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The Cochrane Database of Systematic... Nov 2014The 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 Review
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. As a consequence, it is suggested that 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 Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, LILACS, the metaRegister of Controlled Trials and reference lists of articles (up to 15 October 2014).
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.Types of outcome measures: live birth rate, clinical pregnancy rate, miscarriage rate, incidence of ovarian hyperstimulation syndrome , incidence of participant-reported side effects, serum oestradiol level on the day of trigger, serum androgen level, and fasting insulin and glucose levels.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the studies, extracted the data according to the protocol and assessed study quality. The overall quality of the evidence was assessed using GRADE methods.
MAIN RESULTS
We included nine randomised controlled trials involving a total of 816 women with PCOS. When metformin was compared with placebo there was no clear evidence of a difference between the groups in live birth rates (OR 1.39, 95% CI 0.81 to 2.40, five RCTs, 551 women, I(2) = 52%, low-quality evidence). Our findings suggest that for a woman with a 32 % chance of achieving a live birth using placebo or other treatment, the corresponding chance using metformin treatment would be between 28% and 53%.When metformin was compared with placebo or no treatment, clinical pregnancy rates were higher in the metformin group (OR 1.52; 95% CI 1.07 to 2.15; eight RCTs, 775 women, I(2) = 18%, moderate-quality evidence). This suggests that for a woman with a 31% chance of achieving a clinical pregnancy using placebo or no treatment, the corresponding chance using metformin treatment would be between 32% and 49%.The risk of ovarian hyperstimulation syndrome was lower in the metformin group (OR 0.29; 95% CI 0.18 to 0.49, eight RCTs, 798 women, I(2) = 11%, moderate-quality evidence). This suggests that for a woman with a 27% risk of having OHSS without metformin the corresponding chance using metformin treatment would be between 6% and 15%.Side effects (mostly gastrointestinal) were more common in the metformin group (OR 4.49, 95% CI 1.88 to 10.72, for RCTs, 431 women, I(2)=57%, low quality evidence)The overall quality of the evidence was moderate for the outcomes of clinical pregnancy, OHSS and miscarriage, and low for other outcomes. The main limitations in the evidence were imprecision and inconsistency.
AUTHORS' CONCLUSIONS
This review found no conclusive evidence that metformin treatment before or during ART cycles improved live birth rates in women with PCOS. However, the use of this insulin-sensitising agent increased clinical pregnancy rates and decreased the risk of OHSS.
Topics: Female; Fertilization in Vitro; Humans; Hyperandrogenism; Hyperinsulinism; Hypoglycemic Agents; Live Birth; Metformin; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic
PubMed: 25406011
DOI: 10.1002/14651858.CD006105.pub3 -
Fertility and Sterility Apr 2022To correlate the distinct diagnostic criteria of polycystic ovary syndrome (PCOS) with the development of maternal and neonatal complications. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To correlate the distinct diagnostic criteria of polycystic ovary syndrome (PCOS) with the development of maternal and neonatal complications.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Pregnant women with PCOS.
INTERVENTION(S)
Maternal and neonatal complications were compared among women with PCOS diagnosed with different criteria.
MAIN OUTCOME MEASURE(S)
The primary outcomes of gestational diabetes mellitus and preeclampsia (PE) were assessed for every diagnostic criterion.
RESULT(S)
Seventy-nine studies were included. Regarding gestational diabetes, the overall pooled prevalence was 14% (95% confidence interval [CI], 11%-18%; I, 97%), reaching the highest level when polycystic ovarian morphology on ultrasound and 1 of the remaining 2 Rotterdam criteria (1/2 Rotterdam criteria) were used (18%; 95% CI, 13%-24%; I, 20%) and the lowest when polycystic morphology on ultrasound and hyperandrogenism were used (3%; 95% CI, 0%-19%; I, not applicable). Regarding PE, the overall pooled prevalence was 5% (95% CI, 4%-7%; I, 82%). The highest PE prevalence was reported when the National Institutes of Health criteria were used (14%; 95% CI, 5%-33%; I, 90%) and the lowest when menstrual irregularities and 1 of the 2 Rotterdam criteria were used (2%; 95% CI, 1%-3%; I, not applicable).
CONCLUSION(S)
The prevalence of gestational diabetes mellitus in pregnant women with PCOS does not differ according to the criteria used; however, women diagnosed with PCOS per the National Institutes of Health criteria are at higher risk of PE.
Topics: Diabetes, Gestational; Female; Humans; Hyperandrogenism; Infant, Newborn; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Ultrasonography
PubMed: 35120743
DOI: 10.1016/j.fertnstert.2021.12.027 -
Frontiers in Endocrinology 2020Decreased bone mineral density (BMD) is a concern in patients with congenital adrenal hyperplasia (CAH) due to lifelong glucocorticoid replacement. Studies till date... (Meta-Analysis)
Meta-Analysis
Decreased bone mineral density (BMD) is a concern in patients with congenital adrenal hyperplasia (CAH) due to lifelong glucocorticoid replacement. Studies till date have yielded conflicting results. We wanted to systematically evaluate the available evidence regarding BMD in adult patients with CAH. We searched Medline, Embase and Cochrane Central Register of Controlled Trials to identify eligible studies. Studies comparing BMD in CAH patients with age- and sex-matched controls were included. Age <16 years and absence of controls were exclusion criteria. Two authors independently reviewed abstracts, read full-text articles, extracted data, assessed risk of bias using Newcastle-Ottawa scale, and determined level of evidence using Grading of Recommendations Assessment, Development, and Evaluation methodology. Nine case-control studies with a total sample of 598 (cases = 254, controls = 344) met eligibility criteria. Median age was 31 years (IQR 23.9-37) and 65.7% were female. Total body BMD (Mean Difference [MD]-0.06; 95%CI -0.07, -0.04), lumbar spine BMD (MD -0.05; 95%CI -0.07, -0.03) and femoral neck BMD (MD -0.07; 95%CI -0.10, -0.05) was lower in cases compared to controls. Lumbar spine -scores (MD -0.86; 95%CI -1.16, -0.56) and -scores (MD -0.66; 95%CI -0.99, -0.32) and femoral neck -scores (MD -0.75 95%CI -0.95, -0.56) and -scores (MD -0.27 95%CI -0.58, 0.04) were lower in cases. BMD in adult patients with CAH was lower compared to controls. Although insufficient data precludes a dose-response relationship between glucocorticoid dose and BMD, it would be prudent to avoid overtreatment with glucocorticoids.
Topics: Adrenal Hyperplasia, Congenital; Bone Density; Bone and Bones; Case-Control Studies; Humans
PubMed: 32903805
DOI: 10.3389/fendo.2020.00493 -
Reproductive Biology and Endocrinology... Dec 2021Several clinical studies showed that statins were potential to treat polycystic ovary syndrome (PCOS). Through comprehensive search PubMed, EMBASE, the Web of Science,... (Meta-Analysis)
Meta-Analysis
Several clinical studies showed that statins were potential to treat polycystic ovary syndrome (PCOS). Through comprehensive search PubMed, EMBASE, the Web of Science, BIOSIS, the ClinialTrails.gov, and the Cochrane Library database up to 14 Feb 2020, we identified the randomized controlled trials about the treatment of statins on hyperandrogenism in PCOS women, and performed a systematic review and meta-analysis. The quality of the included studies was assessed by the Cochrane risk of bias tool and the Jadda score. Subgroup analysis and sensitivity analysis were conducted to analyze the pooled results. Nine trials included 682 PCOS patients were identified. Statins showed a significant potential to reduce testosterone (SMD = -0.47; 95% CI, - 0.76-- 0.18; P = 0.002) and dehydroepiandrosterone (SMD = -0.51; 95% CI, - 0.97-- 0.05; P = 0.03) levels, compared to the control treatments. The cutaneous symptoms hirsutism (SMD = -0.61; 95% CI, - 1.13-- 0.10; P = 0.02) and acne (SMD = -0.92; 95% CI, - 1.49-- 0.34; P = 0.002) were significantly improved by statins in PCOS women. Subgroup analysis showed that the two types of statins, and the different control treatments as well, presented no significantly different effect on testosterone and dehydroepiandrosterone. Sensitivity analysis confirmed the stability of the findings from the meta-analysis. In conclusion, statin treatment could significantly reduce androgen levels and improve cutaneous manifestations of hyperandrogenism of PCOS.
Topics: Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperandrogenism; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic
PubMed: 34930305
DOI: 10.1186/s12958-021-00863-5 -
Endocrine Journal Aug 2022Polycystic ovary syndrome (PCOS) is an endocrine disorder that causes menstrual cycle irregularities and infertility. PCOS is diagnosed based on hyperandrogenism,... (Meta-Analysis)
Meta-Analysis
Polycystic ovary syndrome (PCOS) is an endocrine disorder that causes menstrual cycle irregularities and infertility. PCOS is diagnosed based on hyperandrogenism, polycystic ovarian morphology (PCOM), and an-/oligo-ovulation. Upregulation of anti-Müllerian hormone (AMH) in the serum of women with PCOS may be another suitable alternative diagnostic criterion for PCOM. However, previous meta-analyses have reported conflicting results due to the age-dependent decline in serum AMH levels. Therefore, we performed a meta-analysis to evaluate the threshold of AMH for the diagnosis of PCOS in adolescents and women in their early twenties. Fifteen trials were included in this meta-analysis. PCOS is diagnosed with either Rotterdam criteria, NIH, or AE-PCOS. AMH levels were significantly higher in adolescents with PCOS (weighted mean difference, 3.05; 95% confidence interval: 2.09-4.01) than in the control group. The cutoff values of AMH for the diagnosis of adolescent PCOS were 6.1, 6.26, 7.03, 7.11, 7.2, and 7.25 ng/mL in the studies that reported the usefulness of AMH levels. The summary receiver operating characteristic analysis of the diagnostic accuracy demonstrated that the specificity and sensitivity were 81% and 66.3%, respectively. Our meta-analysis demonstrates that AMH may be a useful diagnostic test for adolescent PCOS and, based on the previous studies included in the meta-analysis, its cutoff value was estimated to be 6-7 ng/mL.
Topics: Adolescent; Anti-Mullerian Hormone; Female; Humans; Hyperandrogenism; Infertility; Peptide Hormones; Polycystic Ovary Syndrome; ROC Curve
PubMed: 35675999
DOI: 10.1507/endocrj.EJ22-0081 -
PloS One 2020Polycystic ovarian syndrome (PCOS) is one of the most prevalent endocrine disorders of women of reproductive age. Treatment plans for this chronic condition frequently...
BACKGROUND
Polycystic ovarian syndrome (PCOS) is one of the most prevalent endocrine disorders of women of reproductive age. Treatment plans for this chronic condition frequently include long-term use of a combination of medication and lifestyle interventions. However, treatment outcomes are dependent on adherence to treatment regimens. This study aimed to systematically review the literature for reported adherence to treatments for PCOS.
METHODS
A systematic search of Embase, Cochrane, PubMed, CINAHL, PsychINFO, SCOPUS, and International Pharmaceutical Abstracts from inception until January 2019 utilizing the terms PCOS, adherence, and patient compliance was conducted. A total of 179 possible articles were identified.
RESULTS
Fourteen articles reporting adherence data were included in the review. Self-report was the most commonly reported method of measuring adherence. Adherence to lifestyle interventions, such as prescribed diets and physical activity, was reported in ten studies and adherence to medications was reported in seven studies, with some reporting both.
CONCLUSIONS
Minimal data are available regarding factors associated with adherence in patients with PCOS. Diverse methods of adherence assessment are utilized. Future studies of PCOS treatments should effectively assess and report adherence data as it is essential to evaluating the effectiveness of PCOS treatments and is critically needed to guide clinician efforts to facilitate optimal outcomes for patients.
Topics: Body Mass Index; Female; Humans; Hyperandrogenism; Insulin Resistance; Life Style; Obesity; Patient Compliance; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Self Report; Testosterone; Treatment Outcome
PubMed: 32053629
DOI: 10.1371/journal.pone.0228586 -
International Journal of Molecular... Nov 2021There is increasing evidence that steroid hormone levels and, especially, androgen levels are elevated in autism. An overactivity of 17, 20-lyase with a higher... (Meta-Analysis)
Meta-Analysis
There is increasing evidence that steroid hormone levels and, especially, androgen levels are elevated in autism. An overactivity of 17, 20-lyase with a higher production of the testosterone precursors dehydroepiandrosterone (DHEA) and androstenedione/androstenediol seems especially present in autism. An encompassing literature analysis was performed, searching for altered androgens in children with autism and using preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Included were all studies published before 31 March 2021 found using the following electronic databases: PubMed, Google Scholar, Cochrane Library, Scopus, and TRIP. Eight studies with boys and three studies with girls where steroid hormone measurements were performed from either plasma, urine, or saliva were found and analyzed. Analyses were performed for DHEA(-S/-C), androstenedione/androstenediol, and testosterone. Effect sizes were calculated for each parameter between mean concentrations for children with autism versus healthy controls. Higher levels of androgens in autism were detected, with the majority of calculated effect sizes being larger than one. We found higher levels of the main testosterone precursors DHEA, androstenedione, and androstenediol, likely causing an additionally higher level of testosterone, and an increased 17, 20-lyase activity is therefore implied. Medications already used in PCOS such as metformin might be considered to treat hyperandrogenism in autism following further research.
Topics: Androgens; Androstenediol; Androstenedione; Autistic Disorder; Child; Child, Preschool; Dehydroepiandrosterone; Female; Humans; Hyperandrogenism; Lyases; Male; Saliva; Testosterone
PubMed: 34830216
DOI: 10.3390/ijms222212324 -
Frontiers in Endocrinology 2023[This corrects the article DOI: 10.3389/fendo.2022.982953.].
[This corrects the article DOI: 10.3389/fendo.2022.982953.].
PubMed: 37842302
DOI: 10.3389/fendo.2023.1269711 -
Frontiers in Endocrinology 2023[This corrects the article DOI: 10.3389/fendo.2022.982953.].
[This corrects the article DOI: 10.3389/fendo.2022.982953.].
PubMed: 37842296
DOI: 10.3389/fendo.2023.1276185 -
Journal of Endocrinological... Jan 2023P450 oxidoreductase (POR) deficiency (PORD) is characterized by congenital adrenal hyperplasia (CAH) and disorders of sex development (DSD) in both sexes. PORD can also... (Review)
Review
BACKGROUND
P450 oxidoreductase (POR) deficiency (PORD) is characterized by congenital adrenal hyperplasia (CAH) and disorders of sex development (DSD) in both sexes. PORD can also associate with skeletal defects. However, the prevalence of these phenotypes is unknown.
AIM
To evaluate the prevalence of CAH, DSD, and infertility of patients with POR gene pathogenic variants by a systematic review of the literature.
METHODS
The literature search was performed through PubMed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases. All studies reporting information on CAH, DSD, testicular adrenal rest tumor (TARTs), and fertility in patients with POR gene pathogenic variants were included. Finally, the prevalence of abnormal phenotypes was calculated.
RESULTS
Of the 246 articles initially retrieved, only 48 were included for a total of 119 (46 males and 73 females) patients with PORD. We also included the case of a male patient who consulted us for CAH and TARTs but without DSD. This patient, found to be a carrier of combined heterozygous POR mutation, reached fatherhood spontaneously. All the patients found had CAH. The presence of DSD was found in 65.2%, 82.1%, and 82.1% of patients with compound heterozygosity, homozygosity, or monoallelic heterozygous variants, respectively. The prevalence was significantly higher in females than in males. The prevalence of TARTs in patients with PORD is 2.7%. Only 5 women with PORD became pregnant after assisted reproductive techniques and delivered a healthy baby. Except for the recently reported proband, no other studies focused on male infertility in patients with POR gene variants.
CONCLUSION
This systematic review of the literature reports the prevalence of CAH, DSD, and TARTs in patients with PORD. The unknown prevalence of POR gene pathogenetic variants and the paucity of studies investigating fertility do not allow us to establish whether PORD is associated with infertility. Further studies on both women and men are needed to clarify this relationship.
Topics: Humans; Pregnancy; Male; Female; Adrenal Hyperplasia, Congenital; Infertility, Male; Mutation; Phenotype; Heterozygote
PubMed: 35842891
DOI: 10.1007/s40618-022-01849-9