Association between low fetal fraction and hypertensive disorders of pregnancy in in vitro fertilization-conceived pregnancies

Abstract

Background: Fetal fraction from noninvasive prenatal screening has been used as a predictive marker for hypertensive disorders of pregnancy in spontaneous pregnancies.

Objective: We aimed to determine whether fetal fraction from noninvasive prenatal screening predicts hypertensive disorders of pregnancy in pregnancies conceived by assisted reproductive technology, stratified by fresh and frozen embryo transfer.

Study design: Retrospective cohort study of women with singleton pregnancies who underwent fresh or frozen embryo transfer, had noninvasive prenatal screening, and had a live birth >20 weeks at a single institution from 2013 to 2019. Women with major anomalies, nonreportable noninvasive prenatal screening, or chronic hypertension were excluded. Fetal fraction was corrected for gestational age, noninvasive prenatal screening platform, and defined as low if it is less than fifth percentile for the study population. The primary outcome was hypertensive disorders of pregnancy during delivery hospitalization, stratified by fresh vs frozen embryo transfer. We performed multivariable logistic regression analyses to determine whether low fetal fraction predicts hypertensive disorders of pregnancy for fresh and frozen embryo transfer, controlling for age, prepregnancy body mass index, heparin use, low-dose aspirin use, estradiol level if fresh embryo transfer, and trophectoderm biopsy and cycle type if frozen embryo transfer.

Results: We included 81 women with low fetal fraction and 847 women with normal fetal fraction. The adjusted prevalence of hypertensive disorders of pregnancy in women with low fetal fraction was 24.9% in fresh embryo transfer and 34.5% in frozen embryo transfer. In fresh embryo transfer pregnancies, the odds of hypertensive disorders of pregnancy were higher among women with low fetal fraction (adjusted odds ratio, 2.46; 95% confidence interval, 1.07-5.30; P=.026). In frozen embryo transfer pregnancies, there was no association between low fetal fraction and hypertensive disorders of pregnancy (adjusted odds ratio, 1.43; 95% confidence interval, 0.69-2.88; P=.321).

Conclusion: Low fetal fraction is associated with hypertensive disorders of pregnancy in women who conceive by fresh embryo transfer. Fetal fraction may represent a clinically useful marker for screening for hypertension and allow clinicians to target risk reduction strategies, such as low-dose aspirin, in pregnancies conceived by fresh embryo transfer.

Keywords: adverse pregnancy outcomes; assisted reproductive technology; fetal fraction; fresh embryo transfer; frozen embryo transfer; hypertensive disorders of pregnancy; in vitro fertilization pregnancies; noninvasive prenatal screening.