Absence Of Ovaries Research Articles

Caloric and time restriction diets improve acute kidney injury in experimental menopausal rats: role of silent information regulator 2 homolog 1 and transforming growth factor beta 1.

Estrogen has a protective impact on acute kidney injury (AKI); moreover, reducing the daily intake of calories impedes developing diseases. The present study aimed to determine the effects of calorie restriction (CR) and time restriction (TR) diets on the expression of silent information regulator 2 homolog 1 (SIRT1), transforming growth factor beta 1 (TGF-β1), and other indicators in the presence and absence of ovaries in AKI female rats. The female rats were divided into two groups, ovariectomized (OVX) and sham, and were placed on CR and TR diets for eight weeks; afterward, AKI was induced by injecting glycerol, and kidney injury indicators and biochemical parameters were measured before and after AKI. After AKI, the levels of urine albumin excretion rate, urea, and creatinine in serum, and TGF-β1 increased, while creatinine clearance and SIRT1 decreased in kidney tissue. CR improved kidney indicators and caused a reduction in TGF-β1 and an increase in SIRT1 in ovary-intact rats. Moreover, CR prevented total antioxidant capacity (TAC) decrease and malondialdehyde (MDA) increase resulting from AKI. Before AKI, an increase in body weight, fasting blood sugar (FBS), low-density lipoprotein (LDL), triglyceride (TG), and total cholesterol (TC), and a decrease in high-density lipoprotein (HDL) were observed in OVX rats compared to sham rats, but CR prevented these changes. The effects of TR were similar to those of CR in all indicators except for TGF-β1, SIRT1, urea, creatinine, and albumin. The present study indicated that CR is more effective than TR in preventing AKI, probably by increasing SIRT1 and decreasing TGF-β1 in ovary-intact animals.

Novel Methodology for Identifying the Occurrence of Ovulation by Estimating Core Body Temperature During Sleeping: Validity and Effectiveness Study.

Body temperature is the most-used noninvasive biomarker to determine menstrual cycle and ovulation. However, issues related to its low accuracy are still under discussion. This study aimed to improve the accuracy of identifying the presence or absence of ovulation within a menstrual cycle. We investigated whether core body temperature (CBT) estimation can improve the accuracy of temperature biphasic shift discrimination in the menstrual cycle. The study consisted of 2 parts: experiment 1 assessed the validity of the CBT estimation method, while experiment 2 focused on the effectiveness of the method in discriminating biphasic temperature shifts. In experiment 1, healthy women aged between 18 and 40 years had their true CBT measured using an ingestible thermometer and their CBT estimated from skin temperature and ambient temperature measured during sleep in both the follicular and luteal phases of their menstrual cycles. This study analyzed the differences between these 2 measurements, the variations in temperature between the 2 phases, and the repeated measures correlation between the true and estimated CBT. Experiment 2 followed a similar methodology, but focused on evaluating the diagnostic accuracy of these 2 temperature measurement approaches (estimated CBT and traditional oral basal body temperature [BBT]) for identifying ovulatory cycles. This was performed using urine luteinizing hormone (LH) as the reference standard. Menstrual cycles were categorized based on the results of the LH tests, and a temperature shift was identified using a specific criterion called the "three-over-six rule." This rule and the nested design of the study facilitated the assessment of diagnostic measures, such as sensitivity and specificity. The main findings showed that CBT estimated from skin temperature and ambient temperature during sleep was consistently lower than directly measured CBT in both the follicular and luteal phases of the menstrual cycle. Despite this, the pattern of temperature variation between these phases was comparable for both the estimated and true CBT measurements, suggesting that the estimated CBT accurately reflected the cyclical variations in the true CBT. Significantly, the CBT estimation method showed higher sensitivity and specificity for detecting the occurrence of ovulation than traditional oral BBT measurements, highlighting its potential as an effective tool for reproductive health monitoring. The current method for estimating the CBT provides a practical and noninvasive method for monitoring CBT, which is essential for identifying biphasic shifts in the BBT throughout the menstrual cycle. This study demonstrated that the estimated CBT derived from skin temperature and ambient temperature during sleep accurately captures variations in true CBT and is more accurate in determining the presence or absence of ovulation than traditional oral BBT measurements. This method holds promise for improving reproductive health monitoring and understanding of menstrual cycle dynamics.

P-598 Novel inactivating homozygous mutation of the luteinizing hormone/choriogonadotropin receptor (LHCGR) and first live birth after in vitro maturation (IVM): a breakthrough

Abstract Study question How can pregnancy and live birth be achieved in patients with inactivating homozygous luteinizing hormone/choriogonadotropin receptor (LHCGR) mutation? Summary answer We report the first live birth after IVM in a patient with a novel homozygous inactivating LHCGR mutation (exon 6,c.470A>G). What is known already LH plays a fundamental role in female reproductive physiology and is responsible for steroidogenesis, oocyte maturation, ovulation and subsequent progesterone production by the corpus luteum. LH binds to the LHCGR located on the membrane of theca cells and mature granulosa cells. Inactivating mutations of the LHCG receptor lead to the impossibility to obtain final oocyte maturation both during natural cycles and after ovarian stimulation for in vitro fertilization purpose. Until now, egg donation represented the only option to treat their infertility. Study design, size, duration A case report. Participants/materials, setting, methods A 35 year-old nulliparous patient was referred to our university hospital for primary infertility. Main results and the role of chance The 35-year-old nulliparous patient presented with primary spaniomenorrhea but timely and spontaneous onset of secondary sexual characteristics. Serum LH levels were high (ranging from 15 to 30 IU/L) and to a lesser extent so were FSH levels. The ovarian reserve was normal for age, as assessed by serum AMH levels and ultrasound. There was no argument for polycystic ovarian syndrome, 21-hydroxylase deficiency, Cushing’s syndrome or hyperprolactinemia. Two previous attempts of controlled ovarian stimulation with gonadotropins and ovulation trigger with hCG and GnRH-agonist trigger had failed, resulting in low estradiol levels despite correct follicular growth on ultrasound and absence of ovulation after trigger. We identified by genetic analysis a novel homozygous inactivating LHCGR mutation (exon 6, c.470A>G) that had never been described previously. IVM was performed. A total of 7 oocytes were obtained after IVM, resulting in 4 Day 3 embryos. All embryos were frozen. Subsequently, 2 Day 3 embryos were replaced after endometrial preparation by hormone replacement therapy. The patient became pregnant and gave birth to a healthy baby. Two Day 3 embryos remain. Limitations, reasons for caution By definition, a case-report requires further studies to confirm our findings. Wider implications of the findings We describe a novel inactivating LHCGR mutation with subsequent live birth after IVM. As a growing number of gonadotropin receptor mutations are identified, this live birth successfully obtained places IVM as the only reliable option for these patients to conceive with their own eggs. Trial registration number not applicable

Literatur Review: Faktor Resiko Sindrom Ovarium Polikistik pada Remaja

Polycystic ovary syndrome (PCOS) is a complex metabolic, reproductive, and psychological disorder that impacts women throughout their lives. PCOS is a hormonal imbalance disorder that occurs in women of childbearing age. This can cause symptoms such as irregular menstruation, amenorrhea (absence of menstruation), anovulation (absence of ovulation), hirsutism, acne, and obesity. PCOS also causes metabolic disorders in the body. The exact cause of PCOS is not known but in general it can be caused by genetic and environmental factors. Many studies have proven the factors that influence PCOS. Therefore, to conclude the results of this research, a literature review was carried out. The literature was searched for scientific articles with the keywords "nutritional status", "physical activity", "mental health", "menstrual cycle", "PCOS" and "adolescence". Article search via Google Scholar and PubMed. After conducting a search, 9 articles were found that met the writing criteria. The results of the review show that several factors can significantly increase the risk of PCOS, namely, excessive nutritional status, lack of physical activity, poor mental health (stress and depression), and long and irregular menstrual cycles. The results of the review also prove that the main factors with the highest level of risk in this article are long and irregular menstrual cycles and excessive nutritional status

Dynamic changes in AI-based analysis of endometrial cellular composition: Analysis of PCOS and RIF endometrium

BackgroundThe human endometrium undergoes a monthly cycle of tissue growth and degeneration. During the mid-secretory phase, the endometrium establishes an optimal niche for embryo implantation by regulating cellular composition (e.g., epithelial and stromal cells) and differentiation. Impaired endometrial development observed in conditions such as polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF) contributes to infertility. Surprisingly, despite the importance of the endometrial lining properly developing prior to pregnancy, precise measures of endometrial cellular composition in these two infertility-associated conditions are entirely lacking. Additionally, current methods for measuring the epithelial and stromal area have limitations, including intra- and inter-observer variability and efficiency. MethodsWe utilized a deep-learning artificial intelligence (AI) model, created on a cloud-based platform and developed in our previous study. The AI model underwent training to segment both areas populated by epithelial and stromal endometrial cells. During the training step, a total of 28.36 mm2 areas were annotated, comprising 2.56 mm2 of epithelium and 24.87 mm2 of stroma. Two experienced pathologists validated the performance of the AI model. 73 endometrial samples from healthy control women were included in the sample set to establish cycle phase-dependent dynamics of the endometrial epithelial-to-stroma ratio from the proliferative (PE) to secretory (SE) phases. In addition, 91 samples from PCOS cases, accounting for the presence or absence of ovulation and representing all menstrual cycle phases, and 29 samples from RIF patients on day 5 after progesterone administration in the hormone replacement treatment cycle were also included and analyzed in terms of cellular composition. ResultsOur AI model exhibited reliable and reproducible performance in delineating epithelial and stromal compartments, achieving an accuracy of 92.40% and 99.23%, respectively. Moreover, the performance of the AI model was comparable to the pathologists’ assessment, with F1 scores exceeding 82% for the epithelium and >96% for the stroma. Next, we compared the endometrial epithelial-to-stromal ratio during the menstrual cycle in women with PCOS and in relation to endometrial receptivity status in RIF patients. The ovulatory PCOS endometrium exhibited epithelial cell proportions similar to those of control and healthy women’s samples in every cycle phase, from the PE to the late SE, correlating with progesterone levels (control SE, r2 = 0.64, FDR < 0.001; PCOS SE, r2 = 0.52, FDR < 0.001). The mid-SE endometrium showed the highest epithelial percentage compared to both the early and late SE endometrium in both healthy women and PCOS patients. Anovulatory PCOS cases showed epithelial cellular fractions comparable to those of PCOS cases in the PE (Anovulatory, 14.54%; PCOS PE, 15.56%, p = 1.00). We did not observe significant differences in the epithelial-to-stroma ratio in the hormone-induced endometrium in RIF patients with different receptivity statuses. ConclusionThe AI model rapidly and accurately identifies endometrial histology features by calculating areas occupied by epithelial and stromal cells. The AI model demonstrates changes in epithelial cellular proportions according to the menstrual cycle phase and reveals no changes in epithelial cellular proportions based on PCOS and RIF conditions. In conclusion, the AI model can potentially improve endometrial histology assessment by accelerating the analysis of the cellular composition of the tissue and by ensuring maximal objectivity for research and clinical purposes.

Polycystic Ovary Syndrome

ABSTRACT Polycystic ovary syndrome (PCOS) is a most common but complex, multifunctional, endocrine complaint that occurs substantially in women of reproductive age. It is characterized by irregularity or the absence of ovulation and elevated situations of androgen (hyperandrogenism) and insulin (hyperinsulinemia). It is a chronic condition that can lead to numerous successive and severe conditions such as uterine (endometrial) or ovarian carcinoma, diabetes mellitus, and cardiovascular diseases. The signs and symptoms of polycystic ovary disease may include irregular periods, infertility, weight gain, thinning crown hair, patient acne, dark skin patches, skin markers, pelvic pain, depression, and anxiety. Remaining benighted on PCOS and its management impacts the prognosis.

An Ayurvedic Approach to Stree Vandhyatva (Anovulation) Utilizing Uttar Basti

Infertility has emerged as a significant disorder, primarily influenced by the stresses of the modern world, insufficient consumption of wholesome organic foods, and the evolving lifestyle patterns. Anovulation-related infertility has become a major concern among individuals of reproductive age in the current generation, largely due to unfavourable lifestyle shifts. A notable portion of couples seeking help at fertility clinics grapple with infertility caused by the absence of ovulation. In a remarkable 90% of these cases, Polycystic Ovary Syndrome (PCOS) stands as the predominant culprit. The timeless wisdom of ancient Ayurvedic scholar Sushruta continues to hold relevance today. His delineation of the four crucial factors for conception remains as imperative as it was in the past. Among these factors, the health of the ovum stands out, and disruptions in Vata Dosha often manifest as issues in ovulatory function. This narrative presents a case study involving an infertile couple who had been unable to conceive for three years. The wife's diagnosis indicated Polycystic Ovarian Disease (PCOD). Despite undergoing conventional treatments, including hormonal therapy, their attempts were unsuccessful. The treatment strategy employed an approach called Uttar Basti alongside Prajasthapak Ghrita and Garbhaprada Yoga (a formulation supporting conception) administered orally. Notably, the outcome of this Ayurvedic intervention was the successful conception of the patient within just three months of treatment.

Toward an optimal contraception dosing strategy.

Anovulation refers to a menstrual cycle characterized by the absence of ovulation. Exogenous hormones such as synthetic progesterone and estrogen have been used to attain this state to achieve contraception. However, large doses are associated with adverse effects such as increased risk for thrombosis and myocardial infarction. This study utilizes optimal control theory on a modified menstrual cycle model to determine the minimum total exogenous estrogen/progesterone dose, and timing of administration to induce anovulation. The mathematical model correctly predicts the mean daily levels of pituitary hormones LH and FSH, and ovarian hormones E2, P4, and Inh throughout a normal menstrual cycle and reflects the reduction in these hormone levels caused by exogenous estrogen and/or progesterone. Results show that it is possible to reduce the total dose by 92% in estrogen monotherapy, 43% in progesterone monotherapy, and that it is most effective to deliver the estrogen contraceptive in the mid follicular phase. Finally, we show that by combining estrogen and progesterone the dose can be lowered even more. These results may give clinicians insights into optimal formulations and schedule of therapy that can suppress ovulation.

Polycystic Ovarian Syndrome in Adolescents.

Polycystic ovarian syndrome (PCOS)is a metabolic, reproductive, and psychological complex series of disorders that impacts a woman throughout her lifespan. PCOS is a disorder of hormonal imbalance occurring in women of reproductive age. This disorder is characterized byhigh levels of male androgens like testosterone. This can lead tosymptoms like irregular periods, amenorrhea (absence of menstruation), anovulation (absence of ovulation), hirsutism, acne, and obesity. PCOS also causes metabolic impairment. Multiple peripherally arranged immature follicles of about 2-5mm in diameter are present in the ovary. These follicles do not mature due to hormonal imbalances leading to an irregular menstrual cycle.PCOS is a metabolic, reproductive, and psychological complex series of disorders that impacts a woman throughout her lifespan. Polycystic ovarian syndrome is not a fatal or life-threatening disorder as its main complication is infertility. PCOScan be a root cause ofserious medical conditions like obesity, hypertension, type-2 diabetes mellitus due to insulin resistance, endometrial cancers, ovarian cancer, etc. Stress may causethe hormone levels in the pituitary to fluctuate. Since the menstrual cycle is hormone-based, there are apparent irregularities.

P-625 In vitro maturation of oocytes: a breakthrough for treating infertility in inactivating mutation of the luteinizing hormone/choriogonadotropin receptor

Abstract Study question How can pregnancy and live birth be achieved in patients with inactivating homozygous luteinizing hormone/choriogonadotropin receptor (LHCGR) mutation? Summary answer We report the first live birth after in vitro maturation (IVM) in a patient with a novel homozygous inactivating LHCGR mutation (exon 6, c.470 A&amp;gt;G). What is known already LH plays a fundamental role in female reproductive physiology and is responsible for steroidogenesis, oocyte maturation, ovulation and subsequent progesterone production by the corpus luteum. LH binds to the LHCGR located on the membrane of theca cells and mature granulosa cells. Inactivating mutations of the LHCGR lead to the impossibility to obtain final oocyte maturation both during natural cycles and after ovarian stimulation for in vitro fertilization purposes. Therefore, egg donation represents the only option for treating their infertility. Study design, size, duration A case report. Participants/materials, setting, methods A 35 year-old nulliparous patient referred to our university hospital for primary infertility. Main results and the role of chance The 35-year-old nulliparous patient presented with primary spaniomenorrhea but timely and spontaneous onset of secondary sexual characteristics. Serum LH levels were high (ranging from 15 to 30 IU/L) and to a lesser extent so were FSH levels. The ovarian reserve was normal for age, as assessed by serum AMH levels and ultrasound. There was no argument for polycystic ovarian syndrome, 21-hydroxylase deficiency, Cushing’s syndrome or hyperprolactinemia. Two previous attempts of controlled ovarian stimulation with gonadotropins and ovulation trigger with hCG and GnRH-agonist trigger had failed, resulting in low estradiol levels despite correct follicular growth on ultrasound and absence of ovulation after trigger. However, genetic analysis identified a novel homozygous inactivating LHCGR mutation (exon 6, c.470A&amp;gt;G) which had never been described previously. IVM was performed. A total of 7 oocytes were obtained after IVM, resulting in 4 Day 3 embryos. All embryos were frozen. Subsequently, 2 Day 3 embryos were replaced after endometrial preparation by hormone replacement therapy. The patient became pregnant and gave birth to a healthy baby. Two Day 3 embryos remain. Limitations, reasons for caution By definition, a case-report requires further studies to confirm our findings. Wider implications of the findings We describe a novel inactivating LHCGR mutation with subsequent live birth after IVM. As a growing number of gonadotropin receptor mutations are identified, this successfully achieved live birth places IVM as the only reliable option for these patients to conceive with their own eggs. Trial registration number Not applicable.

Exploring on the comparative merit of allopathy medicine and yoga therapy for PCOD condition

Polycystic Ovary Disorder (PCOD) is a disorder in women characterized by elevated levels of male hormones and infrequent or absence of ovulation. It is the leading cause of infertility in females. However, several treatments are available for treating PCOD, with varying success levels, and are associated with drug-related side effects, repetition of the problem, and is expensive. Alternative therapies attract scientists and health care promoters because of their compatibility and enhancing the yoga therapy programs, which are cost-effective and viable in primarily populated countries like India. The present study attempts to investigate the comparative merit of yoga therapy intervention with allopathy treatment in reducing hormonal imbalance and anxiety levels experienced in women with PCOD. This study was conducted on 50women participants with PCOD who have undergone treatment at a gynecological clinic, Visakhapatnam. All the fifty women participants have satisfied the Rotterdam criteria for PCOD condition. Based on their choice, the 50 participants (of age 20-35 years) have divided into two groups: the Yoga Intervention group Allopathy intervention group.

Novel Technique for Confirmation of the Day of Ovulation and Prediction of Ovulation in Subsequent Cycles Using a Skin-Worn Sensor in a Population With Ovulatory Dysfunction: A Side-by-Side Comparison With Existing Basal Body Temperature Algorithm and Vaginal Core Body Temperature Algorithm.

Objective: Determine the accuracy of a novel technique for confirmation of the day of ovulation and prediction of ovulation in subsequent cycles for the purpose of conception using a skin-worn sensor in a population with ovulatory dysfunction. Methods: A total of 80 participants recorded consecutive overnight temperatures using a skin-worn sensor at the same time as a commercially available vaginal sensor for a total of 205 reproductive cycles. The vaginal sensor and its associated algorithm were used to determine the day of ovulation, and the ovulation results obtained using the skin-worn sensor and its associated algorithm were assessed for comparative accuracy alongside a number of other statistical techniques, with a further assessment of the same skin-derived data by means of the “three over six” rule. A number of parameters were used to divide the data into separate comparative groups, and further secondary statistical analyses were performed. Results: The skin-worn sensor and its associated algorithm (together labeled “SWS”) were 66% accurate for determining the day of ovulation (±1 day) or the absence of ovulation and 90% accurate for determining the fertile window (ovulation day ±3 days) in the total study population in comparison to the results obtained from the vaginal sensor and its associated algorithm (together labeled “VS”). Conclusion: SWS is a useful tool for confirming the fertile window and absence of ovulation (anovulation) in a population with ovulatory dysfunction, both known and determined by means of the timing of ovulation. The body site where the skin-worn sensor was worn (arm or wrist) did not appear to affect the accuracy. Prior diagnosis of known causes of ovulatory dysfunction appeared to affect the accuracy to a lesser extent than those cycles grouped into late ovulation and “early and normal ovulation” groups. SWS is a potentially useful tool for predicting ovulation in subsequent cycles, with greater accuracy obtained for the “normal ovulation” group.

Prenatal dexamethasone exposure and developmental programming of the ovary of the offspring: a structural study in the rat.

Overexposure to glucocorticoids during fetal development alters fetal organ growth and maturation patterns, which can result in adverse programming outcomes in adulthood. The aim of this study was to determine whether exposure to dexamethasone (Dx) during the fetal period programmed ovary development and function in infant (16-day-old) and peripubertal (38-day-old) female offspring. Pregnant Wistar rats were separated into control and Dx-treated (0.5mg kg-1) groups and were injected with Dx or an equivalent volume of vehicle on Days 16, 17 and 18 of gestation. Ovaries from 16- and 38-day-old female offspring were prepared for histological and stereological examination. The volume of the ovary and the number of primordial and primary follicles were significantly reduced in prenatally Dx-exposed infant and peripubertal female offspring compared with control offspring. The number of multilaminar follicles was decreased in infant female offspring. In peripubertal females, prenatal exposure to Dx increased the number of multilaminar and large follicles of all classes. Because vaginal opening did not occur up to Day 38 postpartum in the Dx-exposed offspring, the absence of ovulation and corpora lutea is confirmation that the onset of puberty had been delayed. We can conclude that overexposure to glucocorticoids early in life programs ovary development, which may affect fertility in adulthood.

Pseudo-hermafroditismo em cadela da raça buldogue-francês

Pseudohermaphroditism is a sexual anomaly, rare in dogs, in which the individual has both male and female characteristics; normally ambiguous external genitalia and male or female gonads. This report concerns a 5-month-old female French Bulldog, where the principal concern was the presence of a structure in the internal region of the genitalia with evolution of approximately 2 months. Upon clinical examination, it was found that the patient had a characteristically female phenotype and a vagina with no apparent changes, despite the presence of a hypertrophied structure inside, similar to a clitoris and a probable penile bone. A right lateral abdominal radiography revealed the presence of a probable atrophied penile bone located inside the vulva. An ultrasound examination showed the presence of two oval, coarse and hypoechogenic structures in the inguinal (subcutaneous) region, suggesting ectopic testicles; ovaries and uterus were not observed. However, during laparotomy the absence of ovaries and the presence of uterus and testicles in the subcutaneous tissue were observed.

Biological role of nitric oxide donors in pregravid preparation of women with luteal phase deficiency

Background. At the menstrual cycle beginning there is a proliferation of endometrial cells under the influence of oestrogen, and in the second half, after ovulation there is a differentiation and hypertrophy of cells under the influence of corpus luteum progesterone. Lutein phase deficiency (LPD) can be divided into 3 types: lack of progesterone production (corpus luteum is absent), low progesterone level (corpus luteum hypofunction), and reduction of progesterone production period (short period of corpus luteum existence, luteal phase duration &lt;11 days).&#x0D; Objective. To describe the role of nitric oxide (NO) donors in women with LPD.&#x0D; Materials and methods. Analysis of literature data on this issue.&#x0D; Results and discussion. The main adverse outcome of LPD is the absence or defective transformation and reception of the endometrium required for successful fertilization of the egg. In case of progesterone deficiency, the depth of trophoblast invasion decreases, resulting in abnormal placental development and inadequate uteroplacental blood flow. The latter can further lead to antenatal foetal death and miscarriage, preeclampsia and eclampsia, placental dysfunction. LPD should be suspected in patients with infertility, abnormal uterine bleeding, severe premenstrual syndrome, endometrial hyperplasia, and habitual miscarriage. Ultrasound signs of LPD include the absence of a dominant follicle, absence of ovulation in the presence of a mature follicle (persistence), absence of corpus luteum in the 2nd phase of the cycle, endometrial thickness in the secretion phase &lt;9 mm, increased echogenicity only in the peripheral parts of the endometrium or three-layered endometrium. Functional tests for the detection of LPD include the basal temperature measurement and examination of smears (hypolutein type of smear, preservation of the symptom of cervical mucus crystallization in the 2nd phase of the cycle). A key element of pregravid preparation for women with LPD is the progesterone donation (in oil solution, in etiloleate or micronized). The therapeutic efficacy of different commercial progesterone drugs is the same. Progesterone helps to prepare the endometrium for trophoblast invasion and promotes uterine hypotension. Incomplete secretory transformation of the endometrium during the treatment with progesterone drugs occurs in case of inadequate blood supply to the endometrium due to low density of functional vessels or insufficient content of NO in the endometrium. Back in the late 90’s of last century, it was shown that NO acts as a powerful uterine relaxant, and reduction of its concentration leads to miscarriage. In humans, NO is produced from L-arginine, however, obtaining the required dose of the latter with food is not always possible. When L-arginine (Tivortin aspartate, “Yuria-Pharm”) is used as a NO donor, peripheral vascular dilatation and neoangiogenesis occur, which improves blood supply and endometrial trophic processes; stimulation of gene transcription and cell cycle, which increases the cell population and physiological thickness of the endometrium; regulation of sex hormone synthesis and expression of their receptors, which increases the receptivity of the endometrium. The regimen of Tivortin aspartate administration is the following: 5 ml (1 g) 6 times per day during the menstrual cycle. According to the results of our own study, L-arginine increases the biological effect of progesterone on the endometrium, promotes a more successful restoration of its physiological structure and thickness in women with LPD. The inclusion of L-arginine in the pregravid preparation of women with LPD showed a 1.9-fold decrease in the infertility incidence, a 3.3-fold increase in the number of pregnancies and births, and a 3.4-fold decrease in the number of miscarriages.&#x0D; Conclusions. 1. The main adverse outcome of LPD is the absence or defective transformation and reception of the endometrium required for successful fertilization of the egg. 2. Usage of L-arginine (Tivortin aspartate) as a donor of NO promotes dilatation of peripheral vessels and neoangiogenesis, stimulation of the cell cycle, regulation of the synthesis of sex hormones. 3. Inclusion of L-arginine in the pregravid preparation of women with LPD leads to the decrease in infertility, to the increase in the number of pregnancies and births and to the decrease in the number of miscarriages.

Poor oocyte quality as a cause of embryo fragmentation in IVF program: clinical case report

High degree of embryo fragmentation correlates with absence of implantation in IVF programs. The aim of the work was to determine the most probable cause of embryo fragmentation and ineffective in vitro fertilization (IVF) program on the example of a specific clinical situation and based on the analysis of literature data. In contrast to the common form of infertility, associated with the absence of ovulation and constituting 35-40% in the structure of infertility factors, , this clinical situation is unusual due to the fact that pregnancy as a result of repeated IVF programs did not occur due to the production of fragmented embryos with a preserved ovarian reserve and the exclusion of other infertility factors. The successful solution of reproductive problems in this couple is obviously associated with the use of the oocyte donation program.

PREPL Deficiency: A Homozygous Splice Site PREPL Mutation in a Patient With Congenital Myasthenic Syndrome and Absence of Ovaries and Hypoplasia of Uterus.

Prolyl endopeptidase-like (PREPL) deficiency (MIM 616224) is a very rare congenital disorder characterized by neonatal hypotonia and feeding difficulties, ptosis, neuromuscular symptoms, cognitive impairments, growth hormone deficiency, short stature, and hypergonadotropic hypogonadism. This syndrome is an autosomal recessive disease resulting from mutations in the PREPL gene. Previous reports have associated PREPL deficiency with only one nucleotide substitution, the deletion of four nucleotides, and eight small microdeletions in the PREPL gene In this study, we used whole exome sequencing (WES) to identify a novel homozygous splicing mutation (c.616 + 1G > T) in a 14-year-old Chinese girl with PREPL deficiency. Sequencing of the RT-PCR products from the patient’s blood sample revealed that the c.616 + 1G > T variant disrupted normal splicing in intron 4 leading to an aberrant inclusion of 43 nucleotides in intron, a frameshift, and premature termination codon. Our patient exhibited several of the common phenotypes, including severe neonatal hypotonia, growth impairment and cognitive problems. However, we also observed several unusual phenotypic characteristics: absence of the ovaries, hypoplasia of the uterus, microcephaly and a short neck in patient is alsoobserved. These results provide further evidence for the involvement of PREPL development of the ovaries and uterus. Our findings may provide further insight into the relationship between the genotype and phenotype in collagen-associated diseases and improve the clinical diagnosis of Prolyl endopeptidase-like deficiency.

Endocannabinoid activation and polycystic ovary syndrome: A systematic review

Polycystic Ovarian Syndrome (PCOS) is the major cause of female infertility that affecting 5–10% of women of reproductive age (18–44 years). Many cases, the women do not find that they suffer from this syndrome until they try to get pregnant. The etiology includes the multiple fluid sacs or cysts grow in either or both ovaries where in some cases symptoms persist and others have no symptoms. The syndrome is characterized by chronic absence of ovulation as well as high levels of androgens. The major cause that contributes this syndrome includes mutation of one or more gene that causes hormonal imbalance, life style disturbance as well as environmental factors. Symptoms of PCOS include Infertility, hirsutism, menstrual irregularities, male pattern baldness, excessive hair growth on face, abnormal cholesterol or triglyceride levels etc. Treatment focuses on clinical improvement of patients suffered from the condition. The therapies include insulin sensitizing medications such as metformin that at present has gaining great interest. Use of metformin may reduce the risk of hyperinsulinism, type-2 diabetes, and metabolic syndrome. Other medications include oral contraceptives or anti-androgen medications also proved beneficial in some cases. Clomiphene Citrate was used in many cases alone or in combination for ovulation induction in oligomenorrheic women. In this review, we have tried to explore the beneficial use of non psychoactive Cannabidiol to reduce the stress and pain during the Polycystic Ovarian Syndrome.

New assays reveal opposing effects of 17b‐estradiol in the presence and absence of ovaries on the cardiac network of calmodulin‐binding proteins

Reduced estrogen concentrations following menopause are associated with increases in the incidence of cardiovascular disease. Calmodulin (CaM) is required for the activities of numerous cardiac proteins yet is not sufficiently expressed for its binding targets. We have begun to examine the effects of 17b‐estradiol (E2) on the cardiac network of CaM‐binding proteins. Female rats received sham surgery or ovariectomy, followed by treatment with vehicle or E2 for 2 weeks. E2 treatment in sham animals increases the interaction between endogenous CaM and the cardiac α adrenergic receptor type 1A. Surprisingly, ovariectomy substantially increases this interaction, while E2 replacement now reduces it. To examine the effects of these treatments on the population of cardiac CaM‐binding sites that are unsaturated by endogenous CaM, lysate from left ventricle was subjected to saturating Ca2+ concentration and processed through a CaM sepharose column. Flow through contained CaM‐binding sites saturated by endogenous CaM, while sepharose‐bound fraction represented endogenously unsaturated CaM‐binding sites. The fractions eluted from the CaM sepharose were subsequently used in competitive binding assays using purified CaM and a CaM biosensor. E2 treatment in sham animals increases the number of unsaturated CaM‐binding sites. Ovariectomy further increases this number, while E2 treatment now reduces it. The data indicate that E2 treatment exerts opposing effects in the presence and absence of ovaries on specific endogenous CaM‐target associations and the number of endogenously unsaturable Ca2+‐dependent CaM‐binding sites in the heart. These results suggest that estrogen replacement may have unpredictable functional outcomes.Support or Funding InformationSupported by NIH Grant HL112184 to Quang‐Kim Tran and Grants from the Iowa Osteopathic and Educational Research Funds to Sarah Clayton and Quang‐Kim Tran.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Assessment of the mammary glands in polycystic ovary syndrome during high level of exposure to manganese and nickel

Introduction. The authors of previous studies have found a high level of exposure to manganese and nickel in women with polycystic ovary (PCOS).Objective — to study the condition of mammary glands (MG) in women with PCOS and determine values of estradiol, prolactin (PRL) and Sex hormone-binding globulin (SHBG). To estimate possible consequences of increased exposure to manganese and nickel to the formation of MG pathology during PCOS.Material and methods. Studies were conducted in two groups of women. The first control group consisted of healthy women of reproductive age. The second group consisted of women with PCOS. The women with thyroid disease, diabetes, prolactinomas and other endocrine diseases were excluded from the study. The examination of MG was performed using ultrasound scanners. The number of cases of various forms of mastopathy was monitored. Determination of estradiol, PRL and SHBG in serum was carried out using immunoassay methods. All studies were performed with the consent of the patient and with compliance with ethical standards. Statistical processing was carried out with the definition of arithmetic mean, median. The validity of the obtained results was evaluated using following indicators: Chi-square, Shapiro-Wilka test, Fisher's F-test, Mann-Whitney’s U-test.Results. Ultrasound examination of MG was performed for 108 women in the control group and for 97 women with PCOS. In the control group, the pathology of MG was detected in 29 women (26.85%). In the second group, the pathology of MG was detected in 67 cases (69.7%; p&lt;0.0001). In women with PCOS, the median PRL score was higher by 44.83% (p = 0.0179) compared to control. Level of estradiol did not differ in both groups (p = 0.9616). In the group of women with PCOS, the SHBG indices were slightly lower compared to controls, but differences did not find statistical confirmation (p = 0.2756).Conclusions. In women with polycystic ovary syndrome more than 2 times more often there are benign mammary gland diseases. We did not find differences in the rates of estradiol and SHBG. Exposure to manganese can lead to an increase in prolactin levels. This can stimulate the proliferative processes of MG in the absence of ovulation in women with PCOS.