Pregnancy Outcomes After in Utero Exposure to Immune Checkpoint Inhibitors.

importanceImmune checkpoint inhibitors (ICIs) have transformed the management of cancers affecting reproductive-age patients, yet their impact on pregnancy outcomes remains incompletely understood. We describe two cases of maternal and fetal outcomes associated with ICI exposure during pregnancy and present a comprehensive literature review.

methodsA retrospective chart review was conducted at MD Anderson Cancer Center (1 January 2015 to 31 December 2024) to identify patients exposed to ICIs during pregnancy. Clinical data including cancer type, treatment timing, pregnancy course, and maternal and neonatal outcomes were collected. A narrative literature review was also performed using PubMed to identify reported cases of ICI exposure during pregnancy. OBSERVATIONS: Two patients were identified at our institution, both treated with ICIs for advanced melanoma. One patient received pembrolizumab during early pregnancy, with the final dose administered five days after conception, and subsequently gave birth to a healthy term infant without complications. The second patient conceived while receiving adjuvant nivolumab and experienced a miscarriage at 13 weeks of gestation. Neither patient experienced immune-related toxicity during pregnancy, and both remained without evidence of disease at follow-up. The literature review identified 21 reported pregnancies with ICI exposure and variable outcomes. Most resulted in live births (85.7%), though preterm delivery occurred in approximately 50% of cases, often due to maternal or fetal indications. Additional reported outcomes included miscarriage, neonatal death, fetal growth restriction, preeclampsia, and rare immune-related neonatal effects. Congenital anomalies were reported in a small number of cases. CONCLUSIONS AND RELEVANCE: These findings suggest that, while many pregnancies exposed to ICIs result in live births, there may be an increased risk of adverse maternal and fetal outcomes. However, causality cannot be established due to the limited quality and quantity of available data. These findings underscore the importance of effective contraception during ICI therapy and careful multidisciplinary counseling when exposure occurs during pregnancy.