Effect of Body Weight on Metabolic Hormones and Fatty Acid Metabolism in Follicular Fluid of Women Undergoing In Vitro Fertilization: A Pilot Study.

INTRODUCTION: Obesity is an epidemic affecting more than one-third of adults in the United States. Obese women experience decreased fertility, explained in part by oocyte quality. Since follicular fluid (FF) provides an important microenvironment for oocyte growth, we sought to evaluate the effect of increased body weight on FF levels of 11 metabolic hormones and fatty acid metabolism. METHODS: The FF was collected from 25 women (10 normal weight, 10 overweight, and 5 obese) with diminished ovarian reserve undergoing in vitro fertilization (IVF) following a minimal stimulation protocol. Hormone levels were determined by multiplex immunoassay using the MAGPIX (Luminex, Austin, Texas) instrument. Fatty acid metabolites were determined using gas and ultra-high pressure liquid chromatography coupled with mass spectrometry. RESULTS: Levels of hormones related to glucose and energy homeostasis and regulation of fat stores (insulin, glucagon, glucagon-like peptide-1, C-peptide, and leptin) were increased significantly in FF from obese women compared to FF from nonobese(normal weight and overweight) women. Interestingly, FF levels of branched-chain amino acids (BCAA) isoleucine, leucine, and valine as well as uric acid, isocaproic acid, butanoic acid, tyrosine, threonine, glycine, and methionine correlated positively with body mass index. CONCLUSION: This pilot study demonstrates significant alterations in the FF milieu of obese women undergoing IVF, which may contribute to the decreased fecundity of obese women. Although the impact of this environment on oocyte and embryo development is not fully realized, these changes may also lead to imprinting at the genomic level and long-term sequelae on offspring.

Effect of single-dose ibuprofen on follicular fluid levels of interleukins in poor responders undergoing in vitro fertilization.

Premature follicular rupture during in vitro fertilization (IVF) is a well-known culprit for cycle cancellation. We sought to evaluate whether a single oral dose of ibuprofen will have an effect on the follicular fluid (FF) levels of inflammatory markers involved in ovulation. This is a prospective within-subjects study following nine patients undergoing IVF. Every patient underwent a first cycle of minimal stimulation IVF followed by a second cycle using the same stimulation protocol, except one oral dose of ibuprofen 800 mg was administered 15-18 h post-trigger injection. FF was obtained during oocyte retrievals of both cycles and analyzed for levels of selected inflammatory markers. A total of 27 cytokines and 9 matrix metalloproteinases (MMPs) were tested. Results demonstrate significantly decreased levels of interleukin (IL)-6, IL-8, granulocyte-colony stimulating factor (G-CSF), eotaxin, MMP3, MMP7, MMP12, and MMP13 in FF of cycles where ibuprofen was administered. However, other cytokines levels, such IL-1 and vascular endothelial growth factor (VEGF), were similar with or without ibuprofen. Levels of MMPs described to be involved in ovulation, namely MMP-2 and MMP-9, were either undetectable or unchanged by ibuprofen, respectively. In conclusion, our data show that one dose of ibuprofen administered orally the day after trigger injection revealed a significant impact on the FF inflammatory milieu. Abbreviations: IVF: in vitro fertilization; MMP: matrix metalloproteinase; IL: interleukins; FF: follicular fluid; VEGF: vascular endothelial growth factor; NSAIDS: non-steroidal anti-inflammatories; POR: poor ovarian response; AMH: anti-Mullerian hormone; TAFC: total antral follicle count; HMG: human menopausal gonadotropin; hCG: human chorionic gonadotropin; COX: cyclooxygenase enzymes; PGH2: prostaglandin H2; RANTES: regulated on activation, normal T expressed and secreted; NF-κb: nuclear factor kappa-light-chain-enhancer of activated B cells.

Efficacy of combined contraceptive vaginal ring versus oral contraceptive pills in achieving hypothalamic-pituitary-ovarian axis suppression in egg donor in vitro fertilization cycles.

BACKGROUND: Our study compares the efficacy of the combined contraceptive vaginal ring to oral contraceptive pills (OCPs) for hypothalamic-pituitary-ovarian (HPO) axis suppression in egg donor in vitro fertilization (IVF) cycles. METHODS: Our retrospective cohort study includes patients from the Center for Assisted Reproduction (CARE) in Bedford, Texas undergoing IVF cycles as egg donors from January 2003 through December 2009. Twenty-five and thirty-nine women were treated with OCPs and the combined contraceptive vaginal ring, respectively. Statistical analyses were performed using the SigmaStat Software package (Systat, Chicago, IL). Data were analyzed by t or Mann-whitney test and Chi-square of Fisher exact test. Statistical significance was set at p<0.05. RESULTS: Prior to gonadotropin initiation, endometrial thickness and serum estradiol were 5.6±2.6 mm and 33.6±19.9 pg/ml in the OCP group and 6.0±2.4 mm and 36.6±24.3 pg/ml in the combined contraceptive vaginal ring group, respectively (p=0.49 and p=0.33). Average serum FSH and LH were 1.7±1.9 and 1.7±2.5 mIU/ml in the OCP group and 1.7±1.6 and 1.2±1.4 mIU/ml in the combined contraceptive vaginal ring group, respectively (p=0.45 and p=0.95). No significant differences were found for gonadotropin requirement, peak estradiol, maximal endometrial thickness, number of oocytes retrieved, number of normally fertilized embryos, number of cryopreserved embryos, or live birth rates. CONCLUSION: The combined contraceptive vaginal ring is effective for HPO axis suppression in egg donor IVF cycles and associated with cycle characteristics similar to those observed with OCP treatment. The combined contraceptive vaginal ring may provide an important advantage over OCPs due to improved patient compliance.