Apoptosis of mural granulosa cells is increased in women with diminished ovarian reserve

Abstract

Purpose: To evaluate the relationship between apoptosis of granulosa cells in women with normal ovarian reserve versus diminished ovarian reserve, and relate that to follicular fluid hormones, and to clinical outcomes. Methods: A prospective cohort study was initiated between October 2015 and June 2016 involving a total of 164 women undergoing IVF/ICSI cycles at a single IVF center. Mural and cumulus granulosa cells, and follicularfluid were collected during oocyte retrieval. Annexin V-FITC/PI apoptosis staining and flow cytometryanalysis were performed to evaluate apoptosis rate of mural granulosa cells and cumulus cells. Follicularfluid hormones were measured by ECLIA. Laboratory and clinical outcomes were analyzed. Results: In mural granulosa cells, early, late and total apoptosis rates were significantly increased in women with diminished ovarian reserve when compare to women with normal ovarian reserve, along with lower AMHand progesterone levels (but higher estradiol levels) in follicular fluid. Early apoptosis rate of cumulus cellswas significantly higher in the non-pregnant group. The apoptosis rate of mural cells was negativelycorrelated with parameters related to ovarian response, oocyte yield, MII egg number, 2pn cleavagenumber, D3 good embryos number, blastocyst formation rate and frozen embryos number. A positivecorrelation was found between mural granulosa cell apoptosis and age. Conclusion: A significantly higher apoptosis rate of mural granulosa cells was correlated with worse ovarian response, with fewer egg and embryo numbers in IVF/ICSI, as well as with age. Early apoptosis rate of cumulus cellsmight also have influence on clinical pregnancy.