Suppression of corpus luteum function by the gonadotropin-releasing hormone antagonist Nal-Glu: effect of the dose and timing of human chorionic gonadotropin administration

Abstract

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.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.Participants were studied in Clinique Endocrinologique, Nantes, and in Service d'Endocrinologie, Hôpital Bicêtre, Le Kremlin Bicetre, France.Twenty-nine normal young women (ages 20 to 35) were studied.None.Measurements of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, Progesterone (P) levels were performed by radioimmunoassay before, during, and after the various treatment regimens.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.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.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.