Polycystic ovarian syndrome (PCOS) is a common gynecologic endocrine disorder first described by Stein and Leventhal in 1935 in 7 cases of polycystic ovarian enlargement with symptoms such as scanty menstruation or amenorrhea, chronic anovulatory infertility, hirsutism, and obesity. So far, three international diagnostic consensus have been proposed, namely the NIH criteria by the National Institutes of Health (NIH), the European Society of Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM). ESHRE and the American Society for Reproductive Medicine (ASRM) Rotterdam criteria, and the American Androgen Excess Society (AES) AES criteria. However, there is controversy as to which criteria are more appropriate for clinical application. NIH criteria: (1) sporadic ovulation or anovulation; (2) clinical and/or biochemical manifestations of hyperandrogenism; (3) exclusion of other known diseases that can cause ovulation disorders or hyperandrogenism such as hyperprolactinemia, Cushing’s syndrome, congenital adrenocortical hyperplasia, etc. This criterion focused on ovarian-derived androgen excess and its effect on ovulation, while ultrasound changes of the ovaries were not included in the criteria because of the controversy. The NIH criteria were widely used for more than 10 years afterwards and remained the criteria for case inclusion in some genetic studies until the Rotterdam meeting when the Rotterdam criteria were proposed. According to the Rotterdam Criteria, PCOS is an abnormal ovarian disease characterized by hyperandrogenism and polycystic ovary (CO). This means that the diagnosis can be established by meeting only two of the three criteria: abnormal ovarian function, hyperandrogenism and PCO. The principle conclusion of this report is that PCOS should be first and foremost an androgen excess disorder or hyperandrogenism. In the absence of clinical or biochemical androgen excess (untreated), the diagnosis of PCOS is not sufficient regardless of the presence of ovulatory dysfunction, menstrual disorders or PCO, i.e. hyperandrogenism is a necessary condition for the diagnosis, provided that one of the three conditions, menstrual disorders and PCO, is met and other conditions causing hyperandrogenism are excluded. The diagnosis of PCOS in China can only be made after medical history, physical examination, auxiliary examinations and laboratory tests. The concept of “suspected PCOS” was first introduced in the criteria. The criteria suggest that sporadic menstruation, amenorrhea or irregular uterine bleeding are necessary for the diagnosis. In addition, the diagnosis of suspected PCOS can be made by meeting one of the following two criteria: ① clinical manifestations of hyperandrogenism or hyperandrogenemia. The diagnosis of suspected PCOS can be made only after the above conditions are met and other diseases that may cause hyperandrogenism and abnormal ovulation are ruled out one by one. In addition, the diagnosis of PCOS should also take into account its staging, so that further clinical interventions can be taken accordingly. PCO) and non-hyperandrogenic PCOS (only menstrual abnormalities and PCO). Patients with classic PCOS have a more severe manifestation of metabolic disorders, while those with non-hyperandrogenic PCOS have a less severe manifestation. International consensus on the treatment of PCOS infertility In clinical work, a clear diagnosis is a prerequisite for rational treatment, while the selection of an appropriate treatment plan for clinical intervention is the ultimate goal of the practitioner. 2008 ESHRE/ASRMPCOS working group proposed a consensus based on the Rotterdam criteria, giving important recommendations on the treatment of PCOS infertility. I. Lifestyle modification The importance of pre-pregnancy counseling is often overlooked in the treatment of PCOS infertility. The purpose of pre-pregnancy counseling is to identify risk factors for infertility in women with PCOS (obesity, smoking, alcohol abuse) and to correct them prior to treatment. Its focus is primarily on the presence of obesity, especially central obesity. Obesity has been well documented to be strongly associated with anovulation, miscarriage and mid- to late-term complications of pregnancy (e.g. pre-eclampsia, gestational diabetes). Obesity is a common manifestation of PCOS and can lead to delayed or no response to treatments such as clomiphene citrate (CC), gonadotropins and laparoscopic ovarian surgery (LOS). Weight loss is therefore the treatment of choice for obese women with PCOS, facilitating infertility treatment outcomes and long-term health risk avoidance. A 5% reduction in body mass has been shown to alter menstrual cycle disturbances, clinical hyperandrogenic symptoms, and favorably impact infertility treatment outcomes. Approaches to weight loss include behavioral counseling, lifestyle modification (diet and exercise), pharmacotherapy, and surgery. However, there are no appropriate guidelines for the choice of treatment for obese PCOS, and there are no reliable data to support the effects of low-calorie diets, energy-consuming exercise, and pharmacologic treatments on live birth rates. Because the risk-benefit ratio of the effects of these interventions on pregnancy is unknown, it is recommended that weight loss should precede infertility treatment rather than coincide with it. Second, CC CC is the first choice of ovulation-promoting drug for PCOS and the first-line regimen for ovulation-promoting treatment of PCOS. Its advantages include low cost, high compliance with oral administration, low adverse effects, no need for close monitoring of ovarian response, and high safety, and its mechanism of action is mainly to inhibit the negative feedback of the hypothalamic-pituitary-gonadal axis to increase the secretion of follicle-stimulating hormone (FSH). The effects of obesity, hyperandrogenemia, age, ovarian volume and menstrual status on treatment outcome should be taken into account. The minimum dose of CC is 50 mg/d, starting on the second to fifth day of menstruation (progesterone may be used in the absence of spontaneous menstruation), and may be increased according to the ovarian response of the patient, with a maximum recommended dose of 150 mg/d. Ovarian response monitoring is not mandatory during administration, but most centers monitor the response to the drug by ultrasound and serum progesterone measurement in order to To evaluate the appropriateness of the drug dose and to guide the follow-up treatment. CC therapy is recommended for no more than 6 cycles, with data showing a cumulative live birth rate of 50%-60% within 6 cycles. Adverse effects of CC include hot flashes, headache, and visual symptoms, but are generally tolerable. Its anti-estrogenic effects may be of more concern to clinicians, but there is no evidence that the use of CC to promote ovulation affects pregnancy rates. III. Insulin sensitizers Insulin sensitizers mainly include metformin and thiazolidinediones (pioglitazone and rosiglitazone). The serious adverse effect of metformin is lactic acidosis, although it generally occurs only in people at high risk of liver and kidney impairment or congestive heart failure. Adverse effects of thiazolidinediones are hepatotoxicity and cardiovascular injury. metformin application in women with PCOS reduces fasting blood glucose levels but does not significantly improve body mass index (BMI) or waist-to-hip ratio. In terms of ovulation induction, two randomized controlled trials showed that metformin was less effective than CC alone, and the combination of CC and metformin did not result in higher live birth rates or lower miscarriage rates. However, for patients with BMI >35 kg/m2 and CC resistance, the combination of metformin helped improve treatment outcomes. And for thiazolidinediones there is no evidence that they are superior to metformin. Therefore insulin sensitizers are not the first choice for ovulation treatment in PCOS and are only indicated for patients with abnormal glucose tolerance. Metformin is a class B drug and the decision to continue its use during pregnancy should be made carefully according to the patient’s specific situation. IV. Gonadotropins Gonadotropin therapy is mainly indicated for patients who have failed CC therapy. The currently used regimens are low-dose escalating regimens and decreasing regimens. The recommended starting dose is 37.5~50 IU/d and the treatment usually does not exceed 6 cycles. It has been shown that applying the starting dose up to 14 d in increments of 50% of the starting dose reduces the risk of ovarian hyperstimulation. The application of low-dose regimens resulted in single follicle ovulation rates of up to 70% and pregnancy rates of up to 20%, while the incidence of multiple pregnancies and ovarian hyperstimulation syndrome (OHSS) was low. Nevertheless, ovarian response should be closely monitored by ultrasound and serum estrogen levels during treatment, and the criteria for cycle cancellation should be strictly controlled to reduce the risk of OHSS and multiple pregnancies. In most of the literature, cycle cancellation is recommended when the number of follicles >16 mm in diameter is >3. Some studies have also suggested that the criteria for cancellation should be >14 mm in diameter and ≥4 follicles. More recent studies have also suggested stricter criteria for cycle cancellation, i.e. >2 follicles >14 mm in diameter or more than 3 or 4 follicles >10 mm in diameter. It has also been suggested that cycle cancellation should be considered based on the total follicle count when there are more than 3 follicles >14 mm in diameter. The ASRM Committee on Serum Estradiol (E2) has suggested that an excessive increase in E2 or up to 2,500 ng/L should be a cause for alarm. However, most authors use a threshold of <1,000 ng/L. When applying human chorionic gonadotropin (hCG) for ovulation, care should also be taken to use hCG with caution in women under 38 years of age without other factors of infertility when: (i) ≥2 follicles ≥16 mm in diameter; (ii) ≥1 follicle ≥16 mm in diameter and ≥2 follicles ≥14 mm in diameter. V. LOS For anovulatory PCOS patients with CC resistance, LOS is an alternative to gonadotropin therapy. The advantage is that single follicle ovulation can be obtained without the risk of OHSS and high-sequence multiple births and without the need for repeated monitoring. However, there are also disadvantages such as the risk of routine laparoscopic procedures, adhesions, and damage to normal ovarian tissue.LOS is mainly indicated for: (i) anovulatory PCOS women with CC resistance; (ii) patients with hyperluteinizing hormoneemia; (iii) patients who require laparoscopy; and (iv) patients who cannot receive routine monitoring after gonadotropin therapy. The methods include mainly monopolar electrocoagulation and laser, and the number of perforations is usually in the range of 4 to 10, beyond which premature ovarian failure may result. Nearly 50% of patients still require follow-up ovulation-promoting therapy after surgery. CC can be added if ovulation is still absent at 12 weeks after surgery, and gonadotropins can be applied if ovulation is absent at 6 months. Assisted reproductive techniques In principle, anovulation is not an indication for in vitro fertilization (IVF), and IVF is only indicated when none of the above treatments are effective. Meta-analyses have shown that patients with PCOS have high cycle cancellation rates, long ovarian stimulation times, and low egg quality when treated with IVF. However, their fertilization and clinical pregnancy rates did not differ significantly from those of the general female population. Singleton transfer, on the other hand, can fundamentally address the risk of multiple pregnancies. For patients with PCOS who have ovulation or can successfully induce ovulation, intrauterine insemination treatment is also an option for patients with poor male semen quality but can still meet the requirements for IUI. In summary, PCOS patients with fertility requirements should be screened for other infertility factors in both spouses before relevant fertility treatment, and pre-pregnancy counseling should be performed, especially for overweight women who should pay attention to weight loss. For ovulation treatment, the first-line regimen is CC; the second-line regimen is exogenous gonadotropins or LOS. Both have advantages and disadvantages, and the choice of treatment regimen should be based on the patient's specific situation. Studies have shown that the cumulative singleton live birth rate after the application of ovulatory therapy (including CC and gonadotropins) can reach 72%. The third line of treatment is IVF, and singleton transfer is recommended for young women, which can significantly reduce the rate of multiple pregnancies. However, the treatment of infertility in PCOS should not be too dogmatic, sticking to the above mentioned first-, second- and third-line treatment sequences, but should be individualized according to the patient's own characteristics. The use of metformin should be limited to patients with abnormal glucose tolerance. Numerous studies have shown that the routine use of metformin during ovulation promotion is not recommended for patients with PCOS. However, it is important to note that even in singleton pregnancies, the incidence of maternal and infant complications is higher in patients with PCOS than in the general population.