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Reproductive Biology and Endocrinology... Nov 2023Polycystic ovary syndrome (PCOS) is a heterogeneous functional endocrine disorder associated with a low-grade, chronic inflammatory state. Patients with PCOS present an... (Review)
Review
Polycystic ovary syndrome (PCOS) is a heterogeneous functional endocrine disorder associated with a low-grade, chronic inflammatory state. Patients with PCOS present an increased risk of metabolic comorbidities and often menstrual dysregulation and infertility due to anovulation and/or poor oocyte quality. Multiple mechanisms including oxidative stress and low-grade inflammation are believed to be responsible for oocyte deterioration; however, the influence of nitric oxide (NO) insufficiency in oocyte quality and ovulatory dysfunction in PCOS is still a matter for debate. Higher production of superoxide (O) mediated DNA damage and impaired antioxidant defense have been implicated as contributory factors for the development of PCOS, with reported alteration in superoxide dismutase (SOD) function, an imbalanced zinc/copper ratio, and increased catalase activity. These events may result in decreased hydrogen peroxide (HO) accumulation with increased lipid peroxidation events. A decrease in NO, potentially due to increased activity of NO synthase (NOS) inhibitors such as asymmetric dimethylarginine (ADMA), and imbalance in the distribution of reactive oxygen species (ROS), such as decreased HO and increased O, may offset the physiological processes surrounding follicular development, oocyte maturation, and ovulation contributing to the reproductive dysfunction in patients with PCOS. Thus, this proposal aims to evaluate the specific roles of NO, oxidative stress, ROS, and enzymatic and nonenzymatic elements in the pathogenesis of PCOS ovarian dysfunction, including oligo- anovulation and oocyte quality, with the intent to inspire better application of therapeutic options. The authors believe more consideration into the specific roles of oxidative stress, ROS, and enzymatic and nonenzymatic elements may allow for a more thorough understanding of PCOS. Future efforts elaborating on the role of NO in the preoptic nucleus to determine its influence on GnRH firing and follicle-stimulating hormone/Luteinizing hormone (FSH/LH) production with ovulation would be of benefit in PCOS. Consequently, treatment with an ADMA inhibitor or NO donor may prove beneficial to PCOS patients experiencing reproductive dysfunction and infertility.
Topics: Female; Humans; Polycystic Ovary Syndrome; Luteinizing Hormone; Anovulation; Nitric Oxide; Follicle Stimulating Hormone; Reactive Oxygen Species; Hydrogen Peroxide; Infertility; Oxidative Stress
PubMed: 37996893
DOI: 10.1186/s12958-023-01159-6 -
Journal of Ovarian Research Nov 2023The prolactin receptor gene (PRLR) may contribute to polycystic ovarian syndrome (PCOS) since it plays important roles in physiological ovarian functions. PRLR-knockout...
The prolactin receptor gene (PRLR) may contribute to polycystic ovarian syndrome (PCOS) since it plays important roles in physiological ovarian functions. PRLR-knockout mice have irregular cycles and subfertility and variants in or around the PRLR gene were associated in humans with female testosterone levels and recurrent miscarriage. We tested 40 variants in the PRLR gene in 212 Italian families phenotyped by type 2 diabetes (T2D) and PCOS and found two intronic PRLR-variants (rs13436213 and rs1604428) significantly linked to and/or associated with the risk of PCOS. This is the first study to report PRLR as a novel risk gene in PCOS. Functional studies are needed to confirm these results.
Topics: Humans; Female; Animals; Mice; Polycystic Ovary Syndrome; Receptors, Prolactin; Prolactin; Diabetes Mellitus, Type 2; Infertility; Hyperandrogenism
PubMed: 37993904
DOI: 10.1186/s13048-023-01280-5 -
Journal of Ovarian Research Nov 2023The objective of this study is to investigate the effects of an ethanolic extract derived from Agaricus subrufescens on rat models exhibiting Polycystic Ovarian Syndrome...
OBJECTIVE
The objective of this study is to investigate the effects of an ethanolic extract derived from Agaricus subrufescens on rat models exhibiting Polycystic Ovarian Syndrome (PCOS) induced by Letrozole.
METHODS
A total of thirty female Wistar rats were divided into five groups, each consisting of six rats. The negative control group was administered a volume of 1 mL of a 0.5% solution of carboxy methylcellulose (CMC). Letrozole (1 mg/kg) was administered to additional groups for a duration of 21 days in order to induce polycystic ovary syndrome (PCOS). Animals designated as positive controls were euthanized on the 22nd day. Both the test group and the standard group were subjected to treatment from the 22nd day to the 36th day. The experimental group was administered ethanolic extract of Agaricus subrufescens at doses of 200 mg/kg and 400 mg/kg p.o, while the control group received clomiphene citrate at a dose of 1 mg/kg. The study observed various physiological markers in individuals with polycystic ovarian disease, including estimated blood glucose levels, total cholesterol levels, triglyceride levels, and hormonal fluctuations such as increased testosterone and estrogen levels, as well as decreased progesterone levels. The presence of menstrual irregularities was confirmed through the examination of vaginal smears and histopathological changes in the ovaries.
RESULTS
The consumption of Agaricus subrufescens was found to have a significant impact on various physiological parameters, including blood glucose levels, testosterone levels, anovulation, and menstrual irregularity. All therapeutic interventions significantly normalized the levels of serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT). The rats with polycystic ovary syndrome (PCOS) that were induced by Letrozole exhibited increased levels of urea and creatinine. The findings of this study indicate that the administration of Agaricus subrufescens therapy has a protective effect on renal function, as evidenced by a reduction in serum levels of urea and creatinine. In rats with polycystic ovary syndrome (PCOS) induced by Letrozole, the inhibition of hepatic synthesis, promotion of ovarian follicle immaturity, and elevation of androgen secretions result in an increase in the weight of the liver and ovaries. The weight of endocrine organs exhibited a decrease across all treatment groups. The histopathological examination of PCOS specimens revealed an increased presence of cysts and theca lutein cells. The group of rats with polycystic ovary syndrome (PCOS) that did not receive treatment exhibited a higher number of cysts compared to the groups that received treatment.
CONCLUSION
This study demonstrated that the administration of Letrozole orally resulted in the development of polycystic ovarian disease. The results indicated heightened levels of blood glucose, total cholesterol, and triglycerides, as well as alterations in hormone levels such as increased testosterone and estrogen, and decreased progesterone. These hormonal changes were accompanied by menstrual irregularities, which were confirmed through the examination of vaginal smears and histopathological analysis of the ovaries in the control group with polycystic ovarian disease. The treatment groups that received Agaricus subrufescens exhibited a decrease in blood glucose, total cholesterol, and testosterone levels.
Topics: Humans; Rats; Female; Animals; Polycystic Ovary Syndrome; Letrozole; Progesterone; Blood Glucose; Creatinine; Rats, Wistar; Estrogens; Menstruation Disturbances; Testosterone; Cholesterol; Urea
PubMed: 37993900
DOI: 10.1186/s13048-023-01311-1 -
BMC Women's Health Nov 2023The aim of this study was to compare the efficacy of the combination of clomiphene citrate (CC) and letrozole to that of CC alone in inducing ovulation in infertile... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The aim of this study was to compare the efficacy of the combination of clomiphene citrate (CC) and letrozole to that of CC alone in inducing ovulation in infertile women with ovulatory dysfunction.
METHODS
A randomized controlled trial was conducted at a single academic medical center between November 2020 and December 2021. Anovulatory infertility females, aged 18 to 40, were evenly distributed by a computer-generated block of four into two treatment groups. A "combination group" received a daily dose of CC (50 mg) and letrozole (2.5 mg), while a "CC-alone group" received a daily dose of CC alone (50 mg). The study medications were administered on days 3 through 7 of menstrual cycle. The primary outcome was the ovulation rate, defined by serum progesterone levels exceeding 3 ng/mL at the mid-luteal phase. The secondary outcomes were ovulation induction cycle characteristics, endometrial thickness, conception rate, and adverse events.
RESULTS
One hundred women (50 per group) were enrolled in the study. The mean age was not significantly different in both groups: 31.8 years in the combination group and 32.4 years in the CC-alone groups (P = 0.54). The prevalence of polycystic ovary syndrome in the combination and CC-alone groups was 48% and 44%, respectively (P = 0.841). According to intention-to-treat analysis, the ovulation rates were 78% and 70% in the combination and CC-alone groups, respectively (P > 0.05). There was no significant difference in the mean endometrial thickness or the number of dominant follicles of the groups. No serious adverse events were observed in either group.
CONCLUSIONS
Our study found no significant difference between the combination of CC and letrozole and CC alone in inducing ovulation in infertile women with ovulatory dysfunction in one cycle. The small number of live births precluded any meaningful statistical analysis. Further studies are needed to validate and extend our findings beyond the scope of the current study.
TRIAL REGISTRATION
The study was registered at https://www.thaiclinicaltrials.org with the following number: TCTR20201108004 and was approved on 08/11/2020.
Topics: Pregnancy; Female; Humans; Letrozole; Infertility, Female; Fertility Agents, Female; Pregnancy Rate; Clomiphene; Ovulation Induction; Polycystic Ovary Syndrome; Live Birth
PubMed: 37964246
DOI: 10.1186/s12905-023-02773-7 -
Human Reproduction (Oxford, England) Jan 2024The potential for repeated ovulation and menstruation is thought to have provided a Darwinian advantage during the Palaeolithic. Reproductive conditions remained...
The potential for repeated ovulation and menstruation is thought to have provided a Darwinian advantage during the Palaeolithic. Reproductive conditions remained relatively stable until the pre-industrial era, characterized by late menarche, very young age at first birth, multiple pregnancies, and prolonged periods of lactational amenorrhoea. For hundreds of thousands of years, menstruators experienced few ovulatory cycles, even though they were genetically adapted to ovulate and menstruate every month. In the post-industrial era, the age at menarche gradually declined, the age at first birth progressively increased, and breastfeeding became optional and often of short duration. This created a mismatch between genetic adaptation and socio-environmental evolution, so that what was initially a probable reproductive advantage subsequently contributed to increased susceptibility to diseases associated with lifetime oestrogen exposure, such as ovarian, endometrial and breast cancer and, hypothetically, also those associated with the number of ovulatory menstruations, such as endometriosis and adenomyosis. The incidence of endometriosis shows a steep and progressive increase around the age of 25 years, but given the consistently reported delay in diagnosis, the actual incidence curve should be shifted to the left, supporting the possibility that the disease has its roots in adolescence. This raises the question of whether, from an evolutionary point of view, anovulation and amenorrhoea should not still be considered the physiological state, especially in the postmenarchal period. However, an increase in the frequency of endometriosis in recent decades has not been demonstrated, although this deserves further epidemiological investigation. In addition, as endometriosis occurs in a minority of individuals exposed to retrograde menstruation, other important pathogenic factors should be scrutinised. Research should be resumed to explore in more detail the transtubal reflux of not only blood, but also endometrial cells, and whether they are systematically present in the peritoneal fluid after menstruation. If repetitive ovulatory menstruation during the early reproductive years is shown to increase the risk of endometriosis and adenomyosis development and progression in susceptible individuals, hormonal interventions could be used as secondary prevention in symptomatic adolescents.
Topics: Pregnancy; Female; Adolescent; Humans; Adult; Endometriosis; Adenomyosis; Amenorrhea; Secondary Prevention; Menstruation
PubMed: 37951243
DOI: 10.1093/humrep/dead229 -
JCEM Case Reports Mar 2023The use of platelet-rich plasma (PRP) has become popular as an adjunct to fertility treatment for women with infertility, particularly those with low ovarian reserve and...
The use of platelet-rich plasma (PRP) has become popular as an adjunct to fertility treatment for women with infertility, particularly those with low ovarian reserve and premature ovarian insufficiency. Recent data in a polycystic ovary syndrome (PCOS) animal model demonstrated that intraovarian PRP administration improved folliculogenesis, ovarian antioxidant potential, and serum hormonal imbalance, suggesting that PRP could be considered a novel technique to alleviate PCOS-induced pathogenesis. With injection of PRP into the ovaries, it has been hypothesized that the infusion of cytokines and growth factors may exhibit a local effect that changes the expression of genes important in folliculogenesis and steroidogenesis, decreases inflammation, and partially restores normal ovarian function. This report is the first to present a case of a long-term amenorrheic woman with PCOS who has been trying to conceive, who resumed spontaneous ovulatory cycles, and had improvement in several aspects of her hormonal imbalance following intraovarian PRP administration. The purpose of this case report is to increase awareness regarding the possible benefits of intraovarian PRP injections for women with PCOS. There is a clear need for larger prospective studies to properly elucidate the effect of intraovarian PRP administration on both the reproductive and metabolic dysfunctions observed in women with PCOS.
PubMed: 37908477
DOI: 10.1210/jcemcr/luad038 -
Journal of Medicine and Life Jul 2023Female infertility is often associated with anovulatory polycystic ovary syndrome (PCOS), characterized by high serum levels of anti-Müllerian hormone (AMH)....
Female infertility is often associated with anovulatory polycystic ovary syndrome (PCOS), characterized by high serum levels of anti-Müllerian hormone (AMH). Laparoscopic ovarian drilling (LOD) is commonly used to treat PCOS, especially when drug interventions have failed. This study aimed to evaluate the response to LOD intervention in women with PCOS by assessing AMH serum levels and their ability to restore normal physiological menstrual cycle and achieve conception. Seventy-five infertile women (24-41 years old) with body mass index (BMI) ranging from 19.6-35kg/m2 were included in the study. Among them, 57 had primary infertility, and 18 from secondary infertility, with an average duration of 8.6±4.4 years. Baseline levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and AMH were measured, and post-LOD levels of LH and AMH were evaluated. Menstrual cycle regularity was evaluated before and after LOD. Baseline FSH serum level before LOD was 5.2-1.6IU/L. Following LOD, the serum levels of LH and AMH significantly decreased from 14.3±4.1 to 7.8±2.8 IU/L and from 13.7±5.9 to 7.7±3.9 IU/L, respectively (p<0.05). LOD significantly (p<0.05) decreased the menstrual cycles irregularity, such as oligomenorrhea and amenorrhea, from 55 (73.3%) to 22 (29.3%) women and from 2 (2.7%) to 0 (0%) women respectively. Moreover, regular menstrual cycles significantly (p<0.05) increased from 18 (24%) to 53 (70.7%) women. Importantly, 68% of LOD-treated women showed a significant increase in pregnancy rates, with 52.9%, 35.3%, and 11.8% achieving pregnancy within 3, 6, and 9 months after LOD, respectively (p<0.05). Moreover, spontaneous ovulation was observed in 7/75 (9.3%) women within 90 days after LOD, and 71.4% achieved pregnancy. These findings highlight the success of laparoscopic ovarian drilling as an intervention for PCOS, with AMH serving as a reliable test to assess the response to LOD treatment.
Topics: Pregnancy; Female; Humans; Young Adult; Adult; Polycystic Ovary Syndrome; Anti-Mullerian Hormone; Infertility, Female; Anovulation; Luteinizing Hormone; Follicle Stimulating Hormone; Laparoscopy
PubMed: 37900074
DOI: 10.25122/jml-2023-0067 -
Ugeskrift For Laeger Oct 2023This review describes the current evidence regarding the putative indications of letrozole (LTZ) in fertility treatment. Prior to intrauterine insemination, LTZ is... (Review)
Review
This review describes the current evidence regarding the putative indications of letrozole (LTZ) in fertility treatment. Prior to intrauterine insemination, LTZ is recommended in women with normogonadotrophic oligo-anovulation. In ovulatory women, LTZ is equal to clomiphene and may be used instead of exogenous gonadotrophin. LTZ may be used as co-treatment in poor responders prior to in vitro fertilization/intracytoplasmic sperm injection. In addition, LTZ prior to frozen-thawed embryo transfer is increasingly used in women with normogonadotrophic oligo-anovulation.
Topics: Male; Female; Humans; Letrozole; Anovulation; Fertility Agents, Female; Semen; Clomiphene
PubMed: 37873987
DOI: No ID Found -
Frontiers in Veterinary Science 2023Infertility is one of the primary factors for cattle reproduction in the present scenario. Reproduction-related immunoinfertility mainly involves immunization against... (Review)
Review
Infertility is one of the primary factors for cattle reproduction in the present scenario. Reproduction-related immunoinfertility mainly involves immunization against the antigens related to reproductive hormones (LHRH, GnRH, Gonadal steroids, PGF2α and oxytocin), spermatozoa, seminal plasma and ovum. Anovulation, delayed ovulation, sperm immobilization, failure of fertilization, prolonged uterine involution, extended calving interval, prolonged post-partum estrus and reduced conception rate could be a result of immunoinfertility that occur due to the blockage of receptor site by antibodies formed against hormones, sperm and ovum. Immunoinfertility can be treated in the animal by giving sexual rest to females, by using various reproductive technologies such as fertilization, gamete intra fallopian tube transfer, and intracytoplasmic sperm injection, sperm washing and by treating the animals with immunomodulators such as LPS, Oyster glycogen, etc. This review summarizes the different causes of bovine reproductive immunoinfertility and amelioration strategies to overcome it.
PubMed: 37869494
DOI: 10.3389/fvets.2023.1248604 -
Cureus Sep 2023Introduction Polycystic ovary syndrome (PCOS) is a frequently occurring endocrine condition prevalent in women of reproductive age characterized by chronic anovulation,...
Assessment of Cardiac Autonomic Function in Women With Polycystic Ovary Syndrome Through Ewing's Battery, Heart Rate Variability Analysis, and Composite Autonomic Symptom Score-31 Scale.
Introduction Polycystic ovary syndrome (PCOS) is a frequently occurring endocrine condition prevalent in women of reproductive age characterized by chronic anovulation, hyperandrogenism, insulin resistance, and a low-grade inflammatory state. Patients with PCOS are more vulnerable to developing cardiac and metabolic co-morbidities. Sympathetic overactivity is also reported in PCOS patients. Objective This study aimed to assess cardiac autonomic function in PCOS by Heart Rate Variability Analysis, Ewing's Test, and Composite Autonomic Symptom Scale-31 (COMPASS-31). Methods Thirty female PCOS patients and 30 age-matched control females were enrolled in the study. Both cases and controls were subdivided into sub-groups based on body mass index (BMI) and waist-to-hip ratio (WHR). The cardiac autonomic functions were assessed by the COMPASS-31 questionnaire, Ewing's battery tests, and short-term heart rate variability analysis. Results There was no significant difference in age, BMI, and WHR of both groups. Additionally, cases had a significantly higher low frequency to high frequency (LF/HF) ratio and COMPASS-31 score and also reported more derangement in Ewing's battery test, indicating cardiac autonomic dysfunction in PCOS patients. Conclusion Patients with PCOS are more prone to developing cardiac and metabolic co-morbidities. Early assessment of cardiac autonomic function can prevent future complications with timely interventions. Altered autonomic function in PCOS patients can be due to hyperandrogenism and insulin resistance.
PubMed: 37868510
DOI: 10.7759/cureus.45580