Congenital Anomalies and Hormonal Contraception/Contragestion: A Systematic Review

Background: Concerns remain regarding the potential teratogenic risks of hormonal contraceptives and contragestive agents (such as emergency contraception and mifepristone) when pregnancy occurs despite their use. This systematic review aimed to assess the risk of major congenital anomalies following early pregnancy exposure to these agents, including oral, injectable, implantable contraceptives, intrauterine devices (IUDs), and medical abortion drugs.

Method: A comprehensive search of PubMed, Embase, the Cochrane Library, and related databases through 2024 identified studies reporting congenital outcomes following in utero exposure to these agents. Eligible studies, regardless of design, provided data on exposure timing, type of anomaly, and effect estimates. The risk of bias was evaluated using Cochrane and Newcastle-Ottawa tools as appropriate.

Results: Findings consistently demonstrate no significant increase in major congenital malformations following first-trimester exposure to hormonal contraceptives or emergency contraceptive failure. Meta-analysis of prospective cohorts showed a pooled relative risk near unity (RR ≈1.00; 95% CI 0.83–1.19) for malformations after oral contraceptive use. Studies on levonorgestrel or ulipristal emergency contraception similarly showed no elevated risk. A recent systematic review also found no evidence that mifepristone exposure in early pregnancy results in teratogenesis. Isolated reports have suggested potential associations between injectable progestogens (e.g., depot medroxyprogesterone acetate) and limb anomalies or hypospadias, but the causative linkage is yet to be proof.

An exception is a recent single-center Chinese study reporting a higher rate of congenital malformations in pregnancies continuing with retained copper IUDs. However, this finding conflicts with broader evidence and requires replication.

Conclusion: current data do not support an increased risk of birth defects from early pregnancy exposure to hormonal contraception or contragestive therapies. Patients can be reassured of the high fetal safety profile of these methods, though careful management of inadvertent IUD pregnancies remains essential. Further large-scale surveillance could strengthen these conclusions.