Pharmacokinetics of Human Chorionic Gonadotropin Injection in Obese and Normal-Weight Women

Abstract

Obese women have poorer in vitro fertilization outcomes, but underlying mechanisms remain unclear. The objectives of the study were to compare the pharmacokinetics of human chorionic gonadotropin (hCG) and ovarian steroid hormone production, after subcutaneous (s.c.) and intramuscular (i.m.) injection of hCG in obese and normal-weight women. This was a randomized, experimental study. Twenty-two women aged 18-42 years with body mass index of 18.5-24.9 (normal) or 30-40 kg/m(2) (obese). Participants received im urinary hCG or s.c. recombinant hCG and returned for a second injection type after a 4-week washout. Intramuscular injections were performed under ultrasound guidance. Blood was taken 0, 0.5, 1, 2, 4, 6, 8, 12, 24, and 36 hours after injection. hCG was measured at each time point; estradiol, progesterone, 17-hydroxyprogesterone (17-OHP), testosterone (T), dehydroepiandrosterone, and SHBG were measured at 0 and 36 hours. Twenty-two women completed the study. In both normal-weight and obese women, peak serum concentration (Cmax), area under the curve (AUC), and average hCG concentration were higher after i.m. injection as compared with s.c. injection (all P < .003). Obese women had markedly lower Cmax, AUC, and average hCG concentration after s.c. injection as compared with normal-weight women (P = .02, P = .009, and P = .008, respectively). After i.m. injection, Cmax, AUC, and average concentration were similar for normal-weight and obese women (P = .31, P = .25, and P = .18, respectively). Thirty-six percent of obese women had muscular layers beyond the reach of a standard 1.5 inch needle. hCG caused a significant rise in 17-OHP in both obese and normal-weight women and an increase in T in obese but not normal-weight women (all P < .04). Subcutaneous injection yields lower hCG levels in obese women. Standard-length needles are insufficient to administer i.m. injections in many obese women.