Elevated serum progesterone levels before frozen embryo transfer do not negatively impact reproductive outcomes: a large retrospective cohort study

Abstract

Objective: To evaluate whether patients with high-serum progesterone levels before frozen embryo transfer (FET) under hormonal replacement therapy present with worse reproductive outcomes.

Design: A cohort retrospective study.

Setting: A university-affiliated fertility center.

Patient(s): A total of 3,183 FET cycles in patients receiving hormonal replacement therapy between March 2009 and December 2020 were included. The luteal phase was covered with 200 mg per 8 hours of vaginal micronized progesterone either alone or in combination with a daily subcutaneous injection of 25 mg of progesterone. A total of 1,360 cycles corresponded to frozen homologous embryo transfer (ET) (hom-FET), 1,024 were euploid ET (eu-FET) after preimplantation genetic testing for aneuploidies, and 799 cycles were frozen heterologous ET (het-FET). All patients had adequate serum progesterone levels (≥10.6 ng/mL) before the procedure.

Intervention(s): Frozen embryo transfer cycles.

Main outcome measure(s): Clinical pregnancy, miscarriage, and live birth rates (LBRs).

Results: Median (P25; P75) serum progesterone level before FET was 14.39 (12.43-17.49) ng/mL. Progesterone levels were significantly higher in the group under vaginal plus subcutaneous progesterone (15.96 [13.74-21.60] vs. 14.09 [12.19-16.95]). No differences in clinical pregnancy, miscarriage, and LBR were observed based on the use of vaginal or vaginal plus subcutaneous progesterone for each of the groups (hom-FET, eu-FET, and het-FET). Live birth rates were comparable among patients in the highest centile of serum progesterone levels (≥p90) (22.33 ng/mL) and the rest of the patients (p<90) (43.9% vs. 41.3%). Patients with progesterone levels ≥p90 presented lower body mass index than those in the lower centiles (<p90) (22.62 ± 3.82 vs. 23.32 ± 4.06). After dividing patients into deciles based on serum progesterone levels, no differences in LBRs were observed among the groups. No association was observed using a generalized additive model between progesterone levels and LBR. A multivariable logistic regression adjusted by oocyte age, type of treatment, body mass index, type of luteal phase support, and the number of embryos transferred was applied for centile 90 and centile 95 of progesterone and showed that serum progesterone in their highest levels did not negatively impact LBR.

Conclusions: Elevated serum progesterone levels before FET do not impair reproductive outcomes in patients receiving artificially prepared cycles with vaginal or vaginal plus subcutaneous progesterone.

Keywords: Serum progesterone levels; artificial endometrial preparation; frozen embryo transfer; hormonal replacement therapy; luteal phase support.