Higher risk of hypertensive disorders of pregnancy and preeclampsia in singleton pregnancies following frozen embryo transfer: a systematic review and meta-analysis

Abstract BackgroundHypertensive disorders of pregnancy (HDP) is one of the most common pregnancy complications and causes of maternal morbidity and mortality. Many cohort studies were conducted to study adverse pregnancy outcomes associated with pregnancies from assisted reproductive technology. We aimed to comprehensively review all available evidence to date to compare the odds of HDP and preeclampsia between pregnancies achieved by in vitro fertilization (IVF) and spontaneous pregnancies.MethodsWe conducted a systematic review and meta-analysis based on cohort studies identified from EMBASE, MEDLINE, and Cochrane Library (up to 2020) and manually using a structured search strategy. Cohort studies that compared pregnancies after IVF with or without intracytoplasmic sperm fertilization (ICSI) and SC with HDP or preeclampsia as the outcome of interest were included. The control group was women who conceived spontaneously without ART or fertility medications. Studies published in English, French, Chinese, and Portuguese were reviewed. Eligibility and quality of studies were evaluated by two reviewers independently. Quality assessment was conducted using the Newcastle Ottawa Scale (NOS) for Cohort Studies. The pooled results were reported in odds ratios (OR) with 95% confidence intervals based on random effects models. I-squared (I2) test was used to evaluate heterogeneity and publication bias was assessed using funnel plots.ResultsSeventy-eight studies were included after a screening of 1,879 abstracts and 275 full text articles. Compared to SC, IVF/ICSI singleton pregnancies (OR 1.63; 95% CI 1.54-1.74; I2 = 79%) and multiple pregnancies (OR 1.31; 95% CI 1.18-1.47; I2 = 73%) were both associated with higher odds of HDP. Singleton pregnancies with oocyte donation had the highest odds of HDP out of all groups analyzed (OR 4.11; 95% CI 2.75-6.16; I2 = 85%). Frozen embryo transfer resulted in higher odds of HDP (OR 1.74; 95% CI 1.58-1.92; I2 = 55%) than fresh embryo transfer (OR 1.43; 95% CI 1.33-1.53; I2 = 72%). Similar findings for preeclampsia were also reported.ConclusionsOur meta-analysis confirmed that IVF/ICSI pregnancies are at high odds of HDP and preeclampsia than SC, irrespective of the plurality. The odds were especially high in frozen embryo transfer and oocyte donation pregnancies.

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Assisted reproductive technology and hypertensive disorders of pregnancy: systematic review and meta-analyses

BMC Pregnancy and Childbirth ◽

10.1186/s12884-021-03938-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hui Ju Chih ◽

Flavia T. S. Elias ◽

Laura Gaudet ◽

Maria P. Velez

Keyword(s):

Systematic Review ◽

Embryo Transfer ◽

Oocyte Donation ◽

Reproductive Technology ◽

Frozen Embryo Transfer ◽

Multiple Pregnancies ◽

Hypertensive Disorders Of Pregnancy ◽

Hypertensive Disorders ◽

Meta Analyses ◽

Singleton Pregnancies

Abstract Background Hypertensive disorders of pregnancy (HDP) is one of the most common pregnancy complications and causes of maternal morbidity and mortality. Assisted reproductive technology (ART) has been associated with adverse pregnancy outcomes, including HDP. However, the impact of multiple pregnancies, oocyte donation, as well as fresh and frozen embryo transfer needs to be further studied. We conducted a systematic review and meta-analyses to evaluate the association between ART and HDP or preeclampsia relative to spontaneous conception (SC). Methods We identified studies from EMBASE, MEDLINE, and Cochrane Library (up to April 8, 2020) and manually using structured search strategies. Cohort studies that included pregnancies after in vitro fertilization (IVF) with or without intracytoplasmic sperm fertilization (ICSI) relative to SC with HDP or preeclampsia as the outcome of interest were included. The control group was women who conceived spontaneously without ART or fertility medications. The pooled results were reported in odds ratios (OR) with 95% confidence intervals based on random effects models. Numbers needed to harm (NNH) were calculated based on absolute risk differences between exposure and control groups. Results Eighty-five studies were included after a screening of 1879 abstracts and 283 full text articles. Compared to SC, IVF/ICSI singleton pregnancies (OR 1.70; 95% CI 1.60–1.80; I2 = 80%) and multiple pregnancies (OR 1.34; 95% CI 1.20–1.50; I2 = 76%) were both associated with higher odds of HDP. Singleton pregnancies with oocyte donation had the highest odds of HDP out of all groups analyzed (OR 4.42; 95% CI 3.00–6.51; I2 = 83%). Frozen embryo transfer resulted in higher odds of HDP (OR 1.74; 95% CI 1.58–1.92; I2 = 55%) than fresh embryo transfer (OR 1.43; 95% CI 1.33–1.53; I2 = 72%). The associations between IVF/ICSI pregnancies and SC were similar for preeclampsia. Most interventions had an NNH of 40 to 100, while singleton and multiple oocyte donation pregnancies had particularly low NNH for HDP (16 and 10, respectively). Conclusions Our meta-analysis confirmed that IVF/ICSI pregnancies are at higher odds of HDP and preeclampsia than SC, irrespective of the plurality. The odds were especially high in frozen embryo transfer and oocyte donation pregnancies.

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