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European Heart Journal Open Jul 2023Prior meta-analyses indicate polycystic ovary syndrome (PCOS) is associated with cardiovascular diseases (CVDs), but have high statistical heterogeneity, likely because...
Cardiovascular disease risk in women with hyperandrogenism, oligomenorrhea/menstrual irregularity or polycystic ovaries (components of polycystic ovary syndrome): a systematic review and meta-analysis.
AIMS
Prior meta-analyses indicate polycystic ovary syndrome (PCOS) is associated with cardiovascular diseases (CVDs), but have high statistical heterogeneity, likely because PCOS is a heterogenous syndrome diagnosed by having any two of the three components: hyperandrogenism, oligomenorrhea/menstrual irregularity or polycystic ovaries. Several studies report higher risk of CVDs from individual PCOS components, but a comprehensive assessment of how each component contributes to CVD risk is lacking. This study aims to assess CVD risk for women with one of the PCOS components.
METHODS AND RESULTS
A systematic review and meta-analysis of observational studies was conducted. PubMed, Scopus, and Web of Science were searched without restrictions in July 2022. Studies meeting inclusion criteria examined the association between PCOS components and risk of a CVD. Two reviewers independently assessed abstracts and full-text articles, and extracted data from eligible studies. Where appropriate, relative risk (RR) and 95% confidence interval (CI) were estimated by random-effects meta-analysis. Statistical heterogeneity was assessed using the statistic. Twenty-three studies, including 346 486 women, were identified. Oligo-amenorrhea/menstrual irregularity was associated with overall CVD (RR = 1.29, 95%CI = 1.09-1.53), coronary heart disease (CHD) (RR = 1.22, 95%CI = 1.06-1.41), and myocardial infarction (MI) (RR = 1.37, 95%CI = 1.01-1.88) but not cerebrovascular disease. These results were broadly consistent even after further adjustment for obesity. There was mixed evidence for the role of hyperandrogenism in CVDs. No studies examined polycystic ovaries as an independent exposure for CVD risk.
CONCLUSION
Oligo-amenorrhea/menstrual irregularity is associated with greater risk of overall CVD, CHD, and MI. More research is needed to assess the risks associated with hyperandrogenism or polycystic ovaries.
PubMed: 37404840
DOI: 10.1093/ehjopen/oead061 -
The Cochrane Database of Systematic... Oct 2022Premature ovarian insufficiency (POI) is a clinical syndrome resulting from loss of ovarian function before the age of 40. It is a state of hypergonadotropic... (Review)
Review
BACKGROUND
Premature ovarian insufficiency (POI) is a clinical syndrome resulting from loss of ovarian function before the age of 40. It is a state of hypergonadotropic hypogonadism, characterised by amenorrhoea or oligomenorrhoea, with low ovarian sex hormones (oestrogen deficiency) and elevated pituitary gonadotrophins. POI with primary amenorrhoea may occur as a result of chromosomal and genetic abnormalities, such as Turner syndrome, Fragile X, or autosomal gene defects; secondary amenorrhoea may be iatrogenic after the surgical removal of the ovaries, radiotherapy, or chemotherapy. Other causes include autoimmune diseases, viral infections, and environmental factors; in most cases, POI is idiopathic. Appropriate replacement of sex hormones in women with POI may facilitate the achievement of near normal uterine development. However, the optimal effective hormone therapy (HT) regimen to maximise the reproductive potential for women with POI remains unclear.
OBJECTIVES
To investigate the effectiveness and safety of different hormonal regimens on uterine and endometrial development in women with POI.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two trials registers in September 2021. We also checked references of included studies, and contacted study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) investigating the effect of various hormonal preparations on the uterine development of women diagnosed with POI.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. The primary review outcome was uterine volume; secondary outcomes were endometrial thickness, endometrial histology, uterine perfusion, reproductive outcomes, and any reported adverse events.
MAIN RESULTS
We included three studies (52 participants analysed in total) investigating the role of various hormonal preparations in three different contexts, which deemed meta-analysis unfeasible. We found very low-certainty evidence; the main limitation was very serious imprecision due to small sample size. Conjugated oral oestrogens versus transdermal 17ß-oestradiol We are uncertain of the effect of conjugated oral oestrogens compared to transdermal 17ß-oestradiol (mean difference (MD) -18.2 (mL), 95% confidence interval (CI) -23.18 to -13.22; 1 RCT, N = 12; very low-certainty evidence) on uterine volume, measured after 12 months of treatment. The study reported no other relevant outcomes (including adverse events). Low versus high 17ß-oestradiol dose We are uncertain of the effect of a lower dose of 17ß-oestradiol compared to a higher dose of 17ß-oestradiol on uterine volume after three or five years of treatment, or adverse events (1 RCT, N = 20; very low-certainty evidence). The study reported no other relevant outcomes. Oral versus vaginal administration of oestradiol and dydrogesterone We are uncertain of the effect of an oral or vaginal administration route on uterine volume and endometrial thickness after 14 or 21 days of administration (1 RCT, N = 20; very low-certainty evidence). The study reported no other relevant outcomes (including adverse events).
AUTHORS' CONCLUSIONS
No clear conclusions can be drawn in this systematic review, due to the very low-certainty of the evidence. There is a need for pragmatic, well designed, randomised controlled trials, with adequate power to detect differences between various HT regimens on uterine growth, endometrial development, and pregnancy outcomes following the transfer of donated gametes or embryos in women diagnosed with POI.
Topics: Amenorrhea; Dydrogesterone; Endometrium; Estradiol; Estrogens; Female; Humans; Menopause, Premature; Pregnancy
PubMed: 36200708
DOI: 10.1002/14651858.CD008209.pub2 -
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 Health Jun 2022Menstrual hygiene management (MHM) and practices by adolescent females of low and middle-income countries (LMICs) are a severe public health issue. The current... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Menstrual hygiene management (MHM) and practices by adolescent females of low and middle-income countries (LMICs) are a severe public health issue. The current systematic review and meta-analysis aimed to estimate the pooled proportion of the hygiene practices, menstrual problems with their associated factors, and the effectiveness of educational interventions on menstrual hygiene among adolescent school girls in India.
METHODS
PRISMA checklist and PICO guidelines were used to screen the scientific literature from 2011 to 2021. The Newcastle-Ottawa Scale was used to assess the quality of studies. Four themes were developed for data analysis, including hygiene practices, type of absorbent used, menstruation associated morbidities and interventions performed regarding menstruation. Eighty-four relevant studies were included and a meta-analysis, including subgroup analysis, was performed.
RESULTS
Pooled data revealed a statistically significant increase in sanitary pad usage "(SMD = 48.83, 95% CI = 41.38-57.62, p < 0.00001)" and increased perineum practices during menstruation "(SMD = 55.77, 95% CI = 44.27-70.26, p < 0.00001)". Results also reported that most prevalent disorders are dysmenorrhea "(SMD = 60.24, 95% CI = 50.41-70.06, p < 0.0001)", Pre-menstrual symptoms "(SMD = 62.67, 95% CI = 46.83-78.50, p < 0.00001)", Oligomenorrhea "(SMD = 23.57, CI = 18.05-29.10, p < 0.00001), Menorrhagia "(SMD = 25.67, CI = 3.86-47.47, p < 0.00001)", PCOS "(SMD = 5.50, CI = 0.60-10.40, p < 0.00001)", and Polymenorrhea "(SMD = 4.90, CI = 1.87-12.81, p < 0.0001)". A statistically significant improvement in knowledge "(SMD = 2.06, 95% CI = 0.75-3.36, p < 0.00001)" and practice "(SMD = 1.26, 95% CI = 0.13-2.65, p < 0.00001)" on menstruation was observed. Infections of the reproductive system and their repercussions can be avoided with better awareness and safe menstruation practices.
CONCLUSIONS
Learning about menstrual hygiene and health is essential for adolescent girls' health education to continue working and maintaining hygienic habits. Infections of the reproductive system and their repercussions can be avoided with better awareness and safe menstruation practices.
Topics: Adolescent; Female; Health Knowledge, Attitudes, Practice; Humans; Hygiene; India; Menstrual Hygiene Products; Menstruation; Schools
PubMed: 35739585
DOI: 10.1186/s12978-022-01453-3 -
JBRA Assisted Reproduction Nov 2022Polycystic ovary syndrome is the most common endocrine disorder in women. Today, medicinal plants have been considered by women, especially in the reproductive and...
Polycystic ovary syndrome is the most common endocrine disorder in women. Today, medicinal plants have been considered by women, especially in the reproductive and pregnancy ages. Multiple drug treatments and the length of the treatment period often lead to incomplete treatment by patients. Therefore, due to the side effects of chemical drugs, this study was conducted to assess investigate the effect of pomegranate seed oil on polycystic ovary syndrome. The prevalence of polycystic ovary syndrome is increasing by 15 to 20% and clinically includes oligomenorrhea or amenorrhea, hirsutism, and often infertility. Databases such as Cochran library, Medline, PubMed, SID, and Science Direct were used to access the related articles. To collect the required information, first, the articles that had one of the keywords of medicinal plants, polycystic ovary syndrome, plant, pomegranate extract, and menstrual irregularities in their text were searched in databases. All studies from 1985 to 2021 are included in the study. Conjugated linolenic acid (CLN) is a group of geometric and positional isomers of linolenic acid in which double bonds are conjugated. CLN has been reported to have a very strong cytotoxic effect on tissue tumor cells in the body, preventing cancer, reducing the accumulation of triacylglycerol in the liver, polycystic ovary syndrome, and LDL cholesterol in the blood. So far, seven CLN isomers have been identified, including ponic acid in pomegranate seed oil. Conjugated linoleic acid (CLA) is a group of situational and geometric isomers of linoleic acid in which double bonds are conjugated. The positive effects of the two main CLA isomers (cis-9, trans-11, and trans-10, cis-12) include inhibiting the growth of cancer, reducing the risk of atherosclerosis, and reducing body fat.
Topics: Female; Humans; alpha-Linolenic Acid; Plant Oils; Polycystic Ovary Syndrome; Pomegranate
PubMed: 35257560
DOI: 10.5935/1518-0557.20210121 -
Frontiers in Endocrinology 2021In this article, we present a 31-year-old female who presented with intermittent headache and oligomenorrhea of over 10 years' duration. Imaging revealed a large...
In this article, we present a 31-year-old female who presented with intermittent headache and oligomenorrhea of over 10 years' duration. Imaging revealed a large suprasellar mass with sellar extension. The patient underwent an endoscopic endonasal trans-sphenoidal surgery to resection of the mass. Clinical, radiological, and operative findings from this patient were initially considered to be Rathke's cleft cyst (RCC). However, postoperative histological examinations revealed a mature cystic teratoma. No radiotherapy was performed after surgery. At the most recent follow-up, approximately 1 year later, the patient is doing well with no headache and no recurrence of the teratoma.
Topics: Adult; Female; Humans; Central Nervous System Cysts; Diagnosis, Differential; Endoscopy; Sella Turcica; Teratoma
PubMed: 34659119
DOI: 10.3389/fendo.2021.731088 -
Annals of Palliative Medicine Dec 2021Oligomenorrhea is one of the most frequent gynecologic complaints that interferes with women's life quality. Treatment using traditional Chinese medicine (TCM) is a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oligomenorrhea is one of the most frequent gynecologic complaints that interferes with women's life quality. Treatment using traditional Chinese medicine (TCM) is a preferred alternative therapy for oligomenorrhea. However, systematic reviews (SRs) evaluating the efficacy of TCM treatments for oligomenorrhea remain absent. The present SR and meta-analysis aimed to evaluate the efficacy and safety of TCM treatment for oligomenorrhea.
METHODS
Randomized controlled trials (RCTs) published in English and Chinese were retrieved by searching in the databases in October 2019, including PubMed, Cochrane Library, EMBASE, Sinomed, CNKI, VIP, and WanFang databases. Quantitative analyses and quality assessments were then conducted based on abstracted data. This study protocol is registered PROSPERO, number CRD42018095660.
RESULTS
A total of 26 eligible RCTs involving 2,389 patients were included in our analysis. Overall, we observed an effect of increasing menstrual blood volumes owing to using TCM treatments plus bio-medicine (BM) (n=649; MD, 12.05; 95% CI: 5.23 to 18.87; P<0.00001; I2=96%). Besides, TCM combined with BM yielded a significant prolongation in menstrual periods (MD, 1.20; 95% CI: 0.78 to 1.62; P<0.00001; I2=76%), and had potential improvements on enhancing effectiveness rates, increasing endometrial thickness, and raising the levels of estradiol (E2) and progesterone (P). Concerning adverse events (AEs), no significant difference was found in either group. The quality of evidence was relatively low.
CONCLUSIONS
This study seems to support the potential effect of TCM on treating oligomenorrhea. However, the relatively low quality of prior studies calls for future RCTs to further assess the efficacy of TCM on treating oligomenorrhea using rigorous designs.
Topics: Female; Humans; Medicine, Chinese Traditional; Oligomenorrhea; Quality of Life
PubMed: 33832303
DOI: 10.21037/apm-20-825 -
International Journal of Reproductive... Nov 2018Understanding the prevalence of menstrual disorders has important implications for both health service planning and risk factor epidemiology. (Review)
Review
BACKGROUND
Understanding the prevalence of menstrual disorders has important implications for both health service planning and risk factor epidemiology.
OBJECTIVE
The aim of this review is to identify and collate studies describing the prevalence of menstrual disorders in Iran.
MATERIALS AND METHODS
Studies with original data related to the prevalence of menstrual disorders were identified via searching six electronic databases and reviewing citations. All abstracts or titles found by the electronic searches were independently scrutinized by two reviewers. The Meta-analysis was performed with a random effects model, considering the remarkable heterogeneity among studies. A total of 35 eligible epidemiological studies were included in this review.
RESULTS
Overall, the pooled prevalence of primary dysmenorrhea was 73.27% (95% CI=65.12-81.42). The mean proportion of women with oligomenorrhea was 13.11% (95.5%, 95% CI: 10.04-16.19). We identified 16 studies that reported polymenorrhoea with a random effect of pooled prevalence estimate of 9.94% (95% CI 7.33%-12.56%). The prevalence estimate of hypermenorrhea was 12.94% (95% CI 9.31%-16.57%). Overall prevalence of hypomenorrhea was 5.25% (95% CI 3.20%-7.30%), ranging from 0.9- 12.90%. Pooling six studies that reported estimates for menorrhagia, the overall prevalence was 19.24% (95% CI 12.78-25.69). Overall, 6.04% (95% CI: 1.99-10.08) of the women were shown to have metrorrhagia.
CONCLUSION
This systematic review suggests that the average prevalence of menstrual disorders in Iran is substantial. It has been neglected as a fundamental problem of women's reproductive health. Diagnosis and treatment of these disorders should be included in the primary health care system of reproductive health.
PubMed: 30775681
DOI: No ID Found -
BioMed Research International 2018Melasma is a highly prevalent, chronic, and pigmentary disorder. This systematic review aims to evaluate the efficacy and safety of tranexamic acid (TA) for the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Melasma is a highly prevalent, chronic, and pigmentary disorder. This systematic review aims to evaluate the efficacy and safety of tranexamic acid (TA) for the treatment of adults with melasma.
METHODS
We independently searched 3 databases from beginning to 26 April, 2018. The study included 21 eligible trials. Two writers extracted data at the same time independently. Study outcomes were calculated by standardized mean differences (SMD) with 95% confidence intervals (CIs). All statistical analyses were performed using Review Manager Version 5.3 and STATA Version 15.1.
RESULTS
The combined results showed that the use of TA was associated with reduced Melasma Area and Severity Index (MASI) and Melanin Index (MI). No significant difference in Erythema Index (EI) was observed with TA treatment. Side effects were minor, with a few cases reporting mild gastrointestinal reaction, oligomenorrhoea, hypopigmentation, urticarial rash, and skin irritation xerosis.
CONCLUSION
The meta-analysis suggested that TA treatment appeared to be a promising therapeutic approach for melasma.
Topics: Adolescent; Adult; Case-Control Studies; Erythema; Humans; Melanins; Melanosis; Middle Aged; Publication Bias; Randomized Controlled Trials as Topic; Severity of Illness Index; Tranexamic Acid; Young Adult
PubMed: 30533427
DOI: 10.1155/2018/1683414 -
The Cochrane Database of Systematic... May 2018Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 4% to 8% of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 4% to 8% of women worldwide and often leads to anovulatory subfertility. 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).
OBJECTIVES
To evaluate the effectiveness and safety of aromatase inhibitors for subfertile women with anovulatory PCOS for ovulation induction followed by timed intercourse or intrauterine insemination (IUI).
SEARCH METHODS
We searched the following sources from inception to November 2017 to identify relevant randomised controlled trials (RCTs): the Cochrane Gynaecology and Fertility Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, Pubmed, LILACS, Web of Knowledge, the World Health Organization (WHO) clinical trials register and Clinicaltrials.gov. We also searched the references of relevant articles. 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. We pooled studies 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 and OHSS. Secondary outcomes were clinical pregnancy, miscarriage and multiple pregnancy. We assessed the quality of the evidence for each comparison using GRADE methods.
MAIN RESULTS
This is a substantive update of a previous review. We identified 16 additional studies for the 2018 update. We include 42 RCTs (7935 women). The aromatase inhibitor letrozole was used in all studies.Letrozole compared to clomiphene citrate (CC) with or without adjuncts followed by timed intercourseLive birth rates were higher with letrozole (with or without adjuncts) compared to clomiphene citrate (with our without adjuncts) followed by timed intercourse (OR 1.68, 95% CI 1.42 to 1.99; 2954 participants; 13 studies; I = 0%; number needed to treat for an additional beneficial outcome (NNTB) = 10; moderate-quality evidence). There is high-quality evidence that OHSS rates are similar with letrozole or clomiphene citrate (0.5% in both arms: risk difference (RD) -0.00, 95% CI -0.01 to 0.00; 2536 participants; 12 studies; I = 0%; high-quality evidence). There is evidence for a higher pregnancy rate in favour of letrozole (OR 1.56, 95% CI 1.37 to 1.78; 4629 participants; 25 studies; I = 1%; NNTB = 10; moderate-quality evidence). There is little or no difference between treatment groups in the rate of miscarriage by pregnancy (20% with CC versus 19% with letrozole; OR 0.94, 95% CI 0.70 to 1.26; 1210 participants; 18 studies; I = 0%; high-quality evidence) and multiple pregnancy rate (1.7% with CC versus 1.3% with letrozole; OR 0.69, 95% CI 0.41 to 1.16; 3579 participants; 17 studies; I = 0%; high-quality evidence). However, a funnel plot showed mild asymmetry, indicating that some studies in favour of clomiphene might be missing.Letrozole compared to laparoscopic ovarian drillingThere is low-quality evidence that live birth rates are similar with letrozole or laparoscopic ovarian drilling (OR 1.38, 95% CI 0.95 to 2.02; 548 participants; 3 studies; I = 23%; low-quality evidence). There is insufficient evidence for a difference in OHSS rates (RD 0.00, 95% CI -0.01 to 0.01; 260 participants; 1 study; low-quality evidence). There is low-quality evidence that pregnancy rates are similar (OR 1.28, 95% CI 0.94 to 1.74; 774 participants; 5 studies; I = 0%; moderate-quality evidence). There is insufficient evidence for a difference in miscarriage rate by pregnancy (OR 0.66, 95% CI 0.30 to 1.43; 240 participants; 5 studies; I = 0%; moderate-quality evidence), or multiple pregnancies (OR 3.00, 95% CI 0.12 to 74.90; 548 participants; 3 studies; I = 0%; low-quality evidence).Additional comparisons were made for Letrozole versus placebo, Selective oestrogen receptor modulators (SERMS) followed by intrauterine insemination (IUI), follicle stimulating hormone (FSH), Anastrozole, as well as dosage and administration protocols. There is insufficient evidence for a difference in either group of treatment due to a limited number of studies. Hence more research is necessary.
AUTHORS' CONCLUSIONS
Letrozole appears to improve live birth and pregnancy rates in subfertile women with anovulatory polycystic ovary syndrome, compared to clomiphene citrate. There is high-quality evidence that OHSS rates are similar with letrozole or clomiphene citrate. There is high-quality evidence of no difference in miscarriage rates or multiple pregnancy rates. There is low-quality evidence of no difference in live birth and pregnancy rates between letrozole and laparoscopic ovarian drilling, although there were few relevant studies. For the 2018 update, we added good-quality trials, upgrading the quality of the evidence.
Topics: Abortion, Spontaneous; Anastrozole; Aromatase Inhibitors; Birth Rate; Clomiphene; Coitus; Female; Fertility Agents, Female; Humans; Infertility, Female; Letrozole; Live Birth; Nitriles; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy, Multiple; Randomized Controlled Trials as Topic; Triazoles
PubMed: 29797697
DOI: 10.1002/14651858.CD010287.pub3