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Simple Summary: SMARCA4-mutated tumors are associated with poor prognosis. However, it is not clear if male and female patients have the same or different prognosis and if additional common mutations within the tumor play a role in prognosis. We have found that male patients had substantially worse prognosis than female patients whose tumor carried a SMARCA4 mutation. In addition, different co-existing mutations including the mutation of TP53, KRAS, CDKN2A, STK11, and Keap1 were associated with differential prognosis. Our study provides helpful insight for prognostic stratification in clinical practice and for understanding the pathogenic mechanism of this unique subtype of malignancy. Background: Whether sex and co-mutations impact prognosis of patients with SMARCA4-mutated (mutSMARCA4) malignancies is not clear. Methods: This cohort included patients from Northern California Kaiser Permanente with next-generation sequencing (NGS) performed from August 2020 to October 2022. We used Cox regression modeling to examine the association between sex and overall survival (OS), adjusting for demographics, performance status, Charlson comorbidity index, receipt of treatment, tumor mutation burden (TMB), and TP53, KRAS, CDKN2A, STK11, and Keap1 co-mutations. Results: Out of 9221 cases with NGS performed, 125 cases (1.4%) had a mutSMARCA4. The most common malignancies with a mutSMARCA4 were non-small cell lung cancer (NSCLC, 35.2%), esophageal and stomach adenocarcinoma (12.8%), and cancer of unknown primary (11.2%). The most common co-mutations were p53 (mutp53, 59.2%), KRAS (mutKRAS, 28.8%), CDKN2A (mutCDKN2A, 31.2%), STK11 (mutSTK11, 12.8%), and Keap1 (mutKeap1, 8.8%) mutations. Male patients had substantially worse OS than female patients both among the entire mutSMARCA4 cohort (HR = 1.71, [95% CI 0.92–3.18]) with a median OS of 3.0 versus 43.3 months (p < 0.001), and among the NSCLC subgroup (HR = 14.2, [95% CI 2.76–73.4]) with a median OS of 2.75 months versus un-estimable (p = 0.02). Among all patients with mutSMARCA4, mutp53 versus wtp53 (HR = 2.12, [95% CI 1.04–4.29]) and mutSTK11 versus wtSTK11 (HR = 2.59, [95% CI 0.87–7.73]) were associated with worse OS. Among the NSCLC subgroup, mutp53 versus wtp53 (HR = 0.35, [0.06–1.97]) and mutKRAS versus wtKRAS (HR = 0.04, [0.003-.45]) were associated with better OS, while mutCDKN2A versus wtCDKN2A (HR = 5.04, [1.12–22.32]), mutSTK11 versus wtSTK11 (HR = 13.10, [95% CI 1.16–148.26]), and mutKeap1 versus wtKeap1 (HR = 5.06, [95% CI 0.89–26.61}) were associated with worse OS. Conclusion: In our cohort of patients with mutSMARCA4, males had substantially worse prognosis than females, while mutTP53, mutKRAS, mutCDKN2A, mutSTK11 and mutKeap1were differentially associated with prognosis among all patients and among the NSCLC subgroup. Our results, if confirmed, could suggest potentially unidentified mechanisms that underly this sex and co-mutation-dependent prognostic disparity among patients whose tumor bears a mutSMARCA4. [ABSTRACT FROM AUTHOR]

Background: Debates exist in the repeat ablation strategy for patients with recurrence presenting as persistent atrial fibrillation (AF) after initial persistent AF ablation. Objective: To compare the outcome between the "2C3L" and "extensive ablation" approach in patients undergoing repeat procedures for recurrent persistent AF. Methods: Propensity‐score matching was performed in 196 patients with AF recurrence undergoing repeat ablation, and 79 patients treated with "2C3L" strategy were matched to 79 patients treated with "extensive ablation" strategy. The "2C3L" approach included pulmonary vein isolation, mitral isthmus, left atrial roof, and cavotricuspid isthmus ablation, while the "extensive ablation" strategy included extensive ablation of a variety of other targets aiming to terminate the AF. The primary outcome was freedom from any atrial tachyarrhythmia after 24‐h ambulatory monitoring follow‐up for 12 months. Results: No statistically significant difference was found between the primary outcome between the "2C3L" and the "extensive ablation" group [70.9% vs. 69.6%, p =.862; 95% confidence interval (CI) ‐12.8 to 15.3], although the "extensive ablation" group had a significantly high proportion of AF termination (19.0% for "2C3L" vs. 41.8% for "extensive ablation" group, p =.002; 95% CI 8.5–35.9). And AF termination was not related to the primary outcome in multifactorial regression. At 40 ± 22 months after the repeat procedure, the primary outcome was also comparable (57.0 % for "2C3L" vs. 48.1% for "extensive ablation" group, p =.265; 95% CI ‐6.6 to 23.7). Conclusion: The outcome between the "2C3L" and "extensive ablation" approaches was comparable in patients undergoing repeat procedures for recurrent persistent AF. [ABSTRACT FROM AUTHOR]

Background: Left bundle branch block (LBBB) and atrial fibrillation (AF) are commonly coexisting conditions. The impact of LBBB on catheter ablation of AF has not been well determined. This study aims to explore the long‐term outcomes of patients with AF and LBBB after catheter ablation. Methods: Forty‐two patients with LBBB of 11,752 patients who underwent catheter ablation of AF from 2011 to 2020 were enrolled as LBBB group. After propensity score matching in a 1:4 ratio, 168 AF patients without LBBB were enrolled as non‐LBBB group. Late recurrence and a composite endpoint of stroke, all‐cause mortality, and cardiovascular hospitalization were compared between the two groups. Results: Late recurrence rate was significantly higher in the LBBB group than that in the non‐LBBB group (54.8% vs. 31.5%, p =.034). Multivariate analysis showed that LBBB was an independent risk factor for late recurrence after catheter ablation of AF (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09–4.40, p =.031). LBBB group was also associated with a significantly higher incidence of the composite endpoint (21.4% vs. 6.5%, HR 3.98, 95% CI 1.64–9.64, p =.002). Conclusions: LBBB was associated with a higher risk for late recurrence and a higher incidence of composite endpoint in the patients underwent catheter ablation. [ABSTRACT FROM AUTHOR]

Background: Data on management of maternal arrhythmia among Chinese were limited. Radiofrequency catheter ablation (RFCA) proved to be a reliable treatment choice for sustained tachyarrhythmia but it has rarely been performed during pregnancy due to radiation exposure. Objective: To investigate the incidence of idiopathic sustained maternal arrhythmia and the feasibility of RFCA in the pregnant patients without fluoroscopy. Methods: From January of 2015 to December of 2018, the medical records on pregnancy‐related admissions in Beijing Anzhen Hospital (Beijing, China) were retrospectively analyzed. Patients who had sustained tachyarrhythmia episodes without structural heart disease were identified. Catheter ablation was performed in those with drug resistant and severely frequent tachyarrhythmia under the guidance of electroanatomical mapping system and intracardiac echocardiography catheter (ICE), if appropriate. Results: During the study period, 12 584 consecutive pregnant women were admitted for pregnancy‐related reasons, 156 (1.2%) of them were identified as sustained maternal tachyarrhythmia. Twenty‐eight patients (age 21‐37 years) received catheter ablation because the arrhythmias were drug resistant and severely frequent. The RFCA was successfully performed in all patients with zero fluoroscopy after 72.4 ± 24.7 min. Transseptal puncture was performed in 11 patients under the guidance of ICE. In a median of 37 (interquartile range [IQR]: 34‐39) weeks' pregnancy, 28 healthy fetuses were delivered. No cardiac‐related adverse event occurred during delivery. During later follow‐up, all patients were free of arrhythmia, and all the infants were well developed. Conclusion: Sustained maternal tachyarrhythmia is not uncommon in the clinical practice. To those with drug resistant and severely frequent arrhythmia, RFCA with zero fluoroscopy could be safely performed with acceptable efficacy. [ABSTRACT FROM AUTHOR]

Objective: To describe psychotropic medications prescription patterns among adolescents in Taiwan; focusing on age, gender, duration of treatments and various classes of psychotropic medications.Design: A retrospective description analysis.Setting: Taiwan National Health Insurance Database.Participants: Twelve to seventeen years' patients treated with psychotropic medications.Intervention: None.Main Outcome Measure(s): Percentage and duration of treatment with psychotropic medications during the study periods by medication classes and age groups were calculated. In addition, top three prescribed psychotropic medications were also determined.Results: A total of 3,120 patients were prescribed psychotropic drugs. The percentage of adolescent patients that received anxiolytics and antidepressants in 2002-2012 were 2.89% and 2.15%, respectively. Also, 851 patients (1.21%) were prescribed hypnotics and 638 (0.91%) were given sedatives. The prevalence rate of the prescription of psychotropic drugs increased steadily with age and females were more treated than males except antipsychotic. Among psychotropic drugs, antidepressants (mean: 8.6 times) were refilled more but antipsychotics (mean 188 days) were the long-term treatment drugs. Additionally, the trend of hospital visits fluctuated over the year while May and December showed a higher rate of visits.Conclusions: These findings show that the prevalence of psychotropic drug prescriptions in Taiwanese adolescents is even low but increasing trends in the prescription of these medications raises some concern. As the evidence of psychotropic drug safety and effectiveness in adolescents is still inadequate; we recommend that healthcare providers should consider psychotropic drugs therapy, continuously monitor for outcomes and empower their patients to improve their knowledge, therapeutic outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Objectives: Internal fixation with multiple cannulated compression screws is an optional treatment for femoral neck fracture. Recently, fully threaded cannulated compression screws (FTCCS) have been introduced to fix fresh femoral neck fractures (FNF). The purpose of this study was to investigate the effectiveness of FTCCS. Patients and methods: Patients with FNF fixed by multiple FTCCS from February 1st, 2014 to August 31st, 2017 were included in this study. They were followed for at least 12 months postoperatively. Nonunion, osteonecrosis of the femoral head (ONFH), fixation failure, reoperation, and femoral neck shortening (FNS) were used to evaluate the outcomes. Risk factors including age, sex, fracture side, fracture displacement, fracture stability, fixation configuration, and screw numbers were analyzed. Results: A total of 113 patients including 67 males and 46 females with an average age of 48.4 ± 13.4 years were included. The mean duration of follow-up was 27.1 months (range: 12–51 months). The incidence of nonunion, ONFH, fixation failure, and reoperation was 15.9%, 22.1%, 8.8%, and 24.8%, respectively. The rates of nonunion and reoperation were significantly higher in displaced fractures and unstable fractures. And patients with an unstable fracture had a higher risk of internal fixation failure. The median length of FNS was 2.9 mm (interquartile range: 0.9–6.5 mm, range: 0–17.5 mm). Age was a significant risk factor for FNS. Conclusions: The screw fixation method with FTCCS provided encouraging clinical results which may be a rational choice for the treatment of fresh FNF. Displaced fractures and unstable fractures were attributed to the higher incidence of complications. Trial registration: ChiCTR, ChiCTR1800017200. Registered 17 July 2018-Retrospectively registered, http: www.chictr.org.cn/showprojen.aspx?proj=29182. [ABSTRACT FROM AUTHOR]

Introduction: Catheter ablation for atrial fibrillation (AF‐CA) in patients with situs inversus dextrocardia (SID) can be challenging because of the contrary anatomy and associated anomalies. Cases and literature regarding AF‐CA in SID are rare and provide little information. Our study aims to present an improved procedure, ablation strategies, and evaluate the safety and outcomes of AF‐CA in patients with AF and SID. Methods: A total of 10 patients with AF‐SID (mean age, 60.4 ± 15.7 years; six paroxysmal AF, four persistent atrial fibrillation [PeAF]) were enrolled. For the improved procedure, images obtained by preacquired computed tomography and three‐dimensional electroanatomical mapping, integrating intracardiac echocardiography, and x‐ray imaging data are necessary to optimize the transseptal puncture and ablation procedure. Results: All patients successfully underwent 13 AF‐CA procedures without complications, including three patients received repeat procedures. However, two PeAF patients presented sick sinus syndrome (SSS) after the AF‐CA procedure, and one underwent permanent pacemaker implantation therapy during hospitalization. During the follow‐up period (6‐72 months), the outcomes were not favorable: three patients (30%) maintained sinus rhythm (SR) after the initial procedure; after repeated procedures, the overall SR rate was 40% (four patients). Conclusion: With the improved strategy, AF‐CA can be safely and effectively performed with low radiation exposure in patients with SID. However, the long‐term outcomes were not favorable, even when managed at a tertiary center by a team of specialists. Moreover, patients with PeAF might also have masked SSS, which should be carefully considered. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is common in abdominal solid organ transplant recipients and a cause of morbidity and mortality in this population. However, the outcomes of catheter ablation (CA) in transplant recipients with AF remain unclear. This study aimed to elucidate the outcomes of CA in renal and hepatic transplant recipients. Methods and Results: Between 2015 and 2019, 14 transplant recipients (nine with kidney transplantation and five with liver transplantation) were enrolled from among 10,741 AF patients and underwent CA at Anzhen Hospital. Another 56 patients matched by age, sex, and AF type were selected as the control group (four controls for each transplant recipient). During a mean follow‐up of 30.0 ± 13.3 months after the initial procedure, 10 (71.4%) of the transplant patients, compared to 41 (73.2%) of the control patients, remained free from AF recurrence (p = 1.000). A repeated procedure was performed in one transplant patient and in six control subjects. Consequently, 11 (78.6%) of the transplant patients, compared to 46 (82.1%) of controls, were in sinus rhythm after the repeated ablation (p =.715). Notably, Kaplan–Meier analysis did not demonstrate any significant differences in the atrial arrhythmia‐free rate after the initial and repeated procedure between the two groups. Vascular complications were identified in one transplant patient and two control subjects, while no life‐threatening complications were observed in either group. There was no transient allograft dysfunction in transplant recipients after CA. Conclusion: CA is safe and effective in abdominal solid transplant recipients, and maybe an optimal therapeutic strategy for this group. [ABSTRACT FROM AUTHOR]

Introduction: Repeat ablation strategy for atrial fibrillation (AF) recurrence after multiple ablation procedures is known to be challenging. This study evaluated the insights of adjunctive ablation for epicardial arrhythmogenic substrates in those patients via a percutaneous epicardial approach. Methods and Results: Thirty‐five consecutive patients with AF/atrial tachycardia (AT) recurrence, who had two or more prior ablation procedures, were enrolled from September 2016 to December 2018. In addition to a standard endocardial approach, epicardial mapping and ablation were performed via a percutaneous subxiphoid access in the electrophysiology lab. Adjunctive epicardial ablations for left lateral ridge (LLR) were performed in 31 of 35 patients (88.6%) for efficient transmural lesions with pacing capture loss. Marshall Bundle (MB) potentials were documented on epicardial LLR in three patients and abolished by direct epicardial ablation. Bachmann's bundle (BB) was ablated as an epicardial conduction gap in four patients with a refractory anterior wall line. Two epicardial AT/AF triggers were detected followed by successful termination with epicardial ablation. No periprocedural complications occurred. About 23 of 35 patients (65.7%) remained free from AF/AT after 23.2 ± 9 months of the procedure. Conclusions: Patients with multiple failed prior AF procedures refractory to antiarrhythmic therapy might warrant a percutaneous epicardial mapping and ablation strategy, with adjunctive therapy for targeting LLR/MB, BB, and underlying epicardial triggers in addition to a standard endocardial approach. [ABSTRACT FROM AUTHOR]

Introduction: The outcomes of atrial fibrillation (AF) ablation remain suboptimal. It is important to identify which AF patients will most likely benefit from ablation and who are more likely to show treatment failure, especially in those with structural heart disease such as hypertrophic cardiomyopathy (HCM). Methods and Results: We enrolled 120 HCM patients who underwent primary AF ablation (48 with persistent AF). Preprocedural QTc was measured and corrected using the Bazett's formula, and the distribution of fragmentation of the QRS complex (fQRS) was recorded. Arrhythmia recurrence was defined as any kind of documented atrial tachyarrhythmia of more than 30 seconds. Overall, arrhythmia recurrence occurred in 69 patients after 13.4 months' follow‐up. fQRS was present in 71 (59.17%) patients and was most commonly (81.69%) observed in the inferior leads. QTc more than 448 ms could predict arrhythmia recurrence with a sensitivity of 68.1% and specificity of 68.6%. Patients with QTc more than 448 ms (hazard ratio [HR]: 1.982; 95% confidence interval [CI]: 1.155‐3.402; P = .013) or those with fQRS+ (HR: 1.922; 95% CI: 1.151‐3.210; P = .012) were at an increased risk of recurrence. A combination of fQRS+ and QTc more than 448 ms was superior to fQRS or QTc alone in predicting arrhythmia recurrence. Conclusion: In patients with HCM undergoing AF ablation, QTc prolongation, specifically >448 ms, and presence of fQRS are independent risk factors for arrhythmia recurrence at follow‐up. The combination of these two parameters has greater predictive value and would help to identify patients who are at the highest risk of procedural failure. [ABSTRACT FROM AUTHOR]

We present the case of a 29‐year‐old man who developed ventricular tachycardia (VT) secondary to a cardiac lipoma located adjacent to the interventricular groove, which could not be fully resected. Antiarrhythmic drugs and endocardial and epicardial ablation failed to prevent VT recurrence. Finally, noninvasive stereotactic body radiation therapy (SBRT) targeting the lipoma was performed, with a total dose of 24 Gy delivered in three fractions. The number of VT episodes was reduced from 189/24 h before SBRT to 0 after the procedure. At 4‐month follow‐up, there were no signs of therapy‐related complications. Our experience suggests that SBRT could emerge as a viable treatment option for patients with cardiac tumors who develop refractory ventricular arrhythmias. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: To assess the long‐term outcome of catheter ablation in patients with hypertrophic cardiomyopathy (HCM), especially in patients with apical HCM (ApHCM). Methods and results: From 9,249 AF ablation cases, 97 patients (28 with ApHCM and 69 with non‐ApHCM) were enrolled. Another 97 patients matched by age, AF type, AF duration, and left atrial diameter were selected as the control group. After a mean follow‐up of (44.3 ± 29.6) months, success rate after a single procedure was 42.9% in the ApHCM patients (P  =  0.725), 36.2% in the non‐ApHCM patients (P  =  0.136) versus 50.5% in the control group. After multiple procedures, success rate both in the ApHCM group (50%, P  =  0.047) and in the non‐ApHCM group (50.4%, P  =  0.017) were lower than in the controls (68.0%). More patients in the ApHCM and in the non‐ApHCM group suffered very late recurrence beyond 1 year after the index procedure. Left atrial diameter (hazard ratio [HR] 1.04, 95% confidential interval [CI] 1.01–1.08, P  =  0.018) and AF duration (HR 1.01, 95% CI 1.00–1.01, P  =  0.005) were independent predictors of recurrence after the index ablation. There was no difference in thromboembolic events between the HCM group and the control group (8.2% vs. 3.1%, P  =  0.082). Conclusions: Patients with ApHCM or non‐ApHCM had similar success rate of AF ablation after single procedure and lower success rate after multiple procedure compared with the control group. [ABSTRACT FROM AUTHOR]

Background: Multiple pregnancies are one of the major safety concerns of in vitro fertilization (IVF) due to the increased risk of maternal and neonatal complications. Single embryo transfer is the most effective way to reduce the risk of multiple pregnancies. Selection of the embryo and optimization of the implantation environment are crucial to retain the success rate when the number of transferred embryos is diminished. Fresh embryo transfer with supra-physiological levels of hormones has been suggested to have an adverse effect on implantation. Elective frozen embryo transfer has been suggested to result in a higher rate of live birth than fresh embryo transfer. However, there is still a lack of evidence from randomized clinical trials comparing the efficacy and safety between frozen and fresh single blastocyst transfers.Methods/design: We are conducting a randomized controlled trial in women aged 20-35 undergoing their first cycle of IVF with or without intracytoplasmic sperm injection. After ovarian stimulation with a gonadotropin-releasing hormone antagonist protocol, women who obtain four or more embryos on day 3 of the embryo culture are randomized into two parallel groups: a single fresh blastocyst transfer group and a single frozen blastocyst transfer group (all blastocysts vitrified and a deferred frozen blastocyst transfer). The primary outcome is singleton live birth.Discussion: The results of this study will provide evidence for the efficacy and safety of the strategy of elective frozen single blastocyst transfer in women with a good prognosis.Trial Registration: Chinese Clinical Trial Registry, ChiCTR-IOR-14005405 . Registered on 30 Oct 2014. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether the common variant rs2305957 spanning PLK4 (Polo-like kinase 4) confers risk to embryo development in Northern Chinese Han (CHN) women.Design: Genetic association study.Setting: University hospital.Patient(s): A total of 2,015 infertile women who underwent in vitro fertilization (IVF), 530 women with early recurrent miscarriage (ERM), and 600 fertile control women in the CHN population.Intervention(s): Genotyping of rs2305957 was performed by means of high-resolution melting analysis.Main Outcome Measure(s): Blastocyst formation, implantation, early miscarriage, and live birth rates in infertile women; genotype distribution at rs2305957 in ERM case and control subjects.Result(s): In the first cohort of this study, infertile women with AA genotype had a lower blastocyst formation rate than those with AG or GG genotype. No significant differences were observed in implantation rate, early miscarriage rate, or live birth rate among AA, AG, and GG subgroups. In the second cohort, common variant rs2305957 was related to ERM. Genotype frequency differences were also significant in both additive model and dominant model.Conclusion(s): Common variant rs2305957 is associated with blastocyst formation and ERM in CHN women. Further investigations of PLK4 gene during embryo development could be worthwhile. [ABSTRACT FROM AUTHOR]

Study Question: Do oral contraceptives (OCs) and progestins impact live birth rate of IVF when used for cycle scheduling in women with polycystic ovary syndrome (PCOS)?Summary Answer: OCs used for scheduling IVF cycle were associated with lowered rates of pregnancy and live birth after fresh embryo transfer, whereas progestins used for this purpose yield higher rates of pregnancy and live birth than OCs.What Is Known Already: Due to oligo-menorrhea in PCOS, OCs and progestin are extensively used to schedule the start of an IVF cycle in women with PCOS. Little is known about the effect of such pretreatments on outcomes, especially, the rate of live birth.Study Design, Size, Duration: This was a nested cohort study and secondary analysis of a multicenter randomized trial, which was designed to compare live birth rate after fresh embryo transfer vs frozen embryo transfer (FET) in women with PCOS (Frefro-PCOS). A total of 1508 women were enrolled from 14 centers between June 2013 and May 2014.Participants/materials, Setting, Methods: At the discretion of local investigators, subjects were instructed to wait for spontaneous menses (Control group, n = 323), or were prescribed progestins (P group, n = 283) or OCs (OCs group, n = 902) to induce menstruation prior to the start of ovarian stimulation. GnRH antagonist protocol was initiated at Day 2 or 3 of induced or spontaneous menses cycle. The rates of pregnancy, pregnancy loss and live birth after either fresh embryo transfer or FET were compared among these three groups.Main Results and the Role Of Chance: With fresh embryo transfer, women with OC-induced menses had lower rates of clinical pregnancy (48.8% vs 63.6%, relative rate (RR): 0.77, 95% CI: 0.66-0.89) and live birth (36.1% vs 48.1%, RR: 0.75, 95% CI: 0.61-0.92) than women with spontaneous menses. With freeze-all and deferred FET, women with OC-induced menses had a similar pregnancy rate but a higher pregnancy loss rate (27.7% vs 13.0%, RR: 2.13, 95% CI: 1.28-3.52) after FET than women with spontaneous menses. The live birth rate after FET in women with OC-induced menses, progestin-induced menses and spontaneous menses was 49.4%, 50.7% and 60.2%, respectively (P = 0.06). Progestin-induced menses was associated with similar rates of pregnancy, pregnancy loss and live birth after transfer of either fresh or frozen embryos compared with spontaneous menses. Multivariate logistic regression analysis showed that OCs used for menses induction was associated with lower rate of live birth.Limitations, Reasons For Caution: The methods for menses induction were not assigned randomly, thus selection bias was highly likely because of the study design and significant differences that were observed in the baseline characteristics of the women in the different groups. The mean BMI in this study population was relatively normal; the applicability of this result to obese PCOS women needs to be evaluated in further study.Wider Implications Of the Findings: Our results suggest that either waiting for a spontaneous menses or using progestin is a better option than using OCs to induce menses in women with PCOS prior to ovarian stimulation using GnRH antagonist protocol for IVF. Further randomized controlled studies are needed to confirm our findings.Study Funding/competing Interests: This study was funded by National Basic Research Program of China (973 Program) (2012CB944700), the State Key Program of National Natural Science Foundation of China (81430029), National Natural Science Foundation of China (81471428) and Thousand Talents Program (Drs Legro and Zhang H). Dr Legro reports receiving consulting fees from Euroscreen, Kindex, Bayer and Millendo Pharmaceuticals and research funding from Ferring. Others report no disclosures.Trial Registration Number: Frefro-PCOS was registered at Clinicaltrials.gov: NCT01841528. [ABSTRACT FROM AUTHOR]