A Review of First Line Infertility Treatments and Supporting Evidence in Women with Polycystic Ovary Syndrome.
Ontology highlight
ABSTRACT:
SUBMITTER: Costello M
PROVIDER: S-EPMC6780967 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ObjectiveInsulin resistance has been reported in up to 70% of women with polycystic ovary syndrome (PCOS). Physiologic and genetic data currently implicate post-insulin receptor signaling defects in substrates such as glycogen synthase kinase 3beta (GSK3beta). The AKT2 gene was chosen as a candidate for PCOS because its product affects glucose metabolism and mitogenic signaling, interacts with GSK3beta, and mediates cell survival in the ovary.Research design and methodsSubjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham, and control subjects were recruited from the surrounding community; 287 white women with PCOS and 187 white control subjects were genotyped for four single nucleotide polymorphisms (SNPs) in AKT2. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. SNPs and haplotypes were tested for association with PCOS risk and phenotypic markers of PCOS.ResultsMinor allele carriers of SNPs rs3730051 and rs8100018 had increased odds of PCOS (odds ratio [OR] 2.2, P = 0.004, and 2.4, P = 0.001, respectively). The haplotype T-G-C-T was significantly associated with PCOS (OR 2.0, P = 0.01). Carriers of the risk haplotypes for both AKT2 and GSK3B had a further increased odds of PCOS (OR 3.1, P = 0.005).ConclusionsThese data suggest that polymorphisms in two components of the insulin signaling pathway, AKT2 and GSK3B, are associated with PCOS. The presence of multiple lesions in a single pathway may confer increased risk.
| S-EPMC2584182 | biostudies-literature
Project description:Infertility has been recognized as a civilizational disease. One of the most common causes of infertility is polycystic ovary syndrome (PCOS). Closely interrelated immunometabolic mechanisms underlie the development of this complex syndrome and lead to infertility. The direct cause of infertility in PCOS is ovulation and implantation disorders caused by low-grade inflammation of ovarian tissue and endometrium which, in turn, result from immune and metabolic system disorders. The systemic immune response, in particular the inflammatory response, in conjunction with metabolic disorders, insulin resistance (IR), hyperadrenalism, insufficient secretion of progesterone, and oxidative stress lead not only to cardiovascular diseases, cancer, autoimmunity, and lipid metabolism disorders but also to infertility. Depending on the genetic and environmental conditions as well as certain cultural factors, some diseases may occur immediately, while others may become apparent years after an infertility diagnosis. Each of them alone can be a significant factor contributing to the development of PCOS and infertility. Further research will allow clinical management protocols to be established for PCOS patients experiencing infertility so that a targeted therapy approach can be applied to the factor underlying and driving the "vicious circle" alongside symptomatic treatment and ovulation stimulation. Hence, therapy of fertility for PCOS should be conducted by interdisciplinary teams of specialists as an in-depth understanding of the molecular relationships and clinical implications between the immunological and metabolic factors that trigger reproductive system disorders is necessary to restore the physiology and homeostasis of the body and, thus, fertility, among PCOS patients.
| S-EPMC10295970 | biostudies-literature
Project description:BackgroundClomiphene is the current first-line infertility treatment in women with the polycystic ovary syndrome, but aromatase inhibitors, including letrozole, might result in better pregnancy outcomes.MethodsIn this double-blind, multicenter trial, we randomly assigned 750 women, in a 1:1 ratio, to receive letrozole or clomiphene for up to five treatment cycles, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. The polycystic ovary syndrome was defined according to modified Rotterdam criteria (anovulation with either hyperandrogenism or polycystic ovaries). Participants were 18 to 40 years of age, had at least one patent fallopian tube and a normal uterine cavity, and had a male partner with a sperm concentration of at least 14 million per milliliter; the women and their partners agreed to have regular intercourse with the intent of conception during the study. The primary outcome was live birth during the treatment period.ResultsWomen who received letrozole had more cumulative live births than those who received clomiphene (103 of 374 [27.5%] vs. 72 of 376 [19.1%], P=0.007; rate ratio for live birth, 1.44; 95% confidence interval, 1.10 to 1.87) without significant differences in overall congenital anomalies, though there were four major congenital anomalies in the letrozole group versus one in the clomiphene group (P=0.65). The cumulative ovulation rate was higher with letrozole than with clomiphene (834 of 1352 treatment cycles [61.7%] vs. 688 of 1425 treatment cycles [48.3%], P<0.001). There were no significant between-group differences in pregnancy loss (49 of 154 pregnancies in the letrozole group [31.8%] and 30 of 103 pregnancies in the clomiphene group [29.1%]) or twin pregnancy (3.4% and 7.4%, respectively). Clomiphene was associated with a higher incidence of hot flushes, and letrozole was associated with higher incidences of fatigue and dizziness. Rates of other adverse events were similar in the two treatment groups.ConclusionsAs compared with clomiphene, letrozole was associated with higher live-birth and ovulation rates among infertile women with the polycystic ovary syndrome. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00719186.).
| S-EPMC4175743 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (p<0.030) lipid use as a metabolic substrate during overnight fasting in PCOS compared to normal women. Accompanying urinary analyses showed a trending correlation (p<0.057) between overnight total nitrogen and circulating testosterone in PCOS women, alone. Serum analyzed by NMR spectroscopy following overnight, fast and at 2 h following an oral glucose tolerance test showed that a transient elevation in blood glucose levels decreased circulating levels of lipid, glucose and amino acid metabolic intermediates (acetone, 2-oxocaporate, 2-aminobutyrate, pyruvate, formate, and sarcosine) in PCOS women, whereas the 2 h glucose challenge led to increases in the same intermediates in normal women. These pilot data suggest that PCOS-related inflexibility in fasting-related switching between lipid and carbohydrate/protein utilization for carbon metabolism may contribute to enhanced weight gain.
| S-EPMC3994884 | biostudies-literature
Project description:BackgroundPolycystic ovary syndrome (PCOS) is common and often causes infertility in women of childbearing age. This study adopted the method of bibliometrics to analyze the current research status of research on PCOS and infertility.MethodWe conducted a literature search based on the Science Citation Index Expanded (SCI-E) database. All records of search results were exported and the records were cited r in plain text format to generate source files for analysis. CiteSpace software was then used to analyze the source files. The content of the analysis included: annual changes in the number of publications, the distribution of the countries and institutions of the authors of the literature, the distribution of the journals from which the literature was sourced, the distribution of authors, and the use of keywords.ResultsThere were a total of 2,716 documents retrieved, and the frequency of citations was 86,817. Both the number of documents and the number of citations showed an annually increasing trend. In this field of research, the United States was in a leading position, with many important research institutions and researchers. Emphasis was placed on top-level journals in the field of reproduction and top-level comprehensive journals. The use of keywords changed over time: in recent years, popular keywords included meta-analysis, follicular fluid, oxidative stress, and diagnostic criteria.ConclusionsThere are obvious regional differences in PCOS and infertility research. International cooperation, especially cooperation with developing countries, should be strengthened.
| S-EPMC9011246 | biostudies-literature
Project description:OBJECTIVE:To compare markers of fertility and ovarian reserve between cancer survivors and cancer-free women with and without polycystic ovary syndrome (PCOS). DESIGN:Furthering Understanding of Cancer, Health, and Survivorship in Adult (FUCHSIA) Women's Study-a population-based cohort study. SETTING:Not applicable. PATIENT(S):Female cancer survivors (n = 1,090) aged 22-45 years, diagnosed between ages 20 and 35 years, and at least 2 years after diagnosis; 369 participated in a clinic visit. Three hundred seventy-four reproductive-aged women without cancer also completed a clinic visit. INTERVENTION(S):None. MAIN OUTCOME MEASURE(S):Infertility, time to first pregnancy after cancer diagnosis, and measures of ovarian reserve (antimüllerian hormone [AMH] and antral follicle count [AFC]). RESULTS:Seventy-eight cancer survivors (7.2%) reported a PCOS diagnosis, with 41 receiving gonadotoxic treatment. Survivors with PCOS exposed to gonadotoxic treatment (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.2-4.5) and unexposed (OR 3.4, 95% CI 1.7-6.9) were more likely to report infertility than unexposed survivors without PCOS and were more likely to have fewer children than desired (exposed: OR 2.1, 95% CI 1.0-4.2; unexposed: OR 3.0, 95% CI 1.4-6.8). After adjusting for age, comparison women with PCOS had the highest markers of ovarian reserve (AMH: 2.43 ng/mL, 95% CI 1.22-4.82 ng/mL; AFC: 20.7, 95% CI 15.3-27.8), and cancer survivors without PCOS treated with gonadotoxic agents had the lowest levels (AMH: 0.19 ng/mL, 95% CI 0.14-0.26 ng/mL; AFC: 7.4, 95% CI 6.4-8.5). CONCLUSION(S):Despite having higher AMH and AFC on average after cancer treatment, cancer survivors with PCOS were less likely to meet their reproductive goals compared with survivors without PCOS.
| S-EPMC5866226 | biostudies-literature
Project description:Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation to be of uncertain cause: obesity, insulin resistance, or PCOS itself. The aim of the study was to investigate the WBC (white blood cell) count and CRP (C-reactive protein) concentration in women with PCOS and to determine the factors that affect their concentration. The study included 200 women aged 18-40 with PCOS and 105 healthy women as the control group, recruited in the Department of Gynaecological Endocrinology of Medical University in Warsaw from 2016 to 2018. Each patient underwent clinical, biochemical, and ultrasonographic assessments. WBC and CRP were significantly higher in the PCOS group (Z = -2,353, p = 0,019 and Z = -2,453, p = 0,014). WBC positively correlated with serum insulin at 0, 60, and 120?min during the oral glucose tolerance test (INS0: r = 0,221, p = 0,001; INS1: r = 0,194, p = 0,003; INS2: r = 0,022, p = 0,001), testosterone (r = 0,130, p = 0,046), androstenedione (r = 0,212, p = 0,001), and DHEAS (r = 0,178, p = 0,006) and negatively correlated with progesterone (r = -0,204, p = 0,002), estradiol (r = -0,140, p = 0,032), and SHBG (r = -0,308, p < 0,001). CRP positively correlated with insulin concentration in 0, 60, and 120?min during the oral glucose tolerance test (INS0: r = 0,343, p < 0,001; INS1: r = 0,276, p = 0,001; INS2: r = 0,320, p < 001) and negatively correlated with progesterone (r = -0,194, p = 0,030) and SHBG (-0,244, p = 0,005). We also estimated positive correlation between BMI and serum CRP and WBC concentration. Multiple linear regression analysis showed that CRP values are positively associated with BMI (beta = 0,374, p < 0,001) and insulin level (INS1) (beta = 0,282, p = 0,004); and WBC results are negatively associated with SHGB (beta = -0,284, p < 0,001) but positively associated with testosterone (beta = 0,163, p = 0,024) and BMI (beta = 0,157, p = 0,047). PCOS is associated with increased WBC and CRP concentrations. The main predicting factors of increased CRP are BMI and insulin resistance, but there is also a relationship between WBC count in PCOS and androgen concentration itself so that inflammation may be mediated not only through adiposity but also through increased androgen concentration.
| S-EPMC7079227 | biostudies-literature
Project description: Not available
| S-EPMC6516980 | biostudies-literature
Project description:IntroductionPolycystic ovary syndrome (PCOS) is a common condition characterized by reproductive, hyperandrogenic and dysmetabolic features, and often becomes clinically manifest during adolescence, particularly with weight-gain.Sources of dataPubmed search.Areas of agreementPCOS is heritable and closely associates with obesity (based on data from both epidemiological and genetic studies). Furthermore, insulin resistance forms a central cornerstone of the pathogenesis of PCOS and mediates a close association between obesity and the severity of the phenotypic features of PCOS.Areas of controversyOur understanding of the pathogenesis of PCOS remains incomplete, especially regarding its missing heritability (with only a small fraction having been identified from the genome-wide association studies reported to date), and its developmental origins.Growing pointsA challenge for the future is to explore a role for epigenetic modifications in the development of PCOS, and implications for the in utero environment and novel therapeutic opportunities.
| S-EPMC9494255 | biostudies-literature
Project description:BackgroundPolycystic ovary syndrome (PCOS) affects 8% to 13% of reproductive-aged women and is associated with reproductive and metabolic dysfunction. Obesity worsens the presentation of PCOS and weight management (weight loss, maintenance or prevention of excess weight gain) is proposed as an initial treatment strategy, best achieved through lifestyle changes incorporating diet, exercise and behavioural interventions.ObjectivesTo assess the effectiveness of lifestyle treatment in improving reproductive, anthropometric (weight and body composition), metabolic and quality of life factors in PCOS.Search methodsWe searched the Cochrane Gynaecology and Fertility Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, CINAHL and AMED (date of last search March 2018). We also searched controlled trials registries, conference abstracts, relevant journals, reference lists of relevant papers and reviews, and grey literature databases, with no language restrictions applied.Selection criteriaRandomised controlled trials (RCTs) comparing lifestyle treatment (diet, exercise, behavioural or combined treatments) to minimal or no treatment in women with PCOS.Data collection and analysisTwo authors independently selected trials, assessed evidence quality and risk of bias, and extracted data. Our primary outcomes were live birth, miscarriage and pregnancy. We used inverse variance and fixed-effect models in the meta-analyses. We reported dichotomous outcomes as an odds ratio and continuous outcomes as a mean difference (MD) or standardised mean difference (SMD).Main resultsWe included 15 studies with 498 participants. Ten studies compared physical activity to minimal dietary and behavioural intervention or no intervention. Five studies compared combined dietary, exercise and behavioural intervention to minimal intervention. One study compared behavioural intervention to minimal intervention. Risk of bias varied: eight studies had adequate sequence generation, seven had adequate clinician or outcome assessor blinding, seven had adequate allocation concealment, six had complete outcome data and six were free of selective reporting. No studies assessed the fertility primary outcomes of live birth or miscarriage. No studies reported the secondary reproductive outcome of menstrual regularity, as defined in this review.Lifestyle intervention may improve a secondary (endocrine) reproductive outcome, the free androgen index (FAI) (MD -1.11, 95% confidence interval (CI) -1.96 to -0.26, 6 RCTs, N = 204, I2 = 71%, low-quality evidence). Lifestyle intervention may reduce weight (kg) (MD -1.68 kg, 95% CI -2.66 to -0.70, 9 RCTs, N = 353, I2 = 47%, low-quality evidence). Lifestyle intervention may reduce body mass index (BMI) (kg/m2) (-0.34 kg/m2, 95% CI -0.68 to -0.01, 12 RCTs, N = 434, I2= 0%, low-quality evidence). We are uncertain of the effect of lifestyle intervention on glucose tolerance (glucose outcomes in oral glucose tolerance test) (mmol/L/minute) (SMD -0.02, 95% CI -0.38 to 0.33, 3 RCTs, N = 121, I2 = 0%, low-quality evidence).Authors' conclusionsLifestyle intervention may improve the free androgen index (FAI), weight and BMI in women with PCOS. We are uncertain of the effect of lifestyle intervention on glucose tolerance. There were no studies that looked at the effect of lifestyle intervention on live birth, miscarriage or menstrual regularity. Most studies in this review were of low quality mainly due to high or unclear risk of bias across most domains and high heterogeneity for the FAI outcome.
| S-EPMC6438659 | biostudies-literature