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European Journal of Medical Research Mar 2024Letrozole has been proven to be an effective method for inducing ovulation. However, little attention has been paid to whether the lead follicle size will affect...
BACKGROUND
Letrozole has been proven to be an effective method for inducing ovulation. However, little attention has been paid to whether the lead follicle size will affect the success rate of intrauterine insemination (IUI) with ovulation induction with alone letrozole. Therefore, we hope to investigate the effect of dominant follicle size on pregnancy outcomes on human chorionic gonadotropin (hCG) day of the first letrozole-IUI.
METHODS
A retrospective cohort study design was employed. We included patients with anovulation or unexplained infertility undergoing first IUI treatment with letrozole for ovarian stimulation. According to the dominant follicle size measured on the day of hCG trigger, patients were divided into six groups (≤ 18 mm, 18.1-19.0 mm, 19.1-20.0 mm, 20.1-21.0 mm, 21.1-22.0 mm, > 22 mm). Logistic models were used for estimating the odds ratios (ORs) with their 95% confidence interval (CIs) for achieving a clinical pregnancy or a live birth. A restricted cubic spline was drawn to explore the nonlinear relationship between follicle size and IUI outcomes.
RESULTS
A total of 763 patients underwent first letrozole-IUI cycles in our study. Fisher exact test showed significant differences among the six follicle-size groups in the rates of pregnancy, clinical pregnancy and live birth (P < 0.05 in each group). After adjusting the potential confounding factors, compared with the follicles ≤ 18 mm in diameter group, 19.1-20.0 mm, 20.1-21.0 mm groups were 2.3 or 2.56 times more likely to get live birth [adjusted OR = 2.34, 95%CI (1.25-4.39); adjusted OR = 2.56, 95% CI (1.30-5.06)]. A restricted cubic spline showed an inverted U-shaped relationship between the size of dominant follicles and pregnancy rate, clinical pregnancy rate, and live birth rate, and the optimal follicle size range on the day of hCG trigger was 19.1-21.0 mm. When the E level on the day of hCG trigger was low than 200 pg/mL, the clinical pregnancy rates of 19.1-20.0 mm, 20.1-21.0 mm groups were still the highest.
CONCLUSIONS
The optimal dominant follicle size was between 19.1 and 21.0 mm in hCG-triggered letrozole-IUI cycles. Either too large or too small follicles may lead to a decrease in pregnancy rate. Using follicle size as a predicator of pregnancy outcomes is more meaningful when estrogen on the day of hCG trigger is less than 200 pg/ml.
Topics: Pregnancy; Female; Humans; Letrozole; Pregnancy Outcome; Retrospective Studies; Insemination, Artificial; Pregnancy Rate
PubMed: 38500174
DOI: 10.1186/s40001-024-01794-8 -
Endokrynologia Polska 2024We aimed to evaluate 304 premenopausal women admitted to our clinic for oligomenorrhoea, and to screen for Cushing's syndrome (CS) in this population.
INTRODUCTION
We aimed to evaluate 304 premenopausal women admitted to our clinic for oligomenorrhoea, and to screen for Cushing's syndrome (CS) in this population.
MATERIAL AND METHODS
The study included 304 premenopausal women referred to our clinic for oligomenorrhoea. Anthropometric measurements and Ferriman-Gallwey score were evaluated, and thyroid hormone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, prolactin, dehydroepiandrosterone sulphate (DHEA-S), and 17-hydroxyprogesterone (17-OHP) levels were measured in all patients. If basal 17-OHP was > 2 ng/mL, we evaluated adrenocorticotropic hormone (ACTH)-stimulated 17-OHP levels. CS was screened by 1 mg-dexamethasone suppression test, and if the cortisol value was > 1.8 μg/dL, we performed additional confirmatory tests, and if necessary, pituitary magnetic resonance imaging (MRI) and inferior petrosal sinus sampling (IPSS) were performed.
RESULTS
The most common cause of oligomenorrhoea was polycystic ovary syndrome (PCOS) that was detected in 81.57% of cases, followed by hyperprolactinemia at 7.23% and hypothalamic anovulation at 5.26%. The prevalence of premature ovarian failure (POF) was 1.6%, and non-classical congenital adrenal hyperplasia (NCAH) was 1.97%. CS was detected in 7 (2.30%) patients. All the patients with CS were found to have Cushing's disease (CD). Although 3 patients with CD had classical signs and symptoms, 4 had none. Patients with CD had similar total testosterone values to those in the PCOS and NCAH groups, but they had significantly higher DHEA-S compared to both groups (CD vs. PCOS, p = 0.001 and CD vs. NCAH, p = 0.030).
CONCLUSIONS
We found higher prevalence of CS in patients with oligomenorrhoea even in the absence of clinical signs. Therefore, we suggest routine screening for CS during the evaluation of patients with oligomenorrhoea and/or PCOS. The likelihood of CS is greater in patients with high androgen, especially DHEA-S levels.
Topics: Humans; Female; Polycystic Ovary Syndrome; Oligomenorrhea; Prevalence; Cushing Syndrome; Adrenal Hyperplasia, Congenital; Pituitary ACTH Hypersecretion; Testosterone; Dehydroepiandrosterone
PubMed: 38497394
DOI: 10.5603/ep.96737 -
American Journal of Human Biology : the... Mar 2024Polycystic ovary syndrome (PCOS), characterized by polycystic ovaries, anovulation, and hyperandrogenism, is believed to be an evolutionary mismatch disease. Past...
OBJECTIVES
Polycystic ovary syndrome (PCOS), characterized by polycystic ovaries, anovulation, and hyperandrogenism, is believed to be an evolutionary mismatch disease. Past research has examined PCOS as a uniform disease, despite variation in phenotypes across diagnostic categories, but establishing an evolutionary mismatch requires a focus on individual traits. We suggest PCOS hyperandrogenism may have been beneficial in ancestral environments because it reduced fracture risk and associated morbidity and mortality due to increased bone mineral density (BMD). We test this hypothesis by assessing fracture frequency, a proxy for BMD, in highly active females with and without PCOS hyperandrogenism.
METHODS
Sixty-seven reproductive-aged women were surveyed and grouped as: high intensity interval training (HIIT; a proxy for metabolic and physical stress) athletes with hyperandrogenic PCOS (31.24%), HIIT athletes without PCOS (29.85%), and nonathletes with hyperandrogenic PCOS (38.81%). Fracture occurrence was compared between the groups using independent samples Kruskal-Wallis tests for non-normally distributed data, and multiple regression analysis was used to examine anthropometrics, lifestyle and reproductive factors, PCOS status, and exercise frequency on fracture occurrence.
RESULTS
Fracture occurrence was higher in non-PCOS athletes (3.8 ± 4.3) than PCOS-athletes (1.2 ± 1.4, p = .11) and PCOS-non-athletes (1.0 ± 1.4, p < .01). PCOS-athletes and nonathletes did not differ significantly in fracture occurrence (p = .33). These results were independent of factors associated with bone health.
CONCLUSIONS
These preliminary findings suggest females with PCOS-related hyperandrogenism may be less likely to experience bone fractures and provide an initial step to explaining why PCOS has persisted despite marked negative reproductive consequences in modern populations.
PubMed: 38488301
DOI: 10.1002/ajhb.24070 -
Women's Health (London, England) 2024Polycystic ovary syndrome is a common reproductive endocrine condition that affects women of fertile age and is characterized by three main features, including... (Review)
Review
Polycystic ovary syndrome is a common reproductive endocrine condition that affects women of fertile age and is characterized by three main features, including hyperandrogenism, chronic anovulation, and polycystic ovaries. In addition, half of women with polycystic ovary syndrome have insulin resistance, and obesity or overweight, type 2 diabetes, hypertension, and hyperlipidemia are the most common metabolic abnormalities affecting (30%) women with polycystic ovary syndrome. Weight loss is regarded as the first-line treatment as it can potentially improve polycystic ovary syndrome parameters (androgen levels, menstrual cyclicity, lipid and glucose metabolism). However, achieving and maintaining weight loss can be challenging, and pharmacological agents could be essential to achieve optimal glycemic control and improve the endocrine disturbance associated with polycystic ovary syndrome. Glucagon-like peptide-1 receptor agonist has been demonstrated as monotherapy or in combination with metformin for managing obesity and insulin resistance associated with polycystic ovary syndrome. Yet, its effect on endocrine and metabolic parameters remains elusive, and further research is needed to close the gap. The aim is to evaluate the efficacy of glucagon-like peptide-1 receptor agonist monotherapy and/or a combined treatment between glucagon-like peptide-1 receptor agonist and metformin for improving anthropometric measurements, endocrine and metabolic parameters in lean and obese women with polycystic ovary syndrome. A systematic review of longitudinal cohort studies was conducted across databases including Ovid Medline, PubMed Central, and Cochrane Library between 2015 and 2022. Eligible studies included participants with polycystic ovary syndrome diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health criteria. A total of eight studies including 486 patients with polycystic ovary syndrome were analyzed. The mean age was between 18 and 45 years with mean follow-up period between 12 and 32 weeks. In all these studies, results were comparable for the reduction in body mass index, waist circumference, fat mass, and visceral fat mass; however, it was more in combination therapy versus comparator. In conclusion, glucagon-like peptide-1 receptor agonists effectively reduce body weight and improve some of the endocrine and metabolic parameters of polycystic ovary syndrome. A combined treatment with glucagon-like peptide-1 receptor agonist and metformin had significant effects on weight loss and favorable results on endocrine and metabolic parameters, yet further research is needed to discover the long-term safety of combined therapy in women diagnosed with polycystic ovary syndrome and obesity or overweight.
Topics: Female; Humans; Infant; Male; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor Agonists; Insulin Resistance; Longitudinal Studies; Metformin; Obesity; Overweight; Polycystic Ovary Syndrome; United States; Weight Loss
PubMed: 38444070
DOI: 10.1177/17455057241234530 -
Human Reproduction Update May 2024The World Health Organization (WHO) system for the classification of disorders of ovulation was produced 50 years ago and, by international consensus, has been updated... (Review)
Review
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.
Topics: Humans; Female; Ovulation; Polycystic Ovary Syndrome; Infertility, Female; Anovulation; Ovarian Diseases
PubMed: 38412452
DOI: 10.1093/humupd/dmae003 -
Cell Reports. Medicine Mar 2024Transmasculine people usually reach amenorrhea within 6 months of adequate testosterone treatment. It is often assumed that no ovulation occurs during amenorrhea....
Transmasculine people usually reach amenorrhea within 6 months of adequate testosterone treatment. It is often assumed that no ovulation occurs during amenorrhea. However, in this study, we report recent ovulatory activity in amenorrheic transmasculine people on testosterone therapy at gender-affirming oophorectomy. Histological signs of recent ovulatory activity, including the presence of ovulatory follicles, corpus luteum, and corpus albicans, are observed in 17 of 52 individuals (33%). This is not significantly correlated to the duration, testosterone serum levels, or type of testosterone used. These results suggest that amenorrhea does not equal anovulation in transmasculine people on adequate testosterone therapy, emphasizing the importance of contraception for people who engage in sexual activity that can result in pregnancy.
Topics: Pregnancy; Female; Humans; Testosterone; Amenorrhea; Ovulation
PubMed: 38402622
DOI: 10.1016/j.xcrm.2024.101440 -
Frontiers in Cell and Developmental... 2024Globally, polycystic ovarian syndrome (PCOS) affects approximately 10% of fertile women, leading to great health and economic burden. PCOS is a heterogenous illness that... (Review)
Review
Globally, polycystic ovarian syndrome (PCOS) affects approximately 10% of fertile women, leading to great health and economic burden. PCOS is a heterogenous illness that can cause infertility, irregular menstrual cycles, acne, and hirsutism, among other symptoms. The clinical diagnosis is primarily a diagnosis of exclusion if one or more of the three primary symptoms, namely, oligo- or anovulation, hyperandrogenism, and polycystic ovarian morphology, are present. Obesity and PCOS are often coexisting disorders that may be bidirectionally causally related. Phenotypic heterogeneity throughout the reproductive lifespan, such as the overlap of PCOS symptoms with regular fluctuations in a woman's menstrual cycle and metabolism during the menarche and menopausal transition, further complicates diagnosis. PCOS etiology is mostly unknown and complex, likely due to the fact that it is a group of disorders with overlapping metabolic and reproductive problems. Evidence-based, common, standardized guidelines for PCOS diagnosis and treatment are urgently needed. Genomics and clinical data from populations across diverse ages and ethnicities are urgently needed to build efficient machine learning models for the stratification of PCOS. PCOS subtype-specific strategies for early screening, an accurate diagnosis, and management throughout life will optimize healthcare resources and reduce unnecessary testing. This will pave the way for women to be able to take the best possible care of their own health using the latest clinical expertise combined with their unique needs and preferences.
PubMed: 38389707
DOI: 10.3389/fcell.2024.1358755 -
Reproductive Biology and Endocrinology... Feb 2024Insulin resistance (IR) is known to be prevalent amongst women with polycystic ovarian syndrome (PCOS). Its presence has been linked to chronic anovulation and marked... (Comparative Study)
Comparative Study
BACKGROUND
Insulin resistance (IR) is known to be prevalent amongst women with polycystic ovarian syndrome (PCOS). Its presence has been linked to chronic anovulation and marked long term complications in women. Hence, identification and treatment of IR in women with PCOS is required to prevent the metabolic and reproductive complications of the disease. The aim of this study is to determine if serum adiponectin could be used as a surrogate marker for insulin resistance among women with PCOS.
MATERIALS AND METHODS
A total number of 148 consenting women with PCOS diagnosed using the Rotterdam criteria were recruited for this study. Fifty-two of these women had insulin resistance were compared with 96 of the women who did not have insulin resistance. The serum Adiponectin levels, fasting blood glucose and fasting insulin levels were assayed in all study participants. Insulin resistance was assessed in all the study participants using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). Data were analyzed using relevant inferential statistics at 95% confidence interval and p value of < 0.05.
RESULTS
The prevalence of insulin resistance among the study participants was 35.1%. Majority of the women (83.1%) had a high body mass index (BMI). More than half (68.2%) of the participants were in the age range of 21-30years and 76.4% (113) were nulliparous. There was no statistically significant difference in the median adiponectin level among insulin resistant (3.735 ug/ml) and non-insulin resistant participants vs. (3.705 ug/ml) (p = 0.6762). Both univariate and multivariate regression analysis did not show a statistically significant relationship between adiponectin and insulin resistance in PCOS.
CONCLUSION
The prevalence of insulin resistance in women with PCOS is high and serum adiponectin is not a suitable surrogate marker of insulin resistance in women with PCOS.
Topics: Adult; Female; Humans; Young Adult; Adiponectin; Biomarkers; Blood Glucose; Body Mass Index; Cross-Sectional Studies; Insulin; Insulin Resistance; Polycystic Ovary Syndrome
PubMed: 38378576
DOI: 10.1186/s12958-024-01196-9 -
Journal of Neuroendocrinology Mar 2024Excess levels of circulating androgens during prenatal or peripubertal development are an important cause of polycystic ovary syndrome (PCOS), with the brain being a key...
Excess levels of circulating androgens during prenatal or peripubertal development are an important cause of polycystic ovary syndrome (PCOS), with the brain being a key target. Approximately half of the women diagnosed with PCOS also experience metabolic syndrome; common features including obesity, insulin resistance and hyperinsulinemia. Although a large amount of clinical and preclinical evidence has confirmed this relationship between androgens and the reproductive and metabolic features of PCOS, the mechanisms by which androgens cause this dysregulation are unknown. Neuron-specific androgen receptor knockout alleviates some PCOS-like features in a peripubertal dihydrotestosterone (DHT) mouse model, but the specific neuronal populations mediating these effects are undefined. A candidate population is the agouti-related peptide (AgRP)-expressing neurons, which are important for both reproductive and metabolic function. We used a well-characterised peripubertal androgenized mouse model and Cre-loxP transgenics to investigate whether deleting androgen receptors specifically from AgRP neurons can alleviate the induced reproductive and metabolic dysregulation. Androgen receptors were co-expressed in 66% of AgRP neurons in control mice, but only in <2% of AgRP neurons in knockout mice. The number of AgRP neurons was not altered by the treatments. Only 20% of androgen receptor knockout mice showed rescue of DHT-induced androgen-induced anovulation and acyclicity. Furthermore, androgen receptor knockout did not rescue metabolic dysfunction (body weight, adiposity or glucose and insulin tolerance). While we cannot rule out developmental compensation in our model, these results suggest peripubertal androgen excess does not markedly influence Agrp expression and does not dysregulate reproductive and metabolic function through direct actions of androgens onto AgRP neurons.
Topics: Animals; Female; Humans; Mice; Pregnancy; Agouti-Related Protein; Androgens; Dihydrotestosterone; Mice, Knockout; Neurons; Obesity; Peptides; Polycystic Ovary Syndrome; Receptors, Androgen; Virilism
PubMed: 38344844
DOI: 10.1111/jne.13370 -
Human Reproduction Open 2024Does palmitic acid (PA), the most common saturated free fatty acid (FFA) in individuals with obesity, contribute to anovulation through upregulation of the...
STUDY QUESTION
Does palmitic acid (PA), the most common saturated free fatty acid (FFA) in individuals with obesity, contribute to anovulation through upregulation of the collagen-crosslinking enzyme lysyl oxidase (LOX) in the ovary?
SUMMARY ANSWER
Increased PA in individuals with obesity can cause LOX upregulation via the activation of hypoxia-inducible factor-1α (HIF-1α), resulting in abnormal collagen deposition in the ovary and anovulation, which can be ameliorated by metformin therapy.
WHAT IS KNOWN ALREADY
The underlying cause of anovulation in individuals with obesity is poorly defined, and accumulating evidence indicates that hormonal disturbance, insulin resistance, and inflammation may all play a role in the development of ovulation disorders in individuals with obesity. However, it remains to be determined whether PA plays a role in the regulation of LOX expression, thus disrupting ovarian extracellular matrix (ECM) remodelling in the ovary and resulting in impaired ovulation in individuals with obesity.
STUDY DESIGN SIZE DURATION
PA concentration and LOX protein abundance and activity in follicular fluid and ovarian tissue were compared between control (n = 21) subjects, patients with obesity with ovulation (n = 22), and patients with obesity with anovulation (n = 16). The effect of PA on LOX protein expression, and the underlying mechanism, was examined in primary human granulosa cells . The improvements in obesity conditions induced by LOX inhibition combined with metformin were investigated in a high-fat diet-induced obese rat model.
PARTICIPANTS/MATERIALS SETTING METHODS
The abundance of PA concentration and LOX activity was measured via a LOX activity assay and ELISA, respectively. The effect of PA on LOX protein expression was examined in the presence or absence of inhibitors of signalling molecules and siRNA-mediated knockdown of the putative transcription factor. Chromatin immunoprecipitation assays were subsequently conducted to further identify the responsible transcription factor. The role of metformin in the treatment of anovulation by LOX inhibition was investigated in a high-fat diet (HFD)-induced obese rat model. The numbers of retrieved total oocytes and metaphase II oocytes were recorded upon ovarian stimulation. Masson's trichrome staining was used to measure the total collagen content, and immunohistochemical staining and western blotting were used to measure LOX, HIF-1α, and collagen I and IV in the ovary.
MAIN RESULTS AND THE ROLE OF CHANCE
Significantly increased FFA, LOX, and collagen abundance were observed in the ovaries of obese women with anovulation, compared to healthy controls or obese women with ovulation. In a HFD-induced obese rat model, metformin corrected the distortion of ovarian morphology by decreasing LOX and collagen protein abundance in the ovary and improving oestrous cyclicity and ovulation. PA increased LOX expression via the activation of HIF-1α in human granulosa cells, which was attenuated by metformin.
LARGE SCALE DATA
N/A.
LIMITATIONS REASONS FOR CAUTION
Several other saturated and polyunsaturated FFAs, such as stearic acid and arachidonic acid, are also increased in the blood of individuals with obesity, and increased levels of other FFAs may also contribute to the development of anovulation in individuals with obesity, which needs to be further verified in the future.
WIDER IMPLICATIONS OF THE FINDINGS
Elevated PA in individuals with obesity can cause LOX dysregulation via activation of HIF-1α, resulting in abnormal collagen deposition in the ovary and anovulation. This dysregulation can be ameliorated by metformin therapy through its local effect on ECM remodelling in the ovary, which is independent of its systemic effect on insulin sensitivity and chronic inflammation.
STUDY FUNDING/COMPETING INTERESTS
This work was supported by the National Natural Science Foundation of China (grant numbers 82101730, 82130046, and 31900598) and Innovative Research Team of High-level local Universities in Shanghai (SHSMU-ZLCX20210201). All the authors declare no conflicts of interest in relation to this work.
PubMed: 38333108
DOI: 10.1093/hropen/hoae002