A provider survey assessing fetal impact of CFTR modulator use in males with CF during assisted and unassisted reproduction and partner pregnancy

•The number of males with CF (mwCF) who are becoming fathers is increasing.•Safety of modulator use by mwCF during conception and partner pregnancy is unknown.•For exposed fetuses, miscarriage rates were consistent with US population rates.•No congenital anomalies were reported for exposed infants.•A prospective study is needed to study modulator use by mwCF during reproduction. Most males with cystic fibrosis (mwCF) are infertile but with CF transmembrane conductance regulator (CFTR) modulator-conferred benefits, more are utilizing assisted reproductive technologies (ART). Administration of normal human doses of modulators in animal reproductive models caused no genotoxicity; no human data exists. Potential health decline following modulator discontinuation makes the decision to withhold therapy during reproduction challenging. From August-October 2021, international CF clinicians completed an anonymous questionnaire regarding mwCF who used modulators during reproduction. We received 42 surveys for mwCF with partner pregnancies. Forty of 42 mwCF utilized ART; 35 continued modulators during sperm retrieval and 40/42 during partner pregnancy. One of four males who discontinued modulators experienced clinical deterioration. First trimester miscarriages occurred in 11.9 % of partner pregnancies. No congenital anomalies were reported. Use of CFTR modulators during reproduction and partner pregnancy in mwCF did not result in a higher-than-expected miscarriage rate nor congenital anomalies.