Dose-dependent perinatal risks of clomiphene citrate in US IVF cycles: a national cohort study, 2004-2021.

内容摘要

The relationship between clomiphene citrate (CC) dosing regimens and adverse reproductive outcomes has not been fully elucidated, both with and without use of in vitro fertilisation (IVF). We aimed to study the association between cumulative CC dose and perinatal outcomes among fresh autologous IVF cycles. Retrospective cohort study. We included all fresh autologous IVF embryo transfer cycles performed in the US fertility clinics during 2004-2021 using CC for ovulation induction. We used robust Poisson regression models to estimate adjusted risk ratios (aRRs) and 95% CIs for associations between four categories of CC dose (<500 mg, 500-749&#x2009;mg, 750-999&#x2009;mg and &#x2265;1000&#x2009;mg) and perinatal outcomes of interest. 21&#x2009;004 fresh autologous embryo transfer cycles using CC. The primary outcome measures included biochemical pregnancy, clinical pregnancy, spontaneous abortion, stillbirth, live birth, multiple birth and preterm delivery. Among fresh autologous embryo transfer cycles using CC, 21.3% used <500&#x2009;mg, 67.8% used 500-749&#x2009;mg, 7.2% used 750-999&#x2009;mg and 3.7% used &#x2265;1000&#x2009;mg. After adjustment, rates of spontaneous abortion were higher for patients using 500-749&#x2009;mg (11.8%; aRR, 1.12; 95%&#x2009;CI 1.02 to 1.25)&#x2009;and 750-999&#x2009;mg of CC (14.4%; aRR, 1.38; 95%&#x2009;CI 1.18 to 1.62) than for those using <500&#x2009;mg (10.3%). The &#x2265;1000&#x2009;mg group had a three-fold higher rate of stillbirth than the <500&#x2009;mg group, but these estimates were imprecise (0.7% vs 0.2%; aRR, 3.31; 95%&#x2009;CI 0.88 to 12.40). Multiple birth risk was significantly higher among all CC dosage categories compared with the <500&#x2009;mg group. Our findings extend previous findings on the association between CC exposure and adverse perinatal outcomes by demonstrating a dose-dependent relationship.