Low estradiol responses in oocyte donors do not influence in vitro fertilization cycle outcomes

Abstract

In vitro fertilization (IVF) success correlates with higher estradiol (E2) responses. We have identified a cohort of oocyte donors whose E2 levels defy this observation. We aimed to define the incidence of low E2 (LE2) responses in oocyte donors, and to compare number of oocytes retrieved, fertilization rate, embryo development and IVF outcomes in donors with typical E2 (TE2) versus LE2 responses. We also considered possible mechanisms responsible for LE2. Retrospective Cohort Study A review of donor oocyte cycles performed at a single center from January 2010 to December 2016 was conducted. Donor demographics, ovarian reserve testing, ovarian stimulation characteristics, and IVF cycle outcomes were collected. Only FSH/antagonist cycles were included. TE2 responses were defined as E2 greater than 200 pg/mL per follicle. LE2 responses were defined as E2 less than 100pg/mL per follicle. Low E2 serum levels were confirmed with a different assay system. Antimüllerian hormone (AMH) levels were obtained on the day of peak E2 in LE2 and TE2 groups, and a portion of follicular fluid samples were analysed. Characteristics and outcomes of donor groups with TE2 versus LE2 were compared. 366 donor cycles were identified. 184 (50.2%) cycles had LE2, including 74 (20.2%) with values of E2 less than 50 pg/mL per follicle. LE2 donors were younger (25.6 vs. 27.4 years, LE2 vs. TE2, p=0.0004) with higher percentage Caucasian versus TE2 donors (80.4 vs. 57%, p=0.0024). LE2 donors received higher total doses of gonadotropins (2097.5 vs. 1764.6 IU, p=0.0004), longer stimulation (10.8 vs. 9.8 days, p<0.0001), and demonstrated higher gonadotropin to E2 ratios versus TE2 donors (2.30 vs. 0.55, p<0.0001). Nevertheless, LE2 cycles resulted in a greater number of mature oocytes (22.1 vs. 13.6, p<0.0001), fertilizations (17.5 vs. 10.7, p<0.0001), and transferred or cryopreserved blastocysts (8.0 vs. 4.8, p=0.0002) versus TE2 cycles. The percentage of chromosomally normal embryos after PGS was similar between LE2 and TE2 cycles (68.1 vs. 63.1%, p=0.86). Pregnancy outcomes were also similar. Sixty-two donors with LE2 underwent multiple cycles and 14 (22.6%) had LE2 with all cycles. Mean serum AMH obtained on the day of peak E2 was non-significantly higher in LE2 patients versus TE2 donors (3.21 vs. 1.72, p=0.72). Preliminary data of LE2 follicular fluid E2 showed lower E2 from mature follicles (117.6 ng/mL vs. established values of greater than 300 ng/mL). The prevalence of LE2 responses in donors appears to be high (50.2%), with 20.2% of cycles having extremely low E2 responses. LE2 does not portend poor outcome in oocyte donors. Despite a suboptimal rise in serum E2, which is reflected in follicular fluid, serum AMH of LE2 donors was non-signficantly higher than TE2 at HCG trigger. Despite suggested alterations in granulosa cell function in LE2, clinical results are excellent.