Assisted reproductive technology (ART) and severe preeclampsia (PEC): a maternal and placental implantation interaction

Abstract

OBJECTIVE: We investigated whether ART exposure is associated with a more severe phenotype of PEC, suggesting an interaction between abnormal placentation and maternal host factors. DESIGN: An IRB-approved prospective case control study to investigate PEC risk factors was performed from 2005-2007. Cases were women with PEC (gestational hypertension, mild and severe disease.) Controls were patients presenting for delivery at term without PEC. MATERIALS AND METHODS: Patients were asked about method of conception at enrollment. Chi square analysis was used to evaluate the association between ART and PEC. We also assessed the association between ART and disease severity, abnormal lab values (platelets < 100, creatinine ≥1, and elevated liver function tests) and intra-uterine growth restriction (IUGR.) Stratified analyses and multivariable logistic regression were used to control for confounders. RESULTS: 3.6% of 440 cases and 2.7% of 591 controls utilized ART. Women with PEC were twice as likely to have used ART (AOR 2.20[1.03-4.72] p=0.042). When restricted to IVF pregnancies, PEC women had even higher odds of IVF use (AOR 5.26 [1.74-15.89] p=0.003) after controlling for age and race. Among women with PEC, all women who used ART (n=16) had severe disease. Severe disease in ART women was largely due to abnormal lab values rather than severe hypertension. There was no difference in IV anti hypertensive medication use between ART and non-ART patients (p=0.95.) Women using ART were more likely to have an AST > 45 (AOR=6.01 [1.63-22.21] p=0.007), creatinine ≥1 (AOR 2.92 [0.82-10.4], p=0.09) and platelets <100 (AOR 5.74 [1.00-32.76] p=0.049) after adjusting for race, age and multiple gestation. When restricted to women using IVF, the odds of having these abnormal labs increased. Among PEC women, the association between IUGR and ART was not statistically significant (AOR=1.76 [0.67-2.49] p=0.25). CONCLUSIONS: This study confirms prior reports that ART, particularly IVF, is associated with hypertensive disorders of pregnancy. ART women are significantly more likely to have severe disease with abnormal lab values, even after adjusting for confounders. The etiology of PEC remains largely unknown, but the association between ART and severe PEC suggests that abnormal placentation may trigger a more severe systemic phenotype of PEC. Future research should focus on the mechanism by which ART increases the risk of PEC, particularly severe disease.