Reproductive system status and the algorithm to solve fertility issues in men with cystic fibrosis
Authors: Repina S. A. , Krasovskiy S. A. , Shmarina G. V. , Shtaut M. I. , Zhekayte E. K. , Voronkova A. Yu. , Sherman V. D. , Kondratyeva E. I. , Chernykh V. B. 
Published: February 2019

Rationale: Cystic fibrosis (CF) is a common hereditary disease related to the CFTR gene mutations and characterized by progression and multiple system involvement (primarily of the digestive tract and / or pulmonary system). Most men with CF are infertile. Due to new therapeutic options, the life expectancy of CF patients has increased, with reproductive issues becoming relevant.Aim: A multifaceted assessment of the reproductive system status and fertility in male patients with CF and improvement of the strategies to resolve their reproduction issues.Materials and methods: This cohort prospective study was performed 2006 to 2018 and included 81 unrelated Russian male patients with confirmed CF, aged from 15 to 69 years (mean age 25.6 ± 7.9 years). Forty two (42) patients had pancreatic sufficient and 39 pancreatic insufficient CF. The patients underwent clinical, andrological, laboratory and instrumental examination (scrotal ultrasonography, standard and biochemical semen examination and hormone levels).Results: Reproductive disorders and semen abnormalities found in CF patients varied from preserved fertility to infertility. The following andrological abnormalities were found: delayed puberty (48%), urological disorders (26%), uni- or bilateral testicular hypoplasia (42%), diffuse lesions and cysts of the epididymis (70%), diffuse lesions /calcifications of the prostate (50%), and decreased testosterone levels (24.2%). Azoospermia was diagnosed in 87.5% of the patients, “moderate” or “mild” pathozoospermia (oligo-/astheno-/teratozoospermia) in 11.1%, and normozoospermia in 1.4% of the patients. There were significant differences between the patients with pancreatic sufficient and pancreatic insufficient CF in the ejaculate volume (1.4 ± 1.5 ml vs. 0.6 ± 0.5 ml; р = 0.006), ejaculate pH (6.7 ± 0.7 vs. 6.1 ± 0.4; р < 0.0001), and sperm concentration (19.6 ± 56.0 Mio/mL vs. 0.001 ± 0.008 Mio/ mL; p = 0.011). Normal ejaculate volume was more frequent (21.1% vs 14.7%; p > 0.05) in patients under the age of 25. No bilateral obstruction of vas deferens was found in 71.4% patients with 3849+10kbC>T mutation. There was a significant difference (p < 0.00001) in the frequency of 3849+10kbC>T mutation between the patients with vas deferens obstruction (9.5%) and without it (93.8%). We developed an algorithm to resolve infertility issues (including assisted reproductive technologies) in male CF patients depending on their fertility / presence and type of pathozoospermia and some other factors that may influence the conception and CF risk in the offspring. We also suggested practical recommendations for the andrological assessment, maintenance of reproductive health, and planning of childbirth in these patients.Conclusion: Male CF patients require a multifaceted assessment of their reproductive system. The prognosis of their reproductive functions, the strategy to maintain their reproductive health and making a decision on childbirth depends on the CF type, the CFTR genotype, the results of semen analysis, and the patient’s age. Pancreatic sufficient CF type, 3849+10kbС>T mutation of the CFTR gene and younger age are favorable factors for potential maintenance of vas deferens patency and male fertility in CF patients.