#NACFC2022 – No Unusual Risk in Partners’ Pregnancy With CFTR Modulators

Survey study of fertility outcomes for men with CF choosing to father children

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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CFTR modulators, a highly effective therapy for cystic fibrosis (CF), do not appear to affect fertility outcomes for men using them, data from surveys of these patients indicate.

Miscarriages during pregnancy for a woman whose partner is using modulator therapy and congenital anomalies for the child were not higher than expected, researchers reported.

The findings were shared by Jennifer Taylor-Cousar, MD, with National Jewish Health in Denver, at the 2022 North American Cystic Fibrosis Conference. Her presentation was titled “Fetal Impact of CFTR Modulator use during Assisted and Natural Reproduction and Partner Pregnancy in Men with CF,” and the work was supported by the Asher Family Fund.

As care for CF continues to improve, patients are living longer and healthier lives than was possible before. An increasing number choosing to become parents and to have biological children.

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No higher-than-expected miscarriages, congenital anomalies reported

Nearly all men with CF are born without the tubes that normally transport sperm from the testes during ejaculation, a condition called congenital bilateral absence of the vas deferens or CBAVD. Men with CBAVD cannot conceive a child through vaginal intercourse, but conception is possible through assisted reproductive techniques (ART). Using these techniques, clinicians retrieve sperm cells from a patient’s testes and use them to fertilize an egg cell, usually through in vitro fertilization.

CFTR modulators are a recently developed class of therapies that work to improve the functionality of the CFTR protein, given that CF is caused by mutations that impair its function. Work in animal models have generally suggested that CFTR modulator treatment does not confer risk to a developing fetus, but no research exists on modulator use by males with CF during conception and pregnancy.

An international team of scientists reported on outcomes for men with CF (median age, 32) whose partners became pregnant — 40 pregnancies were achieved via ART and two via vaginal intercourse. All but one of these men carried the most common CF-causing mutation, F508del, in at least one of the CFTR gene copies.

The survey, first distributed in August 2021, was conducted in the U.S, U.K., Israel and Australia. It addressed the use of any CFTR modulator by men with CF during ART.

Most of the men were taking CFTR modulators around the time of conception, most commonly Trikafta. Exceptions included one newly diagnosed man who didn’t start on these treatments until after ART, and four patients who stopped treatment before sperm retrieval. Notably, one man in the latter group experienced a decline in lung function.

Among men whose condom use was known, none reported using condoms during pregnancy. Four switched modulator therapy during the pregnancy.

The average time the men were on CFTR modulators before conception was 18 months.

Five pregnancies ended in a miscarriage during the first trimester. Data show that this rate in the general population is up to 20%.

Other pregnancy- and birth-related complications included cases of COVID-19 during pregnancy, vaginal bleeding, vasa previa (a form of severe blood loss), and breech presentation (when a baby’s feet or buttocks are positioned to come out of the vagina first). Two cases required assisted delivery.

Four babies were born with low oxygen levels requiring intensive care at birth.

None of these complications were considered to be probably related to the use of CFTR modulators by male partners with CF, and none of the infants were found to have CF or to show any congenital abnormality.

“Use of CFTR modulators during partner conception and/or pregnancy in [men with CF] has not resulted in a higher-than-expected miscarriage rate or in congenital anomalies,” Taylor-Cousar said.

“When counseling [men with CF] regarding CFTR modulator use and ART or natural partner conception, providers should discuss both the potential risk to the health of [men with CF] of modulator discontinuation and the data from animal reproductive models and limited safety data in the human fetus,” she added.

Note: The Cystic Fibrosis News Today team is providing in-depth coverage of the 2022 North American Cystic Fibrosis Conference (NACFC) Nov. 3–5. Go here to see the latest stories from the conference.

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