Letrozole Supplementation and the Increased Risk of Elevated Progesterone Levels on Trigger Day

Area of Science:

• Reproductive Endocrinology
• In Vitro Fertilization

Background:

• Letrozole (LE) is used in in vitro fertilization (IVF) and intracytoplasmic sperm injection (IVF/ICSI).
• The effect of LE on progesterone levels during the late follicular phase is not fully understood.

Purpose of the Study:

• To investigate whether letrozole (LE) supplementation increases progesterone levels on trigger day in women undergoing IVF/ICSI using antagonist protocols.

Main Methods:

• Retrospective cohort study of 1,133 women undergoing IVF/ICSI cycles (January 2018 - June 2020).
• Propensity score matching (PSM) was used to create matched cohorts: letrozole + GnRH-antagonist (LE GnRH-ant) vs. GnRH-antagonist, and LE GnRH-ant vs. GnRH-agonist (GnRH-a).
• Progesterone levels on trigger day were compared between groups.

Main Results:

• In both PSM cohorts, patients in the LE GnRH-ant group showed significantly higher progesterone levels on trigger day compared to controls (P < 0.001).
• A higher proportion of patients in the LE GnRH-ant group had progesterone levels > 1.5 ng/mL.
• Progesterone levels increased with each retrieved oocyte in the LE GnRH-ant groups (P < 0.001).

Conclusions:

• Letrozole (LE) supplementation in antagonist protocols may lead to increased progesterone levels in the late follicular stage.
• This finding has implications for understanding the hormonal milieu during controlled ovarian stimulation in IVF/ICSI.