Safety and Risks · Maternal Complications
Solmonovich R et al., 2025 · Fertility and sterility
To determine whether an association exists between in vitro fertilization (IVF) and severe maternal morbidity among low-risk pregnant patients. Retrospective cohort study. Low-risk pregnant patients who delivered between January 2019 and December 2022. Low-risk was defined as having an obstetric comorbidity index score of 0. In vitro fertilization. MAIN OUTCOME MEASURE(S): The primary outcome (dependent variable) was any severe maternal morbidity. The secondary outcome was the need for a cesarean delivery. A modified Poisson regression with robust error variance was used to model the probability of severe maternal morbidity as a function of IVF. Risk ratios and their associated 95% confidence intervals (CIs) were computed. An α value of 0.05 was considered statistically significant. RESULT(S): A total of 39,668 pregnancies were included for analysis, and 454 (1.1%) were conceived by IVF. The overall severe maternal morbidity rate was 2.4% (n = 949), with the most common indicator being blood transfusion. The overall cesarean delivery rate was 18.8% (n = 7,459). On modified Poisson regression, IVF-conceived pregnancies were associated with 2.56 times the risk of severe maternal morbidity (95% CI, 1.73-3.79) and 1.54 times the risk of having a cesarean delivery (95% CI, 1.37-1.74) compared with non-IVF pregnancies. CONCLUSION(S): In vitro fertilization is associated with higher rates of severe maternal morbidity, primarily the need for a blood transfusion, and cesarean delivery in low-risk pregnancies without major comorbidities. Recognizing this association allows healthcare providers to implement proactive measures for better monitoring and tailored postpartum care.
Safety and Risks · Maternal Complications
Landsverk E et al., 2025 · PLoS medicine
A higher risk of placenta previa after assisted reproductive technology (ART) is well established. The underlying mechanisms are poorly understood, but may relate to embryo culture duration, cryopreservation, and cause of infertility. Within-mother analyses, where each woman is her own control (i.e., sibling design), help disentangle treatment contributions from maternal confounders that are stable between pregnancies. We aimed to investigate the risk of placenta previa in pregnancies achieved after ART according to embryo culture duration, cryopreservation, and infertility factors while accounting for stable maternal factors using within-mother analyses. We used linked nationwide registry data from Denmark (1994 to 2014), Finland (1990 to 2014), Norway (1988 to 2015), and Sweden (1988 to 2015). All women who gave their first birth during the study period at age 20 years or older were eligible and contributed up to 4 deliveries (singleton or multifetal) occurring between 22 and 44 weeks of gestation, excluding deliveries where maternal age exceeded 45 years. We used multilevel logistic regression to compare risk of placenta previa after ART (n = 139,694 deliveries) versus natural conception (n = 5,614,512 deliveries), both at the population level and within mothers, adjusting for year of delivery, maternal age, parity, and country. We categorized ART according to culture duration, embryo cryopreservation, and infertility factors. Population level risk of placenta previa was higher for ART versus natural conception (odds ratio [OR], 4.16; 95% confidence interval [CI], 3.96-4.37). Controlling for stable maternal factors, the association attenuated, but risk remained higher for ART versus natural conception (OR within mothers, 2.64; 95% CI, 2.31-3.02). Compared to naturally conceived, a larger difference in risk was seen for pregnancies from fresh embryos than for pregnancies from frozen embryos. Further categorization by culture duration showed the largest risk difference after fresh blastocyst transfer, and the smallest after frozen cleavage stage embryo transfer, which persisted in sensitivity analyses (including restriction to singletons). When stratified according to infertility factors at the population level, women with endometriosis conceiving by ART had the highest risk of placenta previa (OR, 9.35; 95% CI, 8.50-10.29), whereas women with polycystic ovary syndrome (PCOS) conceiving by ART had the lowest risk (OR, 1.52; 95% CI, 1.12-2.09), compared to natural conception. Within mothers, we found a higher risk of placenta previa after ART compared to natural conception for women with endometriosis (OR, 2.08; 95% CI, 1.50-2.90), but not for women with PCOS (OR, 0.88; 95% CI, 0.41-1.89 [unadjusted due to sparse data]). However, within-mother analyses are restricted to multiparous women with deliveries after different conception methods. Therefore, findings from these analyses might not generalize to all women undergoing ART. The risk of placenta previa in pregnancies conceived by ART differed by embryo culture duration, cryopreservation, and underlying infertility. The highest risk was seen after fresh embryo transfer and especially fresh blastocyst transfer. Women with endometriosis had a higher risk than women with other infertility factors, and within mothers, their risk was higher after ART than after natural conception. Identifying the responsible mechanisms might provide opportunities for prevention.
Safety and Risks · Maternal Complications
H Petersen S et al., 2023 · Hypertension (Dallas, Tex. : 1979)
Frozen embryo transfer (frozen-ET) is increasingly common because of improved cryopreservation methods and elective freezing of all embryos. Frozen-ET is associated with higher risk of hypertensive disorders in pregnancy than both natural conception and fresh embryo transfer (fresh-ET), but whether this is attributable to parental factors or treatment is unknown. Using the Medical Birth Registries of Denmark (1994-2014), Norway, and Sweden (1988-2015), linked to data from national quality registries and databases on assisted reproduction, we designed a population-based cohort study with within-sibship comparison. We included 4 426 691 naturally conceived, 78 300 fresh-ET, and 18 037 frozen-ET singleton pregnancies, of which 33 209 sibships were conceived using different conception methods. Adjusted odds ratios (aOR) of hypertensive disorders in pregnancy for fresh-ET and frozen-ET versus natural conception with 95% CI were estimated using multilevel logistic regression, where random effects provided conventional population-level estimates and fixed effects gave within-sibship estimates. Main models included adjustment for birth year, maternal age, parity, and country. Risk of hypertensive disorders in pregnancy was higher after frozen-ET compared to natural conception, both at population-level (7.4% versus 4.3%, aOR, 1.74 [95% CI, 1.61-1.89]) and within sibships (aOR, 2.02 [95% CI, 1.72-2.39]). For fresh-ET, risk was similar to natural conception, both at population-level (aOR, 1.02 [95% CI, 0.98-1.07]) and within sibships (aOR, 0.99 [95% CI, 0.89-1.09]). Frozen-ET was associated with substantially higher risk of hypertensive disorders in pregnancy, even after accounting for shared parental factors within sibships.
Safety and Risks · Maternal Complications
Chih HJ et al., 2021 · BMC Pregnancy and Childbirth
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).
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.
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).
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.