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.
Competing Interests: Declaration of Competing Interest Jennifer L. Taylor-Cousar, MD, MSCS, ATSF Personal financial relationships with commercial interests relevant to medicine within the past 3 years: As faculty in an institution that is part of the CF TDN, I have been site PI on studies for Vertex, 4DMT, and Eloxx. I have done consulting/provided clinical trial design advice for Vertex and 4DMT. I served as Chair of a Data Monitoring Committee for AbbVie. Personal financial support from a non-commercial source relevant to medicine within the past 3 years: I have received grant funding from the CFF and NIH. Personal relationships with tobacco industry entities within the last 3 years: No relationships to disclose. Professional Memberships CFF Clinical Research Executive Committee CFF TDN Sexual Health, Reproduction, and Gender Research Working Group (SHARING) ATS International Conference Committee Chair and Respiratory Health Awards Committee Member National Institutes of Health/National Heart, Blood, Lung Institute Clinical Trials Review Study Section Rachel Janney No relationships to disclose. Peter G. Middleton, MD, PhD, FRACP, FThorSoc. Personal financial relationships with commercial interests relevant to medicine within the past 3 years: I have been site PI on studies for Vertex including the phase III Trikafta study. I have done medico-legal consulting for Shine Lawyers. I have provided lectures and presentations on CF, asthma and COVID amongst other topics for Vertex Pharma, AstraZeneca, Limbic, and MedEd. Family members have shareholdings in Resmed Inc and Sanofi Pharma. Personal financial support from a non-commercial source relevant to medicine within the past 3 years: I have received grant funding from HCF Australia and the Canadian Institutes of Health. I have received support for attending meetings from NSW Health. Personal relationships with tobacco industry entities within the last 3 years: No relationships to disclose. Professional Memberships I am Chair of the Australian Bronchiectasis Registry. I serve on steering committees for the Australian CF Data Registry, the Australian Standards of Care and the ECFS Standards of Care. Raksha Jain, MD, MSc Personal financial relationships with commercial interests relevant to medicine within the past 3 years: As faculty in an institution that is part of the CF TDN, I have been site PI on studies for Vertex, 4DMT, Sound Pharma, Genentech, Armata. I have done consulting/provided clinical trial design advice for Boerhinger-Ingelheim and Recode. I served on a Data Monitoring Committee for Syneos. Personal financial support from a non-commercial source relevant to medicine within the past 3 years: I have received grant funding from the CFF and NIH. Personal relationships with tobacco industry entities within the last 3 years: No relationships to disclose. Professional Memberships CFF TDN Sexual Health, Reproduction, and Gender Research Working Group (SHARING) American Thoracic Society American College of Chest Physicians Julia A. Nightingale BA, BM BCh, MRCP, PhD Personal financial relationships with commercial interests relevant to medicine within the past 3 years: No relationships to disclose. Personal financial support from a non-commercial source relevant to medicine within the past 3 years: I have received grant funding from Chiesi UK. Personal relationships with tobacco industry entities within the last 3 years: No relationships to disclose. Professional Memberships Member of the Royal College of Physicians Adult representative on the UK Cystic Fibrosis Medical Association executive committee Michal Shteinberg Personal financial relationships with commercial interests relevant to medicine within the past 3 years: I have received grants/research support from: GSK, Insmed, Novartis, Trudell pharma, Tel Aviv League for lung diseases; consultation fees: Astra Zeneca, Boehringer Ingelheim, Dexcel, GSK, Kamada, Syncrony-medical, Trumed, Zambon; speaker's fees from Astra Zeneca, Boeringer Ingelheim, GSK, Kamada, Novartis, PhysioAssist, Sanofi, Teva. I serve as a DSMB member for – Bonus biotherapeutics. Personal financial support from a non-commercial source relevant to medicine within the past 3 years: Member of management board of EMBARC; Professional Memberships Executive committee of Israel Society for TB and Mycobacterial diseases; Associate editor- Am J Resp Crit Care med; Editorial board member- Eur Resp J, Chest. Personal relationships with tobacco industry entities within the last 3 years: No relationships to disclose. Danielle Velez, MD Personal financial relationships with commercial interests relevant to medicine within the past 3 years: No relationships to disclose. Personal financial support from a non-commercial source relevant to medicine within the past 3 years: I have received grant funding from the CFF. Personal relationships with tobacco industry entities within the last 3 years: No relationships to disclose. Professional Memberships I am member of the CFF Men's Health Research Subgroup of the CFF TDN Sexual Health, Reproduction, and Gender Research Working Group (SHARING) Natalie E. West, MD, MHS Personal financial relationships with commercial interests relevant to medicine within the past 3 years: As faculty in an institution that is part of the CF TDN, I have been site PI on studies for Corbus, Armata and co-investigator on studies for Vertex. I have done consulting/provided clinical trial design advice for Vertex and Armata. Personal financial support from a non-commercial source relevant to medicine within the past 3 years: I have received grant funding from the CFF and NIH. Personal relationships with tobacco industry entities within the last 3 years: No relationships to disclose. Professional Memberships CFF TDN Sexual Health, Reproduction, and Gender Research Working Group (SHARING) American Thoracic Society Traci M. Kazmerski, MD, MS Personal financial relationships with commercial interests relevant to medicine within the past 3 years: No relationships to disclose. Personal financial support from a non-commercial source relevant to medicine within the past 3 years: I have received grant funding from the CFF and NIH. Personal relationships with tobacco industry entities within the last 3 years: No relationships to disclose. Professional Memberships CFF TDN Sexual Health, Reproduction, and Gender Research Working Group (SHARING) American Thoracic Society
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