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The Journal of Clinical Endocrinology... Dec 2023Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women...
PURPOSE
Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women globally, with associated cardiometabolic dysfunction. Adipose tissue (AT) dysfunction appears to play an important role in the pathophysiology of PCOS even in patients who do not have excess adiposity.
METHODS
We undertook a systematic review concerning AT dysfunction in PCOS, and prioritized studies that assessed AT function directly. We also explored therapies that targeted AT dysfunction for the treatment of PCOS.
RESULTS
Various mechanisms of AT dysfunction in PCOS were identified including dysregulation in storage capacity, hypoxia, and hyperplasia; impaired adipogenesis; impaired insulin signaling and glucose transport; dysregulated lipolysis and nonesterified free fatty acids (NEFAs) kinetics; adipokine and cytokine dysregulation and subacute inflammation; epigenetic dysregulation; and mitochondrial dysfunction and endoplasmic reticulum and oxidative stress. Decreased glucose transporter-4 expression and content in adipocytes, leading to decreased insulin-mediated glucose transport in AT, was a consistent abnormality despite no alterations in insulin binding or in IRS/PI3K/Akt signaling. Adiponectin secretion in response to cytokines/chemokines is affected in PCOS compared to controls. Interestingly, epigenetic modulation via DNA methylation and microRNA regulation appears to be important mechanisms underlying AT dysfunction in PCOS.
CONCLUSION
AT dysfunction, more than AT distribution and excess adiposity, contributes to the metabolic and inflammation abnormalities of PCOS. Nonetheless, many studies provided contradictory, unclear, or limited data, highlighting the urgent need for additional research in this important field.
Topics: Humans; Female; Adult; Polycystic Ovary Syndrome; Insulin Resistance; Phosphatidylinositol 3-Kinases; Adipose Tissue; Insulin; Cytokines; Obesity; Inflammation; Glucose
PubMed: 37329216
DOI: 10.1210/clinem/dgad356 -
Nutrients Aug 2020Zinc is an essential microelement that plays many important functions in the body. It is crucial for the regulation of cell growth, hormone release, immunological...
Zinc is an essential microelement that plays many important functions in the body. It is crucial for the regulation of cell growth, hormone release, immunological response and reproduction. This review focuses on its importance in the reproductive system of women of reproductive and postmenopausal ages, not including its well described role in pregnancy. Only recently, attention has been drawn to the potential role of zinc in polycystic ovary syndrome (PCOS), dysmenorrhea, or endometriosis. This review is mainly based on 36 randomized, controlled studies on reproductive, pre- and post-menopausal populations of women and on research trying to explain the potential impact of zinc and its supplementation in the etiology of selected female reproductive system disorders. In women with PCOS, zinc supplementation has a positive effect on many parameters, especially those related to insulin resistance and lipid balance. In primary dysmenorrhea, zinc supplementation before and during each menstrual cycle seems to be an important factor reducing the intensity of menstrual pain. On the other hand, little is known of the role of zinc in endometriosis and in postmenopausal women. Therefore, further studies explaining the potential impact of zinc and its supplementation on female reproductive system would be highly advisable and valuable.
Topics: Adult; Dietary Supplements; Dysmenorrhea; Endometriosis; Female; Humans; Insulin Resistance; Lipid Metabolism; Male; Menstrual Cycle; Polycystic Ovary Syndrome; Pregnancy; Reproduction; Zinc
PubMed: 32824334
DOI: 10.3390/nu12082464 -
Medicine Apr 2020Polycystic ovary syndrome (PCOS) affects reproductive-aged women and is associated with increased prevalence of serious clinical problems including: reproductive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polycystic ovary syndrome (PCOS) affects reproductive-aged women and is associated with increased prevalence of serious clinical problems including: reproductive implications, metabolic dysfunction, and cardiovascular risk. Physical activity offers several health benefits for women with PCOS. The aim of this systematic review was to synthesize evidence on the effect of different types of exercise on reproductive function and body composition for women with PCOS.
METHODS
This was a systematic review and meta-analysis of randomized controlled trials (RCTs) following recommended review methods. We searched 6 databases: Cumulative Index of Nursing and Allied Health Literature; Embase; MEDLINE (via Ovid); PubMed; Sport Discus; and Web of Science; and we developed search strategies using a combination of Medical Subject Headings terms and text words related to exercise interventions for women with PCOS. There was no restriction on language or publication year. The search was conducted on April 16, 2019 and updated on November 15, 2019. Two authors independently screened citations, determined risk of bias and quality of evidence with Grading of Recommendations Assessment, Development and Evaluation. We conducted meta-analyses following recommended guidelines, and report results using standardized mean difference (SMD).
RESULTS
Ten RCTs (n = 533) were included in this review. Studies tested the following interventions: aerobic, resistance, and combined (aerobic/resistance) training programs. Most studies were small (average 32, range 15-124 participants), and of relatively short duration (8-32 weeks). There was high heterogeneity for outcomes of reproductive function (menstrual cycle, ovulation, and fertility). We noted low certainty evidence for little to no effect of exercise on reproductive hormones and moderate certainty evidence that aerobic exercise reduced body mass index (BMI) in women with PCOS: BMI SMD -0.35, 95% confidence interval -0.56 to -0.14, P = .001.
CONCLUSION
For women with PCOS, evidence is limited to discern the effect of exercise on major health outcomes (e.g., reproductive function). There is moderate certainty evidence that aerobic exercise alone is beneficial for reducing BMI in women with PCOS. Future studies should be conducted with longer duration, larger sample sizes, and should provide detailed information on menstrual cycle and fertility outcomes.PROSPERO Systematic review registration: 2017 CRD42017058869.
Topics: Exercise Therapy; Female; Humans; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic
PubMed: 32311937
DOI: 10.1097/MD.0000000000019644 -
BMC Medicine Aug 2023The results of human observational studies on the correlation between gut microbiota perturbations and polycystic ovary syndrome (PCOS) have been contradictory. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The results of human observational studies on the correlation between gut microbiota perturbations and polycystic ovary syndrome (PCOS) have been contradictory. This study aimed to perform the first systematic review and meta-analysis to evaluate the specificity of the gut microbiota in PCOS patients compared to healthy women.
METHODS
Literature through May 22, 2023, was searched on PubMed, Web of Science, Medline, Embase, Cochrane Library, and Wiley Online Library databases. Unreported data in diversity indices were filled by downloading and processing raw sequencing data. Systematic review inclusion: original studies were eligible if they applied an observational case-control design, performed gut microbiota analysis and reported diversity or abundance measures, sampled general pre-menopausal women with PCOS, and are longitudinal studies with baseline comparison between PCOS patients and healthy females. Systematic review exclusion: studies that conducted interventional or longitudinal comparisons in the absence of a control group. Two researchers made abstract, full-text, and data extraction decisions, independently. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodologic quality. Hedge's g standardized mean difference (SMD), confidence intervals (CIs), and heterogeneity (I) for alpha diversity were calculated. Qualitative syntheses of beta-diversity and microbe alterations were performed.
RESULTS
Twenty-eight studies (n = 1022 patients, n = 928 control) that investigated gut microbiota by collecting stool samples were included, with 26 and 27 studies having provided alpha-diversity and beta-diversity results respectively. A significant decrease in microbial evenness and phylogenetic diversity was observed in PCOS patients when compared with control participants (Shannon index: SMD = - 0.27; 95% CI, - 0.37 to - 0.16; phylogenetic diversity: SMD = - 0.39; 95% CI, -- 0.74 to - 0.03). We also found that reported beta-diversity was inconsistent between studies. Despite heterogeneity in bacterial relative abundance, we observed depletion of Lachnospira and Prevotella and enrichment of Bacteroides, Parabacteroides, Lactobacillus, Fusobacterium, and Escherichia/Shigella in PCOS. Gut dysbiosis in PCOS, which might be characterized by the reduction of short-chain fatty acid (SCFA)-producing and bile-acid-metabolizing bacteria, suggests a shift in balance to favor pro-inflammatory rather than anti-inflammatory bacteria.
CONCLUSIONS
Gut dysbiosis in PCOS is associated with decreased diversity and alterations in bacteria involved in microbiota-host crosstalk.
TRIAL REGISTRATION
PROSPERO registration: CRD42021285206, May 22, 2023.
Topics: Humans; Female; Gastrointestinal Microbiome; Polycystic Ovary Syndrome; Dysbiosis; Phylogeny; Microbiota
PubMed: 37559119
DOI: 10.1186/s12916-023-02975-8 -
The Cochrane Database of Systematic... Dec 2020The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation (IVF) cycles has been widely studied. Metformin reduces hyperinsulinaemia and suppresses the excessive ovarian production of androgens. It is suggested that as a consequence metformin could improve assisted reproductive techniques (ART) outcomes, such as ovarian hyperstimulation syndrome (OHSS), pregnancy, and live birth rates.
OBJECTIVES
To determine the effectiveness and safety of metformin as a co-treatment during IVF or intracytoplasmic sperm injection (ICSI) in achieving pregnancy or live birth in women with PCOS.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL via the Cochrane Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, LILACS, the trial registries for ongoing trials, and reference lists of articles (from inception to 13 February 2020).
SELECTION CRITERIA
Types of studies: randomised controlled trials (RCTs) comparing metformin treatment with placebo or no treatment in women with PCOS who underwent IVF or ICSI treatment.
TYPES OF PARTICIPANTS
women of reproductive age with anovulation due to PCOS with or without co-existing infertility factors. Types of interventions: metformin administered before and during IVF or ICSI treatment.
PRIMARY OUTCOME MEASURES
live birth rate, incidence of ovarian hyperstimulation syndrome.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the studies, extracted the data according to the protocol, and assessed study quality. We assessed the overall quality of the evidence using the GRADE approach.
MAIN RESULTS
This updated review includes 13 RCTs involving a total of 1132 women with PCOS undergoing IVF/ICSI treatments. We stratified the analysis by type of ovarian stimulation protocol used (long gonadotrophin-releasing hormone agonist (GnRH-agonist) or short gonadotrophin-releasing hormone antagonist (GnRH-antagonist)) to determine whether the type of stimulation used influenced the outcomes. We did not perform meta-analysis on the overall (both ovarian stimulation protocols combined) data for the outcomes of live birth and clinical pregnancy rates per woman because of substantial heterogeneity. In the long protocol GnRH-agonist subgroup, the pooled evidence showed that we are uncertain of the effect of metformin on live birth rate per woman when compared with placebo/no treatment (risk ratio (RR) 1.30, 95% confidence interval (CI) 0.94 to 1.79; 6 RCTs; 651 women; I = 47%; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 28%, the chance following metformin would be between 27% and 51%. Only one study used short protocol GnRH-antagonist and reported live birth rate. Metformin may reduce live birth rate compared with placebo/no treatment (RR 0.48, 95% CI 0.29 to 0.79; 1 RCT; 153 women; low-quality evidence). This suggests that if the chance for live birth following placebo/no treatment is 43%, the chance following metformin would be between 13% and 34% (short GnRH-antagonist protocol). We found that metformin may reduce the incidence of OHSS (RR 0.46, 95% CI 0.29 to 0.72; 11 RCTs; 1091 women; I = 38%; low-quality evidence). This suggests that for a woman with a 20% risk of OHSS without metformin, the corresponding risk using metformin would be between 6% and 14%. Using long protocol GnRH-agonist stimulation, metformin may increase clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.32, 95% CI 1.08 to 1.63; 10 RCTs; 915 women; I = 13%; low-quality evidence). Using short protocol GnRH-antagonist, we are uncertain of the effect of metformin on clinical pregnancy rate per woman compared with placebo/no treatment (RR 1.38, 95% CI 0.21 to 9.14; 2 RCTs; 177 women; I = 87%; very low-quality evidence). We are uncertain of the effect of metformin on miscarriage rate per woman when compared with placebo/no treatment (RR 0.86, 95% CI 0.56 to 1.32; 8 RCTs; 821 women; I = 0%; low-quality evidence). Metformin may result in an increase in side effects compared with placebo/no treatment (RR 3.35, 95% CI 2.34 to 4.79; 8 RCTs; 748 women; I = 0%; low-quality evidence). The overall quality of evidence ranged from very low to low. The main limitations were inconsistency, risk of bias, and imprecision.
AUTHORS' CONCLUSIONS
This updated review on metformin versus placebo/no treatment before or during IVF/ICSI treatment in women with PCOS found no conclusive evidence that metformin improves live birth rates. In a long GnRH-agonist protocol, we are uncertain whether metformin improves live birth rates, but metformin may increase the clinical pregnancy rate. In a short GnRH-antagonist protocol, metformin may reduce live birth rates, although we are uncertain about the effect of metformin on clinical pregnancy rate. Metformin may reduce the incidence of OHSS but may result in a higher incidence of side effects. We are uncertain of the effect of metformin on miscarriage rate per woman.
Topics: Abortion, Spontaneous; Bias; Confidence Intervals; Female; Fertilization in Vitro; Humans; Hyperandrogenism; Hyperinsulinism; Hypoglycemic Agents; Live Birth; Metformin; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Placebos; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic
PubMed: 33347618
DOI: 10.1002/14651858.CD006105.pub4 -
Human Reproduction (Oxford, England) Jun 2023What is the influence of body composition during childhood, adolescence, and adulthood, as well as metabolic parameters, on incident polycystic ovary syndrome (PCOS)? (Meta-Analysis)
Meta-Analysis
STUDY QUESTION
What is the influence of body composition during childhood, adolescence, and adulthood, as well as metabolic parameters, on incident polycystic ovary syndrome (PCOS)?
SUMMARY ANSWER
Excess body fat, even during childhood/adolescence, and metabolic parameters, suggestive of hyperinsulinaemia/insulin resistance, significantly impact the risk of PCOS in a linear fashion.
WHAT IS KNOWN ALREADY
Observational and Mendelian randomization (MR) data have demonstrated an association between adulthood overweight/obesity and development of PCOS. However, the contribution of body composition in childhood/adolescence to incident PCOS is unclear, as is the influence of childhood overweight/obesity.
STUDY DESIGN, SIZE, DURATION
We conducted a systematic review and meta-analysis and integrated our results with a previously published systematic review. Two blinded investigators screened abstracts published between November 2010 and May 2021. Furthermore, we incorporated summary statistics from genome-wide association study (GWAS) data in subjects of European ancestry. Adult overweight was defined as BMI ≥ 25 kg/m2 and obesity as BMI ≥ 30 kg/m2; in Asian subjects, overweight was defined as BMI ≥ 23 kg/m2 and obesity as BMI ≥ 25 kg/m2.
PARTICIPANTS/MATERIALS, SETTING, METHODS
We utilized meta-analysis and MR together to allow synthesis of genetic and observational data. For the systematic review, the search revealed 71 studies, of which 63 were included in meta-analysis by calculating odds ratios (ORs) using the random-effects model. Furthermore, we conducted a two-sample MR study of GWAS data to determine the impact of childhood and adult body size (defined categorically by BMI and childhood body size proportions), abnormal body composition and metabolic parameters (higher fasting serum insulin or lower sex hormone-binding globulin (SHBG) concentration) on the odds of incident PCOS via the inverse-variance weighted method.
MAIN RESULTS AND THE ROLE OF CHANCE
Significant associations were shown between body composition and PCOS incidence. From the systematic review/meta-analysis, women with overweight (OR 3.80, 2.87-5.03), obesity (OR 4.99, 3.74-6.67), and central obesity (OR 2.93, 2.08-4.12) had increased odds of PCOS. For adolescents with overweight and/or obesity, the PCOS odds were greater than for adults. From MR, for every standard deviation increase in BMI (4.8 kg/m2), the odds of PCOS increased by 2.76 (2.27-3.35). Childhood body size had an independent effect on PCOS odds after adjusting for adult body size (OR: 2.56, 1.57-4.20). Genetically determined body fat percentage (OR 3.05, 2.24-4.15), whole body fat mass (OR 2.53, 2.04-3.14), fasting serum insulin (OR 6.98, 2.02-24.13), and SHBG concentration (OR 0.74, 0.64-0.87) were all significantly associated with PCOS in a linear relation.
LIMITATIONS, REASONS FOR CAUTION
The meta-analysis included studies which were cross-sectional and retrospective, limiting our ability to determine causality. MR was limited by interrogating subjects only of European ancestry and including cases classified by either self-diagnosis or diagnostic criteria.
WIDER IMPLICATIONS OF THE FINDINGS
Our study demonstrates for the first time a critical role of the impact of excess childhood/adolescent adiposity on the pathophysiology of adult PCOS. Our results, driven by genetically determined childhood/adolescent body composition, higher BMI, hyperinsulinaemia, and lower SHBG, clearly favour obesity driving the metabolic, but not reproductive, PCOS phenotype. Overall, effective weight maintenance, even from the early years, is likely to reduce the risk of this reproductive endocrine disorder.
STUDY FUNDING/COMPETING INTEREST(S)
S.S.Z. was funded by a National Institute for Health and Care Research (NIHR) Academic Clinical Lectureship. U.A. is chair of the NIHR Steering Committee Trial-CASSANDRA-DN. No other authors declare any sources of funding or relevant conflicts of interest. The authors declare that the research was conducted in the absence of any commercial or financial relations that could be construed as a potential conflict of interest.
TRIAL REGISTRATION NUMBER
N/A.
Topics: Humans; Female; Polycystic Ovary Syndrome; Overweight; Adiposity; Retrospective Studies; Genome-Wide Association Study; Mendelian Randomization Analysis; Body Mass Index; Obesity; Insulin Resistance; Insulins
PubMed: 37015099
DOI: 10.1093/humrep/dead053 -
The Cochrane Database of Systematic... Sep 2022Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 5% to 20% of... (Review)
Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 5% to 20% of women worldwide and often leads to anovulatory infertility. Aromatase inhibitors (AIs) are a class of drugs that were introduced for ovulation induction in 2001. Since about 2001 clinical trials have reached differing conclusions as to whether the AI, letrozole, is at least as effective as the first-line treatment clomiphene citrate (CC), a selective oestrogen receptor modulator (SERM).
OBJECTIVES
To evaluate the effectiveness and safety of AIs (letrozole) (with or without adjuncts) compared to SERMs (with or without adjuncts) for infertile women with anovulatory PCOS for ovulation induction followed by timed intercourse or intrauterine insemination.
SEARCH METHODS
We searched the following sources, from their inception to 4 November 2021, to identify relevant randomised controlled trials (RCTs): the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase and PsycINFO. We also checked reference lists of relevant trials, searched the trial registers and contacted experts in the field for any additional trials. We did not restrict the searches by language or publication status.
SELECTION CRITERIA
We included all RCTs of AIs used alone or with other medical therapies for ovulation induction in women of reproductive age with anovulatory PCOS.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, extracted the data and assessed risks of bias using RoB 1. We pooled trials where appropriate using a fixed-effect model to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for most outcomes, and risk differences (RDs) for ovarian hyperstimulation syndrome (OHSS). The primary outcomes were live birth rate and OHSS rate. Secondary outcomes were clinical pregnancy, miscarriage and multiple pregnancy rates. We assessed the certainty of the evidence for each comparison using GRADE methods.
MAIN RESULTS
This is a substantive update of a previous review; of six previously included trials, we excluded four from this update and moved two to 'awaiting classification' due to concerns about validity of trial data. We included five additional trials for this update that now includes a total of 41 RCTs (6522 women). The AI, letrozole, was used in all trials. Letrozole compared to SERMs with or without adjuncts followed by timed intercourse Live birth rates were higher with letrozole (with or without adjuncts) compared to SERMs followed by timed intercourse (OR 1.72, 95% CI 1.40 to 2.11; I = 0%; number needed to treat for an additional beneficial outcome (NNTB) = 10; 11 trials, 2060 participants; high-certainty evidence). This suggests that in women with a 20% chance of live birth using SERMs, the live birth rate in women using letrozole with or without adjuncts would be 27% to 35%. There is high-certainty evidence that OHSS rates are similar with letrozole or SERMs (0.5% in both arms: risk difference (RD) -0.00, 95% CI -0.01 to 0.01; I = 0%; 10 trials, 1848 participants; high-certainty evidence). There is evidence for a higher pregnancy rate in favour of letrozole (OR 1.69, 95% CI 1.45 to 1.98; I = 0%; NNTB = 10; 23 trials, 3321 participants; high-certainty evidence). This suggests that in women with a 24% chance of clinical pregnancy using SERMs, the clinical pregnancy rate in women using letrozole with or without adjuncts would be 32% to 39%. There is little or no difference between treatment groups in the rate of miscarriage per pregnancy (25% with SERMs versus 24% with letrozole: OR 0.94, 95% CI 0.66 to 1.32; I = 0%; 15 trials, 736 participants; high-certainty evidence) and multiple pregnancy rate (2.2% with SERMs versus 1.6% with letrozole: OR 0.74, 95% CI 0.42 to 1.32; I = 0%; 14 trials, 2247 participants; high-certainty evidence). However, a funnel plot showed mild asymmetry, indicating that some trials in favour of SERMs might be missing. Letrozole compared to laparoscopic ovarian drilling (LOD) One trial reported very low-certainty evidence that live birth rates may be higher with letrozole compared to LOD (OR 2.07, 95% CI 0.99 to 4.32; 1 trial, 141 participants; very low-certainty evidence). This suggests that in women with a 22% chance of live birth using LOD with or without adjuncts, the live birth rate in women using letrozole with or without adjuncts would be 24% to 47%. No trial reported OHSS rates. Due to the low-certainty evidence we are uncertain if letrozole improves pregnancy rates compared to LOD (OR 1.47, 95% CI 0.95 to 2.28; I² = 0%; 3 trials, 367 participants; low-certainty evidence). This suggests that in women with a 29% chance of clinical pregnancy using LOD with or without adjuncts, the clinical pregnancy rate in women using letrozole with or without adjuncts would be 28% to 45%. There seems to be no evidence of a difference in miscarriage rates per pregnancy comparing letrozole to LOD (OR 0.65, 95% CI 0.22 to 1.92; I² = 0%; 3 trials, 122 participants; low-certainty evidence). This also applies to multiple pregnancies (OR 3.00, 95% CI 0.12 to 74.90; 1 trial, 141 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Letrozole appears to improve live birth rates and pregnancy rates in infertile women with anovulatory PCOS, compared to SERMs, when used for ovulation induction, followed by intercourse. There is high-certainty evidence that OHSS rates are similar with letrozole or SERMs. There was high-certainty evidence of no difference in miscarriage rate and multiple pregnancy rate. We are uncertain if letrozole increases live birth rates compared to LOD. In this update, we added good quality trials and removed trials with concerns over data validity, thereby upgrading the certainty of the evidence base.
Topics: Abortion, Spontaneous; Anovulation; Aromatase Inhibitors; Clomiphene; Female; Fertility Agents, Female; Humans; Infertility, Female; Letrozole; Live Birth; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Selective Estrogen Receptor Modulators
PubMed: 36165742
DOI: 10.1002/14651858.CD010287.pub4 -
Reproductive Biomedicine Online Aug 2019This meta-analysis aimed to evaluate the efficacy and safety of glucagon-like peptide 1 (GLP-1) receptor agonists for women with polycystic ovary syndrome (PCOS) by... (Comparative Study)
Comparative Study Meta-Analysis
This meta-analysis aimed to evaluate the efficacy and safety of glucagon-like peptide 1 (GLP-1) receptor agonists for women with polycystic ovary syndrome (PCOS) by comparing their effect with that of metformin. Electronic databases (PubMed, EMBASE, Cochrane Library, WanFang Database, CNKI) dating from their establishment to June 2018 were searched to find all randomized controlled trials (RCTs) reporting the efficacy of GLP-1 receptor agonists versus metformin for patients with PCOS. Therapeutic variables included menstrual cycle, sex hormone and clinical manifestations, glucose metabolism and other metabolic indexes. Eight RCTs among 462 related articles were included in the meta-analysis. Compared with metformin, GLP-1 receptor agonists were more effective in improving insulin sensitivity (standard mean difference [SMD] -0.40, 95% confidence interval [CI] -0.74 to -0.06, P = 0.02) and reducing body mass index (SMD -1.02, 95% CI -1.85 to -0.19, P = 0.02) and abdominal girth (SMD -0.45, 95% CI -0.89 to -0.00, P = 0.05). GLP-1 receptor agonists were associated with a higher incidence of nausea and headache than metformin, but there were no significant differences in other data. Therefore, compared with metformin, GLP-1 receptor agonists might be a good choice for obese patients with PCOS, especially those with insulin resistance. The available evidence is, however, inconclusive given its moderate to low quality. More high-quality research is needed to assess the efficacy of a GLP-1 receptor agonist on women with PCOS.
Topics: Adult; Androgens; Blood Glucose; Female; Glucagon-Like Peptide-1 Receptor; Homeostasis; Humans; Metformin; Obesity; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Reproducibility of Results; Sample Size; Testosterone; Treatment Outcome; Young Adult
PubMed: 31229399
DOI: 10.1016/j.rbmo.2019.04.017 -
Scientific Reports Mar 2022Gonadotropin-releasing hormone (GnRH) analogues are commonly used in clinical practice to prevent premature luteinizing hormone (LH) surge during In-Vitro Fertilization/... (Meta-Analysis)
Meta-Analysis
Gonadotropin-releasing hormone (GnRH) analogues are commonly used in clinical practice to prevent premature luteinizing hormone (LH) surge during In-Vitro Fertilization/ Intra-Cytoplasmic Sperm Injection (IVF/ICSI) cycles. This review aimed to summarize the available evidence comparing the effects of conventional GnRH antagonist protocols, the most commonly used GnRH antagonist protocols, and GnRH agonist protocols on IVF/ICSI outcomes in women with polycystic ovary syndrome (PCOS). A comprehensive electronic search was carried out in Pubmed, Cochrane CENTRAL, Scopus, Web of Science, CINAHL, TRIP, ClinicalTrials.gov and ISRCTN registry from inception until 24 November 2020 without any language or date restrictions. In addition, reference lists of eligible studies and previous meta-analyses were hand-searched to identify relevant studies. Eligible randomized controlled trials were those designed to compare the effects of conventional GnRH antagonist protocols and GnRH agonist protocols on IVF/ICSI outcomes in PCOS subjects. The Cochrane ROB 2.0 tool was used to assess the risk of bias of each study, and the GRADE assessment was used to evaluate the overall quality of evidence. Data synthesis and analyses were done using Review Manager 5.3 with the assistance of Revman Web. A random-effects model was used for all meta-analysis. Dichotomous outcomes were reported as Relative Risk (RR) and continuous outcomes as Weighted Mean Difference (WMD), both with 95% CIs. The primary outcomes were Live birth rate, Ongoing pregnancy rate, and Ovarian hyperstimulation syndrome (OHSS) rate. Other IVF outcomes were considered secondary outcomes. We included ten studies with 1214 randomized PCOS women. Using GnRH antagonist protocols led to a significantly lower OHSS rate (RR = 0.58; 95% CI: [0.44 to 0.77], P = 0.0002), shorter stimulation duration (WMD = - 0.91; 95% CI: [-1.45 to - 0.37] day, P = 0.0009), lower gonadotropin consumption (WMD = - 221.36; 95% CI: [- 332.28 to - 110.45] IU, P < 0.0001), lower E2 levels on hCG day (WMD = - 259.21; 95% CI: [- 485.81 to - 32.60] pg/ml, P = 0.02), thinner endometrial thickness on hCG day (WMD = - 0.73; 95% CI: [- 1.17 to - 0.29] mm, P = 0.001), and lower number of retrieved oocytes (WMD = - 1.82; 95% CI: [- 3.48 to - 0.15] oocytes, P = 0.03). However, no significant differences in live birth rate, ongoing pregnancy rate, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate and cycle cancellation rate were seen between the GnRH antagonist protocols and the long GnRH agonist one. Although more cycles were cancelled due to poor ovarian response in the GnRH antagonist protocol (RR = 4.63; 95% CI: [1.49 to 14.41], P = 0.008), similar rates of cancellation due to risk of OHSS were noticed in both groups. The differences in IVF/ICSI outcomes may arise from the different patterns of gonadotropins suppression that the GnRH analogues exhibit during the early follicular phase of IVF/ICSI cycles and the divergent direct impacts of these analogues on ovaries and endometrial receptivity. The main evidence limitation was Imprecision. Conventional GnRH antagonist protocols represent a safer and more cost-effective treatment choice for PCOS women undergoing IVF/ICSI cycles than the standard long GnRH agonist protocol without compromising the IVF/ICSI clinical outcomes. The study had no sources of financial support and was prospectively registered at PROSPERO (International Prospective Register of Systematic Reviews) under registration number (CRD42021242476).
Topics: Clinical Protocols; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Gonadotropins; Hormone Antagonists; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Sperm Injections, Intracytoplasmic
PubMed: 35292717
DOI: 10.1038/s41598-022-08400-z -
The Journal of Clinical Endocrinology... Jan 2024Polycystic ovary syndrome (PCOS) affects more than 1 in 10 women. (Meta-Analysis)
Meta-Analysis
CONTEXT
Polycystic ovary syndrome (PCOS) affects more than 1 in 10 women.
OBJECTIVE
As part of the 2023 International PCOS Guidelines update, comparisons between combined oral contraceptive pills (COCP), metformin, and combination treatment were evaluated.
DATA SOURCES
Ovid Medline, Embase, PsycINFO, All EBM, and CINAHL were searched.
STUDY SELECTION
Women with PCOS included in randomized controlled trials (RCTs).
DATA EXTRACTION
We calculated mean differences and 95% CIs regarding anthropometrics, metabolic, and hyperandrogenic outcomes. Meta-analyses and quality assessment using GRADE were performed.
DATA SYNTHESIS
The search identified 1660 publications; 36 RCTs were included. For hirsutism, no differences were seen when comparing metformin vs COCP, nor when comparing COCP vs combination treatment with metformin and COCP. Metformin was inferior on free androgen index (FAI) (7.08; 95% CI 4.81, 9.36), sex hormone binding globulin (SHBG) (-118.61 nmol/L; 95% CI -174.46, -62.75) and testosterone (0.48 nmol/L; 95% CI 0.32, 0.64) compared with COCP. COCP was inferior for FAI (0.58; 95% CI 0.36, 0.80) and SHBG (-16.61 nmol/L; 95% CI -28.51, -4.71) compared with combination treatment, whereas testosterone did not differ. Metformin lowered insulin (-27.12 pmol/L; 95% CI -40.65, -13.59) and triglycerides (-0.15 mmol/L; 95% CI -0.29, -0.01) compared with COCP. COCP was inferior for insulin (17.03 pmol/L; 95% CI 7.79, 26.26) and insulin resistance (0.44; 95% CI 0.17, 0.70) compared with combination treatment.
CONCLUSIONS
The choice of metformin or COCP treatment should be based on symptoms, noting some biochemical benefits from combination treatment targeting both major endocrine disturbances seen in PCOS (hyperinsulinemia and hyperandrogenism).
Topics: Female; Humans; Metformin; Polycystic Ovary Syndrome; Contraceptives, Oral, Combined; Hypoglycemic Agents; Testosterone; Insulins
PubMed: 37554096
DOI: 10.1210/clinem/dgad465