Superphysiological estradiol level is a risk factor of small for gestational age and low birth weight of fresh embryo transfer

Objective To investigate the relationship between supraphysiologic estradiol levels on the human chorionic gonadotropin (hCG) injection day and small for gestational age (SGA) and low birth weight (LBW). Methods It was a retrospective cohort study. Patients with singleton pregnancies with delivered after transfer of fresh embryos during the period of July 2008 to July 2017 at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University were included. According to the serum estradiol level on the day of hCG trigger, we divided all patients into 6 groups. Group A: estradiol≤2000 ng/L (referent group), group B: estradiol 2001-3000 ng/L, group C: estradiol 3001-4000 ng/L, group D: estradiol 4001-5000 ng/L, group E: estradiol 5001-6000 ng/L, group F: estradiol>6000 ng/L. The outcome measures were SGA, LBW, very low birth weight (VLBW), preterm birth (PT) and full-term LBW. We compared the odds ratio (OR) of SGA, LBW, VLBW, PT and full-term LBW among the groups. Then multivariable logistic regression [age, parity, body mass index (BMI), infertility time, type of infertility, cause of infertility, endometrial thickness of hCG injection day, mode of assisted pregnancy, stage of embryo transfer, the number of transplanted embryos, the sex of the newborn] was used to analyze whether these outcome measures could be explained by the estradiol level on the hCG trigger day. Results Compared with group A, the incidence of SGA, LBW and term LBW in group D, group E and group F increased significantly. However, the incidence of VLBW and PT did not change significantly with the increase of estradiol levels (P=0.70, P=0.85). After adjusting for confounding factors by logistic regression analysis, estradiol ≥ 4001 ng/L was an independent risk factor for SGA (group D: aOR=1.69, 95% CI=1.03-2.75, P=0.04; group E: aOR=1.94, 95% CI=1.12-3.36, P=0.02; group F: aOR=2.31, 95% CI=1.38-3.87, P<0.001), LBW (group D: aOR=1.95, 95% CI=1.11-3.44, P=0.02; group E: aOR=2.57, 95% CI=1.38-4.78, P<0.001; group F: aOR=3.36, 95% CI=1.89-5.98, P<0.001), and full-term LBW (group D: aOR=5.36, 95% CI=2.00-14.37, P<0.001; group E: aOR=7.35, 95% CI=2.64-20.49, P<0.001; group F: aOR=12.02, 95% CI=4.55-31.78, P<0.001). At the same time, we also found that BMI was associated with the incidence of SGA, patients with lower BMI had a higher risk of SGA (aOR=0.88, 95% CI=0.83-0.90, P<0.001). Conclusion Supraphysiological serum estradiol level was an independent risk factor for SGA, LBW and full-term LBW birth of fresh embryo transfer. Key words: Estradiol; Small for gestational age; Fresh embryo transfer; Low birth weight