JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):137
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263772

P-125. Impact of CFTR gene mutations on male fertility: An updated review

Giovanna Garcia Stundis de Farias¹, Rayza Furtado Silva¹, Maria Eduarda Pereira Giunchetti¹, Rodrigo Alessandro Riemma Vela¹, Renato Borges Tesser¹

¹ Centro Universitário São Camilo - São Paulo - SP - Brasil

Objective: To analyze, through a literature review, clinical and genetic studies that investigate alterations in the CFTR gene in CBAVD, a condition associated with male infertility.
Methods: To carry out this study, a bibliographic survey was conducted in the PubMed and ScienceDirect databases, considering publications between 2020 and 2025, in English, using keywords such as "CFTR gene," "CBAVD," and "male infertility." Studies addressing the relationship between mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene and congenital bilateral absence of the vas deferens (CBAVD), characterized by the absence of sperm in the ejaculate (obstructive azoospermia), were considered.
Results: The CFTR gene mutation is predominantly related to classic cases of cystic fibrosis (CF), with F508del being the most common mutation, present in about 70% of cases. This mutation is also related to impaired male fertility, as it can cause obstructive azoospermia due to congenital bilateral absence of the vas deferens (CBAVD), a condition that prevents the passage of sperm and is found in most infertile men with the mutation. Furthermore, the F508del mutation can affect male fertility regardless of the full manifestation of cystic fibrosis, since studies affirm that the CFTR gene is fundamental for sperm capacitation via ionic modulation. Although men with cystic fibrosis show signs of testicular dysfunction, such as elevated FSH levels and primary hypogonadism, these factors do not appear to negatively affect overall reproductive outcomes after assisted reproductive techniques, such as intracytoplasmic sperm injection (ICSI). Additionally, studies show LH and testosterone levels similar to those of men with other CFTR gene variations, suggesting that not all men diagnosed with CF and CBAVD have severe testicular dysfunction. Thus, testicular dysfunction would be associated with the severity of the mutation found in the CFTR gene, which may represent relatively preserved or impaired testicular function. Therefore, fertilization, embryo development, and live birth rates suggest that men with CF can achieve reproductive success after surgical sperm retrieval techniques.
Conclusion: Mutations in the CFTR gene represent one of the main genetic determinants associated with obstructive male infertility, especially in cases of CBAVD. Among the existing variants described in the articles, the F508del mutation stands out as the most prevalent, followed by other mutations such as G542X, W1282X, R117H, and relevant polymorphisms such as M470V and the poly-T region. Recent studies indicate that the role of CFTR may go beyond the classic picture of CBAVD, involving ionic mechanisms mediated by CFTR channels, which, in turn, suggests a broader participation of the gene in sperm physiology. Thus, genetic screening of the CFTR gene, as well as genetic counseling, is indicated in cases of obstructive azoospermia, severe oligozoospermia, or when there is a family history. Therefore, given reproductive intentions, surgical access to sperm through techniques such as TESE (Testicular Sperm Extraction), PESA (Percutaneous Epididymal Sperm Aspiration), or MESA (Microsurgical Epididymal Sperm Aspiration), combined with fertilization using the ICSI technique, enable reproductive success for men with CF and CBAVD. Finally, CFTR modulating therapies, currently used in cystic fibrosis treatment, open new avenues for research into their effects on male reproductive function, raising interesting hypotheses about the possible reversal or attenuation of reproductive dysfunctions associated with mutations.