P-774 Interim analysis: Association Between Early Pregnancy Progesterone Levels and Intrauterine Growth Restriction in In Vitro Fertilization Pregnancies

Abstract

Study question Does early pregnancy progesterone level influence the risk of intrauterine growth restriction (IUGR) in pregnancies conceived through in vitro fertilization (IVF)? Summary answer Interim results showed inverse correlation between higher early pregnancy progesterone levels and lower birthweight, potentially indicating an effect on placental development and fetal growth restriction. What is known already IVF increases the risk of IUGR, likely due to epigenetic changes, but the role of supraphysiologic progesterone remains unclear. A supraphysiologic progestin exposure in HRT could initiate excessively deep placentation, potentially influencing birth weight and obstetric outcomes. Previous studies have linked artificial cycle FET to higher rates of obstetric complications, including hypertensive disorders, placenta accreta, post-term birth, and macrosomia, compared to natural cycle FET. These studies suggest that adverse outcomes may be related to the absence of endogenous progesterone from a functional corpus luteum. However, no study has directly examined whether high early supraphysiologic progesterone levels contribute to IUGR. Study design, size, duration This is an interim analysis of a retrospective cohort study, evaluating 580 IVF pregnancies at a tertiary medical centre. luteal phase support was achieved by intravaginal micronized progesterone. Progesterone levels were measured at 4–5 weeks of gestation, with neonatal birthweight percentiles used to assess the risk of IUGR. The final analysis will include a larger cohort, with ongoing data collection. Participants/materials, setting, methods Singleton IVF pregnancies with available serum progesterone measurements (two time points) 14 days after embryo transfer were included. Birthweight percentiles were analyzed to classify IUGR cases (<10th percentile vs. ≥10th percentile). Statistical methods included: Spearman’s rho test for correlation Mann-Whitney U tests for between-group comparisons ROC analysis to determine potential progesterone cutoffs predicting IUGR risk Main results and the role of chance A moderate but statistically significant inverse correlation was found between first progesterone measurement and birthweight percentile (R.s = -0.407, p = 0.016). A similar trend was observed for second progesterone measurement and birthweight percentile (R.s = -0.487, p = 0.032). Median first progesterone levels were significantly higher in the IUGR group (<10th percentile) compared to the non-IUGR group (p = 0.038, one-sided). Second progesterone measurements showed a non-significant trend (p = 0.057). ROC analysis identified a progesterone cutoff of 48.75 pmol/L for predicting IUGR, with an AUC of 0.603 for the first progesterone measurement and 0.610 for the second progesterone. Limitations, reasons for caution The study is retrospective, and potential confounders (e.g., maternal BMI, embryo quality, placental function) may impact fetal growth. Wider implications of the findings If confirmed in the final analysis, these findings suggest excessively high early pregnancy progesterone levels may contribute to impaired fetal growth, reinforcing the need for personalized progesterone supplementation protocols in IVF pregnancies. Future studies should evaluate progesterone thresholds for optimizing implantation without increasing IUGR risk. Trial registration number No