-
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 -
Frontiers in Endocrinology 2022Many patients with congenital adrenal hyperplasia (CAH) refrain from seeking pregnancy, suffer from infertility or worry about pregnancy complications, mainly due to... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Many patients with congenital adrenal hyperplasia (CAH) refrain from seeking pregnancy, suffer from infertility or worry about pregnancy complications, mainly due to genitalia abnormalities, anovulation, unreceptive endometrium and metabolic disturbances. Despite those challenges, many live births have been reported. In this systematic review, we focused on the key to successful assisted reproduction strategies and the potential pregnancy complications. We did a systematic literature search of Pubmed, Medline and Scopus for articles reporting successful pregnancies in CAH other than 21-hydroxylase deficiency, and found 25 studies reporting 39 pregnancies covering deficiency in steroidogenic acute regulatory protein, 17α-hydroxylase/17,20-lyase, 11β-hydroxylase, P450 oxidoreductase, cytochrome b5 and 3β-hydroxysteroid dehydrogenase. We summarized various clinical manifestations and tailored reproduction strategy for each subtype. Furthermore, a meta-analysis was performed to evaluate the pregnancy complications of CAH patients. A total of 19 cross-sectional or cohort studies involving 1311 pregnancies of classic and non-classic CAH patients were included. Surprisingly, as high as 5.5% (95% CI 2.3%-9.7%) of pregnancies were electively aborted, and the risk was significantly higher in those studies with a larger proportion of classic CAH than those with only non-classical patients (8.43% (4.1%-13.81%) VS 3.75%(1.2%-7.49%)), which called for better family planning. Pooled incidence of miscarriage was 18.2% (13.4%-23.4%) with a relative risk (RR) of 1.86 (1.27-2.72) compared to control. Glucocorticoid treatment in non-classical CAH patients significantly lowered the miscarriage rate when compared to the untreated group (RR 0.25 (0.13-0.47)). CAH patients were also more susceptible to gestational diabetes mellitus, with a prevalence of 7.3% (2.4%-14.1%) and a RR 2.57 (1.29-5.12). However, risks of preeclampsia, preterm birth and small for gestational age were not significantly different. 67.8% (50.8%-86.9%) CAH patients underwent Cesarean delivery, 3.86 (1.66-8.97) times the risk of the control group. These results showed that fertility is possible for CAH patients but special care was necessary when planning, seeking and during pregnancy.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=342642, CRD42022342642.
Topics: Abortion, Spontaneous; Adrenal Hyperplasia, Congenital; Cross-Sectional Studies; Cytochromes b5; Female; Glucocorticoids; Humans; Hydroxysteroid Dehydrogenases; Infant, Newborn; Pregnancy; Pregnancy Complications; Premature Birth; Reproduction; Steroid 17-alpha-Hydroxylase
PubMed: 36120452
DOI: 10.3389/fendo.2022.982953 -
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 -
Frontiers in Endocrinology 2019Twenty-one-hydroxylase-deficient non-classic adrenal hyperplasia (NC-CAH) is a very common autosomal recessive syndrome with prevalence between 1:1,000 and 1:2,000...
Twenty-one-hydroxylase-deficient non-classic adrenal hyperplasia (NC-CAH) is a very common autosomal recessive syndrome with prevalence between 1:1,000 and 1:2,000 individuals and the frequency varies according to ethnicity. On the other hand, polycystic ovary syndrome has a familial basis and it is inherited under a complex hereditary trait. This syndrome affects 6 to 10% of women in reproductive age and it is the most common endocrine disorder in young women. Our aim was to investigate, through a systematic review, the distinct characteristics and common findings of these syndromes. The search period covered January 1970 to November 2018, using the scientific databases PubMed. Inclusion criteria were adult women patients with PCOS or NC-CAH. Search terms were "polycystic ovary syndrome," "PCOS," "non-classical adrenal hyperplasia," "NC-CAH," "21-hydroxylase deficiency." From an initial 16,255 titles, the evaluations led to the final inclusion of 97 papers. The clinical features of NC-CAH are hirsutism and ovulatory and menstrual dysfunction therefore; differentiation between these two syndromes is difficult based on clinical grounds only. Additionally, NC-CAH and PCOS are both associated with obesity, insulin resistance, and dyslipidaemia. Reproductive abnormalities are also common between these hyperandrogenemic disorders since in patients with NC-CAH polycystic ovarian morphology and subfertility are present as they are in women with PCOS. The diagnosis of PCOS, is confirmed once other disorders that mimic PCOS have been excluded e.g., conditions that are related to oligoovulation or anovulation and/or hyperandrogenism, such as hyperprolactinaemia, thyroid disorders, non-classic congenital adrenal hyperplasia, and androgen-producing neoplasms. The screening tool to distinguish non-classic adrenal hyperplasia from PCOS is the measurement of 17-hydroxyprogesterone levels. The basal levels of 17-hydroxyprogesterone may overlap, but ACTH stimulation testing can distinguish the two entities. In this review these two common endocrine disorders are discussed in an effort to unveil their commonalities and to illuminate their shadowed distinctive characteristics.
PubMed: 31275245
DOI: 10.3389/fendo.2019.00388 -
BMJ (Clinical Research Ed.) Oct 2022
PubMed: 36280257
DOI: 10.1136/bmj.o2436 -
Human Reproduction Update 2011Patients with polycystic ovary syndrome (PCOS) are at risk of arterial disease. We examined the risk of (non)fatal coronary heart disease (CHD) or stroke in patients... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with polycystic ovary syndrome (PCOS) are at risk of arterial disease. We examined the risk of (non)fatal coronary heart disease (CHD) or stroke in patients with PCOS and ovulatory women without PCOS, and assessed whether obesity might explain a higher risk of CHD or stroke.
METHODS
We performed a systematic review and meta-analysis of controlled observational studies. Four definitions of PCOS were considered: World Health Organization type II anovulation, National Institutes of Health criteria, Rotterdam consensus and Androgen-excess criteria. Obesity was defined as BMI > 30 kg/m(2) and/or waist circumference >88 cm. Study quality was assessed using the Newcastle-Ottawa Scale. Primary outcome was fatal/non-fatal CHD or stroke. Definitions of CHD and stroke were based on criteria used by the various authors. The effect measure was the pooled relative risk in a random effects model. Risk ratios and rate ratios were combined here.
RESULTS
After identifying 1340 articles, 5 follow-up studies published between 2000 and 2008 were included. The studies showed heterogeneity in design, definitions and quality. In a random effects model the relative risk for CHD or stroke were 2.02 comparing women with PCOS to women without PCOS (95% confidence interval 1.47, 2.76). Pooling the two studies with risk estimates adjusted for BMI showed a relative risk of 1.55 (1.27, 1.89).
CONCLUSIONS
This meta-analysis showed a 2-fold risk of arterial disease for patients with PCOS relative to women without PCOS. BMI adjustment did not affect this finding, suggesting the increased risk for cardiovascular events in PCOS is not completely related to a higher BMI in patients with PCOS.
Topics: Adult; Aged; Body Mass Index; Coronary Disease; Female; Humans; Middle Aged; Obesity; Polycystic Ovary Syndrome; Risk Factors; Stroke
PubMed: 21335359
DOI: 10.1093/humupd/dmr001 -
The Cochrane Database of Systematic... Oct 2007Dysfunctional uterine bleeding (DUB) is excessively heavy, prolonged or frequent bleeding of uterine origin which is not due to pregnancy or to recognisable pelvic or... (Review)
Review
BACKGROUND
Dysfunctional uterine bleeding (DUB) is excessively heavy, prolonged or frequent bleeding of uterine origin which is not due to pregnancy or to recognisable pelvic or systemic disease. Anovulation may be inferred from a number of observations but, in the normal clinical situation, anovulation is often assumed when a woman presents with heavy, prolonged or frequent bleeding, particularly in those who are at the extremes of reproductive life and in women known to have polycystic ovarian syndrome. Menstrual bleeding that is irregular or excessive is poorly tolerated by the majority of women. Changes in the length of the menstrual cycle generally imply disturbances of the hypothalamo-pituitary-ovarian (HPO) axis. In anovulatory DUB with acyclic (irregular) oestrogen production there will be no progesterone withdrawal from oestrogen primed endometrium and so cycles are irregular. Prolonged oestrogen stimulation may cause a build up of endometrium with erratic bleeding as it breaks down and is expelled. 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 already widely used in the management of irregular or excessive bleeding due to DUB but the regime, dose and type of progestogen used varies widely, with little consensus about the optimum treatment approach.
OBJECTIVES
To determine the effectiveness and acceptability of progestogens alone and oestrogens and progestogens in combination in the management of irregular bleeding associated with anovulation.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched 4 May 2007), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2), MEDLINE (1966 to May 2007), EMBASE (1985 to May 2007), CINAHL (1982 to May 2007), Biological Abstracts (1969 to May 2007), Current Contents (1980 to 2007) 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 bleeding associated with anovulation.
DATA COLLECTION AND ANALYSIS
Study quality assessment and data extraction were carried out independently by two review authors. Both authors were experts in the content matter.
MAIN RESULTS
No randomised trials were identified which compared progestogens with oestrogens and progestogens or with placebo in the management of irregular bleeding associated with anovulation. Only one small, non-randomised study compared two progestogen regimes in the management of heavy and irregular bleeding in women with confirmed anovulation. One randomised study compared the effects of two progestogens on endometrial histology in women with a variety of menstrual symptoms, half of whom had cystic glandular hyperplasia.
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 bleeding associated with anovulation. Further research is needed to establish the role of these treatments in the management of this common gynaecological problem.
Topics: Adult; Anovulation; Drug Therapy, Combination; Estrogens; Female; Humans; Menorrhagia; Progestins
PubMed: 17943761
DOI: 10.1002/14651858.CD001895.pub2 -
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 -
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 -
BMJ (Clinical Research Ed.) Oct 2003To assess the effectiveness of metformin in improving clinical and biochemical features of polycystic ovary syndrome. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the effectiveness of metformin in improving clinical and biochemical features of polycystic ovary syndrome.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Randomised controlled trials that investigated the effect of metformin compared with either placebo or no treatment, or compared with an ovulation induction agent.
SELECTION OF STUDIES
13 trials were included for analysis, including 543 women with polycystic ovary syndrome that was defined by using biochemical or ultrasound evidence.
MAIN OUTCOME MEASURE
Pregnancy and ovulation rates. Secondary outcomes of clinical and biochemical features of polycystic ovary syndrome.
RESULTS
Meta-analysis showed that metformin is effective in achieving ovulation in women with polycystic ovary syndrome, with odds ratios of 3.88 (95% confidence interval 2.25 to 6.69) for metformin compared with placebo and 4.41 (2.37 to 8.22) for metformin and clomifene compared with clomifene alone. An analysis of pregnancy rates shows a significant treatment effect for metformin and clomifene (odds ratio 4.40, 1.96 to 9.85). Metformin has an effect in reducing fasting insulin concentrations, blood pressure, and low density lipoprotein cholesterol. We found no evidence of any effect on body mass index or waist:hip ratio. Metformin was associated with a higher incidence of nausea, vomiting, and other gastrointestinal disturbance.
CONCLUSIONS
Metformin is an effective treatment for anovulation in women with polycystic ovary syndrome. Its choice as a first line agent seems justified, and there is some evidence of benefit on variables of the metabolic syndrome. No data are available regarding the safety of metformin in long term use in young women and only limited data on its safety in early pregnancy. It should be used as an adjuvant to general lifestyle improvements and not as a replacement for increased exercise and improved diet.
Topics: Blood Pressure; Body Weight; Double-Blind Method; Female; Fertility Agents, Female; Humans; Insulin; Lipids; Metformin; Ovulation; Polycystic Ovary Syndrome; Pregnancy; Randomized Controlled Trials as Topic; Single-Blind Method; Treatment Outcome
PubMed: 14576245
DOI: 10.1136/bmj.327.7421.951