Human Reproduction, 2025
Abstract
Abstract
Study question What is the predictive performance of first-trimester screening for preeclampsia (PE) following ART with fresh embryo transfer (fresh-ET), frozen ET (FET) and oocyte donation (OD)?
Summary answer Performance of the first-trimester screening for PE in pregnancies following ART with fresh-ET, FET and OD was comparable to naturally conceived (NC) pregnancies.
What is known already The risk of PE is increased in pregnancies following ART compared to NC pregnancies, particularly after FET and OD. Pathophysiology and onset of PE may differ from that of NC and between ART types, possibly affecting screening performance and risk marker effectiveness. It has been shown that the PE biomarker, uterine artery pulsatility index (UtA-PI), is lower after FET than fresh-ET. The Fetal-Medicine-Foundation (FMF) algorithm, which combines maternal factors with biophysical and biochemical markers to predict preterm-PE and guide prophylactic aspirin use, is widely recognized. The algorithm accounts for ART as a maternal risk factor but doesn’t differentiate between ART types.
Study design, size, duration The PRESIDE study was a prospective multicenter study in Denmark including women with a singleton pregnancy attending routine first-trimester ultrasound at 11-14 weeks’ gestation between May 2019 and December 2020. The study aimed to compare the FMF first-trimester PE screening algorithm to the current Danish strategy. This study specifically aimed to assess the screening performance across different types of ART and further explored differences in PE incidence including gestational age (GA) at delivery and birthweight.
Participants/materials, setting, methods Maternal characteristics including type of ART treatment (fresh-ET, FET or OD) were recorded and measurements of serum placental growth factor, pregnancy-associated-plasma-protein A, mean arterial blood pressure and UtA-PI were obtained. According to the FMF algorithm, a risk of preterm-PE (delivery <GA 37 weeks) and PE with delivery at any GA was calculated for each participant. Detection rates were calculated using the cut-off defining a screen-positive-rate of 10% for the entire study population.
Main results and the role of chance Of 8,156 women with a complete risk assessment, 535 conceived by ART. The incidence of PE was 6.4% (14/219) after fresh-ET, 8.3% (18/218) after FET, 12% (7/57) in OD and 3.4% (252/7,387) for NC pregnancies. GA at delivery with PE differed between modes of conception with preterm-PE being most common after OD (58%, 4/7 of PE cases) as compared to fresh-ET (36%, 5/14), FET (11%, 2/18) and NC (17%, 42/252). PE with large-for-gestational-age offspring was only observed after FET (11%, 2/18 of PE cases), while PE with small-for-gestational-age offspring was most common after OD (43%, 3/7) compared to fresh-ET (21%, 3/14), FET (6%, 1/18) and NC (11%, 27/252). The detection rate for preterm-PE was comparable between ART (81.8%, 95% CI 48.2%-97.7%) and NC (61.4%, 45.5%-75.6%). Among ART subgroups, the detection rate was 80% (28.4%-99.5%) for fresh-ET, 100% (15.8%-100%) for FET and 75% (19.4%-99.4%) for OD. For PE at any GA, the detection rate was significantly higher after ART (76.9%, 60.8%-88.7%) than NC (36.9%, 30.9%-43.2%). Among ART subgroups, detection rates were 85.7% for both fresh-ET (57.2%-98.2%) and OD (42.1%-99.6%) and 66.7% (41.0%-86.7%) for FET. The screen-positive-rate after ART was 22.8% for preterm-PE and 28.2% for PE with delivery at any GA.
Limitations, reasons for caution The prospective design is a strength while the limited sample size demands validation in larger cohorts. We didn’t distinguish between types of endometrial protocol in FET, although programmed-cycle-FET is associated with higher risk of PE. A large proportion of ODs received aspirin based on clinical guidelines, likely reducing PE incidence.
Wider implications of the findings Reassuringly, our findings suggest that the FMF-algorithm has high detection and comparable performance following fresh-ET, FET, OD and NC. With the high screen-positive-rate a large proportion of ART patients will be recommended aspirin. Given the low preterm-PE prevalence after FET, alternative interventions may be necessary, as aspirin primarily prevents preterm-PE.