Cesar Cornel

Prevention of premature luteinizing hormone and progesterone rise with a gonadotropin-releasing hormone antagonist, Nal-Glu, in controlled ovarian hyperstimulation *

Objective To report a preliminary study on the efficacy of a gonadotropin-releasing hormone antagonist (Nal-Glu) for preventing premature luteining hormone (LH) and progesterone (P) rise in controlled ovarian hyperstimulation using clomiphene citrate (CC) and human menopausal gonadotropin (hMG). Design Participants in the study formed two groups. Both groups received CC-hMG and Nal-Glu. Group II differs from group I for receiving human chorionic gonadotropin (hCG) and blood samples for 10 days after the second Nal-Glu injection. Setting Centre de Fecondation in Vitro, Hopital Antoine Beclere. Patients Eleven women 25 to 34 years of age and having normal menstrual cycles using barrier method of contraception not attempting pregnancies participated in the study. Intervention Daily blood samples, pelvic ultrasound, and CC-hMG/Nal-Glu/hCG administration. Main Outcome Measures (1) Spontaneous LH surge and P rise, follicular growth, and plasma E 2 levels in cycles with CC-hMG/Nal-Glu administration and (2) luteal phase after hCG injection in subjects previously treated with CC-hMG/Nal-Glu. Results Plasma E 2 level increased from 983 ± 80 pg/mL (mean ± SEM) on the day of the first Nal-Glu administration to 1,159 ± 102 and 1,610 ± 114 pg/mL (mean ± SEM) 24 and 48 hours later. In 10 women, LH and P remained low for at least 96 hours after the first Nal-Glu administration. In one subject, plasma LH was already elevated at the time of the first Nal-Glu injection. In women who received hCG, plasma E 2 and P reached a maximum of 1,258 ±313 pg/mL and 50.3 ± 12.8 ng/mL (mean ± SEM), respectively, on the 6th day of the luteal phase. Conclusion Our results suggest that timely Nal-Glu injections can prevent LH and P rise for at least 96 hours, in spite of increasing levels of plasma E 2 . Moreover, Nal-Glu had no adverse effect on the kinetic of E 2 rise, the follicular growth, or on the post-hCG hormonal profile.

Comparison of short 7-day and prolonged treatment with gonadotropin-releasing hormone agonist desensitization for controlled ovarian hyperstimulation

OBJECTIVE To compare two treatment regimens associating a gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropin (hMG) for controlled ovarian hyperstimulation (COH). DESIGN A prospective randomized trial. SETTING The outpatient fertility clinic of a university tertiary care center, the Hôpital A. Béclère, Clamart, France. PARTICIPANTS One hundred eighty-two in vitro fertilization (IVF) candidates undergoing new or repeat IVF cycles at Hôpital A. Béclère over a 4-month period. TREATMENT Group 1 (7-day protocol): A short-acting preparation of GnRH-a (Tripteriline 0.1) was administered daily for 7 days, starting on cycle day 2. Ovarian stimulation with hMG was started on cycle day 4. Group 2 (long protocol): A timed release preparation of GnRH-a (Tripteriline 3.75 mg) was administered on cycle day 2. Ovarian stimulation with hMG was started after documented ovarian suppression. MAIN OUTCOME MEASURES Response to COH, pregnancy rate (PR), tolerance. RESULTS In the 7-day protocol, the amount of hMG required was markedly lower at 24 +/- 7 than in the long protocol group requiring 42.5 +/- 9.75 vials (75 IU) (mean +/- SD). No elevation of plasma LH occurred in either group. The number of oocytes retrieved was 7.3 +/- 1 and 10.7 +/- 1.2 (mean +/- SD) in the 7-day and long protocols, respectively. Yet, the number of embryos obtained and the PRs were similar in the two treatment groups. CONCLUSIONS We observed that in COH, GnRH-a treatment could be interrupted safely several days before human chorionic gonadotropin administration without risking a premature increase of plasma luteinizing hormone. Moreover, the number of embryos available for fresh transfer and the ongoing PRs were similar in the new 7-day and in the classic long GnRH-a/hMG protocols, despite the smaller number of oocytes suggesting a greater efficiency of the 7-day protocol. The peak estradiol level and the hMG requirement were also lower in the 7-day GnRH-a/hMG protocol.

Prevention of premature luteinizing hormone and progesterone rise with a gonadotropin-releasing hormone antagonist, NaI-Glu, in controlled ovarian hyperstimulation

OBJECTIVE To report a preliminary study on the efficacy of a gonadotropin-releasing hormone antagonist (Nal-Glu) for preventing premature luteinizing hormone (LH) and progesterone (P) rise in controlled ovarian hyperstimulation using clomiphene citrate (CC) and human menopausal gonadotropin (hMG). DESIGN Participants in the study formed two groups. Both groups received CC-hMG and Nal-Glu. Group II differs from group I for receiving human chorionic gonadotropin (hCG) and blood samples for 10 days after the second Nal-Glu injection. SETTING Centre de Fecondation in Vitro, Hôpital Antoine Béclère. PATIENTS Eleven women 25 to 34 years of age and having normal menstrual cycles using barrier method of contraception not attempting pregnancies participated in the study. INTERVENTION Daily blood samples, pelvic ultrasound, and CC-hMG/Nal-Glu/hCG administration. MAIN OUTCOME MEASURES (1) Spontaneous LH surge and P rise, follicular growth, and plasma E2 levels in cycles with CC-hMG/Nal-Glu administration and (2) luteal phase after hCG injection in subjects previously treated with CC-hMG/Nal-Glu. RESULTS Plasma E2 level increased from 983 +/- 80 pg/mL (mean +/- SEM) on the day of the first Nal-Glu administration to 1,159 +/- 102 and 1,610 +/- 114 pg/mL (mean +/- SEM) 24 and 48 hours later. In 10 women, LH and P remained low for at least 96 hours after the first Nal-Glu administration. In one subject, plasma LH was already elevated at the time of the first Nal-Glu injection. In women who received hCG, plasma E2 and P reached a maximum of 1,258 +/- 313 pg/mL and 50.3 +/- 12.8 ng/mL (mean +/- SEM), respectively, on the 6th day of the luteal phase. CONCLUSION Our results suggest that timely Nal-Glu injections can prevent LH and P rise for at least 96 hours, in spite of increasing levels of plasma E2. Moreover, Nal-Glu had no adverse effect on the kinetic of E2 rise, the follicular growth, or on the post-hCG hormonal profile.

Controlled preparation of the endometrium with exogenous estradiol and progesterone in women having functioning ovaries

OBJECTIVE To determine if controlled preparation of the endometrium with exogenous estradiol (E2) and progesterone (P) could be achieved in women retaining their ovarian function without requiring prior ovarian suppression with a long-acting agonist of gonadotropin-releasing hormone (GnRH-a). DESIGN Prospective feasibility study of a new simplified hormone regimen for preparation of endometrium receptivity. Six volunteer women received transdermal E2 and vaginal P without prior suppression of their ovarian function with GnRH-a. The control group consisted of previously reported cases receiving GnRH-a and E2 and P. SETTING Academic tertiary care institution. PATIENTS Six volunteer women. MAIN OUTCOME MEASURES Participants received transdermal E2 and P after a regimen designed to duplicate the plasma E2 and P levels seen in the menstrual cycle. INTERVENTION Endometrial biopsy. RESULTS Plasma luteinizing hormone increased to surge levels in one woman on day 11, in two on day 12, and on day 14 in the remaining three women. No follicular growth was noticed on ultrasound, and no increase in plasma P occurred before the onset of P administration on day 15. Day 20 endometrium specimens showed early secretory changes as previously reported in women deprived of ovarian function receiving similar hormonal treatment. CONCLUSIONS Our results indicate that controlled preparation of the endometrium can be achieved with exogenous E2 and P without prior ovarian suppression with a GnRH-a in women having functioning ovaries. Hence, administration of exogenous E2 and P appears to be a viable simpler alternative to the combined administration of GnRH-a and exogenous E2 and P, which avoids the side effects and the cost of GnRH-a.