Lauren W. Roth

Altered microRNA and gene expression in the follicular fluid of women with polycystic ovary syndrome

PurposeTo determine if microRNAs are differentially expressed in the follicular fluid of women with PCOS compared to fertile oocyte donors and identify associated altered gene expression.MethodsWomen undergoing IVF who met Rotterdam criteria for PCOS or who were fertile oocyte donors were recruited from a private IVF center. Individual follicle fluid was collected at the time of oocyte retrieval. MicroRNA analysis was performed using microarray and validated using real-time PCR on additional samples. Potential gene targets were identified and their expression analyzed by real time PCR.ResultsMicroarray profiling of human follicular fluid revealed expression of 235 miRNAs, 29 were differentially expressed between the groups. Using PCR validation, 5 miRNAs (32, 34c, 135a, 18b, and 9) showed significantly increased expression in the PCOS group. Pathway analysis revealed genes involved in insulin regulation and inflammation. Three potential target genes were found to have significantly decreased expression in the PCOS group (interleukin 8, synaptogamin 1, and insulin receptor substrate 2).ConclusionsMicroRNAs are differentially expressed in the follicular fluid of women with PCOS when compared to fertile oocyte donors. There is also altered expression of potential target genes associated with the PCOS phenotype.

Can we live longer by eating less? A review of caloric restriction and longevity

Caloric restriction, decreasing caloric intake by 20-30%, was first shown to extend life in rats nearly 80 years ago. Since that time, limiting food intake for longevity has been investigated in species from yeast to humans. In yeast and lower animals, caloric restriction has repeatedly been demonstrated to lengthen the life span. Studies of caloric restriction in non-human primates and in humans are ongoing and initial results suggest prolongation of life as well as prevention of age-related disease. There is also data in rodents suggesting that short term caloric restriction has beneficial effects on fertility. Although caloric restriction has many positive effects on health and longevity, quality of life on a restricted diet as well as the ability to maintain that diet long term are concerns that must be considered in humans.

Physicians' perspectives and practices regarding the fertility management of obese patients

To assess the practice patterns and personal beliefs of fertility physicians who care for obese patients seeking assisted reproduction, we conducted a national survey of fertility program directors from both private and academic practices and discovered that although few practices have firm guidelines regarding the management of obese patients, the overwhelming majority of providers believe that body mass index guidelines or cutoffs should exist.

Clomiphene citrate in the management of male infertility.

Clomiphene citrate, a selective estrogen receptor modulator, has been used to treat infertility in women and men for 50 years. In men, clomiphene citrate has been employed in the management of unexplained infertility, oligo and asthenospermia, hypogonadism, and nonobstructive azoospermia. The available evidence reveals mixed results and suggests that clomiphene citrate may be appropriate for the management of male infertility in specific clinical scenarios. Further research is needed to clarify when clomiphene citrate is indicated in the treatment of male infertility.

The correlation between self-reported and measured height, weight, and BMI in reproductive age women

This prospective, cross-sectional study of 60 women compares self-reported height, weight, and BMI with measured values. Self-reported BMI (29.0±8.37 kg/m(2)) was slightly lower than measured BMI (29.1±8.38 kg/m(2)) (p=0.4). Eighty percent of participants reported a BMI in the same category in which their BMI was measured. Pearsons correlation coefficient for height (0.96, p<0.001), weight (0.99, p<0.001), and BMI (0.99, p<0.001) were high. Reproductive age women accurately reported their height and weight.

Predictors of intimate partner violence in women seeking medication abortion

BACKGROUNDnHigh rates of intimate partner violence (IPV) have been reported among women seeking surgical abortion. Women seeking medication abortion differ from surgical abortion patients on many measures. The rate of IPV among medication abortion patients is unknown.nnnSTUDY DESIGNnThe Modified Abuse Assessment Questionnaire was administered to 1128 women at enrollment into a prospective, multicenter medication abortion trial.nnnRESULTSnTwenty-three percent of subjects reported ever experiencing IPV. Women reporting IPV were significantly more likely to be white and less likely to be married. They were more likely to have had previous spontaneous and induced abortions, and were more likely to incorrectly estimate their gestational age (GA).nnnCONCLUSIONnThe rate of IPV in this study was similar to the background US rate. Few demographic variables are predictive of IPV among women seeking medication abortion. Gynecologic variables associated with IPV are consistent with less control over reproductive health.

Evidence of GnRH Antagonist Escape in Obese Women

CONTEXTnAssisted 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.nnnOBJECTIVEnThe objective of the study was to investigate the impact of female obesity on the pharmacokinetics of cetrorelix (GnRH antagonist).nnnDESIGNnThis was an interventional study.nnnSETTINGnThe study was conducted at a university clinical and translational research center.nnnPARTICIPANTSnRegularly menstruating obese (n = 10) and normal-weight (n = 10) women participated in the study.nnnINTERVENTIONSnA frequent blood sampling study was performed after a GnRH antagonist was administered, followed by recombinant LH.nnnMAIN OUTCOMES MEASUREDnPharmacokinetics of cetrorelix in obese vs normal weight women were measured.nnnRESULTSnFive 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).nnnCONCLUSIONSnThe 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.

Luteal Phase Dynamics of Follicle Stimulating and Luteinizing Hormones in Obese and Normal Weight Women

Female obesity is a state of relative hypogonadotrophic hypogonadism. The aim of this study is to examine gonadotrophin secretion and response to gonadotrophin‐releasing hormone (GnRH) in the luteal phase of the menstrual cycle and to investigate the pharmacodynamics and pharmacokinetics of endogenous and exogenous luteinizing hormone (LH) in obese women.

Altering hirsutism through ovulation induction in women with polycystic ovary syndrome

OBJECTIVE: Many women with polycystic ovary syndrome (PCOS) experience infertility and hirsutism and often seek treatment for both concurrently. We investigated whether women who ovulate in response to treatment with clomiphene citrate, metformin, or both would have greater improvement in hirsutism compared with those who did not ovulate. METHODS: This is a secondary analysis evaluating the change in Ferriman-Gallwey score for the hirsute women (n=505 [80.7%]) from the Pregnancy in Polycystic Ovary Syndrome I study. This was a prospective, randomized, doubled-blind trial of 626 women with PCOS and infertility recruited from 12 university sites. They were treated with clomiphene citrate, metformin, or both (combination) for up to six cycles, and hirsutism evaluators were blinded to group assignment. RESULTS: There was a significant decrease in the Ferriman-Gallwey score between baseline and completion of the study in each of the three individual groups (clomiphene citrate, P=.024; metformin, P=.005; combination, P<.001). There was no significant difference in the degree to which the hirsutism score changed when comparing the three groups (P=.44). The change in hirsutism was not associated with the duration of treatment or with the presence or absence of ovulation. CONCLUSION: In infertile hirsute women with PCOS, treatment with clomiphene citrate, metformin, or both for up to six cycles does not alter hirsutism. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00068861. LEVEL OF EVIDENCE: II

Elevated Insulin in Obese Women Relates to Low Endogenous Luteinizing Hormone

INTRODUCTION: Obesity is a state of insulin resistance as it is also a state of relative hypogonadotropic hypogonadism. The physiology behind this is still unclear and may be the result of hypothalamic or pituitary factors or pharmacokinetics of gonadotropins. We sought to investigate if insulin, directly or indirectly, suppresses pituitary luteinizing hormone (LH) secretion. METHODS: A luteal phase frequent blood sampling study was undertaken in regularly menstruating obese (n=10) and normal-weight women (n=10). The study included 12 hours of unstimulated monitoring (to evaluate endogenous hypothalamic–pituitary function) with subsequent administration of intravenous bolus of gonadotropin-releasing hormone (to evaluate pituitary sensitivity). Luteinizing hormone was measured with an immunofluorometric assay. Luteinizing hormone pulsatility was evaluated using an objective, widely accepted method. RESULTS: All women were ovulatory. The obese group was significantly older than the normal weight group (32.5±4.7 compared with 27.3±2.6 years, P=.006). Insulin was significantly higher in the obese group than the normal-weight group (21.5 [14.3–28.7] compared with 11.7 [8.9–14.5] mU/L, P=.01). In the 2-hour postprandial period, there was a rise in insulin that was significantly higher (35.6 [17.1–54.1] compared with 16.5 [8.4–24.7] mU/L, P=.04) and LH that trended lower in the obese women (8.1 [3.5–12.7] compared with 4.2 [2.8–5.6] IU/L) (Figure 1). Composite of mean endogenous luteinizing hormone (LH) (±standard error of mean). CONCLUSIONS: Higher insulin in obese women may be associated with lower endogenous LH output. A direct role of insulin in suppressing pituitary LH secretion should be further investigated.