Chih, H. J., Elias, F. T. S., Gaudet, L., & Velez, M. P. (2021). Assisted reproductive technology and hypertensive disorders of pregnancy: systematic review and meta-analyses. BMC Pregnancy and Childbirth. https://doi.org/10.1186/s12884-021-03938-8
Chih HJ, Elias FTS, Gaudet L, Velez MP. Assisted reproductive technology and hypertensive disorders of pregnancy: systematic review and meta-analyses. BMC Pregnancy and Childbirth. 2021. doi:10.1186/s12884-021-03938-8
Chih, Hui Ju, et al. "Assisted reproductive technology and hypertensive disorders of pregnancy: systematic review and meta-analyses." BMC Pregnancy and Childbirth, 2021.
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IVF and ICSI pregnancies carry higher odds of hypertensive disorders
IVF and ICSI pregnancies had higher odds of hypertensive disorders than spontaneous ones. This 2021 meta-analysis pooled 85 cohort studies. Donated-egg singleton pregnancies had the highest odds, an odds ratio of 4.42.
Key Findings
Singleton IVF/ICSI pregnancies had an odds ratio of 1.70 (95% CI 1.60–1.80) for hypertensive disorders of pregnancy, and multiple pregnancies 1.34 (95% CI 1.20–1.50), each against spontaneous conception.
Frozen embryo transfer singleton pregnancies had an odds ratio of 1.74 (95% CI 1.58–1.92), against 1.43 (95% CI 1.33–1.53) for fresh embryo transfer, each compared with spontaneous conception.
Singleton pregnancies with oocyte donation had odds ratios of 4.42 (95% CI 3.00–6.51) for these disorders and 5.20 (95% CI 4.02–6.73) for preeclampsia, the highest of all groups.
Numbers needed to harm were 40 to 100 for most groups. Oocyte donation pregnancies had 16 (singleton) and 10 (multiple) for hypertensive disorders of pregnancy.
IVF-only multiple pregnancies (OR 1.13; 95% CI 0.98–1.29) and ICSI-only multiple pregnancies (OR 1.11; 95% CI 0.91–1.36) showed no statistically significant difference from spontaneous conception.
Interpretation
The paper pools observational cohort studies, so it shows an association and cannot show that IVF caused the higher odds. Underlying infertility, maternal age and weight differ between the groups, and the authors say uncontrolled confounders remain a concern. Many pooled analyses had high heterogeneity, meaning the studies disagreed on the size of the effect. The IVF-only and ICSI-only subgroups rested on few studies. Each group was pooled against spontaneous conception. The authors say the mechanism behind the higher preeclampsia odds remains unknown.
RRM Context
The authors note that the underlying infertility diagnosis may lead to varying maternal and perinatal outcomes. IVF bypasses that diagnosis without resolving it. Restorative reproductive medicine begins by finding and treating the cause, and pregnancy risk adds a reason to do so. A spontaneous ovulatory cycle forms a corpus luteum. Five cohort studies suggested that a missing corpus luteum in frozen cycles may explain the gap between frozen and fresh transfer.
Our editorial summary of this paper, not the article's abstract.
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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