Abstract
Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by periodic fever, serositis, and arthritis. In women, FMF attacks can sometimes be triggered by the menstrual cycle. Once diagnosed, prophylactic treatment with colchicine is generally recommended. Here, we report the case of a 34-year-old nulligravid Japanese woman who met the Tel-Hashomer criteria for FMF with menstruation-associated attacks and experienced a severe FMF episode following controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) without prophylactic colchicine. We also discuss management strategies for menstruation-associated FMF in patients who do not receive prophylactic therapy. Although prophylactic colchicine treatment was advised, the patient declined, and a plan for symptomatic management was established. She was referred to our clinic for infertility and subsequently underwent IVF due to endometriosis. At the initial examination, an increase in follicle-stimulating hormone (FSH) levels was observed, and endogenous endocrine function was regulated by administering estrogen and progestin. She experienced two withdrawal bleeding episodes without FMF attacks. Subsequently, COH using a gonadotropin-releasing hormone (GnRH) antagonist protocol was initiated, and oocyte retrieval was performed when her estradiol (E2) level reached 953 pg/mL. Immediately after the withdrawal bleeding following oocyte retrieval, she experienced her most severe FMF attack to date, presenting with fever above 38°C, diffuse abdominal pain, vomiting, and joint pain. To prevent further FMF attacks during the waiting period before embryo transfer, colchicine or dienogest was administered, effectively suppressing additional episodes. This case suggests that in patients with menstruation-associated FMF, withdrawal bleeding after COH may strongly provoke FMF attacks due to the abrupt decline in estrogen levels. It underscores the importance of prophylactic therapy with colchicine or other agents during assisted reproductive technology (ART). Furthermore, when prophylactic treatment is not feasible, alternative strategies such as fresh embryo transfer should be considered.