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Biological Trace Element Research Feb 2017Polycystic ovary syndrome (PCOS) is a prevalent condition in women of reproductive age. PCOS is characterized by androgen excess and chronic anovulation and associated... (Meta-Analysis)
Meta-Analysis Review
Polycystic ovary syndrome (PCOS) is a prevalent condition in women of reproductive age. PCOS is characterized by androgen excess and chronic anovulation and associated with low-grade inflammation and metabolic comorbidities. Some trace elements have been linked to pathophysiological mechanisms of oxidative stress and inflammation in different disorders. Therefore, we conducted a systematic review and meta-analysis of the available evidence regarding trace element concentrations in PCOS. We reviewed MEDLINE and EMBASE in search of case-control, cross-sectional, and cohort studies published until September 2015. Of 183 studies identified, six were selected for systematic review. All used the Rotterdam criteria for the diagnosis of PCOS. Two studies evaluating chromium and one assessing cobalt levels did not observe differences between PCOS and controls. Another study recorded similar nickel and vanadium levels between the groups, but lower selenium concentrations in women with PCOS compared to controls. Four studies were included in the random effects model meta-analysis, for a total of 264 PCOS and 151 control women. Copper levels were found to be higher in women with PCOS than in controls [mean difference 0.12 ppm (95 % CI 0.07; 0.17 ppm); I = 0 %]. Manganese [mean difference 0.04 ppm (95 % CI -0.05; 0.13 ppm); I = 94.4 %] and zinc concentrations [mean difference 0.02 ppm (95 % CI -0.12; 0.16 ppm); I = 92.4 %] were similar between the groups. The present results suggest a relationship between increased copper concentration and PCOS. This systematic review and meta-analysis is registered in PROSPERO under number CRD42016034036.
Topics: Adult; Female; Humans; Oxidative Stress; Polycystic Ovary Syndrome; Trace Elements
PubMed: 27301656
DOI: 10.1007/s12011-016-0774-4 -
Journal of Medicine and Life 2015To elucidate the prepubertal risk factors associated with the development of Polycystic Ovary Syndrome (PCOS) and determine the special clinical manifestations of the... (Review)
Review
RATIONALE
To elucidate the prepubertal risk factors associated with the development of Polycystic Ovary Syndrome (PCOS) and determine the special clinical manifestations of the syndrome in this transitional time of a woman's life.
OBJECTIVE
To propose therapeutic targets and regimens, not only to prevent the long-term complications of the syndrome, but also to improve the self-esteem of a young girl who matures into womanhood.
METHODS AND RESULTS
A systematic review of literature was performed through electronic database searches (Pubmed, Medline and Embase). Studies published in English-language, peer-reviewed journals from 1996 to 2013 were included. The selected studies focused on the risk factors, the unique features and treatment options of the PCOS in puberty. The pathogenesis of the PCOS was hypothesized to be based on interactions between genetic and certain environmental factors. The diagnosis was usually difficult in young girls. The syndrome was related to a greater risk of future infertility, type II diabetes mellitus, the metabolic syndrome and cardiovascular disease. Early treatment was crucial to prevent the long-term complications of the syndrome, especially infertility and cardiovascular disease.
DISCUSSION
The recognition of the early signs of PCOS during or even before adolescence is of great importance. It is essential to establish the correct diagnosis for PCOS and rule out other causes of androgen excess in young women with hyperandrogenism. The type of treatment applied should be considered on an individual basis.
ABBREVIATIONS
PCOS = Polycystic Ovary Syndrome.
Topics: Adolescent; Diagnosis, Differential; Diagnostic Imaging; Female; Humans; Polycystic Ovary Syndrome; Puberty; Risk Factors
PubMed: 26351529
DOI: No ID Found -
Complementary Therapies in Medicine Feb 2015To assess the effect of Traditional Chinese herbal medicine (CHM) in the management of female infertility and on pregnancy rates compared with Western medical (WM)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the effect of Traditional Chinese herbal medicine (CHM) in the management of female infertility and on pregnancy rates compared with Western medical (WM) treatment and update previous meta-analyses.
METHODS
We searched the Medline and Cochrane databases until December 2013 for randomized controlled trials and meta-analyses investigating Chinese herbal medicine therapy for female infertility and compared clinical pregnancy rates achieved with CHM versus WM drug treatment.
RESULTS
Forty RCTs involving 4247 women with infertility were included in our systematic review. Meta-analysis suggested a 1.74 higher probability of achieving a pregnancy with CHM therapy than with WM therapy alone (risk ratio 1.74, 95%CI: 1.56-1.94; p<0.0001; odds ratio 3.14; 95%CI: 2.72-3.62; p<0.0001) in women with infertility. Trials included women with PCOS, endometriosis, anovulation, fallopian tube blockage, or unexplained infertility. Mean pregnancy rates in the CHM group were 60% compared with 33% in the WM group.
CONCLUSIONS
Our review suggests that management of female infertility with Chinese herbal medicine can improve pregnancy rates 2-fold within a 3-6 month period compared with Western medical fertility drug therapy. In addition, fertility indicators such as ovulation rates, cervical mucus score, biphasic basal body temperature, and appropriate thickness of the endometrial lining were positively influenced by CHM therapy, indicating an ameliorating physiological effect conducive for a viable pregnancy.
Topics: Drugs, Chinese Herbal; Female; Humans; Infertility, Female; Medicine, Chinese Traditional; Phytotherapy
PubMed: 25637159
DOI: 10.1016/j.ctim.2014.12.004 -
International Journal of Gynaecology... Apr 2015Infertility associated with polycystic ovary syndrome (PCOS) could be related to many mechanisms including endometrial factors. (Review)
Review
BACKGROUND
Infertility associated with polycystic ovary syndrome (PCOS) could be related to many mechanisms including endometrial factors.
OBJECTIVES
To review cell adhesion molecule and estrogen receptor expression in the endometrium.
SEARCH STRATEGY
A systematic review was performed of the Medline and Cochrane databases for papers published in any language between 2004 and 2014. The search term was "'polycystic ovary syndrome' OR 'Stein Leventhal syndrome' OR 'anovulation' AND 'endometrium' OR 'endometria.'"
SELECTION CRITERIA
Research studies on endometrial cell adhesion molecules and estrogen receptor expression among women with PCOS diagnosed according to the Rotterdam criteria were included.
DATA COLLECTION AND ANALYSIS
Data were extracted from identified studies and the quality of assessment was analyzed.
MAIN RESULTS
Six studies were included. Data were controversial with respect to MUC1 and αVβ3 integrin expression with significantly higher and lower levels, respectively, in women with PCOS. Estrogen receptor expression was enhanced among patients with PCOS as compared with healthy women.
CONCLUSIONS
Endometrial factors influence embryo receptivity as indicated by the molecular mediators identified in the studies, including cell adhesion molecules and the estrogen receptor.
Topics: Cell Adhesion Molecules; Endometrium; Female; Humans; Polycystic Ovary Syndrome; Receptors, Estrogen
PubMed: 25554522
DOI: 10.1016/j.ijgo.2014.10.022 -
The Cochrane Database of Systematic... Nov 2014The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation (IVF) cycles has been widely studied. Metformin reduces hyperinsulinaemia and suppresses the excessive ovarian production of androgens. As a consequence, it is suggested that metformin could improve assisted reproductive techniques (ART) outcomes, such as ovarian hyperstimulation syndrome (OHSS), pregnancy and live birth rates.
OBJECTIVES
To determine the effectiveness and safety of metformin as a co-treatment during IVF or intracytoplasmic sperm injection (ICSI) in achieving pregnancy or live birth in women with PCOS.
SEARCH METHODS
We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, LILACS, the metaRegister of Controlled Trials and reference lists of articles (up to 15 October 2014).
SELECTION CRITERIA
Types of studies: randomised controlled trials (RCTs) comparing metformin treatment with placebo or no treatment in women with PCOS who underwent IVF or ICSI treatment.
TYPES OF PARTICIPANTS
women of reproductive age with anovulation due to PCOS with or without co-existing infertility factors.Types of interventions: metformin administered before and during IVF or ICSI treatment.Types of outcome measures: live birth rate, clinical pregnancy rate, miscarriage rate, incidence of ovarian hyperstimulation syndrome , incidence of participant-reported side effects, serum oestradiol level on the day of trigger, serum androgen level, and fasting insulin and glucose levels.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the studies, extracted the data according to the protocol and assessed study quality. The overall quality of the evidence was assessed using GRADE methods.
MAIN RESULTS
We included nine randomised controlled trials involving a total of 816 women with PCOS. When metformin was compared with placebo there was no clear evidence of a difference between the groups in live birth rates (OR 1.39, 95% CI 0.81 to 2.40, five RCTs, 551 women, I(2) = 52%, low-quality evidence). Our findings suggest that for a woman with a 32 % chance of achieving a live birth using placebo or other treatment, the corresponding chance using metformin treatment would be between 28% and 53%.When metformin was compared with placebo or no treatment, clinical pregnancy rates were higher in the metformin group (OR 1.52; 95% CI 1.07 to 2.15; eight RCTs, 775 women, I(2) = 18%, moderate-quality evidence). This suggests that for a woman with a 31% chance of achieving a clinical pregnancy using placebo or no treatment, the corresponding chance using metformin treatment would be between 32% and 49%.The risk of ovarian hyperstimulation syndrome was lower in the metformin group (OR 0.29; 95% CI 0.18 to 0.49, eight RCTs, 798 women, I(2) = 11%, moderate-quality evidence). This suggests that for a woman with a 27% risk of having OHSS without metformin the corresponding chance using metformin treatment would be between 6% and 15%.Side effects (mostly gastrointestinal) were more common in the metformin group (OR 4.49, 95% CI 1.88 to 10.72, for RCTs, 431 women, I(2)=57%, low quality evidence)The overall quality of the evidence was moderate for the outcomes of clinical pregnancy, OHSS and miscarriage, and low for other outcomes. The main limitations in the evidence were imprecision and inconsistency.
AUTHORS' CONCLUSIONS
This review found no conclusive evidence that metformin treatment before or during ART cycles improved live birth rates in women with PCOS. However, the use of this insulin-sensitising agent increased clinical pregnancy rates and decreased the risk of OHSS.
Topics: Female; Fertilization in Vitro; Humans; Hyperandrogenism; Hyperinsulinism; Hypoglycemic Agents; Live Birth; Metformin; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic
PubMed: 25406011
DOI: 10.1002/14651858.CD006105.pub3 -
The Cochrane Database of Systematic... Jan 2014Anovulation is a common cause of infertility. Drugs used to treat anovulation include selective oestrogen receptor modulators, aromatase inhibitors and gonadotrophins.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anovulation is a common cause of infertility. Drugs used to treat anovulation include selective oestrogen receptor modulators, aromatase inhibitors and gonadotrophins. Ovulation triggers are used with these drugs, as a surrogate for the hormonal surge seen in spontaneous menstrual cycles, to control the timing of ovulation and the timing of sexual intercourse. Ovulation triggers given without reliable evidence of oocyte maturity could be inappropriately timed; they increase costs, and the need to time intercourse precisely after the ovulation trigger is given adds to psychological stress.This is an update of a Cochrane review first published in Issue 3, 2008, of the Cochrane Database of Systematic Reviews.
OBJECTIVES
To determine the benefits and harms of administering an ovulation trigger to anovulatory women receiving treatment with ovulation-inducing agents in comparison with spontaneous ovulation following ovulation induction.
SEARCH METHODS
We updated searches of the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and PsycINFO to November 2013. We checked conference proceedings, trial registries and reference lists and contacted researchers.
SELECTION CRITERIA
Parallel-group, randomised, controlled trials (RCTs) evaluating the administration of an ovulation trigger to anovulatory women receiving treatment with ovulation-inducing agents.
DATA COLLECTION AND ANALYSIS
We independently assessed trial eligibility and trial quality and extracted data. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous data and used the random-effects model in meta-analyses when significant heterogeneity was present. We assessed overall quality of the evidence by using the GRADE approach.
MAIN RESULTS
No new trials were identified. This review includes two RCTs with low risk of bias that compared urinary human chorionic gonadotrophin (hCG) versus no treatment in anovulatory women receiving clomiphene citrate. Urinary hCG did not result in an increase in live birth rate over no hCG (OR 0.97, 95% CI 0.52 to 1.83; two trials, 305 participants, I(2) = 16%; low-quality evidence), but very serious imprecision around the effect estimate reduces our confidence in the apparent lack of effect of hCG as an ovulation trigger in clomiphene-induced cycles in anovulatory women.Among this review's secondary outcomes, urinary hCG may not increase ovulation rate (OR 0.99, 95% CI 0.36 to 2.77; two trials, 305 participants, I(2) = 55%; low-quality evidence), clinical pregnancy rate (OR 1.02, 95% CI 0.56 to 1.89; two trials, 305 participants, I(2) = 35%; low-quality evidence) or miscarriage rate in pregnant women (OR 1.19, 95% CI 0.17 to 8.23; two trials, 54 participants, I(2) = 0%; low-quality evidence). Multiple pregnancies and preterm deliveries were uncommon, and ovarian hyperstimulation syndrome, adverse events and deaths were not reported as outcomes in either trial. We found no trials evaluating other ovulation triggers.
AUTHORS' CONCLUSIONS
Evidence is inadequate to recommend or refute the use of urinary hCG as an ovulation trigger in anovulatory women treated with clomiphene citrate. We found no trials evaluating the use of ovulation triggers in anovulatory women treated with other ovulation-inducing agents.
Topics: Anovulation; Chorionic Gonadotropin; Clomiphene; Female; Fertility Agents, Female; Humans; Ovulation Induction; Pregnancy; Randomized Controlled Trials as Topic; Reproductive Control Agents
PubMed: 24482059
DOI: 10.1002/14651858.CD006900.pub3 -
Human Reproduction Update 2014BACKGROUND The measurement of circulating anti-Müllerian hormone (AMH) has been applied to a wide array of clinical applications, mainly based on its ability to reflect... (Review)
Review
BACKGROUND The measurement of circulating anti-Müllerian hormone (AMH) has been applied to a wide array of clinical applications, mainly based on its ability to reflect the number of antral and pre-antral follicles present in the ovaries. AMH has been suggested to predict the ovarian response to hyperstimulation of the ovaries for IVF and the timing of menopause, and to indicate iatrogenic damage to the ovarian follicle reserve. It has also been proposed as a surrogate for antral follicle count (AFC) in the diagnosis of polycystic ovary syndrome (PCOS). METHODS This paper is a summary of presentations at a European Society of Human Reproduction and Embryology campus workshop on AMH, with literature cited until September 2013. Published peer-reviewed medical literature about AMH was searched through MEDLINE and was subjected to systematic review and critical assessment by the panel of authors. RESULTS Physiologically, recent data confirm that AMH is a follicular gatekeeper limiting follicle growth initiation, and subsequently estradiol production from small antral follicles prior to selection. AMH assays continue to evolve and technical issues remain; the absence of an international standard is a key issue. The dynamics of circulating AMH levels throughout life can be split into several distinct phases, with a peak in the early 20s before a decline to the menopause, with a strong and positive correlation with non-growing follicle recruitment. There is a more complex rise during childhood and adolescence, which is likely to be more reflective of different stages of follicle development. AMH shows limited short-term variability, but the influence of states such as prolonged oral contraceptive use need to be considered in clinical assessment. There are only very limited data on relationships between AMH and natural fertility at different stages of reproductive life, and while it has a relationship to age at menopause the marked variability in this needs further exploration. AMH may be useful in assessing the need for fertility preservation strategies and detecting post-chemotherapy or surgical damage to the ovarian reserve. Long-term follow-up of patients to ascertain fully the value of post-cancer serum AMH in predicting long-term ovarian function is required. There is a linear relationship between AMH and oocyte yield after ovarian stimulation, which is of value in predicting ovarian hyperstimulation. AMH can also identify 'poor responders', but it seems inappropriate at present to withhold IVF purely on this basis. Women with PCOS show markedly raised AMH levels, due to both the increased number of small antral follicles and intrinsic characteristics of those granulosa cells, and this may contribute to anovulation. The value of AMH in the diagnosis of PCOS remains controversial, but it may replace AFC in the future. CONCLUSIONS For the first time in female reproductive biology, it is possible to measure the submerged part of the iceberg of follicle growth, i.e. the intrinsic, so-called 'acyclic' ovarian activity. An international standard for AMH and improved assay validity are urgently needed to maximize the clinical utility of this very promising biomarker of ovarian function in a large array of clinical situations, both in childhood and adulthood.
Topics: Aging; Anti-Mullerian Hormone; Biomarkers; Estradiol; Female; Humans; Infertility; Menopause; Ovarian Diseases; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Reproduction
PubMed: 24430863
DOI: 10.1093/humupd/dmt062 -
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 -
Journal of Alternative and... Dec 2012The aim of this systematic review is to assess the effectiveness and safety of Chinese herbal medicine (CHM) in treatment of anovulation and infertility in women. Eight... (Meta-Analysis)
Meta-Analysis Review
The aim of this systematic review is to assess the effectiveness and safety of Chinese herbal medicine (CHM) in treatment of anovulation and infertility in women. Eight (8) databases were extensively retrieved. The Chinese electronic databases included VIP Information, CMCC, and CNKI. The English electronic databases included AMED, CINAHL, Cochrane Library, Embase, and MEDLINE(®). Randomized controlled trials using CHM as intervention were included in the study selection. The quality of studies was assessed by the Jadad scale and the criteria referred to Cochrane reviewers' handbook. The efficacy of CHM treatment for infertility with anovulation was evaluated by meta-analysis. There were 692 articles retrieved according to the search strategy, and 1659 participants were involved in the 15 studies that satisfied the selection criteria. All the included trials were done in China. Meta-analysis indicated that CHM significantly increased the pregnancy rate (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.50-3.88) and reduced the miscarriage rate (OR 0.2, 95% CI 0.10-0.41) compared to clomiphene. In addition, CHM also increased the ovulation rate (OR 1.55, 95% CI 1.06-2.25) and improved the cervical mucus score (OR 3.82, 95% CI 1.78-8.21) compared to clomiphene, while there were no significant difference between CHM and clomiphene combined with other medicine. CHM is effective in treating infertility with anovulation. Also, no significant adverse effects were identified for the use of CHM from the studies included in this review. However, owing to the low quality of the studies investigated, more randomized controlled trials are needed before evidence-based recommendation regarding the effectiveness and safety of CHM in the management of infertility with anovulation can be provided.
Topics: Anovulation; Cervix Uteri; Clomiphene; Drugs, Chinese Herbal; Female; Fertility Agents, Female; Humans; Infertility, Female; Mucus; Ovulation; Phytotherapy; Pregnancy; Pregnancy Rate
PubMed: 23198826
DOI: 10.1089/acm.2011.0371 -
The Cochrane Database of Systematic... Sep 2012Irregular menstrual bleeding may arise due to exogenous sex steroids, lesions of the genital tract or be associated with anovulation. Irregular bleeding due to... (Review)
Review
BACKGROUND
Irregular menstrual bleeding may arise due to exogenous sex steroids, lesions of the genital tract or be associated with anovulation. Irregular bleeding due to oligo/anovulation (previously called dysfunctional uterine bleeding or DUB) is more common at the extremes of reproductive life, and in women with ovulatory disorders such as polycystic ovary syndrome (PCOS). In anovulatory cycles there may be prolonged oestrogen stimulation of the endometrium without progesterone withdrawal and so cycles are irregular and bleeding may be heavy. This is the rationale for using cyclical progestogens during the second half of the menstrual cycle, in order to provoke a regular withdrawal bleed. Continuous progestogen is intended to induce endometrial atrophy and hence to prevent oestrogen-stimulated endometrial proliferation. Progestogens, and oestrogens and progestogens in combination, are widely used in the management of irregular menstrual bleeding, but the regime, dose and type of progestogen used vary widely, with little consensus about the optimum treatment approach.
OBJECTIVES
To determine the effectiveness and acceptability of progestogens alone or in combination with oestrogens in the regulation of irregular menstrual bleeding associated with oligo/anovulation.
SEARCH METHODS
We searched the following databases in February 2012: Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and reference lists of articles.
SELECTION CRITERIA
All randomised controlled trials of progestogens (via any route) alone or in combination with oestrogens in the treatment of irregular menstrual bleeding associated with oligo/anovulation.
DATA COLLECTION AND ANALYSIS
Study quality assessment and data extraction were carried out independently by two review authors. All authors were experts in the content of this review.
MAIN RESULTS
No randomised trials were identified that compared progestogens with oestrogens and progestogens or with placebo in the management of irregular bleeding associated with oligo/anovulation.
AUTHORS' CONCLUSIONS
There is a paucity of randomised studies relating to the use of progestogens and of oestrogens and progestogens in combination in the treatment of irregular menstrual bleeding associated with anovulation. There is no consensus about which regimens are most effective. Further research is needed to establish the role of these hormonal treatments in the management of this common gynaecological problem.
Topics: Adult; Anovulation; Drug Therapy, Combination; Estrogens; Female; Humans; Menorrhagia; Progestins
PubMed: 22972055
DOI: 10.1002/14651858.CD001895.pub3