Obesity contributes to reduced fertility, infertility and adverse maternal and infant outcomes through multiple mechanisms. Individuals with obesity encounter numerous impediments during fertility treatments and subsequent pregnancy, leading to intensified physical, psychological, and socio-economic burdens. Given the recent progress in research and the expansion of treatment modalities, there is an imperative need to refine the diagnostic and therapeutic frameworks for obese patients with infertility through a multidisciplinary approach. The Reproductive Medicine Specialized Committee of the Chinese Medical Doctor Association (CMDA) has established a multidisciplinary team of experts to develop an evidence-based guideline. This guideline's development will adhere to both national and international standards for guideline development and reporting. This proposal mainly describes the significance and purpose of guideline development, the method of evidence retrieval and quality assessment, the process of guideline development, and the plan for publication, implementation and dissemination of the guideline.

Objective Recurrent pregnancy loss(RPL)presents a formidable challenge for individuals undergoing in vitro fertilization-embryo transfer(IVF-ET),forming both a clinical dilemma and a focal point for scientific inquiry.This study endeavors to investigate the intricate interplay between clinical features,such as age,body mass index(BMI),and waist-to-hip ratio(WHR),and routine laboratory parameters,including sex hormones,blood composition,liver and thyroid functions,thyroid antibodies,and coagulation indicators,in RPL patients undergoing IVF-ET.By meticulously analyzing these variables,we aim to uncover the latent risk factors predisposing individuals to RPL.Identifying potential factors such as advanced maternal age,obesity,and insulin resistance will provide clinicians with vital insights and empirical evidence to strengthen preventive strategies aimed at reducing miscarriage recurrence.Methods This retrospective case-controlled study included RPL patients who underwent IVF-ET treatment at Sun Yat-sen Memorial Hospital,Sun Yat-sen University,between January 2012 and March 2021 as the case cohort,compared with women receiving assisted reproductive treatment due to male infertility as the control cohort.The fasting peripheral blood was collected 5 days before the first menstrual cycle at least 12 weeks after the last abortion.The clinical characteristics and relevant laboratory indexes of the two groups were compared.Employing both univariate and multivariate logistic regression analyses,we sought to unearth potential high-risk factors underlying RPL.Additionally,a linear trend analysis was conducted to assess the linear relationship between total testosterone(TT)levels and the number of miscarriages.Results In contrast to the control cohort,the RPL cohort exhibited significant increases in age,BMI,and WHR(P<0.05).Notably,TT levels were markedly lower in the RPL cohort(P=0.022),while no significant differences were observed between the two groups concerning basal follicle-stimulating hormone,luteinizing hormone,estradiol,progesterone,prolactin levels,and anti-Müllerian hormone levels(P>0.05).Moreover,fasting insulin(FINS)levels and HOMA-IR index were notably elevated in the RPL cohort relative to the control cohort(P<0.001),although no significant differences were observed in fasting blood glucose levels(P>0.05).Furthermore,the neutrophil(NEU)count and NEU-to-lymphocyte ratio were notably higher in the RPL cohort(P<0.01).Univariate logistic regression analysis identified several factors,including age≥35 years old,BMI≥25 kg/m2,WHR>0.8,FINS>10 mU/L,HOMA-IR>2.14,NEU count>6.3×109 L-1,and an elevated NEU/lymphocyte ratio(NLR),as significantly increasing the risk of RPL(P<0.05).Although TT levels were within the normal range for both cohorts,higher TT levels were associated with a diminished RPL risk(odds ratio[OR]=0.67,95% confidence interval[CI]:0.510-0.890,P=0.005).After adjustments for confounding factors,age≥35 years old(OR=1.91,95% CI:1.06-3.43),WHR>0.8(OR=2.30,95% CI:1.26-4.19),and FINS>10 mU/L(OR=4.50,95% CI:1.30-15.56)emerged as potent risk factors for RPL(P<0.05).Conversely,higher TT levels were associated with a reduced RPL risk(OR=0.59,95% CI:0.38-0.93,P=0.023).Furthermore,the linear trend analysis unveiled a discernible linear association between TT levels and the number of miscarriages(Ptrend=0.003),indicating a declining trend in TT levels with escalating miscarriage occurrences.Conclusion In patients undergoing IVF-ET,advanced maternal age,lower TT levels,increased WHR,and elevated FINS levels emerged as potent risk factors for RPL.These findings provide clinicians with valuable insights and facilitate the identification of patients who are at high risks and the formulation of preventive strategies to reduce the recurrence of miscarriages.

Obesity contributes to reduced fertility, infertility and adverse maternal and infant outcomes through multiple mechanisms. Individuals with obesity encounter numerous impediments during fertility treatments and subsequent pregnancy, leading to intensified physical, psychological, and socio-economic burdens. Given the recent progress in research and the expansion of treatment modalities, there is an imperative need to refine the diagnostic and therapeutic frameworks for obese patients with infertility through a multidisciplinary approach. The Reproductive Medicine Specialized Committee of the Chinese Medical Doctor Association (CMDA) has established a multidisciplinary team of experts to develop an evidence-based guideline. This guideline's development will adhere to both national and international standards for guideline development and reporting. This proposal mainly describes the significance and purpose of guideline development, the method of evidence retrieval and quality assessment, the process of guideline development, and the plan for publication, implementation and dissemination of the guideline.

Objective To explore the technology frontiers for neuroblastoma treatment from the perspective of patent citation network. Methods Through patent analysis for neuroblastoma treatment, highly cited patents and highly cited papers in the citation network were taken as the research objects. The title and abstract of the citing patents were analyzed by text clustering to identify the technology frontiers. Through social network analysis, the core patents were identified from the indices of degree centrality, betweenness centrality, closeness centrality, and eigenvector centrality. Results A total of 6240 patent applications for neuroblastoma treatment were found, including 71304 patent citations and 88698 journal-article citations. Four technology frontiers were identified based on patent citation network, namely, drug target, drug design, tumor-indication expansion, and gene-expression regulation. Three technology frontiers were identified based on journal-article citation network. They were drug target, drug design, and tumor-indication expansion. Conclusion The development of technology for neuroblastoma treatment continues to be active. Drug target and drug design are the most important technology frontiers. This study could provide certain reference for neuroblastoma treatment from the perspective of information science.

Objective:To evaluate the efficacy and safety of domestic recombinant human chorionic gonadotropin (r-hCG) for injection in Chinese women undergoing assisted reproductive technology (ART) of controlled ovarian hyperstimulation (COH).Methods:In a multicenter, randomized, double-blind, positive, parallel controlled clinical trial, the infertile women with normal ovarian reserve who received COH in seven reproductive medical centers from July 2017 to October 2018 were randomly divided into two groups: experimental group (domestic r-hCG, n=112) and control group (imported r-hCG, n=116). Interactive web response system was used to randomize. The total number of oocytes obtained, cleavage cells, two pronuclei fertilization, mid-division oocytes rate, positive serum hCG rate, early embryo loss rate, clinical pregnancy rate, sustained pregnancy rate and the incidence of adverse reactions were compared between the two groups during the cycle of COH. Results:During the initiation cycle of ovulation induction therapy, the total number of oocytes obtained in experimental group and control group were (12.1±5.6) and (12.0±6.7) respectively, with no statistically significant difference ( P>0.05). There were no significant differences in the rate of mid-division oocytes, the number of cleavage cells, the number of double pronuclear fertilization, the positive rate of serum hCG during the transplantation cycle, the loss rate of early embryo, the clinical pregnancy rate, and the sustained pregnancy rate between the two groups (all P>0.05), and the 90% confidence interval ( CI) of the difference between the two groups fell within the preset equivalence threshold (-3, +3). The difference in immunogenicity assessment between the two groups was not statistically significant ( P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) and other adverse reactions in treatment period were not significantly different between the two groups (all P>0.05), which were known adverse reaction occurred in the imported r-hCG. Conclusion:In the COH cycle of Chinese infertile women with normal ovarian reserve, the effectiveness and safety of domestic r-hCG are equivalent to imported r-hCG.

Objective:To assess the efficacy of Zishen Yutai Pill compared with placebo on live birth rate among women following fresh embryo transfer cycles.Methods:We conducted a double-blind, multicenter, placebo-controlled, randomized trial to investigate whether administration of Zishen Yutai Pill would improve pregnancy outcomes among women undergoing fresh embryo transfer following in vitro fertilization or intracytoplasmic sperm injection. The primary outcome was live birth rate. Secondary outcomes were rates of implantation, biochemical pregnancy, clinical pregnancy, pregnancy loss, cycle cancellation, maternal, fetal and neonatal complications. A total of 2265 sample size (1∶1 in two groups) was used to detect a live birth rate difference between Zishen Yutai Pill and placebo. Participants were enrolled and randomized to receive 5 g of Zishen Yutai Pill or placebo orally, three times per day during the study using block randomization method. Results:Recruitment was completed between April 2014 and June 2017, with 2580 patients screened. Follow-up was completed in June 2018. Totally 2265 patients were randomized, 1131 to Zishen Yutai Pill group and 1134 to placebo group. Characteristics were similar between the two groups. In intention-to-treat analysis, the rates of live birth in Zishen Yutai Pill group and placebo group were 26.8% (303/1131) and 23.0% (261/1134), respectively, the difference was statistically significant ( RR=1.16, 95% CI=1.01-1.34, P=0.038). The implantation rates were 36.8% (482/1310) and 32.6% (410/1256) in Zishen Yutai Pill group and placebo group, respectively, the difference was statistically significant ( RR=1.13, 95% CI=1.01-1.25, P=0.027). The biochemical pregnancy rate in Zishen Yutai Pill group was 35.5% (402/1131) vs. 31.1% (353/1134) in placebo group, the difference was statistically significant ( RR=1.14, 95% CI=1.02-1.28, P=0.026). The rates of clinical pregnancy in Zishen Yutai Pill group and placebo group were 31.2% (353/1131) and 27.3% (310/1134), respectively, the difference was statistically significant ( RR=1.14, 95% CI=1.00-1.30, P=0.043). There were no significant differences between the two groups in the rates of pregnancy loss, maternal, or neonatal complications (all P>0.05). Conclusion:Zishen Yutai Pill increased the rate of live birth after fresh embryo transfer compared with placebo.

Objective:To evaluate the efficacy and safety of domestic recombinant human chorionic gonadotropin (r-hCG) for injection in Chinese women undergoing assisted reproductive technology (ART) of controlled ovarian hyperstimulation (COH).Methods:In a multicenter, randomized, double-blind, positive, parallel controlled clinical trial, the infertile women with normal ovarian reserve who received COH in seven reproductive medical centers from July 2017 to October 2018 were randomly divided into two groups: experimental group (domestic r-hCG, n=112) and control group (imported r-hCG, n=116). Interactive web response system was used to randomize. The total number of oocytes obtained, cleavage cells, two pronuclei fertilization, mid-division oocytes rate, positive serum hCG rate, early embryo loss rate, clinical pregnancy rate, sustained pregnancy rate and the incidence of adverse reactions were compared between the two groups during the cycle of COH. Results:During the initiation cycle of ovulation induction therapy, the total number of oocytes obtained in experimental group and control group were (12.1±5.6) and (12.0±6.7) respectively, with no statistically significant difference ( P>0.05). There were no significant differences in the rate of mid-division oocytes, the number of cleavage cells, the number of double pronuclear fertilization, the positive rate of serum hCG during the transplantation cycle, the loss rate of early embryo, the clinical pregnancy rate, and the sustained pregnancy rate between the two groups (all P>0.05), and the 90% confidence interval ( CI) of the difference between the two groups fell within the preset equivalence threshold (-3, +3). The difference in immunogenicity assessment between the two groups was not statistically significant ( P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) and other adverse reactions in treatment period were not significantly different between the two groups (all P>0.05), which were known adverse reaction occurred in the imported r-hCG. Conclusion:In the COH cycle of Chinese infertile women with normal ovarian reserve, the effectiveness and safety of domestic r-hCG are equivalent to imported r-hCG.

Objective:To assess the efficacy of Zishen Yutai Pill compared with placebo on live birth rate among women following fresh embryo transfer cycles.Methods:We conducted a double-blind, multicenter, placebo-controlled, randomized trial to investigate whether administration of Zishen Yutai Pill would improve pregnancy outcomes among women undergoing fresh embryo transfer following in vitro fertilization or intracytoplasmic sperm injection. The primary outcome was live birth rate. Secondary outcomes were rates of implantation, biochemical pregnancy, clinical pregnancy, pregnancy loss, cycle cancellation, maternal, fetal and neonatal complications. A total of 2265 sample size (1∶1 in two groups) was used to detect a live birth rate difference between Zishen Yutai Pill and placebo. Participants were enrolled and randomized to receive 5 g of Zishen Yutai Pill or placebo orally, three times per day during the study using block randomization method. Results:Recruitment was completed between April 2014 and June 2017, with 2580 patients screened. Follow-up was completed in June 2018. Totally 2265 patients were randomized, 1131 to Zishen Yutai Pill group and 1134 to placebo group. Characteristics were similar between the two groups. In intention-to-treat analysis, the rates of live birth in Zishen Yutai Pill group and placebo group were 26.8% (303/1131) and 23.0% (261/1134), respectively, the difference was statistically significant ( RR=1.16, 95% CI=1.01-1.34, P=0.038). The implantation rates were 36.8% (482/1310) and 32.6% (410/1256) in Zishen Yutai Pill group and placebo group, respectively, the difference was statistically significant ( RR=1.13, 95% CI=1.01-1.25, P=0.027). The biochemical pregnancy rate in Zishen Yutai Pill group was 35.5% (402/1131) vs. 31.1% (353/1134) in placebo group, the difference was statistically significant ( RR=1.14, 95% CI=1.02-1.28, P=0.026). The rates of clinical pregnancy in Zishen Yutai Pill group and placebo group were 31.2% (353/1131) and 27.3% (310/1134), respectively, the difference was statistically significant ( RR=1.14, 95% CI=1.00-1.30, P=0.043). There were no significant differences between the two groups in the rates of pregnancy loss, maternal, or neonatal complications (all P>0.05). Conclusion:Zishen Yutai Pill increased the rate of live birth after fresh embryo transfer compared with placebo.

Objective:To evaluate the efficacy and safety of domestic recombinant human follicle-stimulating hormone (rhFSH) in assisted reproductive technology (ART) of controlled ovarian hyperstimulation (COH).Methods:In a multicenter, randomized, double-blind, positive, parallel controlled non-inferiority clinical trial, the infertile women with normal ovarian reserve who received ART-COH in six reproductive medical centers from July 2017 to June 2019 were randomly divided into two groups: experimental group (domestic rhFSH, n=134) and control group (imported rhFSH, n=133). Eight subjects were excluded due to various reasons during the experimental process, 7 in experimental group and 1 in control group. At last, 127 subjects in experimental group and 132 subjects in control group complete the experiment following the research protocol. The total number of oocytes, usage of FSH, fertilization rate of oocytes, the number of high-quality embryos, clinical pregnancy rate, live birth rate, neonatal characteristics and the incidence of adverse reactions were compared between the two groups during the cycle of COH. Results:During the initiation cycle of ovulation induction therapy, the total number of oocytes obtained in experimental group and control group were 13.0±5.8 and 12.9±5.7, respectively, with no statistically significant difference ( P>0.05). Among the 82 intracytoplasmic sperm injection (ICSI) patients, the number of M II oocytes obtained in experimental group (39 cases) was markedly higher than that in control group (43 cases) (9.9±3.9 vs. 7.5±3.0, P=0.003). The fertilization rate of oocytes in experimental group was obviously higher than that in control group [63.82% (1048/1642) vs. 56.19% (958/1705), P<0.001]. There were no significant differences of stimulated duration and dosage of rhFSH, number of high-quality embryos, clinical pregnancy rate, preterm rate, live birth rate, incidence of neonatal abnormalities, neonatal weight or Apgar score between the two groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome and other adverse reactions in treatment period were not significantly different between the two groups (all P>0.05), which were known adverse reaction occurred in the imported rhFSH. Conclusion:The efficacy and safety of domestic rhFSH were the same as that of imported rhFSH in infertile patients with normal ovarian reserve under the same ovarian stimulation regimen.

Objective:To evaluate the efficacy and safety of domestic recombinant human follicle-stimulating hormone (rhFSH) in assisted reproductive technology (ART) of controlled ovarian hyperstimulation (COH).Methods:In a multicenter, randomized, double-blind, positive, parallel controlled non-inferiority clinical trial, the infertile women with normal ovarian reserve who received ART-COH in six reproductive medical centers from July 2017 to June 2019 were randomly divided into two groups: experimental group (domestic rhFSH, n=134) and control group (imported rhFSH, n=133). Eight subjects were excluded due to various reasons during the experimental process, 7 in experimental group and 1 in control group. At last, 127 subjects in experimental group and 132 subjects in control group complete the experiment following the research protocol. The total number of oocytes, usage of FSH, fertilization rate of oocytes, the number of high-quality embryos, clinical pregnancy rate, live birth rate, neonatal characteristics and the incidence of adverse reactions were compared between the two groups during the cycle of COH. Results:During the initiation cycle of ovulation induction therapy, the total number of oocytes obtained in experimental group and control group were 13.0±5.8 and 12.9±5.7, respectively, with no statistically significant difference ( P>0.05). Among the 82 intracytoplasmic sperm injection (ICSI) patients, the number of M II oocytes obtained in experimental group (39 cases) was markedly higher than that in control group (43 cases) (9.9±3.9 vs. 7.5±3.0, P=0.003). The fertilization rate of oocytes in experimental group was obviously higher than that in control group [63.82% (1048/1642) vs. 56.19% (958/1705), P<0.001]. There were no significant differences of stimulated duration and dosage of rhFSH, number of high-quality embryos, clinical pregnancy rate, preterm rate, live birth rate, incidence of neonatal abnormalities, neonatal weight or Apgar score between the two groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome and other adverse reactions in treatment period were not significantly different between the two groups (all P>0.05), which were known adverse reaction occurred in the imported rhFSH. Conclusion:The efficacy and safety of domestic rhFSH were the same as that of imported rhFSH in infertile patients with normal ovarian reserve under the same ovarian stimulation regimen.