Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization

Elevated serum estradiol level on the day of human chorionic gonadotropin administration is associated with adverse obstetrical outcomes.


Anthony N. Imudia, M.D., Awoniyi O. Awonuga, M.D., Joseph O. Doyle, M.D., Anjali J. Kaimal, M.D., Diane L. Wright, Ph.D., Thomas L. Toth, M.D., Aaron K. Styer, M.D.

Vol 97, Issue 6 , Pages 1374-1379



To assess the impact of elevated peak serum E2 levels (EPE2; defined as levels >90th percentile) on the day of hCG administration during controlled ovarian hyperstimulation (COH) for IVF on the likelihood for small for gestational age (SGA), preeclampsia (PreE), and preterm delivery (PTD) in singleton pregnancies.


Retrospective cohort study.


Tertiary-care academic medical center.


Singleton live-birth pregnancies conceived after fresh IVF-ET.



Main Outcome Measure(s):

The delivery rate of SGA infants and the development of PreE and PTD in patients with and without EPE2.


Patients with EPE2 during COH were more likely to deliver SGA infants (7 [26.9%] vs. 10 [3.8%]; odds ratio [OR], 95% confidence interval [CI] {9.40, 3.22–27.46}) and develop PreE (5 [18.5%] vs. 12 [4.5%]; adjusted OR, 95% CI {4.79, 1.55–14.84}). No association was found between EPE2 and the likelihood for delivery before 37 weeks, 35 weeks, or 32 weeks of gestation. Receiver operating characteristic analysis revealed that EPE2 level predicted adverse obstetrical outcome (SGA + PreE) with 38.5% and 91.7% sensitivity and specificity, respectively. Using a serum peak E2 cutoff value of 3,450 pg/mL (>90th percentile level), the positive predictive value was 37%, while the negative predictive value was 92%.


EPE2 level (>3,450 pg/mL) on the day of hCG administration during COH is associated with greater odds of developing PreE and delivery of an SGA infant in singleton pregnancies resulting from IVF cycles.

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