Levels of steroid-binding proteins and steroids in human preovulatory follicle fluid and serum as predictors of success in in vitro fertilization-embryo transfer treatment

Abstract

In an attempt to identify the embryos and cycles that have the best chances of resulting in establishment of pregnancies, after in vitro fertilization-embryo transfer (IVF-ET) treatment, the concentrations of sex hormone-binding globulin (SHBG) and cortisol-binding protein (CBP) were measured, using two new enzyme-linked immunosorbent assays in serum and follicle fluid (FF) from 30 women (125 FF) undergoing IVF-ET. The concentrations were compared to those of total estradiol and total progesterone, and correlated to oocyte cleavage and the establishment of pregnancies. Serum concentrations of CBP were significantly higher in women who became pregnant (1469 ± 108) nM (±SEM)) than in those who did not (CBP, 1200 ± 58 nM; P ≤ 0.05). The concentrations of SHBG were not significant different in these two groups of women (72.4 ± 9.3 and 60.8 ± 4.2 nM, respectively; P ≥ 0.10). By contrast, in FF significantly higher concentrations of both SHBG and CBP were found in women achieving pregnancy (SHBG, 56.1 ± 2.8 nM; CBP, 1198 ± 37 nM) than in those who did not (SHBG, 45.5 ± 1.4 nM; P ≤ 0.001; CBP, 1079 ± 29 nM; P ≤ 0.01). A positive correlation was found between serum and FF levels of both SHBG (r = 0.85; P ≤ 0.001) and CBP (r = 0.70; P ≤ 0.001). FF levels of estradiol and progesterone did not differ regardless of whether the oocyte cleaved. However, a significant reduction of estradiol was found in fluid from follicles in which the oocyte cleaved and resulted in pregnancy (3046 ± 180 nM) than in fluid from follicles in which the oocyte cleaved but without establishment of pregnancy (4162 ± 282 nM; P ≤ 0.001). There was no correlation between estradiol and SHBG and between progesterone and CBP. However, levels of FF progesterone above 15,000 nM combined with CBP concentrations above the mean concentration found in FF (1,127 nM) were related with oocyte cleavage in 87% of the cases. The overall cleavage rate is 56%. The higher levels of SHBG and CBP in serum compared to those in FF, and the positive relationship between serum and FF levels suggest that both proteins arise from the circulation. The similar levels in serum and FF indicate that neither SHBG nor CBP is responsible for maintaining the concentration gradient of estradiol and progesterone from follicle to plasma. These results suggest that levels of CBP in serum and levels of SHBG and CBP in FF may serve as predictors of successful IVF cycles. This study also emphasizes the need for studies of other parameters in addition to ovarian factors in understanding cycles resulting in pregnancy in women undergoing IVF-ET treatment.