Infertile Polycystic Ovary Syndrome Research Articles

Comparison of Various Therapeutic Approaches to Manage Infertility in Polycystic Ovarian Syndrome.

To compare the efficacies of common therapeutic regimens and their combinations, used in polycystic ovarian syndrome (PCOS) to improve fertility in reproductive-age women. A descriptive study. Place and Duration of the Study: Department of Obstetric Gynaecologist, Medicare Cardiac and General Hospital, Karachi, Pakistan, from November 2022 to July 2023. Out of 300 patients with the symptoms of menstrual irregularities and infertility, 152 were diagnosed as PCOS patients based on the ultrasound and hormonal assays and selected for study purpose. They were divided according to their therapeutic regimen into four treatment groups, treated by different therapeutic agents. Group A received metformin 500 mg/day (n = 38); Group B received metformin + myo-inositol 1g (n = 49); Group C received metformin + letrozole 2.5 mg (n = 36), and Group D received metformin + letrozole + myo-inositol (n = 29), orally for three months. All continuous variables, such as body mass index (BMI), FSH, LH, FT4, and FSI were analysed by applying t-test to all therapeutic groups, keeping p ≤0.05 as the level of significance. HCG-positive was found as 86% (n = 33) in Group A, 63% (n = 31) in Group B, 52% (n = 19) in Group C, and 27% (n = 08) in Group D. There were statistically significant (p <0.001) changes in BMI, FSH, LH, FT4, and FSI as well. Metformin alone and metformin plus myo-inositol came out to be more effective than other regimens. Metformin alone and myo-inositol plus metformin are effective therapeutic options in PCOS-induced infertility problems. Polycystic ovarian syndrome, Infertility, Metformin, Myo-inositol, Letrozole, Menstrual irregularities.

The effect of coenzyme Q10 intake on metabolic profiles in women candidates for in-vitro fertilization: a randomised trial

Objective: Infertility and the pathogenesis of polycystic ovarian syndrome (PCOS) are both influenced by insulin resistance and dyslipidemia. Presumably, adding coenzyme Q10 (CoQ10) to these patients’ diets will be beneficial. Therefore, this study aimed to examine the effects of CoQ10 supplementation on metabolic profiles in women candidates for in-vitro fertilization (IVF). Trial design and methods: For this randomized, double-blinded, parallel, placebo-controlled clinical experiment, 40 PCOS-positive infertile women who were IVF candidates were included. They ranged in age from 18 to 40. The 20 participants in the two intervention groups received either CoQ10 or a placebo for 8 weeks. The expression of glucose transporter 1 (GLUT-1), peroxisome proliferator-activated receptor gamma (PPAR-γ), low-density lipoprotein receptor (LDLR), as well as metabolic profiles such as insulin metabolism and lipid profiles were evaluated. Quantitative RT-PCR determined the expression of GLUT-1, PPAR-γ, and LDLR on peripheral blood mononuclear cells. Lipid profiles and fasting glucose were assessed using enzymatic kits, and insulin was determined using Elisa kit. Results: In comparison to the placebo, CoQ10 supplementation significantly reduced blood insulin levels (−0.3±1.0 vs. 0.5±0.7, P=0.01) and insulin resistance (−0.1±0.2 vs. 0.1±0.2, P=0.01), and increased PPAR-γ expression (P=0.01). In infertile PCOS patients’ candidates for IVF, CoQ10 supplementation showed no appreciable impact on other metabolic profiles. Also, CoQ10 supplementation revealed no significant impact on GLUT-1 (P=0.30), or LDLR (P=0.27) expression. Within-group changes in insulin levels (P=0.01) and insulin resistance (P=0.01) showed a significant elevation in the placebo group. When we adjusted the analysis for baseline BMI, baseline values of variables, and age, our findings were not affected. Conclusions: Eight weeks of CoQ10 supplementation demonstrated positive benefits on PPAR-γ expression, insulin resistance, and serum insulin in infertile PCOS women candidates for IVF.

Metabolic landscape and pathogenic insights: a comprehensive analysis of high ovarian response in infertile women undergoing in vitro fertilization.

In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients' unique serum metabolic profiles and provide insights into the disease's pathogenesis. We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-Müllerian Hormone (AMH) levels > 4.5ng/mL. The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR. Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes.

Letrozole and Clomiphene Compared With Letrozole Alone for Ovulation Induction in Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis [ID 2683666

INTRODUCTION: Nearly 70% of patients with polycystic ovary syndrome (PCOS) have anovulatory infertility. One therapeutic option is letrozole; however, its comparative efficacy and safety when compared with the association of letrozole and clomiphene citrate are unclear. Therefore, we aimed to compare letrozole and the combined use of letrozole and clomiphene citrate for ovulation induction in PCOS. METHODS: We systematically searched EMBASE, PubMed, and Cochrane databases for randomized controlled trials (RCTs) and observational studies comparing letrozole and clomiphene citrate versus letrozole alone in patients with PCOS. The primary endpoints rate of mature follicles and ovulation were calculated via a random-effects meta-analysis. Statistical analysis was performed using RevMan 5.4.1. Heterogeneity was assessed with I2 statistics and random-risk effect was used. RESULTS: Two RCTs and one observational study comprising 223 patients (mean age, 28.7 years; 49.3% combined therapy) were included. The combined therapy was associated with a higher number of women with mature follicles (&gt;15 mm) (odds ratio [OR] 2.94; 95% CI, 1.66–5.21; P=.0002; I2=0) and ovulations (OR 3.31; 95% CI, 1.91–5.73; P&lt;.0001; I2=0). There was no significant difference between groups in the number of pregnancies and thickness of the endometrial lining. Adverse events, including headache, abdominal bloating, fatigue, back pain, breast discomfort, and night sweats, were similar between groups. CONCLUSION: In women with PCOS and anovulatory infertility, letrozole and clomiphene citrate combined therapy promoted a significant benefit for the maturation of follicles and ovulation, with a similar safety profile compared to letrozole alone.

Progestin Primed Ovarian Stimulation with Dydrogesterone as an Oral Alternative to the Conventional GnRH Antagonist Protocol in Infertile PCOS Women Undergoing IVF: A Retrospective Study in Egypt

Progestin Primed Ovarian Stimulation with Dydrogesterone as an Oral Alternative to the Conventional GnRH Antagonist Protocol in Infertile PCOS Women Undergoing IVF: A Retrospective Study in Egypt

Comparative analysis of conventional in vitro fertilization and intracytoplasmic sperm injection in patients with polycystic ovarian syndrome, tubal factor infertility, and unexplained infertility whose partners exhibit normal semen parameters: a retrospective study of sibling oocytes.

This study compared the outcomes of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in patients with polycystic ovarian syndrome (PCOS), tubal factor (TF) infertility, and unexplained infertility whose partners had normal semen parameters. This retrospective study included 360 couples diagnosed with infertility involving PCOS (n=157), unexplained infertility (n=140), and TF infertility (n=63). Sibling oocytes were randomly assigned to undergo ICSI or conventional IVF insemination. The fertilization rate and embryo morphology were evaluated as outcomes. Retrieved cumulus-oocyte complexes from patients with PCOS (2,974), unexplained infertility (1,843), and TF infertility (844) were split and inseminated by conventional IVF and ICSI respectively. In comparison to the ICSI method, the conventional IVF approach was linked to a significantly higher fertilization rate in groups with PCOS (68.81% vs. 77.49%), unexplained infertility (67.62% vs. 78.84%), and TF issues (69.23% vs. 78.63%) (p<0.05). The proportion of embryos with grade A produced by the conventional IVF method was significantly higher than that produced using the ICSI method in the PCOS and unexplained infertility groups (p<0.05). Additionally, the percentage of grade B embryos produced with the ICSI method was significantly higher than that produced with the conventional IVF method in PCOS patients (p=0.002). Our results indicated that the conventional IVF method was associated with higher zygote production and a higher proportion of grade A embryos when all infertile groups were evaluated together. Thus, ICSI is not suggested for patients with these causes of infertility if their partner has normal semen parameters.

Vitamin D, anti-Mullerian hormone and glycemic status in infertile polycystic ovarian syndrome (PCOS), infertile non PCOS and fertile non PCOS at Mediheal Fertility Center - Western Kenya

Background: Diabetes of the bearded women was first described by Achard and Theirs in 1921 and since then insulin resistance and hyperinsulinemia in women with polycystic ovary syndrome (PCOS) remains one of the commonest metabolic problems. Insulin resistance and type II diabetes mellitus occurs in 70% of women with PCOS. The mechanism of insulin resistance has not been well established and inconsistent study results have complicated treatment modalities and management of insulin resistance and PCOS in general. There is evidence that 80% of women with PCOS are deficient in Vitamin D and this could be the missing link between Vitamin D and insulin resistance.&#x0D; Objective: To determine the correlation of Vitamin D, AMH and glycemic status in infertile PCOS, infertile non PCOS patients and fertile non PCOS attending Mediheal Fertility Center in Western Kenya as there is dearth of such studies within Kenyan population.&#x0D; Methods: A case control design with 20 patients per group for infertile PCOS, infertile non PCOS and fertile non PCOS which served as normal controls. Quantification of HbA1c was done at AMPATH reference laboratories using fluorescence immunoassay while Vitamin D and AMH was done at MTRH laboratories using ECLIA Roche. Data was analyzed using Statistical Package for Social Sciences (SPSS) version 25.&#x0D; Results: The mean HbA1c and median serum AMH in infertile PCOS, infertile non PCOS and infertile non PCOS were 6.1±0.4 and 7.5(6.2, 11.1), 5.5±0.3, and (1.2, 4.4), 5.6±0.3 and 2.0(1.7, 2.3) respectively. The study revealed statistically significant increase in HbA1c and serum AMH in infertile PCOS as compared to infertile non PCOS and fertile non PCOS (F=15.7, p&lt;0.001 and F=46.7, p&lt;0.001) respectively. In addition, Vitamin D was significantly deficient among infertile PCOS versus infertile non PCOS and fertile non PCOS (F=41.8, p&lt;0.001).&#x0D; Conclusion: Infertile patients with PCOS have deficiency in Vitamin D and increase in HbA1c and AMH hence there might be a link of Vit D and AMH in pathophysiology of insulin resistance among PCOS patient

Knowledge graph construction based on granulosa cells transcriptome from polycystic ovary syndrome with normoandrogen and hyperandrogen

PCOS is a widespread disease that primarily caused in-pregnancy in pregnant-age women. Normoandrogen (NA) and Hyperandrogen (HA) PCOS are distinct subtypes of PCOS, while bio-markers and expression patterns for NA PCOS and HA PCOS have not been disclosed. We performed microarray analysis on granusola cells from NA PCOS, HA PCOS and normal tissue from 12 individuals. Afterwards, microarray data were processed and specific genes for NA PCOS and HA PCOS were identified. Further functional analysis selected IL6R and CD274 as new NA PCOS functional markers, and meanwhile selected CASR as new HA PCOS functional marker. IL6R, CD274 and CASR were afterwards experimentally validated on mRNA and protein level. Subsequent causal relationship analysis based on Apriori Rules Algorithm and co-occurrence methods identified classification markers for NA PCOS and HA PCOS. According to classification markers, downloaded transcriptome datasets were merged with our microarray data. Based on merged data, causal knowledge graph was constructed for NA PCOS or HA PCOS and female infertility on NA PCOS and HA PCOS. Gene-drug interaction analysis was then performed and drugs for HA PCOS and NA PCOS were predicted. Our work was among the first to indicate the NA PCOS and HA PCOS functional and classification markers and using markers to construct knowledge graphs and afterwards predict drugs for NA PCOS and HA PCOS based on transcriptome data. Thus, our study possessed biological and clinical value on further understanding the inner mechanism on the difference between NA PCOS and HA PCOS.

Evaluation of effectiveness of Letrozole in treatment of infertility in women with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disease, characterized by hyperandrogenism, oligomenorrhea, and polycystic ovaries. PCOS is one of the most causes that affect the women of childbearing age, and often leads to infertility. Various managements were proposed for infertile women with PCOS. However, the optimal management option has not been addressed satisfied. Although multiple treatments including weight reduction, clomiphene citrate, metformin, gonadotropins, and ovary cauterization have been reported to treat such condition, the efficacy still has insufficient evidence to support. Objectives: Purpose of this study was to evaluate the effectiveness of Letrozole in treatment of infertility in women with polycystic ovary syndrome. Materials &amp; method: This study was carried out to assess the effectiveness of letrozole and on pregnancy outcomes including the ovulation induction, pregnancy rate, and endometrial thickness in infertile women with polycystic ovarian syndrome (PCOS). Total 106 infertile PCOS patients were recruited and allocated in two groups, Group-L (received letrozole at 2.5 mg twice daily on the 3rd–5th days of menstrual cycle for 5 consecutive days), Group-G 75 U/d−1 gonadotropin through intramuscular injection for 5 days starting from the third day of menstrual cycle). All patient in both arm completed treatment and follow-up. Patients in both groups were treated up to 5 treatment cycles. During follow up, transvaginalultrasonogram (TVS) was performed to see the details of the follicles and the endometrium. Data was processed and analysed with the help of computer program SPSS and Microsoft excel. Quantitative data expressed as mean and standard deviation and qualitative data as frequency and percentage. Comparison was done by tabulation and graphical presentation in the form of tables, pie chart, graphs, bar diagrams, histogram &amp; charts etc. Result: Mean age of the patient was 26.3 ± 5.7 years in group-L and 25.9 ± 6.1 years in group-G. There were no statistical significant differences between the 2 groups regarding age, body weight, height, body mass index (BMI). Present study results showed that patients who received letrozole exert better outcomes in primary endpoint, including ovulation rate (86.7% in group-L &amp; 62.2% in group-G, P =0.004), endometrial thickness (9.3 ± 1.1 mm in group-L &amp; 8.5 ± 1.1 mm in group-G, P = 0.003) and pregnancy rate (64.1% in group-L &amp; 30.1% in group-G, P =0.005). Abortion rate (till the end of 12th week) and multiple pregnancy rate were higher in group-G, but result were non-significant in between groups. Live birth rate in the letrozole group was higher 29(54.7%) than group-G 14(26.4%), the difference was statistically significant (P &lt; .05). Conclusion: Patients who took Letrozole had significantly higher endometrial thickness than other group. Due to the higher pregnancy rate and lower incidence of abortion or multiple pregnancy, letrozole can be an effective for the treatment of anovulatory subfertility of the PCOS patients. Central Medical College Journal Vol 7 No 1 January 2023 Page: 13-19

Progesterone-Primed Ovarian Stimulation might be a Safe and Effective Alternative to GnRH-antagonist Protocol for Controlled-Ovarian Stimulation of Infertile PCOS Women

Progesterone-Primed Ovarian Stimulation might be a Safe and Effective Alternative to GnRH-antagonist Protocol for Controlled-Ovarian Stimulation of Infertile PCOS Women

Comparison between Letrozole with and without Gonadotropins Injection on Pregnancy Rates in Infertile PCOS Patients: A Multicenter Randomized Observational Trial

Comparison between Letrozole with and without Gonadotropins Injection on Pregnancy Rates in Infertile PCOS Patients: A Multicenter Randomized Observational Trial

#226 : Comparison of Letrozole vs Letrozole Plus Metformin as First Line Ovulation Induction Drug for Infertile PCOS Women

Background: Letrozole is currently considered as first line ovulation induction drug in anovulatory PCOS women. Insulin sensitizers like Metformin have a proven role as an adjuvant to improve ovulatory function in resistant PCOS women. Letrozole and Metformin combined as first line ovulation induction option has not been studied much, neither has been compared to other options. Objective: The aim of this study was to compare Letrozole plus Metformin vs Letrozole alone as first line ovulation induction drug in treatment naive infertile PCOS women. Materials &amp; Methods: 125 PCOS patients with anovulatory infertility were randomized by a computer generated randomization list to receive either Letrozole 5 mg from day 3-7 of menses plus Metformin daily (65 patients,150 cycles, Group I) or Letrozole 5mg/day from day 3-7 (60 patients, 121 cycles, Group II). The primary outcome studied was live birth rates and the secondary outcomes reported were ovulation rate, mono / multifollicular development, endometrial thickness, pregnancy rates, abortion and twinning rates. Results: Live birth rate was 33.8% in group I and 45.8% in group II (p=0.17) which was not statistically significantly different. The ovaluation rate was 85.9% and 86.7% (P=0.85) respectively. Multi follicular ovulation was slightly more in Group 2 (38.6% vs 48.1%). Conclusion: There was no significant benefit of adding Metformin to Letrozole as first line ovulation induction drug in terms of live birth rate or ovulation rates.

Myo-inositol versus metformin effects on clinical features, endocrine and metabolic profiles in infertile women with polycystic ovary syndrome: A randomized controlled trial

Objective: To compare the effectiveness of inositol and metformin on the clinical characteristics, and endocrine and metabolic profiles of infertile polycystic ovarian syndrome (PCOS) women from Vietnam. Methods: From June 2018 to August 2022, a randomized trial was undertaken at the Hue Center for Endocrinology and Reproduction on infertile women aged 18 to 40 years with polycystic ovarian syndrome. The clinical, endocrine, and metabolic features of these individuals were assessed before and after 3 months of treatment with 2 g of inositol or 1700 mg of metformin per day. Natural pregnancy rates, adverse effects, and tolerance of inositol were recorded. Results: The study included 171 infertile PCOS women who were eligible to participate and took part in the baseline assessment, of whom 132 women participated in data analysis after 3 months. After metformin treatment, 42.1% of women with oligomenorrhea experienced regular menstruation. Metformin significantly lowered body mass index (BMI), waist circumference and testosterone levels, but had no effect on other clinical characteristics, endocrine profiles, or metabolic profiles. 29.2% Of women reported experiencing side effects. 21% Of them attained pregnancy, which resulted in 17.1% of live births. In the inositol group, the rate of regular cycle increased by 18.2% and the total testosterone concentration significantly decreased. In overweight/obese women with PCOS, inositol significantly decreased weight, BMI, waist and hip circumferences (P&lt;0.05). 100% Of women tolerated inositol and continued treatment. 18.9% Of them became pregnant, leading to 17% of live births. Conclusions: Metformin and inositol can improve weight and waist circumference in overweight/obese infertile women with PCOS. Metformin is associated with a higher rate of regular menstruation, whereas inositol is associated with a lower rate of adverse effects. The spontaneous conception, clinical pregnancy, and live birth rates between two groups are comparable.

Retracted: Higher Chronic Endometritis Incidences within Infertile Polycystic Ovary Syndrome Clinical Cases

Retracted: Higher Chronic Endometritis Incidences within Infertile Polycystic Ovary Syndrome Clinical Cases

Estimation of Fibulin-1, Chemerin and Omentin-1 in Iraqi Women with Polycystic Ovary Syndrome-Associated Infertility

Background: Adipokines (fibulin-1, chemerin, and omentin-1) affect the hypothalamic-pituitary-gonadal axis and ovarian steroidogenesis. Adipocyte-secreted adipokines are dysregulated in females with polycystic ovarian syndrome (PCOS). Objective: To investigate the role of serum fibulin-1, chemerin, omentin-1, total cholesterol (TC), high-density lipoprotein (HDL), triglyceride (TG), progesterone (PROG), and prolactin (PRL) in PCOS and the development of infertility. Methods: 150 PCOS, infertile PCOS women and control women aged 20–40 years were enrolled in this observational study and divided into three groups: 40 women who were control, 60 women who had PCOS only, and 50 women who had infertility and PCOS. Analyses of fibulin-1, chemerin, omentin-1, lipid profile, PROG, and PRL were performed for all participants. Results: The results showed elevated levels of fibulin-1, chemerin, and PRL in both PCOS and infertile PCOS when compared with control, while omentine-1 and PROG decreased in both PCOS and infertile PCOS when compared with control. The levels of TC, HDL, and TG weren’t affected in PCOS alone, but in cases of infertility, TC and TG increased while HDL decreased. Conclusions: The increased level of fibulin-1 may be a new marker for PCOS and infertility. Chemerin shows a high level in both infertile PCOS and PCOS women, while omentin-1 shows a low level in both infertile PCOS and PCOS women.

Endometrial changes in Infertile Women with Polycystic Ovary Syndrome after taking Letrozole in Comparison to Clomiphene Citrate

Background: The endometrium is a receptor organ for most of the hormones involved in fertility and therefore the study of its morphology is thought to explain the mysteries of implantation failure. Many studies showed that Clomiphene Citrate impairs endometrial development due to antiestrogenic effects and long half-life. Conversely Letrozole shows a positive effect on follicle and endometrium. Objective: To assess the endometrium in infertile Polycystic Ovary Syndrome women by Transvaginal Sonography after giving ovulation induction by Clomiphene Citrate versus Letrozole. Materials and Methods: This Comparative cross-sectional study was conducted on sixty diagnosed Polycystic Ovary Syndrome infertile women in the Reproductive Endocrinology &amp; Infertility Unit of Dhaka medical College Hospital, Dhaka, from January 2021 to December 2021. The patients who took Letrozole is called Letrozole group and who took Clomiphene citrate is called Clomiphene citrate group. Serial folliculometry were done to every patient from Day 7. At day 12, the patients were assessed by Transvaginal Sonography for endometrial study. The hyporesponsive and non-responsive patients took higher dose of clomiphene citrate or letrozole in next cycle and serial folliculometry were done as before. Endometrial thickness, pattern and zone of vascularity was compared between the two groups. Preovulatory S. Estradiol was done in case of optimum response. All the relevant data were collected in a predesigned and pretested case record form. Data was processed and analyzed with the help of the computer program SPSS in version 26. Results: Clomiphene Citrate and Letrozole achieved optimum response in 15(50%) and 21(70%) patients, respectively. The Letrozole group had a significantly greater endometrial thickness than the Clomiphene Citrate group (8.85±1.33 vs.7.37±1.07, p=0.001s). Moreover, the Letrozole group showed a greater number of triple line endometrium (76.2% vs 60.0%, p=0.298ns), grade A (42.9% vs 26.7%, p=0.500 ns ) and Zone 3 vascularity (33.3%vs 22.2%, p=0.325 ) than the clomiphene citrate group. Conclusion: Letrozole induces significantly better endometrial development in terms of endometrial thickness than clomiphene citrate. Bangladesh J Obstet Gynaecol, 2022; Vol. 37(1): 5-13

Effect of Letrozole and Clomiphene Citrate versus Letrozole Alone for Ovulation Induction in Women with Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterized by oligo-ovulation or anovulation signs of androgen excess and multiple small ovarian cysts. It is thought to be one of the leading causes of female sub-fertility. It has been estimated that PCOS affects 5-10% of females in reproductive age. In this study, we used combination of letrozole and clomiphene vs letrozole alone in ovulation induction in infertile PCOS women. Objective: The objective of the study was to compare the effectiveness of the combination of letrozole and clomiphene citrate and letrozole alone in ovulation induction in infertile women with PCOS. Methods: Randomized controlled trial conducted in the Department of Reproductive Endocrinology and Infertility, Bangabandhu Sheikh Mujib Medical University, Dhaka, from July 2020 to June 2021. A total of 50 women 18-40 years of age with a diagnosis of infertility and PCOS as defined by the Rotterdam criteria and no other known cause of infertility were included in this study. Participants were randomly assigned into two groups by using a computer-generated random table to either 5 mg letrozole alone or the combination of 2.5 mg letrozole and 50 mg CC daily on cycle days 3-7 for two treatment cycle. Statistical analysis was performed by the SPSS program for Windows, version 22.0. Main outcome measured by number &amp; size of mature follicles, endometrial thickness, day 21 serum progesterone &amp; ovulation rate in both groups. The secondary outcome includes pregnancy rate and complication of both treatment arms. Results: Regarding demographic criteria, there was no significant difference between two groups. In the current study, clinical characteristics, laboratory parameters and cycle characteristics were also comparable to both groups and showed no significant difference. Dominant follicles were found 24(52.2%) in group A (CC+Letrozole) and 29(63.0%) in group B (Letrozole Alone) without any significant difference. Mono follicular development was found 18(75.0%) in group A and 24(82.8%) in group B which was not statistically significant. Endometrial thickness and serum progesterone level at 1st and 2nd cycle were not statistically significant between two groups (p&gt;0.05). Ovulation rate was higher in group B than group A (76.0% vs 72.0%) with absolute difference 4.0 and relative ratio 0.95. Pregnancy rate was also higher in group B than group A (24.0% vs 16.0%) with absolute difference 8.0 and relative ratio 0.67. Ovulation and pregnancy rate were not statistically significant between two groups. Regarding side effects, no significant difference was found between two groups. Conclusion: Although it was not statistically significant, ovulation and pregnancy rate was a little higher in alone letrozole group than combined group. The results of this preliminary study suggested that letrozole may have a better role as a first-line treatment for anovulatory patients with PCOS.

Live Birth Outcomes for PCOS Patients Under the Follicular-Phase Long-Acting GnRH Agonist Protocol or Antagonist Protocol - A Retrospective Chinese Cohort.

For patients with polycystic ovary syndrome (PCOS) to undergo in vitro fertilization (IVF) and embryo transfer (ET), there has been no consensus regarding which protocol is the most optimal for live birth rate in fresh cycles. We sought to evaluate depot gonadotropin-releasing hormone (GnRH) agonist protocol versus GnRH antagonist protocol in IVF outcomes for PCOS patients in a single fertility center. In this retrospective cohort, PCOS patients who visited the Second Hospital of Hebei Medical University reproductive center between February 2012 and December 2019 were screened, and 533 PCOS infertility patients were included undergoing their first IVF cycle, with 470 in the depot GnRH agonist group and 63 in the GnRH antagonist group. The primary of this study outcome was the fresh live birth rate (LBR). PCOS women in the depot GnRH agonist group had a higher LBR (49.79%) than those in the GnRH antagonist group (34.92%, p = 0.027). The multivariable logistic regression also confirmed that women in the depot GnRH agonist group had a higher LBR than those in the GnRH antagonist group (OR = 1.83, 95% CI 1.05~3.18, p = 0.032). After propensity score matching (PSM), the LBR in the depot GnRH agonist group was higher (50.32%) than that of the GnRH antagonist group (35.48%), p = 0.033. The ovarian hyperstimulation syndrome (OHSS) rates were similar between the two groups, with 35 in the depot GnRH group and 6 in the GnRH antagonist group (p = 0.561). For PCOS patients in fresh embryo transfer cycles, the depot GnRH agonist protocol may lead to a higher LBR than the antagonist protocol with satisfied lower OHSS rates.

Cluster analysis reveals a homogeneous subgroup of PCOS women with metabolic disturbance associated with adverse reproductive outcomes.

Polycystic ovarian syndrome (PCOS) is a heterogeneous and complex reproductive endocrinological disease that could lead to infertility. There were many attempts to classify PCOS but it remains unclear whether there is a specific subgroup of PCOS that is associated with the best or worst reproductive outcomes of assisted reproductive techniques (ART). Infertile PCOS patients who underwent their first cycle of in vitro fertilization (IVF) in West China Second University Hospital, Sichuan University from January 2019 to December 2021 were included. Basic clinical and laboratory information of each individual were extracted. Unsupervised cluster analysis was performed. Controlled ovarian stimulation parameters and reproductive outcomes were collected and compared between the different clusters of PCOS. Our analysis clustered women with PCOS into "reproductive", "metabolic", and "balanced" clusters based on nine traits. Reproductive group was characterized by high levels of testosterone (T), sex hormone-binding globulin (SHBG), follicular stimulation hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH). Metabolic group was characterized by high levels of body mass index (BMI), fasting insulin, and fasting glucose. Balanced group was characterized by low levels of the aforementioned reproductive and metabolic parameters, except for SHBG. Compared with PCOS patients in reproductive and balanced clusters, those in metabolic cluster had lower rates of good quality day 3 embryo and blastocyst formation. Moreover, PCOS patients in the reproductive cluster had greater fresh embryo transfer (ET) cancelation rate and clinical pregnancy rate after fresh ET than metabolic cluster (odds ratio [OR] = 3.37, 95% confidence interval [CI]: 1.77-6.44, and OR = 6.19, 95% CI: 1.58-24.24, respectively). And compared with PCOS of metabolic cluster, PCOS of balanced cluster also had higher chance for fresh ET cancelation (OR = 2.83, 95% CI: 1.26-6.35). Our study suggested that PCOS patients in metabolic cluster may be associated with adverse reproductive outcomes and might need individualized treatment and careful monitoring before and during ART.

Individualized lifestyle intervention in PCOS women (IPOS): a study protocol for a multicentric randomized controlled trial for evaluating the effectiveness of an individualized lifestyle intervention in PCOS women who wish to conceive

BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine condition which affects women in the reproductive age group. South Asian women with PCOS have a higher risk of insulin resistance and metabolic disorder compared to women from other ethnic backgrounds. Lifestyle interventions such as dietary advice and physical exercise are recommended as a first-line management option for infertile women with PCOS. Most of the randomized controlled trials evaluating the role of lifestyle interventions in infertile PCOS women were characterized by methodological issues. The uptake of lifestyle modifications as a treatment strategy in the South Asian population is complicated by a difficult-to-change conventional high-carbohydrate diet and limited availability of space for physical activity in the region.MethodsThe study is designed as an open-label, multicentre, randomized controlled trial in South Asian women with PCOS. Women attending the fertility clinic will be screened for eligibility, and women aged between 19 and 37 years who have been diagnosed with PCOS and wishing to conceive will be invited to participate in the trial. We will include women with body mass index (BMI) between ≥ 23 and ≤ 35 kg/m2 and duration of infertility ≤ 3 years. We plan to randomize women with PCOS into two groups: group A will receive the intervention which will consist of individualized advice on diet and physical exercise along with a telephonic reminder system and follow-up visits, and group B (control) will receive one-time advice on diet and physical exercise. Both groups will receive up to three cycles of ovulation induction with letrozole after 3 months of randomization during the 6-month treatment period. The primary outcome of the trial will be the live birth following conception during the intervention period. The secondary outcomes include clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, ectopic pregnancy rate, stillbirth, time to pregnancy, mean weight loss, differences in anthropometric parameters, improvement in menstrual regularity and quality of life score.DiscussionThe IPOS trial results could help clarify and provide more robust evidence for advocating an individualized lifestyle intervention in PCOS women who wish to conceive.Trial registrationClinical Trial Registry of India CTRI/2023/04/051620. Registered on 13 April 2023.