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.

Endometrial stromal cell attachment and matrix homeostasis in abdominal wall endometriomas.

STUDY QUESTION: How does progesterone alter matrix remodeling in abdominal wall endometriomas compared with normal endometrium? SUMMARY ANSWER: Progesterone may prevent attachment of endometrial cells to the abdominal wall, but does not ameliorate abnormal stromal cell responses of abdominal wall endometriomas. WHAT IS KNOWN ALREADY: Menstruation is a tightly orchestrated physiologic event in which steroid hormones and inflammatory cells cooperatively initiate shedding of the endometrium. Abdominal wall endometriomas represent a unique form of endometriosis in which endometrial cells inoculate fascia or dermis at the time of obstetrical or gynecologic surgery. Invasion of endometrium into ectopic sites requires matrix metalloproteinases (MMPs) for tissue remodeling but endometrium is not shed externally. STUDY DESIGN SIZE, DURATION: Observational study in 14 cases and 19 controls. PARTICIPANTS /MATERIALS, SETTING, METHODS: Tissues and stromal cells isolated from 14 abdominal wall endometriomas were compared with 19 normal cycling endometrium using immunohistochemistry, quantitative PCR, gelatin zymography and cell attachment assays. P values < 0.05 were considered significant and experiments were repeated in at least three different cell preps to provide scientific rigor to the conclusions. MAIN RESULTS AND THE ROLE OF CHANCE: The results indicate that MMP2 and MMP9 are not increased by TGFß1 in endometrioma stromal cells. Although progesterone prevents attachment of endometrioma cells to matrix components of the abdominal wall, it does not ameliorate these abnormal stromal cell responses to TGFß1. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: Endometriomas were collected from women identified pre-operatively. Not all endometriomas were collected. Stromal cells from normal endometrium were from different patients, not women undergoing endometrioma resection. WIDER IMPLICATIONS OF THE FINDINGS: This work provides insight into the mechanisms by which progesterone may prevent abdominal wall endometriomas but, once established, are refractory to progesterone treatment. STUDY FUNDING/COMPETING INTEREST(S): Tissue acquisition was supported by NIH P01HD087150. Authors have no competing interests.

In Vitro Fertilization Versus Mild Stimulation Intrauterine Insemination in Women Aged 40 and Older.

INTRODUCTION: The objective of this study was to compare clinical pregnancy rates (PRs) and pregnancy outcomes (POs) in patients undergoing in vitro fertilization (IVF) and a specific controlled ovarian hyperstimulation (mild-stimulation or mini-stim) and intrauterine insemination (IUI) protocol in women older than 40. METHODS: It is a retrospective chart review of 770 cycles of all women aged 40 and older who underwent a first cycle of either IVF or mini-stim IUI between the years 2007 and 2012 at a single infertility center. RESULTS: The PR in all women aged 40 and above was 12% (65/531) for IVF and 5% (13/239) for mini-stim IUI ( P = .004). When divided into age-groups, the PR of IVF at age 40 was superior to that at age 41 and above (15% vs 7%, P = .002), while the PR of mini-stim IUI remains similar (3% vs 7%, P = .307). When comparing the outcomes of the 2 treatments in the different age-groups, it showed that in women aged 40, IVF PR was superior to that of mini-stim IUI (15% vs 3%, P = .032); while in women aged 41 and above, IVF and mini-stim IUI have similar PR (7% vs 7%, P = .866). When POs were compared, the rate of live birth per cycle initiated was 9.2% for IVF versus 1.28% for mini-stim IUI ( P < .001). CONCLUSIONS: While IVF and mini-stim IUI were found to have similar PRs in women aged 41 and above, POs are significantly better in IVF. A larger study is required to clarify the above results.

Has testosterone passed the test in premenopausal women with low libido? A systematic review.

BACKGROUND: There are limited evaluation and treatment options for low libido in premenopausal women. This review sought to evaluate the available evidence supporting the evaluation of testosterone serum levels and testosterone treatment of premenopausal women with low libido. METHODS: MEDLINE, PubMed, and ClinicalTrials.gov were searched for articles that referenced the evaluation of testosterone serum level and/or testosterone treatment on premenopausal women with low libido from 1995 to 2015. Additional references were obtained from the reference sections of other papers and from peer review. Studies that included only postmenopausal women were excluded. A total of 13 studies were reviewed in detail. Nine studies examined the relationship between testosterone serum levels and sexuality, an additional three studies examined the effect of testosterone treatment on premenopausal women with low libido, and one study examined both the topics. RESULTS: Six of the ten testosterone serum evaluation studies failed to show a significant association between testosterone serum level and libido. Only one out of four studies examining testosterone treatment in premenopausal women was able to show any clear improvement in libido; however, the effect was limited to only the intermediate dose of testosterone, with the low and high doses of testosterone not producing any effect. CONCLUSION: The currently available evidence does not support testosterone serum evaluation or treatment in premenopausal women with low libido. Hence, further studies are warranted.

The Labor Games.

OBJECTIVE: To develop and evaluate a simulation laboratory designed to stimulate learning and increase medical students' preparedness for an obstetrics and gynecology clinical clerkship. METHODS: Ninety-seven medical students participated in the games during their obstetrics and gynecology clerkship in 1 year. Using the resident-as-teacher model, students rotated through seven stations, each with a simulated obstetric task. Points were awarded at each station, and the student with the highest score won. Self-perceived proficiency level and general preparedness for the clerkship were evaluated through paired pregame and postgame assessments. RESULTS: Postassessment results showed statistically significant (P<.001) increases in self-perceived competence performing all tested skills including reading fetal heart tracings, knot-tying, measuring cervical dilation, amniotomy, estimating fetal weight, and estimating blood loss. Approximately 97% enjoyed The Labor Games, 97.9% reported increased knowledge, and 96.9% learned valuable skills. Students also reported feeling more prepared for the obstetrics and gynecology rotation (2.6 compared with 3.3, P<.001). DISCUSSION: The Labor Games improved medical students' self-confidence and self-perceived skill level on obstetric tasks. Students also felt more prepared for the obstetrics and gynecology clerkship. This study creates a low-cost and reproducible simulation laboratory that is identified as effective by medical students in teaching skills, knowledge, and preparedness for an obstetrics and gynecology clerkship.