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Human Reproduction Update Nov 2022To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones...
BACKGROUND
To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones produced by the ovaries. Mature oocytes may be fertilized in the fallopian tubes, and the resulting zygote is transported toward the uterus, where it can implant and continue developing. The cervix acts as a physical barrier to protect the fetus throughout pregnancy, and the vagina acts as a birth canal (involving uterine and cervix mechanisms) and facilitates copulation. Fertility can be compromised by pathologies that affect any of these organs or processes, and therefore, being able to accurately model them or restore their function is of paramount importance in applied and translational research. However, innate differences in human and animal model reproductive tracts, and the static nature of 2D cell/tissue culture techniques, necessitate continued research and development of dynamic and more complex in vitro platforms, ex vivo approaches and in vivo therapies to study and support reproductive biology. To meet this need, bioengineering is propelling the research on female reproduction into a new dimension through a wide range of potential applications and preclinical models, and the burgeoning number and variety of studies makes for a rapidly changing state of the field.
OBJECTIVE AND RATIONALE
This review aims to summarize the mounting evidence on bioengineering strategies, platforms and therapies currently available and under development in the context of female reproductive medicine, in order to further understand female reproductive biology and provide new options for fertility restoration. Specifically, techniques used in, or for, the uterus (endometrium and myometrium), ovary, fallopian tubes, cervix and vagina will be discussed.
SEARCH METHODS
A systematic search of full-text articles available in PubMed and Embase databases was conducted to identify relevant studies published between January 2000 and September 2021. The search terms included: bioengineering, reproduction, artificial, biomaterial, microfluidic, bioprinting, organoid, hydrogel, scaffold, uterus, endometrium, ovary, fallopian tubes, oviduct, cervix, vagina, endometriosis, adenomyosis, uterine fibroids, chlamydia, Asherman's syndrome, intrauterine adhesions, uterine polyps, polycystic ovary syndrome and primary ovarian insufficiency. Additional studies were identified by manually searching the references of the selected articles and of complementary reviews. Eligibility criteria included original, rigorous and accessible peer-reviewed work, published in English, on female reproductive bioengineering techniques in preclinical (in vitro/in vivo/ex vivo) and/or clinical testing phases.
OUTCOMES
Out of the 10 390 records identified, 312 studies were included for systematic review. Owing to inconsistencies in the study measurements and designs, the findings were assessed qualitatively rather than by meta-analysis. Hydrogels and scaffolds were commonly applied in various bioengineering-related studies of the female reproductive tract. Emerging technologies, such as organoids and bioprinting, offered personalized diagnoses and alternative treatment options, respectively. Promising microfluidic systems combining various bioengineering approaches have also shown translational value.
WIDER IMPLICATIONS
The complexity of the molecular, endocrine and tissue-level interactions regulating female reproduction present challenges for bioengineering approaches to replace female reproductive organs. However, interdisciplinary work is providing valuable insight into the physicochemical properties necessary for reproductive biological processes to occur. Defining the landscape of reproductive bioengineering technologies currently available and under development for women can provide alternative models for toxicology/drug testing, ex vivo fertility options, clinical therapies and a basis for future organ regeneration studies.
Topics: Animals; Female; Humans; Pregnancy; Bioengineering; Embryo Implantation; Genitalia, Female; Reproduction; Uterus
PubMed: 35652272
DOI: 10.1093/humupd/dmac025 -
BMC Complementary and Alternative... Nov 2017Polycystic ovary syndrome (PCOS) is a common, reproductive endocrinopathy associated with serious short and long term health risks. Many women with PCOS use ingestible... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is a common, reproductive endocrinopathy associated with serious short and long term health risks. Many women with PCOS use ingestible complementary medicines. This systematic review examined the effect on menstrual regulation and adverse effects from randomised controlled trials.
METHODS
Randomised controlled trials (RCTs) that compared herbal or nutritional supplements to placebo or active controls in women with PCOS were eligible for inclusion. Electronic databases were searched to July 2017. Study selection and assessment of quality were conducted independently by two review authors.
RESULTS
Twenty four studies (1406 women) investigating seven nutritional supplements and four herbal medicines were included. No one study was assessed as having a low risk of bias. Four trials reported on the primary endpoint menstrual regulation. There was no evidence on improved menstrual regularity for calcium plus vitamin D compared to Metformin (RR: 0.66, 95% CI 0.35 to 1.23, p = 0.19), reduced amenorrhoea for Camellia sinensis compared to placebo (RR: 0.17, 95% CI 0.02 to 1.72, p = 0.13) and no difference in the number of menses per month for Cinnamomum sp. against placebo (MD 0.05, 95% CI -0.36 to 1.36, p = 0.26). Adverse effects were investigated in seven studies (164 women). Mild adverse effects were found for Cinnamomum sp. compared to placebo (17 women, RR: 0.36, 95% CI 0.03 to 0.70, p = 0.03). No difference was found for adverse effects between inositol, B complex vitamins, vitamin D, chromium and placebo. Improved reproduction, metabolic hormones and hyperandrogenism was found for inositol and improved cholesterol for omega three fish oils.
CONCLUSION
There is no high quality evidence to support the effectiveness of nutritional supplements and herbal medicine for women with PCOS and evidence of safety is lacking. High quality trials of nutritional supplements and herbal medicines examining menstrual regulation and adverse effects in women with PCOS are needed.
Topics: Dietary Supplements; Female; Humans; Phytotherapy; Plant Preparations; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Vitamins
PubMed: 29178904
DOI: 10.1186/s12906-017-2011-x -
International Journal of Endocrinology 2016Polycystic ovary syndrome (PCOS) is a common endocrine disorder, with complex etiology and pathophysiology, which remains poorly understood. It affects about 5-10% of... (Review)
Review
Polycystic ovary syndrome (PCOS) is a common endocrine disorder, with complex etiology and pathophysiology, which remains poorly understood. It affects about 5-10% of women of reproductive age who typically suffer from obesity, hyperandrogenism, ovarian dysfunction, and menstrual irregularity. Indeed, PCOS is the most common cause of anovulatory infertility in industrialized nations, and it is associated with insulin resistance, type 2 diabetes mellitus, and increased cardiovascular risk. Although insulin resistance is not included as a criterion for diagnosis, it is a critical pathological condition of PCOS. The purpose of this systematic review is the analysis of recent randomized clinical trials of inositol(s) in PCOS, in particular myo- and D-chiro-inositol, in order to better elucidate their physiological involvement in PCOS and potential therapeutic use, alone and in conjunction with assisted reproductive technologies, in the clinical treatment of women with PCOS.
PubMed: 27843451
DOI: 10.1155/2016/1849162 -
Human Reproduction Update 2014Polycystic ovary syndrome (PCOS) is a common condition affecting ∼8% of women. The objective of the present study was to quantify separately the risk of endometrial... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Polycystic ovary syndrome (PCOS) is a common condition affecting ∼8% of women. The objective of the present study was to quantify separately the risk of endometrial cancer, ovarian cancer and breast cancer in women with PCOS compared with non-PCOS controls, and quantify separately the risk to women of all ages as well as the risk to premenopausal women.
METHODS
We conducted a systematic review and meta-analysis of observational studies. Studies were eligible for inclusion if they compared women with PCOS to non-PCOS groups for fatal or non-fatal gynaecological cancers. Studies listed in MEDLINE and EMBASE published up to 7 October 2013 in any language were identified, and relevant papers were also searched by hand. Relevant data (for example, study design, source of control data, diagnostic criteria) were extracted and tabulated.
RESULTS
From 698 references, 11 studies (5 of endometrial cancer and 3 each of ovarian and breast cancer) met the inclusion criteria for the meta-analysis (919 women with PCOS and 72054 non-PCOS controls). Using the Mantel-Haenszel method, with fixed or random effects model as appropriate, women with PCOS were at a significantly increased risk of endometrial cancer (odds ratio (OR), 2.79; 95% confidence interval (CI), 1.31-5.95, P < 0.008), but the risk of ovarian and breast cancers was not significantly increased (OR, 1.41; 95% CI, 0.93-2.15, P < 0.11 and OR, 0.95; 95% CI, 0.64-1.39, P < 0.78, respectively). However when studies which included women aged over 54 years were excluded from the analysis, the risk for women with PCOS increased further for endometrial cancer (OR, 4.05; 95% CI, 2.42-6.76, P < 0.00001), became significantly increased for ovarian cancer (OR, 2.52; 95% CI, 1.08-5.89, P < 0.03), but remained non-significant for breast cancer (OR, 0.78; 95% CI, 0.46-1.32, P < 0.35).
CONCLUSIONS
This is the first meta-analysis to examine gynaecological cancers in women with PCOS younger than 54 years of age compared with controls of similar age. Current data suggest that women of all ages with PCOS are at an increased risk of endometrial cancer but the risk of ovarian and breast cancer was not significantly increased overall. These results highlight the potential risk of gynaecological cancer morbidities associated with PCOS. However, the available evidence is far from robust and variation in diagnostic criteria for PCOS, associated risk factors (particularly obesity), and selection bias in the studies may have resulted in an exaggeration of the increased risk. Furthermore, women who have PCOS should also be made aware that any increased risk for endometrial cancer must be judged in the context of its relatively low incidence in the general population. A large well-controlled prospective study is required in order to gain a more accurate estimate of the risk of gynaecological cancers in women with PCOS.
PROSPERO CRD REGISTRATION NUMBER
CRD42012003500.
Topics: Breast Neoplasms; Endometrial Neoplasms; Female; Genital Neoplasms, Female; Humans; Ovarian Neoplasms; Polycystic Ovary Syndrome; Research Design; Risk Assessment
PubMed: 24688118
DOI: 10.1093/humupd/dmu012 -
The Cochrane Database of Systematic... Mar 2019Polycystic ovary syndrome (PCOS) affects 8% to 13% of reproductive-aged women and is associated with reproductive and metabolic dysfunction. Obesity worsens the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polycystic ovary syndrome (PCOS) affects 8% to 13% of reproductive-aged women and is associated with reproductive and metabolic dysfunction. Obesity worsens the presentation of PCOS and weight management (weight loss, maintenance or prevention of excess weight gain) is proposed as an initial treatment strategy, best achieved through lifestyle changes incorporating diet, exercise and behavioural interventions.
OBJECTIVES
To assess the effectiveness of lifestyle treatment in improving reproductive, anthropometric (weight and body composition), metabolic and quality of life factors in PCOS.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, CINAHL and AMED (date of last search March 2018). We also searched controlled trials registries, conference abstracts, relevant journals, reference lists of relevant papers and reviews, and grey literature databases, with no language restrictions applied.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing lifestyle treatment (diet, exercise, behavioural or combined treatments) to minimal or no treatment in women with PCOS.
DATA COLLECTION AND ANALYSIS
Two authors independently selected trials, assessed evidence quality and risk of bias, and extracted data. Our primary outcomes were live birth, miscarriage and pregnancy. We used inverse variance and fixed-effect models in the meta-analyses. We reported dichotomous outcomes as an odds ratio and continuous outcomes as a mean difference (MD) or standardised mean difference (SMD).
MAIN RESULTS
We included 15 studies with 498 participants. Ten studies compared physical activity to minimal dietary and behavioural intervention or no intervention. Five studies compared combined dietary, exercise and behavioural intervention to minimal intervention. One study compared behavioural intervention to minimal intervention. Risk of bias varied: eight studies had adequate sequence generation, seven had adequate clinician or outcome assessor blinding, seven had adequate allocation concealment, six had complete outcome data and six were free of selective reporting. No studies assessed the fertility primary outcomes of live birth or miscarriage. No studies reported the secondary reproductive outcome of menstrual regularity, as defined in this review.Lifestyle intervention may improve a secondary (endocrine) reproductive outcome, the free androgen index (FAI) (MD -1.11, 95% confidence interval (CI) -1.96 to -0.26, 6 RCTs, N = 204, I = 71%, low-quality evidence). Lifestyle intervention may reduce weight (kg) (MD -1.68 kg, 95% CI -2.66 to -0.70, 9 RCTs, N = 353, I = 47%, low-quality evidence). Lifestyle intervention may reduce body mass index (BMI) (kg/m) (-0.34 kg/m, 95% CI -0.68 to -0.01, 12 RCTs, N = 434, I= 0%, low-quality evidence). We are uncertain of the effect of lifestyle intervention on glucose tolerance (glucose outcomes in oral glucose tolerance test) (mmol/L/minute) (SMD -0.02, 95% CI -0.38 to 0.33, 3 RCTs, N = 121, I = 0%, low-quality evidence).
AUTHORS' CONCLUSIONS
Lifestyle intervention may improve the free androgen index (FAI), weight and BMI in women with PCOS. We are uncertain of the effect of lifestyle intervention on glucose tolerance. There were no studies that looked at the effect of lifestyle intervention on live birth, miscarriage or menstrual regularity. Most studies in this review were of low quality mainly due to high or unclear risk of bias across most domains and high heterogeneity for the FAI outcome.
Topics: Abdominal Fat; Exercise; Female; Humans; Insulin Resistance; Life Style; Obesity; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Virilism; Waist Circumference; Weight Loss
PubMed: 30921477
DOI: 10.1002/14651858.CD007506.pub4 -
Human Reproduction Update Jul 2023Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as... (Review)
Review
BACKGROUND
Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as well as the elimination of infected or damaged cells throughout life. Quality control through regulation of cell death pathways is particularly important in the germline, which is responsible for the generation of offspring. Women are born with their entire supply of germ cells, housed in functional units known as follicles. Follicles contain an oocyte, as well as specialized somatic granulosa cells essential for oocyte survival. Follicle loss-via regulated cell death-occurs throughout follicle development and life, and can be accelerated following exposure to various environmental and lifestyle factors. It is thought that the elimination of damaged follicles is necessary to ensure that only the best quality oocytes are available for reproduction.
OBJECTIVE AND RATIONALE
Understanding the precise factors involved in triggering and executing follicle death is crucial to uncovering how follicle endowment is initially determined, as well as how follicle number is maintained throughout puberty, reproductive life, and ovarian ageing in women. Apoptosis is established as essential for ovarian homeostasis at all stages of development and life. However, involvement of other cell death pathways in the ovary is less established. This review aims to summarize the most recent literature on cell death regulators in the ovary, with a particular focus on non-apoptotic pathways and their functions throughout the discrete stages of ovarian development and reproductive life.
SEARCH METHODS
Comprehensive literature searches were carried out using PubMed and Google Scholar for human, animal, and cellular studies published until August 2022 using the following search terms: oogenesis, follicle formation, follicle atresia, oocyte loss, oocyte apoptosis, regulated cell death in the ovary, non-apoptotic cell death in the ovary, premature ovarian insufficiency, primordial follicles, oocyte quality control, granulosa cell death, autophagy in the ovary, autophagy in oocytes, necroptosis in the ovary, necroptosis in oocytes, pyroptosis in the ovary, pyroptosis in oocytes, parthanatos in the ovary, and parthanatos in oocytes.
OUTCOMES
Numerous regulated cell death pathways operate in mammalian cells, including apoptosis, autophagic cell death, necroptosis, and pyroptosis. However, our understanding of the distinct cell death mediators in each ovarian cell type and follicle class across the different stages of life remains the source of ongoing investigation. Here, we highlight recent evidence for the contribution of non-apoptotic pathways to ovarian development and function. In particular, we discuss the involvement of autophagy during follicle formation and the role of autophagic cell death, necroptosis, pyroptosis, and parthanatos during follicle atresia, particularly in response to physiological stressors (e.g. oxidative stress).
WIDER IMPLICATIONS
Improved knowledge of the roles of each regulated cell death pathway in the ovary is vital for understanding ovarian development, as well as maintenance of ovarian function throughout the lifespan. This information is pertinent not only to our understanding of endocrine health, reproductive health, and fertility in women but also to enable identification of novel fertility preservation targets.
Topics: Adult; Animals; Female; Humans; Apoptosis; Granulosa Cells; Mammals; Oocytes; Ovarian Follicle; Ovary; Regulated Cell Death; Homeostasis
PubMed: 36857094
DOI: 10.1093/humupd/dmad005 -
Medicine Apr 2020Polycystic ovary syndrome (PCOS) affects reproductive-aged women and is associated with increased prevalence of serious clinical problems including: reproductive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polycystic ovary syndrome (PCOS) affects reproductive-aged women and is associated with increased prevalence of serious clinical problems including: reproductive implications, metabolic dysfunction, and cardiovascular risk. Physical activity offers several health benefits for women with PCOS. The aim of this systematic review was to synthesize evidence on the effect of different types of exercise on reproductive function and body composition for women with PCOS.
METHODS
This was a systematic review and meta-analysis of randomized controlled trials (RCTs) following recommended review methods. We searched 6 databases: Cumulative Index of Nursing and Allied Health Literature; Embase; MEDLINE (via Ovid); PubMed; Sport Discus; and Web of Science; and we developed search strategies using a combination of Medical Subject Headings terms and text words related to exercise interventions for women with PCOS. There was no restriction on language or publication year. The search was conducted on April 16, 2019 and updated on November 15, 2019. Two authors independently screened citations, determined risk of bias and quality of evidence with Grading of Recommendations Assessment, Development and Evaluation. We conducted meta-analyses following recommended guidelines, and report results using standardized mean difference (SMD).
RESULTS
Ten RCTs (n = 533) were included in this review. Studies tested the following interventions: aerobic, resistance, and combined (aerobic/resistance) training programs. Most studies were small (average 32, range 15-124 participants), and of relatively short duration (8-32 weeks). There was high heterogeneity for outcomes of reproductive function (menstrual cycle, ovulation, and fertility). We noted low certainty evidence for little to no effect of exercise on reproductive hormones and moderate certainty evidence that aerobic exercise reduced body mass index (BMI) in women with PCOS: BMI SMD -0.35, 95% confidence interval -0.56 to -0.14, P = .001.
CONCLUSION
For women with PCOS, evidence is limited to discern the effect of exercise on major health outcomes (e.g., reproductive function). There is moderate certainty evidence that aerobic exercise alone is beneficial for reducing BMI in women with PCOS. Future studies should be conducted with longer duration, larger sample sizes, and should provide detailed information on menstrual cycle and fertility outcomes.PROSPERO Systematic review registration: 2017 CRD42017058869.
Topics: Exercise Therapy; Female; Humans; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic
PubMed: 32311937
DOI: 10.1097/MD.0000000000019644 -
BMC Medicine Aug 2023The results of human observational studies on the correlation between gut microbiota perturbations and polycystic ovary syndrome (PCOS) have been contradictory. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The results of human observational studies on the correlation between gut microbiota perturbations and polycystic ovary syndrome (PCOS) have been contradictory. This study aimed to perform the first systematic review and meta-analysis to evaluate the specificity of the gut microbiota in PCOS patients compared to healthy women.
METHODS
Literature through May 22, 2023, was searched on PubMed, Web of Science, Medline, Embase, Cochrane Library, and Wiley Online Library databases. Unreported data in diversity indices were filled by downloading and processing raw sequencing data. Systematic review inclusion: original studies were eligible if they applied an observational case-control design, performed gut microbiota analysis and reported diversity or abundance measures, sampled general pre-menopausal women with PCOS, and are longitudinal studies with baseline comparison between PCOS patients and healthy females. Systematic review exclusion: studies that conducted interventional or longitudinal comparisons in the absence of a control group. Two researchers made abstract, full-text, and data extraction decisions, independently. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodologic quality. Hedge's g standardized mean difference (SMD), confidence intervals (CIs), and heterogeneity (I) for alpha diversity were calculated. Qualitative syntheses of beta-diversity and microbe alterations were performed.
RESULTS
Twenty-eight studies (n = 1022 patients, n = 928 control) that investigated gut microbiota by collecting stool samples were included, with 26 and 27 studies having provided alpha-diversity and beta-diversity results respectively. A significant decrease in microbial evenness and phylogenetic diversity was observed in PCOS patients when compared with control participants (Shannon index: SMD = - 0.27; 95% CI, - 0.37 to - 0.16; phylogenetic diversity: SMD = - 0.39; 95% CI, -- 0.74 to - 0.03). We also found that reported beta-diversity was inconsistent between studies. Despite heterogeneity in bacterial relative abundance, we observed depletion of Lachnospira and Prevotella and enrichment of Bacteroides, Parabacteroides, Lactobacillus, Fusobacterium, and Escherichia/Shigella in PCOS. Gut dysbiosis in PCOS, which might be characterized by the reduction of short-chain fatty acid (SCFA)-producing and bile-acid-metabolizing bacteria, suggests a shift in balance to favor pro-inflammatory rather than anti-inflammatory bacteria.
CONCLUSIONS
Gut dysbiosis in PCOS is associated with decreased diversity and alterations in bacteria involved in microbiota-host crosstalk.
TRIAL REGISTRATION
PROSPERO registration: CRD42021285206, May 22, 2023.
Topics: Humans; Female; Gastrointestinal Microbiome; Polycystic Ovary Syndrome; Dysbiosis; Phylogeny; Microbiota
PubMed: 37559119
DOI: 10.1186/s12916-023-02975-8 -
Journal of Human Reproductive Sciences 2020Polycystic ovary syndrome (PCOS), the major endocrinopathy among reproductive-aged women, is not yet perceived as an important health problem in the world. It affects... (Review)
Review
BACKGROUND
Polycystic ovary syndrome (PCOS), the major endocrinopathy among reproductive-aged women, is not yet perceived as an important health problem in the world. It affects 4%-20% of women of reproductive age worldwide. The prevalence, diagnosis, etiology, management, clinical practices, psychological issues, and prevention are some of the most confusing aspects associated with PCOS.
AIM
The exact prevalence figures regarding PCOS are limited and unclear. The aim of this review is to summarize comprehensively the current knowledge on the prevalence of PCOS.
MATERIALS AND METHODS
Literature search was performed through PubMed, ScienceDirect, Cochrane Library, and Google Scholar (up to December 2019). All relevant articles published in English language were identified following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
Our analysis yielded 27 surveys with a pooled mean prevalence of 21.27% using different diagnostic criteria. The proportion of women with PCOS also increased in the last decade.
CONCLUSION
The current review summarizes and interprets the results of all published prevalence studies and highlights the burden of the syndrome, thereby supporting early identification and prevention of PCOS in order to reverse the persistent upward trend of prevalence.
PubMed: 33627974
DOI: 10.4103/jhrs.JHRS_95_18 -
Fertility and Sterility Dec 2016Ovarian hyperstimulation syndrome (OHSS) is an uncommon but serious complication associated with assisted reproductive technology (ART). This systematic review aims to... (Review)
Review
Ovarian hyperstimulation syndrome (OHSS) is an uncommon but serious complication associated with assisted reproductive technology (ART). This systematic review aims to identify who is at high risk, how to prevent OHSS, and the treatment for existing OHSS.
Topics: Female; Humans; Infertility; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation; Ovulation Induction; Risk Assessment; Risk Factors; Severity of Illness Index; Treatment Outcome
PubMed: 27678032
DOI: 10.1016/j.fertnstert.2016.08.048