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Editorial: Polycystic ovary syndrome (PCOS): Mechanism and management

COPYRIGHT © 2022 Wang, Leung, Li, Wu and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Editorial PUBLISHED 07 October 2022 DOI 10.3389/fendo.2022.1030353

criteria in 2003 requires any two of the three criteria: hyperandrogenemia, ovulatory dysfunction, and polycystic ovaries (4,5); (iii) the AE-PCOS criteria by the Androgen Excess Society in 2006 underscores that the diagnosis is made only if they have hyperandrogenemia and either ovarian dysfunction, polycystic ovaries or both.
We asked the authors who participated in this Research Topic to consider the following questions: How to dive deep into the pathophysiology of PCOS? What are the new insights into metabolic dysfunctions, such as basal/glucose stimulated hyperinsulinemia and insulin resistance (IR), obesity, hyperandrogenism, and subfertility in PCOS? Among the repertoire of clinical management of PCOS, is there any exciting progress in pharmacological and lifestyle interventions? Is it possible to make a clinical diagnosis of PCOS through specific biomarkers? Can we effectively personalize assisted reproductive technology (ART) procedures for PCOS patients? How does PCOS influence maternal and offspring health? Why is it always associated with obstetrical complications including preeclampsia, very preterm birth (defined as <32 weeks of gestation), and gestational diabetes mellitus (GDM)? For the offspring of patients with PCOS, what symptoms are they inclined to display? What is the mechanistic role of the microbiome in PCOS? The result of this call is a relatively comprehensive collection of 33 articles regarding such aspects.

Pathophysiology of PCOS
In reports of pioneering studies, the most consistent feature of PCOS is an elevated level of testosterone and/or androstenedione in serum (6)

Maternal and offspring health of PCOS
Patients with PCOS are at risk of experiencing obstetrical complications including preeclampsia, very preterm birth, and GDM (7). Their offspring have a significantly higher risk of large for gestational age, meconium aspiration syndrome, and low Apgar scores at 5 minutes. Definitely, PCOS is a threat to maternal and child health.
The issue of cumulative live birth rate (CLBR) in PCOS is dealt with by two articles. Mai et al. demonstrate that PCOS exhibited higher CLBR and better ovarian reserve and response. When it comes to the independent variables for determining CLBR of aged patients with PCOS, this view is counter-argued by Guan et al., with a retrospective cohort study presenting significantly decreased CLBR for females of advanced reproductive age up to 37. Compared to regular menstruation or oligomenorrhea, a higher overall incidence of adverse pregnancy outcomes in PCOS patients with amenorrhea is presented by Yu et al. In addition, Du et al. point out that preterm birth in PCOS is associated with a BMI≥24 kg/m2 plus serum AMH>6.45 ng/ml. According to Jiang et al., advanced age, obesity, total cholesterol, triglycerides, and insulin resistance (IR) are all independent risk factors for a lower chance of achieving a live birth.
Two articles, by Zhang et al. and Jiang et al. respectively, focus on the health of PCOS offspring and broaden our understanding of PCOS offsprings' cardiometabolic status and autistic traits. Xie et al. have generated letrozole-induced PCOS-IR rat models and treated them with metformin. In this article, they interpret that metformin might improve obesity, hyperinsulinemia, and IR in female offspring.

Management of PCOS
As the primary treatment of metabolic dysfunction in PCOS, lifestyle interventions prevent progression to T2DM and lower cardiovascular risk as well as improve ovulation in 40-50% of patients with PCOS (8,9). Gu et al. review the current evidence of the role of lifestyle modifications in PCOS, including diet modifications, exercise modifications, sleep modifications, mood modifications, and weight modifications. A meta-analysis by Shang et al., involving 20 RCTs with 1113 participants, depicts that diet intervention significantly improves fertility outcomes, reproductive endocrine, and clinical hyperandrogenism. Shen et al. submit another meta-analysis, which regards tea supplements as adjuvant therapy for improvement in body weight, fasting blood glucose, and insulin. Through remodeling gut microbiota, Wang et al. show that a high-fiber diet could alleviate chronic metabolic inflammation, reproductive function, and brain-gut peptides secretion in their study.
Functional abnormalities of adipose tissue do exist in PCOS patients, mainly manifesting as IR and inflammation (10). As anticipated from previous reports, human PCOS patients had lower brown adipose tissue (BAT) activity (11). The BAT transplantation experiment was conducted by Yao et al., which underscores the role of metabolome changes for BAT transplantation in improving reproductive and metabolic phenotypes in PCOS. Furthermore, Ye et al. pinpoint that cold treatment could also improve ovulation and hormone disorders via activating endogenous BAT.
Sleeve gastrectomy (SG) is a popular bariatric surgical procedure. However, its suitability and potential mechanisms in PCOS remain ambiguous. Lin et al. provide a novel perspective on the regulation of microbial taxa and SCFA content after SG, which might explain the mechanism of the amelioration of PCOS-related reproductive and metabolic disorders.
Due to the poor quality of oocytes retrieved from patients with PCOS, IVF treatment is always accompanied by lowerquality embryos with a low implantation rate (12). Chen et al.
compare the implantation rate, clinical pregnancy rate, and live birth rate between progestin-primed ovarian stimulation and the short protocol. The former shows significantly more positive results.

Concluding remarks
Although a substantial fraction of information has been added to the existing pool of knowledge of PCOS in the past decades, much remains to be elucidated. We sincerely thank all contributors and reviewers for their support in putting this timely collection of articles together and hope that the readers will find useful answers to their questions.

Author contributions
YiW drafted this editorial. PL, RL, YaW and HH revised and approved the final submitted version.