Midluteal endometrial biopsy and alphavbeta3 integrin expression in the evaluation of the endometrium in infertility: implications for fecundity.

It has been recently proposed that the immunohistochemical evaluation of alphavbeta3 integrin in combination with histologic dating in midluteal endometrial biopsy specimens should be performed to evaluate the endometrial receptivity in the infertile patient. However, no studies have attempted to correlate these findings with subsequent fecundity. In 100 consecutive infertile patients (mean age 31.9+/-3.4 years) undergoing a routine work-up, two endometrial biopsies were performed during a single menstrual cycle: a midluteal biopsy on postovulatory days 6 to 8 and another biopsy 4 days later. Histological dating and immunohistochemical evaluation of alphavbeta3 integrin expression were done in all endometrial biopsy specimens. All patients were followed without treatment during 18 to 24 months (mean 23.5+/-1.4, range 18 to 24). Twenty-five midluteal biopsies showed out-of-phase endometria, whereas all but one late-luteal biopsy specimens were in-phase. Glandular alphavbeta3 integrin expression was observed in 50% of midluteal specimens with this expression being significantly more frequent among in-phase (63%) than among out-of-phase (12%) specimens (p<0.001). However, all late-luteal specimens strongly expressed this integrin. Thirty-eight women became spontaneously pregnant during the follow-up period, 32 ended in a live birth and 6 in first trimester spontaneous abortion. The Cox regression method showed no differences between the hazard of pregnancy when the alphavbeta3 integrin-positive and -negative groups were compared (odds ratio 1.25; 95% confidence interval [CI] 0.66-2.36; p=0.49) or when patients with in-phase endometria were compared with those with delayed endometrial maturation (odds ratio 1.12; 95% CI 0.53-2.37; p=0.76). In conclusion, neither midluteal histological evaluation nor alphavbeta3 integrin expression in mid- or late-luteal endometrial biopsy specimens correlated with outcome for subsequently untreated infertile women.