While repeated use of clomiphene may be associted with a higher risk of neural tube defects and severe hypospadias, overall increased risk for congenital anomaly is only about 1% to 2%.
While repeated use of clomiphene may be associated with a slightly higher risk of neural tube defects and severe hypospadias, the overall increased risk for a congenital anomaly from the various infertility drugs is only about 1% to 2%, according to the findings of a recent review of the literature.
The authors of the review found no conclusive evidence linking letrozole or other aromatase inhibitors, metformin, or estrogen to congenital anomalies. Similarly, they found no evidence for an association between gonadotropin releasing hormone (GnRH) agonists or antagonists and congenital anomalies, but they noted that a paucity of information exists after 1991, and that too little research exists on GnRH antagonists to be certain one way or the other. While micronized progesterones do not appear to increase the risk of nongenital birth defects, other progestational agents may increase the risk of hypospadias.
Lastly, the authors of the review remind us that infertility in and of itself is a risk factor for congenital anomalies.