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Recent methodological recommendations suggest the use of the "3-step method," consisting of calendar-based counting, urinary ovulation testing, and serum blood sampling, for the identification of subtle menstrual disturbances (SMDs). However, the use of the 3-step method is not always feasible, so a less demanding combination of calendar-based counting and urinary ovulation testing, that is, the 2-step method, may be a viable alternative. Purpose: To investigate the agreement between the 2- and 3-step methods for the detection of SMDs. Methods: Menstrual cycles (MCs, 98) of 59 athletes were assessed using the 2- and 3-step methods. Regular-length MCs (ie, ≥21 and ≤35 d) were classified as either having no SMD (luteal phase length ≥10 d, midluteal progesterone concentration ≥16 nmol·L−1, and being ovulatory) or having an SMD (eg, short luteal phase [<10 d], inadequate luteal phase [midluteal progesterone concentration <16 nmol·L−1], or being anovulatory). Method agreement was assessed using the McNemar test and Cohen kappa (κ). Results: Substantial agreement was observed between methods (κ =.72; 95% CI,.53–.91), but the 2-step method did not detect all MCs with an SMD, resulting in evidence of systematic bias (χ2 = 5.14; P =.023). The 2-step method detected 61.1% of MCs that had an SMD ([51.4, 70.8]), as verified using the 3-step method, and correctly identified 100% of MCs without an SMD. Conclusions: MCs classified as being disturbed using the 2-step method could be considered valid evidence of SMDs. However, MCs classified without SMDs do not definitively confirm their absence, due to the proven underdetection via the 2-step method. [ABSTRACT FROM AUTHOR]

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Background Although polycystic ovary syndrome (PCOS) is a very common endocrinopathy, there are several issues related to this disorder which perplex clinicians in their everyday practice. Objective To determine the current state of knowledge among European endocrinologists concerning the full spectrum of PCOS. Methods An online survey comprising 41 items covering various aspects of PCOS diagnosis and management was distributed to members of the European Society of Endocrinology. Results A total of 505 European endocrinologists (64% females), with a mean age of 47 ± 11.6 years, participated in the survey. The Rotterdam criteria were the primary diagnostic tool for 85% of respondents. Most referrals (87.1%) occurred between ages 20 and 40 years. Twenty-five percent of physicians have access to mass spectrometry for the evaluation of androgen levels. While an extended metabolic profile was commonly employed as part of the workup, there was uncertainty regarding chronic anovulation diagnosis. Diabetes, including gestational or type 2, was recognized as a significant risk factor with universal screening irrespective of BMI status. Lifestyle modification and metformin were considered as standard interventions by all participants alongside oral contraceptives, though there was significant discrepancy in treatment duration. Conclusions The Rotterdam diagnostic criteria are widely adopted for PCOS diagnosis among European endocrinologists. The current updated survey shows an emphasis on steroid profiling as an important part of diagnostic workup and a strong position held for recognition of PCOS as a metabolic condition with potentially serious implications. Current therapy thus shifted to the demand for prioritizing lifestyle interventions and metabolic therapies, either as monotherapy or in combination with standard hormone compounds. [ABSTRACT FROM AUTHOR]

BACKGROUND The increasing prevalence of obesity worldwide poses a significant threat to reproductive function owing, in part, to hormonal disturbances caused by negative feedback between excess adiposity and the hypothalamic–pituitary–ovarian axis. Consequently, finding the most appropriate strategies to lose weight and improve ovulation in women with overweight or obesity is a clinically relevant matter that needs to be investigated. A comprehensive comparison of the independent and combined efficacy of lifestyle and/or pharmacological interventions on BMI, ovulation, and hormonal profile in women with overweight or obesity at risk of anovulatory infertility would facilitate improving fertility strategies in this population. OBJECTIVE AND RATIONALE This study aimed to evaluate the comparative efficacy of exercise, diet, and pharmacological interventions on BMI, ovulation, and hormonal profile in reproductive-aged women with overweight or obesity. SEARCH METHODS A systematic review was performed by searching PubMed, Scopus, Web of Science, PsycINFO, and Cochrane Library up to 14 December 2023, for randomized controlled trials assessing the effects of exercise, diet and/or pharmacological interventions (i.e. weight-lowering drugs or ovulation inducers) on BMI, ovulation, and/or hormonal profile in reproductive-aged women with overweight or obesity. We performed frequentist random-effect network meta-analyses and rated the certainty of the evidence. The primary outcomes were BMI and ovulation rate, and the secondary outcomes were serum reproductive hormone levels (gonadotrophins, androgens, or oestrogens). We performed sensitivity analyses, including the studies that only involved women with PCOS. OUTCOMES Among 1190 records screened, 148 full texts were assessed for eligibility resulting in 95 trials (9910 women), of which 53% presented a high or unclear risk of bias. The network meta-analyses revealed that, compared to control: diet combined with weight-lowering drugs (mean difference (MD) −2.61 kg/m2; 95% CI −3.04 to −2.19; τ2 = 0.22) and adding exercise (MD −2.35 kg/m2; 95% CI −2.81 to −1.89; τ2 = 0.22) led to the greatest decrease in BMI; exercise combined with diet and ovulation inducers (risk ratio (RR) 7.15; 95% CI 1.94–26.40; τ2 = 0.07) and exercise combined with diet and weight-lowering drugs (RR 4.80; 95% CI 1.67–13.84; τ2 = 0.07) produced the highest increase in ovulation rate; and exercise combined with diet and weight-lowering drugs was the most effective strategy in reducing testosterone levels (standardized mean difference (SMD) −2.91; 95% CI −4.07 to −1.74; τ2 = 2.25), the third most effective strategy in increasing sex hormone-binding globulin levels (SMD 2.37; 95% CI 0.99–3.76; τ2 = 2.48), and it was coupled with being ranked first in terms of free androgen index reduction (SMD −1.59; 95% CI −3.18 to 0.01; τ2 = 1.91). The surface under the cumulative ranking curve scores suggested that: diet combined with weight-lowering drugs is the strategy most likely (94%) to produce the highest BMI reduction; and exercise combined with diet and ovulation inducers is the strategy most likely (89%) to produce the highest ovulation rate improvement. The sensitivity analyses, which exclusively included studies involving women diagnosed with PCOS, were consistent with the results presented above. WIDER IMPLICATIONS Overall, the findings of this network meta-analysis indicate that the combination of exercise, diet, and pharmacological interventions is effective for weight loss, improving ovulation, and normalizing the androgen levels of women with overweight or obesity. Although higher quality studies are needed, these results support that the optimal treatment strategy for women with overweight or obesity wishing to conceive must consider exercise, diet, and pharmacological interventions during the shared decision-making process. [ABSTRACT FROM AUTHOR]

Background: The causal relationship between sex hormone-binding globulin (SHBG) and infertility has remained unclear. Thus, we used Mendelian randomization (MR) to investigate this relationship. Methods: Risk factors for SHBG were extracted from European individuals within the UK Biobank using single-nucleotide polymorphism (SNP) data. Summary-level data for infertility outcomes were obtained from the FinnGen dataset. The causal relationship between SHBG and infertility was examined using inverse variance weighted, weighted model, weighted median, and MR-Egger regression analyses. Additionally, Cochran's Q test and Egger intercept tests were used to confirm the heterogeneity and pleiotropy of identified instrumental variables (IVs). Results: Our findings revealed a significant negative association between sex hormone-binding globulin (SHBG) levels and infertility, particularly with anovulation, a specific form of female infertility. However, SHBG did not exert a causal impact on male infertility or on female infertility of tubal origin. Conclusions: SHBG expression offers protection against the development of certain types of female infertility, suggesting it is a potential therapeutic target for infertility. [ABSTRACT FROM AUTHOR]

Exercising women have a high prevalence of menstrual disturbances. In 2003, it was suggested that disruption in luteinizing hormone (LH) pulsatility occurs below a threshold of energy availability (EA) of 30 kcal/kg lean body mass (LBM)/day. This paper is a critical review of the evidence regarding the theory that disruptions to the reproductive axis and menstrual disturbances occur below the proposed threshold. Short-term laboratory studies demonstrated that 4–5 days of an EA below 30 kcal/kg LBM/day, induced with or without exercise, decreased serum triiodothyronine and LH pulse frequency, and increased LH pulse amplitude in sedentary, regularly menstruating women. Fewer studies have investigated downstream ovarian effects after long-term exposure to low EA. The Sargent Camp Study was the first randomized trial that induced luteal phase defects, delayed menses, and anovulation by causing weight loss (−4 ± 0.3 kg) with an abrupt increase in exercise volume for two menstrual cycles. The BioEnergetics Study was a randomized controlled trial that induced varying levels of energy deficits by manipulating energy intake and expenditure for three menstrual cycles. LH pulse frequency and triiodothyronine decreased, and 57% of women developed luteal phase defects, anovulation, and/or oligomenorrhea. An EA below 30 kcal/kg fat free mass/day increased the chance of experiencing a menstrual disturbance by 50%. However, menstrual disturbances were observed above and below that EA threshold, and changes in LH pulse frequency predicted only luteal phase defects, not oligomenorrhea or anovulation. The proposed EA threshold is not a cut-off below which menstrual disturbances occur, but represents an increased risk of experiencing menstrual disturbances. [ABSTRACT FROM AUTHOR]

BACKGROUND The World Health Organization (WHO) system for the classification of disorders of ovulation was produced 50 years ago and, by international consensus, has been updated by the International Federation of Gynecology and Obstetrics (FIGO). OBJECTIVE AND RATIONALE This review outlines in detail each component of the FIGO HyPO-P (hypothalamic, pituitary, ovarian, PCOS) classification with a concise description of each cause, and thereby provides a systematic method for diagnosis and management. SEARCH METHODS We searched the published articles in the PubMed database in the English-language literature until October 2022, containing the keywords ovulatory disorders; ovulatory dysfunction; anovulation, and each subheading in the FIGO HyPO-P classification. We did not include abstracts or conference proceedings because the data are usually difficult to assess. OUTCOMES We present the most comprehensive review of all disorders of ovulation, published systematically according to the logical FIGO classification. WIDER IMPLICATIONS Improving the diagnosis of an individual's ovulatory dysfunction will significantly impact clinical practice by enabling healthcare practitioners to make a precise diagnosis and plan appropriate management. [ABSTRACT FROM AUTHOR]

Background: This study was designed to evaluate the effects of low-frequency electroacupuncture (EA) on glucose and lipid disturbances in a rat model of polycystic ovary syndrome (PCOS) characterized by insulin resistance (IR) and hepatic steatosis. Methods: The PCOS rat model was induced by continuous administration of letrozole (LET) combined with a high-fat diet (HFD). Female Sprague–Dawley rats were divided into the following four groups: control, control + EA, LET + HFD and LET + HFD + EA. EA was administered five or six times a week with a maximum of 20 treatment sessions. Body weight, estrous cyclicity, hormonal status, glucose and insulin tolerance, lipid profiles, liver inflammation factors, liver morphology and changes in the phosphatidylinositol 3-kinase (PI3-K)/Akt (protein kinase B) pathway were evaluated. Results: The rat model presented anovulatory cycles, increased body weight, elevated testosterone, abnormal glucose and lipid metabolism, IR, liver inflammation, hepatic steatosis and dysregulation of the insulin-mediated PI3-K/Akt signaling axis. EA reduced fasting blood glucose, fasting insulin, area under the curve for glucose, homeostasis model assessment of IR indices, triglycerides and free fatty acids, and alleviated hepatic steatosis. Furthermore, low-frequency EA downregulated mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6, upregulated mRNA expression of peroxisome proliferator-activated receptor (PPAR)-α, increased protein expression of phosphorylated (p)-Akt (Ser473), p-glycogen synthase kinase (GSK) 3β (Ser9) and glucose transporter 4 (GLUT4), increased the ratio of p-GSK3β to GSK3β and downregulated protein expression of GSK3β. Conclusion: An obese PCOS rat model with IR and hepatic steatosis was successfully established by the combination of LET and HFD. EA improved dysfunctional glucose and lipid metabolism in this PCOS-IR rat model, and the molecular mechanism appeared to involve regulation of the expression of key molecules of the PI3-K/Akt insulin signaling pathway in the liver. [ABSTRACT FROM AUTHOR]

Ovulatory disorders are common causes of amenorrhea, abnormal uterine bleeding, and infertility, and are frequent manifestations of polycystic ovary syndrome (PCOS). There are many potential causes and contributors to ovulatory dysfunction that challenge clinicians, trainees, educators, and those who perform basic, translational, clinical, and epidemiological research. Similarly, therapeutic approaches to ovulatory dysfunction potentially involve a spectrum of lifestyle, psychological, medical, and procedural interventions. Collaborative research, effective education, and consistent clinical care remain challenged by the absence of a consensus comprehensive system for classification of these disorders. The existing and complex system, attributed to WHO, was developed more than three decades ago and did not consider more than 30 years of research into these disorders in addition to technical advances in imaging and endocrinology. This manuscript describes the development of a new classification of ovulatory disorders performed under the aegis of the International Federation of Gynecology and Obstetrics (FIGO) and conducted using a rigorously applied Delphi process. The stakeholder organizations and individuals who participated in this process comprised specialty journals, experts at large, national, specialty obstetrical and gynecological societies, and informed lay representatives. After two face-to-face meetings and five Delphi rounds, the result is a three-level multi-tiered system. The system is applied after a preliminary assessment identifies the presence of an ovulatory disorder. The primary level of the system is based on an anatomic model (Hypothalamus, Pituitary, Ovary) that is completed with a separate category for PCOS. This core component of the system is easily remembered using the acronym HyPO-P. Each anatomic category is stratified in the second layer of the system to provide granularity for investigators, clinicians, and trainees using the "GAIN-FIT-PIE" mnemonic (Genetic, Autoimmune, Iatrogenic, Neoplasm; Functional, Infectious and Inflammatory, Trauma and Vascular; Physiological, Idiopathic, Endocrine). The tertiary level allows for specific diagnostic entities. It is anticipated that, if widely adopted, this system will facilitate education, clinical care, and the design and interpretation of research in a fashion that better informs progress in this field. Integral to the deployment of this system is a periodic process of reevaluation and appropriate revision, reflecting an improved understanding of this collection of disorders.

Objective: The primary aim of this study was to investigate the effects of autologous intrauterine platelet-rich plasma (IU-PRP) infusion during ovulation induction with clomiphene citrate (CC) on endometrial thickness (EMT) and clinical pregnancy in patients with polycystic ovary syndrome (PCOS) and thin endometrium. The secondary outcome was to detect possible transformations in oligomenorrheic cycles after PRP. Methods: This study was conducted on 35 anovulatory PCOS patients aged between 22 and 29 years who applied for infertility treatment. The patients had a thin endometrium in their past history. EMT 7 mm was considered thin endometrium. The diagnosis of PCOS was made according to the revised Rotterdam criteria. A total of 35 patients were divided into two groups according to whether they received PRP or not. Twenty patients received CC plus PRP treatment, whereas 15 patients received CC treatment alone. Patients in both groups were administered CC at a dose of 100 mg/day for 5 days, starting from the 3rd day of progesterone-related withdrawal bleeding. Follicular development and EMT were recorded using transvaginal ultrasonography. In cases with EMT <7 mm, approximately 0.5-1 mL of autologous PRP was infused with the IUI catheter, four days after CC treatment, i.e., on the ninth day of the cycle. EMT was measured and recorded again 3 and 6 days after PRP. Timed intercourse was recommended for cases with a follicle with a mean diameter of at least 16-18 mm. The biochemical and clinical pregnancy rates of both groups were recorded. Results: Both groups were similar in terms of participant age and body mass index. All participants in the CC plus PRP group were successfully infused with autologous PRP on the ninth day of the cycle. The serum estradiol, testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and LH/FSH ratios of both groups were similar. Biochemical pregnancy and clinical pregnancy rates of the CC plus PRP group were significantly higher than those of the CC alone group (p<0.03 and p<0.02, respectively). Although clinical pregnancy was detected in 5 individuals in the PRP group (25%), clinical pregnancy was recorded in 2 individuals in the CC alone group (13.3%). There was no significant change in the oligo/anovulatory cycle patterns of patients with and without PRP. EMT values on the sixth (4.96±2.11 mm vs. 4.68±2.47 mm, p<0.37) and eighth days were similar between the two groups (5.11±3.10 mm vs. 5.29±3.01 mm, p<0.51). Compared with the CC alone group, the EMT values measured both at day 12 (6.34±1.09 mm vs. 5.47±3.90 mm, p<0.02) and at day 15 (7.44±2.60 mm vs. 6.23±2.70 mm, p<0.01) in the PRP group were found to be significantly higher. Conclusion: IU-PRP infusion in PCOS patients with thin endometrium who underwent ovulation stimulation with CC significantly increased both EMT and clinical pregnancy rates. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrinopathy characterized by oligo or anovulation, hyperandrogenism, and/or polycystic ovarian morphology. While women in both developed and developing nations are affected, it is also the leading cause of ovulatory infertility among women of reproductive age. This article discusses the epidemiology, risk factors, pathophysiology, diagnosis, and particular emphasis to its treatment. Global prevalence of PCOS ranges from 4 to 21% whereas it is between 9.1 and 36% among adolescents. Clinical presentation of PCOS can be mainly attributed to hyperandrogenism and chronic anovulation. Symptoms of hyperandrogenism include hirsutism, acne, and/or male pattern alopecia. Chronic anovulation proceeds with features such as oligomenorrhea, amenorrhea, and/or infertility. Even though a specific gene responsible is not found yet, it's clear that women with PCOS have two major genetic alterations involving androgen synthesis, insulin action, and also an increased incidence of other genetic alterations. Family history, obesity, and an unhealthy diet are found to be significant risk factors for the development of PCOS. The fundamental pathological changes in PCOS include hyperandrogenism, abnormality of gonadotropin secretion, and insulin resistance. It has been noted that genes, HAS2 & CBLN1 that are associated with ovulation are expressed less in granulosa cells of PCOS patients. These cells also show significantly differentially expressed genes for transcription factors and secretory proteins in addition to having increased Toll-& NOD-like receptors. Presently, there is no universal treatment for PCOS. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome is one of the escalating, but underdiagnosed hormonal disorder in women of reproductive age. The present study is an attempt to explore long term health implications in four Rotterdam the phenotypes of Polycystic ovary syndrome. For this purpose, a total of 223 PCOS women with age ranged from 18 to 45 years and living in the Chandigarh Capital Region were selected from the OPD, PGIMER, Chandigarh, (North India). Polycystic ovary syndrome among women were diagnosed as per the Rotterdam Criteria (2004). Findings of the study indicated that hirsutism (47.5%), acne (30.9%), seborrhoea (32.2%), menstrual irregularity (55.6%), and ovarian size >10 cm³ (54.7%) were most frequently encountered symptoms in women having classic PCOS phenotype as compared to women with non-PCO PCOS, non-hyperandrogenic and ovulatory PCOS phenotype. The correspondence analysis depicted that classic PCOS phenotype were more closely and significantly associated with all the symptoms of PCOS with 83.6% variance, while ovulatory PCOS depicted least association with the symptoms of PCOS indicating that oligoanovulation play a vital role in the manifestation of symptoms related to PCOS. The classic PCOS phenotype showed higher prevalence of metabolic perturbations than other phenotypes, thereby confirming classic PCOS phenotypes are at greater risk of long-term health consequences. [ABSTRACT FROM AUTHOR]

Objective • A large proportion of patients undergoing assisted reproductive therapy (ART) suffer from premature ovarian insufficiency (POI). The knowledge structure, research hotspots, and research trends related to ART for patients with POI are still unclear and have not been systematically summarized. We aimed to analyze the research status of ART for patients with POI and deeply explore its knowledge structure and research trends. Our findings may provide treatment recommendations for clinicians and guidance for researchers in further research. Methods • The PubMed database for publications on ART for patients with POI was searched. The Bibliographic Item Co-occurrence Matrix Builder (BICOMB) obtained the Co-word matrix and co-occurrence matrix. The H-index method was used to extract high-frequency main Medical Subject Headings (MeSH) terms/subheadings. Then we used software such as graphical clustering toolkit (gCluto), Microsoft Excel, Ucinet and NetDraw to carry out the biclustering analysis, strategic diagram analysis and social network analysis of the major MeSH terms/subheadings. Results • The high-frequency major MeSH terms/ subheadings were analyzed by biclustering, strategic diagram, and social network analyses. A total of 431 articles from 1983 to 2023 were retrieved. Analysis showed that a total of 176 journals published relevant papers, including FERTILITY AND STERILITY, ranking first. In addition, we extracted 20 high-frequency major MeSH terms/subheadings. We grouped them into five categories: cryopreservation of oocyte and ovarian tissue, oocyte donation, in vitro activation (IVA) of primordial follicles, overview of therapy for patients with POI, therapy of iatrogenic POI. Within these five categories, there were 4, 4, 3, 4, and 5 major MeSH terms/subheadings, respectively. The major MeSH terms/subheadings were evenly distributed, and no particular group had a particular central tendency. Conclusion • The therapy of Iatrogenic POI is in the core position of research and is becoming increasingly mature. Oocyte donation and IVA of primordial follicles are the trends of future research. This study is helpful to understand the current research status, knowledge structure, and research trends of ART for patients with POI, and provide reference for improving ART for patients with POI in the future. Our study may guide clinicians to apply more established research to treat patients, which may lead to better treatment outcomes for patients. At the same time, we also suggest that researchers can conduct research in the field of future research trends, which may lead to greater research results. [ABSTRACT FROM AUTHOR]

Background: Women of reproductive age are frequently affected with Polycystic Ovarian Syndrome, an endocrine disorder that causes anovulation and infertility. There is a paucity in the evidence of comparing the effectiveness of the Swiss ball and resistance training among PCOS subjects. Purpose: To compare the effect of Swiss ball exercise and Resistance training in symptoms females with Polycystic Ovarian Syndrome. Materials and Method: A total of 30 subjects were selected from Private Institute. As outcome measures, the menstrual irregularity questionnaire (MIQ), BMI, and abdominal girth measurement were used. Subjects were divided randomly into resistance training group (n = 15) received exercises with dumbbells and Swiss ball training group (n = 15) received exercises with Swiss ball, in addition to aerobic exercise. Results: Females with PCOS symptoms in RTG experienced statistically significant improvement in BMI from 28.3 ± 3.3 to 25.3 ± 3.3, in Abdominal girth 93.6 ± 4.6 to 88.8 ± 4.6, in MIQ 18.3 ± 3.8 to 13.5 ± 3.3, with a p value of < 0.05 than in SBG which had BMI from 28.3 ± 3.7 to 27.9 ± 3.5, Abdominal girth 93.6 ± 5.3 to 92.6 ± 5.3, MIQ 18.1 ± 3.5 to 16.4 ± 3.8, with a p value < 0.05. Conclusion: In comparison to a Swiss ball exercise, resistance training programme combined with aerobic activity is more effective at helping women with PCOS symptoms. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this study was to compare the efficacy of the combination of clomiphene citrate (CC) and letrozole to that of CC alone in inducing ovulation in infertile women with ovulatory dysfunction. Methods A randomized controlled trial was conducted at a single academic medical center between November 2020 and December 2021. Anovulatory infertility females, aged 18 to 40, were evenly distributed by a computer-generated block of four into two treatment groups. A “combination group” received a daily dose of CC (50 mg) and letrozole (2.5 mg), while a “CC-alone group” received a daily dose of CC alone (50 mg). The study medications were administered on days 3 through 7 of menstrual cycle. The primary outcome was the ovulation rate, defined by serum progesterone levels exceeding 3 ng/mL at the mid-luteal phase. The secondary outcomes were ovulation induction cycle characteristics, endometrial thickness, conception rate, and adverse events. Results One hundred women (50 per group) were enrolled in the study. The mean age was not significantly different in both groups: 31.8 years in the combination group and 32.4 years in the CC-alone groups (P = 0.54). The prevalence of polycystic ovary syndrome in the combination and CC-alone groups was 48% and 44%, respectively (P = 0.841). According to intention-to-treat analysis, the ovulation rates were 78% and 70% in the combination and CC-alone groups, respectively (P > 0.05). There was no significant difference in the mean endometrial thickness or the number of dominant follicles of the groups. No serious adverse events were observed in either group. Conclusions Our study found no significant difference between the combination of CC and letrozole and CC alone in inducing ovulation in infertile women with ovulatory dysfunction in one cycle. The small number of live births precluded any meaningful statistical analysis. Further studies are needed to validate and extend our findings beyond the scope of the current study. Trial registration The study was registered at https://www.thaiclinicaltrials.org with the following number: TCTR20201108004 and was approved on 08/11/2020.

Background: Polycystic Ovarian Syndrome (PCOS) is associated with menstrual irregularities, hyper-androgenism, and polycystic ovaries. Prevalence of PCOS is around 4-18%. PCOS attribute 75% of infertility, due to lack of ovulation. PCOS patients has high level of AMH and in these patients during treatment of infertility there is possibility of developing ovarian hyperstimulation. Laparoscopic ovarian drilling (LOD) frequently performed in PCOS patients, we have decided to compare the level of AMH before and after Laparoscopic Ovarian Drilling (LOD) in these patients and its effect on fertility. Material & Method: The present study was a cohort study consisting of 88 women with PCOS who underwent laparoscopic ovarian drilling in hitech medical college & hospital Bhubaneswar, odisha in 2021. AMH and estradiol levels of the patients were calculated before the surgery and one week after the surgery. Also, the success rate of fertility was assessed within the twelve months after the surgery, which was indicated by Intrauterine insemination (IUI) or in vitro fertilization (IVF). Result: The relationship between mean AMH after drilling with BMI category was investigated using a one-way analysis of variance. The results showed that the mean AMH after ovarian drilling was not significantly different in the BMI categories (P = 0.181). The relationship between AMH after ovarian drilling with age, BMI and previous menstrual cycle was examined using linear regression. Age and BMI variables were not significantly associated with the previous menstrual cycle (P > 0.05). Conclusion: Based on the results of this study, it seems that measuring serum AMH concentration before treatment can be a useful tool in predicting LOD outcomes. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is the most prevalent, chronic endocrine-metabolic disorder of adolescents and young women (AYAs), affecting 5–10% of AYAs worldwide. There is no approved pharmacological therapy for PCOS. Standard off-label treatment with oral contraceptives (OCs) reverts neither the underlying pathophysiology nor the associated co-morbidities. Pilot studies have generated new insights into the pathogenesis of PCOS, leading to the development of a new treatment consisting of a fixed, low-dose combination of two so-called insulin sensitisers [pioglitazone (PIO), metformin (MET)] and one mixed anti-androgen and anti-mineralocorticoid also acting as an activator of brown adipose tissue [spironolactone (SPI)], within a single tablet (SPIOMET). The present trial will evaluate the efficacy, tolerability and safety of SPIOMET, on top of lifestyle measures, for the treatment of PCOS in AYAs. Methods: In this multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial, AYAs with PCOS will be recruited from 7 clinical centres across Europe. Intention is to randomise a total of 364 eligible patients into four arms (1:1:1:1): Placebo, PIO, SPI + PIO (SPIO) and SPI + PIO + MET (SPIOMET). Active treatment over 12 months will consist of lifestyle guidance plus the ingestion of one tablet daily (at dinner time); post-treatment follow-up will span 6 months. Primary endpoint is on- and post-treatment ovulation rate. Secondary endpoints are clinical features (hirsutism, menstrual regularity); endocrine-metabolic variables (androgens, lipids, insulin, inflammatory markers); epigenetic markers; imaging data (carotid intima-media thickness, body composition, abdominal fat partitioning, hepatic fat); safety profile; adherence, tolerability and acceptability of the medication; and quality of life in the study participants. Superiority (in this order) of SPIOMET, SPIO and PIO will be tested over placebo, and if present, subsequently the superiority of SPIOMET versus PIO, and if still present, finally versus SPIO. Discussion: The present study will be the first to evaluate—in a randomised, double-blind, placebo-controlled way—the efficacy, tolerability and safety of SPIOMET treatment for early PCOS, on top of a lifestyle intervention. Trial registration: EudraCT 2021–003177-58. Registered on 22 December 2021. https://www.clinicaltrialsregister.eu/ctr-search/search?query=%092021-003177-58. [ABSTRACT FROM AUTHOR]

This review is intended to serve as an aid in decision-making and patient counseling for the reproductive urologist when female factor infertility is found concurrently with male factor infertility. This review pairs the pathophysiology of female infertility with its implications for the treatment of male infertility, which most commonly includes ovulatory disorders, tubal abnormalities, and uterine abnormalities. By gaining a deeper understanding of these factors, reproductive urologists can employ a tailored approach to managing male factor infertility, taking into account the female partner's specific medical history. [ABSTRACT FROM AUTHOR]

Aim: The genetic basis of empty follicle syndrome (EFS) is largely unknown, and the aim of this study was to investigate the genetic causes of EFS in primary infertile women. Methods: Four affected women diagnosed with anovulation were recruited, and whole exome sequencing (WES) was requested for the genetic diagnosis of the cases. One hundred healthy controls were verified by Sanger sequencing. Results: A novel homozygous variant of the LHCGR gene (NM_000233:c.1847C>A) was revealed in one affected individual by WES. Trios analysis of the mutation revealed an autosomal recessive pattern. This LHCGR variant was absent in 100 healthy controls and predicted to be highly damaging to the function of LHCGR. Conclusions: The novel variant extends the mutational spectrum of the LHCGR gene associated with female sterility, which promotes the prognostic value of testing for LHCGR mutations in infertile women with EFS. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Approximately half of the diagnosed individuals also experience the metabolic syndrome. Central and peripheral resistance to the hormones insulin and leptin have been reported to contribute to both metabolic and reproductive dysregulation. In PCOS and preclinical PCOS animal models, circulating insulin and leptin levels are often increased in parallel with the development of hormone resistance; however, it remains uncertain whether these changes contribute to the PCOS state. In this study, we tested whether central actions of protein tyrosine phosphatase 1B (PTP1B) and suppressor of cytokine signaling 3 (SOCS3), negative regulators of insulin and leptin signaling pathways, respectively, play a role in the development of PCOS-like phenotype. A peripubertal dihydrotestosterone (DHT) excess PCOS-like mouse model was used, which exhibits both metabolic and reproductive dysfunction. Mice with knockout of the genes encoding PTP1B and SOCS3 from forebrain neurons were generated, and metabolic and reproductive functions were compared between knockout and control groups. DHT treatment induced mild insulin resistance but not leptin resistance, so the role of SOCS3 could not be tested. As expected, DHT excess abolished estrous cycles and corpora lutea presence and caused increased visceral adiposity and fasting glucose levels. Knockout mice did not show any rescue of reproductive dysfunction but did have reduced adiposity compared to the control DHT mice. These data suggest that negative regulation of central insulin signaling by PTP1B is not responsible for peripubertal DHT excess-induced reproductive impairments but may mediate its increased adiposity effects. [ABSTRACT FROM AUTHOR]

(1) Background: Infertility is a prevalent issue that affects 10–18% of couples worldwide, and up to 30% in Eastern Europe. Infertility of unknown etiology is one of the most challenging forms of infertility. Vitamin D has recently been extensively studied and researchers are investigating its possible role in ovulation and pregnancy. While the evidence suggests a positive association between vitamin D and ovulation, more research is needed to understand the role that vitamin D plays in ovulation. (2) Methods: In this study, 86 infertile patients were studied retrospectively in a single center by analyzing their anthropometric (body mass index), biochemical (total cholesterol, insulin resistance) and hormonal data in correlation with their vitamin D status. (3) Results: It was found that the mid-luteal progesterone level was significantly related to the 25-hydroxy vitamin D level in a multivariate linear regression model. An analysis of subgroups of ovulatory and anovulatory patients suggests that serum 25-hydroxy vitamin D levels of approximately 20 ng/mL may be necessary to trigger ovulation or to support progesterone secretion. (4) Conclusions: Vitamin D deficiency should be considered when infertility of unknown etiology and progesterone-related disorders occur. [ABSTRACT FROM AUTHOR]

Abstract Background In sub-Saharan Africa, tubal factors are described as the main aetiological factors of infertility. Under these conditions, medically assisted procreation is particularly indicated. However, Assisted Reproductive Technology centres are less available. Thus, infertile couples are quickly oriented towards available alternative conventional treatments. The present study aimed to determine the aetiological factors of infertility, the outcomes of the therapeutic options offered, and the factors associated with the success of conventional treatment among infertile couples seeking tertiary care in Kisangani. Methods A cross-sectional study was conducted at two tertiary health facilities in Kisangani. Infertile couples who provided consent underwent specific examinations necessary for the exploration of infertility and were treated and followed up for a minimum of 6 months. The therapeutic options that were offered were expectant attitude, medical treatment, surgical treatment or transfer to an in vitro fertilization unit. The pregnancy diagnosis was performed by ultrasound. Results A total of 272 infertile couples underwent specific examinations, were treated and were followed up for a minimum of 6 months. Many determinant causes were mostly linked to wives rather than husbands. Overall, only 34 women among 211 who were treated became pregnant during the follow-up period; 61 couples were advised to resort to IVF or adoption, but the couples for whom expectant the attitude was indicated immediately rejected it. The patients who therapeutically succeeded at the end of the treatment were those who were younger than 35 years (OR = 2.27; 95% CI = 1.06–4.87; P = 0.017), had a duration of infertility of less than five years (OR = 6.08; 95% CI = 1.79–20.69; P = 0.001) and had secondary infertility (OR = 6.08; 95% CI = 1.79–20.69; P = 0.001). Conclusion Kisangani faces a major issue in the treatment of infertility. Treatment of patients using conventional methods is limited by the predominance of tubal factors as aetiological determinants of infertility. The low pregnancy rate found in this study provided additional evidence of this. This paper represents a serious plea to national policy-makers to encourage them to pay attention to issues surrounding infertility.

IntroductionThe release of luteinising hormone (LH) before ovulation is disrupted during a state of low energy availability (EA). However, it remains unknown whether a threshold EA exists in athletic populations to trigger ovulatory disturbances (anovulation and luteal phase deficiency) as indicated by peak/mid-luteal serum progesterone concentration (Pk-PRG) during the menstrual cycle.MethodsWe assessed EA and Pk-PRG in 15 menstrual cycles to investigate the relationship between EA and Pk-PRG in free-living, competitive (trained-elite) Guatemalan racewalkers (n = 8) and runners (n = 7) [aged: 20 (14–41) years; post-menarche: 5 (2–26) years; height: 1.53 ± 0.09 m; mass: 49 ± 6 kg (41 ± 5 kg fat-free mass “FFM”)]. EA was estimated over 7 consecutive days within the follicular phase using food, training, and physical activity diaries. A fasted blood sample was collected during the Pk-PRG period, 6–8 days after the LH peak, but before the final 2 days of each cycle. Serum progesterone concentration was quantified using electrochemiluminescence immunoassay.ResultsParticipants that reported an EA of 9.40 ng·mL−1), except for a single racewalker with the lowest reported protein intake (1.1 g·kg body mass−1·day−1). EA was positively associated with Pk-PRG [r(9) = 0.79, 95% confidence interval (CI): 0.37–0.94; p = 0.003; 1 − β = 0.99] after excluding participants (n = 4) that likely under-reported/reduced their dietary intake.ConclusionsThe result from the linear regression analysis suggests that an EA ≥ 36 kcal·kg FFM−1·day−1 is required to achieve “normal ovulation.” The threshold EA associated with ovulatory disturbances in athletes and non-invasive means of monitoring the ovulatory status warrant further research.

Simple Summary: Cystic ovarian disease is an important ovarian disorder that leads to anovulatory infertility in dairy cows. In the present study, we used spontaneous ovarian follicular cysts to show the first evidence that the deregulation of Hippo pathway effector yes-associated protein expression and/or activity can be a potential key to better understand cystic ovarian disease pathogenesis. This finding also allows us to point towards Hippo pathway as a potential therapeutic target for the treatment of this major ovarian disorder in cattle. Cystic ovarian disease (COD) in dairy cattle is characterized by preovulatory follicles that become cysts, fail to ovulate and persist in the ovary; consequently, interfering with normal ovarian cyclicity. The intraovarian key players that orchestrate the alterations occurring in the preovulatory follicle and that culminate with cyst formation and persistence, however, remain uncertain. Interestingly, the Hippo pathway effector yes-associated protein (YAP) has been described in humans and mice as a key player of anovulatory cystic disorders. To start elucidating if YAP deregulation in ovarian follicle cells can be also involved in the pathogenesis of COD, we have generated a series of novel results using spontaneously occurring cystic follicles in cattle. We found that mRNA and protein levels of YAP are significantly higher in granulosa (GCs) and theca cells (TCs) isolated from cystic follicles (follicular structures of at least 20 mm in diameter) in comparison to respective cell types isolated from non-cystic large follicles (≥12 mm). In addition, immunohistochemistry and Western blot analyses used to determine YAP phosphorylation pattern suggest that YAP transcriptional activity is augmented is cystic GCs. These results were confirmed by a significant increase in the mRNA levels encoding for the classic YAP-TEAD transcriptional target genes CTGF, BIRC5 and ANKRD1 in GCs from follicle cysts in comparison to non-cystic large follicles. Taken together, these results provide considerable insight of a completely novel signaling pathway that seems to play an important role in ovarian cystic disease pathogenesis in dairy cattle. [ABSTRACT FROM AUTHOR]

Objective: Abnormal uterine bleeding (AUB) is the most common gynecologic complaint in adolescent girls. The aim of this study was to identify the diagnostic and management differences between those with/without heavy menstrual bleeding. Methods: Retrospective data was collected from adolescents aged 10-19 years, diagnosed with AUB. Adolescents with known bleeding disorders at admission were excluded. All girls were classified according to the degree of anemia; group 1 had heavy bleeding [hemoglobin (Hb) <10 g/dL] and group 2 had moderate or mild bleeding (Hb >10 g/dL). Admission and follow-up characteristics were compared between the two groups. Results: The cohort consisted of 79 girls with a mean age of 14.3±1.8 years and mean age of menarche of 11.9±1.4 years, with 85% experiencing menstrual irregularity in the two years after menarche, rising to 95.3% in group 1 (p<0.01). Anovulation was evident in 80% of the cohort. Of these 79 girls, 13 (16.5%) had polycystic ovary syndrome and two (2.5%) had structural anomalies (uterus didelphys). Three girls (group 1, n=2) had previously undiagnosed clotting factor VII deficiency; no other clotting deficiencies were diagnosed. Nineteen of 34 (56%) with personal (n=2)/family history of thrombosis had MTHFR mutation. None had venous thromboembolism during follow-up of >6 months. Conclusion: The majority of AUB (85%) occurred in the first two years after menarche. A small proportion (3.8%) had undiagnosed clotting factor deficiency. The frequency of MTHFR mutation was 50% in girls with history of thrombosis; however this did not increase the risk of bleeding/thrombosis and so routine evaluation does not appear to be justified. [ABSTRACT FROM AUTHOR]

Infertility is defined as the inability to conceive after unprotected sexual intercourse for at least 12 consecutive months. Our objective is to present an updated narrative review on the endocrine causes of infertility in women. A comprehensive review was conducted using Scielo, Scopus, and EMBASE databases, comprising 245 articles. The pathophysiology of infertility in women was described, including endocrinopathies such as hypothalamic amenorrhea, hyperprolactinemia, polycystic ovary syndrome, primary ovarian insufficiency, obesity, thyroid dysfunction, and adrenal disorders. The diagnostic approach was outlined, emphasizing the necessity of hormonal studies and ovarian response assessments. Additionally, the treatment plan was presented, commencing with non-pharmacological interventions, encompassing the adoption of a Mediterranean diet, vitamin supplementation, moderate exercise, and maintaining a healthy weight. Subsequently, pharmacological treatment was discussed, focusing on the management of associated endocrine disorders and ovulatory dysfunction. This comprehensive review highlights the impact of endocrine disorders on fertility in women, providing diagnostic and therapeutic algorithms. Despite remaining knowledge gaps that hinder more effective treatments, ongoing research and advancements show promise for improved fertility success rates within the next five years. Enhanced comprehension of the pathophysiology behind endocrine causes and the progress in genetic research will facilitate the delivery of personalized treatments, thus enhancing fertility rates. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Transcription factor 7-like 2 (TCF7L2) gene variants confer risk for type 2 diabetes and metabolic traits. We investigated the role of TCF7L2-variants in polycystic ovarian syndrome (PCOS), which is a common endocrine metabolic disorder affecting women of reproductive age. We tested whether TCF7L2 variants are in linkage to and/or in linkage disequilibrium [(LD), namely linkage and association)] with PCOS. PATIENTS AND METHODS: Within 212 families from the Italian peninsular population, we analyzed 78 variants using Pseudomarker software for linkage to and LD with PCOS under the dominant model with complete penetrance (D1). In a secondary analysis, we tested the variants under the recessive models with complete penetrance (R1), dominant with incomplete penetrance (D2), and recessive with incomplete penetrance (R2). We tested through in silico analysis the risk variants to detect any potential functional effects. RESULTS: We identified a total of 14 variants in the TCF7L2 gene significantly linked to and/or in LD with the risk of PCOS (p < 0.05) across different models. CONCLUSIONS: This study is the first to report TCF7L2 linkage and linkage disequilibrium in Italian families with PCOS. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome is a common endocrine disorder characterized by hormonal imbalances and various metabolic abnormalities linked to insulin resistance via a vicious cycle. Genetic and environmental factors underlie its pathogenesis and evolution. Nutrition, in terms of nutrient composition, dietary patterns, endocrine-disrupting chemicals, and food processing and preparation, has gained significant attention in the pathogenesis and the therapeutic approach of polycystic ovary syndrome. Carbohydrate intake seems to be a critical point in the diet assignment. Glycemic index and glycemic load constitute indexes of the impacts of dietary carbohydrates on postprandial glucose levels. Numerous studies have indicated that a high glycemic index and glycemic load diet may exacerbate insulin resistance, a key feature of the syndrome, and offer a risk for its development and its complications. Conversely, low-glycemic index and low-glycemic load diets seem to improve insulin sensitivity, regulate menstrual cycles, and mitigate the risk of comorbidities associated with polycystic ovary syndrome, such as obesity, alterations in body composition, type 2 diabetes, cardiovascular disease, and quality of life. This comprehensive review aims to explore the relevance of nutrition and more specifically, the association of glycemic index and glycemic load with the various aspects of polycystic ovary syndrome, as well as to assess the potential benefits of manipulating those indexes in the dietary approach for the syndrome. [ABSTRACT FROM AUTHOR]