Familial Mediterranean Fever and infertility: a possible role of inflammation

Article title: Novel use of interleukin-1 antagonists in male familial Mediterranean

fever patients with infertility: Case series

First author: Bugra Egeli

Journal: Archives of rheumatology

Link to the article: https://pubmed.ncbi.nlm.nih.gov/39507831/

Author of the abstract: Dr. Catherine Grandpeix-Guyodo

Introduction:

The main treatment for familial Mediterranean fever (FMF) is colchicine. Interleukin-1 (IL-1) inhibitors are used in cases of colchicine resistance in FMF.

Fertility disorders with azoospermia or oligospermia have been described in FMF; colchicine is often held responsible but this could be related to chronic inflammation induced by FMF.

Patients and methods: This article reports the cases of 2 men followed for FMF and suffering from infertility who successfully conceived embryos in vitro after stopping colchicine and starting treatment with IL-1 inhibitors.

Results:

Case N°1: A 38-year-old man with FMF, with homozygous M69V mutation of MEFV, treated with 2 mg colchicine/day had failed to conceive for 15 years despite 5 IVF attempts and stopping colchicine after the first 2 IVF. Semen analysis was macroscopically normal, with normal sperm count but decreased motility. Treatment with anakinra (IL-1 RA) was started, resulting in satisfactory semen analysis after 4 months and the obtaining of 2 genetically normal embryos compatible with transfer.

• Case N°2: A 33-year-old man suffering from FMF, with a heterozygous M694V mutation of MEFV, treated with colchicine for 14 years, presented with infertility with azoospermia. The failure of a first IVF under colchicine motivated its discontinuation and the prescription of Canakinumab. Successive sperm analyses showed progressive improvement in sperm motility which allowed, during the 5th IVF, the conception of a child.

Discussion:

These two cases show reversibility of Infertility under IL-1 inhibitors in FMF in 2 men: The introduction of anti-IL1 instead of colchicine allowed improvement in sperm quality in both cases.

Colchicine resistance is suggested as a predictive factor for infertility in FMF patients, suggesting that better control of inflammation may improve it.

Conclusion:

Infertility in men with FMF could be reversible and anti-IL1 could become the treatment of choice in FMF men with fertility disorders.