Regulation Of Menstrual Cycle Research Articles

Therapeutic Potential of Pomegranate Extract for Women's Reproductive Health and Breast Cancer.

Pomegranate extract has potential benefits for women's reproductive health, including fertility enhancement, menstrual cycle regulation, pregnancy support, and polycystic ovary syndrome (PCOS) treatment. It possesses antioxidant properties, reducing oxidative stress and improving fertility. Pomegranate extract may help regulate hormonal imbalances and promote regular menstrual cycles. The extract's rich nutrient profile supports placental development and fetal growth and may reduce the risk of preterm birth. Additionally, pomegranate extract shows promise in improving insulin sensitivity and reducing inflammation and oxidative damage in PCOS. Some studies suggest its potential anticancer properties, particularly against breast cancer. However, further research, including human clinical trials, is necessary to establish its effectiveness and safety. The current evidence is limited and primarily based on in vitro studies, animal studies, and clinical trials. This review provides a comprehensive summary of the benefits of pomegranate extract for women's reproductive health and breast cancer, serving as a reference for future research.

Which is the current knowledge on man-made endocrine- disrupting chemicals in follicular fluid? An overview of effects on ovarian function and reproductive health.

The increase in female reproductive disorders, such as polycystic ovary syndrome, endometriosis, and diminished ovarian reserve that lead to subfertility and infertility, has encouraged researchers to search and discover their underlying causes and risk factors. One of the crucial factors that may influence the increasing number of reproductive issues is environmental pollution, particularly exposure to man-made endocrine-disrupting chemicals (EDCs). EDCs can interfere with the ovarian microenvironment, impacting not only granulosa cell function but also other surrounding ovarian cells and follicular fluid (FF), which all play essential roles for oocyte development, maturation, and overall reproductive function. FF surrounds developing oocytes within an ovarian follicle and represents a dynamic milieu. EDCs are usually found in biological fluids, and FF is therefore of interest in this respect. This narrative review examines the current knowledge on specific classes of EDCs, including industrial chemicals, pesticides, and plasticizers, and their known effects on hormonal signaling pathways, gene expression, mitochondrial function, oxidative stress induction, and inflammation in FF. We describe the impact of EDCs on the development of reproductive disorders, oocyte quality, menstrual cycle regulation, and their effect on assisted reproductive technique outcomes. The potential transgenerational effects of EDCs on offspring through animal and first-human studies has been considered also. While significant progress has been made, the current understanding of EDCs' effects on ovarian function, particularly in humans, remains limited, underscoring the need for further research to clarify actions and effects of EDCs in the ovary.

P-790 Engineering Vascularized Human Endometrial Organoids for In Vivo Tissue Regeneration and Repair Applications

Abstract Study question Is it possible to construct a vascularized endometrial organoid in vitro using endometrial epithelial organoids, endometrial stromal cells, and HUVECs? And its application value? Summary answer We have successfully engineered a vascularized endometrial organoid and demonstrated its remarkable ability to repair damaged endometrium. ScRNA-sequencing revealed intricate regulatory relationships among the cells. What is known already In vivo, endometrial epithelial organoids (EEOs) have been proven effective in repairing damaged endometrium. In vitro, when co-cultured with endometrial stromal cells (ESCs) in matrigel, EEOs self-assemble into endometrial assembloids that accurately replicate the native tissue’s characteristics. Endothelial cells play a critical regulatory role in various physiological processes across different tissues, such as lipid metabolism in hepatocytes, neurogenesis within the brain, and the menstrual cycle regulation in uterine endometrium. By leveraging organ-on-a-chip technology using HUVECs (commonly utilized endothelial cells), it is possible to construct functional and complex organoids with vascularization, including liver buds, brain organoids, and pancreatic islets. Study design, size, duration Different ratios of Fibrin and Matrigel were explored to optimize the hydrogel conditions. The composite medium was optimized with ExM and ECM. Cellular interactions were identified through cell-specific staining. Addition of reproductive hormones was performed to determine if the complexes exhibited hormone-responsive behavior. Transplantation of the organoid complexes into mice with endometrial injury was conducted to assess their repair capacity. Single-cell RNA sequencing was employed to identify cell clusters and analyze intercellular interactions. Participants/materials, setting, methods EEOs, ESCs, and HUVECs self-assemble into HEO complexes. EEOs and ESCs self-assemble into EO complexes as controls. Immunofluorescence and immunohistochemical analysis are conducted to detect cell-specific markers. PBS, Matrigel, EO and HEO complexes are transplanted into mice with endometrial injury. JC-1 staining and transmission electron microscopy are used to verify mitochondrial functionality. Electrical resistance measured by EVOM2, HUVEC tubule formation and sprouting assays are performed to investigate the formation of vascular networks within the complexes. Main results and the role of chance Under dynamic flow conditions of ExM and ECM at a ratio of 5:5, HEO complexes and EO complexes were self-assembled in a fibrin-matrigel hydrogel. The HEO complexes exhibited a capillary network-like structure, intricate cellular interactions, and a transcriptome profile similar to that of the in vivo endometrium. Moreover, HEO complexes responded to sex hormones, facilitating endometrial regeneration and improving the reproductive capacity of mice with endometrial injury. The subcutaneous transplantation of HEO complexes in mice revealed the perfusion of mouse blood within the human blood vessel network in the grafts, highlighting the participation of HUVECs in the vascular formation of the transplanted grafts. ScRNA sequencing analysis of HEO complexes demonstrated a notable rise in the proportion of proliferative subclusters of endometrial epithelial cells and stromal cells compared to EO complexes, especially under estrogen culture conditions. Additionally, HUVECs enhanced the mitochondrial functionality of endometrial cells and remodeled the extracellular matrix. Cell communication analysis revealed that endometrial epithelial and stromal cells enhance the formation of vascular networks in HUVECs within the HEO complexes through WNT7A and WNT5A signaling pathways. Limitations, reasons for caution Due to the time constraints of the study, we did not observe the birth rate of offspring mice following endometrial repair. ScRNA sequencing also uncovered that HUVECs promote ribosomal functionality in endometrial cells within HEO complexes, but further validation of this finding is necessary. Wider implications of the findings The implantation of HEO complexes derived from woman EEOs, ESCs, and HUVECs into the endometrium holds potential for “endometrial re-engineering” in the therapeutic management of Asherman’s syndrome or thin endometrium. Trial registration number not applicable

Pre-pregnancy preparation of women with hypoandrogenism and female sexual dysfunction

The onset of pregnancy in the natural cycle is a task that requires the coordinated work of both central and peripheral levels of regulation of hypothalamic‑pituitary hormones. An analysis of the reproductive health of women with a menstrual cycle disorder against the background of hypoandrogenism indicates an unsatisfactory course of the early stages of the pregnancy process with the subsequent formation of infertility against the background of a reduced ovarian reserve. Hypolubrication is considered a clinical marker of hypoandrogenism in women of reproductive age.
 Objective — Optimization of pre‑pregnancy training in women with hypoandrogenism, menstrual cycle disorders and early pregnancy losses in the anamnesis.
 Materials and methods. A comprehensive clinical, laboratory and instrumental examination involved 90 women with menstrual cycle disorders and hypoandrogenism, from them 45 women received the proposed therapy (group Ia), and 45 patients traditional therapy (group IIa). The control group consisted of 30 healthy women at the stage of pre‑gravid examination. The age of women was 18 to 35 years. Hormonal reproductive background was determined on the 5 ‑ 7th day of the menstrual cycle in all examined women, as well as levels of thyroid‑stimulating hormone (TSH), thyroid peroxidase antibody, vitamin D, homocysteine. The proposed algorithm of pre‑gravid measures included: 1) optimization of thyroid gland function (after consultation with an endocrinologist); 2) restoration of pituitary‑ovarian relationships in case of functional central hypogonadism; 3) therapy aimed at optimizing the prolactin level (target value 12.5ng/ml); 4) reduction of homocysteine level (target level 5.6 mmol/l); 5) normalization of vitamin D level (norm is 75—125 nM/l, insufficiency defined as 50—75 nM/l, and deficiency <50 nM/l). The target control parameters included restoration of lubrication, ovulatory menstrual cycle, onset and progression of pregnancy. IBM SPSS Statistics version 25.0 software was used for statistical processing of the obtained data. The control periods of therapy were 3, 6 and 9 months.
 Results. In women with proposed treatment algorithm, therapy resulted in the recovery of vitamin D levels, starting from the 6th month of therapy, and complete normalization was recorded at the 9th month of treatment. This indicates the need for long‑term supplementation of vitamin D in women with hypoandrogenism. A decrease in the homocysteine levels was also noted on the 6th month of treatment, and its normalization after 9 months of treatment. Elevated homocysteine levels and vitamin D insufficiency/deficiency were observed throughout the follow‑up period in the conventional therapy group. In women with the proposed therapy, the levels of follicle‑stimulating hormone (FSH), TSH, luteinizing hormone (LH) and prolactin tend to normalize already from the 3rd month of therapy, while the highest positive increase was noted in the LH indicator on the 3rd‑6th month of treatment. Ovarian steroidogenesis approached the indicators of the control group after 6—9 months of therapy. Proandrogenic steroidogenesis began to increase on the 3rd month of therapy, reaching maximum on the 9th month. Unsatisfactory indicators of changes in free testosterone and dehydroepiandrosterone sulfate (DHEA‑C) were noted in women from the group of the traditional pre‑pregnancy preparation even after 9 months.
 The specified features of steroid support of the hormonal background of women’s reproductive health demonstrated the following: signs of female sexual dysfunction in the group with the proposed therapy completely disappeared after the 9th month of treatment, and in the group of traditional therapy they continued to bother 91.1% of women. At the end of the observation period, the regular menstrual cycle was gained in 40.0% of women with the proposed therapy and in 6.7% with the traditional one. Progressive pregnancies in the group with the proposed algorithm were achieved in 37.5% of women (successfully overcame the luteoplacental barrier), and in 8.8% in the group of the traditional approach (ended by early termination of pregnancy).
 Conclusions. The period of formation of the luteal phase insufficiency is the specific feature of the restoration of menstrual cycle fullness in women with hypoandrogenism, which requires additional therapy to ensure the conditions for a full‑fledged secretory endometrium transformation. The pregnancy process takes place in unfavorable conditions, which can lead to early pregnancy losses. The period of pre‑pregnancy measures in this group of patients should last at least 6—9 months. Traditional pre‑pregnancy preparation does not contribute to the restoration of the central mechanisms of menstrual cycle regulation in women with hypoandrogenism, nor does it contribute to the restoration of full‑fledged ovarian steroidogenesis, it is accompanied by anovulation and insufficiency of the luteal phase, early pregnancy losses. Symptoms of female sexual dysfunction do not disappear under the influence of traditional treatment.

Efficacy of metformin combined with vitamin D in the treatment of polycystic ovarian syndrome: A meta-analysis.

Polycystic ovary syndrome (PCOS), as an endocrine and metabolic disorder, affects approximately 6% -20% of women of childbearing age. This study aims to assess the therapeutic effects of Metformin combined with vitamin D in PCOS patients. Eight databases were searched to obtain randomized controlled trials, both domestically and internationally, on the effects of Metformin combined with vitamin D in patients with PCOS. Data analysis was performed using RevMan 5.3 software. Nine studies were ultimately included in this meta-analysis. Six studies reported the homeostatic model assessment for insulin resistance of the test group and the control group, which was significantly lower (SMD: -0.23; 95% Cl: -0.42,-0.04; P<0.05) than the control group, body mass index (BMI) (SMD: -1.86; 95% Cl: -2.77,-0.96; P<0.01), Serum 25 (OH) D (SMD: 14.28; 95% Cl: 12.26,16.29; P<0.01), testosterone (SMD: -0.11; 95% Cl: -0.15,-0.07; P<0.01) and regulated menstrual cycles (OR: 1.27; 95% Cl: 0.99,1.63; P=0.063). Our meta-analysis of nine trials demonstrates significant reductions in insulin resistance, BMI, and testosterone levels, along with increased serum vitamin D levels and improved menstrual cycle regulation after Metformin and vitamin D treatment. These findings suggest the potential of this combined therapy in managing the multifaceted aspects of PCOS.

Impact of varied temperature living conditions stress levels and sleeping duration on oligomenorrhea: a comprehensive study among women

Purpose: secondary oligomenorrhea, characterized by infrequent menstrual cycles, is a significant concern in women's reproductive health. Understanding the multifaceted determinants of this menstrual disorder is essential for developing effective interventions and improving women's well-being. This study aims to comprehensively investigate the interplay between diverse temperature living conditions, stress levels, and sleeping duration in relation to secondary oligomenorrhea. Material &amp; Methods: to achieve our objectives, we conducted a cross-sectional survey involving a diverse cohort of women aged 18 to 23 years, all of whom had experienced secondary oligomenorrhea. We employed a carefully crafted questionnaire to collect extensive data on various aspects, including demographic information, menstrual history, exposure to different temperature conditions, and sleeping patterns. Subsequently, the collected data underwent statistical analyses, including correlation and regression analyses, to unravel the intricate associations between temperature, stress, sleeping duration, and secondary oligomenorrhea. Results: the study unveiled intriguing correlations across a spectrum of temperature conditions and identified a consistent negative correlation between sleeping duration and menstrual cycle length, regardless of temperature fluctuations. This finding suggests that longer sleeping durations are associated with slightly shorter menstrual cycles. However, the impact of stress on secondary oligomenorrhea displayed variability depending on temperature conditions, indicating a more complex relationship. Conclusion: this investigation significantly enhances our understanding of how diverse temperature living conditions, stress levels, and sleeping patterns collectively influence secondary oligomenorrhea. While the observed correlations are of moderate strength, they underscore the intricate and multifaceted nature of menstrual cycle regulation. These findings emphasize the need for a holistic approach when addressing secondary oligomenorrhea, considering factors beyond temperature, stress, and sleeping duration.

Synthesis of dydrogesterone by aromatization-dearomatization strategy

Dydrogesterone as an agonist of the progesterone receptor is an important and selective synthetic progesterone used for the treatment of a variety of conditions associated with progesterone deficiency including menstrual cycle regulation, infertility, and prevention of miscarriage. Its manufacturing process employing photochemical reactions remains a significant challenge. Herein we report the first total synthesis of dydrogesterone via a key 10α-substitution-selective dearomative cyclizationfree of photochemical protocols starting from Hajos-Parrish ketone. A gram-scale synthesis is also accomplished from readily available 9-hydroxy-4-androstene-3,17-dione through a novel aromatization-dearomatization strategy of ring A in steroid chemistry. Key synthetic features include a facile chemical aromatization of 9-hydroxy-4-androstene-3,17-dione, efficient ligand-controlled asymmetric dearomative cyclization to install the 10α-Me group, and an effective hydroxyl-directed hydrogenation of sterically congested tetrasubstituted olefin to establish the 8β-H,9β-H stereochemistry.

PATHOLOGICAL UTERINE BLEEDING DURING REPRODUCTIVE AGE AND PREMENOPAUSE (ASPECTS OF DIAGNOSIS AND TREATMENT)

Pathological uterine bleeding is one of the significant problems in gynecology. Different aspects of abnormal bleeding are discussed (classification, causal factors, mechanisms, diagnosis, treatment). Medications are assessed according their priorities (haemostatic effect; regulation of menstrual cycle). Preferences of dufaston are underlined: a) It doesn’t characterize by undrogenic, glucocorticoidal and mineralocorticoidal action; b) It doesn’t aggravate insuline resistance and dyslipidemic disorders, or affect the haemostatic system.

Non-Hormonal Treatment Options for Regulation of Menstrual Cycle in Adolescents with PCOS

Menstrual irregularities are one of the main clinical symptoms caused by polycystic ovary syndrome (PCOS). Pharmacological treatment options for non-fertility indications to restore menstrual frequency play an important role in the management of PCOS. Oral contraceptive pills are commonly prescribed for adolescents with menstrual irregularities, however, when contraindicated or poorly tolerated, further pharmacological therapy is required. This systematic literature research aims to provide an overview concerning the effects of non-hormonal pharmacological treatment options on menstrual irregularities in adolescents suffering from PCOS. A systematic literature search in PubMed, Cochrane, Embase, Bio-SISS and Web of Science was performed, including literature from January 1998 to September 2022, using specific keywords in order to find related studies. n = 265 studies were identified of which n = 164 were eligible for further evaluation. Only four placebo-controlled studies were identified, with diverging inclusion and exclusion criteria. Available data on specific non-hormonal off-label use medication primarily consisted of metformin, Glucagon-like peptide 1 receptor agonists, thiazolidinediones, anti-androgen agents (spironolactone, finasteride, flutamide) and supplements (chromium picolinate, myo-inositol). However, only a few have partly pointed out beneficial effects on improving menstrual frequency in patients diagnosed with PCOS. In summary, metformin in dosages of 1500-2550 g/day, GLP-1-analogues and supplements were effective in regulation of menstrual cycles in adolescents diagnosed with PCOS. Menstrual frequency in adolescents with PCOS is essential to prevent hypoestrogenism with long-term consequences. In this context, MET is the most effective and cost- efficient in overweight adolescent girls, also showing beneficial effects in the regulation of insulin sensitivity, especially if COCs are contraindicated or not well-tolerated. Further studies are needed to evaluate therapies in lean and normal-weight girls with PCOS.

Efficacy of Myo-inositol in Improving Pregnancy Rate and Regulation of Menstrual Cycle for Patients With Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis

Background: Polycystic ovarian syndrome (PCOS) is a common, reproductive endocrinopathy associated with ovarian dysfunction, cardiovascular disorders, obesity, and infertility. Myo-inositol is a novel treatment for women with PCOS that claimed to have improved fertility rate in this population. This systematic review and meta-analysis examined the effect of myo-inositol on pregnancy rate, menstrual cycle, and adverse effects from randomized controlled trials (RCTs). Methods: RCTs that evaluated the efficacy of myo-inositol in improving pregnancy rate and regulation of menstrual cycle in women with PCOS. Electronic databases were searched and studies published up to October 24, 2021 were included in the systematic review and meta-analysis. Study selection and assessment of quality were conducted independently by two review authors. Results: Seven studies with 729 patients treated with myo-inositol and 677 patients treated with placebo and/or metformin were included in the analysis. The research groups did not diverge significantly in terms of basic characteristics, such as age, adnexal or uterine pathology, body mass index, and duration of infertility. In the myo-inositol group, regulation of the normal menstrual cycle is at 20%, significantly higher than the metformin group at 12%, (p&lt;0.001). However, there is no significant difference in the pregnancy rate between myoinositol and placebo (p=0.42) and/or metformin (p=0.17). Conclusion: This systematic review and meta-analysis showed that myo-inositol can be an alternative treatment for PCOS in terms of regulation of menses and may improve the success of spontaneous pregnancies. However, additional randomized, double-blind controlled trials with larger sample sizes, low heterogeneity, and uniform inclusion criteria are recommended to establish the effects of myo-inositol on PCOS treatment and pregnancy rate.

Sexual Patterns, Menstrual Health Status and Prevalence of Modern Contraceptive Use Among Reproductive Aged Females in Bosnia and Herzegovina During the Covid-19 Pandemic.

Background:Nowadays, most women of reproductive age utilize various methods of contraception to avoid undesired pregnancy and regulate menstrual cycles.Objective:The aim of this study is to evaluate current sexual patterns, menstrual health status and use of contraceptive methods in reproductive aged females in Bosnia and Herzegovina during the COVID-19 pandemic.Methods:This cross-sectional study was conducted in the period between February 21st and March 5th 2022 via an online anonymous questionnaire which was distributed using social media platforms.Results:Menstrual periods were normally regular in 269 (85.7 %) of the females, whereas 45 (14.3 %) experienced irregular menstrual cycles. Females report having either one sexual partner 149 (47.5%) or no sexual partners 76 (24.2%) and typically no 92 (29.3%) or frequent (more than 8 sexual intercourses) sexual intercourses per month. The usage of contraceptive methods was reported among the majority 212 (67.5%) and mostly by using of male condom 104 (33.1%), followed by the withdrawal method 64 (20.4%), oral contraceptive pills 35 (11.1%), emergency contraceptive pills “after 24h” 2 (0.6%) and intrauterine device 7 (2.2%). The usage of contraceptive methods was higher among younger females (X2=18.07, p<0.001) and among those who were employed (X2=10.86, p<0.001). Those who used oral contraceptive pills used mostly pills that are combination of progesterone and oestrogen 32 (91.4%) and for the purpose of regulation of menstrual cycles 26 (74.2%) and to prevent unwanted pregnancies 9 (25.8%). Females who had no sexual intercourses per month (OR+0.27, 95% CI 0.09-0.79, p=0.018) were less likely, while those who had irregular menstrual cycles (OR=2.44, 95% CI 1.04-5.71, p=0.039) were more prone to use oral contraceptive pills.Conclusion:Bosnia and Herzegovina reproductive aged female had relatively regular menstrual cycles, the majority used modern contraceptive methods to prevent unwanted pregnancies or for the regulation of menstrual cycles during the COVID-19 pandemic.

Factors Affecting Menstrual Cycle Developmental Trajectory in Adolescents: A Narrative Review.

ContextThe time interval between the age at menarche and regulation of menstrual cycles (menstrual cycle developmental trajectory) is considered an indicator of the function of the reproductive system later in life. This study aimed to summarize the factors affecting this trajectory.Evidence AcquisitionA comprehensive literature search in PubMed, Scopus, Google Scholar, and Web of Science was performed to identify studies investigating factors influencing the regularity of the menstrual cycle in adolescents.ResultsThe interval between menarche and the onset of the regular menstrual cycle in adolescent girls may vary from several months to several years. Several factors, including genetic, race/ethnicity, intrauterine situation, social factors, geographical factors, lifestyle, and chronic diseases, are considered the predisposing factors for the trajectory.ConclusionsAge at menarche and the onset of regular menstrual cycles are directly and indirectly influenced by several genetic, environmental, and lifestyle factors. Understanding these factors may improve our practice in managing irregular menstrual cycles that commonly happen in the first years after menarche.

Sexual Patterns, Menstrual Health Status and Prevalence of Modern Contraceptive Use Among Reproductive Aged Females in Bosnia and Herzegovina During the Covid-19 Pandemic

Background: Nowadays, most women of reproductive age utilize various methods of contraception to avoid undesired pregnancy and regualte menstrual cycles. Objective: The aim of this study is to evaluate current sexual patterns, menstrual health status and use of contraceptive methods in reproductive aged females in Bosnia and Herzegovina during the COVID-19 pandemic. Methods: This cross-sectional study was conducted in the period between February 21st and March 5th 2022 via an online anonymous questionnaire which was distributed using social media platforms. Results: Menstrual periods were normally regular in 269 (85.7 %) of the females, whereas 45 (14.3 %) experienced irregular menstrual cycles. Females report having either one sexual partner 149 (47.5%) or no sexual partners 76 (24.2%) and typically no 92 (29.3%) or frequent (more than 8 sexual intercourses) sexual intercourses per month. The usage of contraceptive methods was reported among the majority 212 (67.5%) and mostly by using of male condom 104 (33.1%), followed by the withdrawal method 64 (20.4%), oral contraceptive pills 35 (11.1%), emergency contraceptive pills “after 24h” 2 (0.6%) and intrauterine device 7 (2.2%). The usage of contraceptive methods was higher among younger females (X2=18.07, p&lt;0.001) and among those who were employed (X2=10.86, p&lt;0.001). Those who used oral contraceptive pills used mostly pills that are combination of progesterone and oestrogen 32 (91.4%) and for the purpose of regulation of menstrual cycles 26 (74.2%) and to prevent unwanted pregnancies 9 (25.8%). Females who had no sexual intercourses per month (OR+0.27, 95% CI 0.09-0.79, p=0.018) were less likely, while those who had irregular menstrual cycles (OR=2.44, 95% CI 1.04-5.71, p=0.039) were more prone to use oral contraceptive pills. Conclusion: Bosnia and Herzegovina reproductive aged female had relatively regular menstrual cycles, the majority used modern contraceptive methods to prevent unwanted pregnancies or for the regulation of menstrual cycles during the COVID-19 pandemic.

Analysis of the mechanism of menstrual cycle regulation based on “pivotal movement”

Based on Huang Yuan-Yu's theory of "pivotal movement", the mechanism of menstrual regulation in women of childbearing age was investigated. It is suggested that the spleen-liver-rush-rush-uterus is the key axis of menstrual regulation in women of childbearing age, and the existing theory that the kidney-tiankui-rush-rush-uterus is the main axis of menarche and menopause in women.

Roles of Nitric Oxide in the Regulation of Reproduction: A Review.

Nitric oxide (NO) has attracted significant attention as a stellar molecule. Presently, the study of NO has penetrated every field of life science, and NO is widely distributed in various tissues and organs. This review demonstrates the importance of NO in both male and female reproductive processes in numerous ways, such as in neuromodulation, follicular and oocyte maturation, ovulation, corpus luteum degeneration, fertilization, implantation, pregnancy maintenance, labor and menstrual cycle regulation, spermatogenesis, sperm maturation, and reproduction. However, the mechanism of action of some NO is still unknown, and understanding its mechanism may contribute to the clinical treatment of some reproductive diseases.

Efficacy of myo-inositol and d-chiro-inositol combination on menstrual cycle regulation and improving insulin resistance in young women with polycystic ovary syndrome: A randomized open-label study.

To compare the effect of myo-inositol and d-chiro-inositol in combination (MI+DCI) with combined hormonal contraceptive (CHC) on menstrual cycle regulation in young Indian women with polycystic ovary syndrome (PCOS). Seventy young women with PCOS aged 15-24years with delayed cycles were randomized into two groups and were treated for 6months with MI+DCI (550+150mg, 3.6:1 ratio) twice a day and CHC (ethinyl estradiol 20µg+drospirenone 3mg) once a day. Spontaneous menses resumed in 28 (84.85%) young women on MI+DCI, compared with withdrawal bleeding in 34 (100%) on CHC. The mean cycle length reduced with both MI+DCI (124.54±8.08 to 57.75±3.00days, P<0.001) and CHC (105.88±7.96 to 30.53±2.95days, P<0.001). Regular menstrual cycles were established in 9 (27.27%) young women with MI+DCI (P=0.001) and 30 (88.23%) with CHC (P<0.001). Three months after stopping the treatment, 24 young women (85.71%) on MI+DCI and 25 (73.53%) on CHC continued to have spontaneous cycles. Anti-Müllerian hormone decreased with both the drugs (P=0.001), whereas luteinizing hormone (P=0.001) and testosterone (P=0.04) decreased with CHC and homeostatic model assessment of insulin resistance (P<0.001) with MI+DCI. Myo-inositol and d-chiro-inositol in combination (3.6:1 ratio) are effective in regularizing menstrual cycles and improving insulin resistance. Clinical Trials Registry of India (CTRI/2018/03/012643). http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=20969&EncHid=&userName=myo-inositol.

Therapeutic Effect of Vitamin D3 Supplementation to Clomiphene Citrate Resistant PCOS Women: A Randomized Controlled Trial

Abstract Background Polycystic ovary syndrome (PCOS) is considered one of the most common endocrine disorders affecting females in their reproductive age. In PCOS, an imbalance between androgens, anti-Müllerian hormone (AMH) and follicle stimulating hormone (FSH), cause a halt of follicular growth. Insulin resistance (IR) is another important component of PCOS. There is increasing evidence that vitamin D affects insulin and glucose metabolism, Vitamin D plays a vital role in the regulation of glucose-insulin homeostasis. Objectives to assess the efficacy of vitamin D supplementation in improving ovulation induction in PCOS women (1ry outcome) and increasing pregnancy rate (secondary outcome). Patients and Methods 120 women diagnosed PCOS according to Rotterdam criteria and were resistant to CC treatment were randomly allocated into equal two groups: Group V: number of 60 patients received cholecalciferol + Metformin for 2 months. Group C: 60 patients received Metformin 2 months. After two months from the start:Both study groups started induction with Clomiphene Citrate added every month starting from the 3rd month to the 5th month (3 cycles of ovulation induction) in addition to previous drugs mentioned. Results In our study results, regulation of menstrual cycle occured in 63.6% of women who recieved vitamin D + metformin (group V) and ovulation was confirmed in 34.5% of the total number (55 women). Later, 18% of them got pregnant after 3 months of treatment. Added to that 16 women out of 39 (41%) got pregnant by the end of the follow up period with cumulative pregnancy rate (53%). On the other hand menstrual regularity in (group C: metformin) recorded 61% with ovulation percentage of 26.9% (n = 54). Followed by 14.8% pregnancy rate at the 3rd month., which increased to 27.5% by the end of the study out of 47.5% ovulated women (n = 40). Cumulative pregnancy rate 40%. Conclusion From the current study we can conclude that there is no significant difference of adding vitamin D to CC resistant PCOS regarding ovulation and pregnancy rates. However, it can augment metformin action and improves its outcome.

The Role of Low Dosage Combined Oral Contraceptive Pill in Perimenopausal Women

The perimenopausal period refers to the time period of the menstrual cycle and endocrine changes. Usually, it starts with a variation in the menstrual cycle length and ending with FMP. The rates of unwanted pregnancies for these women are reported to be around 40–45%. Thus, contraceptive counselling and contraceptive use among perimenopausal women are important aspects of their overall health care if they are sexually active and do not wish to become pregnant. One of them is by using low dose combined oral contraceptive pill containing ethynylestradiol (EE) containing less than 50 µg EE/day. It acts by supressing gonadotropin. There are several positive effects of COC, namely pregnancy prevention; regulation of menstrual cycle; relieving menopausal symptoms; bone protection; protection against ovarian, endometrial and colorectal cancer; lipid metabolism; and blood pressure lowering effect. In contrast, the negative effects of COC are increases the risk of breast cancer, venous thromboembolism, and myocardial infarction. We presented a literature review to describe the usage of low dosage combined oral contraceptive pill as one of contraception method in perimenopausal women, including its positive and negative effects.

Impact of bariatric surgery on androgen profile and ovarian volume in obese polycystic ovary syndrome patients with infertility.

Obesity has major adverse effects on reproductive performance and fertility potential especially in women with polycystic ovary syndrome. In this study, we aimed to evaluate the consequences of excess weight reduction by bariatric surgery on androgen levels, and ovarian volume by ultrasonography in obese polycystic ovary patients. This one year Cohort study was carried out in Zagazig university hospitals. The study included 36 infertile women with PCOS and obesity, who underwent bariatric surgery(sleeve gastrectomy or gastric bypass). Patients were evaluated for free and total serum testosterone levels, Sex hormone binding globulin (SHBG), free androgen index (FAI) and also ovarian volume by ultrasound pre-operatively, 6 months and 1 year after surgery. The results showed significant reduction in Body Mass Index, free and total serum testosterone levels and rise in SHBG and regulation of menstrual cycle at 6 and 12 months after operation. Free androgen index and ovarian volume by ultrasound also significantly decreased (p < 0.001) .As a conclusion, Bariatric surgery results in durable loss of weight and restores the normal physiological balance of androgenic milieu and ovarian morphology by ultrasound, in infertile women who have Polycystic ovary syndrome.

Factors affecting the choice of drospirenone as the component of combined contraceptive pill in daily clinical practice: the results of nation-wide survey.

The aim of the multicenter, open-label, post-marketing, observational survey was to assess doctors' preferences in choosing the progestogen component of the combined contraceptive pill (CCP) and factors affecting this choice in daily clinical practice as well as non-contraceptive reasons use of CCP containing drospirenone (CCPD) and patients' tolerance and satisfaction with the treatment. This multicenter, open-label, post-marketing, survey was performed nation-wide with the participation of 222 doctors involving and 10,345 patients treated with CCPD. The study questionnaire included questions concerning factors affecting the choice of drospirenone as a component of CCP and assessing prescription pattern of the drug as well as tolerance and satisfaction with the use of CCPD. The doctors frequently declared their choice of drospirenone as the progestogen component of CCP. The most important factors affecting the choice of drospirenone, declared by doctors, were tolerance level, consistent regulation of menstrual cycle and not causing spotting. CCPD was prescribed to patients with irregular menstrual cycles (62.7%) and painful menstruation (46.8%). During follow-up, significantly increased percentage of patients assessed the tolerance of treatment with CCPD as very good (52.5% vs 68.0%; p < 0.01) and very satisfied with its use (61.9% vs 77.8%, p < 0.01). 1) Drospirenone is frequently chosen progestogen component in CCP by Polish gynecologists due to its good tolerance, consistent regulation of the menstrual cycle and no spotting in patients opinion. 2) CCPD was most frequently used in patients with irregular menstrual cycles and painful menstruation. 3) The patients were satisfied with the use CCPD and treatment was well tolerated.