Objective: To assess the effect of gonadotropin-releasing hormone antagonist Nal-Glu administration in the luteal phase and the potential rescue by exogenous human chorionic gonadotropin (hCG) of corpus luteum (CL) after antagonist treatment.
Design: We studied the dose of Nal-Glu required for luteolysis and subsequently we coadministered low doses of hCG for 3 consecutive days either simultaneously to Nal-Glu administration (n = 5), or 48 (n = 5), or 72 hours (n = 5) later. Six additional participants received pharmacological doses of hCG 48 hours after the luteolytic dose of Nal-Glu.
Setting: Participants were studied in Clinique Endocrinologique, Nantes, and in Service d'Endocrinologie, Hôpital Bicêtre, Le Kremlin Bicetre, France.
Participants: Twenty-nine normal young women (ages 20 to 35) were studied.
Interventions: None.
Main outcome measure: Measurements of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, Progesterone (P) levels were performed by radioimmunoassay before, during, and after the various treatment regimens.
Results: Complete luteolysis occurred in women who received 10 mg of Nal-Glu daily on days 4 and 5 after the LH surge. The coadministration of Nal-Glu and hCG overrode the effect of the antagonist (P = 48.8 +/- 22.5 versus 60.8 +/- 3.1 nmol/L in controls treated with hCG alone [NS]). When hCG treatment was started 48 hours after Nal-Glu, a partial luteolysis occurred (P = 33.8 +/- 10.9 versus 117 +/- 12.9 nmol/L, P less than 0.01). When hCG was started 72 hours after Nal-Glu, a complete luteolysis occurred (P = 5.8 +/- 2.05 versus 36.2 +/- 0.6 nmol/L, P less than 0.01). Higher doses of hCG (1,500 or 5,000 IU) administered 72 hours after Nal-Glu resulted in a significant rescue of CL function (P = 37.7 +/- 4.8 and P = 43.8 +/- 22.2 versus 74.5 +/- 19.8 and 130.2 +/- 14.3 nmol/L, P less than 0.05), respectively.
Conclusions: These results confirm the LH dependence of CL function. The suppression of CL LH support for 72 hours induced a compromise of the CL nonreversible by low doses of hCG mimicking early pregnancy but reversible with pharmacological doses.
PIP: Researchers studied 29 women 20-35 years old at endocrinology clinics in Nantes and Kremlin Bicetre, France to determine if administering human chorionic gonadotropin (hCG) in addition to the pulsatile gonadotropin releasing hormone antagonist called Nal-Glu would rescue corpus luteum (CL) function. The study consisted of 3 parts: single and repeated administration of Nal-Glu; administration of Nal-Glu and low doses of hCG; and administration of Nal-Glu and pharmacological doses and hCG. The results showed that suppressing the release of luteinizing hormone (LH) for at least 3 days caused luteolysis, but small doses of exogenous hCG did not rescue CL function. On the other hand, if suppression lasted only 2 days, small doses of hCG partially rescued CL function. Nevertheless most participants who experienced suppression for at least 3 days had a spontaneous recovery of CL function, perhaps because suppression did not persist long enough to cause complete luteolysis. 2 injections of Nal-Glu on days 4-5 of the luteal phase did, however, suppress LH support for 72 hours thereby inducing complete luteolysis. 1 woman did not experience complete luteolysis though. Higher doses of hCG did rescue CL function, albeit incompletely. In conclusion, Nal-Glu administration progressively damages CL dose of hcg which maintains CL function may be reached if implantation occurs within 3 days after administration of the antagonist. Therefore it is questionable if hCG can be used as a postcoital contraception.