Overweight and obesity affect the efficacy of vaginal vs. intramuscular progesterone for luteal-phase support in vitrified-warmed blastocyst transfer

Abstract

Objective: To compare the difference in the live birth rates (LBRs) between vaginal progesterone and intramuscular progesterone as luteal-phase support in programmed vitrified-warmed blastocyst transfer cycles and determine whether the association was moderated by overweight/obesity.

Design: Retrospective cohort study.

Setting: Tertiary reproductive medicine center.

Patient(s): Patients who underwent transfer of single vitrified-warmed blastocyst in a programmed cycle between January 2018 and June 2021.

Intervention(s): Vaginal or intramuscular progesterone as luteal-phase support. Analysis was performed using the generalized estimating equation framework and multivariate regression models. Interaction testing was used to determine whether overweight/obesity (body mass index of ≥25 kg/m²) moderated the association between progesterone replacement and LBRs.

Main outcome measure(s): The primary outcome was live birth. The secondary outcomes were biochemical pregnancy, clinical pregnancy, miscarriage, and total pregnancy loss.

Result(s): A total of 6,905 programmed cycles (4,616 with vaginal progesterone and 2,289 with intramuscular progesterone) were included in the analysis. In the general cohort who underwent cryopreserved blastocyst transfer, the LBRs were 46.23% and 48.62% in the vaginal and intramuscular progesterone groups, respectively (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.82-1.01; adjusted OR [aOR], 0.89; 95% CI, 0.81-0.98), with a significantly increased rate of pregnancy losses in the vaginal progesterone group compared with that in the intramuscular progesterone group (22.22% vs. 18.90%; OR, 1.23; 95% CI, 1.08-1.39; aOR, 1.23; 95% CI, 1.08-1.40). Among normal-weight women, the LBR in the vaginal progesterone group was lower than that in the intramuscular progesterone group (aOR, 0.84; 95% CI, 0.75-0.95). On the other hand, among women with overweight/obesity, the LBRs were similar between the 2 groups of progesterone replacement (aOR, 1.06; 95% CI, 0.86-1.33). Interaction testing of the routes of progesterone administration and overweight/obesity was significant.

Conclusion(s): Luteal-phase support with vaginal progesterone was associated with reduced LBRs compared with intramuscular progesterone for vitrified-warmed blastocyst transfer, and the association was modified by maternal overweight/obesity. Further research is needed to better understand the mechanisms behind the association.

Keywords: Progesterone; cryopreserved blastocyst transfer; live birth; luteal-phase support; overweight.