The threshold of estradiol level for fresh embryo transfer differs between blastocyst and cleavage-stage embryo

Ovarian stimulation can cause supraphysiological estradiol levels and adverse effects on endometrial receptivity. Since patients could undergo cleavage or blastocyst stage embryo transfer, the threshold value of peak estradiol level for each transfer stage that impacts the pregnancy outcomes of fresh versus frozen embryo transfer remains unclear. This work aims at answering the following questions: what is the threshold of peak estradiol level that modifies the difference in pregnancy outcomes between fresh and frozen embryo transfer and whether the threshold value varies with the stage of embryo transferred?

A secondary analysis of data from four multicenter randomized trials with similar design comparing the rate of live birth between fresh and frozen embryo transfer in a total of 6153 patients. Peak serum estradiol level was measured on the day of hCG administration. Live birth rate is the primary outcome.

Multivariable regression modeling showed an interaction between the stage of embryo transferred and the intervention (frozen vs fresh embryo transfer) on the live birth rate (p = 0.016). In the cleavage-stage embryo transfer group, frozen embryo transfer resulted in a higher rate of live birth when peak estradiol level >3900 pg/mL (55.4% vs 44.9%; OR, 1.57; 95% CI, 1.24-1.99) and a similar live birth rate (OR, 1.10; 95% CI, 0.93-1.31) when peak estradiol level was 1600-3900 pg/mL. However, in the blastocyst transfer group, frozen embryo transfers yielded a higher live birth rate when peak estradiol level >2000 pg/mL (54.3% vs 37.7%; OR, 2.00; 95% CI, 1.59-2.51).

A freeze-all strategy may result in a higher rate of live birth when the peak estradiol level >3900 pg/mL for cleavage-stage embryo transfer and when the peak estradiol level >2000 pg/mL for blastocyst transfer.