Impact of serum progesterone levels and rescue progesterone supplemental luteal support on pregnancy outcomes in frozen embryo transfer: a controlled trial

The role of serum progesterone levels and the benefit of rescue luteal support in frozen embryo transfer (FET) cycles remain debated. While low serum progesterone has been linked to poorer outcomes, evidence on whether supplementation improves pregnancy rates is inconsistent. To evaluate the impact of serum progesterone levels and additional progesterone supplementation on pregnancy outcomes in women undergoing FET. In this controlled, single-blind trial, 74 women were allocated into three groups: Group I (n = 26, progesterone < 10 ng/mL, standard luteal support), Group II (n = 23, progesterone < 10 ng/mL, standard luteal support + 400 mg progesterone), and Group III (n = 25, progesterone ≥ 10 ng/mL, standard luteal support). Primary outcome was clinical pregnancy; secondary outcomes included biochemical and ongoing pregnancy, and pregnancy loss. Logistic regression identified independent predictors. Progesterone levels differed significantly between groups both on transfer day and three days later (p < .001). Pregnancy outcomes did not differ significantly: biochemical pregnancy (50.0%, 34.8%, 44.0%), clinical pregnancy (42.3%, 34.8%, 44.0%), ongoing pregnancy (42.3%, 30.4%, 44.0%), and pregnancy loss (7.7%, 4.3%, 0%) for Groups I–III, respectively. Maternal age was the only consistent predictor across models, negatively associated with pregnancy outcomes (OR 0.85–0.87, p < .05). Supplemental luteal support in women with low progesterone mitigate negative effects, as outcomes were comparable to women with normal progesterone even though it did not significantly improve pregnancy outcomes. Maternal age remained the strongest predictor. Larger trials are needed to clarify benefits in high-risk subgroups and to define optimal progesterone thresholds. Iranian Registry of Clinical Trials (IRCT), IRCT20200905048630N2, registered on 22 Aguest 2021.