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Aims: Insulin-like peptide 5 (INSL5) plays an important part in metabolic processes in vitro and in vivo. We hypothesized that INSL5 levels are associated with the presence of polycystic ovary syndrome (PCOS) and insulin resistance (IR)., Methods: Circulating INSL5 levels were measured by an enzyme-linked immunosorbent assay in the PCOS group (n = 101) and control (n = 78) groups. The relationship between INSL5 and IR was evaluated by using regression models., Results: The levels of circulating INSL5 were elevated in the individuals with PCOS (P < 0.001) and significantly associated with homeostasis model assessment of insulin resistance (HOMA-IR, r = 0.434, P < 0.001; HOMA-IS, r = 0.432, P < 0.001; QUICKI, r = -0.504, P < 0.001). The subjects in the highest tertile of INSL5 levels were more likely to have PCOS (odds ratio: 12.591, 95 % confidence interval 2.616-60.605) as compared with the lowest tertile after adjustment for potential confounders. Furthermore, the multiple linear regression analyses after adjustment for confounders showed an independent association between INSL5 levels and HOMA-IR (β = 0.024, P < 0.001)., Conclusions: Circulating INSL5 concentration is linked to PCOS, possibly through increased insulin resistance., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To investigate the efficacy of oral letrozole (LE) starting on day 3 or 5 of the menstrual cycle in patients with polycystic ovary syndrome (PCOS)., Design: Retrospective cohort study., Setting: Reproductive Endocrinology Department of Hangzhou Women's Hospital., Methods: In this retrospective analysis, we analyzed patients who received oral LE for ovulation induction (OI) at the Hangzhou Women's Hospital from January 2016 to January 2021. In total, 539 PCOS patients with fertility requirements were classified into the D3 group and D5 group according to the different starting times of oral LE, that is, from the 3rd or 5th day of the menstrual cycle or LE is taken orally for 5 days starting on day 3 or 5 of progesterone withdrawal bleeding. Treatment started with one tablet (LE 2.5 mg), continue the regimen from the previous cycle in non-responders and continued until pregnancy or for up to three ovulatory cycles, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. The primary outcome was to compare ovulation rates, conception rates, live birth rates, pregnancy complications, and pregnancy outcomes at different initiation times., Results: Women who started LE on the 5th day of their menstrual cycle had more cumulative conception rates than those who started LE on the 3rd day(173 of 228[75.9%] vs . 201 of 311[64.6%], P= 0.005; rate ratio for conception, 1.174; 95% confidence interval,1.052 to 1.311) without significant differences in overall live birth rate, though there were 142 of 228[62.3%] in the D5 group versus 172 of 311[55.3%] in the D3 group (P= 0.105). The median (IQR) endometrial thickness was significantly (P = 0.013) greater during the D5 group treatment compared to the D3 group, which may be related to higher conception and clinical pregnancy rates. The median (IQR) maximum follicle diameter was not statistically (P = 0.073) different between the two groups. The cumulative ovulation per cycle rate was higher with D5 than with D3 (287 of 405 treatment cycles [70.9%] vs . 388 of 640 treatment cycles [60.6%], P=0.001). There were no significant between-group differences in pregnancy loss (31 of 173 conceptions in the D5 group [17.9%] and 29 of 201 conceptions in the D3 group [14.4%]) or multiples pregnancy (8.2% and 10.5%, respectively). Rates of other adverse events during pregnancy were similar in the two treatment groups., Conclusion: As compared with D3 group, D5 group was associated with higher ovulation and conception rates, shorter time-to-pregnancy among infertile women with the PCOS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shi, Ye, Gao, Chen, Jin and Zhang.)

Background: Insulin-like peptide 5 (INSL5) is involved in both reproductive and metabolic processes in polycystic ovary syndrome (PCOS). This study aimed to evaluate the relationship between INSL5 and anti-Müllerian hormone (AMH)., Methods: A retrospective case-control study was conducted in a university-based reproductive centre between December 2019 and January 2021. We included 117 women with PCOS and 100 healthy subjects from Zhejiang Province. All subjects were divided into four groups (1st-4th) based on quartiles of serum INSL5 levels. Serum INSL5 concentration was assayed using an enzyme-linked immunosorbent assay., Results: A significant direct association was observed between serum INSL5 and AMH levels in women with PCOS. The mean AMH level in the 1st-4th INSL5 level quartiles were 4.64, 5.20, 6.46, and 9.48 ng/ml, respectively (P < 0.001). After adjusting for age, body mass index, metabolic indices, and serum levels of oestradiol and total testosterone, AMH levels remained positively and significantly associated with INSL5 levels (P for trend < 0.001). The diagnostic value of AMH was better than that of INSL5., Conclusions: INSL5 and AMH levels were significantly correlated and elevated in women with PCOS. INSL5 and AMH might be associated with increased androgen secretion and chronic anovulation in PCOS., (© 2022. The Author(s).)

Polycystic ovary syndrome (PCOS) is associated with low-grade chronic inflammation. This was a retrospective case-control study. In the present study, the risk coefficients of neutrophil to lymphocyte ratio (NLR), high-sensitive C-reactive protein (hs-CRP), and mean platelet volume (MPV) in obese patients with PCOS were determined. This study was designed to investigate NLR, hs-CRP, and MPV levels in 68 obese patients with PCOS and 44 nonobese patients with PCOS, and our study group was matched with 47 obese and 43 nonobese controls, respectively. PCOS group had higher MPV, NLR, insulin, glucose, and HOMA-IR rates than those of the controls. Subgroup analyses revealed that the obese PCOS group had higher NLR, hs-CRP, and MPV levels compared to those of controls. The obese PCOS group had higher NLR, hs-CRP, and MPV levels compared to those of the nonobese PCOS group. The odds ratios and 95% confidence intervals of those variables (NLR, hs-CRP, MPV) were found significant (P < .05). NLR, hs-CRP, and MPV variables were found statistically significant in the analysis of receiver operating characteristics. Our study demonstrated that NLR, hs-CRP, and MPV levels are increased in patients with obese PCOS., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Several published articles have investigated the association between the -174 G/C (rs1800795) polymorphism in the interleukin-6 (IL-6) gene and the risk of polycystic ovary syndrome (PCOS). However, the results were inconsistent. In the present study, a meta-analysis was performed to resolve this inconsistency., Methods: Eligible studies reporting an association between the IL-6 rs1800795 polymorphism and PCOS susceptibility were included from PubMed, Embase, Web of Science, and the Cochrane Library up to December 1, 2017. The odds ratio (OR) with the 95% confidence interval (CI) was used to calculate the strength of the associations. Publication bias detection was conducted using Begg test. We used STATA 11.0 software to perform the statistical analyses., Results: Six articles detailing case-control studies were included, reporting a total of 512 cases and 606 controls. The meta-analysis results indicated that rs1800795 was associated with decreased PCOS susceptibility in the overall population under the allelic model (G vs. C, OR = 0.59, 95% CI: 0.41-0.85, P = .005), the homozygous model (GG vs. CC, OR = 0.45, 95% CI: 0.28-0.73, P = .001), heterozygous model (GG vs. CG, OR = 0.50, 95% CI: 0.26-0.95, P = .036), and the dominant model (GC + CC vs. GG, OR = 0.48, 95% CI: 0.26-0.89, P = .020). However, a threshold P value of .05 was found under the recessive model (CC vs. GG + CG, OR = 0.62, 95% CI: 0.39-1.00)., Conclusions: This meta-analysis concluded that IL-6 rs1800795 polymorphism has a decreased association with PCOS risk among all populations studied. The results suggested that the IL-6 rs1800795 polymorphism is a protective factor for PCOS susceptibility. Given the limited ethnic groups and sample size, further studies are required to validate the association.

An increasing number of studies have reported that microRNAs (miRNAs) have an important role in polycystic ovary syndrome (PCOS). Downregulation of miR-206 in patients with PCOS has been found, however, its specific role remains unclear. The present study aimed to investigate the roles of miR-206 in (PCOS) and to determine the underlying molecular mechanisms. Reverse transcription-quantitative PCR (RT-qPCR) was performed to analyze the expression levels of miR-206 in normal ovarian surface epithelial IOSE80 cells and human ovarian granulosa cell-like KGN cells. TargetScan was used to predict the target gene of miR-206, which was subsequently verified using a dual-luciferase reporter gene assay. The mRNA expression levels of cyclin D2 (CCND2) and the transfection efficiencies of the miR-206 mimic and CCDN2 overexpression plasmid were determined using RT-qPCR analysis. The protein expression levels of CCND2, cleaved-caspase-3 and pro-caspase-3 were analyzed using western blotting, and an MTT assay and flow cytometric analysis were used to evaluate the cell viability and levels of apoptosis, respectively, in the cells following transfection. Finally, the activity of caspase-3 was analyzed using a caspase-3 activity assay kit. The results of the present study revealed that the expression levels of miR-206 were downregulated in KGN cells compared with IOSE80 cells. CCND2 was predicted and verified to be a direct target gene of miR-206, and the mRNA and protein expression levels of CCND2 were discovered to be upregulated in KGN cells compared with IOSE80 cells. The miR-206 mimic and CCND2 overexpression plasmid significantly upregulated the expression levels of miR-206 and CCND2, respectively, in KGN cells. The miR-206 mimic also downregulated the expression levels of CCND2 in KGN cells, while this effect was reversed following the transfection with the CCND2 overexpression plasmid. Compared with the mimic control group, the miR-206 mimic significantly decreased the cell viability, induced the levels of apoptosis, increased the activity of caspase-3, upregulated cleaved-caspase-3 protein expression levels and downregulated pro-caspase-3 protein expression levels in KGN cells following transfection; these effects were reversed following the overexpression of CCND2. In conclusion, the findings of the present study suggested that miR-206 may serve an important role in PCOS through modulating ovarian granulosa cell viability and apoptosis. [ABSTRACT FROM AUTHOR]