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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 -
Reproductive Sciences (Thousand Oaks,... Apr 2024Clomiphene citrate (CC) and letrozole are the predominant medical interventions for the management of infertility in patients with polycystic ovary syndrome (PCOS). To... (Meta-Analysis)
Meta-Analysis Review
Clomiphene citrate (CC) and letrozole are the predominant medical interventions for the management of infertility in patients with polycystic ovary syndrome (PCOS). To comprehensively summarize the evidence, a systematic review and meta-analysis of randomized clinical trials (RCTs) was carried out to assess the effect of letrozole and CC on pregnancy outcomes in PCOS patients. We searched PubMed/MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials from inception to January 2023. We included RCTs conducted on PCOS women comparing letrozole to CC and assessing endometrial thickness, the number and size of follicles, and ovulation and pregnancy rates. The endpoints were summarized as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI) using the random-effects model. Heterogeneity was examined using the I statistic. Fifty trials met our inclusion criteria. The mean endometrial thickness was significantly higher in the letrozole group compared to CC group (SMD: 0.89; 95% CI: 0.49, 1.28; I=97.72%); however, the number of follicles was higher in the CC group (SMD: -0.56; 95% CI: -0.96, -0.17; I=96.34%). Furthermore, letrozole intake induced higher ovulation rate (RR: 1.20; 95% CI: 1.13, 1.26; I=54.49%) and pregnancy rate (RR: 1.44; 95% CI: 1.28, 1.62; I=65.58%) compared to CC. Compared to CC, letrozole has a positive effect on endometrial thickness, monofollicular development, and ovulation and pregnancy rates suggesting that letrozole may be a strong alternative to CC as a first-line medical intervention for chronic anovulation in PCOS women. Larger studies are warranted to further clarify these findings.
Topics: Pregnancy; Female; Humans; Letrozole; Pregnancy Outcome; Polycystic Ovary Syndrome; Fertility Agents, Female; Infertility, Female; Birth Rate; Ovulation Induction; Clomiphene; Pregnancy Rate
PubMed: 38030814
DOI: 10.1007/s43032-023-01404-8 -
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 -
Human Reproduction Update Sep 2020A dynamic balance between pro- and anti-inflammatory factors contributes to regulating human female reproduction. Chronic low-grade inflammation has been detected in...
BACKGROUND
A dynamic balance between pro- and anti-inflammatory factors contributes to regulating human female reproduction. Chronic low-grade inflammation has been detected in several female reproductive conditions, from anovulation to embryo implantation failure. C-reactive protein (CRP) is a reliable marker of inflammation that is extensively used in clinical practice. Recent studies quantified CRP in the serum of infertile women undergoing ART and suggested its potential for the prediction of ART reproductive outcomes.
OBJECTIVE AND RATIONALE
The first objective of this systematic review of the available literature was to evaluate the association between pre-implantation circulating CRP concentration and pregnancy rates in women undergoing ART. The second objective was to describe serum CRP concentration changes after early embryo implantation. The changes in circulating CRP throughout the ART cycle, clinical implications of CRP quantification for the management of women undergoing ART, and future therapeutic options will also be discussed.
SEARCH METHODS
The MEDLINE database was systematically searched from inception to March 2019 using the following key words: (C-reactive protein) AND (assisted reproductive techniques OR ovulation induction OR insemination OR in vitro fertilization). Only articles in English were considered. Studies were selected based on title and abstract. The full text of potentially relevant articles was retrieved and assessed for inclusion by two reviewers (S.B. and S.H.). The protocol was registered in the International prospective register of systematic reviews (PROSPERO; registration number: CRD148687).
OUTCOMES
In total, 10 studies were included in this systematic review. Most of these studies reported lower circulating CRP values before the window of implantation and higher circulating CRP values during the peri-implantation period in women with successful ART outcome (biochemical or clinical pregnancy) compared to women without a successful outcome. Several lifestyle factors and/or drugs that reduce the concentration of circulating CRP significantly improve ART outcomes. Subgroup analyses according to female BMI and baseline circulating CRP concentration are highly recommended in future analyses.
WIDER IMPLICATIONS
These findings highlight a possible detrimental impact of preconception high circulating CRP concentration on ART outcomes. However, the biochemical or clinical pregnancy rate endpoints used in the studies examined here are insufficient (there were no data on live birth outcome), and the impact of major variables that can influence CRP and/or ART, for example maternal age, BMI, number of transferred embryos, and use of anti-inflammatory drugs, were not considered in the analyses. CRP quantification may be a potential marker of ART outcome, but its predictive value still needs to be investigated in large prospective studies. In future, the quantification of circulating CRP before starting ART could help to identify patients with a poor ART prognosis, leading to ART cycle cancellation or to preconception treatment to minimize the medical risks and costs.
Topics: Anovulation; C-Reactive Protein; Embryo Transfer; Female; Fertilization in Vitro; Humans; Infertility, Female; Maternal Age; Ovulation Induction; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Reproductive Techniques, Assisted; Treatment Outcome
PubMed: 32469070
DOI: 10.1093/humupd/dmaa012 -
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 -
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 -
Reproductive Sciences (Thousand Oaks,... Jul 2024Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder that is frequently linked to anovulation in women who are experiencing infertility.... (Meta-Analysis)
Meta-Analysis Review
Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder that is frequently linked to anovulation in women who are experiencing infertility. Intestinal flora, also known as the "second genome" of the host, is closely associated with chronic metabolic diseases. Recently, there has been increasing attention on the connection between PCOS and the gut microbiome, and experiments have been conducted. However, the results were unsatisfactory and inconsistent. This review aims to provide a comprehensive overview of the literature investigating the associations between the gut microbiome and PCOS in adults. The goal is to identify whether there are changes in the composition of the gut microbiome in individuals with PCOS. This is the first systematic review to focus on functional alterations in the gut microbiome, which could provide insights into potential mechanisms of microbial involvement in the development of PCOS. We found that there was no significant change in gut microbiome biodiversity in PCOS. Meta-analyses of three studies revealed a significantly higher abundance of Proteobacteria (1.12, 95% CI, 0.21, 2.02, I = 0%) in adults with PCOS. At the genus level, Bacteroides, Enterococcus, and Escherichia-Shigella were found to be enriched in patients with PCOS. Species such as Ruminococcus gnavus group, Parabacteroides distasonis, and Bacteroides fragilis showed an increase in PCOS. Metabolic pathways associated with glucose, lipid metabolism, bile acid metabolism, and protein absorption were found to be enriched in individuals with PCOS. The gut microbiome in PCOS is not characterized by lower diversity, but the composition is altered at the phylum, family, genus, or species level. Consequently, the metabolic pathway differs according to the phenotype of PCOS.
Topics: Polycystic Ovary Syndrome; Humans; Gastrointestinal Microbiome; Female; Adult; Observational Studies as Topic
PubMed: 38212581
DOI: 10.1007/s43032-023-01440-4 -
BMJ (Clinical Research Ed.) Oct 2022
PubMed: 36280257
DOI: 10.1136/bmj.o2436 -
Obesity Reviews : An Official Journal... Aug 2021Women with polycystic ovary syndrome (PCOS) exhibit reduced muscle insulin-mediated glucose uptake, potentially attributed to altered muscle mass; however, this is... (Meta-Analysis)
Meta-Analysis Review
Obesity, but not hyperandrogenism or insulin resistance, predicts skeletal muscle mass in reproductive-aged women with polycystic ovary syndrome: A systematic review and meta-analysis of 45 observational studies.
Women with polycystic ovary syndrome (PCOS) exhibit reduced muscle insulin-mediated glucose uptake, potentially attributed to altered muscle mass; however, this is inconclusive. Altered muscle mass may aggravate PCOS complications. Our systematic review and meta-analysis evaluated whether PCOS alters muscle mass and function. Databases (MEDLINE, Web of Science, Scopus) were searched through September 2, 2020, for studies documenting skeletal muscle mass (lean tissue mass) and function (strength) in PCOS and control groups. The primary outcome was total lean body mass (LBM) or fat-free mass (FFM). Data were pooled by random-effects models and expressed as mean differences and 95% confidence intervals. Forty-five studies (n = 3676 participants) were eligible. Women with PCOS had increased total (0.83 [0.08,1.58] kg; p = 0.03; I = 72.0%) yet comparable trunk (0.84 [-0.37,2.05] kg; p = 0.15; I = 73.0%) LBM or FFM versus controls. Results of meta-regression analyses showed no associations between mean differences between groups in total testosterone or homeostatic model assessment of insulin resistance and total or trunk LBM or FFM (All: p ≥ 0.75). Mean differences in body mass index (BMI) were associated with total (0.65 [0.23,1.06] kg; p < 0.01; I = 56.9%) and trunk (0.56 [0.11,1.01] kg; p = 0.02; I = 42.8%) LBM or FFM. The PCOS subgroup with BMI ≥ 25 kg/m had greater total LBM or FFM versus controls (1.58 [0.82,2.34] kg; p < 0.01; I = 64.0%) unlike the PCOS subgroup with BMI < 25 kg/m (-0.45 [-1.94,1.05] kg; p = 0.53; I = 69.5%). Appendicular lean mass and muscle strength data were contradictory and described narratively, as meta-analyses were impossible. Women with PCOS have higher total and trunk lean tissue mass attributed to overweight/obesity, unlike hyperandrogenism or insulin resistance.
Topics: Adult; Body Mass Index; Female; Humans; Hyperandrogenism; Insulin Resistance; Muscle, Skeletal; Obesity; Polycystic Ovary Syndrome
PubMed: 33855800
DOI: 10.1111/obr.13255 -
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