Due to the comprehensive examination of 50 patients with ovarian polycystosis the authors suggested that ultrasound, laparoscopic, hormonal and endometrial parameters should be employed as diagnostic criteria.

Diagnostic criteria for polycystic ovary syndrome

Background Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. An endometrial component has been suggested to contribute to subfertility and poor reproductive outcomes in affected women. Objective and rationale The aim of this review was to determine whether there is sufficient evidence to support that endometrial function is altered in women with PCOS, whether clinical features of PCOS affect the endometrium, and whether there are evidence-based interventions to improve endometrial dysfunction in PCOS women. Search methods An extensive literature search was performed from 1970 up to July 2020 using PubMed and Web of Science without language restriction. The search included all titles and abstracts assessing a relationship between PCOS and endometrial function, the role played by clinical and biochemical/hormonal factors related to PCOS and endometrial function, and the potential interventions aimed to improve endometrial function in women with PCOS. All published papers were included if considered relevant. Studies having a specific topic/hypothesis regarding endometrial cancer/hyperplasia in women with PCOS were excluded from the analysis. Outcomes Experimental and clinical data suggest that the endometrium differs in women with PCOS when compared to healthy controls. Clinical characteristics related to the syndrome, alone and/or in combination, may contribute to dysregulation of endometrial expression of sex hormone receptors and co-receptors, increase endometrial insulin-resistance with impaired glucose transport and utilization, and result in chronic low-grade inflammation, immune dysfunction, altered uterine vascularity, abnormal endometrial gene expression and cellular abnormalities in women with PCOS. Among several interventions to improve endometrial function in women with PCOS, to date, only lifestyle modification, metformin and bariatric surgery have the highest scientific evidence for clinical benefit. Wider implications Endometrial dysfunction and abnormal trophoblast invasion and placentation in PCOS women can predispose to miscarriage and pregnancy complications. Thus, patients and their health care providers should advise about these risks. Although currently no intervention can be universally recommended to reverse endometrial dysfunction in PCOS women, lifestyle modifications and metformin may improve underlying endometrial dysfunction and pregnancy outcomes in obese and/or insulin resistant patients. Bariatric surgery has shown its efficacy in severely obese PCOS patients, but a careful evaluation of the benefit/risk ratio is warranted. Large scale randomized controlled clinical trials should address these possibilities.

Endometrial function in women with polycystic ovary syndrome: a comprehensive review

Facts and hypotheses

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility; however, whether women with PCOS and spontaneous or drug-induced ovulatory cycles have the same reproductive potential as non-PCOS controls is a matter of debate. In the present opinion paper, the author takes the opportunity to summarize the collective evidence supporting the hypothesis of reduced fertility potential in women with PCOS, regardless of ovulatory status, and speculate that reduced reproductive potential may be caused by altered oocytes, embryo and endometrial competence, and infertility-related co-morbidities as well as an increased risk of pregnancy complications.

Is fertility reduced in ovulatory women with polycystic ovary syndrome? An opinion paper.

Background：The risk of spontaneous abortion in patients with polycystic ovary syndrome (PCOS) undergoing assisted reproductive treatment (ART) is higher than that in patients without PCOS, however, no definitive risk factors have been confirmed to associate with the high spontaneous abortion rate in PCOS patients undergoing ART. This study was performed to assess the impact of relevant risk factors on spontaneous abortion in patients with PCOS. Clinical questions were formulated and organized according to the PICOS principle. Methods: A systematic review and meta-analysis were conducted on all published studies on PCOS and spontaneous abortion in Embase, PubMed, Web of Science and Cochrane Library. Related risk factors included body mass index (BMI), age, insulin resistance (IR), hyperandrogenism, and chromosome aberrations. All patients were diagnosed as PCOS using the Rotterdam criteria. The primary endpoint was miscarriage and live birth rate. Fixed-effect models were used to analyze homogeneous data, and subgroup and sensitivity analyses were performed on heterogeneous data. The source of heterogeneity was evaluated, and the random effect model was used to summarize the heterogeneity. Results: Among 1836 retrieved articles, 22 were eligible and included in the analysis with 11182 patients. High BMI (OR = 1.48, 95% CI [1.32, 1.67], MD = 1.35, 95% CI [0.58,2.12]) and insulin resistance (MD = 0.32, 95% CI [0.15, 0.49]) were associated with an increased risk of spontaneous abortion in PCOS patients undergoing ART. Older age (OR = 0.29, 95% CI [ 0.29, 0.44]，MD = 2.01, 95% CI [0.04, 4.18]), embryonic chromosomal aberrations (OR=0.75, 95%CI [0.31,1.77]), and hyperandrogenism (MD = 0.10, 95% CI [- 0.02, 0.22]) were not associated with the high spontaneous abortion rate in patients with PCOS. A subgroup analysis of BMI showed that there was no statistically significant difference in the effect between overweight and obesity on spontaneous abortion in PCOS patients undergoing ART (OR = 1.34, 95% [0.97, 1.85]). Conclusion: High BMI and insulin resistance are two risk factors for an increased risk of spontaneous abortion in PCOS patients undergoing ART, and losing weight and mitigating insulin resistance may decrease the spontaneous abortion rate in these patients undergoing ART.

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High BMI and Insulin Resistance Are Risk Factors for Spontaneous Abortion in Patients With Polycystic Ovary Syndrome Undergoing Assisted Reproductive Treatment: A Systematic Review and Meta-Analysis.

Background When ovarian response to FSH stimulation for IVF/ICSI is unsatisfactory, the FSH dose is often adjusted in the treatment cycles, thereby assuming that hormone status and follicular development were insufficient for optimal stimulation. Objectives To evaluate whether serum delta FSH levels between D6 of gonadotrophin use and basal serum FSH or between D6 of gonadotrophin use and D1 of gonadotrophin use predict ovarian response in IVF/ICSI cycles. Method The participants of this retrospective study were chosen from the Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University between August 2015 and December 2017 (n = 3,109), and during the COS, each participant was given a fixed dose of rFSH in the first 6 days. Delta FSH1: The difference of serum FSH between D6 of gonadotrophin use and basal serum FSH. Delta FSH2: The difference of serum FSH between D6 of gonadotrophin use and D1 of gonadotrophin use. Logistic regression was used to analyze the association between delta FSH1 level and delta FSH2 level and ovarian response. Besides, we also use the tertile statistics to divide the groups. Results Part I: Delta FSH1 levels (mean: 1.41 ± 3.46) in normal responders were higher than delta FSH1 levels (mean: 1.07 ± 23.89) in hyper responders (P = 0.0248). The tertile of delta FSH1 is dif ≤ 0, 0 2.25. Compared with the hyper responder, the delta FSH1 (0 2.25) in the normal responder has a higher ratio and is statistically significant. Part II: Delta FSH2 levels (mean: 4.90 ± 2.84) in normal responders were similar with delta FSH2 levels (mean: 4.74 ± 2.09) in hyper responders (P = 0.103). The tertile of delta FSH1 is dif ≤ 3.91, 3.91 5.69. Compared with the hyper responders, the delta FSH2 (3.91 5.69) in the normal responders has a higher ratio and is statistically significant. Conclusions There is a weak relationship between ovarian response and serum delta FSH levels.

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The Relationship Between Serum Delta FSH Level and Ovarian Response in IVF/ICSI Cycles

Polycystic ovary syndrome (PCOS) is a multifactorial reproductive and endocrine disease, believed to be caused by aberrant steroid biosynthesis pathways involving cytochrome P450, 17α-hydroxylase (CYP17A1). This meta-analysis aimed to evaluate the association between CYP17A1 polymorphism rs743572 and PCOS risk. Studies on the CYP17A1 gene were retrieved by searching PubMed, Embase and Web of Science and statistical analyses were performed by STATA software. Fifteen eligible studies were included, dated from January 1994 to 19 November 2020, involving 2277 patients with PCOS and 1913 control individuals. Overall, the results showed that the rs743572 T>C mutation was most likely to be associated with PCOS risk under the recessive model, which was further confirmed by heterogeneity analysis and publication bias detection (CC versus CT + TT, odds ratio [OR] 1.24, 95% confidence interval [CI] 1.02–1.50, P = 0.028, I² = 35.9%). Moreover, subgroup analysis by ethnicity demonstrated that Caucasian but not Asian women carrying the CC genotype of rs743572 had an elevated risk of PCOS (CC versus CT + TT, OR 1.45, 95% CI 1.03–2.06, P = 0.035, I² = 15.10%, six studies). In conclusion, rs743572 is highly likely to be a risk factor for PCOS, and the mutant genotype CC may increase susceptibility to PCOS in Caucasians rather than Asians.

The single-nucleotide polymorphism rs743572 of CYP17A1 shows significant association with polycystic ovary syndrome: a meta-analysis

Objectives: To evaluate the combined impact of male and female BMI on cumulative pregnancy outcomes after the first ovarian stimulation. Design: Retrospective cohort study. Setting: University-affiliated reproductive medicine center. Patients: A total of 15,972 couples undergoing their first ovarian stimulations from June 2009 to June 2016 were included. During the follow-up period between June 2009 and June 2018, 14,182 couples underwent a complete ART cycle involving fresh embryo transfer and subsequent frozen embryo transfers (FETs) after their first ovarian stimulations. Patients with a BMI <24 kg/m2 served as the reference group. Patients with a BMI ≥ 24 kg/m2 were considered to be overweight, and those with a BMI ≥28 kg/m2 were considered to be obese. Intervention(s): None. Primary Outcome Measure: The primary outcome was the cumulative live birth rate (CLBR), which defined as the delivery of at least one live birth in the fresh or in the subsequent FET cycles after the first ovarian stimulation. Results: In the analyses of females and males separately, compared with the reference group, overweight and obese females had a reduced CLBR (aOR 0.83, 95% CI 0.7.92 and aOR 0.76, 95% CI 0.64–0.90). Similarly, overweight males had a reduced CLBR (aOR 0.91, 95% CI 0.83–0.99) compared with that of the reference group. In the analyses of couples, those in which the male was in the reference or overweight group and the female was overweight or obese had a significantly lower CLBR than those in which both the male and female had a BMI <24 kg/m2. Conclusions: The CLBR is negatively impacted by increased BMI in the female and overweight status in the male, both individually and together.

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The Combined Impact of Female and Male Body Mass Index on Cumulative Pregnancy Outcomes After the First Ovarian Stimulation

Background: Oocyte maturation arrest is a disease that produces immature oocytes and cannot be mature after culturing in vitro, which leads to female primary infertility. We aimed to summarize nine representative patients in our center to retrospectively analyze the genetic variants and clinical characteristics of oocyte maturation arrest. Methods: This study examined and analyzed nine families with oocyte maturation arrest. Whole-exome sequencing (WES) of the probands was performed to detect the pathogenic variants. Sanger sequencing verified the WES findings in patients and available parents. ExAC database was used to search the variant frequency. The variants were assessed by pathogenicity and conservational property prediction analysis and according to the American College of Medical Genetics and Genomics (ACMG). Phenotypes of oocytes were evaluated by a light microscopy, and the phenotype-genotype correlation was also evaluated. Results: Nine pathogenic variants in five genes were detected in nine patients, of which three were novel variants, including PATL2 [c.1374A > G (p. Ile458Met)] and [1289-1291del TCC (p. Leu430del)] and ZP2 [c.1543C > T (p. Pro515Ser)]. Nine variants were predicted to be pathogenic, resulting in different types of oocyte maturation arrest and clinical phenotypes. Conclusion: Three novel pathogenic variants were identified, enabling the expansion of the gene variant spectrum. The related pathogenic mutations of the PATL2, TUBB8, and ZP1∼3 genes were highly suggestive of being causative of oocyte maturation arrest.

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Gene Spectrum and Clinical Traits of Nine Patients With Oocyte Maturation Arrest

BACKGROUND Patients with endometriosis (EMs) are routinely advised to take GnRH-a for 3-6 months to improve the internal reproductive environment, but this may not be necessary. MATERIAL AND METHODS This retrospective study examined the effects of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) with shortened (n=311) or conventional (n=213) long-term pituitary downregulation in EMs patients between January 2013 and July 2017. RESULTS The 2 groups showed no significant differences in gonadotropin (Gn) dose, number of oocytes retrieved, or miscarriage rate. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels on the initiation day and the LH level on human chorionic gonadotropin (hCG) day (1.22±1.39 vs. 0.74±0.55 P=0.0026) were higher in the study group than in the control group. The cumulative live birth rates in the second cycle were 69.13% in the study group (95% confidence interval (CI), 64-74.27%) vs. 68.54% in the control group (95% CI, 62.31-74.78%, P=0.88, respectively). CONCLUSIONS This study showed that the shortened regimen and the ultralong regimen did not produce different pregnancy outcomes after ART, and the single-application, long-term GnRH-a protocol may serve as a cost-effective and safe treatment protocol for EMs patients.

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Efficacy and Safety of In Vitro Fertilization (IVF)/Intracytoplasmic Sperm Injection (ICSI) Among Patients with Endometriosis After a Shortened Protocol of Long-Term Pituitary Downregulation.

Hao Shi

Papers

The Relationship Between Serum Delta FSH Level and Ovarian Response in IVF/ICSI Cycles

The single-nucleotide polymorphism rs743572 of CYP17A1 shows significant association with polycystic ovary syndrome: a meta-analysis

The Combined Impact of Female and Male Body Mass Index on Cumulative Pregnancy Outcomes After the First Ovarian Stimulation

Gene Spectrum and Clinical Traits of Nine Patients With Oocyte Maturation Arrest

Efficacy and Safety of In Vitro Fertilization (IVF)/Intracytoplasmic Sperm Injection (ICSI) Among Patients with Endometriosis After a Shortened Protocol of Long-Term Pituitary Downregulation.