Do spontaneously decreasing estradiol levels prior to triggering of ovulation adversely impact in vitro fertilization outcomes?

Objective: The aim of this study was to explore the potential adverse effect of spontaneously decreasing serum estradiol (SE) levels on in vitro fertilization (IVF) outcomes. Methods: This retrospective single-subject study analyzed IVF cycles conducted at a hospital IVF unit between 2010 and 2017. Overall, 2,417 cycles were analyzed. Only cycles with spontaneously decreasing SE before human chorionic gonadotropin (hCG) triggering were included. Each patient served as her own control, and subsequent cycles were analyzed for recurrent SE decreases. The main outcome was the number of oocytes retrieved. Results: Cycle characteristics were similar between the study (SE decrease) and control groups, with the exception of the median SE on the day of hCG triggering (899.7 pg/mL; interquartile range [IQR], 193-2,116 pg/mL vs. 1,566.8 pg/mL; IQR, 249-2,970 pg/mL; p<0.001). The study group, relative to the control group, had significantly fewer total oocytes (5 [IQR, 2-9] vs. 7 [IQR, 3-11]; p=0.002) and significantly fewer metaphase II (MII) oocytes (3 [IQR, 1-6] vs. 4 [IQR, 2-8]; p=0.001) retrieved. The study group had fewer cleavage-stage embryos than the control cycles (3 [IQR, 1-6] vs. 4 [IQR, 2-7]; p=0.012). Compared to cycles with a ≤20% SE decrease, cycles with a >20% decrease had significantly fewer total and MII oocytes retrieved. SE decrease recurred in 12% of patients. Conclusion: A spontaneous decrease in SE levels adversely affected IVF outcomes, with a linear correlation between the percentage decrease and the number of oocytes retrieved. SE decrease can repeat in later cycles.