A model for predicting low progesterone levels on the day of embryo transfer in hormonally prepared vitrified-warmed embryo transfer cycles: A secondary analysis of a prospective cohort study.

Aim: To develop a model that predicts low progesterone (P) levels on the day of embryo transfer (ET) based on patient and cycle characteristics, including serum estradiol (E ) concentration after vaginal administration of micronized E for endometrial preparation.

Methods: A prospective cohort of 193 patients scheduled for cryopreserved blastocyst transfer during an artificial endometrial preparation cycle, using micronized E vaginally for first 4 days (4 mg/day), followed by oral administration (6 mg/day). Blood sampling for E was performed prospectively on day-5 of vaginal administration and analysis was performed retrospectively. On sixth day of P treatment (daily 300 mg of vaginal micronized P tablets), P levels were measured on ET day. Primary outcome measure was serum P levels after vaginal E administration.

Results: Patients with low P levels on the day of ET (<7.8 ng/mL, 25th percentile) were heavier (p < 0.001) and exhibited lower day 5 serum E levels (p < 0.001) compared with patients with adequate P levels. Multivariate linear regression analysis revealed that weight (p = 0.003) and day 5 E levels (p < 0.001) were independently associated with the P levels. The sensitivity, specificity, and positive and negative predictive values (%) were 71.4, 55.6, 35.4, and 85.1 for weight ≥ 65 kg; 71.4, 61.8, 38.9, and 86.4 for day 5 E  ≤ 1615 pg/mL; 59.2, 83.3, 54.7, and 85.7 for the combination of these two variables; and 82.9, 62.5, 54.7, and 87.0 for the sequential inclusion of these variables, respectively.

Conclusions: Low day 5 E levels following vaginal administration and high weight are independently associated with low P levels on the day of ET. Predictive performance is enhanced when these variables are considered sequentially or in combination.