%) rates. In the HH group, the miscarriage rate was 3.4%, and none of these patients developed severe OHSS.Conclusion:IVF in HH patients, in which there was a background of previous failed ovulation induction, was as successful as in women with TF infertility.     

Secondary hypogonadism in hemochromatosis

Hemochromatosis is a rare disorder of iron storage. This report illustrates a case of hypogonadotropic-hypogonadism in a female with biopsy-proven hemochromatosis. Dynamic pituitary and gonadal testing revealed subnormal gonadotropin responses to gonadotropin-releasing hormone (GnRH) but normal ovarian reserve, as shown by normal follicular stimulation with hMG. Thus, abnormalities of ovulation and menstruation in patients with hemochromatosis are most likely because of inadequate pituitary responsiveness to GnRH.     

Influence of pituitary suppression with triphasic or monophasic oral contraceptives on the outcome of in vitro fertilization and embryo transfer

Purpose: To compare the clinical outcome of IVF treatment after pituitary suppression with two different oral contraceptives (OCs). Methods: 65 patients who received IVF treatment was classified into 2 groups based on the difference of OCs they used for pituitary suppression before ovarian hyperstimulation. Group 1 included 36 patients who received monophasic OCs. Group 2 included 29 patients who received triphastic OCs. Both groups received the OCs from the 5th day of the cycle for consecutive 21 days. The hormone profiles after OCs and clinical outcome of IVF treatment were compared between two groups. Two-sample t-tests and X2 tests were used for statistical analyses. P < 0.05 was considered statistically significant. Results: The mean age and basal hormone profiles were comparable between two groups. After ovulation suppression with different OCs, the day 2 FSH and LH value revealed statistically significant difference between two groups(4.2±1.8 vs 6.0±2.6; 2.7±2.0 vs 4.2±3.3 respectively). The numbers of oocyte per retrieval and fertilization rate were comparable between two groups, but higher quality embryos as revealed by the cleavage speed were noted in the triphastic OCs group. Although statistically not significant, higher implantation rate and pregnancy rate were also noted in the triphastic OCs group. Conclusions: Different OCs for pituitary suppression can result in different hormone profiles. Ovulation induction in IVF treatment should be individualized according to these hormone changes to achieve the optimal clinical outcome. Triphastic OCs exceeds monophastic OCs in producing good quality embryo in IVF-ET treatment.     

Ovarian suppression with leuprolide acetate: Comparison of luteal,follicular, and flare-up administration in controlled ovarian hyperstimulation for oocyte retrieval

Adjunct use of leuprolide (LA) in patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins (hMG) was evaluated by three protocols: Group F(n=24) began LA on day 2 of the cycle and Group L(n=38) began LA on day 23 of the cycle until ovarian suppression, at which time hMG was added. Group FL (n=17) began LA on day 1 and hMG on day 3. Compared to FL, more ova were collected, more ova fertilized, and more pregnancies resulted per initiated cycle in groups achieving suppression before hMG stimulation. Fewer days were necessary to attain suppression for L vs F. After achieving suppression, patients were maintained on either 0.5 mg LA or 0.25 mg LA daily during hMG coadministration with similar results. Lower maintenance doses of LA during hMG did not decrease the amount of hMG needed but retained the benefits of LA. We recommend luteal initiation of LA to achieve suppression before hMG.Presented in part at the 45th Annual Meeting of the American Fertility Society, San Francisco, California, November 1989.     

Pretreatment with an Oral Contraceptive Is Effective in Reducing the Incidence of Functional Ovarian Cyst Formation During Pituitary Suppression by Gonadotropin-Releasing Hormone Analogues

Purpose: Our purpose was to assess the effect of pretreatment with oral contraceptives (OCs) on the formation of functional ovarian cysts during pituitary supression with gonadotropin-releasing hormone (GnRH) agonists, subsequent follicular development, and pregnancy rates. Methods: A retrospective case-controlled study of 31 in vitro fertilization (IVF) patients, all of whom in a previous cycle had commenced the long protocol of GnRH-agonist (Buserelin) in the early follicular phase and were pretreated in a subsequent cycle with 2 weeks of an OC containing 30 g of ethinyl estradiol and 150 g of desogestrel prior to GnRH-agonist administration, was undertaken. Follow-up visits were arranged after a minimum of 11 days of GnRH-agonist administration and weekly thereafter until pituitary suppresion was achieved. Results: Cysts were detected in 16 (51.6%) of the 31 patients not pretreated with OCs, and in 0 (0%) of the 31 patients pretreated with OCs (odds ratio = 67.1; 95% confidence interval = 5.6–350.7). Patients pretreated with OCs achieved pituitary suppression more rapidly (median difference = 4 days; 95% confidence interval = 2–7) and had comparable gonadotropin requirements and pregnancy rates. Conclusions: Pretreatment with OCs prior to pituitary suppression in the early follicular phase decreases ovarian cyst formation, without an apparent effect on subsequent follicular recruitment or pregnancy rates.     

Pregnancy following induction of ovulation with pure FSH after suppression of endogenous gonadotropins with subcutaneous Buserelin

Summary Ovarian stimulation in patients with disorders of ovulation or an inadequate luteal phase using human menopausal gonadotropins (hMG) gives a low pregnancy rate with a high incidence of overstimulation and a premature LH surge. In order to overcome these problems, a new approach has been used, namely prior suppression of endogenous gonadotropins with a gonadotropin-releasing-hormone analog (LHRH) and subsequent ovarian stimulation with hMG. We present a case of ovarian stimulation with pure FSH during suppression of endogenous gonadotropins with the LHRH analog Buserelin. A clinical pregnancy was achieved in the first treatment cycle and led us to conclude that follicular development does not depend on LH stimulation. This could be of substantial interest in IVF programs.     

Comparison between a single dose of goserelin (depot) and multiple daily doses of leuprolide acetate for pituitary suppression in IVF treatment: a clinical endocrinological study of the ovarian response

Purpose : Compare the efficacy and safety of two different GnRHa, used for pituitary suppression in IVF cycles. Methods : A total of 292 patients using depot goserelin (Group 1) and 167 using daily leuprolide acetate (Group 2) were compared. Days required to achieve pituitary function suppression, duration of ovarian stimulation, total dose of HMG, number of aspirated follicles, number of oocytes retrieved, and presence of functional ovarian cyst were analyzed. Results : The time taken to achieve downregulation was similar. The mean number of ampoules used for superovulation was higher in Group 1; however, this difference was observed only for patients >40 years old that started GnRHa in the follicular phase. There was no difference between the two groups in the duration of superovulation, in the number of follicles aspirated, and the number of oocytes retrieved. In the group of patients with >40 years the incidence of ovarian cysts was higher in Group 2. Conclusions : Both routes of GnRHa have similar effects for pituitary suppression and ovulation induction in assisted reproductive technology. Therefore the long-acting GnRHa is an excellent option, as only a single subcutaneous dose is necessary, decreasing the risk of the patient to forget its use and, most important, it does not interfere in the patient's quality of life.     

Atypical response to luteinizing hormone-releasing hormone (LH-RH) agonist (Suprefact nasal) in induction of ovulation in in vitro fertilization (IVF)

Animal and human research has indicated the presence of receptors to luteinizing hormone-releasing hormone (LH-RH) in the ovaries. However, the role of these receptors is not yet clear. Forty-five patients were treated with Suprefact (d-Serg-Des-Gly10-GnRGH), starting in the midluteal phase of a nonstimulatory menstrual cycle. The Suprefact (300 g t.i.d.) was administered as a nasal spray until the administration of human chorionic gonadotropin (hCG). On the third to fifth day of the following menstrual cycle, the patients were treated with a high dose of human menopausal gonadotropin (hMG). hCG was administered when at least two follicles reached a mean diameter of 18 mm. Five of these patients who ovulated spontaneously and had normal menstrual cycles did not respond to the stimulation with hMG. Treatment was stopped after 12 days of hMG administration. During the following cycle of the five patients, levels of gonadotropins were found to be in the normal range, and all of them responded as expected to hMG administered for 3 days only (hMG test). These findings suggest that LH-RH agonist may interfere with ovarian steroidogenesis.