Successful Ovulation Induction, Conception, and Normal Delivery after Chronic Therapy with Etanercept: A Recombinant Fusion Anti‐cytokine Treatment for Rheumatoid Arthritis

Etanercept (Enbrel®; Wyeth‐Ayerst/Immunex Inc, Seattle, WA, USA) is a subcutaneously administered novel fusion protein consisting of the extracellular ligand‐binding domain of the 75 kD receptor for tumor necrosis factor‐alpha (anti‐TNFα) and the FC portion of human IgG1. The agent is synthesized by plasmid transfection of a Chinese hamster ovary cell line, utilizing recombinant DNA technology. Etanercept was approved by the US FDA for treatment of multi‐drug resistant rheumatoid arthritis in 1998, but no human data exist regarding the impact of anti‐TNFα therapy on human reproductive function or its use before ovulation induction. As TNFα potentiates collagenolysis via matrix metalloproteinase gene expression (thereby facilitating ovulation), there exists a theoretical risk that TNFα‐inhibition could exert an undesirable effect on ovulation and pregnancy. In this report, we describe the first case of ovulation induction, intrauterine insemination, normal pregnancy and singleton delivery of a healthy infant following chronic (>1 year) pre‐ovulatory TNFα‐inhibitor therapy for rheumatoid arthritis. Reproductive endocrinologists and obstetrician‐gynecologists should be familiar with etanercept therapy in the context of severe rheumatic disease, and offer appropriate reassurance regarding its safe use for infertility patients planning ovulation induction.