CONTEXT: Assisted reproductive technology (ART) cycle cancelation rates are increased among overweight and obese women; however, the reasons for this are not completely clear. Premature luteinization due to inadequate endogenous gonadotropin suppression is a possibility for this higher risk of cancellation. OBJECTIVE: The objective of the study was to investigate the impact of female obesity on the pharmacokinetics of cetrorelix (GnRH antagonist). DESIGN: This was an interventional study. SETTING: The study was conducted at a university clinical and translational research center. PARTICIPANTS: Regularly menstruating obese (n = 10) and normal-weight (n = 10) women participated in the study. INTERVENTIONS: A frequent blood sampling study was performed after a GnRH antagonist was administered, followed by recombinant LH. MAIN OUTCOMES MEASURED: Pharmacokinetics of cetrorelix in obese vs normal weight women were measured. RESULTS: Five of the obese women (50%) and none of the normal-weight women had a rebound of LH (defined as >50% increase in LH level from nadir) over the 14-hour postdose observation period. The obese group had a significantly decreased distributional half-life of cetrorelix compared with the normal-weight group (8.1 ± 1.6 vs 12.7 ± 6.2 hours, P = .02). The obese group exhibited increased clearance of cetrorelix compared with the normal-weight group (25.8 ± 6.8 vs 20.1 ± 8.3 L/h, P = .058). CONCLUSIONS: The altered pharmacokinetics of cetrorelix in obese women may lead to premature ovulation during ART, and this could be one of the mechanisms that results in increased cycle cancelation in this group of women. In accordance with the higher gonadotropin requirements for obese women undergoing ART, weight-based dosing of GnRH antagonists may be required.
CONTEXT: Assisted reproductive technology (ART) cycle cancelation rates are increased among overweight and obesewomen; however, the reasons for this are not completely clear. Premature luteinization due to inadequate endogenous gonadotropin suppression is a possibility for this higher risk of cancellation. OBJECTIVE: The objective of the study was to investigate the impact of female obesity on the pharmacokinetics of cetrorelix (GnRH antagonist). DESIGN: This was an interventional study. SETTING: The study was conducted at a university clinical and translational research center. PARTICIPANTS: Regularly menstruating obese (n = 10) and normal-weight (n = 10) women participated in the study. INTERVENTIONS: A frequent blood sampling study was performed after a GnRH antagonist was administered, followed by recombinant LH. MAIN OUTCOMES MEASURED: Pharmacokinetics of cetrorelix in obese vs normal weight women were measured. RESULTS: Five of the obesewomen (50%) and none of the normal-weight women had a rebound of LH (defined as >50% increase in LH level from nadir) over the 14-hour postdose observation period. The obese group had a significantly decreased distributional half-life of cetrorelix compared with the normal-weight group (8.1 ± 1.6 vs 12.7 ± 6.2 hours, P = .02). The obese group exhibited increased clearance of cetrorelix compared with the normal-weight group (25.8 ± 6.8 vs 20.1 ± 8.3 L/h, P = .058). CONCLUSIONS: The altered pharmacokinetics of cetrorelix in obesewomen may lead to premature ovulation during ART, and this could be one of the mechanisms that results in increased cycle cancelation in this group of women. In accordance with the higher gonadotropin requirements for obesewomen undergoing ART, weight-based dosing of GnRH antagonists may be required.
Authors: Barbara Luke; Morton B Brown; Stacey A Missmer; Orhan Bukulmez; Richard Leach; Judy E Stern Journal: Fertil Steril Date: 2011-08-06 Impact factor: 7.329
Authors: Justin Chosich; Andrew P Bradford; Amanda A Allshouse; Jane E B Reusch; Nanette Santoro; Irene E Schauer Journal: Obesity (Silver Spring) Date: 2017-02-03 Impact factor: 5.002
Authors: Sarah A Kohn; Angela J Fought; Katherine Kuhn; Kelsey Jones Slogett; Andrew P Bradford; Nanette Santoro; Irene Schauer Journal: J Endocr Soc Date: 2021-11-24
Authors: Ali Abbara; Tia Hunjan; Vu N A Ho; Sophie A Clarke; Alexander N Comninos; Chioma Izzi-Engbeaya; Tuong M Ho; Geoffrey H Trew; Artsiom Hramyka; Tom Kelsey; Rehan Salim; Peter Humaidan; Lan N Vuong; Waljit S Dhillo Journal: Front Endocrinol (Lausanne) Date: 2020-10-06 Impact factor: 5.555