Basal Serum Anti-Miillerian Hormone Level as a Predictor of Clinical Outcomes in Freezing-all Embryo Transfer Program

As a novel biomarker,there is inconsistent evidence regarding the association between anti-Miillerian hormone (AMH) and live birth rate in freezing-all embryo transfer cycles.We aim to assess the prognostic effect of baseline AMH on clinical outcomes,especially live birth rate in freezing-all embryo transfer cycles.A total of 828 non-polycystic ovary patients that underwent their first frozen-thawed embryo transfers in our center between January 2010 and January 2015 were recruited in this retrospective analysis.Patients were stratified into three groups based on their baseline AMH concentration:low AMH group (<1.4ng/mL),middle AMH group (1.4-5.8 ng/mL)and high AMH group (>5.8 ng/mL).The results showed that low AMH level was associated With adverse clinical outcomes.The differences in implantation rate (21.9% vs.43.2% vs.58.8%,P<0.001),clinical pregnancy rate (32.0% vs.55.2% vs.65.7%, P<0.001),live birth delivery rate (21.8% vs.43.6% vs.52.7%,P<0.001)and miscarriage rate (31.8% vs.17.5% vs.15.4%,P=0.014)among the three groups were statistically significant.After adjusting confounders (i.e.age,baseline FSH level,AFC,endometrium thickness,endometriurn preparation protocols,number of embryos transferred,etiologies of infertility),differences in live birth rate,clinical pregnancy rate and implantation rate between groups remained significant.The further age subgroup analysis demonstrated that low AMH concentration was significantly associated with poor outcomes both in young and advanced patients.The area under the curve for serum AMH,age,AFC and FSH were 0.635,0.634,0.615 and 0.543 respectively,for predicting live birth.In conclusion, baseline AMH was an independent prognostic factor of live birth rate of freezing-all embryo transfers,but its predictive value on live birth rate was of limited clinical value.

Allograft pretreatment for the repair of sciatic nerve defects: green tea polyphenols versus radiation

Pretreatment of nerve allografts by exposure to irradiation or green tea polyphenols can elimi- nate neuroimmunogenicity, inhibit early immunological rejection, encourage nerve regeneration and functional recovery, improve tissue preservation, and minimize postoperative infection. In the present study, we investigate which intervention achieves better results. We produced a 1.0 cm sciatic nerve defect in rats, and divided the rats into four treatment groups： autograft, fresh nerve allograft, green tea polyphenol-pretreated （1 mg/mL, 4~C） nerve allograft, and irradiation-pre- treated nerve allograft （26.39 Gy/min for 12 hours; total 19 kGy）. The animals were observed, and sciatic nerve electrophysiology, histology, and transmission electron microscopy were carried out at 6 and 12 weeks after grafting. The circumference and structure of the transplanted nerve in rats that received autografts or green tea polyphenol-pretreated nerve allografts were similar to those of the host sciatic nerve. Compared with the groups that received fresh or irradiation-pre- treated nerve allografts, motor nerve conduction velocity in the autograft and fresh nerve allograft groups was greater, more neurites grew into the aUografts, Schwann cell proliferation was evident, and a large number of new blood vessels was observed; in addition, massive myelinated nerve fibers formed, and abundant microfilaments and microtubules were present in the axoplasm. Our findings indicate that nerve allografts pretreated by green tea polyphenols are equivalent to trans- planting autologous nerves in the repair of sciatic nerve defects, and promote nerve regeneration. Pretreatment using green tea polyphenols is better than pretreatment with irradiation.

Advances in the genetic etiology of premature ovarian insufficiency

Premature ovarian insufficiency(POI),defined as the loss of ovarian function in women before the age of 40 years,is a challenging reproductive issue that affects hundreds of millions of people globally with compromised fertility and a higher risk of cardiovascular disease.POI is highly heterogeneous in etiology,including genetic,infectious,metabolic,environmental,iatrogenic,and immunological factors.

电针和经皮穴位电刺激技术在生殖医学中的应用:专家共识（英文）

本文从传统针刺治疗不孕症的选穴依据与现代电针/经皮穴位电刺激技术的相关原理着手,从最优刺激参数选择、穴位辨证、疗程与治疗次数的确定及基本原理等方面阐述了电针/经皮穴位电刺激技术在多囊卵巢综合症、取卵镇痛、卵巢储备功能降低、胚胎移植以及男性少/弱精症等生殖领域中的具体应用。首次对电针/经皮穴位电刺激技术在生殖领域优势病种中的应用进行了系统的分析和总结,在最优刺激参数选择、穴位辨证、疗程与治疗次数的确定等方面提出了一系列专家共识,并为临床实践提供了指导意见和理论依据。

Epidemiological Survey and Risk Factor Analysis of Recurrent Spontaneous Miscarriages in Infertile Women at Large Infertility Centers

Background：A higher frequency of spontaneous miscarriage has been observed in infertile couples,and there is a higher prevalence of infertility among patients with a history of recurrent spontaneous miscarriages （RSMs;〉2 miscarriages）.This study aimed to determine the proportion of infertile patients with RSM and examine risk factors associated in patients with RSM being treated with assisted reproductive technologies.Methods：This cross-sectional observational study was conducted at six reproductive medicine centers in three cities of China.Data of 751 patients with at least one spontaneous miscarriage were analyzed.Demographic data and etiological factors associated with infertility were compiled and compared between patients with a single spontaneous miscarriage （SSM） and those with RSM.Results：Two hundred （26.6%,95% confidence interval [CI]：23.50-29.95%） patients experienced RSMs and 551 （73.4%） had a single miscarriage.The odds of RSM increased with increasing age （odds ratio [OR] =1.06）,uterine disorders （OR =2.09）,endocrine disorders （OR =2.48）,and immune disorders （OR =2.98）.Higher education level,masters or above,and a pelvic cavity disorder were associated with lower risk of RSM （OR =0.27 and 0.46,respectively）.Late spontaneous miscarriages were more frequent in patients with RSM than in those with a SSM （31.5% vs.14.2%,respectively,P 〈 0.001） and were associated with a history of uterine cavity procedures （OR =2.095） and cervical factors related to infertility （OR =4.136,95% CI：1.012-16.90）.Conclusions：Compared to patients with only a SSM,the conditions of patients with RSM are more complicated.To increase the success rate of assisted reproductive technology,factors including uterus cavity adhesion,cervical relaxation,endocrine disorders,and immune disorders should be treated before assisted reproduction is initiated.These data may provide treatment guidance for infertile patients with a history of RSM.

Establishing a nonlethal and efficient mouse model of male gonadotoxicity by intraperitoneal busulfan injection

An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell(SSC)transplantation.Busulfan has been commonly used to develop such a model,but 30%–87%of mice die when administered an intraperitoneal injection of 40 mg kg^?1.In the present study,hematoxylin and eosin staining,Western blot,immunofluorescence,and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses(20,30,and 40 mg kg^?1)on day 36 or a dose of 40 mg kg^?1 at different time points(0,9,18,27,36,and 63 days).The survival rate of the mice was 100%.When the mice were treated with 40 mg kg^?1 busulfan,dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36.In addition,the gene expressions of glial cell line-derived neurotrophic factor(GDNF),fibroblast growth factor 2(FGF2),chemokine(C-X-C Motif)ligand 12(CXCL12),and colony-stimulating factor 1(CSF1)were moderately increased by day 36.A 63-day,long-term observation showed the rare restoration of endogenous germ cells in the testes,suggesting that the potential period for SSC transplantation was between day 36 and day 63.Our results demonstrate that the administration of two intraperitoneal injections of busulfan(40 mg kg^?1 in total)at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity.

Logistic Regression Analysis of Risk Factors Associated with Spontaneous Abortion after In Vitro Fertilization/Intracytoplasmic Sperm Injection-Embryo Transfer in Polycystic Ovary Syndrome Patients

Objective:To analyze spontaneous abortion rate and its associated risk factors in patients with polycystic ovary syndrome(PCOS)after in vitro fertilization/intracytoplasmic sperm injection-embryo transfer(IVF/ICSI-ET).Methods:This was a retrospective cohort study on 2,231 PCOS patients undergoing IVF/ICSI treatment.For comparison,we enrolled another 2,231 patients with tubular factors in control group.Spontaneous abortion rate and chromosomal abnormality rate were compared between the two groups.Furthermore,clinical data were compared between the patients with spontaneous abortion and those with ongoing pregnancy using univariate and multivariate analysis for risk factors of spontaneous abortion in PCOS patients.Results:Patients in the PCOS group had significantly higher spontaneous abortion rate(24.15%)than that in the control group(12.75%,P<0.001).Chromosomal abnormality rate was significantly lower in the PCOS group(36.05%,31/86)than in the control group(55.56%,50/90,P=0.009).In the PCOS group,patients with spontaneous abortion had significantly elder age,higher body mass index(BMI),and homeostasis model assessment for insulin resistance(HOMA-IR)than those with ongoing pregnancy.The logistic regression analysis confirmed that the age,BMI,and HOMA-IR were the risk factors of spontaneous abortion in the PCOS patients.There were no significant differences between groups in the type of cycles,the quality of embryos transferred,the number of embryos transferred,fasting blood glucose,fasting insulin,and so on.Conclusions:Compared with non-PCOS patients,PCOS patients had higher spontaneous abortion rate,but the chromosomal abnormality was not a major factor for the high spontaneous abortion rate in the PCOS patients.Age,BMI,and HOMA-IR were risk factors for spontaneous abortion after IVF/ICSI-ET in PCOS patients.

Diagnostic Guidelines for Infertility

Infertility seriously endangers the reproductive health of women at childbearing age.It is defined as the failure to achieve successful pregnancy after 1 year or more of regular unprotected intercourse.Broadly defined,infertility includes two aspects-failure to conceive or have a live birth.This guideline only addressed content relevant to the former.It was proposed by the gynecological endocrine group of the Chinese Society of Obstetrics and Gynecology,Chinese Medical Association,based on relevant guidelines of the World Health Organization,the American Society for Reproductive Medicine,the National Institute for Health and Clinical Excellence,as well as the clinical practice in China.The guideline was reviewed by experts and doctors from medical institutions at all levels,which is applicable to the diagnosis of infertility by physicians in obstetrics,gynecology,and andrology at various medical institutions nationwide.