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Objective To determine whether infertility diagnoses differ between Black ethnic subgroups. Design Retrospective review Setting An urban safety net hospital. Patients Women seeking infertility care between 2005-2015. Interventions Charts of women with infertility and PCOS ICD-9 diagnoses were reviewed to confirm diagnoses. Data was stratified by race and subsequently by ethnicity to evaluate differences in infertility diagnoses between Black American, Black Haitian, and Black African women. White American women were used as the comparison group. Main Outcome Measures Infertility diagnoses between Black ethnic subgroups and White women. Results A total of 358 women met inclusion criteria including 99 Black American, 110 Black Haitian, 61 Black African, and 88 White American women. Anovulation/polycystic ovarian syndrome (PCOS) was the most common diagnosis in each ethnic group, accounting for 40% of infertility among White American, 57% among Black American, 25% among Black Haitian, and 21% among Black African women. There were no significant differences in individual infertility diagnoses between Black and White women. Between ethnic subgroups, multivariate analysis showed significantly higher odds of infertility due to anovulation/PCOS in Black American women compared to Black African women (odds ratio [OR]=4.9; 95% CI=1.4-17.0). Compared to Black African women, higher odds of tubal factor infertility were observed in Black American (OR=4.7; 95% CI=1.16-18.7) and Black Haitian women (OR=4.0; 95% CI=1.1-14.0). Conclusions Infertility diagnoses were not homogeneous across Black ethnic groups. Studies examining infertility should specify ethnic subgroups within race as this may affect results.

Introduction. In this article, the authors present the results of studies on reproductive health features in 25 women with obesity seeking medical help for infertility. Objective: to study the nature of menstrual disorders in women of childbearing age with obesity. Materials and methods. We have studied the features of reproductive health in 25 obese women seeking medical assistance for infertility in the Republican specialized scientific and practical centre of endocrinology in 2014–2015, who were included in the first study group. The second group consisted of 25 women with normal weight-for-stature values and without menstrual disorders. All the patients underwent the following tests, including complete blood count, blood biochemistry, radioimmunoassays of the blood hormones (prolactin, luteinizing hormone (LH), follicle stimulating hormone (FSH), insulin, estradiol, progesterone, free testosterone, thyroxine, anti-Műllerian hormone, dehydroepiandrostenedione, ultrasound of the uterus and ovaries with folliculometry on 11–14th days of the menstrual cycle. All patients underwent magnetic resonance imaging of the pituitary gland. Results. In the history of the patients in both groups, diseases of the upper respiratory tract and gastrointestinal diseases were most common among somatic pathology. Among gynecological diseases, in both groups the most frequent disorders were chronic urogenital infection, candida vaginitis and bacterial vaginosis. Emphasis is placed on the data about the presence of hormone-dependent proliferative diseases in women with overweight: cervical pseudoerosions, endocervicosis, uterine fibroids, a history of endometriosis. The analysis of biochemical parameters in the first study group found increased triglycerids levels < 1.7 mmol/L in 15 %, a decrease in high-density lipoprotein cholesterol 3.0 mmol/L — in 34 %. The first group of patients had low values of the average parameters of LH, FSH, free and total testosterone (normogonadotropic hypogonadism) against normoprolactinemia. The levels of adrenocorticotropic hormone, thyroid-stimulating hormone, free thyroxine, and cortisol were within normal limits. Folliculometry results showed a high incidence of follicular persistence, anovulatory disorders and follicular atresia. Conclusions. In young women with the metabolic syndrome, secondary amenorrhea prevails in the structure of menstrual dysfunction — 8 (32.0 %) cases. Hyperandrogenic anovulation following hyperinsulinemia underlies the menstrual dysfunction.

Background Polycystic ovary syndrome (PCOS) is a metabolic disease that causes infertility due to anovulation in women in reproductive age. It is known that clomiphene citrate (CC) and tamoxifen citrate (TMX) induce ovulation in women with PCOS. In this study, we aimed to investigate the effects of CC and TMX on the autophagy pathway in PCOS. Methods and results Experimental PCOS model was induced by letrozole (1 mg/kg) in rats by gavage for 21 days. After the last letrozole administration, rats were treated TMX (1 mg/kg) or CC (1 mg/kg) for 5 days. At the end of the experimental procedures, rats in all groups were sacrificed and ovarian tissues were removed. It was observed that mRNA and protein expressions of LC3-II were significantly higher in TMX and CC groups than control and PCOS groups (p < 0.05), while mRNA and protein expressions of mTOR in TMX and CC groups were found significantly lower than control and PCOS groups (p < 0.05). Conclusions In conclusion, present study suggests that TMX and CC induce autophagy in ovaries with PCOS. Autophagy is a promising target for understanding pathophysiology of this disease and for developing more effective and safe new protocols for the treatment of PCOS-related anovulation., Ege University Research Fund [BAP-17-TIP-029], This study was supported by the Ege University Research Fund [Grant number BAP-17-TIP-029 (to Altug Yavasoglu)].

Polycystic ovary syndrome (PCOS) is a global health concern for women of reproductive age, as 6.5% of women worldwide are affected by this syndrome. PCOS is marked by hyperandrogenism, anovulation, menstrual abnormalities, and polycystic ovaries. Metals such as arsenic, cadmium, lead and mercury are considered to be systemic toxicants/human carcinogens and seem to have devastating effects on humans, even at minimal exposures. One of the probable aetiological factors for PCOS has been identified as oxidative stress. In view of the probable associations among oxidative stress, metal toxicity and PCOS, the present study examined the role of heavy metals in the generation of oxidative stress among females. This prospective study included 106 women (56 women diagnosed with PCOS and 50 women who were not diagnosed with PCOS as control women). There were no significant differences in the sociodemographic characteristics between the two groups except for the irregularity of menses and the presence of acne. The serum As, Cd, Pb, and Hg levels increased and the serum glutathione (GSH) and superoxide dismutase (SOD) levels diminished significantly in the PCOS group compared to the control group at P P P P P P

Background Even though polycystic ovary syndrome (PCOS) is a common reproductive disorder affecting young women, its impact on their sexual health is not well known. Aim To examine the different aspects of female sexuality in young women with PCOS and attempt to associate hormonal changes and ovulatory status with their sexual function. Methods Anthropometric characteristics, hormonal levels and sexual function based on the Female Sexual Function Index (FSFI) questionnaire were assessed in 76 young women with PCOS and 133 matched controls. Outcomes Sexual function is significantly impaired in young women with PCOS. RESULTS Women with PCOS demonstrated lower scores than controls in arousal (5.04 ± 1.19 vs 4.48 ± 1.44, P < .001), lubrication (5.29 ± 1.17 vs 4.69 ± 1.54, P < .001), orgasm (4.78 ± 1.40 vs 4.11 ± 1.61, P = .001), satisfaction (5.22 ± 1.10 vs 4.78 ± 1.31, P = .016), and total score of the FSFI (29.51 ± 5.83 vs 26.76 ± 6.81, P < .001), even after correction for BMI. When corrected for total testosterone, the domains of lubrication, satisfaction, and total score of FSFI remained significantly impaired in women with PCOS (P values .037, .024, & .044 respectively). In multivariate logistic regression analysis, after adjusting for the effect of BMI and hormone levels, dysfunction in orgasm, satisfaction and the total FSFI score were still 3–4 times more common in PCOS (adjusted OR [95% CI]: 3.54, P = .020; 2.96, P = .050; 3.87, P = .027). Even though no statistically significant differences were observed between women with ovulatory PCOS and controls, we detected statistically significant differences in all domains of sexual function apart from pain between controls and PCOS women with anovulation (desire P value .04, arousal P value Clinical Implications Women with PCOS have compromised sexual function, which is independent of their BMI and highly dependent on their ovulatory status. Strengths and Limitations This is the first study in women with PCOS that implicates anovulation as a risk factor for sexual impairment in PCOS. Further studies are needed to elucidate the mechanisms implicated and to examine the effect of PCOS therapy on the patients’ sexual function. CONCLUSION The adverse effect of PCOS status on the female sexual function is independent of BMI and only partially dependent on hormonal changes characterizing the syndrome. Anovulation appears to be the major determinant of sexual impairment among women with PCOS.

Study Objective This study aimed to evaluate the presence of anovulation in adolescents with primary dysmenorrhea (PD). Design Prospective cohort study. Setting Hacettepe University Children's Hospital, Adolescent Medicine outpatient clinic between September 2018 and September 2019. Participants Healthy female adolescents (between 11 and 18 years of age), with regular menstruation with a score of 1-3 according to the Numerical Rating Scale (NRS) and grade 0 (no limitation for daily activities, no analgesic need and systemic symptoms) according to the Verbal Multidimensional Scoring System (VBSS) were recruited as a control group. The participants who met the diagnostic criteria for PD with an NRS score ≥4, had analgesic need in at least the last 3 menstrual cycles, had defined moderate-to-severe PD according to VMSS (Grade 2-3), and had analgesic need every time were accepted as the PD group. Intervention and Main Outcome Measures For the determination of ovulation, suprapubic pelvic ultrasound and luteal SP levels were used. The first day of menstruation (DOM) was accepted as the first day of the menstrual cycle. The participants were called to the outpatient clinic for a total of 3 visits during 1 cycle; the first visit was for the suprapubic pelvic ultrasound imaging on the 12th-18th DOM, the second visit was for the first SP level measurement on the 21st-24th DOM, and the third visit was for the second SP level measurement on the 28th-31st DOM, if the next expected menstruation has not started yet. Participants’ anthropometric measurements, menstrual history, family history of dysmenorrhea, and additional symptoms accompanying pain were recorded. Results Anovulatory cycle rates according to 2 different references for SP threshold values (3 and 5 ng/mL) were 31.7% and 36.6% in the PD group, and 44.4% and 55.6% in the control group, respectively (P = .250, P = .095). In the PD group, NRS scores were similar for the ovulatory and anovulatory cycles for both SP threshold values (P = .320, P = .205). When the reference value for SP threshold was accepted as ≥5 ng/mL, the NRS score was significantly higher in the ovulatory group (P = .0017). When the distribution percentages of SP levels were evaluated among all participants, the median value was 5.5 ng/mL. Conclusion Contrary to classical information, anovulatory cycles are not rare in PD patients, and pain severity is at the same level in these cycles. The pathogenesis of PD in adolescents requires further study.

Background: Polycystic ovary syndrome [PCOS] is an important and common etiology for anovulatory infertility. Clomiphene citrate [CC] is the first line of treatment. One fourth of females are resistant to CC. Laparoscopic ovarian drilling [LOD] has developed manage CC-resistant cases. However, no consensus was established on the ideal drilling method.Aim of the work: This study aimed to evaluate the efficacy of different LOD methods for anovulatory infertility in CC-resistant PCOS patients.Patients and Methods: The study participants [200] were assigned randomly to one of four equal groups. Group [I] treated by unilateral cutting LOD. Group [II] treated by unilateral electro- coagulative LOD. Group [III] treated by bilateral cutting LOD. Group [IV] treated by bilateral electro-coagulative LOD. All participants were submitted to history taking, clinical examination, laboratory investigation, antral follicular count [AFC], and transvaginal ultrasound. After LOD, follow up included regularity of menstrual cycle, ovulation, and hormonal assay [at six months after ovarian drilling]. Also, ovulation, pregnancy and miscarriage rates were documented.Results: The study groups showed no significant difference regarding patient characteristics [e.g., body mass index, infertility duration and menstrual cycle history], and hormonal profile before and after LOD. The spontaneous ovulation rate was 40%, 42.0%, 46.0% and 40.0% in groups I, II, III and IV, respectively. The pregnancy rate was 32.0%, 38.0%, 44.0% and 42.0% in groups I, II, III and IV, respectively.in all groups, hormonal profile and AFC showed significant improvement after LOD compared with corresponding pre-LOD values. However, levels of FSH are significantly non-significant.Conclusion: Different techniques of LOD are equally effective and safe [e.g., unilateral ovarian drilling is as effective and safe as bilateral drilling, regardless of the drilling method [coagulative or cutting] with comparable ovulation, pregnancy and miscarriage rates.

Persistent anovulation, menstrual disorders lead to the development of endocrine-dependent gynecological diseases, one of the manifestations of which is primary infertility. The aim of the study: to assess the clinical features of history and reproductive status in women with psycho-emotional disorders associated with prenatal stress. The study involved 120 patients, 80 of whom suffered prenatal stress: 1 – the main group, which is divided into 1A subgroup – women who underwent in vitro fertilization, and 1B subgroup – women who did not undergo in vitro fertilization. For comparison, a 2 – control group of 40 women without prenatal stress with exclusively tubal factor of infertility, in which the parameters of the functional state of the reproductive system corresponded to the normal ovarian reserve. The age of patients ranged from 22 to 45 years. Complaints, anamnesis of disease and life, gynecological anamnesis, level of education were studied in all patients, the causes of infertility were assessed. The results of the study were processed using the statistical package of the licensed program “STATISTICA® for Windows 13.0”. The normality of the distribution of indicators was established by the Shapiro-Wilk criterion. Descriptive statistics are presented as the arithmetic mean and standard deviation of M±SD or the median and quartile interval Me (Q1-Q2) depending on the distribution of the trait. It was found that in place of residence, social status, the presence of bad habits, gynecological history of infertile patients in in vitro fertilization programs do not differ from healthy women with tubal-peritoneal factor infertility. There was a significant difference between the indicators of the nature of the menstrual cycle in the comparison groups. It has been found that a menstrual cycle of less than 23 days is a predictor of reduced functional activity of the hypothalamic-pituitary-ovarian axis in women. Analysis of hormonal regulation of reproductive function of the examined groups of women found the prevalence of FSH in the main group over the control (9,611±0,212 vs. 6,221±0,113 mMod/ml, respectively, (p

Цель исследования — изучить нарушение секреции гормона роста у женщин с синдромом поликистозных яичников (СПКЯ) в сравнении с больными с неактивными аденомами гипофиза (НАГ). Под амбулаторным наблюдением в период с сентября 2015 по март 2016 года было обследовано 15 взрослых пациенток фертильного возраста с СПКЯ и 15 — с НАГ. Средний возраст больных составил 25,5 и 28,9 года соответственно. Давность заболевания колебалась в пределах от 7 месяцев до 9 лет. Было установлено, что в обеих группах наблюдались нейроэндокринные нарушения, свойственные каждой из патологий. Так, в первой группе пациенток с СПКЯ наиболее часто встречались такие нарушения, как ожирение, стрии, акантоз, акне, гиперандрогения, гиперполименорея, а во второй — вторичная аменорея, гиперпролактинемия, пангипопитуитаризм. В обеих группах наблюдалась ановуляция, а также снижение секреции соматотропного гормона (СТГ), инсулиноподобного фактора роста‑1 (ИФР‑1). Кроме того, в группе пациенток с НАГ были выявлены наиболее достоверно сниженные базальные уровни тропных гормонов гипофиза — СТГ, лютеинизирующего гормона (ЛГ), фолликулостимулирующего гормона (ФСГ) на фоне гиперпролактинемии и нормальных значений ИФР‑1, в то время как у пациенток с СПКЯ отмечалось снижение СТГ, ЛГ, ФСГ на фоне гиперандрогении и снижения ИФР‑1. Таким образом, установлено, что в группе больных с СПКЯ было выявлено наиболее достоверное снижение базальных уровней ИФР‑1, в то время как дефицит СТГ встречался реже. У пациенток с НАГ имел место пангипопитуитаризм, а именно — сочетанный дефицит СТГ, ЛГ, ФСГ, тиреотропного гормона, в то время как дефицит ИФР‑1 встречался реже. Выявленные в нашем исследовании нарушения секреции СТГ и ИФР‑1 подтверждают данные литературы о том, что у пациенток с СПКЯ имеет место снижение уровней СТГ и ИФР‑1 на фоне гиперинсулинемии и гиперандрогении.

Background. The polycystic ovary syndrome (PCOS) is the most frequent form of endocrine pathology and occurs in 5–10 % women of reproductive age and makes up 80 %, and according to some data, even 90 % of all forms of hyperandrogenism. The information about pathogenesis of PCOS is contradictory. The main step of the SPCO pathogenesis is hyperproduction of LH of by the hypophysis, revealed in 40–80 % patients. According to one of numerous theories, an increase secretion results in the increase of LH by the hypothalamus of the gonadotropin-releasing hormone (GRH), secreted in the discrete mode under control sexual steroid hormones, monoamines and opioid peptides. The aim of the investigation is to study the functional status of hypophysis — gonads axis for women with SPCO. Material and methods. In the department of neuroendocrinology of the Center of Endocrinology of Health Ministry of the Republic of Uzbekistan in a period from September 2015 till July 2016 120 outpatients of fertile age with PCOS were inspected. Mean age of patients was 25.5 ± 4.3 years. The duration of the disease hesitated from 7 months to 9 years. 20 healthy women of corresponding age made a control group. The complex of researches, including clinical, biochemical (glycemia, glucose tolerance test), hormonal (LH, FSH, prolactin, estradiol, progesterone, dehydroepiandrostendion (ДGEA), 17-oxyprogesterone, аntimuller hormone (АМH), insulin) was performed in all patients, ultrasonic examination of uterus and ovaries (transabdominal and transvaginal) on the 14th day of cycle with folliculometria in dynamics, and also magnetically-resonant tomography of hypophysis and questionnaire of patients were carried out. Results. Patients were divided into two groups: with primary sterility (94 cases) and with secondary sterility (26 cases). In the first group of patients with primary sterility the reliable decline of both pituitary and ovarian hormones was determined on a background of hyperandrogenemia and hyperprolactinemia. So, as compared to the group of control on the 14th day of cycle LH, FSH, and estradiol, progesterone, while free testosterone, DGEA were enhanced as compared to control data. In the second group of patients the reliable decline of pituitary hormones was also educed on a background of hyperandrogenemia and hyperprolactinemia while an ovarian function was within the normal limits. So, as compared to the group of control on the 14th day of cycle the LH, FSH, here free testosterone, DGEA and АМH levels were enhanced as compared to control data. The neuroimaging of hypophysis in patients with PCOS educed hyperplasia (adenomatosis) of hypophysis in 49 from 120 (40.8 %), that can be explained by ovarian insufficiency in these patients. On the second place by incidence there was the syndrome of the empty sella (26 cases, 21.6 %), and on the third — the microadenoma of hypophysis in 16 persons (13.3 %). Conclusions. In the first group of patients with primary sterility the reliable decline of both pituitary and ovarian hormones was marked on a background of hyperandrogenemia and hyperprolactinemia. In the second group of patients the significant decline of pituitary hormones was also educed on a background of hyperanrogenemia and hyperprolactinemia, while an ovarian function was within the normal limits. In both groups of patients hypogonadotropinemia occurred combined with moderate hyperprolactinemia and hyperandrogenemia. Thus, the most expressed violations of the system of pituitary — ovarian function were found out in the first group of patients with PCOS with primary sterility, at that the significant decline of the functional status of pituitary — gonads axis was marked, namely decline of LH, FSH, estradiol and progesterone levels on the 14th day of menstrual cycle, that was confirmed by ultrasouns examination of uterus and ovaries by impoverishment of follicle vehicle of ovaries, anovulation signs. Thus, the most expressed violations of the system of pituitary-ovarial function were found out in the first group of patients with PCOS with primary sterility, at that the significant decline of the functional state of hypophysis-gonads was marked, namely decline of LH, FSH, estradiol and progesterone levels that was confirmed by ultrasound investigation of uterus and ovaries.

OBJECTIVE: The purpose of this study was to ascertain the extent to which the ocular surface of women with polycystic ovary syndrome is impacted. STUDY DESIGN: Included in this case-control study were 23 eyes of 23 patients (Group I) with polycystic ovary syndrome and 10 eyes of 10 healthy subjects (Group II). Polycystic ovary syndrome was diagnosed when two of the following conditions were met: oligo- or anovulation, clinical and/or biochemical signs of hyperandrogenism, and ultrasonographic documentation of polycystic ovaries. Ocular surface disease grading was performed using the Ocular Surface Disease Index questionnaire, slit lamp examination, meibomian gland secretion scoring, tear film breakup time, staining scores of ocular surfaces, the Schirmer's test, and tear osmolarity assessment. RESULTS: The study observed no significant difference in age (p=0.896). Group I was found to have a significantly higher median luteinizing hormone level (p=0.027). The Ocular Surface Disease Index scores in group I were significantly higher than those in group II (p=0.031). The prevalence of anterior blepharitis was significantly greater in group I (p=0.05). Tear film breakup time was higher in group I than in group II (p=0.026). The ocular surface disease severity was found to be significantly higher in group I (p=0.03). In group I, Ocular Surface Disease Index scores were significantly positively correlated with free testosterone, while tear osmolarity was significantly positively correlated with estradiol levels but significantly negatively correlated with dehydroepiandrosterone sulfate levels (p

Context Polycystic ovary syndrome (PCOS), a highly prevalent endocrine disorder characterized by hyperandrogenism, is the leading cause of anovulatory infertility. Objective This proof-of-concept study evaluated clinical efficacy and safety of the neurokinin 3 (NK3) receptor antagonist fezolinetant in PCOS. Methods This was a phase 2a, randomized, double-blind, placebo-controlled, multicenter study (EudraCT 2014-004409-34). The study was conducted at 5 European clinical centers. Women with PCOS participated in the study. Interventions included fezolinetant 60 or 180 mg/day or placebo for 12 weeks. The primary efficacy end point was change in total testosterone. Gonadotropins, ovarian hormones, safety and tolerability were also assessed. Results Seventy-three women were randomly assigned, and 64 participants completed the study. Adjusted mean (SE) changes in total testosterone from baseline to week 12 for fezolinetant 180 and 60 mg/day were −0.80 (0.13) and −0.39 (0.12) nmol/L vs −0.05 (0.10) nmol/L with placebo (P .10). Fezolinetant was well tolerated. Conclusion Fezolinetant had a sustained effect to suppress hyperandrogenism and reduce the LH-to-FSH ratio in women with PCOS.

Polycystic ovary syndrome (PCOS) is a disease with reproductive dysfunction and abnormal endocrine metabolism. It is characterized by hyperandrogenism, insulin resistance (IR) and persistent anovulation. At present, the pathogenesis and pathological mechanism of PCOS are still unclear, and there is no unified standard for the diagnosis and treatment of PCOS locally nor abroad. It is still a famous and difficult problem to explore the pathogenesis of PCOS and seek effective prevention and treatment methods.

OBJECTIVE: In humans, polycystic ovary syndrome (PCOS) is an androgen-dependent ovarian disorder. Aberrant gene expression in folliculogenesis can arrest the transition of preantral to antral follicles, leading to PCOS. We explored the possible role of altered gene expression in preantral follicles of estradiol valerate (EV) induced polycystic ovaries (PCO) in a mouse model. METHODS: Twenty female balb/c mice (8 weeks, 20.0±1.5 g) were grouped into control and PCO groups. PCO was induced by intramuscular EV injection. After 8 weeks, the animals were killed by cervical dislocation. Blood serum (for hormonal assessments using the enzyme-linked immunosorbent assay technique) was aspirated, and ovaries (the right ovary for histological examinations and the left for quantitative real-time polymerase) were dissected. RESULTS: Compared to the control group, the PCO group showed significantly lower values for the mean body weight, number of preantral and antral follicles, serum levels of estradiol, luteinizing hormone, testosterone, and follicle-stimulating hormone, and gene expression of TGFB1, GDF9 and BMPR2 (p\textless0.05). Serum progesterone levels were significantly higher in the PCO animals than in the control group (p\textless0.05). No significant between-group differences (p\textgreater0.05) were found in BMP6 or BMP15 expression. CONCLUSIONS: In animals with EV-induced PCO, the preantral follicles did not develop into antral follicles. In this mouse model, the gene expression of TGFB1, GDF9, and BMPR2 was lower in preantral follicles, which is probably related to the pathologic conditions of PCO. Hypoandrogenism was also detected in this EV-induced murine PCO model.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility; however, whether women with PCOS and spontaneous or drug-induced ovulatory cycles have the same reproductive potential as non-PCOS controls is a matter of debate. In the present opinion paper, the author takes the opportunity to summarize the collective evidence supporting the hypothesis of reduced fertility potential in women with PCOS, regardless of ovulatory status, and speculate that reduced reproductive potential may be caused by altered oocytes, embryo and endometrial competence, and infertility-related co-morbidities as well as an increased risk of pregnancy complications.

The aim of the study is to present the problem of functional hypothalamic amenorrhea, taking into account any disease and treatment, diagnosis, and consequences of this disease. We searched PubMed (MEDLINE) and included 38 original and review articles concerning functional hypothalamic amenorrhea. Functional hypothalamic amenorrhea is the most common cause of secondary amenorrhea in women of childbearing age. It is a reversible disorder caused by stress related to weight loss, excessive exercise and/or traumatic mental experiences. The basis of functional hypothalamic amenorrhea is hormonal, based on impaired pulsatile GnRH secretion in the hypothalamus, then decreased secretion of gonadotropins, and, consequently, impaired hormonal function of the ovaries. This disorder leads to hypoestrogenism, manifested by a disturbance of the menstrual cycle in the form of amenorrhea, leading to anovulation. Prolonged state of hypoestrogenism can be very detrimental to general health, leading to many harmful short- and long-term consequences. Treatment of functional hypothalamic amenorrhea should be started as soon as possible, and it should primarily involve lifestyle modification. Only then should pharmacological treatment be applied. Importantly, treatment is most often long-term, but it results in recovery for the majority of patients. Effective therapy, based on multidirectional action, can protect patients from numerous negative impacts on fertility, cardiovascular system and bone health, as well as reducing mental morbidity.

Polycystic ovary syndrome (PCOS) causes anovulation and hyperandrogenism. Hormonal imbalance is known to contribute to systemic autoimmune diseases.To examine the frequency of certain rheumatic diseases in PCOS.This retrospective study utilized and analyzed electronic medical records from January 2004 through February 2020. A diagnosis of PCOS and specified rheumatic diseases was searched using ICD-9 and ICD-10 codes. A total of 754 adult patients with PCOS and 1,508 age- and body mass index-matched patients without PCOS were included. Frequencies of the rheumatic diseases were compared between PCOS and non-PCOS subjects or literature data.The prevalence of rheumatoid arthritis (RA) was found to be 2.25% (17/737) in the PCOS patients, numerically higher than 1.26% (19/1489) in the non-PCOS subjects. The difference was significant with a confidence level of 90% (1.04-3.15) but not at 95% with an odds ratio of 1.808 (95% CI = 0.934-3.4, p = 0.0747). When compared with the literature data from the US female population, the prevalence of RA in PCOS patients was significantly higher (2.25% vs. 1.40%, p 0.0001). Among the autoimmune diseases examined, both systemic sclerosis (0.40% vs. 0.0%, p = 0.0369) and undifferentiated connective tissue disease (0.53% vs. 0.0%, p = 0.0123) were significantly more frequent in the PCOS patients than the non-PCOS. Additionally, PCOS patients had a significantly higher frequency of osteoarthritis than non-PCOS patients (5.44% vs. 2.92%, p = 0.0030) with an odds ratio of 1.913 (95% CI = 1.239-2.955).We have shown unprecedentedly that certain rheumatic diseases are more prevalent in PCOS. This study provides important insight into autoimmunity in association with PCOS. Key Points • Polycystic ovary syndrome is postulated to cause systemic autoimmune disease due to its hormonal imbalance. • We conducted the first epidemiologic assessment of the prevalence of systemic autoimmune diseases. • Certain autoimmune and rheumatic diseases are more prevalent in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disease in females that is characterized by hyperandrogenemia, chronic anovulation, and polycystic ovaries. However, the exact etiology and pathogenesis of PCOS are still unknown. The aim of this study was to clarify the bacterial, stress status, and metabolic differences in the gut microbiomes of healthy individuals and patients with high body mass index (BMI) PCOS (PCOS-HB) and normal BMI PCOS (PCOS-LB), respectively. Here, we compared the gut microbiota characteristics of PCOS-HB, PCOS-LB, and healthy controls by 16S rRNA gene sequencing, FK506-binding protein 5 (FKBP5) DNA methylation and plasma metabolite determination. Clinical parameter comparisons indicated that PCOS patients had higher concentrations of total testosterone, androstenedione, dehydroepiandrosterone sulfate, luteinizing hormone, and HOMA-IR while lower FKBP5 DNA methylation. Significant differences in bacterial diversity and community were observed between the PCOS and healthy groups but not between the PCOS-HB and PCOS-LB groups. Bacterial species number was negatively correlated with insulin concentrations (both under fasting status and 120 min after glucose load) and HOMA-IR but positively related to FKBP5 DNA methylation. Compared to the healthy group, both PCOS groups had significant changes in bacterial genera, including Prevotella_9, Dorea, Maihella, and Slackia, and plasma metabolites, including estrone sulfate, lysophosphatidyl choline 18:2, and phosphatidylcholine (22:6e/19:1). The correlation network revealed the complicated interaction of the clinical index, bacterial genus, stress indices, and metabolites. Our work links the stress responses and gut microbiota characteristics of PCOS disease, which might afford perspectives to understand the progression of PCOS.

Background: Clomiphene citrate is considered first line therapy for ovulation induction for women with polycystic ovary syndrome (PCOS) and infertility the benefits of metformin on insulin sensitivity have been demonstrated in non-diabetic women with PCOS. Objective: Comparing the efficacy of Clomiphene citrate + Metformin, and Clomiphene citrate alone in treatment of anovulation. Patients and Methods: Sixty patients were included in this study and were divided into two equal groups: The first group received (Clomiphene citrate for induction of ovulation starting from day 2 of the cycle for 5 days in a dose of 100 mg/day and Metformin 500mg tablets twice daily; while the second group received only Clomiphene citrate for induction of ovulation starting from day 2 of the cycle for 5 days with a dose of 100mg/day. Results: Both lines of treatment were effective in treatment of PCOS patients without statistically significant difference between Clomiphene citrate +Metformin group, and Clomiphene citrate group as regard ovulation rate. There was a statistically significant decrease in oligomenorrhea after treatment in comparison to their values before treatment in both groups. Conclusion: Both CC+Metformin, and CC alone were effective in treatment of infertility in PCOS patients.

Endocrine axes (prolactin, thyroid and adrenal axes) directly and indirectly modulate and drive human female central functions, mainly behavior and reproduction. Though having distinct abilities, they greatly act both at peripheral as well as at neuroendocrine levels, so as to participate in the control of reproduction. Any event that changes these balanced activities produces specific peripheral signals that induce abnormal functions centrally, thus triggering menstrual disorders such as oligomenorrhea or amenorrhea. It is clear that the knowledge of the relationships that exist between the different endocrine axes becomes essential for the choice of therapeutical approach. This review aims to focus on the main aspects of the physiopathology of the endocrine diseases that might be at the basis of that interference with female reproductive capacity.

Polycystic Ovarian Syndrome (PCOS) is a common endocrinopathy typified by oligo-ovulation or anovulation, signs of androgen excess, and multiple small ovarian cysts. In case of Polycystic Ovarian Syndrome, it is the Psoric miasm which initially brings about functional changes followed by involvement of Sycotic miasm which leads to cystic changes in ovary. Polycystic Ovarian Syndrome, therefore, is the result of combinations of Psoric and Sycotic miasms in the sick individual, which through neuro-hormonal pathway, leads to imbalance of hormones and formation of cysts. The reportorial it is been emphasized with best possible rubrics which can be used while treating Polycystic Ovarian Syndrome.

Polycystic ovary syndrome (PCOS), i.e., anovulation, hyperandrogenemia and polycystic ovary, is an endocrine-metabolic disease affecting reproductive aged women. Women with PCOS are likely to develop obesity, dyslipidemia, type 2 diabetes mellitus (T2DM) and cardiovascular diseases at a younger age. Despite high frequency and severe disease burden, the pathophysiological mechanisms of PCOS remain poorly defined and correspondingly have no therapeutic options. Emerging evidence has demonstrated that PCOS is accompanied with low-grade chronic inflammation and biomarkers thereof. Interestingly, serum amyloid A (SAA) has recently been identified as a potential marker of infection and inflammation and a number of studies have reported an association with PCOS. In this review, we explore the relationship between SAA and hyperandrogenemia, inflammation, obesity and insulin resistance, and provide convincing evidence for SAA as a potential inflammatory biomarker in PCOS.

Aim: To determine the efficacy of metformin on clinical profile and metabolic disorders in women with polycystic ovarian syndrome. Polycystic ovarian syndrome, is a heterogeneous endocrinological disorder affecting women of reproductive age and metformin was introduced to influence the pathogenesis. Materials and Methods: A prospective observational study was conducted on 100 women with polycystic ovarian syndrome, attending department of gynaecology in a tertiary care setting and were divided into two group of 50 each. Metformin was used in 50 patients for one year. Rest 50 patients were advised about diet control and exercise. The parameters like body mass index (BMI), weight, hormonal imbalance, ovulation, and menstrual changes were analysed in both groups. Descriptive statistics for mean, SD were carried and chi-square test was used to test statistical significance using coGuide version V.1.0 and p value set at Results: The mean age was 25±10 years. Both the groups were comparable with respect to BMI and weight. There was a significant difference between the groups with respect to fasting insulin, which reduced to 7.44±1.12 from 11.97±2 mIU/ml, testosterone levels reduced to 0.59±0.1 from 0.760.3 mIU/ml, luteinizing hormone levels reduced to 8.55±2 from 20.01±7.3 mIU/ml, and LH:FSH ratio reduced to 1.11±0.1 from 2.31±0.2 mIU/ml. In the metformin group, 22 (44%) participants were anovulation before treatment, and ovulation started in 15 (30%) after treatment which was not seen other group. Conclusion: Clinical, hormonal, and biochemical changes in polycystic ovarian syndrome may effectively be treated by metformin. Keywords: Hyperplasia, Ovary, Metformin, Obesity, Lifestyle, Insulin.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 10% of reproductive-aged women and leads to hyperandrogenism, anovulation, and infertility. PCOS has been associated with elevated serum homocysteine as well as altered methylation status; however, characterization of one-carbon metabolism (OCM) in PCOS remains incomplete. OBJECTIVES: The aim of our research was to assess OCM in a letrozole-induced Sprague Dawley rat model of PCOS. METHODS: Five-week-old female rats (n = 36) were randomly assigned to letrozole [0.9 mg/kg body weight (BW)] treatment or vehicle (carboxymethylcellulose) control that was administered via subcutaneously implanted slow-release pellets every 30 d. For both treatment groups, 12 rats were randomly assigned to be euthanized during proestrus at one of the following time points: 8, 16, or 24 wk of age. Daily BW was measured and estrous cyclicity was monitored during the last 30 d of the experimental period. Ovaries were collected to assess mRNA and protein abundance of OCM enzymes. RESULTS: Letrozole-induced rats exhibited 1.9-fold higher cumulative BW gain compared with control rats across all age groups (P

Polycystic ovary syndrome (PCOS) is a common cause of anovulatory infertility. According to the latest guidelines, letrozole should be considered as the first-line pharmacological treatment for women with WHO Group II anovulation or PCOS. However, the use of letrozole as an ovulation induction agent is not FDA or EMA approved, and its use is “off-label.” The main concern with respect to letrozole regards its potential teratogenic effect on the fetus. To determine whether the probability of ovulation is higher with letrozole as compared to clomiphene citrate (CC) in anovulatory women with PCOS. Randomized controlled trials (RCTs) comparing letrozole versus CC used for ovulation induction in infertile women with PCOS followed by timed intercourse (TI) or intrauterine insemination (IUI) were included in this meta-analysis. Primary outcome was ovulation. Secondary outcomes were live birth, clinical pregnancy, miscarriage, multiple pregnancy, and congenital anomalies. Subgroup analysis included patients who received letrozole or CC as first-line treatment, and patients with PCOS diagnosed according to the Rotterdam criteria. Twenty-six RCTs published between 2006 and 2019, involving 4168 patients who underwent 8310 cycles of ovulation induction, were included. The probability of ovulation was significantly higher in letrozole as compared to CC cycles (RR: 1.148, 95% CI: 1.077 to 1.223, 3017 women, 19 trials, I2: 47.7%, low-quality evidence). A higher probability of ovulation is expected in infertile patients with PCOS treated with letrozole as compared to CC. The higher ovulation rate might have contributed to the higher clinical pregnancy and live birth rate. This finding is also true for patients who were administered letrozole as first-line treatment. CRD42019125166

Polycystic ovary syndrome (PCOS) is a frequent gynecological female endocrinopathy, characterized by chronic anovulation, hyperandrogenism, and insulin resistance (IR). Menstrual disorders are one of the main clinical manifestations of PCOS. Other symptoms include hirsutism and/acne. At present, the treatment of PCOS with irregular menstruation is mainly based on oral contraceptives, but there are some side effects and adverse reactions. In recent years, more and more attention has been paid to the complementary and alternative medicine (CAM), which has been widely used in clinical practice. Modern Western medicine is called “conventional medicine” or “orthodox medicine,” and the complementary and alternative medicine is called “unconventional medicine” or “unorthodox medicine.” CAM includes traditional medicine and folk therapy around the world. Around 65–80% of world health management business is classified into traditional medicine by the World Health Organization, which is used as alternative medicine in Western countries. In our country, Chinese medicine, acupuncture, and other therapies are commonly used due to their significant efficacy and higher safety. Therefore, this review aims to summarize and evaluate the mechanisms and the effect of current complementary replacement therapy in the treatment of menstrual disorders caused by PCOS, so as to provide guidance for the following basic and clinical research.

Objective To establish if the cessation of testosterone (T) therapy reverses T-induced acyclicity in a transgender mouse model that allows for well-defined T cessation timing. Design Experimental laboratory study using a mouse model. Setting University-based basic science research laboratory. Animals A total of 10 C57BL/6NHsd female mice were used in this study. Intervention(s) Postpubertal C57BL/6NHsd female mice were subcutaneously implanted with T enanthate (n = 5 mice) or placebo (n = 5 mice) pellets. Pellets were surgically removed after 6 weeks to ensure T cessation, after which the mice were followed for four estrous cycles after the resumption of cyclicity. Main Outcome Measure(s) Primary outcomes included daily vaginal cytology and weekly T levels before, during, and after T enanthate or placebo pellet implantation and removal. Secondary outcomes included ovarian follicle distribution and corpora lutea numbers, body metrics, and terminal diestrus hormone levels. Result(s) T-treated mice (100%) resumed cycling within one week of T pellet removal after six weeks of T therapy. T levels were significantly elevated during T therapy and decreased to control levels after surgical pellet removal. No detectable differences were observed in the follicle count, corpora lutea formation, diestrus hormone levels, or body metrics after four estrous cycles, with the exception of persistent increased clitoral area between T-treated mice and controls. One T-treated mouse was sacrificed early due to vaginal prolapse and not included in subsequent analyses. Conclusion(s) Our results demonstrated a close temporal relationship between estrous cycle return and T levels dropping to control levels following T pellet removal. The return of regular cyclic ovulatory function is also supported by the formation of corpora lutea and the lack of detectable differences in key reproductive parameters as compared to controls four cycles after T cessation. These results may be relevant to understanding the reversibility of T-induced amenorrhea and possible anovulation in transgender men interested in pausing T to pursue pregnancy or oocyte donation. Results may be limited by the duration of T treatment, lack of functional testing, and physiological differences between mice and humans.

Background: Polycystic ovarian syndrome (PCOS) is the most common cause of anovulatory infertility. Oxidative stress (OS), which plays an important role in determining the developmental competence of an oocyte, may be involved in understanding infertility and poor outcomes cycles in PCOS women undergoing in vitro fertilization (IVF). Objective: To measure OS biomarkers in the follicular fluid of PCOS women undergoing IVF. Materials and Methods: In this cross-sectional study, 100 women with PCOS (n = 43) and tubal factor (n = 57) undergoing IVF, who were referred to a tertiary medical center between January 2016 and September 2017 were enrolled. OS markers like reactive oxygen species (ROS), total antioxidant capacity (TAC), and 8-Isoprostane (8-IP) were tested in the follicular fluid and various IVF outcomes in the form of oocytes retrieved, fertilized, cleavage rate, grading of embryos and pregnancy outcomes were compared between the two groups. Results: The results indicated that the levels of ROS, TAC, and 8-IP were higher in the PCOS group compared to the tubal group (p = 0.21, p = 0.95, and p < 0.05, respectively). Biomarkers based on the number of retrieved oocytes, cleavage rate, and grades of embryos did not differ significantly in the two groups. The median ROS, TAC, and 8-IP were not significantly different in the two groups in relation to the pregnancies, although the 8-IP levels were significantly raised in the PCOS women who had a miscarriage (p = 0.02). Conclusion: This study concluded the possible role of OS in PCOS women with increased higher level of 8-IP biomarker as a potential biomarker that needs further evaluation. Key words: Oxidative stress, ART, PCOS, Infertility, 8-IP.

Background Cadmium is an endocrine disrupting chemical that affects the hypothalamic-pituitary-gonadal axis. Though evidence suggests its potential role in altering androgen synthesis and metabolic pathways that are characteristic of polycystic ovary syndrome (PCOS), its relation in healthy women of reproductive age is largely unknown. As women with mild sub-clinical features of PCOS who do not meet the diagnostic criteria of PCOS may still experience reduced fecundability, investigating associations between cadmium and PCOS-phenotypes among healthy women may provide unique insight into the reproductive implications for many on the PCOS spectrum. Therefore, the objective of this study was to evaluate associations between cadmium and androgens, anti-Müllerian hormone (AMH), and metabolic markers in women of reproductive age. Methods This was a prospective cohort study of 251 healthy premenopausal women without self-reported PCOS (mean age 27.3 years and BMI 24.1 kg/m2). Cadmium was measured in blood collected at baseline. Reproductive hormones and metabolic markers were measured in fasting serum 8 times per menstrual cycle for 2 cycles. Linear mixed models and Poisson regression with a robust error variance were used to examine associations between cadmium and reproductive hormones and metabolic markers and anovulation, respectively. Results Median (interquartile range) blood cadmium concentrations at baseline were 0.30 (0.19–0.43) µg/L. Higher levels of testosterone (2.2 %, 95 % confidence interval [CI] 0.4, 4.1), sex hormone-binding globulin (2.9 %, 95 % CI 0.5, 5.5), and AMH (7.7 %, 95 % CI 1.1, 14.9) were observed per 0.1 µg/L increase in cadmium concentrations. An 18 % higher probability of a mild PCOS-phenotype (95 % CI 1.06, 1.31), defined by a menstrual cycle being in the highest quartile of cycle-averaged testosterone and AMH levels, was also found per 0.1 µg/L increase in cadmium levels. No associations were observed for insulin and glucose. These findings were consistent even after analyses were restricted to non-smokers or further adjusted for dietary factors to account for potential sources of exposure. Conclusions Overall, among healthy reproductive-aged women, cadmium was associated with endocrine features central to PCOS, but not with metabolic markers. These suggest its potential role in the hormonal milieu associated with PCOS even at low levels of exposure.

This review explores the pathophysiology associated with anovulation which affects 30% of cases of infertility . It provides an overview of the evidence based management of different groups of anovulation including role of adjuvant therapies. Anovulation can be effectively managed with induction of ovulation , the aim of which is to restore normal physiological ovulatory function. Weight optimization is the cornerstone of management in functional hypogonadotropic hypogonadism and polycystic ovarian syndrome (PCOS). The aim is to achieve monofollicular development, minimizing the risk of ovarian hyperstimulation and multiple pregnancies. The holistic approach involves induction of ovulation along with health education regarding lifestyle modifications and need for long term hormone replacement therapy in appropriate cases.

Background Polycystic ovary syndrome (PCOS) causes anovulation and is associated with a reduced clinical pregnancy rate. Metformin, which is widely used for treating PCOS, can lead to successful pregnancy by restoring the ovulation cycle and possibly improving endometrial abnormality during the implantation period. However, the mechanism by which metformin improves endometrial abnormality remains unknown. Women with PCOS have an aberrant expression of steroid hormone receptors and homeobox A10 (HOXA10), which is essential for embryo implantation in the endometrium. Methods In this study, we examined whether metformin affects androgen receptor (AR) and HOXA10 expression in PCOS endometrium in vivo and in human endometrial cell lines in vitro. Expression of AR and HOXA10 was evaluated by immunohistochemistry, fluorescent immunocytochemistry, and western blot analysis. Results AR expression was localized in both epithelial and stromal cells; however, HOXA10 expression was limited to only stromal cells in this study. In women with PCOS, 3 months after metformin treatment, the expression of AR was reduced in epithelial and stromal cells in comparison to their levels before treatment. In contrast, HOXA10 expression in the stromal cells with metformin treatment increased in comparison to its level before treatment. Further, we showed that metformin counteracted the testosterone-induced AR expression in both Ishikawa cells and human endometrial stromal cells (HESCs); whereas, metformin partly restored the testosterone-reduced HOXA10 expression in HESCs in vitro. Conclusions Our results suggest that metformin may have a direct effect on the abnormal endometrial environment of androgen excess in women with PCOS. Trial registration The study was approved by the Ethical Committee of Fukushima Medical University (approval no. 504, approval date. July 6, 2006), and written informed consent was obtained from all patients. https://www.fmu.ac.jp/univ/sangaku/rinri.html

STUDY QUESTION Are children of mothers with polycystic ovary syndrome (PCOS) or anovulatory infertility at increased risks of obesity or diabetes? SUMMARY ANSWER Maternal PCOS/anovulatory infertility is associated with an increased risk of offspring obesity from early age and diabetes in female offspring from late adolescence. WHAT IS KNOWN ALREADY Women with PCOS often have comorbid metabolic disorders such as obesity and diabetes, and children of mothers with PCOS have an increased risk of subtle signs of cardiometabolic alterations. STUDY DESIGN, SIZE, DURATION This was a nationwide cohort study of all live births (n = 1 105 997) during 1996–2014 in Finland, excluding those with maternal diagnoses sharing signs and symptoms with PCOS (n = 8244). A total of 1 097 753 births were included and followed up until 31 December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS National registries were linked to identify births with maternal PCOS or anovulatory infertility (n = 24 682). The primary outcomes were diagnoses of obesity (ICD-10: E65, E66) and diabetes (ICD-10: E10–E14) in offspring recorded in the Finnish Care Register for Health Care. Cox proportional hazards regression was modeled to analyze the risk of offspring obesity and diabetes in relation to prenatal exposure to maternal PCOS/anovulatory infertility. Differently adjusted models and stratified analyses were used to assess whether the risk was modified by maternal obesity or diabetes diagnoses, pre-pregnancy BMI, fertility treatment or perinatal problems. MAIN RESULTS AND THE ROLE OF CHANCE Exposure to maternal PCOS/anovulatory infertility was associated with a higher cumulative incidence of obesity in the children (exposed: 1.83%; 95% CI 1.66–2.00% vs unexposed: 1.24%; 95% CI 1.22–1.26%). Accounting for birth factors and maternal characteristics such as obesity and diabetes diagnoses, the hazard ratio (HR) for obesity was increased in offspring below 9 years of age (HR 1.58; 95% CI 1.30–1.81), and in those 10–16 years of age (HR 1.37; 95% CI 1.19–1.57), but not in those aged 17–22 years (HR 1.24; 95% CI 0.73–2.11). Sex-stratified analyses revealed similar risk estimates for boys (HR 1.48; 95% CI 1.31–1.68) and girls (HR 1.45; 95% CI 1.26–1.68). Notably, the joint effect of PCOS/anovulatory infertility and BMI-based pre-pregnancy obesity on offspring obesity (HR 8.89; 95% CI 7.06–11.20) was larger than that of either PCOS/anovulatory infertility or obesity alone. Furthermore, PCOS/anovulatory infertility was associated with offspring obesity in children without perinatal problems (HR 1.27; 95% CI 1.17–1.39), with larger effect size for maternal PCOS/anovulatory infertility and joint perinatal problems (HR 1.61; 95% CI 1.35–1.91). However, the risk estimates were comparable between maternal PCOS/anovulatory infertility with (HR 1.54; 95% CI 1.17–2.03) and without fertility treatment (HR 1.46; 95% CI 1.32–1.61). For offspring diabetes, the HR was increased only between 17 and 22 years of age (HR 2.06; 95% CI 1.23–3.46), and specifically for Type 1 diabetes in females (HR 3.23; 95% CI 1.41–7.40). LIMITATIONS, REASONS FOR CAUTION The prevalence of PCOS/anovulatory infertility in this study was 2.2%, lower than that reported in previous studies. In addition, the incidence of obesity in offspring was lower than that reported in studies based on measured or self-reported weight and height and may include mainly moderate and severe obesity cases who needed and/or actively sought medical care. Moreover, mothers with PCOS/anovulatory infertility were identified based on ICD codes, with no information on PCOS phenotypes. Furthermore, maternal pre-pregnancy BMI was available only from 2004. The PCOS/anovulatory infertility association with female offspring diabetes was based on only a few cases. Mothers’ weight gain during pregnancy, use of fertility treatment other than fresh or frozen IVF/ICSI, offspring lifestyle, as well as fathers’ age, medical disorders or medication prescriptions were not available for this study. WIDER IMPLICATIONS OF THE FINDINGS These findings support that prenatal PCOS/anovulatory infertility exposure influences metabolic health in the offspring from early age. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by Shandong Provincial Natural Science Foundation, China [ZR2020MH064 to X.C.], Shandong Province Medical and Health Technology Development Plan [2018WS338 to X.C.], the joint research funding of Shandong University and Karolinska Institute [SDU-KI-2019-08 to X.C. and C.L.], the Finnish Institute for Health and Welfare: Drug and Pregnancy Project [M.G.], the Swedish Research Council [2014-10171 to C.L.], the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute Stockholm County Council [SLL20170292 and SLL20190589 to C.L.], the Swedish Brain Foundation [FO2018-0141 and FO2019-0201 to C.L.]. X.C. received grants from the China Scholarship Council at the beginning of the study. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER N/A.

Assessment of the hormonal levels in different management strategies for women with cervical insufficiency and a history of anovulatory infertility Cervical insufficiency (CI) is one of the causes of preterm birth. The rate of CI is higher in women after in vitro fertilization treatment for infertility compared to the general population. The aim. To assess the hormonal level in women with CI and a history of anovulatory infertility in the second and third trimesters of pregnancy in different management strategies for CI. Materials and methods. 60 pregnant women with CI who conceived through in vitro fertilization treatment for anovulatory infertility were divided into two groups: in the I group (30 women), CI was corrected only with cervical cerclage / pessary in the II trimester of pregnancy, in the II group (30 persons), cervical cerclage / pessary was combined with vaginal progesterone 200 mg ones a day until 34 full weeks of gestation. 30 pregnant women without СІ or infertility with the physiological course of pregnancy were controls. The concentrations of estradiol, progesterone, placental lactogen, prolactin and cortisol were determined in the terms of 19–22 and 30–32 weeks of gestation in the maternal blood serum. Results. In the patients with CI at 19–22 gestational weeks, the estradiol and placental lactogen concentrations were slightly lower in the I and II groups than those in the control women, the level of progesterone was less in the I group by 13.44 %, in the II group – by 17.30 % (P < 0.05) compared to the controls; the levels of prolactin and cortisol in the I and II groups were increased significantly (P < 0.001). At 30–32 gestational weeks, the levels of estradiol (P < 0.05), progesterone (a decrease of 23.10 %, P < 0.001) and placental lactogen (a decrease of 10.74 %, P < 0.05) were significantly less as compared to the physiological ranges, while these parameters in the II group patients were on the lower limit of normal. In the I group, the concentrations of prolactin and cortisol were higher by 41.70 % (P < 0.001) and 27.36 % (P < 0.001), respectively, than the controls, in the II group – only by 24.10 % (P < 0.05) and 13.70 % (P < 0.05), respectively. Conclusions. In the women with cervical insufficiency after in vitro fertilization treatment for anovulatory infertility, the levels of estradiol, progesterone and placental lactogen are not significantly different from physiological indices, but the prolactin and cortisol concentrations are much higher. Adjunctive vaginal progesterone treatment to cervical cerclage/pessary in the third trimester of pregnancy promotes the normalization of progesterone, estradiol and placental lactogen levels, the decrease in prolactin and cortisol indices at 30–32 gestational weeks compared to the women with cervical cerclage/pessary alone.

Multiple interactions between sleep and the ovarian axis are operative in physiological and pathological conditions. Both estradiol and progesterone contribute to the regulation of specific sleep stages, which in turn contribute to the regulation of pulsatile secretion of gonadotropins. Sleep troubles, in particular sleep deprivation, may be associated with menstrual cycle irregularity, anovulation, and miscarriage. In addition, insufficient sleep favors the development of obesity and insulin resistance, which in turn favors the development of polycystic ovary syndrome (PCOS). Conversely, PCOS is associated with sleep disturbances, in particular with obstructive sleep apnea (OSA), eventually leading to a vicious cycle. Improving sleep quality and duration could provide a cost-effective and patient-centered avenue to reduce incidence and severity of PCOS.

The objective: on the basis of a comprehensive examination of women of reproductive age to establish the frequency of phenotypes (clinical variants) of polycystic ovary syndrome (PCOS).Materials and methods. 34 patients (main group) who complained of menstrual disorders and/or dermatopathies by recommendation of a dermatologist were examined. The control group is represented by 30 women without gynecological and somatic pathology. The mean age of women in the main group was 26,4±0,9 years and 29,1±0,9 years in the control group (p>0,05). The age of women in the study groups ranged from 18 to 35 years. Patients underwent a comprehensive examination to assess the severity of hirsutism and the severity of acne, as well as the body mass index was determined. All women underwent ultrasound examination in the dynamics and quantitative assessment of the concentration of hormones in the blood plasma, namely cortisol, thyroid-stimulating hormone, prolactin, free testosterone and its index, androstenedione, dehydroepiandrosterone sulfate, 17-α-OH-progesterone, sex hormone binding globulin. Variation-statistical processing of the results was carried out using the program «STATISTICA 13».Results. The results of the conducted research show that 73,5% had menstrual irregularities, and 52,9% – infertility. Acne and hirsutism in every 3rd woman were combined and were diagnosed in 47,1% and 41,2% of women, respectively. Ultrasound signs of polycystic ovaries were found in 94,1% of patients according to the criteria for the diagnosis of PCOS, and in 88,2% – anovulation. According to the laboratory examination, hyperadrogenism was found in 55,9%, which is confirmed by statistically significant (p

Background: Polycystic ovary syndrome (PCOS) is one of the most common causes of endocrinological disorders affecting 5-10% of women in reproductive age. It is the most important cause of anovulation and infertility. Objective: To examine the relation of body mass index in PCOS patients with dose and duration of Human Menopausal Gonadotropin (HMG), ovulation rate and pregnancy rate. Patients and Methods: The study was retrospectively conducted on 150 women selected from patients attending the infertility clinic of Al-Azhar hospitals, Faculty of Medicine, Al-Azhar University during the period from August 2018 till July 2020, and we revised and collected that data from the records. All cases were selected after fulfilling inclusion and exclusion criteria. The patients were divided into three equal groups according to their body mass index, Group A: patients with normal body mass index (BMI 19-24.9), Group B: patients with overweight (BMI 25-29.9) and group C: patients with obesity (BMI equals or more than 30). Results: There was a statistical significance as regards pregnancy rates between studied groups. In the current study there was a statistical significant difference between three groups as regards the mean age. There was no statistical significant difference between three groups as regards the mean Follicular Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2), Prolactin (PRL) and Thyroid stimulating Hormone (TSH). According to the days of stimulation, group C showed a significant increase than group A and B. The dose of HMG used in the three studied groups, showed a significantly higher dose used in group C than group A and B. The ovulation rate was 68% in group A, 56% in group B and 28% in group C. The results were compared with other studies of similar scope and most of them were recent ones. In our study, obesity had negative impact on ovulatory functions. It seemed that obesity was a negative prognostic factor for women referred to vitro fertilization (IVF) treatment. They should be encouraged to change lifestyle habits in order to lose weight before starting fertility treatment. Although our findings did not support a policy of excluding obese and overweight women from IVF treatment on the grounds of likely failure of ovulation induction or IVF, Beyond the IVF results, obesity increased morbidity for both mother and fetus. There was an increased risk in pregnancy hypertension, toxemia, gestational diabetes, Cesarean section, increased hospitalization, and the risk to their offspring of their abnormality in BMI. Conclusion: Programs of weight loss are recommended for obese women undergoing in vitro fertilization, and the institution of a process of weight loss where appropriate, HMG can be given to patients with PCO adjusting dose according to their BMI and response with expecting satisfactory ovulation, and pregnancy rate.

Polycystic ovary syndrome (PCOS) is an endocrine disorder and affects 5-10% of reproductive-age women. Chronic anovulation, polycystic ovaries, and hyperandrogenism are the important features of this syndrome. Furthermore, hyperinsulinemia and central obesity are frequent in PCOS women. In recent years, noncoding RNAs detection provided new ideas to explain the etiology of female reproductive disorders. Long noncoding RNAs (lncRNAs) as a subset of noncoding RNAs are associated with the pathogenesis of manifold reproductive-related disorders. Various investigations emphasized the potential involvement of lncRNAs in PCOS development. Therefore, in this paper, we will summarize the function of numerous lncRNAs in the apoptosis and proliferation of granulosa cells (GCs), insulin resistance (IR), and steroidogenesis in PCOS.

The lack of ovulatory cycles may be considered as a major problem for women seeking pregnancy. This is reflected by the fact that about 20 percent of couples visiting a fertility clinic with an unfulfilled wish to conceive present with anovulation. Clinical manifestation of anovulation is oligomenorrhea (intermenstrual period > 35 days) or amenorrhea (intermenstrual period > 6 months). Although ovulation may occur in oligomenorrhea, the longer the time period between menstruations the smaller the chance of that cycle being ovulatory. Classification of anovulatory patients may be performed using the criteria of the World Health Organization (WHO) as determined by Rowe et al. Criteria needed to classify patients are 1) serum prolactin in the normal range, 2) oligo- or amenorroea, and 3) serum concentrations of follicle-stimulating hormone (FSH) and estradiol (E2).In case of a hyperprolactinemia, a macro-prolactinoma should be ruled out by a scan (CT or MRI) of the sella turcica, and hyperprolactinemia should be treated with a dopamine-agonist. In case of normoprolactinemia or when the oligo- or amenorrea persists after correction of the hyperprolactinemia, these patients may be classified according to WHO criteria as follows: WHO1) ± 10% hypogonadotropic, hypoestrogenic status; WHO2) ± 80% normogonadotropic, normoestrogenic status; or WHO3) ± 10% hypergonadotropic, hypoestrogenic status. The vast majority of these patients, the WHO2 group, appear to be a very heterogeneous population in which – besides anovulation – obesity, biochemical, or clinical hyperandrogenism (alopecia, acne, or hirsutism) and insulin resistance play an important role.

Secondary infertility is defined as the inability of a couple to conceive who had at least one prior conception. Ovarian factor and tubal factor are the most frequent causes of secondary infertility in woman. Polycystic Ovarian Syndrome is a common endocrinological disorder and it is characterized by menstrual irregularities and anovulation. It can be correlated with Nashtartava in Ayurveda. Tubal factor infertility occurs when an obstruction in fallopian tube and it can be correlated with Sanga srotodushti of Artavavaha srotas or Beejavaha srotas. A 36 year old female presented with a complaint of secondary infertility a diagnosed case of Polycystic Ovarian Syndrome and tubal block with a history of neonatal death due to preterm delivery at 24 week gestation and husband aged 38 year with normal semen analysis. The present case was treated on Ayurvedic management protocol including shodhana, samana therapies and uttaravasti. Treatment was started with Deepana - Pachana medicines. Then Udwarthanam, Virechanam, Mathra vasti and Uttaravasti were done which removes the srotorodha and helps in proper formation of each dhatu. Uttaravasti is the most effective local treatment in gynaecological disorders. Uttaravasti with hot potency medicine is very effective in treating tubal blockage. The outcome of the treatment resulted in twin pregnancy and delivered two female babies. So the present case signifies the fruitful outcome of Ayurvedic treatment in the field of infertility. Keywords: Secondary infertility, Polycystic Ovarian Syndrome, Tubal block, Nashtartava, Artavavaha srotas, Uttaravasti

Context Diets high in plant-based protein have gained popularity due to increasing health concerns regarding consumption of animal products. Though links between intakes of certain protein-rich foods and reproductive disorders have been suggested, the relationship of overall animal and vegetable proteins with reproductive hormones among reproductive-aged women is unknown. Objective To evaluate the associations between the intake of dietary protein with reproductive hormones and sporadic anovulation among reproductive-aged women. Design A prospective cohort study, 2005–2007. Setting University at Buffalo, western New York, United States. Participants A total of 259 premenopausal women (18–44 years) without dietary restrictions. Main Outcome Measure(s) Serum reproductive hormones were determined up to 8 times per cycle for 2 cycles. Protein intake was assessed the day prior to hormone assessment at 4 visits/cycle using 24-hour recalls. Results Overall, 84% of participants met the recommended dietary allowance for total protein set for reproductive-aged women. Neither total nor animal protein intake were associated with reproductive hormones or anovulation. However, vegetable protein intake in the lowest tertile was associated with lower luteal phase progesterone (-18.0%, 95% confidence interval [CI] -30.2, -3.6), higher follicle-stimulating hormone (3.8%, 95% CI 0.2, 7.6), and a higher risk of anovulation (risk ratio [RR] 2.53, 95% CI 1.21, 5.26), compared with the middle tertile. Nuts and seeds were the only protein-rich foods associated with an elevated risk of anovulation (RR 2.12, 95% CI 1.17, 3.85). Conclusions Findings suggest that among women who meet the recommended dietary allowance for total protein, low intake of vegetable, but not animal, protein may disturb normal ovulatory function.

Hyperandrogenic anovulation refers to the constellation of disorders that present in women with irregular menses, hirsutism and/or acne across the lifespan. Understanding the clinical signs and symptoms of each diagnosis in the differential and laboratory testing to confirm or exclude a diagnosis allows a clinician to appropriately counsel and treat the patient.

Infertility is defined as when a couple failed to conceive within one or more years of regular unprotected coitus. Primary infertility denotes those patients who have never conceived. Secondary infertility denotes previous pregnancy but failure to conceive subsequently. 80% of the couples achieve conception if they so desire, within one year of having regular intercourse with adequate frequency. Another 10% will achieve the objective by the end of second year. As such, 10% remain infertile by the end of second year. Now days, PCOS is one of the most common cause of infertility in women. In PCOS the hormonal imbalance interferes with the development and release of ovum from the ovaries. PCOS manifested by amenorrhoea, hirsutism and obesity associated with enlarged polycystic ovaries. PCOS is characterised by excessive androgen production by ovaries and adrenals which interferes with growth of the ovarian follicles. Therefore PCOS is a state of androgen excess and chronic anovulation. A 27 years old female visited OPD of PTSR NIA with complaints of wants issue since two years. After thorough examination, she was diagnosed as PCOS in Ultrasonography. At first, medicine for withdrawal bleeding was given. Then Shatapushpa churna and Phalasarpi was given for two months and then after she was conceived.

Background: Intrauterine Insemination (IUI) is anage old reliable and safe procedure for couples having infertility. Success rate of IUI with ovulation induction ranges from 8-20% depending on many factors. Aims and Objectives: The current study was to assess the factors which are responsible for favourable outcome of IUI after ovulation induction. Materials and Methods: Total 67 couples were included fulfilling inclusion and exclusion criteria. They underwent 90 cycles of IUI with each couple having maximum of 3 cycles. Ovulation induction was done byeitherclomiphene citrate or letrozole or gonadotrophins. Semen preparation was done by density gradient method. The participant’s demographic parameters were analyzed. Results: Out of 90 IUI, 8 were successful resulting in a success rate of 8.8% per cycle and 11.9% per couple. Factors which had positive impact were age less than 35 years, less than 10 years of infertility, normal and overweight BMI. Anovulation and unexplained infertility had better outcome. Type of infertility did not have any impact on the outcome. Conclusion: The study concluded that IUI after ovulation induction is more useful in cases like unexplained infertility and anovulation in a patient aged less than 35 years with less than 10 years of infertility and normal or overweight BMI.

Hypothesis/Aims of study. Currently, the frequency of suboptimal response (4-9 retrieved oocytes) to controlled ovarian stimulation (COS) in woman is quite high; however, its efficacy is poorly studied. The aim of this study was to evaluate the main characteristics of IVF / ICSI programs in patients with a suboptimal response to COS. Study design, materials and methods. We performed a retrospective study of 412 IVF / ICSI cycles in women with a suboptimal response to COS, including a comparative analysis of clinical and embryological parameters, ovarian reserve and the efficacy of IVF / ICSI protocols. Results. Clinical pregnancy rate in ovarian stimulation cycles with a suboptimal response to COS was 27.9%. The efficacy of assisted reproductive technology (ART) programs in women with uterine fibroids was significantly lower than in patients without fibroids (19.1% vs. 30.5%, p = 0.03; OR = 0.54; 95% CI: 0.31-0.95). Clinical pregnancy rate in patients with male factor infertility was significantly higher than in women with anovulation (37.1% vs. 20.9%, р = 0.005; OR = 2.24; 95% CI: 1.27-3.94) or tubal factor infertility (37.1% vs. 24.8%, р = 0.02; OR = 1.79; 95% CI: 1.09-2.94). There were significant correlations between the number of retrieved oocytes with serum anti-Mullerian hormone (AMH) concentration ( r = 0.32, p < 0.001) and antral follicle count (AFC) ( r = 0.38, p < 0.001). In addition, the need for follicle-stimulating hormone (FSH) preparations during COS correlated significantly with ovarian reserve parameters (AMH and AFC) ( r = –0.45 and –0.44, both p < 0.001, respectively) and the age of patients ( r = 0.47; p < 0.001). Conclusion. The clinical pregnancy rate in women with a suboptimal response to COS was low. Concomitant uterine fibroids represented an additional factor of negative influence on IVF / ICSI outcomes in women with a suboptimal response to COS. The male factor of infertility in patients with a suboptimal response did not reduce the efficacy of ART programs. Ovarian reserve parameters in women with a suboptimal response correlated with the need for FSH preparations during COS and the number of retrieved oocytes.

Polycystic ovarian syndrome (PCOS) is the most prevalent metabolic disorder in reproductive-age women. It is indeed a multifactorial condition evidenced by ovarian dysfunction, hyperandrogenaemia, infertility, hormonal imbalance and chronic anovulation. Experimental evidence infers that PCOS women are prone to cardiovascular problems and insulin resistance. To furnish the details about the association of inflammatory markers in PCOS. An extensive literature search on PubMed, science direct and google scholar has been performed for articles about PCOS and inflammation in PCOS. A comprehensive analysis using original articles, reviews, systemic and meta-analysis was conducted for better understanding the relationship between inflammatory cytokines and PCOS. The inflammatory markers perform a substantial part in managing the functions of the ovary. Any disturbances in their levels can lead to ovarian dysfunction. Inflammatory markers are associated with PCOS pathogenesis. The interplay between inflammatory cytokines in the PCOS ovary strongly implies that inflammation is one of the most potent risk factors of PCOS. Inflammatory markers have a significant role in regulating the ovary. This manuscript highlights the significance of metabolic and inflammatory markers with PCOS. Since PCOS is always considered as a metabolic disorder, researchers can also consider focusing on the relationship between the inflammatory markers in PCOS to establish a new treatment or management of the disease and to improve women's health.

Introduction Functional hypothalamic amenorrhoea (FHA) is a common form of secondary amenorrhoea without an identifiable structural cause. Suppression of gonadotrophin-releasing hormone (GnRH) pulsatility results in reduced luteinizing hormone (LH) levels, with subsequent reduction in oestradiol, anovulation and cessation of menstruation. GnRH pulsatility suppression is a recognized complication of psychological stress, disordered eating, low body weight, excessive exercise or a combination of these factors. Pathophysiology of fha Individuals with FHA demonstrate low energy availability (EA), body fat percentage and energy expenditure. Documented adipocytokine changes notably, raised adiponectin, ghrelin, PYY, and decreased leptin, are associated with GnRH suppression. Other endocrine responses seen in this low EA state include low insulin levels, low total T3, increased basal cortisol levels and a reduced response to corticotrophin-releasing hormone (CRH) administration. FHA is associated with raised growth hormone (GH) and low insulin-like growth factor (IGF-1), suggesting relative GH resistance. Kisspeptins are a group of polypeptides, recently discovered to play a major role in the regulation of the reproductive axis through influencing GnRH release. KNDy (kisspeptin/neurokinin B/dynorphin) act on GnRH neurons and a multitude of factors result in their release. Implications for future treatment Management of FHA is imperative to prevent adverse outcomes in bone density, cardiovascular risk profile, psychological well-being and fertility. Outwith modification of nutritional intake and exercise, limited therapeutic strategies are currently available for women with FHA. Advancements in the understanding of the pathophysiological basis of this under-recognized and under-treated clinical entity will aid management and may result in the development of novel therapeutic approaches.

Most of the women in the reproductive age group are affected by PCOD. Emphasis on prevention of PCOD, as the incidents of PCOD, are increasing. The current incident of PCOD is (5%to 15%) is increasing fastly due to lifestyle and stress. It is also becoming a common problem amongst adolescent, developing soon after puberty. Amongst infertile women, about 15% to 20% of infertility cases are due to anovulation caused by PCOD. This study was done to assess the knowledge of PCOD among women and to make them aware of lifestyle modification is an important part of treatment. Some of the women who developed cardiovascular disease, hypertension, endometrial cancer and type 2 diabetes later in life appear to have suffered from PCOD in earlier years. A cross-sectional observational study was conducted in Chennai with 100 women of reproductive age (18~45 yrs) from January to June 2020 using standardized questionnaire. According to the study, 28% of the subjects are very well aware of the PCOD. 58% had expressed somewhat aware, 64% aware that Exercise help in the management of PCOD, in that 27% are maintaining diet and exercise every day. 14% of the respondents are not aware of the PCOD. This study indicated that more awareness should be made in the general public about PCOD as the majority of the participants are ignorant about lifestyle modification.

To identify which positive prognostic parameters contribute to successful treatment outcomes and the probability of pregnancy by analyzing the results of infertile couples underwent ovulation stimulation (OS) and intra-uterine insemination (IUI) in our clinic.Five hundred and nineteen couples who underwent OS-IUI treatment because of a mild-moderate male factor, unexplained infertility, or anovulation were retrospectively analyzed. The data collected included patient demographics, cycle characteristic, sperm parameters and pregnancy rates. The main outcome measure was pregnancy rate (PR).Our overall PR was 17.72% (n = 92). In women who did not achieve pregnancy, age, BMI and duration of infertility were significantly higher (P 0.001, P 0.001 and P = 0.03, respectively). The IUI indications of higher PR were unexplained infertility (P = 0.018) and primary infertility (P = 0.003). AFC was significantly lower and the total dosage of gonadotropins was significantly higher in women who did not achieve pregnancy (P = 0.001 and P = 0.017, respectively). The number of progressive motile spermatozoa inseminated and the morphology were significantly higher in women who did not achieve pregnancy (P = 0.056 and P = 0.001, respectively). Female age ≤ 30 (OR = 0.87; 95% CI: 0.81-0.95; P 0.01), BMI ≤23.3 kg/mYounger women, especially those with unexplained infertility, primary infertility, shorter duration of infertility, normal ovarian reserve, higher motile spermatozoa inseminated and sperm morphology, could benefit from OS-IUI.

Polycystic ovary syndrome (PCOS) is a common disorder that affects various facets of fertility. Although the ovarian and metabolic aspects of the disease is well studied, its role in uterine dysfunction is not well understood. Our objective was to review the features of endometrial and uterine aberrations in women with PCOS. A systematic literature search was performed in PubMed, Medline, and the Cochrane Library databases for papers published in English up to March 2020. The following key words were used for the search: polycystic ovary syndrome, poly cystic ovarian disease, polycystic ovaries, PCOS, PCOD, PCO, PCOM, oligoovulation, anovulation, oligomenorrhea, amenorrhea, hyperandrogenism and this was combined with terms; endometrium, infertility, uterus, progesterone resistance, endometrial hyperplasia, pregnancy outcomes, preterm delivery. In this review, we highlight various uterine pathologies that are associated with PCOS and explore its impact on fertility. We also discuss key uterine molecular pathways that are altered in PCOS that may be related to infertility, endometrial hyperplasia and cancer.