Familial Mediterranean fever-associated infertility and underlying factors

Familial Mediterranean fever (FMF) is characterized by recurrent attacks of fever, serositis, and arthritis, but some patients may experience long-term complications of disease such as infertility/subfertility. The published data about FMF-associated infertility is still limited. The aim of this study is to investigate the frequency and to determine potential factors for FMF-associated infertility/subfertility.

We enrolled 971 adult patients with FMF. We defined infertility as the failure to conceive after 12 months of regular, unprotected intercourse. All patients fulfilled Tel Hashomer criteria. Demographic data, FMF disease characteristics and genotype data (if available), disease complications, laboratory parameters, and treatment features were recorded.

There were 582 subjects eligible for the present study (mean age 41.05 ± 10.6 years, 65.8% female). MEFV mutations were available in 482 subjects, and 74.9% of subjects were harboring M694 V mutation (25.1% homozygous for M694 V). Infertility was present in 64 patients (14.6% of females and 4% of males). Multivariate analysis showed female sex [odds ratio (OR), 4.47; 95% confidence interval (CI95%) 1.75-11.42; p = 0.002], FMF disease onset < 20 years [OR, 2.99; (CI95% 1.04-8.61);p = 0.04], disease severity (ISSF) [OR, 4.81; (CI95% 2.28-10.17); p < 0.001], and colchicine nonresponse [OR, 2.80; (CI95% 1.17-6.74) p = 0.021] were the independent predictors of infertility. We also observed reversal of infertility in five patients who were treated with IL-1 β antagonists.

Disease severity, FMF disease onset < 20 years, colchicine nonresponse, and female sex were found to be the independent predictors of infertility. The value of effective therapeutic interventions must be determined to treat infertility in these patients.Key Points•The prevalence of infertility increased in female patients with FMF.• Female sex, FMF disease onset < 20 years, disease severity, and colchicine nonresponse were risk factors for FMF-associated infertility.• With effective treatment of FMF, reversal of infertility was observed in five patients.