Fresh and Frozen Embryo Transfer-Related Hypertensive Disorders in Pregnancy

Significantly higher risk for hypertensive disorders in pregnancy (HDP) are associated with frozen embryo transfer even when accounting for parental characteristics within sibships, according to study findings published in Hypertension.

Researchers sought to determine whether parental factors or treatment lead to increased risk for hypertensive disorders in frozen embryo transfer pregnancy.

They conducted a population-based observational cohort study with within-sibship comparison using nationwide data from 3 countries across almost 3 decades. Data were sourced from the Medical Birth Registries of Sweden (1985-2015), Norway (1984-2015), and Denmark (1994-2014) and linked to databases and registries on assisted reproduction. Data included 4,426,691 naturally conceived, 78,300 fresh embryo transfer, and 18,037 frozen embryo transfer singleton pregnancies. Of these pregnancies, 33,209 sibships were conceived using different conception methods. Adjustment for maternal age, birth year, country, and parity were included in the main models.

The researchers noted that women who gave birth after fresh embryo transfer (mean age, 33.8 years) or frozen embryo transfer (mean age, 34.3 years) were older than women with natural conception (mean age, 29.6 years). They found parity was lower following fresh embryo transfer (75.3% primiparous) than natural conception (51.2%) and frozen embryo transfer (58.0%). Chronic hypertension was low for all groups and mean BMI was similar.

Preterm pregnancies that were naturally conceived (5.0%) were less frequent than preterm fresh embryo transfer (8.1%) pregnancies and preterm frozen embryo transfer (6.6%) pregnancies. Naturally conceived pregnancies were also less frequently induced and/or delivered via cesarean section.

The researchers found that risk for HDP was higher following frozen embryo transfer vs natural conception within sibships (adjusted odds ratio [aOR], 2.02 [95% CI, 1.72-2.39]) and at population level (7.4% vs 4.3%; aOR, 1.74 [95% CI, 1.61-1.89]). Risk was similar when compared with fresh embryo transfer within sibships (aOR, 0.99 [95% CI, 0.89-1.09]) and at population level (aOR, 1.02 [95% CI, 0.98-1.07]).

The researchers observed that risk for HDP declined from the first to the second pregnancy for all combination of conception methods among women with consecutive singletons. They noted that for all conception methods, women in first pregnancy who experienced HDP were less likely to have a second pregnancy than women without HDP.

Significant study limitations include residual confounding and misclassification of conception. There is also selection bias and limited generalizability of results.

“Frozen-ET [embryo transfer] was associated with substantially higher risk of hypertensive disorders in pregnancy, even after accounting for shared parental factors within sibships,” the study authors wrote. They added that HDP is relatively common with potential severe consequences and “…identifying subgroups at higher risk could provide opportunities for more targeted monitoring and interventions.”