Effects of gonadotropin-releasing hormone receptor antagonists on ectopic human trophoblast cell invasion

Ectopic pregnancy (EP) is a life-threatening condition responsible for 6.5% of Canadian mothers’ death between 1993-2004. EP occurs when an embryo implants outside the uterine endometrium, commonly in the Fallopian tube (98%). Tubal EP often requires surgical intervention as a life-saving measure. Early and precise diagnosis allow many women to choose methotrexate, the only available medical option, for treatment. Methotrexate is effective in 70% of patients; however, they may require multiple treatments, suffer moderate-to-severe side effects, or experience sub-optimal responses. The remaining 30% fail to respond to the treatment. Gonadotropin-releasing hormone (GnRH) has an inducing effect on intrauterine placental cell invasion and human chorionic gonadotropin hormone (hCG) production. GnRH receptor (GnRH-R) antagonists have been used safely to treat endometriosis, chronic pelvic pain, and in the artificial fertilization techniques. For the first time, we separated primary trophoblast cells from tubal EP placentas. We validated their trophoblastic origin using trophoblast-validating markers. The preliminary findings showed that primary EP trophoblast cells express GnRH and GnRH receptor. Treating these cells with clinical GnRH-R antagonist, cetrorelix, suppressed their viability. We used primary trophoblast cells from tubal pregnancies, immortalized HTR-8/SVneo cell line, and placental villous explants established from the first-trimester human intrauterine placenta in this study. We investigated the effect of clinical GnRH-R antagonists, cetrorelix and ganirelix, on the invasion of different trophoblast models. Finding a safe, effective, and more tolerant medical treatment for tubal pregnancy will significantly improve women’s health and reduce healthcare-related costs.Medicine, Faculty ofObstetrics and Gynaecology, Department ofGraduat