THE LUTEAL-PHASE OF CYCLES UTILIZING CONTROLLED OVARIAN HYPERSTIMULATION AND THE POSSIBLE IMPACT OF THIS HYPERSTIMULATION ON EMBRYO IMPLANTATION

OBJECTIVE: Our purpose was to evaluate the early luteal phase of assis ted reproductive cycles utilizing controlled ovarian hyperstimulation and to compare these results with those obtained in unstimulated cycle s. STUDY DESIGN: We undertook a descriptive study analyzing luteal pha se serum progesterone levels, endometrial histologic features, and end ometrial surface ultrastructure by scanning electron microscopy of cyc les utilizing controlled ovarian hyperstimulation. Study samples were obtained from 7 oocyte donors undergoing controlled ovarian hyperstimu lation for the purpose of follicle aspiration in oocyte donation. Cont rol (unstimulated) serum progesterone samples were obtained from 19 pa tients undergoing in vitro fertilization in unstimulated cycles. Prosp ective recipients of oocyte donation (n = 20) undergoing mock cycles o f exogenous estradiol and progesterone acted as controls for the endom etrial biopsies. RESULTS: Serum progesterone levels on the day of huma n chorionic gonadotropin administration were twofold higher in the stu dy group than in the unstimulated group (1.1 +/- 0.6 vs 0.5 +/- 0.2 ng /ml, mean +/- SD, p < 0.01). On the day of follicle aspiration, proges terone levels were much higher in the study group (8.5 +/- 2.2 vs 0.5 +/- 0.1 ng/ml, p < 0.001). Histologic dating of endometrial biopsies r evealed that the study group was advanced by nearly 2 days as compared with the group having artificial cycles. Pinopods, ultrastructural ma rkers of the implantation window, were present in only one of seven st udy cycles as compared with all of the four artificial cycles. CONCLUS IONS: The early luteal phase of cycles undergoing controlled ovarian h yperstimulation is characterized by markedly elevated serum progestero ne levels during the periovulatory period, advanced endometrial histol ogic features, and an absence of endometrial pinopods at the time of e mbryo implantation. We speculate that these high levels of progesteron e in the early luteal phase cause premature endometrial luteinization and a premature appearance of the implantation window, thus providing an explanation for the observed decrease in endometrial receptivity.