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Reproductive Sciences (Thousand Oaks,... Feb 2020Polycystic ovary syndrome (PCOS) affects 6% to 20% of reproductive age women and is the most frequent cause of anovulatory infertility. Its physiopathology may result in...
Polycystic ovary syndrome (PCOS) affects 6% to 20% of reproductive age women and is the most frequent cause of anovulatory infertility. Its physiopathology may result in part from hypothalamic alterations in the pulsatile secretion of gonadotropin-releasing hormone (GnRH). The neuropeptide kisspeptin participates in the mechanism through stimulation of the hormone's production. The purpose of this study was to review the articles which compared kisspeptin levels in women with PCOS with those of controls. A systematic review of observational studies was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) recommendations. The selected studies encompassed a population of patients with PCOS and controls, whose serum kisspeptin levels were evaluated. The studies were retrieved from the Medline, Cochrane, and Embase databases, and four of them were chosen for the review. In most studies, the serum kisspeptin levels were higher in women with PCOS than in controls notwithstanding the BMI. One of the articles showed that circulating plasma levels of kisspeptin were significantly higher in women with PCOS whose BMI was lower than 25 than in obese and overweight women. Our data suggest a higher concentration of serum kisspeptin in women with PCOS irrespective of their BMI. Further experimental and clinical studies are needed to ascertain the role of kisspeptin in PCOS.
Topics: Animals; Female; Humans; Kisspeptins; Observational Studies as Topic; Polycystic Ovary Syndrome
PubMed: 31919796
DOI: 10.1007/s43032-019-00085-6 -
The Cochrane Database of Systematic... May 2012Polycystic ovary syndrome (PCOS) is characterised by infrequent or absent ovulation (anovulation), high levels of male hormones (hyperandrogenaemia) and high levels of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is characterised by infrequent or absent ovulation (anovulation), high levels of male hormones (hyperandrogenaemia) and high levels of insulin (hyperinsulinaemia secondary to increased insulin resistance). Hyperinsulinaemia is associated with an increase in cardiovascular risk and the development of diabetes mellitus. Insulin-sensitising agents such as metformin may be effective in treating the features of PCOS, including anovulation.
OBJECTIVES
To assess the effectiveness of insulin-sensitising drugs in improving reproductive outcomes and metabolic parameters for women with PCOS.
SEARCH METHODS
We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (October 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 3rd Quarter 2011), CINAHL (October 2011), MEDLINE (January 1966 to October 2011), and EMBASE (January 1985 to October 2011).
SELECTION CRITERIA
Randomised controlled trials of insulin sensitising drugs compared with either placebo, no treatment, or an ovulation induction agent for women with PCOS, menstrual disturbance and subfertility.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion and trial quality, and extracted data.
MAIN RESULTS
Forty-four trials (3992 women) were included for analysis, 38 of them using metformin and involving 3495 women.There was no evidence that metformin improved live birth rates, whether it was used alone (pooled OR 1.80, 95% CI 0.52 to 6.16, 3 trials, 115 women) or in combination with clomiphene (pooled OR 1.16, 95% CI 0.85 to 1.56, 7 trials, 907 women). However, clinical pregnancy rates were improved for metformin versus placebo (pooled OR 2.31, 95% CI 1.52 to 3.51, 8 trials, 707 women) and for metformin and clomiphene versus clomiphene alone (pooled OR 1.51, 95% CI 1.17 to 1.96, 11 trials, 1208 women). In the studies that compared metformin and clomiphene alone, there was evidence of an improved live birth rate (pooled OR 0.3, 95% CI 0.17 to 0.52, 2 trials, 500 women) and clinical pregnancy rate (pooled OR 0.34, 95% 0.21 to 0.55, 2 trials, 500 women) in the group of obese women who took clomiphene.Metformin was also associated with a significantly higher incidence of gastrointestinal disturbances than placebo (pooled OR 4.27, 95% CI 2.4 to 7.59, 5 trials, 318 women) but no serious adverse effects were reported.
AUTHORS' CONCLUSIONS
In agreement with the previous review, metformin was associated with improved clinical pregnancy but there was no evidence that metformin improves live birth rates whether it is used alone or in combination with clomiphene, or when compared with clomiphene. Therefore, the role of metformin in improving reproductive outcomes in women with PCOS appears to be limited.
Topics: Anovulation; Clomiphene; Female; Humans; Hypoglycemic Agents; Infertility, Female; Inositol; Insulin Resistance; Live Birth; Metformin; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Thiazolidinediones
PubMed: 22592687
DOI: 10.1002/14651858.CD003053.pub5 -
Reproductive Sciences (Thousand Oaks,... Sep 2021Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders in women of reproductive age. It is characterized by an increase in the...
Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders in women of reproductive age. It is characterized by an increase in the biosynthesis of androgens, anovulation, and infertility. PCOS has been reported as a polygenic entity in which multiple single nucleotide polymorphisms (SNPs) are associated with the clinical features of the pathology. Herein, we describe the common polymorphic variants in genes related to PCOS, their role in its pathogenesis, and etiology. Whole-genome association studies have been focused on women from Asian and European populations. The most common genes associated with PCOS are DENND1A, THADA, FSHR, and LHCGR. However, other genes have been associated with PCOS such as AMH, AMHR2, ADIPOQ, FTO, HNF1A, CYP19, YAP1, HMGA2, RAB5B, SUOX, INSR, and TOX3. Nevertheless, the relationship between the biological functions of these genes and the development of the pathology is unclear. Studies in each gene in different populations do not always comply with a general pattern, so researching these variants is essential for better understanding of this polygenic syndrome. Future population studies should be carried out to evaluate biological processes, incidence rates, allelic and genotypic frequencies, and genetic susceptibility factors that predispose PCOS.
Topics: Female; Genetic Predisposition to Disease; Humans; Phenotype; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors
PubMed: 33174186
DOI: 10.1007/s43032-020-00375-4 -
The Cochrane Database of Systematic... Nov 2017Polycystic ovary syndrome (PCOS) is a common endocrine condition, affecting approximately one in 10 women. PCOS is defined by two of three features: oligo- or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is a common endocrine condition, affecting approximately one in 10 women. PCOS is defined by two of three features: oligo- or anovulation, clinical or biochemical hyperandrogenism or both, or polycystic ovaries.Women with PCOS can have a wide range of health problems, including infrequent and irregular periods, unwanted hair growth and acne, and subnormal fertility. Long-term health concerns include an increased risk of heart disease, diabetes and the development of precancerous disease of the womb.
OBJECTIVES
To assess the effectiveness and harms of ovarian surgery as a treatment for symptomatic relief of hirsutism, acne and menstrual irregularity in PCOS.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group specialized register, CENTRAL, MEDLINE, Embase and PsycINFO (from inception to 17 October 2016). We handsearched citation lists, registers of ongoing trials and conference proceedings.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of women undergoing ovarian drilling in comparison to no treatment, medical treatment, or other forms of surgical treatment for the symptoms of PCOS.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. The primary outcome measures were improvement in menstrual regularity and androgenic symptoms of PCOS (hirsutism, acne); the secondary outcome measures included harms, change of body mass index (BMI), waist circumference, androgen levels, metabolic measures and quality of life. We assessed the quality of the evidence using GRADE methods.
MAIN RESULTS
We included 22 RCTs (2278 women analyzed) of participants with PCOS and symptoms of acne, hirsutism or irregular menstrual cycles, all of which included laparoscopic ovarian drilling (LOD) as an intervention.Two studies reported their funding source (Farquhar 2002 - supported in part by the Auckland Medical Research Foundation; Sarouri 2015 - the authors thank the Vice Chancellor for Research of Guilan University of Medical Sciences for funding this project).The quality of the evidence ranged from very low to moderate quality. The main limitations were imprecision associated with the low number of studies, inconsistency and risk of bias associated with the inability to blind participants. There were too few studies to assess risk of publication bias. Menstrual RegularityTwo studies compared LOD versus metformin (n=226) but no conclusions could be drawn with regard to menstrual regularity, as their findings were inconsistent and they were unsuitable for pooling. There appeared to be little or no difference in the rate of women reporting improvement in menstrual regularity when LOD was compared with medical treatment including metformin + clomiphene (OR 1.02, 95% CI 0.64 to 1.64, 2 studies, 332 women, I = 13%, low-quality evidence), letrozole (OR 1.08, 95% CI 0.64 to 1.84, 1 study, 260 women, low-quality evidence), or metformin + letrozole (OR 0.95, 95% CI 0.49 to 1.81, 1 study, 146 women, low-quality evidence). However, one study reported that LOD was superior to gonadotrophin (OR 19.2, 95% CI 3.17 to 116.45, 1 study, 35 women, very low-quality evidence).There appeared to be little or no difference in the rate of women reporting improvement in menstrual regularity when bilateral unipolar LOD was compared to unilateral LOD (OR 1.51, 95% CI 0.62 to 3.71, 2 studies, 104 women, I = 0%, moderate-quality evidence), transvaginal ultrasound-guided LOD (OR 1.23, 95% CI 0.64 to 2.37, 1 study, 147 women, low-quality evidence), LOD using adjusted thermal dose in accordance with the ovarian volume (OR 0.42, 95% CI 0.16 to 1.14, 1 study, 115 women, low-quality evidence) or bipolar LOD (OR 1.00, 95% CI 0.05 to 18.57, 1 study, 18 women, low-quality evidence).Four to five punctures per ovary may improve the rate of women reporting menstrual regularity compared with two or fewer (OR 16.04, 95% CI 4.19 to 61.34, 2 studies, 73 women, I = 0%, low-quality evidence). Androgenic SymptomsThere was probably little or no difference in improvement in androgenic symptoms when LOD was compared to metformin (OR 1.00, 95% CI 0.42 to 2.37, 1 study, 126 women, moderate-quality evidence) or gonadotrophins; acne (OR 3.20, 95% CI 0.33 to 30.94, 1 study, 25 women, low-quality evidence), hirsutism (OR 2.31, 95% CI 0.22 to 23.89, 1 study, 25 women, low-quality evidence).There appeared to be little or no difference in improvement of androgenic symptoms when LOD was compared to transvaginal ultrasound-guided LOD, with respect to hirsutism (OR 1.09, 95% CI 0.30 to 3.91, 1 study, 39 women, low-quality evidence) or acne (OR 0.84, 95% CI 0.20 to 3.50, 1 study, 31 women, low-quality evidence). HarmsLOD was associated with fewer gastrointestinal side effects than metformin plus clomiphene (OR 0.05, 95% CI 0.01 to 0.36, 2 studies, 332 women, I = 0%, moderate-quality evidence). One study suggested little or no difference in rates of ovarian hyperstimulation syndrome between LOD and gonadotrophins (OR 0.08, 95% CI 0.00 to 1.61, 1 study, 33 women, low-quality evidence).There were fewer adhesions with transvaginal hydrolaparoscopy compared to LOD (OR 0.10, 95% CI 0.05 to 0.18, 1 study, 246 women, moderate-quality evidence). There appeared to be little or no difference in adhesions when variable energy LOD was compared with standard LOD (OR 0.96, 95% CI 0.32 to 2.88, 1 study, 64 women, low-quality evidence). Another study (44 women) reported that none of the women who returned for surgery following either traditional or unilateral LOD were found to have adhesions.
AUTHORS' CONCLUSIONS
There was no clear evidence that LOD improves menstrual regularity or the androgenic symptoms of PCOS, compared to most of the medical treatments used in the included studies. LOD was associated with fewer gastrointestinal side effects compared to metformin and clomiphene.There was also no clear evidence of different effectiveness between types of LOD, except that LOD with four to five punctures per ovary may be more effective than two or fewer punctures. There was little evidence comparing LOD with different types of surgery, although one study concluded that transvaginal hydrolaparoscopy had a lower risk of adhesions than LOD.There was evidence from one small study of benefit from LOD compared to gonadotrophins for menstrual regulation. However, gonadotrophins are seldom used for this indication.
Topics: Acne Vulgaris; Clomiphene; Female; Gonadotropins; Hirsutism; Humans; Laparoscopy; Letrozole; Menstruation Disturbances; Metformin; Nitriles; Ovary; Polycystic Ovary Syndrome; Punctures; Randomized Controlled Trials as Topic; Triazoles
PubMed: 29125183
DOI: 10.1002/14651858.CD009526.pub2 -
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 Cochrane Database of Systematic... Jan 2010Polycystic ovary syndrome (PCOS) is characterised by anovulation, hyperandrogaenemia and insulin resistance. Hyperinsulinaemia is associated with an increase in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is characterised by anovulation, hyperandrogaenemia and insulin resistance. Hyperinsulinaemia is associated with an increase in cardiovascular risk and the development of diabetes mellitus. If insulin sensitising agents such as metformin are effective in treating features of PCOS, then they could have wider health benefits than just treating the symptoms of the syndrome.
OBJECTIVES
To assess the effectiveness of insulin sensitising drugs in improving reproductive outcomes and metabolic parameters for women with PCOS and menstrual disturbance.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (searched September 2008), the Cochrane Central Register of Controlled Trials (Cochrane Library, third Quarter 2008), CINAHL (searched September 2008), MEDLINE (January 1966 to September 2008), and EMBASE (January 1985 to September 2008). All searches were rerun 13 August 2009 17 RCTs were located and await classification.
SELECTION CRITERIA
Randomised controlled trials which investigated the effect of insulin sensitising drugs compared with either placebo or no treatment, or compared with an ovulation induction agent.
DATA COLLECTION AND ANALYSIS
Thirty one trials (2537 women) were included for analysis, 27 of them using metformin and involving 2150 women.
MAIN RESULTS
There is no evidence that metformin improves live birth rates whether it is used alone (Pooled OR = 1.00, 95% CI 0.16 to 6.39) or in combination with clomiphene (Pooled OR = 1.48, 95% CI 1.12 to 1.95). However, clinical pregnancy rates are improved for metformin versus placebo (Pooled OR = OR 3.86, 95% C.I. 2.18 to 6.84) and for metformin and clomiphene versus clomiphene alone (Pooled OR =1.48, 95% C.I. 1.12 to 1.95) ). In the studies that compared metformin and clomiphene alone, there was no evidence of an improved live birth rate (OR= 0.67, 95% CI 0.44 to 1.02) but the pooled OR resulted in improved clinical pregnancy rate in in the clomiphene group (OR = 0.63 , 95% 0.43 to 0.92), although there was significant heterogeneity.There is also evidence that ovulation rates are improved with metformin in women with PCOS for metformin versus placebo (Pooled OR 2.12, 95% CI 1.50 to 3.0) and for metformin and clomiphene versus clomiphene alone (Pooled OR = 3.46, 95% CI 1.97 to 6.07).Metformin was also associated with a significantly higher incidence of gastrointestinal disturbance, but no serious adverse effects were reported.
AUTHORS' CONCLUSIONS
In agreement with the previous review, metformin is still of benefit in improving clinical pregnancy and ovulation rates. However, there is no evidence that metformin improves live birth rates whether it is used alone or in combination with clomiphene, or when compared with clomiphene. Therefore, the use of metformin in improving reproductive outcomes in women with PCOS appears to be limited.
Topics: Anovulation; Clomiphene; Female; Humans; Hypoglycemic Agents; Inositol; Insulin Resistance; Live Birth; Metformin; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Thiazolidinediones
PubMed: 20091537
DOI: 10.1002/14651858.CD003053.pub4 -
Journal of Obstetrics and Gynaecology :... Nov 2003The effectiveness of laparoscopic ovarian drilling for treatment of anovulation in polycystic ovarian syndrome (PCOS) has been proved. The role of ovarian surgery in the... (Review)
Review
The effectiveness of laparoscopic ovarian drilling for treatment of anovulation in polycystic ovarian syndrome (PCOS) has been proved. The role of ovarian surgery in the treatment of symptoms related to hyperandrogenaemia, such as hirsutism and acne, has been less clear. This review sought to evaluate the effectiveness of ovarian surgery in the treatment of non-infertility symptoms related to PCOS. A systematic literature review was undertaken, by searching the Medline database for the years 1966-2002 inclusive. The search yielded 19 studies recording the outcomes of hirsutism, acne or androgen levels from surgical treatment for women with PCOS: three assessed unilateral oophorectomy; two ovarian wedge resection; and 14 ovarian drilling. There was no consensus of a clear improvement in hirsutism or acne in women undergoing surgery. There was a trend towards a decrease in serum androgen levels in most studies. We conclude that, while there is evidence that ovarian surgery may decrease androgen levels in some women with PCOS, the evidence that this translates into a clear improvement in hirsutism and acne is less clear. Further high quality clinical research, including data from randomisation, would be required to answer this question.
Topics: Acne Vulgaris; Female; Hirsutism; Humans; Hyperandrogenism; Laparoscopy; Ovariectomy; Ovary; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic
PubMed: 14617458
DOI: 10.1080/01443610310001604330 -
The Cochrane Database of Systematic... Oct 2009Polycystic ovary syndrome (PCOS) is characterised by anovulation, hyperandrogaenemia and insulin resistance. Hyperinsulinaemia is associated with an increase in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is characterised by anovulation, hyperandrogaenemia and insulin resistance. Hyperinsulinaemia is associated with an increase in cardiovascular risk and the development of diabetes mellitus. If insulin sensitising agents such as metformin are effective in treating features of PCOS, then they could have wider health benefits than just treating the symptoms of the syndrome.
OBJECTIVES
To assess the effectiveness of insulin sensitising drugs in improving reproductive outcomes and metabolic parameters for women with PCOS and menstrual disturbance.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (searched September 2008), the Cochrane Central Register of Controlled Trials (Cochrane Library, third Quarter 2008), CINAHL (searched September 2008), MEDLINE (January 1966 to September 2008), and EMBASE (January 1985 to September 2008). All searches were rerun 13 August 2009 17 RCTs were located and await classification.
SELECTION CRITERIA
Randomised controlled trials which investigated the effect of insulin sensitising drugs compared with either placebo or no treatment, or compared with an ovulation induction agent.
DATA COLLECTION AND ANALYSIS
Thirty one trials (2537 women) were included for analysis, 27 of them using metformin and involving 2150 women.
MAIN RESULTS
There is no evidence that metformin improves live birth rates whether it is used alone (Pooled OR = 1.00, 95% CI 0.16 to 6.39) or in combination with clomiphene (Pooled OR = 1.48, 95% CI 1.12 to 1.95). However, clinical pregnancy rates are improved for metformin versus placebo (Pooled OR = OR 3.86, 95% C.I. 2.18 to 6.84) and for metformin and clomiphene versus clomiphene alone (Pooled OR =1.48, 95% C.I. 1.12 to 1.95) ). In the studies that compared metformin and clomiphene alone, there was no evidence of an improved live birth rate (OR= 0.67, 95% CI 0.44 to 1.02) but the pooled OR resulted in improved clinical pregnancy rate in in the clomiphene group (OR = 0.63 , 95% 0.43 to 0.92), although there was significant heterogeneity.There is also evidence that ovulation rates are improved with metformin in women with PCOS for metformin versus placebo (Pooled OR 2.12, 95% CI 1.50 to 3.0) and for metformin and clomiphene versus clomiphene alone (Pooled OR = 3.46, 95% CI 1.97 to 6.07).Metformin was also associated with a significantly higher incidence of gastrointestinal disturbance, but no serious adverse effects were reported.
AUTHORS' CONCLUSIONS
In agreement with the previous review, metformin is still of benefit in improving clinical pregnancy and ovulation rates. However, there is no evidence that metformin improves live birth rates whether it is used alone or in combination with clomiphene, or when compared with clomiphene. Therefore, the use of metformin in improving reproductive outcomes in women with PCOS appears to be limited.
Topics: Anovulation; Clomiphene; Female; Humans; Hypoglycemic Agents; Inositol; Metformin; Ovulation Induction; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Thiazolidinediones
PubMed: 19821299
DOI: 10.1002/14651858.CD003053.pub3 -
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 -
Fertility and Sterility Jul 2013To summarize the evidence for the use of commonly accepted fertility tests in subfertile women with ovulation problems. (Review)
Review
OBJECTIVE
To summarize the evidence for the use of commonly accepted fertility tests in subfertile women with ovulation problems.
DESIGN
Systematic review.
SETTING
Not applicable.
PATIENT(S)
The study population included women starting with clomiphene citrate (CC) as first-line treatment, women starting with second-line treatment if CC failed to result in pregnancy, and women starting with second-line treatment if CC failed to result in ovulation (CC resistant).
INTERVENTION(S)
Performance of a semen analysis or tubal patency test before or during treatment.
MAIN OUTCOME MEASURE(S)
Prevalence of abnormal tests as well as the diagnostic and prognostic performance of these tests.
RESULT(S)
Four studies reported on 3,017 women starting with CC as first-line treatment. The prevalence of male factor infertility was 10%, and in 0.3% of couples azoospermia was found (two studies). Semen parameters were not associated with pregnancy chance (one study). The prevalence of bilateral tubal disease was 4% (two studies). Three studies reported on 462 women starting with second-line treatment if CC failed to result in a pregnancy. Semen parameters were not predictive for pregnancy (one study). The prevalence of bilateral tubal disease in these women was 8% (three studies). Two studies reported on 168 CC-resistant women and total motile sperm count did not predict live birth (two studies). For all other outcomes, no studies were available.
CONCLUSION(S)
Data on the basic fertility workup in subfertile women with anovulation are scarce. Based on the available data, the workup should contain a semen analysis, and, for women who need to start second-line treatment if CC failed to result in pregnancy or women with CC resistance, assessment of tubal patency.
Topics: Animals; Azoospermia; Female; Fertility; Humans; Infertility, Female; Male; Polycystic Ovary Syndrome; Pregnancy; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 23582439
DOI: 10.1016/j.fertnstert.2013.03.015