Premature luteinizing hormone surges in menopausal gonadotropin-stimulated cycles in monkeys: Lack of initiation by progesterone

The occurrence of spontaneous luteinizing hormone (LH) surges in women receiving human menopausal gonadotropins (hMG) for in vitro fertilization-embryo transfer is a significant clinical problem. One hypothetical mechanism is that premature progesterone (P) secretion occurring in the high estradiol (E₂) milieu produced by hMG triggers the spontaneous LH surge. To investigate this possibility, 11 rhesus and cynomolgus monkeys were stimulated with hMG. At maximal ovarian stimulation, monkeys were injected with 15 μg/kg P (n = 3), 30 μg/kg P (n = 3), or 1,000 IU human chorionic gonadotropin (hCG) (n = 5; controls). Blood for E₂, P, and LH was drawn twice daily in the periovulatory period and daily before and after this period. Laparoscopy was performed after P or hCG injection. In the 6 monkeys receiving P, no LH surges were detected. Further, postinjection P profiles and laparoscopy showed no evidence of ovulation. Controls demonstrated laparoscopic and hormonal evidence of ovulation. These findings suggest that P does not trigger LH surges in hMG-stimulated cycles.