Uterine artery pulsatility index is a key biomarker for preeclampsia screening and the most reliable indicator of uterine perfusion across all pregnancy trimesters. Although recent findings reveal a significant decrease in uterine artery pulsatility index during first trimester in artificial cycle frozen embryo transfer pregnancies, no previous study evaluated whether this decrease persists throughout the second and third trimesters, when hormonal treatment is discontinued. Considering the crucial role of uterine artery pulsatility index during the second half of pregnancy risk assessment, recommended by international guidelines to ensure early preeclampsia detection and proper pregnancy monitoring, we set out to perform a large retrospective study to evaluate the impact of endometrial preparation on second and third trimesters uterine artery pulsatility index.

The study aims to evaluate the possible impact of endometrial preparation for frozen embryo transfer on uterine vascular resistance during the second and third trimesters.

This retrospective single-center study analyzed 27,495 singleton pregnancies that underwent Uterine Artery Pulsatility Index evaluation during the second trimester (20–22 weeks) of pregnancy at our University Hospital between January 2010 and November 2024. Among them, 23,547 were naturally conceived and 3948 resulted from Assisted Reproductive Technology (385 ovulation induction and intrauterine insemination, 864 in vitro fertilization frozen embryo transfer, and 2699 after frozen embryo transfer) (356 natural cycle frozen embryo transfer and 2343 artificial cycle frozen embryo transfer). Additionally, third trimester (35–37 weeks) Uterine Artery Pulsatility Index evaluations were available for 11,096 pregnancies. Pregnancies with fetal congenital abnormalities, aneuploidies, and twin pregnancies were excluded. The primary aim of the study was to investigate Uterine Artery Pulsatility Index values throughout pregnancy based on different types of conception. Analysis of covariance and linear mixed model (including potential confounders such as smoking, diabetes, race, chronic hypertension, aspirin administration, thrombophilia, age, weight, and oocyte donation) were used to analyze the association between mode of conception and log10-transformed multiple of the median values of Uterine Artery Pulsatility Index.

The use of hormonal treatment in artificial cycle frozen embryo transfer cycles was associated with a significantly lower second-trimester Uterine Artery Pulsatility Index values 0.73 (artificial cycle frozen embryo transfer) as compared with all other modes of conception vs 0.89 (naturally conceived), 0.92 (ovulation induction and intrauterine insemination), 0.94 (fresh embryo transfer), and 0.89 (natural cycle frozen embryo transfer) ( P < .001). Differences persisted during the third trimester with Uterine Artery Pulsatility Index values 0.95 for artificial cycle frozen embryo transfer vs 1.00 (naturally conceived), 1.03 (ovulation induction and intrauterine insemination), 1.00 (in vitro fertilization frozen embryo transfer), and 1.02 (natural cycle frozen embryo transfer) ( P < .001). The results were confirmed after applying the multivariable regression analysis. Despite the improved uterine perfusion, artificial cycle frozen embryo transfer was associated with a 4-fold higher incidence of preeclampsia (5.2%) compared to natural cycle frozen embryo transfer (1.1%), naturally conceived (1.4%), ovulation induction and intrauterine insemination (1%), and fresh embryo transfer (2.2%) ( P < .001).

The present study demonstrates that artificial cycle frozen embryo transfer is associated with reduced uterine vascular resistance across all pregnancy trimesters. This finding strongly supports the urgent need to revise the current second and third trimester preeclampsia risk assessment algorithm to ensure accurate early detection and proper management of high-risk pregnancies.