The luteal phase of cycles utilizing controlled ovarian hyperstimulation and the possible impact of this hyperstimulation on embryo implantation

B A Kolb, R J Paulson
American Journal of Obstetrics and Gynecology 1997, 176 (6): 1262-7; discussion 1267-9

OBJECTIVE: Our purpose was to evaluate the early luteal phase of assisted reproductive cycles utilizing controlled ovarian hyperstimulation and to compare these results with those obtained in unstimulated cycles.

STUDY DESIGN: We undertook a descriptive study analyzing luteal phase serum progesterone levels, endometrial histologic features, and endometrial surface ultrastructure by scanning electron microscopy of cycles utilizing controlled ovarian hyperstimulation. Study samples were obtained from 7 oocyte donors undergoing controlled ovarian hyperstimulation for the purpose of follicle aspiration in oocyte donation. Control (unstimulated) serum progesterone samples were obtained from 19 patients undergoing in vitro fertilization in unstimulated cycles. Prospective recipients of oocyte donation (n = 20) undergoing mock cycles of exogenous estradiol and progesterone acted as controls for the endometrial biopsies.

RESULTS: Serum progesterone levels on the day of human chorionic gonadotropin administration were twofold higher in the study 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, progesterone 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 revealed that the study group was advanced by nearly 2 days as compared with the group having artificial cycles. Pinopods, ultrastructural markers of the implantation window, were present in only one of seven study cycles as compared with all of the four artificial cycles.

CONCLUSIONS: The early luteal phase of cycles undergoing controlled ovarian hyperstimulation is characterized by markedly elevated serum progesterone levels during the periovulatory period, advanced endometrial histologic features, and an absence of endometrial pinopods at the time of embryo implantation. We speculate that these high levels of progesterone 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.

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