High doses of oral contraceptives do not alter endometrial alpha 1 and alpha v beta 3 integrins in the late implantation window

Abstract

Objective: To assess the effects of an emergency contraceptive agent on the distribution of integrin heterodimers during that part of the implantation window.

Design: Prospective, case-controlled study in a university-based Population Program. In the first ovulatory control cycle after the detection of LH surge, patients had endometrial sampling 11 days after the surge. In the next cycle the procedure was repeated 2 days after the administration of a postcoital contraceptive agent on day 9 after LH surge (100 g ethinyl E2 and 2 mg norgestrel).

Main outcome measures: The effects of postcoital contraceptives on the expression of integrin heterodimers (alpha 1 and alpha v beta 3 subunits) reported to be unique to secretory phase was determined.

Results: All six specimens were consistent histologically with days 24 and 25 of the menstrual cycle by light microscopy. Using immunohistochemistry, strong membrane staining of endometrial glandular cells and superficial epithelium for both alpha 1 subunit and vitronectin (alpha v beta 3) receptor was observed in treatment and controls. No diminution of intensity or distribution was observed relative to pretreatment controls.

Conclusions: There is no apparent change in the level of these two integrins in the human endometrium when high-dose oral contraceptives are given in the later stages of the implantation window. This suggests that the high doses of steroids used in emergency contraceptives may exert their effect through more complex mechanisms than endometrial cell surface changes.

PIP: In the human female, high doses of estrogen have been used to prevent implantation of the fertilized egg. Integrins function as receptors and play an important role in blastocyst attachment to the uterine wall. This article reports the findings of a study which tested what effects an emergency contraceptive agent has on integrin spread during the effective implantation window. Three women with regular menstrual cycles volunteered for this study. Endometrial biopsies were performed before any hormonal treatment; these samples were considered controls. These same patients were then orally given 100 g ethinyl E2 and 2 mg norgestrel. 11 days later a second endometrial biopsy was taken. All samples were divided into two groups. One group was fixed in glutaraldehyde and prepared for light microscopy examination. The second group was frozen in liquid nitrogen and subsequently used for cryosection examination. Immunohistochemistry techniques were performed on the tissues. No morphological differences were observed between the two groups. Immunohistochemistry results were unremarkable. Expected luteal phase endometrial changes were not observed. These results show that there is no apparent change in the level of different integrins in the human endometrium when high doses of oral contraceptives are administered. This further suggests that high doses of steroids used for preventing blastocyst implantation may not work through changes in the endometrial cell surface receptivity as previously believed.