Dose-Dependent Link Seen for Clomiphene Citrate, Adverse Perinatal Outcomes

MONDAY, Aug. 17, 2026 (HealthDay News) — There is a dose-dependent relationship between clomiphene citrate (CC) and adverse perinatal outcomes among fresh autologous in vitro fertilization (IVF) cycles, according to a study published in the August issue of BMJ Open.

Sheree Boulet, Dr.P.H., M.P.H., from the Boston University Chobanian and Avedisian School of Medicine, and colleagues conducted a retrospective cohort study to examine the association between cumulative CC dose and perinatal outcomes among fresh autologous IVF cycles. The adjusted risk ratios were estimated for the associations between four categories of CC dose and perinatal outcomes of interest among 21,004 fresh autologous embryo transfer cycles.

Among the cycles using CC, 21.3, 67.8, 7.2, and 3.7 percent used <500 mg, 500 to 749 mg, 750 to 999 mg, and ≥1,000 mg, respectively. The researchers found that the rates of spontaneous abortion were higher for patients using 500 to 749 mg and 750 to 999 mg of CC compared with those using <500 mg after adjustment (11.8 and 14.4 percent, respectively, versus 10.3 percent; adjusted risk ratios, 1.12 and 1.38, respectively). Compared with the <500-mg group, the ≥1,000-mg group had a threefold higher rate of stillbirth, but the estimates were imprecise and not statistically significant (0.7 versus 0.2 percent). Compared with the <500-mg group, all dosage categories had a significantly higher multiple birth risk.

“Our findings suggest there may be a point where increasing the dose offers little additional benefit while exposing women to greater risk, highlighting the importance of carefully balancing effectiveness with safety when making treatment decisions,” Boulet said in statement.

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