Familial Mediterranean fever and its implications for fertility and pregnancy

Familial Mediterranean fever (FMF) is a recessively inherited disease of episodic fever in combination with severe abdominal pain, pleurisy, arthritis or erysipelas-like skin rashes. The disease is mainly prevalent in Sephardic Jews, Armenians, Turks and Arabs. The gene responsible for FMF was cloned in 1997. The gene expresses a protein called pyrin which is believed to play a role in the downregulation of mediators of inflammation. Several mutations have been identified of which the homozygous form of the M694V mutation is associated with a more severe expression of FMF. Prophylactic administration of colchicine is effective in relieving most patients from their attacks and preventing the development of amyloidosis, which usually leads to end-stage renal disease. Unfortunately, there is little awareness of the disease in gynaecological practice although a FMF full blown episode may mimic an acute abdominal calamity suggesting several possible gynaecological diagnoses. FMF is also associated with subfertility. In females, infertility was mainly related to oligomenorrhea although the causes remain unclear. In male FMF patients, progression of the disease may induce testicular impairment, consequently affecting spermatogenesis. Some controversy exists as to the adverse effects of colchicine on sperm production and function although the impression is that the occurrence of sperm pathology in FMF patients, using the recommended dosage of colchicine, is very low. In pregnant FMF patients, an increased occurrence of miscarriage has been found. However, the mechanisms involved remain unclear. Although colchicine is a mitotic inhibitor and transplacental crossing of colchicine has been demonstrated, no increased risk of foetal abnormalities in colchicine-treated pregnant FMF patients has been found. Therefore, amniocentesis should not be done for reassurance alone.