Polycystic Ovary Syndrome and the Role of Metformin in Ovulation Induction

The Polycystic Ovary Syndrome (PCOS) is frequently associated with comorbidities such as obesity, reduced glucose tolerance, hypertension, macrovascular disease and dyslipidemia. The Metabolic syndrome occurs in 30% of women with PCOS. Metformin has increasingly been used in this therapy due to its effects in reducing insulin resistance. Treatment of PCOS aims to reduce the symptoms of hyperandrogenism, regularize the menstrual cycle, reduce metabolic abnormalities, and lower the risk of type 2 diabetes mellitus and of cardiovascular disease. Additionally it is important to prevent hyperplasia and endometrial cancer, and to offer contraception to those who do not wish pregnancy, and to help to induce ovulation to those who do. The effectiveness of metformin in this treatment is assessed in the light of the current best evidence.

Polycystic Ovary Syndrome (PCOS) and Fertility

The polycystic ovary syndrome (PCOS) is defined as a combination of hyperandrogenism (hirsutism and acne) and anovulation (oligomenorrhea, infertility, and dysfunctional uterine bleeding), with or without the presence of polycystic ovaries on ultrasound. It represents the main endocrine disorder in the reproductive age, affecting 6% - 15% of women in menacme. It is the most common cause of infertility due to anovulation, and the main source of female infertility. When in the presence of a menstrual disorder, the diagnosis of PCOS is reached in 30% - 40% of patients with primary or secondary amenorrhoea and in 80% of patients with oligomenorrhea. PCOS should be diagnosed and treated early in adolescence due to reproductive, metabolic and oncological complications which may be associated with it. Treatment options include drugs, diet and lifestyle improvement.

The Effect of Balanced Hypocaloric Diet on the Anthropometric and Basic Metabolic Indicators in Infertile Women with Gluteofemoral Obesity

Purpose: To evaluate the effect of balanced hypocaloric diet therapy on the anthropometric and basic metabolic indicators in obese women with infertility. Methods: The follow up interventional clinical study included 23 infertile women in reproductive age with grade I gluteofemoral obesity. All patients have prescribed a balanced hypocaloric diet (1200 kcal/day), underwent exercise and behavioral therapy. Before and after 12-month treatment, an anthropometric study was conducted, determining the level of metabolic and hormonal indicators. Results: The total final number of study participants was 20 patients. A decrease in body weight was achieved in 87% of patients from 4 to 24 kg, on the average, by 10.58 ± 5.70 kg, there was also a decrease in BMI from 32.53 ± 1.40 to 28.55 ± 2.50 kg/m2 (p 0.001). The decrease in body weight was accompanied by a statistically significant decrease in leptin levels (p 0.001), E1 (p = 0.049), E2 (p = 0.032), fasting glucose (p 0.001), HOMA-IR (p = 0.002), cholesterol (p < 0.001), TG (p = 0.004), LDL-C (p = 0.001), atherogenic index of plasma (p <0.001) and an increase in progesterone levels (p = 0.030). Ovulatory menstrual cycles were resumed in all women (p = 0.007) and pregnancy occurred within a year in 1 patient. Conclusion: The implementation of a hypocaloric diet for 12 months in infertile women with first-degree obesity helps to normalize metabolic and hormonal indicators, reduces body weight and restores ovulatory menstrual cycle in all patients.

Polycystic Ovarian Syndrome and Female Infertility

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, associated with chronic anovulation and hyperandrogenism. The cause of PCOS is multi-factorial and the mechanism is still unclear. A number of complications are closely related with PCOS such as infertility, hairy and obesity. Approximately up to one-third of females with PCOs have issues with infertility. Obesity is an independent factor which exacerbates infertility in PCOS, reduces the efficacy of infertility treatment and provokes a greater risk of miscarriage. Preconception counseling and guidelines play an initial major role in infertility treatment. The option of the most appropriate treatment depends upon various factors such as age, tubal patency, quality of sperm, experience, and duration of previous treatments and the level of anxiety of the couple. Tubal patency test and semen analysis are mandatory to decide the suitable treatment. Treatment modalities have two measures—non-pharmacological and the pharmacological. Oral clomiphene citrate remains the first line treatment to trigger ovulation. Gonadotrophin and laparoscopic ovarian drilling (LOD) surgery are the other treatment option. In vitro fertilization (IVF) and embryo transfer are the third line treatment and IVF remains the first option in the patient with diagnosed and established bilateral tubal occlusion and/or concentration of recovered motile sperm less than or equal to 5 million. Here, etiology, pathophysiology and molecular mechanisms of PCOS are reviewed, and perspectives are given for further research. The recent development, treatment, and diagnosis of PCOS are also highlighted. The summary will be of guiding significance in the prevention and treatment of PCOS.

An overview of the physiopathology and various treatment strategies for polycystic ovary syndrome

Polycystic ovary syndrome(PCOS),a common endocrine disorder with metabolic and reproductive consequences,affects a significant percentage of women of reproductive age.Because of its complexity and impact on the quality of life,PCOS requires timely diagnosis and screening for complications.The most common clinical manifestations of PCOS are hirsutism,hyperandrogenism,acne,irregular cycles,amenorrhea,and anovulation.Although PCOS has different clinical manifestations in women,hyperandrogenism,and anovulation are the most common symptoms.A good medical history,examination,blood tests,and ultrasound findings facilitate the diagnosis of PCOS.Novel treatments have also undergone clinical trials to improve the symptoms of PCOS.However,comprehensive review articles investigating the different communities of this disease are limited,and this review aimed to collect data on the different etiologies of PCOS along with the latest diagnostic methods and the most common and up-to-date treatments for this disease.

Drug discovery and potential gene and pathway associated with polycystic ovary syndrome through text mining and biomedical databases

Objectives:Polycystic ovary syndrome(PCOS)is a common endocrine disease in women of childbearing age.Although it is a leading cause of menstrual disorders,infertility,obesity,and other diseases,its molecular mechanism remains unclear.This study aimed to analyze the target genes,pathways,and potential drugs for PCOS through text mining.Methods:First,three different keywords("polycystic ovary syndrome","obesity/adiposis",and"anovulation")were uploaded to GenCLiP3 to obtain three different gene sets.We then chose the common genes among these gene sets.Second,we performed gene ontology and signal pathway enrichment analyses of these common genes,followed by protein-protein interaction(PPI)network analysis.Third,the most significant gene module clustered in the protein-protein network was selected to identify potential drugs for PCOS via gene-drug analysis.Results:A total of 4291 genes related to three different keywords were obtained through text mining,72 common genes were filtered among the three gene sets,and 69 genes participated in PPI network construction,of which 23 genes were clustered in the gene modules.Finally,six of the 23 genes were targeted by 30 existing drugs.Conclusions:The discovery of the six genes(CYP19A1,ESR1,IGF1R,PGR,PTGS2,and VEGFA)and 30 targeted drugs,which are associated with ovarian steroidogenesis(P<0.001),may be used in potential therapeutic strategies for PCOS.

Identifying miRNA biomarkers of polycystic ovary syndrome through text mining

Objective:Polycystic ovary syndrome(PCOS)is an endocrine disorder with diverse clinical manifestations that often occurs in women of childbearing age.However,its molecular pathogenesis remains unclear,and this study aimed to identify miRNA targets in PCOS through text mining and database analysis.Methods:First,three different sets of text mining genes(TMGs)associated with"polycystic ovary syndrome","obesity/adiposis",and"anovulation"keywords were retrieved from the GenCLiP3 database,and overlapping genes were selected.Second,Gene ontology annotation and biological pathway enrichment analyses of these overlapping TMGs were performed,followed by protein-protein interaction(PPI)network analysis.Third,genes in the gene module clustered in the PPI were selected to predict potential miRNAs for PCOS via miRNA-mRNA analysis.Results:A total of 4291 TMGs related to three different keywords were obtained through text mining;72 intersect TMGs were retained among the three gene sets,and 62 TMGs participated in the establishment of the PPI network,of which 18 were aggregated in the gene module.Finally,11 miRNAs that simultaneously bound to two TMGs(IGF1,ESR1,MAPK1,NAMPT,PIK3CA,and SERPINE1)could be prioritized as targets to study PCOS.Conclusion(s):The discovery of 11 miRNAs(miR-301a-3p,miR-301b-3p,miR-3666,miR-454-3p,miR-130a-3p,miR-130b-3p,miR-4295,miR-190a-3p,miR-5011-5p,miR-548c-3p,and miR-4799-5p)and 6 TMGs,which are associated with the HIF-1 signaling pathway(P=4.799E-08),could be used as potential targets for PCOS.

Treatment of anovulatory infertility with acupuncture and Chinese herbal medicine

Objective To observe the therapeutic effects on anovulatory infertility with acupuncture and Chinese herbal medicine. Methods Fifty patients with anovulatory infertility were divided randomly into 2 groups with 25 in the observation group and 25 in the control group. Both herbal decoctions and acupuncture treatment were applied to the observation group. For Chinese herbal medicine, according to different phases of menstrual cycle, Cu Luanpao Tang （促卵泡汤 follicle promote decoction）, Cu Pailuan Tang （促卵泡汤 ovulation induce decoction） and Cu Huangti Tang （促黄体汤 corpora luteum promote decoction） was given to the patients; and acupoints such as Guanyuan （关元 CV 4）, Zhongji （ 中极 CV 3） and LuSnchao Xue（卵巢穴 Extra point） were selected. The control group was asked to take Clomiphene as well as Chorionic Gonadotropin （HCG） injection. Observation is undertaken continuously for 6 cycles, and statistics of ovulation rate and pregnancy rate were collected. Results There were no statistical significance of difference of ovulation rate between the two groups（P〉0.05） ; the pregnancy rate of the observation group is 44. 0%（11/25）, which is obviously higher than 16.0% （4/25） of the control group （P〈0.05）. Comparison was made on Insler score of the cervical mucus and thickness of the endometrium between the 2 groups, and the result showed that both of the indexes of the observation group were better than those of the control group （P〈0.05, P〈0.01）. Conclusion Both of the methods, namely ovulation induction with acupuncture and herbal decoctions and with Clomiphene and HCG injection, are effective for enhancing the ovulation rate, while the former one is better than the later one in the pregnancy rate.

LHCGR and ALMS1 defects likely cooperate in the development of polycystic ovary syndrome indicated by double-mutant mice

Polycystic ovary syndrome(PCOS)is a heterogeneous disorder with evidence of polygenetic components,and obesity may be a risk factor for hyperandrogen ism.Previous studies have shown that LHCGR is en riched in the ovary and LHCGR deficiency causes infertility without typical PCOS phenotypes.ALMS1 is implicated in obesity and hyperandrogenism,the common phenotypes among PCOS patients.Through whole-exome sequencing of 22 PCOS families and targeted candidate gene sequencing of additional 65 sporadic PCOS patients,we identified potential causative mutations in LHCGR and ALMS1 in a sibling-pair PCOS family and three sporadic PCOS patients.The expression of LHCGRL638 P in granulosa-like tumor cell line(KGN)cells promoted cyclic adenosine monophosphate production and granulosa cell proliferation,indicating that LHCGRL638 P is an activating mutation.Lhcgr~(L642 P/L642 P)mice showed an irregular estrous cycle,reduced follicles with dynamic folliculogenesis,and increased testosterone(T),estradiol(E2),and dehydroepiandrosterone.Lhcgr~(+/L642 P)AIms1~(+/PB)mice displayed increased T and E2 but decreased late secondary and preovulatory follicles.We showed that activating mutation of LHCGR likely plays important roles in the pathophysiology of PCOS involving abnormal reproductive physiology,whereas ALMS1 deficiency may promote anovulatory infertility via elevated androgens,suggesting that the disturbed LHCGR and ALMS1 cooperatively induce PCOS phenotypes,characterized as anovulation and hyperandrogenemia frequently observed in PCOS patients with obesity.

Distinctive Genes Involved in Steroidogenesis Associated with Follicular Abnormal Development in Polycystic Ovary Syndrome Model

Objective:Polycystic ovary syndrome(PCOS),a heterogeneous endocrine disorder,affects female reproductive function,but its etiology has not been elucidated.In this study,we analyzed the differential genes related to ovarian steroid biosynthesis in patients with PCOS,to explore the mechanism of PCOS.Methods:The GSE59456 data were downloaded from the Gene Expression Omnibus database.We identified differentially expressed genes(DEGs)in ovaries between the female Sprague-Dawley rats those implanted with 5α-dehydrotestestrone(DHT)and those in control(CTL,implanted with empty capsule).Gene ontology,pathway enrichment analysis,and protein-protein interaction(PPI)network construction were subsequently performed.Results:In total,530 upregulated DEGs and 522 downregulated DEGs were identified.The identified DEGs were mostly associated with steroid biosynthesis.In the PPI network,the module M1 was mainly related to steroid biosynthesis,and five genes(Hsd17b7,Tm7sf2,Idi1,Msmo1,and Sqle)of the module M1 were from the aforementioned group of upregulated genes.Furthermore,the 19 DEGs(Idi1,Cga,C1qb,Thy1,Gpx1,Ctss,Lpl,A2m,Cited2,Plppr4,Prkar2b,Slc44a1,Inha,Rbp4,Pla2g2a,Gata4,Fabp3,Cpa2,and Cpa1)between DHT and CTL groups were associated with the process of the transformation of primordial follicles to primary follicles.Conclusions:These DEGs,such as Hsd17b7,Tm7sf2,Idi1,Msmo1,Sqle,Rbp4,Gata4,Inha,and Cited2,may be used to elucidate the etiology of PCOS,which may provide new insights into the exploration of pathological mechanism and biomarkers for polycystic ovary.