Endometrial preparation before the transfer of single, vitrified-warmed, euploid blastocysts: does the duration of estradiol treatment influence clinical outcome?

Objective: To investigate whether the duration of estrogen administration before euploid embryo transfer affects clinical outcome. Design: Retrospective cohort study. Setting: Private, academic fertility center. Patient(s): Patients (n = 1,439) undergoing autologous freeze-only in vitro fertilization with preimplantation genetic testing (PGT) followed by endometrial preparation with estrogen and progesterone in a frozen, euploid blastocyst transfer cycle. Intervention(s): None. Main Outcome Measure(s): Primary outcome was live birth, and secondary outcomes included implantation, clinical pregnancy, early pregnancy loss, live birth, infant birthweight, low birth weight, infant gestational age at delivery, and preterm birth. Result(s): The duration of estrogen administration (mean: 17.5 ± 2.9 days; range: 10–36 days) before frozen embryo transfer did not impact implantation (odds ratio [OR] 0.99; 95% confidence interval [CI], 0.95–1.03), clinical pregnancy (OR 0.98; 95% CI, 0.94–1.01), early pregnancy loss (OR 1.03; 95% CI, 0.95–1.12), or live birth (OR 0.99; 95% CI, 0.95–1.03). The duration of estrogen exposure did not affect infant birthweight (in grams) (β= −10.65 ± 8.91) or the odds of low birth weight (OR 0.87; 95% CI, 0.68–1.13). For every additional day of estrogen administration, we observed a reduction in gestational age at delivery (in weeks) (β= −0.07 ± 0.03), but the odds of preterm delivery were not affected (OR 1.05; 95% CI, 0.95–1.17). Conclusion(s): Variation in the duration of estradiol supplementation before progesterone initiation does not impact frozen, euploid blastocyst transfer outcome. The duration of estrogen administration was inversely correlated with gestational age at delivery, but this did not translate into an increase in preterm delivery. Further studies are required on the downstream effects of endometrial preparation on the placental–endometrium interface.