The impact of estradiol on pregnancy outcomes in letrozole-stimulated frozen embryo transfer cycles

Assisted Reproduction

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VOLUME 2, ISSUE 3, P320-326, SEPTEMBER 01, 2021

Authors:

Wendy Y. Zhang, M.D., Rebecca M. Gardner, M.S., Kristopher I. Kapphahn, M.S., Maya K. Ramachandran, M.D., Gayathree Murugappan, M.D., Lusine Aghajanova, M.D., Ph.D., Ruth B. Lathi, M.D.

Abstract:

Objective

To assess the impact of low estradiol (E2) levels in letrozole-stimulated frozen embryo transfer (FET) cycles on pregnancy and neonatal outcomes.


Design

Retrospective cohort.


Setting

University-affiliated fertility center.


Patient(s)

All patients who underwent letrozole-stimulated FET cycles from January 2017 to April 2020 (n = 217). The “Low E2” group was defined as those with E2 serum levels on the day of trigger <10th percentile level (E2 <91.16 pg/mL, n = 22) and the “Normal E2” group was defined as those with E2 serum levels ≥10th percentile level (E2 ≥91.16 pg/mL, n = 195).


Intervention(s)

None.


Main Outcome Measure(s)

Pregnancy outcomes including rates of clinical pregnancy, clinical miscarriage, and live birth. Neonatal outcomes including gestational age at delivery, birth weight, and Apgar score.


Result(s)

The mean ± SD estradiol level was 66.8 ± 14.8 pg/mL for the “Low E2” group compared with 366.3 ± 322.1 pg/mL for the “Normal E2” group. There were otherwise no substantial differences in cycle characteristics such as endometrial thickness on the day of ovulation trigger and progesterone levels in early pregnancy. The “Low E2” group had a significantly higher clinical miscarriage rate (36.4% vs. 8.8%, adjusted odds ratio 8.06) and lower live birth rate (31.8% vs. 57.9%, adjusted odds ratio 0.28). Neonatal outcomes such as gestational age at delivery, mean birth weight, Apgar scores, and incidence of newborn complications were not clinically different between the groups.


Conclusion

Low E2 levels were associated with a significantly higher miscarriage rate and lower live birth rate, suggesting that E2 levels in the follicular phase may have an effect on cycle outcomes. Given the rise in use of FET, further studies are needed to confirm our findings and understand the mechanisms.

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.