The Impact of High BMI on Pregnancy Outcomes and Complications in Women with PCOS Undergoing IVF-A Systematic Review and Meta-Analysis.

(1) Background: Current evidence indicates that women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilization (IVF) have an increased likelihood of adverse pregnancy outcomes. The objective of this systematic review was to clarify the role of a PCOS-related high body mass index (BMI) in these unfavourable pregnancy outcomes. (2) Methods: A comprehensive search of electronic databases was conducted to identify studies investigating the impact of high BMI on pregnancy outcomes in women with PCOS undergoing IVF. RevMan software (v5.4) was used to calculate the odds ratio (OR) and 95% confidence interval (CI). (3) Results: Nineteen eligible studies (n = 7680) were identified, including 16 retrospective cohort studies (n = 6934), two prospective cohort studies (n = 525), and one cross-sectional study (n = 221). Pooled analysis showed significantly higher odds of clinical pregnancy (OR, 1.16 [95% CI, 1.04-1.29]; z = 2.73; p = 0.006; I2 = 30%) and livebirths (OR, 1.88 [95% CI, 1.56-2.27]; z = 6.54; p < 0.0001; I2 = 55%) in women with PCOS with a normal versus a high BMI. Meta-analysis showed significantly increased odds of miscarriages in women with PCOS with a high versus a normal BMI (OR, 0.76 [95% CI, 0.60-0.95]; z = 2.42; p = 0.02; I2 = 53%). Pooled analysis of three studies (n = 993) showed significantly higher ORs of gestational diabetes mellitus (OR 3.96 [95% CI 1.62-9.68]; z = 3.01; p = 0.003; I2 = 58%) and gestational hypertension (OR 2.16 [95% CI 1.32-3.54]; z = 3.05; p = 0.002; I2 = 68%) in women with PCOS with a high versus a normal BMI. Meta-analysis of three studies reported significantly greater odds of a caesarean section for women with PCOS with a high versus a normal BMI (OR 0.45 [95% CI 0.29-0.69]; z = 3.66; p = 0.0003; I2 = 0%). (4) Conclusions: The increased likelihood of adverse pregnancy outcomes observed in women with PCOS undergoing IVF seems to be attributable to a PCOS-related high BMI.

The Role of NLRP3 Inflammasome in Obesity and PCOS-A Systematic Review and Meta-Analysis.

Inflammasomes have recently been implicated in the pathogenesis of several chronic inflammatory disorders, such as diabetes and obesity. The aim of this meta-analysis was to investigate the possible role of the NLRP3 inflammasome in obesity and polycystic ovarian syndrome (PCOS). A comprehensive search of electronic databases was conducted to identify studies investigating NLRP3 its related components (Caspase 1, ASC and IL-1ß) in adipose tissue and/or blood from obese individuals compared to non-obese controls. Another search was conducted for studies investigating NLRP3 in PCOS women and animal models. The ssearched databases included Medline, EMBASE, Cochrane Library, PubMed, Clinicaltrials.gov, the EU Clinical Trials Register and the WHO International Clinical Trials Register. The quality and risk of bias for the included articles were assessed using the modified Newcastle-Ottawa scale. Data were extracted and pooled using RevMan software for the calculation of the standardized mean difference (SMD) and 95% confidence interval (CI). Twelve eligible studies were included in the obesity systematic review and nine in the PCOS review. Of the obesity studies, nine (n = 270) were included in the meta-analysis, which showed a significantly higher adipose tissue NLRP3 gene expression in obese (n = 186) versus non-obese (n = 84) participants (SMD 1.07; 95% CI, 0.27, 1.87). Pooled analysis of adipose tissue IL-1ß data from four studies showed significantly higher IL-1ß gene expression levels in adipose tissue from 88 obese participants versus 39 non-obese controls (SMD 0.56; 95% CI, 0.13, 0.99). Meta-analysis of adipose tissue ASC data from four studies showed a significantly higher level in obese (n = 109) versus non-obese (n = 42) individuals (SMD 0.91, 95% CI, 0.30, 1.52). Of the nine PCOS articles, three were human (n = 185) and six were animal studies utilizing PCOS rat/mouse models. All studies apart from one article consistently showed upregulated NLRP3 and its components in PCOS women and animal models. In conclusion, obesity and PCOS seem to be associated with upregulated expression of NLRP3 inflammasome components. Further research is required to validate these findings and to elucidate the role of NLRP3 in obesity and PCOS.

HRT in Women Undergoing Pelvic Clearance for Endometriosis-A Case Report and a National Survey.

The optimal hormone replacement therapy (HRT) in women who have undergone pelvic clearance for endometriosis remains uncertain with insufficient evidence. The purpose of this case report and the national survey was to highlight the potential HRT-related risks and to establish current HRT practice in this group of women. The case was a 45-year-old woman presenting with recurrence of severe chronic pelvic pain while on oestrogen-only HRT (EO-HRT) for five years after subtotal hysterectomy and bilateral oophorectomy for severe endometriosis. MRI revealed multiple peri-cervical endometriomas and severe right hydroureter/hydronephrosis with complete right renal parenchymal loss. The survey was a 21-item questionnaire administered electronically using SurveyMonkey. It was reviewed and approved by British Menopause Society and British Society of Gynaecological endoscopy and was sent to their members as well as NHS Gynaecologists. A total of 216 physicians responded including 120 (55.6%) Gynaecology Consultants and 96 (44.4%) GPs/Nurses in Menopause clinics. Overall, 68.6% of responders prescribe combined HRT (C-HRT), 11.1% tibolone, 13.0% EO-HRT and 7.8% varied HRT. Fifty-one percent prescribe the progestogen component of C-HRT indefinitely, 22% for 3-6 months and 27% for varied durations. In conclusion, this study highlights the real risk of endometriosis recurrence in EO-HRT users after pelvic clearance for endometriosis. The survey revealed that only two thirds of Gynecologists/Menopause practitioners prescribe combined HRT in this group of women.

Integrating Youth Perspectives: Adopting a Human Rights and Public Health Approach to Climate Action.

Climate change is a multidimensional issue that affects all aspects of society, including public health and human rights. Climate change is already severely impacting people's health and threatening people's guaranteed fundamental rights, including those to life, health, self-determination, and education, among others. Across geographical regions, population groups and communities who are already marginalized due to age, gender, ethnicity, income, and other socioeconomic factors, are those who are disproportionately affected by climate impacts despite having contributed the least to global emissions. Although scholars have been calling for a human rights-based approach and a health perspective to climate action, the literature looking at this multidisciplinary intersection is still nascent, and governments have yet to implement such intersectoral policies. This commentary begins to reflect on the relationship between climate change, human rights, and public health from the perspective of young people engaged in climate action and discourse at the national and international levels. It presents a way forward on what we, as youth climate advocates and researchers, believe is a priority to bring intersectoral integration of human rights and public health approaches to climate change to fruition. First, scholars and practitioners should examine and support youth-led climate interventions that tackle human rights and public health violations incurred by the climate crisis. Second, participatory approaches to climate change must be designed by working synergistically with climate-vulnerable groups, including children and young people, practitioners and scholars in public health and human rights sectors to holistically address the social, health, and environmental impacts of the climate crisis and root causes of injustice. Finally, we recommend more holistic data collection to better inform evidence-based climate policies that operationalize human rights and public health co-benefits.

The prevalence of hyperprolactinaemia in subfertile ovulatory women and its impact on fertility treatment outcome.

Subtle hyperprolactinaemia is not an uncommon finding in ovulatory subfertile women. The objective of this study is to evaluate the prevalence of hyperprolactinaemia in subfertile ovulatory and oligo-anovulatory women, and to determine if hyperprolactinaemia influences fertility treatment outcome. All women (n = 1010) who attended the fertility clinic of a UK tertiary hospital during 2015-2019 were included. Out of 804 eligible women analysed, 575 women (71.5%) were ovulatory and 229 (28.5%) were oligo-anovulatory. Prevalence of hyperprolactinaemia was higher in the ovulatory group than in the oligo-anovulatory group (26.8% vs. 14.4%; OR: 2.2; 95% confidence interval (CI): 1.4-3.2). On sub-group analysis, the prevalence of mild, moderate and severe hyperprolactinaemia was 23.0%, 3.7% and 0.2% in ovulatory women and 11.8%, 1.7% and 0.9% in oligo-anovulatory women. Mild hyperprolactinaemia was found to be more prevalent in the ovulatory group (OR: 2.2; 95%CI: 1.4-3.5). Ongoing pregnancy/livebirth rates were similar between hyperprolactinaemic and normoprolactinaemic women (42.8% vs. 46.7%). Hyperprolactinaemia did not have an impact on ongoing pregnancy/livebirth rates in both ovulatory and oligo-anovulatory women (OR:0.8; 95%CI: 0.5-1.1; OR: 1.2; 95%CI: 0.6-2.5, respectively). Hyperprolactinaemia is prevalent among ovulatory women, although most had mildly raised clinically insignificant levels. Elevated prolactin levels in ovulatory women do not seem to impact on pregnancy outcome. Impact StatementWhat is already known on this subject? Prolactin has been linked to ovulation and fertility. Prolactin testing is not generally recommended for subfertile women with regular menstrual cycles, which is a surrogate marker of ovulation. However, some clinicians, particularly in the general practice, still perform prolactin test as part of baseline endocrine profile.What do the results of this study add? Prevalence of hyperprolactinaemia in subfertile ovulatory women was 26.8% (154/575), of which 86% (132/154) were mild. Further, the livebirth/ongoing pregnancy rates were similar between hyperprolactinaemic and normoprolactinaemic women. Prolactin being a sensitive hormone, responsive to even minimal stress and its high levels not influencing clinical pregnancy outcome, prolactin measurement is not needed in women having regular menstrual cycles.What are the implications of these findings for clinical practice and/or further research? Hyperprolactinaemia was not uncommon in ovulatory women, although most had mildly elevated levels. Hyperprolactinaemia did not have any impact on fertility treatment outcome. Serum prolactin should not be tested in ovulating women, as mild elevations are commonly present and have no clinical significance.

The Impact of High Circulating Anti-Müllerian Hormone on Endometrial Thickness and Outcome of Assisted Reproductive Technology in Women with Polycystic Ovarian Syndrome: A Cohort Study.

Background: Elevated circulating anti-Müllerian hormone (AMH) in women with the polycystic ovarian syndrome (PCOS) has been found to have a detrimental effect on endometrial function. This may adversely affect the outcome of in vitro fertilisation (IVF) in PCOS women. Aims: To investigate the impact of high serum AMH concentrations on endometrial thickness (ET) and the outcome of IVF in women with PCOS. Settings and Design: This retrospective cohort study included all PCOS women who underwent fresh IVF\intracytoplasmic sperm injection cycles between January 2016 and December 2021 in one major IVF centre. Materials and Methods: PCOS diagnosis was based on Rotterdam criteria, and participants were identified from centre database. All women received antagonist protocol. Primary outcomes were trigger-day ET and live birth rate (LBR). Circulating AMH was correlated with ET and ovarian response. Statistical Analysis Used: AMH levels were compared between women with and without live birth. ET and LBRs were compared between women with AMH <7.0 ng/ml versus those with AMH ≥7.0 ng/ml. Results: The study included 102 PCOS women, of which six were excluded due to poor response (n = 4), hyperresponse (n = 1) or fertilisation failure (n = 1). Of the remaining 96 women, 42 (43.8%) achieved a live birth. There was no statistically significant (P > 0.05) correlation between AMH and ET. Mean ± standard deviation AMH concentration was not significantly (P > 0.05) different between women with live birth (6.5 ± 3.4 ng/ml) and those without (6.5 ± 2.4 ng/ml). High AMH positively correlated with the number of oocytes retrieved, metaphase II oocytes and embryos (P = 0.003, 0.006 and 0.006, respectively). There was no statistically significant (P > 0.05) difference in ET or LBR between women with AMH <7.0 ng/ml (n = 72; ET, 10.7 ± 1.8 mm; LBR, 45.8% [33/72] versus those with AMH ≥7.0 ng/ml (n = 24; ET, 10.8 ± 1.7 mm; LBR, 37.5% [9/24]). Conclusions: High circulating AMH in PCOS women does not seem to negatively affect ET or LBRs during assisted reproductive technology.

The Role of Chronic Inflammation in Polycystic Ovarian Syndrome-A Systematic Review and Meta-Analysis.

Although the current literature associates polycystic ovarian syndrome (PCOS) with chronic inflammation, the evidence for this link remains inconclusive and its causal nature remains unclear. The purpose of this systematic review was to assess the inflammatory status in PCOS women and to determine whether it is related to PCOS or to its associated adiposity. We searched electronic databases including PUBMED, EMBASE and MEDLINE, SCOPUS, DynaMed plus, TRIP, ScienceDirect and Cochrane Library, for studies investigating C-reactive protein (CRP) and other inflammatory makers in PCOS women versus healthy controls. Quality and risk of bias for selected studies were assessed using the modified Newcastle-Ottawa scale. CRP data were extracted and pooled using RevMan for calculation of the standardized mean difference (SMD) and 95% confidence interval (CI). Eighty-five eligible studies were included in the systematic review, of which 63 were included in the meta-analysis. Pooled analysis of the 63 studies revealed significantly higher circulating CRP in PCOS women (n = 4086) versus controls (n = 3120) (SMD 1.26, 95%CI, 0.99, 1.53). Sensitivity meta-analysis of 35 high quality studies including non-obese women showed significantly higher circulating CRP in PCOS women versus controls (SMD 1.80, 95%CI, 1.36, 2.25). In conclusion, circulating CRP is moderately elevated in PCOS women independent of obesity, which is indicative of low-grade chronic inflammation.

Assessment of Circulating Anti-Müllerian Hormone in Women Using Hormonal Contraception: A Systematic Review.

Background: The status of ovarian reserve markers during hormonal contraception (HC) remains uncertain with conflicting literature data. The purpose of this study was to assess the impact of HC on circulating anti-Müllerian hormone (AMH) and other ovarian reserve markers. Materials and Methods: A systematic review was conducted, including all cohort, cross-sectional, and randomized controlled studies assessing serum anti Müllerian hormone concentration in women using HC. Data sources included MEDLINE, EMBASE, DynaMed Plus, ScienceDirect, TRIP database, ClinicalTrials.gov, and the Cochrane Library from January 2000 to October 2018. Results: A total of 366 studies were identified, of which 15 were eligible, including 3280 women, mostly using combined HC (CHC). Articles were divided according to duration of HC into short- (2-3 weeks), medium- (2-6 months), long- (>1 year), and varied-term studies. Two study designs were identified, including studies comparing AMH before and during/after CHC and studies comparing CHC users versus nonusers. Short- and medium-term studies (n = 284) reported no change in circulating AMH in women using cyclical CHC for one to six cycles. Apart from one study, all long- and varied-term studies (six studies, n = 1601) consistently showed a marked decline in AMH, antral follicle count, and ovarian volume. Three long-term studies (n = 1324) provided evidence of AMH recovery after discontinuation of HC. Conclusion: Circulating AMH seems to remain unchanged in women using cyclical CHC for up to 6 months, but appears to markedly decline in long-term users with recovery after discontinuation.

The impact of uterine artery embolization on ovarian reserve: A systematic review and meta-analysis.

INTRODUCTION: Uterine artery embolization (UAE) has been gaining increasing popularity as an effective and minimally invasive treatment for uterine fibroids. However, there has been growing concern over the risk of unintended embolization of the utero-ovarian circulation, leading to reduction of ovarian blood supply with subsequent impairment of ovarian reserve. The purpose of this study was to investigate the impact of UAE on circulating anti-Müllerian hormone (AMH) and other markers of ovarian reserve. MATERIAL AND METHODS: This meta-analysis included all published cohort, cross-sectional and case-control studies, as well as randomized trials that investigated the impact of UAE on circulating AMH. Data sources included MEDLINE, EMBASE, Dynamed Plus, ScienceDirect, TRIP database, ClinicalTrials.gov and the Cochrane Library from January 2000 to June 2019. All identified articles were screened, and articles were selected based on the inclusion and exclusion criteria. AMH and other data were extracted from the eligible articles and entered into RevMan software to calculate the weighted mean difference between pre- and post-embolization values. PROSPERO registration number: CRD42017082615. RESULTS: This review included 3 cohort and 3 case-control studies (n = 353). The duration of follow up after UAE ranged between 3 and 12 months. Overall pooled analysis of all studies showed no significant effect of UAE on serum AMH levels (weighted mean difference -0.58 ng/mL; 95% CI -1.5 to 0.36, I2  = 95%). Subgroup analysis according to age of participants (under and over 40 years) and according to follow-up duration (3, 6 and 12 months) showed no significant change in post-embolization circulating AMH. Pooled analysis of serum follicle-stimulating hormone (FSH) concentrations (4 studies, n = 248) revealed no statistically significant change after UAE (weighted mean difference 4.32; 95% CI -0.53 to 9.17; I2  = 95%). Analysis of 2 studies (n = 62) measuring antral follicle count showed a significant decline at 3-month follow up (weighted mean difference -3.28; 95% CI -5.62 to -0.93; I2  = 94%). CONCLUSIONS: Uterine artery embolization for uterine fibroids does not seem to affect ovarian reserve as measured by serum concentrations of AMH and FSH.

First-line ovulation induction for polycystic ovary syndrome: an individual participant data meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most frequent cause of anovulatory infertility. In women with PCOS, effective ovulation induction serves as an important first-line treatment for anovulatory infertility. Individual participant data (IPD) meta-analysis is considered as the gold standard for evidence synthesis which provides accurate assessments of outcomes from primary randomised controlled trials (RCTs) and allows additional analyses for time-to-event outcomes. It also facilitates treatment-covariate interaction analyses and therefore offers an opportunity for personalised medicine. OBJECTIVE AND RATIONALE: We aimed to evaluate the effectiveness of different ovulation induction agents, in particular letrozole alone and clomiphene citrate (CC) plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility, and to explore interactions between treatment and participant-level baseline characteristics. SEARCH METHODS: We searched electronic databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to 20 December 2018. We included RCTs comparing the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. We excluded studies on treatment-resistant women. The primary outcome was live birth. We contacted the investigators of eligible RCTs to share the IPD and performed IPD meta-analyses. We assessed the risk of bias by using the Cochrane risk of bias tool for RCTs. OUTCOMES: IPD of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women. Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43, 95% confidence interval [CI] 1.17-1.75, moderate-certainty evidence) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45, 95% CI 1.23-1.70, moderate-certainty evidence) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72, 95% CI 1.38-2.15, moderate-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29, 95% CI 1.01-1.65). Eight RCTs compared CC plus metformin to CC alone in 1039 women. Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18, 95% CI 1.00-1.39, low-certainty evidence) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25, 95% CI 1.00-1.57, low-certainty evidence), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08, 95% CI 0.87-1.35, low-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01-1.06). WIDER IMPLICATIONS: In women with PCOS, letrozole improves live birth and clinical pregnancy rates and reduces time-to-pregnancy compared to CC and therefore can be recommended as the preferred first-line treatment for women with PCOS and infertility. CC plus metformin may increase clinical pregnancy and may reduce time-to-pregnancy compared to CC alone, while there is insufficient evidence of a difference on live birth. Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS.

The role of oxidative stress in ovarian toxicity induced by haloperidol and clozapine-a histological and biochemical study in albino rats.

Oxidative stress has been implicated in reproductive toxicity induced by antipsychotics (APs). This study aims to further investigate the role of AP-induced oxidative stress in reproductive dysfunction. Thirty adult female albino rats were divided into three groups including a control group (n = 10) receiving distilled water, HAL group (n = 10) receiving haloperidol (HAL) (2 mg/kg/day), and CLZ group (n = 10) receiving clozapine (CLZ) (20 mg/kg/day). After 28 days, the rats were anesthetized, blood was withdrawn from their hearts, and ovaries were removed before they were sacrificed. Serum prolactin concentrations were measured. For each rat, one ovary was used for biochemical studies including mitochondrial complexes I and III activities and oxidative stress markers (lipid peroxidation, super oxide dismutase [SOD], catalase [CAT], and reduced glutathione [GSH]). The other ovary was used for histopathological examination and immunohistochemistry staining for p53 and Ki-67. HAL-treated rats showed significantly (p < 0.001) higher serum prolactin concentrations compared with other groups. HAL significantly inhibited complexes I (p < 0.001) and III activities (p < 0.05), while CLZ inhibited only complex I (p < 0.001). Lipid peroxidation was increased by HAL (p < 0.001) and CLZ (p < 0.01). HAL caused significant (p < 0.001) reductions in SOD, CAT, and GSH. CLZ caused a significant decrease in SOD (p < 0.001) and GSH (p < 0.01) with no effect on CAT. Histopathological studies of CLZ- and HAL-treated ovaries showed features suggestive of hyperprolactinemia and oxidative stress. Ki-67- and P53-immunostained sections were suggestive of disruption of cellular proliferation. These findings support the hypothesis that HAL and CLZ induce reproductive dysfunction through mechanisms involving ovarian mitochondrial dysfunction and oxidative stress.

Excess androgen production in subcutaneous adipose tissue of women with polycystic ovarian syndrome is not related to insulin or LH.

The purpose of this study was to investigate androgen production and the role of insulin and LH in its regulation in subcutaneous adipose tissue (SAT) of women with polycystic ovarian syndrome (PCOS). Protein and mRNA expression of androgen synthesis enzymes (Cytochrome P450 17A1 [CYP17A1] and Aldo-keto reductase 1C3 [AKR1C3]) were measured in SAT biopsies from women with PCOS, diagnosed according to the Rotterdam criteria (n=15) and healthy controls (n=15). Cultured mature adipocytes (differentiated from SAT biopsies) were treated with insulin ± phosphoinositol-3-kinase inhibitor (LY294002) or LH ± insulin. CYP17A1 and AKR1C3 mRNA expression and testosterone concentrations were measured in treated and untreated adipocyte cultures. AKR1C3 mRNA was significantly (P<0.001) greater in PCOS versus non-PCOS SAT, but CYP17A1 was not significantly different between the two groups. AKR1C3 and CYP17A1 protein expression was not significantly different in PCOS versus non-PCOS SAT. In untreated adipocyte cultures, CYP17A1, AKR1C3 and testosterone levels were significantly higher in the PCOS versus the non-PCOS groups. Addition of insulin increased AKR1C3 mRNA and testosterone levels, but not CYP17A1 mRNA in non-PCOS with no effect on PCOS adipocytes. The stimulatory effects of insulin were not inhibited by LY294002. Addition of LH increased CYP17A1, AKR1C3 and testosterone in non-PCOS adipocytes with no effect in PCOS adipocytes. In conclusion, SAT of women with PCOS produces excess androgen, which may contribute to PCOS-related hyperandrogenaemia. This SAT androgen excess is independent of obesity and is not directly stimulated by insulin or LH.

Evaluation of the National Guard Health Promotion Program for Chronic Diseases and Comorbid Conditions Among Military Personnel in Jeddah City, Saudi Arabia, 2016.

OBJECTIVE: Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Preventive efforts mainly target the reduction of modifiable CVD risk factors through community-based promotion programs. One of these programs is the National Guard Health Promotion Program for Chronic Diseases and Comorbid Conditions among military personnel in Jeddah City, Saudi Arabia. Researchers have asserted that to improve every intervention program, especially those targeting public health issues, regular monitoring and evaluation are needed to determine the strength and weakness of the program. The objective of this study was to assess the effectiveness of National Guard Health Promotion Program for Chronic Diseases and Comorbid Conditions among military personnel in Jeddah City by estimating Framingham risk score, diabetes risk score, and satisfaction level for the participants covered by the program for at least 6 months. METHODS: Through pre- and poststudy design, a systematic random sample of military personnel who fulfilled the inclusion criteria (n = 267) were enrolled in the study. To assess the program's effectiveness, participants were subjected to clinical and laboratory assessment based mainly on Framingham risk scores before and after involvement in the program; satisfaction was assessed concurrently using a self-administered questionnaire. The Wilcoxon signed rank test was used to compare changes in non-normally distributed quantitative variables. Multiple logistic regression analysis was used to identify independent predictors of risk of CVDs. RESULTS: The subjects were all military men, with mean age of 35.8 ± 6.6 years; 6% officers with the remainder "non-officers" primarily working in the combat services. After at least 6 months of the preventive program, there were statistically significant decreases in body mass index (-0.4 ± 1.5 kg/m2), waist circumference (-0.9 ± 6.2 cm), fasting blood glucose (-12.3 ± 29.6 mg/dL), and total cholesterol (-15.4 ± 40.2 mg/dL). Despite this observed improvement, the overall Framingham risk score showed a modest nonsignificant change (-0.1 ± 2.1 points). Similarly, although specific predictors scores of diabetes mellitus showed significant improvement (decreased blood glucose [-0.4 ± 1.8 points] and increased fruit and vegetable consumption [-0.2 ± 0.6 points]), there was no significant change in the overall diabetes risk score (-0.01 ± 2.5). The majority of the participants (96%) expressed that they were satisfied with the program. CONCLUSION: The National Guard Health Promotion Program is effective in improving specific risk factors such as body mass index, waist circumference, blood glucose, and intake of fruits and vegetables; in addition, it was perceived as being satisfactory. Nevertheless, it had no statistically significant impact on the overall total risk scores for CVDs and diabetes mellitus.

The role of oxidative stress in antipsychotics induced ovarian toxicity.

This study tested the hypothesis that oxidative stress could be an underlying mechanism for APs-induced ovarian cytotoxicity and reproductive dysfunction. Rat ovarian theca interstitial cells (TICs) were isolated and treated with four APs [chlorpromazine (CPZ), haloperidol (HAL), risperidone (RIS) and clozapine (CLZ)]. MTT assay was used to test the effects of these antipsychotics on TICs viability and to estimate their 50% inhibitory concentrations (IC50s). The effects of APs (IC50s and 1µM concentrations) on the activities of caspases-3, -8 and -9, reactive oxygen species (ROS) production, total intracellular glutathione and lipid peroxidation (LPO) in TICs were assessed. The effect of antioxidants (reduced glutathione (GSH) and quercetin) on the APs-induced cytotoxicity on TICs was investigated. MTT assay showed all APs to reduce TICs viability. CPZ, HAL and CLZ significantly increased the activity of caspases-3, -8 and -9 (P<0.0001, <0.0001 and <0.01, respectively). All APs at IC50s significantly (P<0.0001) increased ROS production, decreased total intracellular glutathione and increased LPO. MTT assay in the presence of antioxidants (reduced GSH (5mM) or quercetin (50mM)) showed each antioxidant to significantly inhibit the effects of APs at their IC50s on TICs viability. In conclusion, oxidative stress seems to be a possible mechanism for APs-induced ovarian and reproductive toxicity.

Ovarian reserve after salpingectomy: a systematic review and meta-analysis.

INTRODUCTION: Although there has been a growing concern over the possible damaging effect of salpingectomy on ovarian reserve, this issue remains uncertain. The purpose of this meta-analysis was to test the hypothesis that salpingectomy may compromise ovarian reserve. MATERIAL AND METHODS: A detailed search was conducted using MEDLINE, Embase, Dynamed Plus, ScienceDirect, TRIP database and the Cochrane Library from January 2000 to November 2016. All cohort, cross-sectional and randomized controlled studies investigating changes in circulating anti-Müllerian hormone (AMH) after salpingectomy were considered. Thirty-seven studies were identified, of which eight were eligible. Data were extracted and entered into RevMan software for calculation of the weighted mean difference (WMD) and 95% CI. Two groups of studies were analyzed separately: group 1 (six studies, n = 464) comparing data before and after salpingectomy and group 2 (two studies) comparing data in women who have undergone salpingectomy (n = 169) vs. healthy controls (n = 154). RESULTS: Pooled results of group 1 studies showed no statistically significant change in serum AMH concentration after salpingectomy (WMD, -0.10 ng/mL; 95% CI -0.19 to 0.00, I2 = 0%). Similarly, meta-analysis of group 2 showed no statistically significant difference in serum AMH concentration between salpingectomy group and controls (WMD, -0.11 ng/mL; 95% CI -0.37 to 0.14, I2 = 77%). Subgroup analyses based on laterality of surgery, type of AMH kit and participants' age (<40 years) still showed no statistically significant changes in circulating AMH. CONCLUSION: Salpingectomy does not seem to compromise ovarian reserve in the short-term. However, the long-term effect of salpingectomy on ovarian reserve remains uncertain.

The impact of laparoscopic ovarian drilling on AMH and ovarian reserve: a meta-analysis.

Laparoscopic ovarian drilling (LOD) has been widely used as an effective treatment of anovulatory women with polycystic ovarian syndrome (PCOS). However, there has been a growing concern over a possible damaging effect of this procedure on ovarian reserve. The objective of this study was to investigate the hypothesis that LOD compromises ovarian reserve as measured by post-operative changes in circulating anti-Müllerian hormone (AMH). This meta-analysis included all cohort studies as well as randomised controlled trials (RCTs) investigating serum AMH concentrations and other ovarian reserve markers in women with PCOS undergoing LOD. Various databases were searched including MEDLINE, EMBASE, Dynamed Plus, ScienceDirect, TRIP database, ClinicalTrials.gov and Cochrane Library from January 2000 to December 2016. Sixty studies were identified, of which seven were deemed eligible for this review. AMH data were extracted from each study and entered into the RevMan software to calculate the weighted mean difference (WMD) between pre- and post-operative values. Pooled analysis of all studies (n = 442) revealed a statistically significant decline in serum AMH concentration after LOD (WMD -2.13 ng/mL; 95% confidence interval (CI) -2.97 to -1.30). Subgroup analysis based on duration of follow-up, AMH kit, laterality of surgery and amount of energy applied during LOD consistently showed a statistically significant fall in serum AMH concentration. In conclusion, although LOD seems to markedly reduce circulating AMH, it remains uncertain whether this reflects a real damage to ovarian reserve or normalisation of the high pre-operative serum AMH levels. Further long-term studies on ovarian reserve after LOD are required to address this uncertainty.

Effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells.

BACKGROUND: Antipsychotics (APs) are widely prescribed drugs, which are well known to cause reproductive adverse effects through mechanisms yet to be determined. The purpose of this study was to investigate the effect of antipsychotics on mitochondrial bioenergetics of rat ovarian theca cells as a possible mechanism of reproductive toxicity. METHODS: Isolated rat theca interstitial cells (TICs) were treated with two typical (chlorpromazine [CPZ] and haloperidol [HAL]) and two atypical APs (risperidone [RIS] and clozapine [CLZ]). The effects of these APs on TICs bioenergetics (ATP content, mitochondrial complexes I and III activities, oxygen consumption rates (OCRs), mitochondrial membrane potential (MPP) and lactate production) and on steroidogenesis (androstenedione and progesterone synthesis) were investigated. RESULTS: All APs resulted in a concentration-dependent decrease in the ATP content of TICs. All APs at their estimated IC50s (6µM, 21µM, 35µM and 37µM for CPZ, HAL, CLZ and RIS respectively) significantly decreased TICs OCRs (p<0.0001), MPP (p<0.0001) and significantly (p=0.0003) inhibited mitochondrial complex I activity. Only typical APs inhibited complex III (p=0.005). Also, APs at IC50s increased TICs lactate production to varying degrees. All APs used at their IC50s significantly inhibited progesterone (p=0.0022) and androstenedione (p=0.0027) production. Only CPZ was found to inhibit these hormones at the low concentration (1µM). CONCLUSION: All four antipsychotics seem to inhibit mitochondrial bioenergetics and steroidogenesis in rat's ovarian theca cells. These findings support the hypothesis that APs-induced reproductive toxicity may be through mechanisms involving mitochondrial insult>. Further research is required to establish the link between APs-induced mitochondrial dysfunction and disordered steroidogenesis.

The impact of excision of benign nonendometriotic ovarian cysts on ovarian reserve: a systematic review.

BACKGROUND: Benign nonendometriotic ovarian cysts are very common and often require surgical excision. However, there has been a growing concern over the possible damaging effect of this surgery on ovarian reserve. OBJECTIVE: The aim of this metaanalysis was to investigate the impact of excision of benign nonendometriotic ovarian cysts on ovarian reserve as determined by serum anti-Müllerian hormone level. DATA SOURCES: MEDLINE, Scopus, ScienceDirect, and Embase were searched electronically. STUDY DESIGN: All prospective and retrospective cohort studies as well as randomized trials that analyzed changes of serum anti-Müllerian hormone concentrations after excision of benign nonendometriotic cysts were eligible. Twenty-five studies were identified, of which 10 were included in this analysis. DATA EXTRACTION: Two reviewers performed the data extraction independently. RESULTS: A pooled analysis of 367 patients showed a statistically significant decline in serum anti-Müllerian hormone concentration after ovarian cystectomy (weighted mean difference, -1.14 ng/mL; 95% confidence interval, -1.36 to -0.92; I(2) = 43%). Subgroup analysis including studies with a 3-month follow-up, studies using Gen II anti-Müllerian hormone assay and studies using IOT anti-Müllerian hormone assay improved heterogeneity and still showed significant postoperative decline of circulating anti-Müllerian hormone (weighted mean difference, -1.44 [95% confidence interval, -1.71 to -1.1; I(2) = 0%], -0.88 [95% confidence interval, -1.71 to -0.04; I(2) = 0%], and -1.56 [95% confidence interval, -2.44 to -0.69; I(2) = 22%], respectively). Sensitivity analysis including studies with low risk of bias and excluding studies with possible confounding factors still showed a significant decline in circulating anti-Müllerian hormone. CONCLUSION: Excision of benign nonendometriotic ovarian cyst(s) seems to result in a marked reduction of circulating anti-Müllerian hormone. It remains to be established whether this reflects a real compromise to ovarian reserve.

Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome.

This study examined whether a defect of steroid synthesis in ovarian theca cells may lead to the development of PCOS, through contributions to excess androgen secretion. Polycystic ovarian syndrome (PCOS) is one of the leading causes of infertility worldwide affecting around 1 in 10 of women of a reproductive age. One of the fundamental abnormalities in this syndrome is the presence of hormonal irregularities, including hyperandrogenemia, hyperinsulinemia and hypersecretion of luteinizing hormone (LH). Studies suggest that insulin treatment increases progesterone and androstenedione secretion in PCOS theca cells when compared to insulin treated normal theca cells. Furthermore the augmented effects of LH and insulin have been seen to increase ovarian androgen synthesis in non-PCOS theca cultures whilst also increasing the expression of steroidogenic enzymes specific to the PI3-K pathway. Our examination of primary thecal cultures showed an increase in both the expression of the steroidogenic enzyme CYP17 and androgen secretion in PCOS theca cells under basal conditions, when compared to non-PCOS cells. This was increased significantly under treatments of LH and insulin combined. Our results support the previous reported hypothesis that a dysfunction may exist within the PI3-K pathway. Specifically, that sensitivity exists to physiological symptoms including hyperinsulinemia and hyper secretion of LH found in PCOS through co-stimulation. The impact of these findings may allow the development of a therapeutic target in PCOS.

Long-term reproductive performance after surgery for ovarian endometrioma.

OBJECTIVE: To determine the long-term impact of different types of endometrioma surgery on reproductive performance and on age of menopause. STUDY DESIGN: This was a longitudinal observational cohort study of 68 women with previous endometrioma surgery and 68 age- and weight-matched healthy controls. All participants' hospital records were reviewed and each woman completed a questionnaire and attended an interview. Pregnancy rates were compared between the study and control groups. In the study group, pregnancy rates were compared before and after surgery. RESULTS: Amongst the 38 women desiring pregnancy after endometrioma surgery, 19 (50%) achieved a spontaneous pregnancy during the follow-up period. This was not significantly different from a pre-operative pregnancy rate of 48% (22/46). Of these 19 patients, four achieved another pregnancy with fertility treatment. An additional eight patients conceived only with the help of fertility treatment, giving an overall long-term post-operative pregnancy rate of 71% (27/38). These results were significantly lower (p=0.0001) than the 98% (57/58) long-term natural pregnancy rate in the control group. Pregnancy rates in patients receiving fertility treatment significantly (p=0.001) increased from 7% (1/15) before surgery to 63% (12/19) post-operatively. In post-menopausal women, the median (quartile) age at menopause was similar in the study (n=9) and control groups (n=6) [48 (45-52) versus 49 (44-52) years, respectively]. CONCLUSION: Endometriomas per se appear to be the main cause of the reduced long-term reproductive performance of the affected patients, with little or no contribution from surgery. Furthermore, endometrioma surgery seems to improve the success rates of fertility treatment.