Study suggests that standard dose of GnRH antagonist clears out of obese women's systems more quickly than in normal-weight women.
Study suggests that standard dose of GnRH antagonist clears out of obese women’s systems more quickly than in normal-weight women.
A higher dose of in vitro fertilization (IVF) medication may be needed for obese women to have their eggs successfully harvested, according to the results of a study published online on March 20, 2014, in the Journal of Clinical Endocrinology & Metabolism.
The study examines the impact of obesity on the pharmacokinetics of the GnRH antagonist cetrorelix, while also assessing a known increase in assisted reproductive technology (ART) cycle cancelation rates among obese and overweight women. The researchers found that the GnRH antagonist cleared out of obese women’s system at a more rapid pace than it did in normal-weight women. In addition, half of the obese women in the study experienced a rebound of luteinizing hormone (LH), causing their ovaries to discharge eggs more quickly.
“The findings of this study may be highly relevant to ART protocols because obese women had significantly increased clearance of cetrorelix compared with normal-weight women, resulting in premature recovery of LH after GnRH antagonist suppression less than 14 hours after administration,” the study authors write.
Obese women make up a large percentage of those undergoing ART treatment, with more than one-third of reproductive age women in the United States categorized as obese, according to the study. While the most common reason for a high ART cancelation rate among obese women is poor response to exogenous gonadotropins, the study authors note that a significant portion of cancelled cycles are unexplained.
To determine the speed of medication absorption, researchers gave a dose of cetrorelix to 10 obese and 10 normal-weight women, who then had their blood sampled frequently over a 6-hour period, starting 8 hours after taking the medication. Five of the obese women had an increase in their LH levels during the 14-hour observation period, ranging from 68% to 498%. By contrast, none of the women in the normal weight group had a rebound in LH.
In comparing the obese women who had an LH rebound with the obese women who did not, the researchers identified no differences in terms of age, body mass index, waist and hip circumference, visceral fat, or anti-Mulerian hormone, which is thought to reflect the size of the remaining egg supply.
Those in the obese group were also found to have a significantly decreased distributional half-life of cetrorelix when compared with those in the normal-weight group.
The results of the study are noteworthy in that GnRH antagonists such as cetrorelix are typically used in ART treatments, so the effectiveness of a single dose of these antagonists might be overestimated in obese women, researchers note.
“Our findings indicate obese women may need a different or increased dosing regimen to improve fertility treatment outcomes,” said one of the study’s authors, Nanette Santoro, MD, in a press release. “Given the cost of IVF and stress of infertility, it is important to maximize each woman’s chances of conceiving a child.”