The risk for the development of hypertensive complications in oocyte donation pregnancy: a systematic review and individual participant data meta-analysis (DONOR IPD)

Abstract

BACKGROUND Oocyte donation (OD) is an established ART involving an oocyte donor and recipient with a rising number of treatments. Previous meta-analyses highlight increased risks of hypertensive complications compared to naturally conceived (NC) and IVF/ICSI pregnancies, including pregnancy-induced hypertension (PIH) and preeclampsia (PE), but limitations exist due to study quality and heterogeneity. OBJECTIVE AND RATIONALE The DONOR (DONation of Oocytes in Reproduction) individual participant data (IPD) meta-analysis aims to generate clinically relevant and robust evidence regarding the development of hypertensive complications in OD pregnancies compared to autologous pregnancies. IPD meta-analyses offer an advantage over current meta-analyses, as bias is reduced by using IPD of original studies, allowing reliability checks, correction for confounders, and examining causes of heterogeneity by subgroup analyses. Furthermore, using IPD increases statistical power and generalizability of results. SEARCH METHODS A literature search was conducted using PubMed, EMBASE, and Cochrane up to March 2024, with a last update performed in February 2025. We included observational studies that compared a cohort of women pregnant after OD beyond 20 weeks of gestation with an autologous pregnancy cohort (NC or IVF/ICSI), and reported on hypertensive pregnancy complications. Risk of bias was assessed using the ROBINS-I tool. Authors of eligible articles were invited to share IPD. The DONOR IPD meta-analyses were executed using both a one- and two-stage approach, adjusted for maternal age, parity, and multiple gestation. Furthermore, sensitivity, meta-regression and subgroup analysis were performed. OUTCOMES IPD was requested for 48 cohorts, and provided from 16 cohorts with data of 2747 OD, 4699 IVF/ICSI, and 33 323 NC pregnancies. The one- and two-stage approach comparing OD to autologous pregnancies showed adjusted ORs of respectively 2.62 (95% CI 2.22–3.10) and 2.85 (95% CI 2.30–3.54; I2 44%; moderate certainty) for hypertensive complications in total, 2.15 (95% CI 1.73–2.68) and 1.49 (95% CI 0.80–2.80; I2 74%; low certainty) for PIH, and 2.28 (95% CI 1.88–2.78) and 2.39 (95% CI 1.94–2.94; I2 0%; high certainty) for PE. When the autologous group was split into NC and IVF/ICSI pregnancies, higher risks for hypertensive complications, including PIH and PE, persisted in the OD group. The results of the IPD meta-analyses for HELLP syndrome show a higher risk in OD pregnancy, though with a broad 95% CI. Sensitivity meta-analyses for risk of bias showed comparable results. Subgroup analyses indicated increased risks for hypertensive complications in OD pregnancy, regardless of maternal age, BMI, multiple pregnancy, parity, ethnicity, medical history, and number of transferred embryos. A potential lower risk for hypertensive complications was found when acetylsalicylic acid or heparin is used during OD pregnancy compared to both autologous and NC pregnancy. WIDER IMPLICATIONS The DONOR IPD meta-analysis provided a unique opportunity to assess the risk for hypertensive complications in OD compared to autologous pregnancy. The results must increase alertness of health care professionals who are involved in OD health care towards the risk profile of these pregnancies, as the DONOR IPD meta-analysis results in the best evidence-based statement for international guidelines in obstetrics to date. Possibly, preventive treatment with low-dose acetylsalicylic acid is successful in lowering the risk for hypertensive complications, though more evidence is needed to confirm this effect, alongside the underlying pathological mechanism. REGISTRATION NUMBER CRD42021267908.