Ovarian Stimulators, Intrauterine Insemination, and Assisted Reproductive Technologies Use and the Risk of Major Congenital Malformations—The AtRISK Study

OBJECTIVE

To quantify the risk of major congenital malformations (MCMs) associated with the use of ovarian stimulators alone, intrauterine insemination (IUI), and assisted reproductive technologies (ARTs).

METHODS

We conducted a case–control analysis using a birth cohort, built with the linkage of data obtained by a self-administered questionnaire, medical, pharmaceutic, and birth databases. Cases were pregnancies with at least one live birth with an MCM. Controls were pregnancies that did not result in major or minor congenital malformations. Multiple logistic regression models were used to calculate the odds ratios (ORs) and confidence intervals (CIs).

RESULTS

Among the 5021 pregnancies identified, 825 were cases of MCM and 4196 were controls. Compared with spontaneous conception, the use of ART increased the risk of major urogenital malformations (adjusted OR, 3.11; 95% CI, 1.33–7.27). The use of IUI was associated with an increased risk of major musculoskeletal malformations (adjusted OR, 2.02; 95% CI, 1.10–3.71). Among the 471 women who used fertility treatments for conception, the use of ART was associated with an increased risk of any MCM (adjusted OR, 1.66; 95% CI, 1.00–2.79) and urogenital malformations (adjusted OR, 7.18; 95% CI, 1.59–32.53) when compared with ovarian stimulators used alone.

CONCLUSIONS

The use of ART and IUI was associated with an increased risk of major musculoskeletal and urogenital malformations. ART was associated with a higher risk of MCM compared to ovarian stimulators used alone. Even the adjustment, a contribution of the underlying subfertility problems cannot completely ruled out given the differences in the severity of subfertility