Ongoing pregnancy rate is associated with trigger-day progesterone level in letrozole/clomiphene intrauterine insemination cycles

Prior studies in fresh embryo transfer IVF cycles have associated elevated serum progesterone level on day of ovulatory trigger, particularly if ≥ 1.5 ng/ml, with decreased pregnancy rates. A similar association has been found in intrauterine insemination (IUI) cycles using gonadotropins for ovulation induction. The purpose of this study was to evaluate the association of trigger-day progesterone level with pregnancy rates in IUI cycles using oral ovulation induction agents.

A retrospective cohort study was conducted at a multicenter private practice. 4,866 IUI cycles using letrozole or clomiphene were analyzed from January 1, 2017, to December 31, 2023. The primary outcome measure was ongoing pregnancy per cycle as a function of the serum progesterone level obtained on the day of ovulatory trigger. Secondary outcome measures were positive pregnancy, clinical pregnancy, and pregnancy loss.

When compared to cycles with trigger-day progesterone < 1 ng/ml, ongoing pregnancy was significantly lower when progesterone was ≥ 1.5 ng/ml (11.9% versus 5.6%; Risk Ratio (RR) 0.46 (95% CI 0.25-0.84)). Ongoing pregnancy was comparable when progesterone was < 1 ng/ml or 1-1.49 ng/ml (11.9% versus 9.2%; (RR 0.75 (95% CI 0.55-1.03)). Positive pregnancy and clinical intrauterine pregnancy outcomes were also significantly lower in the ≥ 1.5 ng/ml versus < 1 ng/ml group, but comparable in the < 1 ng/ml and 1-1.49 ng/ml groups. Pregnancy loss was not significantly different between groups.

Pregnancy outcomes are optimized when trigger-day progesterone level is < 1.5 ng/ml in IUI cycles using oral ovulation induction agents, highlighting the value of obtaining a progesterone level on the day of ovulatory trigger.