Successful ovulation induction, conception, and normal delivery after chronic therapy with etanercept: A recombinant fusion anti-cytokine treatment for rheumatoid arthritis

Etanercept (Enbrel((R)); Wyeth-Ayerst/Immunex Inc, Seattle, WA, USA) is a s ubcutaneously administered novel fusion protein consisting of the extracell ular ligand-binding domain of the 75 kD receptor for tumor necrosis factor- alpha (anti-TNF alpha) and the F-C portion of human IgG1. The agent is synt hesized by plasmid transfection of a Chinese hamster ovary cell line, utili zing recombinant DNA technology. Etanercept was approved by the US FDA for treatment of multi-drug resistant rheumatoid arthritis in 1998, but no huma n data exist regarding the impact of anti-TNF alpha therapy on human reprod uctive function or its use before ovulation induction. As TNF alpha potenti ates collagenolysis via matrix metalloproteinase gene expression (thereby f acilitating ovulation), there exists a theoretical risk that TNF alpha -inh ibition could exert an undesirable effect on ovulation and pregnancy. In th is report, we describe the first case of ovulation induction, intrauterine insemination, normal pregnancy and singleton delivery of a healthy infant f ollowing chronic ( > 1 year) pre-ovulatory TNF alpha -inhibitor therapy for rheumatoid arthritis. Reproductive endocrinologists and obstetrician-gynec ologists should be familiar with etanercept therapy in the context of sever e rheumatic disease, and offer appropriate reassurance regarding its safe u se for infertility patients planning ovulation induction.