Abstract Study question What is the preterm preeclampsia (pPE) incidence in selected high-risk ART patient populations when applying a first trimester screening approach to recommend prevention via aspirin? Summary answer One in five high-risk ART patients had a calculated risk >1/100 and despite aspirin prophylaxis still 22.2% of them developed pPE. What is known already Preeclampsia (PE) is an obstetrical complication defined by new-onset hypertension after 20 weeks’ gestation with proteinuria, end-organ (including placental) dysfunction or both. First trimester pPE screening is gaining ground in prenatal care since a study on approximately 60.000 singleton pregnancies reported an algorithm able to detect 76% of pPE and 38% of term PE (tPE). A RCT showed that aspirin, prescribed upon positive screening, led to an effective (62%) reduction of pPE incidence. This screening/prevention strategy has not been validated in the context of ART pregnancies, while some ART patient groups are known to be at higher risk for PE. Study design, size, duration This is a retrospective, single-center, observational cohort study, including 242 patients between 18 and 48 years old, pregnant after ART and considered at higher risk of PE because of one of the following characteristics: diagnosed with polycystic ovary syndrome (PCOS), being an oocyte recipient (OR) or pregnant from a frozen embryo transfer in an artificially prepared cycle (HRT-FET). Patients were included from May 2021 until July 2022. Participants/materials, setting, methods Screening was systematically offered between 11-14 weeks’ gestation, according to the Fetal Medicine Foundation (FMF) algorithm including maternal factors, mean arterial pressure, uterine arteries pulsatility index and serum placental growth factor. If the risk of developing PE was >1/100, administration of 160mg aspirin was started until 36 weeks’ gestation. Primary outcome was the incidence of pPE(<37 weeks). Secondary outcomes were the incidence of tPE(≥37 weeks) and the incidence of positive first trimester screening (risk >1/100). Main results and the role of chance A total of 242 unique patients were screened: 58 oocyte recipients (ORs), 89 PCOS and 95 HRT-FET patients (the latter having no PCOS and using autologous oocytes). The overall positive screening incidence was 21.9%(53/242), with the highest positive screening rate in ORs (27.6%, 16/58). In PCOS and HRT-FET patients, we observed a positive screening test in 20.2%(18/89) and 20.0%(19/95), respectively. For comparison, the positive screening rate reported for the general population was 10.5%. Despite the prophylactic aspirin regimen started upon positive screening, in the current study an overall pPE incidence of 22.6%(12/53) was observed while the reported pPE incidence in the general population in this setting was only 1.6%. More specifically, 31.2%(5/16) ORs with positive screening developed pPE although they used aspirin. For PCOS and HRT-FET patients, this was 11.1%(2/18) and 21.1% (4/19), respectively. tPE occurred in 7.5%(4/53) of women with positive screening and aspirin intake (1/16 in ORs, 1/18 in PCOS patients and 2/19 following HRT-FET). For comparison, in the general population this was 6.7%. Following a negative first trimester screening test, 2.1%(4/189) of patients developed pPE and 3.7%(7/189) tPE. In a non-selected population, these incidences have been reported to be 0.2% and 1.1%, respectively. Limitations, reasons for caution This study is limited by its retrospective study design, small sample size and observational nature. Nevertheless, it is of major importance to communicate the strikingly high pPE incidences in specific subtypes of ART patients despite first trimester screening and aspirin prophylaxis. Wider implications of the findings Our findings suggest that current screening algorithms are not optimized for women pregnant following ART. In pregnancies from oocyte donation, aspirin might be less effective. Future research should aim at finetuning PE screening methods specifically for ART patients and differential mechanisms of PE origin need to be further investigated. Trial registration number Not applicable