Follow-up of Babies Born after Treatment with Aromatase Inhibitor, an Off-label Ovulation-inducing Agent

Abstract

Background: Anovulation is the leading cause of infertility. Among causes of anovulation, polycystic ovarian syndrome (PCOS) is the prime one. Ovulation induction (OI) is the most common mode of treatment for anovulatory infertility. Clomiphene citrate (CC) has been used as a first-line drug for ovulation induction for a long back. Letrozole, an aromatase inhibitor (AI), is now a widely used ovulation-inducing agent because of the lack of antiestrogenic side effects, which is a significant concern in CC. Different studies reported congenital abnormalities in babies born with letrozole use. Any search instrument has not seen studies on developmental milestone delays in babies born by letrozole use. Objective: The purpose of the study was to follow-up on the growth and developmental milestones of babies born after treatment with AI, an off-labeled OI drug. Materials and methods: This cohort study was conducted in the infertility care and research center (ICRC), Dhaka, Bangladesh. A total of 1,895 babies were recruited in this study. Among them, 1,059 babies were in the “study group”who were born by OI with letrozole and 836 were in the “control group”who were born spontaneously. The main outcome measures were postnatal growth and developmental milestones of the babies born using letrozole as OI. Others are congenital abnormalities, birth weight, and birth asphyxia. A p-value < 0.05 was considered significant. Results: Gestational age, birth weight, and birth defect rate were similar in both groups. The height and weight of the babies in both groups were compared to observe whether there was any developmental delay in babies born by letrozole, and it was not significant between the study and control groups. Physical, mental, and cognitive development of babies were assessed according to CDC criteria; the difference between the two groups is not statistically significant. There was a milestone developmental delay in 3.12% of babies in the letrozole group and 3.83% of babies in the spontaneous group. Three babies (0.28%) had delayed mental development due to autism in the letrozole group, and 2 (0.24%) in the spontaneous group. However, the difference is not statistically significant. Conclusion: According to the study’s results, there does not appear to be a higher risk of congenital anomalies, postnatal growth retardation, or developmental delay in babies of women who received letrozole as OI compared to spontaneous pregnancies.