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

Jennifer L Taylor-Cousar; Rachel Janney; Peter G Middleton; Raksha Jain; Julia Nightingale; Natalie E West; Michal Shteinberg; Danielle Velez; Traci M Kazmerski

doi:10.1016/j.jcf.2023.10.022

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

J Cyst Fibros. 2023 Nov 10:S1569-1993(23)01667-3. doi: 10.1016/j.jcf.2023.10.022. Online ahead of print.

Authors

Jennifer L Taylor-Cousar¹, Rachel Janney², Peter G Middleton³, Raksha Jain⁴, Julia Nightingale⁵, Natalie E West⁶, Michal Shteinberg⁷, Danielle Velez⁸, Traci M Kazmerski⁹

Affiliations

¹ National Jewish Health, Departments of Medicine and Pediatrics; University of Colorado Anschutz Medical Campus, Departments of Medicine and Pediatrics. Electronic address: Taylor-CousarJ@NJHealth.org.
² National Jewish Health, Clinical Research Services.
³ University of Sydney, Discipline of Medicine.
⁴ University of Texas Southwestern, Department of Medicine.
⁵ University Hospital Southhampton NHS Trust.
⁶ Johns Hopkins University, Department of Medicine.
⁷ Pulmonology institute and CF center, Carmel Medical center, Haifa, Israel; Technion-Israel institute of technology, the B. Rappaport school of medicine.
⁸ Rutgers Robert Wood Johnson Medical School, Division of Urology.
⁹ University of Pittsburgh, Department of Pediatrics; Center for Innovative Research on Gender Health Equity (CONVERGE).

PMID: 37953181
DOI: 10.1016/j.jcf.2023.10.022

Abstract

Background: 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.

Methods: From August-October 2021, international CF clinicians completed an anonymous questionnaire regarding mwCF who used modulators during reproduction.

Results: 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.

Conclusions: Use of CFTR modulators during reproduction and partner pregnancy in mwCF did not result in a higher-than-expected miscarriage rate nor congenital anomalies.

Keywords: Assisted reproduction; CFTR; Conception; Cystic fibrosis; Modulators.