卵巢组织冻存(OTC)与移植目前主要用于青春期前或需尽快接受抗癌治疗的年轻肿瘤患者生育力保存,至今已有二十余年的历史,通过冻存卵巢组织再移植获得的活产已有超过200例的报道,近年来OTC与移植得到了快速发展,但仍存在许多亟待解决的问题.有效性方面,大部分患者自体冻存卵巢组织再移植后,卵巢内分泌功能可恢复至正常,活产率高达40％,然而冻存卵巢组织的回输利用率仍处于较低水平.安全性方面,通过卵母细胞体外成熟、人工卵巢等新兴技术减少肿瘤细胞在卵巢组织移植中转移、复发的风险是近年来众多研究者关注的方向.如何最大限度地保证OTC与移植过程中卵泡的存活也一直是研究的重点,目前有添加生长因子、激素、抗凋亡药物、干细胞等多种方法防治卵泡的凋亡和丢失.然而这些新兴技术大多尚处于实验室阶段,未来期待更多基础和临床研究来为OTC与移植这项生育力保存技术提供更多的有效性和安全性保障.
Objective:To investigate the clinical value of micro-vascular flow(MV-flow)imaging in evaluating the difference of endometrial micro-flow vascularization index(ⅥMV)between recurrent spontaneous abortion and normal reproductive age women.Methods:From June 2022 to June 2023,87 patients with unexplained recurrent spontaneous abortion in West China Second University Hospital,Sichuan University were selected as the abortion group,including 51 patients with 2 miscarriages,26 patients with 3 miscarriages,and 10 patients with≥4 miscar-riages.In addition,90 normal women of childbearing age who did not have a history of miscarriage and visited our hospital during the same period were selected as the healthy group.Endometrial ⅥMV was measured by transvag-inal ultrasound using MV-flow imaging technology in mid-luteal phase of the two groups.The mean values of en-dometrial ⅥMV in 177 women was measured repeatedly within and between observers.The endometrial ⅥMVand clinical data were compared between the two groups.The differences of endometrial ⅥMV and clinical data in pa-tients with different miscarriage times in the abortion group were compared simultaneously.Results:There was no statistically significant difference in age,body mass index,follicle stimulating hormone and luteinizing hormone be-tween the healthy group and the abortion group(P＞0.05).The ⅥMV of endometrium in healthy group was higher than that in abortion group,and the difference was statistically significant(6.10％vs.3.70％,P＜0.05).In the abortion group,endometrial ⅥMV in patients with 2 miscarriages(5.30％)was higher than that in patients with 3(3.25％)miscarriages and≥ 4(3.30％)miscarriages,and the difference was statistically significant(P＜0.05).There was no statistically significant difference in endometrial ⅥMV between patients with 3 miscarriages and ≥4 miscarriages(P＞0.05).The intraobserver and interobserver correlation coefficients of endometrial ⅥMV were 0.978 and 0.945,respectively.Conclusions:MV-flow imaging technology can effectively evaluate the difference of endometrial ⅥMV between recurrent spontaneous abortion and normal childbearing age women,and endometri-al ⅥMV may decrease with the increase of miscarriage frequency.
下丘脑-垂体-性腺轴调控系统、内分泌器官(胰岛、肾上腺、甲状腺)功能及卵巢自分泌和旁分泌等任何一个环节出现异常,均可导致排卵障碍(ovula-tion disorder),其主要表现为月经紊乱(如月经频发、稀发、闭经或异常子宫出血)及不孕[1].2022年FI-GO排卵障碍新的分类系统为HyPO-P系统,分别对应Ⅰ型:下丘脑;Ⅱ型:垂体;Ⅲ型:卵巢;Ⅳ型:PCOS.而针对排卵障碍的病因,HyPO-P系统进行二级分类,分别为GAIN(遗传、自身免疫、医源性、肿瘤)-FIT(功能性、感染或炎症、创伤和血管)-PIE(生理性、特发性、内分泌),并最终形成了以HyPO-P及GAIN-FIT-PIE的缩写组成的FIGO分类系统[2],用以规范排卵障碍的分类及临床应用.
外泌体是细胞外囊泡的一种亚型,广泛存在于机体的各种体液中,含有核酸、蛋白质、脂质等,是细胞间交流的重要介质.在正常生理和病理条件下,其内容物的种类和数量会发生变化,与免疫反应、癌症进展及心血管、神经相关疾病发生发展有关.配子形成、受精卵发育及着床是胚胎早期发育的重要过程,任何影响该过程的因素均可导致不孕或早期流产.本文阐述了外泌体在参与调节配子发育及成熟、受精、早期胚胎发育和母胎交流等多种生殖生理功能中的作用机制.由于外泌体具有较高的稳定性和保守性,有望成为生殖生物学中具有前景的诊断和治疗新手段.
1病例报告 患者,30岁,因卵巢囊肿8年,明显增大3+月,腹胀半月,于2021年11月8日入河北医科大学第二医院治疗.8年前患者孕前检查行超声检查发现卵巢囊肿,直径约2 cm,未处理,间断复查未见明显增大.1年前患者在接受辅助生殖助孕监测排卵过程中发现囊肿增大至5 cm,遂行经阴道注水腹腔镜检查,术中未见明显异常.3+月前患者孕前检查行超声检查示卵巢囊肿增大约14.5 cm,无腹痛、腹胀,未处理.半月前患者出现腹胀,进食减少,偶有胸闷,遂就诊于本院.门诊超声检查提示盆腹腔巨型包块,以卵巢肿瘤收入院.患者月经规律,G6P0,自然流产或胚胎停育共6次.末次妊娠于2021年9月因胚胎停育行清官术.2010年于本院确诊为肝豆状核变性(hepatolenticular degeneration,HLD),药物治疗后震颤症状消失,但3年前自行停药且未复查,自诉无症状.2020年体检发现亚临床甲状腺功能减退,口服左甲状腺素钠片(优甲乐)50µg,每日1次,服药至今.
未破裂卵泡黄素化综合征(luteinized unruptured follicles syndrome,LUFS)是一种排卵紊乱的临床症候群,特指在卵泡未破裂的情况下,呈现出正常的排卵周期表现,超声检查可见未破裂的卵泡依次黄素化、萎缩.自1975年Jewelewicz首次报道以来[1],LUFS日益引起临床的重视.关于其发病率的报道不一,在有生育力的妇女中约为5％～10％,在不孕症妇女中可能达到9％～55％.但即使LUFS患者也不是每个周期的卵泡均发生未破裂卵泡黄素化(LUF),因此Kerin等[2]在一项前瞻性研究中提出,LUF仅为生殖调节中的暂时性偏移,并不构成一种综合征群.
卵泡正常发育并排出卵子,是维持正常月经,实现生育的必备条件.下丘脑-垂体-卵巢轴的控制与反馈正常与否,是决定卵泡发育及排出是否正常的核心,该轴线疾病、影响该轴线功能的相关生理状态或疾病、药物或手术干预等将引起卵泡发育缓慢、停滞、异期或排出受阻,将导致异常子宫出血(cabnormal uterine bleeding,AUB)、闭经和不孕.在排除妊娠、哺乳、药物避孕或手术导致双侧卵巢功能丧失等状态下的卵泡发育异常或排出障碍,称之为排卵障碍.2022年 10 月,国际妇产科联盟(International Federation of Gynecology and Obstetrics,FIGO)在人类生殖《Human Reproduction》、生育与不育《Fertility and Sterility》和国际妇产科杂志《International Journal of Gynecology &Obstetrics》发表了基于德尔菲共识方法(Delphi con-sensus process)形成的排卵障碍分类系统[1].
垂体位于蝶鞍的垂体窝内,分为腺垂体和神经垂体.腺垂体作为下丘脑-腺垂体-靶器官轴的重要环节,主要分泌催乳素(PRL)、生长激素(GH)、促肾上腺皮质激素(ACTH)、促甲状腺激素(TSH)和促性腺激素,在调控生长、发育、代谢、生殖等方面发挥重要作用.
Objective:To explore the correlation between choline,betaine,dimethylglycine,methionine and tri-methylamine oxide,metabolites related to the methionine cycle in carbon metabolism,and preeclampsia(PE)in di-chorionic diamniotic(DCDA)twin pregnancy.Methods:175 pregnant women with twin pregnancies who under-went regular prenatal examinations were registered in Peking University Third Hospital from July 2017 to April 2019 were included as the study subjects.According to whether PE had occurred,they were divided into non-PE group(138 cases)and PE group(37 cases).The fasting peripheral blood of pregnant women during the second trimester of pregnancy was collected,and the metabolites were quantitatively analyzed by ultra-high performance liquid chromatogrey-triple quadrupole tandem mass spectrometry(UHPLC-QqQ MS).The basic characteristics and plasma metabolite concentrations were compared between PE group and non-PE group.Poisson regression was used for plasma metabolite-related PE relative risk(RR)analysis,and receiver operating characteristic(ROC)curve was used to evaluate the accuracy of PE model prediction.Results:①Compared with the non-PE group,the rate of elderly pregnant women was higher,the concentration of betaine was lower,and the concentra-tion of choline was higher in PE group.The differences were statistically significant(P＜0.05).②Poisson regres-sion analysis showed that in the model adjusted for all confounding factors,there was a positive correlation be-tween maternal choline levels and PE risk(RR＞1,P＜0.05).The risk of PE occurrence increased as the in-crease of choline levels(Ptrend＜0.05).Betaine levels were negatively associated with PE risk(RR＜1,P＜0.05).The risk of PE occurrence decreased as the increase of betaine level(Ptrend＜0.05).There was no corre-lation between plasma levels of dimethylglycine,methionine and trimethylamine oxide and the risk of PE.③Pois-son regression analysis showed that the relative risk of PE was lowest when the plasma betaine/choline ratio was highest(RR0.32,95％Cl 0.14-0.75).When the dimethylglycine/betaine ratio was in the thirdpercentile,the risk of PE was increased in pregnant women(RR 2.53,95％Cl 1.01-6.32).(4)ln terms of PE prediction,the AUC combined with general risk factors and methionine metabolites was 0.80.Conclusions:Maternal choline and be-taine levels in the second trimester are related to the occurrence of PE in DCDA twin pregnancy,and provide a new idea for early prediction and intervention of PE.It is still necessary to expand the sample size to further verify and explore the mechanism.
Objective:To evaluate the clinical effect of high-intensity focused ultrasound(HIFU)and drug con-servative treatment on the treatment of type Ⅰ and type Ⅱ cesarean scar pregnancy(CSP).Methods:A retrospec-tive analysis was performed on 191 patients diagnosed with type Ⅰ and type Ⅱ CSP by ultrasonography and trea-ted in Mianyang Central Hospital from January 2018 to December 2021,and they were divided into drug group(n=67)and HIFU group(n=124)according to different treatment methods before curettage surgery.After receiv-ing conservative drug treatment or HIFU treatment,preformnegative pressure suction curettage under ultrasound monitoring to evaluate the effectiveness and safety of the two pretreatment methods.Results:There were no sig-nificant differences in age,number of cesarean sections,gestational age,the maximum diameter of the gestational sac,number of incision pregnancies,the β-hCG level before pretreatment,the heart tube pulse in the gestational sac,size of fetal bud,and fertility requirements between the medication group and HIFU group(P＞0.05).The proportion of type Ⅱ incision in HIFU group was higher than that in drug group(P＜Q.05).There were no signifi-cant differences between the two groups in intraoperative bleeding,treatment outcome effective rate after pretreat-ment,postoperative vaginal bleeding duration,postoperative uterine cavity residual,rate of reoperation and rate of repregnancy(P＞0.05).There were statistical differences between the two groups in the operation time of curet-tage surgery,whether the operation method was changed after pre-treatment,total hospital stay,β-hCG recovery time and hospitalization cost(P＜0.05).Following up to November 2022,there were 12 cases re-pregnancies in the drug group and 16 cases re-pregnancies in the HIFU group.Conclusions:For type Ⅰ and type Ⅱ CSP,HIFU pretreatment before negative pressure suction curettage under ultrasound monitoring is a safe and effective treat-ment,which improves the treatment effect and reduces the hospitalization time of patients.It may be an effective clinical therapy for type Ⅰ and type Ⅱ CSP treatment.
多囊卵巢综合征(polycystic ovary syndrome,PCOS)是一种生殖功能障碍与糖脂代谢异常并存的内分泌紊乱综合征.PCOS以月经稀发或闭经、不孕、高雄激素血症、卵巢多囊样改变等为主要临床表现,在无排卵性不孕中占30％～60％,常伴有代谢异常如肥胖、胰岛素抵抗、血脂异常等,可增加2型糖尿病、心脑血管疾病和子宫内膜癌的发病几率,危害女性健康.在全球范围内,PCOS患病率5％～15％,我国是全球PCOS患病率增长最决的国家之一[1].我国育龄人群PCOS的患病率从2010年的5.61％上升到2020年的8.6％[2].PCOS的病因迄今未明,治疗以生活方式调整为主,应用药物治疗代谢并发症,合并不孕症者可诱导排卵或行人类辅助生殖技术(ART)助孕治疗.
Objective:To investigate the effect of early selective reduction of twin pregnancies or spontaneous reduction on the improvement of clinical outcome in IVF-ET treatment.Methods:The clinical data of 6535 cycles(6535 cases)of single or twin pregnancy obtained from fresh and frozen-thawed embryo transfer(FET)of IVF or ICSI-ET in the Department of Reproductive Medicine,Women and Children's Hospital Affiliated to Xiamen Univer-sity from November 2011 to December2021 were analyzed retrospectively,The propensity score matching(PSM)method(1∶4)was used to include the study subjects.The surgical reduction group and the spontaneous single-ton group were included in 128 cycles and 510 cycles,respectively.The spontaneous reduction group and the ini-tial singleton group were included in 511 cycles and 2038 cycles,respectively.The pregnancy outcomes of each groups were compared.Results:After PSM,the number of transferred embryos in the surgical and spontaneous reduction group was higher than that in the initial singleton group.The gestational week of delivery was earlier than that of the initial singleton group,and the birth weight of the newborn was lower than that in the initial single-ton group.The rate of premature delivery and low birth weight was higher than that in the initial singleton group,and the difference was statistically significant(P＜0.05).The incidence of pregnancy complications(postpartum hemorrhage,gestational diabetes,hypertensive disorders of pregnancy)and the rate of cesarean section were not significantly different(P＞0.05).The abortion rate and neonatal birth defect rate were missing after adjusting the PSM model.According to the calculation before adjustment,the early abortion rate of the surgical reduction group and the spontaneous reduction group were significantly lower than that in the initial singleton group(P＜0.05),and the late abortion rate of the spontaneous reduction group was lower than that in the initial singleton group,the difference was statistically significant(P＜0.05).There was no significant difference in the neonatal birth defect rate between the surgical/spontaneous reduction group and the initial singleton group(P＞0.05).Conclusions:Patients with multiple pregnancies caused by assisted reproductive technology(ART)may have a relatively poor prognosis in the perinatal period even if the effect of early pregnancy reduction surgery or spontaneous reduction is limited.Reducing the number of embryos transferred cannot completely reverse the pregnancy outcome.Limiting the number of embryos transferred is the fundamental solution to the adverse outcomes of ART assisted pregnancy.
目的:探讨脆性X染色体智力缺陷(FMR1)基因CGG重复扩增突变在产前筛查高危人群中的分布情况.方法:选取2020年9月至2022年12月在重庆市妇幼保健院产前诊断中心就诊的365例具有FMR1基因CGG重复扩增突变高危因素的人群,通过三核苷酸重复引物PCR扩增及毛细管电泳仪检测,计算FMR1基因CGG重复数,对于阳性结果进行家系分析.结果:365例高危人群中女性279例,男性86例.其中因智力障碍、孤独症、发育迟缓检测的有282例(77.3％),因卵巢功能减退检测的有83例(22.7％),365例检测对象中共发现中间突变7例,前突变3例,全突变3例,FMR1基因CGG重复扩增突变的检出率为1∶61.结论:FMR1基因CGG重复扩增突变在产前筛查高危人群中的检出率较高,通过在产前高危人群中检测FMR1基因CGG重复扩增突变可以有效预防脆性X综合征患儿的出生.
1病历摘要 患者,32岁,因反复移植失败3次合并种植窗延迟,再次取卵术后1月,于2023年2月2日至四川大学华西第二医院就诊.患者12岁初潮,平素月经周期规律,周期28～32天,经期6天,经量中等,无痛经,G0P0,因原发不孕于3年前在外院行子宫输卵管碘油造影术,结果提示双侧输卵管阻塞.于外院行体外受精-胚胎移植(IVF-ET)辅助助孕,促排卵前患者于外院宫腔镜检查提示慢性子宫内膜炎,给予多西环素100 mg(每天2次,连用2周)规范治疗,采用黄体期短效长方案促排卵,共计获卵8枚,其中成熟卵7枚,获得第3天卵裂期胚胎5枚,行卵裂期新鲜胚胎移植1枚,余囊胚培养形成优质可移植囊胚3枚,行囊胚冷冻.
排卵障碍是指女性卵巢中卵子正常的生长、发育、成熟及排出过程受到影响,导致排卵不规律、无排卵或卵泡发育不良等现象.排卵障碍主要表现为月经不调(包括月经频发、稀发、闭经或异常子宫出血)及不孕.正常排卵直接依赖于功能完善的下丘脑-垂体-卵巢(hypothalamic-pituitary-ovarian,HPO)轴.HPO轴受到直接或间接影响可导致排卵障碍.其中HPO轴的直接功能障碍及多囊卵巢综合征(PCOS)是临床上导致排卵障碍的常见原因,因此探讨较多.非HPO轴内分泌异常,包括甲状腺功能异常、肾上腺皮质增生症及糖脂代谢异常引起的肥胖也与排卵障碍密切相关,针对这些异常也应给予妥善治疗.
Objective:To investigate the diagnostic value of peripheral blood systemic immune inflammatory in-dex(SII)in histological chorioamnionitis(HCA)and the predictive value of adverse pregnancy outcomes.Meth-ods:A total of 138 pregnant women with suspected HCA were included from January 2021 to June 2022 in Peo-ple's Hospital of Zhengzhou as the research objects.According to the results of placental pathology examination,they were divided into non-HCA group(66 cases)and HCA group(72 cases).The general clinical data,laboratory indicators and adverse outcome indicators of the two groups were compared,and the relationship between the a-bove indicators and HCA was analyzed by multivariate Logistic regression.ROC curve was used to analyze the predictive value of SII for HCA and adverse pregnancy outcomes.Results:①Logistic regression analysis showed that increased neutrophil percentage(Neut％)and SII could increase the risk of HCA(OR＞1,P＜0.05),and in-creased lymphocyte percentage(Lym％)was beneficial for reducing the risk of HCA(OR＜1,P＜0.05).②ROC curve analysis showed that the area under the curve(AUC)of Neut％and Lym％for diagnosing HCA were 0.628 and 0.638,respectively,while the AUC of SII was higher(0.722),and the diagnostic threshold of SII was 974.49 ×109/L.③The rates of postpartum hemorrhage,neonatal infection and premature delivery in high SII group(SII＞974.49 ×103/L)were higher than those in low SII group(SII ≤974.49 ×109/L),and the difference was statistically significant(P＜0.05).The value of SII in predicting postpartum hemorrhage(AUC 0.708)and neonatal infection(AUC 0.848)were higher than that in preterm birth(AUC 0.637).Conclusions:Abnormal Neut％and Lym％levels increase the risk of HCA to some extent,but the diagnostic value of HCA is average.Peripheral blood SII has high diagnostic value in HCA,and has good predictive value for postpartum hemorrhage and neonatal infection,which is expected to be a new indicator for prenatal diagnosis and prognosis prediction of adverse pregnancy outcomes in HCA.
排卵功能障碍是育龄期女性的常见病、难治病,其发病率逐年增高.排卵功能障碍同时也是女性不孕的主要原因之一,主要表现为持续性不排卵、稀发排卵、不恰当排卵.根据FIGO(2022年)排卵障碍的分类方法[1],主要分为以下4种类型:Ⅰ类下丘脑型、Ⅱ类垂体型、Ⅲ类卵巢型、Ⅳ类PCOS,各类型下再进行细分.卵巢性排卵障碍根据病因主要分为以下儿类:遗传因素、自身免疫因素、医源性因素、肿瘤因素、功能性、感染及炎症性因素、心理因素、特发性、内分泌性等.本文针对卵巢性排卵障碍的几类常见病因的诊疗提供参考意见并进行简要分析总结,为卵巢性排卵障碍临床诊疗提供参考,同时为今后的研究方向找寻新的思路.
Objective:To explore the economic applicability and safetyof the novel uterovaginal pubic comb suspension(UPCS)surgery with Mersilene tape in the treatment of pelvic organ prolapse(POP).Methods:A ret-rospective analysis was conducted on the clinical data of patients who underwent UPCS surgery due to POP from January 1st,2021 to February 28,2023.They were divided to the UPCS surgery with Mersilene tape group(group A)and suspension surgery with Y-shaped mesh group(group B)respectively.The POP-Q indication points,sus-pension surgery duration,intraoperative bleeding volume,material expense,postoperative catheter retention time,anal exhaust time and hospitalization duration were recorded for both groupbefore and after surgery.Evaluate the severity of POP related symptoms in patients before and after surgery using the pelvic Floor Distress Invento-ry-short Form 20(PFDI-20)and Pelvic Organ Prolapsed/Urinary Incontinence Sexual Questionnaire-12(PISQ-12),and follow up and observe the patients and analyze the complications.Results:A total of 17 POP patients were included in the study.There were 12 patients in group A while 5 patients in group B.The suspension material expense of group A was considerably lower than that of group B(P＜0.05).There was no significant difference between the two groups in preoperative PFDI-20 score,preoperative PISQ-12 score,UPCS surgery duration,intr-aoperative bleeding volume,postoperative urinary catheter retention time,postoperative anal exhaust time and hospitalization duration.All patients showed stable vital signs during the surgery and no severe complications were reported.Compared with the preoperative status,the positions of the Aa,Ba,and C indicatorpoint in group A and group B were all increased significantly(P＜0.05).The PFDl-20 and PISQ-12 scores of the two groups at the last follow-up after surgery showed significant improvement compared to those before surgery(P＜0.05).No signifi-cant difference was found in the PFDI-20 and PISQ-12 scores between the two groups after surgery(P＞0.05).There were no significant differences in the postoperative complications between the two groups(P＞0.05).Con-clusions:Compared with suspension surgery with Y-shaped mesh,UPCS surgery with Mersilene tape is safe and effective in the treatment of POP.The UPCS surgery with Mersilene tape showed better cost-effectiveness in the treatment of POP,and the surgical steps are relatively simple.Therefore,UPCS surgery with Mersilene tape was worthy of promotion in clinical practice.
子宫内膜癌(endometrial carcinoma,EC)是全球女性中常见的癌症,排名第6位[1],主要发生于绝经期,其中5％的患者在40岁之前发病,并且大多数还未完成生育[2].EC的标准手术治疗方式包括全子宫切除术+双侧附件切除术,患者将因此失去生育能力,由于女性生育年龄的推迟和EC的良好预后,保留生育功能治疗备受关注.保留生育功能治疗主要包括大剂量的孕激素制剂、宫内孕激素缓释系统、促性腺激素释放激素激动剂(GnRHa)及联合宫腔镜手术[3].
女性的生育年龄和生育力主要取决于原始卵泡库的大小和卵子质量.原始卵泡库的大小在出生时即已确定,随着年龄的增长,原始卵泡被不断激活和耗竭,直至绝经.卵泡生长发育通常指从原始卵泡形成到发育成熟直至排卵的整个过程,卵泡生长发育的每个阶段都要受到内部因素与外部环境精密有序的协同调控.任何一个环节出现问题,卵泡都不会排出成熟健康的卵子,所以了解卵泡生长发育的调控机制是至关重要的.为此,本文主要概述了当前对哺乳动物卵泡生长发育调控机制的一些认识和进展,为提高女性生育能力和辅助生殖的临床效果提供参考.
