Mid-luteal serum progesterone concentrations in modified natural cycles for embryo transfer: a prospective blinded...

Does mid-luteal serum progesterone concentration influence pregnancy outcomes in modified natural cycle frozen embryo transfer (mNC-FET) with ovulation triggering and luteal phase support (LPS)?

This prospective, blinded, single-centre cohort study was conducted at IVIRMA Valencia (Spain) between February 2020 and June 2021. A total of 241 infertile patients under 50 years old, with body mass index (BMI) <40 kg/m², undergoing mNC-FET were included. Ovulation was triggered with recombinant human chorionic gonadotrophin when the dominant follicle measured ≥16 mm and endometrial thickness was >6.5 mm. LPS was provided with micronized vaginal progesterone 200 mg every 12 h. Serum progesterone was measured within 2 h of embryo transfer, and results were blinded until study completion.

Mean serum progesterone on embryo transfer day was 26.2 ± 9.0 ng/ml, with 99% of patients exceeding the clinically relevant threshold (>10 ng/ml). Participants were stratified into quartiles by progesterone concentration, with no significant differences in ongoing pregnancy rates: Q1 (<20.2 ng/ml), 56.7%; Q2 (20.2-24.8 ng/ml), 47.5%; Q3 (24.9-31.1 ng/ml), 51.7%; Q4 (>31.1 ng/ml), 48.3% (P = 0.74). Live birth rates were also comparable (P = 0.66). In multivariable logistic regression, mid-luteal serum progesterone was not significantly associated with ongoing pregnancy (odds ratio 0.86, 95% CI 0.40-1.85; P = 0.70) after adjusting for clinical covariates. Female age, oocyte age, BMI, number of previous transfers, embryos transferred, embryo quality, and oocyte origin were also unrelated to pregnancy probability.

In mNC-FET cycles with HCG triggering and LPS, mid-luteal serum progesterone concentrations were consistently adequate and not associated with pregnancy outcomes. Routine progesterone monitoring appears unnecessary in this setting.