Weight-Based Dosing in Obese Women May Improve IVF Success

Jennifer Garcia

March 24, 2014

Obese women undergoing in vitro fertilization (IVF) may benefit from weight-based dosing of reproductive hormones used during IVF cycles, according to a study published online March 20 in the Journal of Clinical Endocrinology and Metabolism.

Lauren W. Roth, MD, from the University of Colorado, Aurora, and colleagues evaluated regularly menstruating obese women (n = 10) and normal-weight women (n = 10) with normal baseline prolactin, thyroid-stimulating hormone, and blood count. A single 3-mg dose of a gonadotropin-releasing hormone (GnRH) antagonist (cetrorelix) was administered subcutaneously during the luteal phase of ovulation, and cetrorelix levels in the serum were then measured at 8, 10, and 14 hours postadministration. Beginning 8 hours after cetrorelix administration, blood samples to evaluate luteinizing hormone (LH) levels were drawn every 10 minutes for 6 hours.

The researchers defined obesity as a body mass index (BMI) of 30 kg/m2 or higher. Participants were between 18 and 40 years of age.

Cetrorelix had a decreased distribution half-life in obese women compared with normal-weight women (8.1 ± 1.6 vs 12.7 ± 6.2 h; P = .02). The researchers also found that obese women exhibited increased clearance of cetrorelix compared with normal-weight women (25.8 ± 6.8 vs 20.1 ± 8.3 L/h; P = .058), although the difference did not reach statistical significance.

In addition, 50% of women in the obese group experienced a rebound in their LH levels (defined as an increase of more than 50% from the nadir) during the 14-hour observation period after cetrorelix administration; none of the women in the normal-weight group experienced an LH rebound.

The authors point out that a single dose of cetrorelix should result in LH suppression for 96 hours; however, the duration of effectiveness may be overestimated in obese women. "The altered pharmacokinetics of cetrorelix in obese women may lead to premature ovulation during [assisted reproductive technology], and this could be one of the mechanisms that results in increased cycle cancelation in this group of women," the authors write.

"Up until now there has been no weight-based dosing of [cetrorelix]. This study will need verification, but it now raises the possibility that these standard doses of cetrorelix are not adequate for women with overweight or obesity," J. Michael Gonzalez-Campoy, MD, PhD, medical director of the Minnesota Center for Obesity, Metabolism, and Endocrinology in Eagan and spokesperson for the American Association of Clinical Endocrinologists, told Medscape Medical News.

"The major question that remains unanswered is whether the observations of this study can be independently confirmed in women with overweight or obesity," noted Dr. Gonzalez-Campoy, who was not involved in the study.

The researchers note that women in the obese group were significantly older than women in the normal-weight group but point out that "[a]ge was not a significant covariate for the pharmacokinetic variables in our study." In addition, ovarian reserve parameters and menstrual cycle intervals were similar between the 2 groups.

They also acknowledge limitations of the study, such as the small sample size and nonideal pharmacokinetic sampling times.

"More than one third of reproductive-age women in the United States are obese, and overweight and obese women make up a large percentage of those undergoing ART," Dr. Roth and colleagues write.

"In accordance with the higher gonadotropin requirements for obese women undergoing ART, weight-based dosing of GnRH antagonists may be required," the authors conclude.

Funding for this study was provided by the National Institutes of Health, the Center for the Study of Reproductive Biology, the National Center for Research Resources Colorado Clinical and Translational Science Institute, and the University of Colorado Cancer Center. The study authors and independent commentator have disclosed no relevant financial relationships.

J Clin Endocrinol Metabol. Published online March 20, 2014. Abstract


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