Infertility in aa renal amyloidosis secondary to familial mediterranean fever

Abstract

Background and Objectives: Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide, affecting mainly Mediterranean populations. AA amyloidosis is its most severe complication, with renal involvement being the primary determinant of prognosis. While infertility has been historically associated with FMF, particularly before the colchicine era, the specific impact of AA amyloidosis on fertility outcomes remains poorly characterized^{1, 2} . This study aims to evaluate fertility in patients with FMF‑related AA amyloidosis compared to FMF patients without amyloidosis. Methods: Retrospective study of all FMF patients seen at our center over a 4‑year period (2015 to 2019). Diagnosis was established according to Livneh criteria³ . Fertility data were collected from medical records, including number of pregnancies, parity for women, and number of children for men. Patients with biopsy‑proven AA amyloidosis were compared to those without amyloidosis. Results: Eighty FMF patients were included, of whom 52 had histologically confirmed AA amyloidosis. Median age at diagnosis was 33.7 years (range 6 to 70). Median age at symptom onset was 6 years (range 4 to 45). Forty‑nine patients were homozygous or compound heterozygous for pathogenic MEFV mutations, while 31 were simple heterozygous. Median age at colchicine initiation was 38.1 years (range 28 to 70). Among men (44 patients, median age 42 years), mean number of children was 2 (range 0 to 7). Declared infertility was observed in 2 men (4.5%) within the AA amyloidosis group. Among women (36 patients, median age 37 years), mean number of pregnancies was 2.2 (range 0 to 9); 22% were under 25 years and 35% under 30 years. Infertility was diagnosed in 4 women (11.1%), all of whom had developed AA renal amyloidosis. Overall, 47 patients (58.8%) with secondary amyloidosis had children. AA amyloidosis complicating FMF significantly increased infertility risk compared to FMF patients without amyloidosis (11.5% versus 0%, p = 0.03). Conclusion: AA amyloidosis complicating FMF significantly increases infertility risk compared to FMF patients without amyloidosis. Early and sustained colchicine prescription can restore fertility rates to normal levels and prevent the development of systemic amyloidosis ^{4, 5} .

Keywords: Familial Mediterranean fever; AA amyloidosis; infertility; colchicine; MEFV mutation; renal amyloidosis.