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Ultrasound in Obstetrics & Gynecology :... Jan 2018To compare the impact of clomiphene citrate (CC) vs other drug regimens on mid-cycle endometrial thickness (EMT), ovulation, pregnancy and live birth rates in women with... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVES
To compare the impact of clomiphene citrate (CC) vs other drug regimens on mid-cycle endometrial thickness (EMT), ovulation, pregnancy and live birth rates in women with World Health Organization (WHO) group II ovulatory disorders.
METHODS
We searched MEDLINE, EMBASE, Scopus, Web of Science, The Cochrane Central Register of Clinical Trials (CENTRAL) and the non-MEDLINE subset of PubMed from inception to December 2016 and cross-checked references of relevant articles. We included only randomized controlled trials (RCTs) comparing CC used alone vs other drug regimens for ovulation induction in women with WHO group II anovulation. Outcomes were mid-cycle EMT, ovulation, pregnancy and live birth rates. We pooled weighted mean differences (WMD) with 95% confidence intervals (CI) for continuous variables (EMT) and risk ratios (RR) with 95% CI for binary variables (ovulation, pregnancy and live birth rates).
RESULTS
We retrieved 1718 articles of which 33 RCTs (4349 women, 7210 ovulation induction cycles) were included. In 15 RCTs that compared CC with letrozole, EMT was lower in the CC group (1957 women, 3892 cycles; WMD, -1.39; 95% CI, -2.27 to -0.51; I = 100%), ovulation rates after CC and letrozole were comparable (1710 women, 3217 cycles; RR, 0.97; 95% CI, 0.90-1.04; I = 47%), while CC led to a lower pregnancy rate (1957 women, 3892 cycles; RR, 0.78; 95% CI, 0.63-0.95; I = 43%) and a lower live birth rate (RR, 0.70; 95% CI, 0.49-0.98; I = 35%). In two RCTs that compared CC with CC plus metformin, EMT, ovulation and pregnancy rates were comparable (101 women, 140 cycles; WMD, -0.23; 95% CI, -0.92 to 0.45; I = 78%; RR, 0.84; 95% CI, 0.67-1.06; I = 0%; and RR, 0.79; 95% CI, 0.33-1.87; I = 0%). In three studies that compared CC with CC plus N-acetyl cysteine (NAC), EMT was lower in the CC group (340 women, 300 cycles; WMD, -1.51; 95% CI, -1.98 to -1.04; I = 45%). In two studies that compared CC with CC + nitric oxide (NO) donor, EMT was lower in the CC group (120 women, 304 cycles; WMD, -1.75; 95% CI, -2.08 to -1.41; I = 0%). Compared with CC plus NO donor or NAC, CC showed statistically significant lower ovulation and pregnancy rates. Compared with tamoxifen in three studies, CC showed a tendency towards lower EMT (571 women, 844 cycles; WMD, -1.34; 95% CI, -2.70 to 0.01; I = 96%) with comparable ovulation and pregnancy rates.
CONCLUSIONS
In women with WHO group II ovulatory disorders, ovulation induction with CC might result in lower EMT than other ovulation induction regimens. Whether the lower EMT caused the lower pregnancy and live birth rates remains to be elucidated. Letrozole seems to be beneficial for these women. However, our findings should be interpreted with caution as the quality of evidence was very low. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Anovulation; Birth Rate; Clomiphene; Endometrium; Estrogen Antagonists; Female; Fertility Agents, Female; Humans; Infant, Newborn; Live Birth; Ovulation Induction; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Randomized Controlled Trials as Topic; Tamoxifen
PubMed: 29055102
DOI: 10.1002/uog.18933 -
BJOG : An International Journal of... Feb 2018Polycystic ovary syndrome is a common cause of anovulation and infertility, and a risk factor for development of metabolic syndrome and endometrial cancer. Systematic... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Polycystic ovary syndrome is a common cause of anovulation and infertility, and a risk factor for development of metabolic syndrome and endometrial cancer. Systematic review and meta-analysis of randomised controlled trials (RCT) that evaluated the effects of inositol as an ovulation induction agent. We searched MEDLINE, EMBASE, Cochrane and ISI conference proceedings, Register and Meta-register for RCT and WHO trials' search portal. We included studies that compared inositol with placebo or other ovulation induction agents. Quality of studies was assessed for risk of bias. Results were pooled using random effects meta-analysis and findings were reported as relative risk or standardised mean differences. We included ten randomised trials. A total of 362 women were on inositol (257 on myo-inositol; 105 on di-chiro-inositol), 179 were on placebo and 60 were on metformin. Inositol was associated with significantly improved ovulation rate (RR 2.3; 95% CI 1.1-4.7; I = 75%) and increased frequency of menstrual cycles (RR 6.8; 95% CI 2.8-16.6; I = 0%) compared with placebo. One study reported on clinical pregnancy rate with inositol compared with placebo (RR 3.3; 95% CI 0.4-27.1), and one study compared with metformin (RR 1.5; 95% CI 0.7-3.1). No studies evaluated live birth and miscarriage rates. Inositol appears to regulate menstrual cycles, improve ovulation and induce metabolic changes in polycystic ovary syndrome; however, evidence is lacking for pregnancy, miscarriage or live birth. A further, well-designed multicentre trial to address this issue to provide robust evidence of benefit is warranted.
TWEETABLE ABSTRACT
Inositols improve menstrual cycles, ovulation and metabolic changes in polycystic ovary syndrome.
Topics: Anovulation; Female; Humans; Infertility; Inositol; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Vitamin B Complex
PubMed: 28544572
DOI: 10.1111/1471-0528.14754 -
The European Journal of Contraception &... Jun 2017Hyperandrogenism affects approximately 10-20% of women of reproductive age. Hyperandrogenic skin symptoms such as hirsutism, acne, seborrhea and alopecia are associated... (Review)
Review
INTRODUCTION
Hyperandrogenism affects approximately 10-20% of women of reproductive age. Hyperandrogenic skin symptoms such as hirsutism, acne, seborrhea and alopecia are associated with significant quality of life and psychological impairment. Women with abnormalities in androgen metabolism may have accompanying anovulation and/or polycystic ovary syndrome (PCOS), both of which have reproductive and metabolic implications if left untreated. Cyproterone acetate (CPA), combined with ethinylestradiol (EE), is indicated for the treatment of moderate to severe acne related to androgen-sensitivity (with or without seborrhea) and/or hirsutism, in women of reproductive age.
OBJECTIVE
To review the data on the efficacy and safety of CPA 2 mg/EE 35 μg for the treatment of hyperandrogenic skin symptoms in women.
METHODS
A non-systematic narrative review based on a literature search of the PubMed database.
RESULTS
Seventy-eight studies were identified. The majority of sufficiently powered studies show a high efficacy of CPA 2 mg/EE 35 μg in the treatment of severe acne and hirsutism. Studies show that therapeutic response in women with hirsutism requires a long-term approach and that hyperandrogenic skin symptoms in patients with PCOS are efficiently treated. Additional benefits include cycle control and, in some women, improvement in mood and perception of body image. Safety and tolerability data are summarized by the pharmacovigilance risk assessment committee (PRAC) of the European Medicine's Agency's (EMA).
CONCLUSIONS
This review provides a comprehensive overview about the efficacy of CPA 2 mg/EE 35 μg in the treatment of hyperandrogenic skin symptoms, thus allowing both health care professionals and women to balance the risks and benefits of treatment based on evidence.
Topics: Acne Vulgaris; Adult; Androgen Antagonists; Cyproterone Acetate; Drug Combinations; Ethinyl Estradiol; Female; Hirsutism; Humans; Hyperandrogenism; Skin Diseases; Treatment Outcome
PubMed: 28447864
DOI: 10.1080/13625187.2017.1317339 -
Reproductive Biology and Endocrinology... Feb 2017Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting 9-18% of women in reproductive age that causes hyperandrogenism and infertility due to... (Review)
Review
Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting 9-18% of women in reproductive age that causes hyperandrogenism and infertility due to dysfunctional follicular maturation and anovulation. The etiology of PCOS is still poorly known, and information from experimental animal models may help improve current understanding of the mechanisms of PCOS initiation and development. Therefore, we conducted a systematic review of currently available methods for simulation of PCOS in experimental models, focusing on two main endocrine traits: ovarian morphology changes and circulating levels of sex hormones and gonadotropins.We searched the MEDLINE database for articles in English or Spanish published until October 2016. Of 933 studies identified, 39 were included in the systematic review. One study compared interventions with androgens versus estrogens, 18 used androgen-induced stimulation, 9 used estrogens or drugs with estrogen action, including endocrine disruptors, to induce PCOS-like models, and 12 used miscellaneous interventions. Broad differences were found among the studies concerning hormonal interventions, animal species, and developmental stage at the time of the experiments, and most models resulted in ovarian morphology changes, mainly increases in the number of cystic and antral follicles and decreases in the corpus luteum. Hyperandrogenism was produced by using androgens and other drugs as the stimulatory agent. However, studies using drugs with estrogenic effect did not observe changes in circulating androgens.In conclusion, medium- or long-term testosterone administration in the pre- and postnatal periods performed best for induction of a PCOS-like phenotype, in rhesus macaque and rat models respectively. In rats, postnatal exposure to androgens results in reprogramming of the hypothalamic-pituitary-ovarian-axis. Thus, comparisons between different intervention models may be useful to define the timing of reproductive PCOS phenotypes in experimental animal models.
Topics: Animals; Disease Models, Animal; Female; Gonadal Steroid Hormones; Gonadotropins; Humans; Hyperandrogenism; MEDLINE; Ovary; Polycystic Ovary Syndrome
PubMed: 28183310
DOI: 10.1186/s12958-017-0231-z -
BMJ (Clinical Research Ed.) Jan 2017To compare the effectiveness of alternative first line treatment options for women with WHO group II anovulation wishing to conceive. (Review)
Review
OBJECTIVE
To compare the effectiveness of alternative first line treatment options for women with WHO group II anovulation wishing to conceive.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Cochrane Central Register of Controlled Trials, Medline, and Embase, up to 11 April 2016.
STUDY SELECTION
Randomised controlled trials comparing eight ovulation induction treatments in women with WHO group II anovulation: clomiphene, letrozole, metformin, clomiphene and metformin combined, tamoxifen, gonadotropins, laparoscopic ovarian drilling, and placebo or no treatment. Study quality was measured on the basis of the methodology and categories described in the Cochrane Collaboration Handbook. Pregnancy, defined preferably as clinical pregnancy, was the primary outcome; live birth, ovulation, miscarriage, and multiple pregnancy were secondary outcomes.
RESULTS
Of 2631 titles and abstracts initially identified, 54 trials reporting on 7173 women were included. All pharmacological treatments were superior to placebo or no intervention in terms of pregnancy and ovulation. Compared with clomiphene alone, both letrozole and the combination of clomiphene and metformin showed higher pregnancy rates (odds ratio 1.69, 95% confidence interval 1.33 to 2.14; 1.71, 1.28 to 2.27; respectively). Letrozole led to higher live birth rates when compared with clomiphene alone (1.67, 1.11 to 2.49). Metformin led to lower multiple pregnancy rates compared with clomiphene alone (0.22, 0.05 to 0.93).
CONCLUSIONS
In women with WHO group II anovulation, letrozole and the combination of clomiphene and metformin are superior to clomiphene alone in terms of pregnancy. Compared with clomiphene alone, letrozole is the only treatment showing a significantly higher rate of live birth.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42015027579.
READERS' NOTE
This is the second version of this paper. The original version was corrected following the retraction of two studies and removal of another which were ineligible (references 40, 41, and 75 of the original paper). These studies are not shown in this version. A tracked changes version of the original version is attached as a supplementary file to the correction notice, which explains the issue further.
Topics: Anovulation; Clomiphene; Drug Therapy, Combination; Female; Humans; Infertility, Female; Letrozole; Metformin; Network Meta-Analysis; Nitriles; Ovulation Induction; Pregnancy; Pregnancy Rate; Treatment Outcome; Triazoles
PubMed: 28143834
DOI: 10.1136/bmj.j138 -
The Cochrane Database of Systematic... Jan 2017Clomiphene citrate (CC) is generally considered first-line treatment in women with anovulation due to polycystic ovary syndrome (PCOS). Ovulation induction with... (Meta-Analysis)
Meta-Analysis Review
Metformin during ovulation induction with gonadotrophins followed by timed intercourse or intrauterine insemination for subfertility associated with polycystic ovary syndrome.
BACKGROUND
Clomiphene citrate (CC) is generally considered first-line treatment in women with anovulation due to polycystic ovary syndrome (PCOS). Ovulation induction with follicle-stimulating hormone (FSH; gonadotrophins) is second-line treatment for women who do not ovulate or conceive while taking CC. Metformin may increase the effectiveness of ovulation induction with gonadotrophins and may promote safety by preventing multiple pregnancy.
OBJECTIVES
To determine the effectiveness and safety of metformin co-treatment during ovulation induction with gonadotrophins with respect to rates of live birth and multiple pregnancy in women with PCOS.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility (CGF) Group specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and the Cumulative Index to Nursing and Allied Health Literature (CINAH) on 8 June 2016, and the reference lists of included and other relevant studies. We searched ongoing trials registries in the World Health Organization (WHO) portal and on clinicaltrials.gov on 4 September 2016.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) reporting data on comparison of clinical outcomes in women with PCOS undergoing ovulation induction with gonadotrophins plus metformin versus gonadotrophins alone or gonadotrophins plus placebo.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. Primary review outcomes were live birth rate and multiple pregnancy rate. Secondary outcomes were ovulation rate, clinical pregnancy rate, ovarian hyperstimulation syndrome (OHSS) rate, miscarriage rate, cycle cancellation rate and adverse effects.
MAIN RESULTS
We included five RCTs (with 264 women) comparing gonadotrophins plus metformin versus gonadotrophins. The gonadotrophin used was recombinant FSH in four studies and highly purified FSH in one study. Evidence was of low quality: The main limitations were serious risk of bias due to poor reporting of study methods and blinding of participants and outcome assessors. Live birth Metformin plus FSH was associated with a higher cumulative live birth rate when compared with FSH (odds ratio (OR) 2.31, 95% confidence interval (CI) 1.23 to 4.34; two RCTs, n = 180; I = 0%; low-quality evidence). This suggests that if the chance of live birth after FSH is assumed to be 27%, then the chance after addition of metformin would be between 32% and 60%. Other pregnancy outcomes Metformin use was associated with a higher ongoing pregnancy rate (OR 2.46, 95% CI 1.36 to 4.46; four RCTs, n = 232; I = 0%; low-quality evidence) and a higher clinical pregnancy rate (OR 2.51, 95% CI 1.46 to 4.31; five RCTs, n = 264; I = 0%; low-quality evidence). Multiple pregnancy Results showed no evidence of a difference in multiple pregnancy rates between metformin plus FSH and FSH (OR 0.55, 95% CI 0.15 to 1.95; four RCTs, n = 232; I = 0%; low-quality evidence) and no evidence of a difference in rates of miscarriage or OHSS. Other adverse effects Evidence was inadequate as the result of limited available data on adverse events after metformin compared with after no metformin (OR 1.78, 95% CI 0.39 to 8.09; two RCTs, n = 91; I = 0%; very low-quality evidence).
AUTHORS' CONCLUSIONS
Preliminary evidence suggests that metformin may increase the live birth rate among women undergoing ovulation induction with gonadotrophins. At this moment, evidence is insufficient to show an effect of metformin on multiple pregnancy rates and adverse events. Additional trials are necessary before we can provide further conclusions that may affect clinical practice.
Topics: Coitus; Combined Modality Therapy; Drug Therapy, Combination; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropins; Humans; Infertility, Female; Live Birth; Metformin; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Pregnancy, Multiple; Randomized Controlled Trials as Topic
PubMed: 28118681
DOI: 10.1002/14651858.CD009090.pub2 -
Sports Medicine (Auckland, N.Z.) Aug 2017Infertility has been described as a devastating life crisis for couples, and has a particularly severe effect on women, in terms of anxiety and depression. Anovulation... (Review)
Review
BACKGROUND
Infertility has been described as a devastating life crisis for couples, and has a particularly severe effect on women, in terms of anxiety and depression. Anovulation accounts for around 30% of female infertility, and while lifestyle factors such as physical activity are known to be important, the relationship between exercise and ovulation is multi-factorial and complex, and to date there are no clear recommendations concerning exercise regimes.
OBJECTIVES
The objective of this review was to systematically assess the effect of physical activity on ovulation and to discuss the possible mechanisms by which exercise acts to modulate ovulation in reproductive-age women. This was done with a view to improve existing guidelines for women wishing to conceive, as well as women suffering from anovulatory infertility.
SEARCH METHODS
The published literature was searched up to April 2016 using the search terms ovulation, anovulatory, fertility, sport, physical activity and exercise. Both observational and interventional studies were considered, as well as studies that combined exercise with diet. Case studies and articles that did not report anovulation/ovulation or ovarian morphology as outcomes were excluded. Studies involving administered drugs in addition to exercise were excluded.
RESULTS
In total, ten interventions and four observational cohort studies were deemed relevant. Cohort studies showed that there is an increased risk of anovulation in extremely heavy exercisers (>60 min/day), but vigorous exercise of 30-60 min/day was associated with reduced risk of anovulatory infertility. Ten interventions were identified, and of these three have studied the effect of vigorous exercise on ovulation in healthy, ovulating women, but only one showed a significant disruption of ovulation as a result. Seven studies have investigated the effect of exercise on overweight/obese women suffering from polycystic ovary syndrome (PCOS) or anovulatory infertility, showing that exercise, with or without diet, can lead to resumption of ovulation. The mechanism by which exercise affects ovulation is most probably via modulation of the hypothalamic-pituitary-gonadal (HPG) axis due to increased activity of the hypothalamic-pituitary-adrenal (HPA) axis. In heavy exercisers and/or underweight women, an energy drain, low leptin and fluctuating opioids caused by excess exercise have been implicated in HPA dysfunction. In overweight and obese women (with or without PCOS), exercise contributed to lower insulin and free androgen levels, leading to the restoration of HPA regulation of ovulation.
CONCLUSIONS
Several clear gaps have been identified in the existing literature. Short-term studies of over-training have not always produced the disturbance to ovulation identified in the observational studies, bringing up the question of the roles of longer term training and chronic energy deficit. We believe this merits further investigation in specific cohorts, such as professional athletes. Another gap is the complete absence of exercise-based interventions in anovulatory women with a normal body mass index (BMI). The possibly unjustified focus on weight loss rather than the exercise programme means there is also a lack of studies comparing types of physical activity, intensity and settings. We believe that these gaps are delaying an efficient and effective use of exercise as a therapeutic modality to treat anovulatory infertility.
Topics: Anovulation; Exercise; Female; Humans; Infertility, Female; Ovulation; Polycystic Ovary Syndrome
PubMed: 28035585
DOI: 10.1007/s40279-016-0669-8 -
The Cochrane Database of Systematic... Dec 2016Subfertility due to anovulation is a common problem in women. First-line oral treatment is with antioestrogens such as clomiphene citrate, but resistance may be apparent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Subfertility due to anovulation is a common problem in women. First-line oral treatment is with antioestrogens such as clomiphene citrate, but resistance may be apparent with clomiphene. Alternative and adjunctive treatments have been used including tamoxifen, dexamethasone, and bromocriptine. The effectiveness of these is to be determined.
OBJECTIVES
To determine the relative effectiveness of antioestrogen agents including clomiphene alone or in combination with other medical therapies in women with subfertility associated with anovulation, possibly caused by polycystic ovarian syndrome.
SEARCH METHODS
We conducted a search of the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL (all from inception to August 2016) to identify relevant randomised controlled trials (RCTs). We searched the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs. We also searched the clinical trial registries for ongoing trials (inception until August 2016).
SELECTION CRITERIA
We considered RCTs comparing oral antioestrogen agents for ovulation induction (alone or in conjunction with medical therapies) in anovulatory subfertility. We excluded insulin-sensitising agents, aromatase inhibitors, and hyperprolactinaemic infertility.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed data extraction and quality assessment. The primary outcome was live birth; secondary outcomes were pregnancy, ovulation, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome, and adverse effects.
MAIN RESULTS
This is a substantive update of a previous review. We identified an additional 13 studies in the 2016 update. The review now includes 28 RCTs (3377 women) and five RCTs awaiting classification. Five of the 28 included trials reported live birth/ongoing pregnancy. Secondary outcomes were poorly reported.The quality of the evidence ranged from low to very low. The primary reasons for downgrading the evidence were imprecision and risk of bias associated with poor reporting. Antioestrogen versus placebo Live birth rate, miscarriage rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome (OHSS)No data were reported for these outcomes. Clinical pregnancy rateClomiphene citrate was associated with an increased chance of a clinical pregnancy compared with placebo, though the size of the benefit was very uncertain (odds ratio (OR) 5.91, 95% confidence interval (CI) 1.77 to 19.68; 3 studies; 133 women; low-quality evidence). If the chance of a clinical pregnancy was 5% in the placebo group, then between 8% and 50% of women would have a clinical pregnancy in the clomiphene group. Clomiphene citrate versus tamoxifen Live birth rateThere was no clear evidence of a difference in the chance of a live birth between the clomiphene citrate and tamoxifen groups (OR 1.24, 95% CI 0.59 to 2.62; 2 studies; 195 women; low-quality evidence). If 20% of women in the tamoxifen group had a live birth, then between 13% and 40% of women in the clomiphene citrate group would have a live birth. Miscarriage rateThere was no clear evidence of a difference in the chance of a miscarriage between the clomiphene citrate and tamoxifen groups (OR 1.81, 95% CI 0.80 to 4.12; 4 studies; 653 women; low-quality evidence). If 3% of women in the tamoxifen group had a miscarriage, then between 2% and 10% in the clomiphene citrate group would have a miscarriage. Clinical pregnancy rateThere was no clear evidence of a difference in the chance of a clinical pregnancy between the clomiphene citrate and tamoxifen groups (OR 1.30, 95% CI 0.92 to 1.85; 5 studies; 757 women; I = 69%; low-quality evidence). If 22% of women in the tamoxifen group had a clinical pregnancy, then between 21% and 35% in the clomiphene citrate group would have a clinical pregnancy. Multiple pregnancy rate There was insufficient evidence of a difference in the chance of a multiple pregnancy between the clomiphene citrate group (OR 2.34, 95% CI 0.34 to 16.04; 3 studies; 567 women; very low-quality evidence). If 0% of women in the tamoxifen group had a multiple pregnancy, then between 0% and 0.5% of women in the clomiphene group would have a multiple pregnancy. OHSSThere were no instances of OHSS in either the clomiphene citrate or the tamoxifen group reported from three studies. Clomiphene citrate with tamoxifen versus tamoxifen alone Clinical pregnancy rateThere was insufficient evidence to determine whether there was a difference between groups (OR 3.32, 95% CI 0.12 to 91.60; 1 study; 20 women; very low-quality evidence). No data were reported for the other outcomes. Other comparisons of interestLimited evidence suggested that compared with a gonadotropin, clomiphene citrate was associated with a reduced chance of a pregnancy, ongoing pregnancy, or live birth, with no clear evidence of a difference in multiple pregnancy rates.The comparison of clomiphene citrate plus medical adjunct versus clomiphene alone was limited by the number of trials reporting the comparison and poor reporting of clinical outcomes relevant to this systematic review and by the number of adjuncts reported (ketoconazole, bromocriptine, dexamethasone, combined oral contraceptive, human chorionic gonadotropin, hormone supplementation). The addition of dexamethasone or combined oral contraceptive suggested a possible benefit in pregnancy outcomes, but findings were very uncertain and further research is required to confirm this.There was limited evidence suggesting that a 10-day regimen of clomiphene citrate improves pregnancy outcomes compared with a 5-day regimen. Data for early versus late regimens of clomiphene citrate were insufficient to be able to make a judgement on differences for pregnancy outcomes.
AUTHORS' CONCLUSIONS
We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo, but may reduce the chance of live birth or ongoing pregnancy when compared with a gonadotropin. Due to low event rates, we advise caution interpreting these data.The comparison of clomiphene citrate plus medical adjunctive versus clomiphene alone was limited by the number of trials reporting the comparison. The evidence was very low quality and no firm conclusions could be drawn, but very limited evidence suggested a benefit from adjunctive dexamethasone or combined oral contraceptives. Low-quality evidence suggested that a 10-day regimen of clomiphene citrate improves pregnancy rates compared with a 5-day regimen, but further research is required.
Topics: Anovulation; Clomiphene; Contraceptives, Oral, Combined; Dexamethasone; Drug Therapy, Combination; Estrogen Antagonists; Female; Gonadotropins; Humans; Infertility, Female; Live Birth; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Tamoxifen
PubMed: 27976369
DOI: 10.1002/14651858.CD002249.pub5 -
Human Reproduction (Oxford, England) Dec 2016What is the reported overall prevalence of polycystic ovary syndrome (PCOS) according to the criteria of the National Institutes of Health (NIH), Rotterdam or the... (Meta-Analysis)
Meta-Analysis Review
STUDY QUESTION
What is the reported overall prevalence of polycystic ovary syndrome (PCOS) according to the criteria of the National Institutes of Health (NIH), Rotterdam or the Androgen Excess and PCOS Society (AE-PCOS Society)?
SUMMARY ANSWER
The reported overall prevalence of PCOS (95% CI) according to diagnostic criteria of the NIH, Rotterdam and the AE-PCOS Society is 6% (5-8%, n = 18 trials), 10% (8-13%, n = 15 trials) and 10% (7-13%, n = 10 trials), respectively.
WHAT IS ALREADY KNOWN
PCOS is the most common endocrine disorder among women of reproductive age. Although many studies have investigated the prevalence of PCOS, there are discrepancies in their results, in part due to the use of various definitions of the syndrome and its subphenotypes, differences between study cohorts, ethnicities, and types of recruitment and sampling.
STUDY DESIGN, SIZE, DURATION
A systematic review and meta-analysis were performed on all published studies that have reported the prevalence of PCOS according to at least one subset of diagnostic criteria.
PARTICIPANTS/MATERIALS, SETTING, METHODS
To identify relevant studies based on the PRISMA statement, PubMed and Ovid databases were searched up to September 2015 by two blind investigators using the terms 'PCOS', 'polycystic ovarian disease', 'Stein Leventhal syndrome', 'Androgen Excess Society', 'National Institute of Health', 'Rotterdam', 'ESHRE/ASRM', 'criteria' and 'prevalence'. Articles that represented the prevalence of PCOS according to at least one subset of diagnostic criteria were included. Exclusion criteria were a focus on adolescent subjects, an absence of data on prevalence, inappropriate design or non-English reporting. An appraisal tool to evaluate the methodological quality of the available studies was generated by the authors.
MAIN RESULTS AND THE ROLE OF CHANCE
A total of 55 reports remained following screening of the abstracts and text for the subject of the study. Of these, 24 articles were eligible and evaluated for qualitative and quantitative synthesis. Since heterogeneity was observed among studies, a random-effects model was used to estimate the prevalence and its 95% CI. The proportions of PCOS prevalence (95% CI) according to the diagnostic criteria of NIH, Rotterdam and AE-PCOS Society were 6% (5-8%, n = 18 trials), 10% (8-13%, n = 15 trials) and 10% (7-13%, n = 10 trials), respectively. When only unselected population studies were included, the given rates were 6% (5-8%, n = 3 trials), 9% (7-12%, n = 6 trials) and 10% (7-14%, n = 3 trials). The respective proportions for hirsutism, hyperandrogenaemia, polycystic ovaries (PCO) and oligo-anovulation were 13% (8-20%, n = 14 trials), 11% (8-15%, n = 9 trials), 28% (22-35%, n = 12 trials) and 15% (12-18%, n = 19 trials), respectively.
LIMITATIONS, REASONS FOR CAUTION
The effects of ethnic differences, particularly, on the presence or severity of hirsutism cannot be ruled out in any way. In addition, there was a lack of standardization in defining phenotypes of the syndrome and selection bias was evident in most of the studies regarding recruitment of the cohorts.
WIDER IMPLICATIONS OF THE FINDINGS
Geographical differences in frequencies of the components of the syndrome, such as oligo-anovulation and clinical/biochemical androgen excess, must be taken into account in the development and implementation of regional diagnostic and precision treatment strategies. Further efforts and resources are required to increase standardization of the methods and comparability of the study results on prevalence and phenotypic characterization of PCOS around the globe.
STUDY FUNDING/COMPETING INTERESTS
No funding to declare. The authors have no conflicts of interest to declare.
REGISTRATION NUMBER
None.
Topics: Female; Humans; Phenotype; Polycystic Ovary Syndrome; Prevalence
PubMed: 27664216
DOI: 10.1093/humrep/dew218 -
Fertility and Sterility Nov 2016To compare the prevalence of polycystic ovary syndrome (PCOS) phenotypes and obesity among patients detected in referral versus unselected populations. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the prevalence of polycystic ovary syndrome (PCOS) phenotypes and obesity among patients detected in referral versus unselected populations.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Thirteen thousand seven hundred ninety-six reproductive-age patients with PCOS, as defined by the extended Rotterdam 2003 criteria.
INTERVENTION(S)
Review of PUBMED, EMBASE, and Cochrane Library, 2003-2016. Only observational studies were included. Data were extracted using a web-based, piloted form and combined for meta-analysis.
MAIN OUTCOME MEASURE(S)
PCOS phenotypes were classified as follows: phenotype A, clinical and/or biochemical hyperandrogenism (HA) + oligo-/anovulation (OA) + polycystic ovarian morphology (PCOM); phenotype B, HA+OA; phenotype C, HA+PCOM; and phenotype D, OA+PCOM.
RESULT(S)
Forty-one eligible studies, reporting on 43 populations, were identified. Pooled estimates of detected PCOS phenotype prevalence were consequently documented in referral versus unselected populations, as [1] phenotype A, 50% (95% confidence interval [CI], 46%-54%) versus 19% (95% CI, 13%-27%); [2] phenotype B, 13% (95% CI, 11%-17%) versus 25% (95% CI, 15%-37%); [3] phenotype C, 14% (95% CI, 12%-16%) versus 34% (95% CI, 25-46%); and [4] phenotype D, 17% (95% CI, 13%-22%) versus 19% (95% CI, 14%-25%). Differences between referral and unselected populations were statistically significant for phenotypes A, B, and C. Referral PCOS subjects had a greater mean body mass index (BMI) than local controls, a difference that was not apparent in unselected PCOS.
CONCLUSION(S)
The prevalence of more complete phenotypes in PCOS and mean BMI were higher in subjects identified in referral versus unselected populations, suggesting the presence of significant referral bias.
Topics: Body Mass Index; Female; Humans; Obesity; Observational Studies as Topic; Ovulation; Phenotype; Polycystic Ovary Syndrome; Prevalence; Referral and Consultation; Selection Bias
PubMed: 27530062
DOI: 10.1016/j.fertnstert.2016.07.1121