Risk of preeclampsia in pregnancies conceived by assisted reproductive technology: a systematic review and meta-analysis of cohort studies

Objectives Aims of the meta-analysis are to assess whether in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) increase the risk of preeclampsia and to identify potential risk factors. Methods Relevant cohort studies published between 1990 and 2020 were identified from EMBASE, MEDLINE, and Cochrane Library or manually using a structured search strategy. Eligibility and quality of studies were evaluated by two reviewers independently (HC, FE). Exposures were IVF, ICSI, multiplicity, oocyte donation, and type of embryo transfer; the outcome was preeclampsia. The pooled results were reported in odds ratios (OR) with 95% confidence intervals based on random effects models. Seventy eight studies were included after a screening of 2098 abstracts and 494 full text articles. Results Compared to spontaneous pregnancies, IVF/ICSI singleton pregnancies (OR = 1.59; 95% CI = 1.46–1.73; I2 = 72%) and multiple pregnancies (OR = 1.14; 95% CI = 1.06–1.23; I2 = 0%) were both associated with higher odds of preeclampsia. Pregnancies with oocyte donation had the highest odds of preeclampsia out of all groups analyzed (OR = 4.96; 3.52–7.00; I2 = 29%). Frozen embryo transfer resulted in higher odds of preeclampsia (OR = 1.82; 1.71–1.95; I2 = 0%) than fresh embryo transfer (OR = 1.48; 1.37–1.60; I2 = 39%). Conclusions Our findings support that IVF/ICSI pregnancies have a higher incidence of preeclampsia compared to spontaneous conceptions. Oocyte donation and frozen embryo transfer contribute particularly to a higher risk. Care plans for IVF/ICSI pregnancies need to be implemented to decrease the risk of preeclampsia and to allow for timely diagnosis. Aims of the meta-analysis are to assess whether in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) increase the risk of preeclampsia and to identify potential risk factors. Relevant cohort studies published between 1990 and 2020 were identified from EMBASE, MEDLINE, and Cochrane Library or manually using a structured search strategy. Eligibility and quality of studies were evaluated by two reviewers independently (HC, FE). Exposures were IVF, ICSI, multiplicity, oocyte donation, and type of embryo transfer; the outcome was preeclampsia. The pooled results were reported in odds ratios (OR) with 95% confidence intervals based on random effects models. Seventy eight studies were included after a screening of 2098 abstracts and 494 full text articles. Compared to spontaneous pregnancies, IVF/ICSI singleton pregnancies (OR = 1.59; 95% CI = 1.46–1.73; I2 = 72%) and multiple pregnancies (OR = 1.14; 95% CI = 1.06–1.23; I2 = 0%) were both associated with higher odds of preeclampsia. Pregnancies with oocyte donation had the highest odds of preeclampsia out of all groups analyzed (OR = 4.96; 3.52–7.00; I2 = 29%). Frozen embryo transfer resulted in higher odds of preeclampsia (OR = 1.82; 1.71–1.95; I2 = 0%) than fresh embryo transfer (OR = 1.48; 1.37–1.60; I2 = 39%). Our findings support that IVF/ICSI pregnancies have a higher incidence of preeclampsia compared to spontaneous conceptions. Oocyte donation and frozen embryo transfer contribute particularly to a higher risk. Care plans for IVF/ICSI pregnancies need to be implemented to decrease the risk of preeclampsia and to allow for timely diagnosis.