Heterotopic pregnancy after assisted reproductive techniques with favorable outcome of the intrauterine pregnancy:A case report

BACKGROUND Heterotopic pregnancy(HP)is a rare condition in which both ectopic and intrauterine pregnancies occur.HP is uncommon after natural conception but has recently received more attention due to the widespread use of assisted reproductive techniques(ART)such as ovulation promotion therapy.CASE SUMMARY Here,we describe a case of HP that occurred after ART with concurrent tubal and intrauterine singleton pregnancies.This was treated successfully with surgery to preserve the intrauterine pregnancy,resulting in the birth of a low-weight premature infant.This case report aims to increase awareness of the possibility of HP during routine first-trimester ultrasound examinations,especially in pregnancies resulting from ART and even if multiple intrauterine pregnancies are present.CONCLUSION This case alerts us to the importance of comprehensive data collection during regular consultations.It is important for us to remind ourselves of the possibility of HP in all patients presenting after ART,especially in women with an established and stable intrauterine pregnancy that complain of constant abdominal discomfort and also in women with an unusually raised human chorionic gonadotropin level compared with simplex intrauterine pregnancy.This will allow symptomatic and timeous treatment of patients with better results.

Russian Collaborative Development of Reproduction Technologies for the Sustainable Management of Amphibian Biodiversity

Reproduction technologies(RTs)can provide for the reliable reproduction of amphibians,as well as perpetuation of species genetic variation with the use of biobanks.In 1982,in anticipation of the biodiversity conservation crisis,major Russian institutions collaborated in a dynamic program to develop and implement RTs for the sustainable management of amphibian biodiversity.An initial primary focus was the captive breeding of threatened Russian endemic anuran and caudate species,using RTs that varied from environmental manipulation to the use of exogenous gonadotropic hormones to stimulate reproduction.These species were mostly from Palearctic or cool mountain regions,but also included a wide range of species from warm regions.Other early achievements included the successful cryopreservation of anuran spermatozoa and anuran diploid pluripotent cell nuclei,in order to store both the matrilineal and patrilineal genomes in biobanks,with their subsequent development to the blastula stage after implantation into enucleated oocytes.After the turn of the 21st Century,in support of the priorities of the Amphibian Conservation Action Plan(2007),we developed RTs for the refrigerated storage of testicular or urinary spermatozoa for days to weeks at 4℃,the cryopreservation of urinary spermatozoa using anovel cryoprotectant,the in vitro fertilisation of hormonally induced oocytes either fresh or after refrigerated ex situ or in situ storage,and the artificial insemination of salamanders with fresh spermatozoa.In this article,we describe previously unpublished techniques and techniques from obscure Russian sources.

Hepatitis B virus infection, infertility, and assisted reproduction

Background:Hepatitis B virus(HBV)is one of the most widespread viruses worldwide and a major cause of hepatitis,cirrhosis,and hepatocellular carcinoma.Previous studies have revealed the impacts of HBV infection on fertility.An increasing number of infertile couples with chronic hepatitis B(CHB)virus infection choose assisted reproductive technology(ART)to meet their fertility needs.Despite the high prevalence of HBV,the effects of HBV infection on assisted reproduction treatment remain limited and contradictory.Objective:The aim of this study was to provide a comprehensive overview of the effect of HBV infection on fertility and discuss its effects on pregnancy outcomes,vertical transmission,pregnancy complications,and viral activity during ART treatment.Methods:We conducted a literature search in PubMed for studies on HBV infection and ART published from 1996 to 2022.Results:HBV infection negatively affected fertility in both males and females.Existing research shows that HBV infection may increase the risk of pregnancy complications in couples undergoing assisted reproduction treatment.The impact of HBV infection on the pregnancy outcomes of ART is still controversial.Current evidence does not support that ART increases the risk of vertical transmission of HBV,while relevant studies are limited.With the development of ART,the risk of HBV reactivation(HBVr)is increasing,especially due to the wide application of immunosuppressive therapy.Conclusions:Regular HBV infection screening and HBVr risk stratification and management are essential to prevent HBVr during ART.The determination of optimal strategy and timing of prophylactic anti-HBV therapy during ART still needs further investigation.

A laboratory modification to testicular sperm preparation technique improves spermatogenic cell yield

Testicular sperm extraction is a common procedure used to find spermatogenic cells in men with nonobstructive azoospermia. The laboratory processing of biopsied testicular tissues needs to be performed meticulously to acquire a high yield of cells. In this study, the effectiveness of mincing the tissues after testicular biopsy was assessed using histological evaluation, as was the possible adverse effect of residual tissue on the migration of spermatogenic cells during density gradient centrifugation. Our results indicate that testicular residual tissue, when laid on the density gradient medium along with the sperm wash, hinders the spermatogenic cells＇ forming a pellet during centrifugation, and therefore impairs the intracytoplasmic sperm injection procedure. Whereas the mean number of recovered cells from the sperm wash medium （SWM） with residual tissue is 39.435 ~ 24.849, it was notably higher （60.189 ~ 28.214 cells） in the SWM without minced tissues. The remaining tissue contained no functional seminiferous tubules or spermatogenic cells in histological sections. In conclusion, the remaining residual tissue after mincing biopsied testicular tissue does not add any functional or cellular contribution to spermatogenic cell retrieval; in fact, it may block the cellular elements in the accompanying cell suspension from migrating through the gradient layers to form a pellet during centrifugation and cause loss of spermatogenic cells.

Assisted Reproductive Technology for HIV-1 Serodiscordant Couples: A Review of Current Controversies

Since 1992, assisted reproductive technology （ART） has been reported as a viable means of helping HIV-1 serodiscordant couples achieve pregnancy while theoretically reducing the risk for viral transmission. While the sum of the evidence suggests that ART is effective and safe, numerous controversies still exist, The follow- ing review addresses several of the important issues involved in the use of ART for HIV-serodiscordant couples, including patient selection, semen processing techniques, post-process HIV testing, the use of lUI vs IVF-ICSI.

Towards better meta-analyses in assisted reproductive technology: Fixed, random or multivariate models?

AIM: To study the validity of the fixed, random, and multivariate meta-analytical models applied in meta-analyses in artificial reproduction technique. METHODS: Based on common characteristics of in vitro fertilization(IVF) meta-analyses, we simulated a large number of data to compare results issued from the fixed model(FM) with the random model(RM). For multiple endpoints meta-analysis(MA), we compared the univariate RM with the multivariate model(MM). Finally, we illustrate our findings in re-analyzing a recent MA. RESULTS: In our review, although a homogeneous effect was excluded in 89% of the MAs(11%), FM was utilized in 41 studies(82%). From simulations, a concordance of 59% ± 6% was found between the two tests, with up to 65% of falsely significant results with FM. The Q-test on studies characterized by substantial heterogeneity falsely accepted homogeneity in 46% of studies. Comparing separate univariate RM and MM on multiple endpoints studies, MM reduces the between endpoint discrepancy(BED) of 68%, and increases the power of 57% ± 8%. In the example dealing with the controversial effect of luteneizing hormone supplementation to follicle stimulating hormone during ovarian stimulation in IVF cycles, MM reduced BED by 66%, and consistent effects were found for all the endpoints, irrespective of partial reporting. CONCLUSION: The FM generally may produce falsely significant differences. The RM should always be used. For multiple endpoints, the MM constitutes the best option.

Impact of COVID-19 pandemic on the pregnancy outcomes of women undergoing assisted reproductive techniques(ARTs):a systematic review and meta-analysis

The global outbreak of the coronavirus disease 2019(COVID-19) led to the suspension of most treatments with assisted reproductive technique(ART). However, with the recent successful control of the pandemic in China, there is an urgent public need to resume full reproductive care. To determine whether the COVID-19 pandemic had any adverse effects on female fertility and the pregnancy outcomes of women undergoing ART, a systematic review and meta-analysis was conducted using the electronic Chinese and English databases. Dichotomous outcomes were summarized as prevalence, and odds ratios(ORs)and continuous outcomes as standardized mean difference(SMD) with 95% confidence interval(CI). The risk of bias and subgroup analyses were assessed using Stata/SE 15.1 and R 4.1.2. The results showed that compared with women treated by ART in the pre-COVID-19 time frame, women undergoing ART after the COVID-19 pandemic exhibited no significant difference in the clinical pregnancy rate(OR 1.07, 95% CI 0.97 to 1.19;I^(2)=0.0%), miscarriage rate(OR 0.95, 95% CI 0.79 to1.14;I^(2)=38.4%), embryo cryopreservation rate(OR 2.90, 95% CI 0.17 to 48.13;I^(2)=85.4%), and oocyte cryopreservation rate(OR 0.30, 95% CI 0.03 to 3.65;I^(2)=81.6%). This review provided additional evidence for gynecologists to guide the management of women undergoing ART treatment during the COVID-19 pandemic timeframe.

卵泡期高孕激素状态下促排卵方案的应用进展

辅助生殖技术中,控制性促排卵过程中预防内源性黄体生成素(luteinizing hormone,LH)峰的过早出现至关重要。传统的控制性促排卵方案使用促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)类似物(GnRH激动剂或拮抗剂)抑制内源性LH水平,存在成本高、使用不方便等缺点。卵泡期高孕激素状态下促排卵(progestin-primed ovarian stimulation,PPOS)方案利用外源性孕激素对垂体的负反馈作用抑制LH水平,已被证实在各种人群中均可获得较好的临床结局,其子代安全性也得到初步证实。综述PPOS方案的具体机制、不同外源性孕激素类药物的应用、不同人群的应用效果及子代安全性等。

不孕不育人群生育生活质量评价及其影响因素分析

生育生活质量量表(Fertility Quality of Life Questionnaire,FertiQoL)是不孕不育人群生活质量测量的特异性量表。生育生活质量下降会影响不孕不育人群的治疗积极性及治疗依从性,从而影响患者的助孕结局。大量研究表明,不孕不育人群生育生活质量各模块及维度均有受损,但影响因素及对不同维度的影响程度尚无统一结论。中国和国外不孕不育人群生育生活质量受损情况不同,中国患者治疗模块受损更严重,国外患者核心模块受损更严重。社会支持、心理韧性是生育生活质量的保护因素,焦虑、抑郁、述情障碍、生育压力、病耻感则与生育生活质量呈负相关。除此之外,性别、年龄、居住地、受教育程度及不孕年限等一般特征也是不孕不育人群生育生活质量的重要影响因素。但目前对于提高患者生育生活质量的干预措施及干预后临床妊娠率是否得到提升的研究尚不充分。

促性腺激素释放激素激动剂长方案促排卵后鲜胚移植的临床妊娠列线图预测模型构建

目的探讨促性腺激素释放激素激动剂(GnRH-a)长方案促排卵并鲜胚移植后临床妊娠结局的影响因素,构建临床妊娠的列线图预测模型,并验证模型。方法纳入2019年1月—2023年4月于兰州大学第一医院生殖医学中心行GnRH-a长方案促排卵并鲜胚移植共4627个周期的临床资料,统计分析纳入患者的一般临床资料、临床妊娠结局。采用最小绝对收缩和选择算子(LASSO)回归技术和多因素Logistic回归筛选数据维度和预测因子,按照7∶3的比例将最终纳入的3470个周期随机分配为训练集(2429个)和测试集(1041个)。采用多因素Logistic回归分析建立临床妊娠结局的预测模型并用列线图将其可视化。采用曲线下面积(AUC)、Hosmer-Lemeshow拟合优度检验和决策曲线分析(DCA)评估模型。结果根据LASSO回归分析计算选择18个非零系数变量,多因素Logistic回归分析结果显示年龄、多囊卵巢综合征、反复妊娠丢失、高血压家族史、促性腺激素启动日剂量、扳机用药、扳机日孕酮水平、扳机日子宫内膜厚度、移植胚胎数量、移植优质胚胎数量、移植胚胎类型(囊胚与否)和男方弱精子症患病与否共12个因素作为预测因子建立Logistic模型并用列线图可视化;训练集AUC为0.657,验证集AUC为0.617,Hosmer-Lemeshow检验显示该模型拟合好(P=0.208,平均绝对误差=0.008),DCA提示当患者临床妊娠的阈值概率在11%~67%时,应用该列线图可增加净获益。结论该模型可为GnRH-a长方案促排卵并鲜胚移植周期临床妊娠结局预测提供参考,但该模型的预测精度有限,有待于进一步开发。

辅助生殖技术助孕后卵巢过度刺激综合征合并卵巢扭转一例

随着辅助生殖技术(assisted reproductive technology,ART)的发展,其主要的医源性并发症卵巢过度刺激综合征的出现亦是难以避免的,也进一步增加了卵巢扭转的风险。卵巢过度刺激综合征合并卵巢扭转患者的临床症状及影像学检查等特异度较低,故对该类急腹症的早期识别和诊断比较困难。本文报告1例ART治疗的患者,在取卵前发生卵巢过度刺激综合征合并卵巢扭转,在取卵后保守治疗效果欠佳,最终仍不可避免地需行手术治疗。该案例提示,ART治疗中加强对卵巢过度刺激综合征合并卵巢扭转的认识,对此类急腹症做到早识别、早诊断及早治疗。

抗苗勒管激素和抑制素B预测卵巢反应性及ART结局的研究进展

女性生育力是人类繁衍的珍稀资源,卵巢储备是生育力的决定者和体现者;随着女性年龄增加,卵巢内卵子的数量和质量均呈下降趋势,是影响辅助生殖技术助孕成功率的主要因素。为了指导个体化用药,获得优质卵子,越来越多的临床指标用于预测卵巢储备,成为体外受精前常规检测指标。现对抗苗勒管激素(AMH)和抑制素B(INH B)在预测卵巢功能和ART结局方面的最新研究进展进行综述,认为AMH对卵巢低反应、高反应及卵巢过度刺激综合征(OHSS)均有良好的预测价值;INH B的预测价值并不优于其他指标;目前尚无预测辅助生殖技术妊娠结局的良好指标。

辅助生殖技术助孕患者痛苦表露的潜在剖面分析

目的:了解辅助生殖技术助孕患者痛苦表露潜在类别,分析各类别的影响因素。方法:采用便利抽样法,选取2023年8-10月在南京医科大学附属妇产医院接受辅助生殖技术治疗的患者作为调查对象。采用一般资料问卷和痛苦表露指数量表进行调查。采用Mplus 8.0软件进行潜在剖面分析,使用SPSS 27.0软件进行单因素分析和多分类Logistic回归分析。结果:本研究共调查192例辅助生殖技术助孕患者,痛苦表露指数量表中位得分为39.00(31.00,47.00)分。痛苦表露共分为3种潜在剖面:低水平表露型(n=41,21.4%)、中等水平表露型(n=82,42.7%)和高水平表露型(n=69,35.9%)。多分类Logistic回归分析结果显示,文化程度、长期居住地、辅助生殖技术治疗周期数、生育压力主要来源、感知治疗期间经济负担、不孕原因是不同类别辅助生殖技术助孕患者痛苦表露的影响因素(均P<0.05)。结论:辅助生殖技术助孕患者痛苦表露具有明显的分类特征,医护人员应对不同痛苦表露特征的患者进行鉴别并针对性地采取护理支持措施,鼓励患者通过自我表露,减轻心理困扰。

基于数据挖掘探讨中医药在辅助生殖技术中的分期应用

目的:基于数据挖掘技术整合分析名医名家临证应用中医药配合辅助生殖技术(assisted reproductive technology,ART)的各期方药分布规律。方法:计算机系统检索中国知网、维普中文科技期刊数据库、万方数据库和中国生物医学文献数据库中名医名家临证应用中医药配合ART的相关文献,建立文献分析数据库进行整合归纳,获得其中药物分布规律。结果:本研究纳入合格文献共112篇,涉及名家36人。降调期药物共获得总类别13种,相关药物77味,累计出现频次224次,频率较高者为“补虚药”(55.94%)、“活血化瘀药”(10.89%)、“清热药”(6.44%)、“收涩药”(5.45%)、“利水渗湿药”(5.45%)等;促排期药物共获得总类别13种,相关药物92味,累计出现频次398次,频率较高者为“补虚药”(61.34%)、“活血化瘀药”(8.68%)、“收涩药”(8.40%)、“清热药”(5.88%)、“利水渗湿药”(5.32%)等;移植期药物共获得总类别14种,相关药物70味,累计出现频次372次,频率较高者为“补虚药”(68.78%)、“祛风湿药”(5.80%)、“活血化瘀药”(5.52%)等;确认妊娠后用药物共获得总类别11种,相关药物47味,累计出现频次182次,频率较高者为“补虚药”(59.88%)、“祛风湿药”(9.30%)、“清热药”(7.56%)、“收涩药”(5.23%)等。四期用药关联分析显示降调期分析得18组药物组合,促排期分析得14组药物组合,移植期分析得41组药物组合,确认妊娠后分析得22组药物组合。四期用药聚类分析结果显示降调期得到核心药物组:党参-甘草-白术-黄芪-酸枣仁、菟丝子-枸杞子-熟地黄-当归-香附、熟地黄-白芍-阿胶-菟丝子-生地黄;促排期得到核心药物组:菟丝子-熟地黄-山药-枸杞子-桑椹、菟丝子-熟地黄-当归-枸杞子-丹参、熟地黄-山茱萸-山药-菟丝子-生地黄;移植期得到核心药物组:白术-续断-桑寄生-党参-菟丝子、桑寄生-菟丝子-续断-黄芩-阿胶、当归-菟丝子-甘草-山药-巴戟天;确认妊娠后得到核心药物组:白术-黄芪-甘草-党参-续断、菟丝子-续断-白术-桑寄生-阿胶、白术-续断-甘草-苎麻根-杜仲。结论:“补虚药”是四期主要应用的药物种类,药物主要归肝肾脾经,“以补为主,攻补兼施,性以温平,味以甘苦”是四期用药的共同特点,临床应根据四期不同特点进行相应的遣方用药以提高疗效,降调期以防气血躁动为主;促排期应以补肾精为主,同时应加用少量温阳药物,在补肾的同时应涩促结合,防止肾精过耗;移植期与胚胎着床后中药的功效主要在于“稳固胎元”,应注重补养母体气血。

辅助生殖技术助孕后三胎合并双胎反向动脉灌注序列征一例并文献复习

双胎反向动脉灌注序列征(twin reversed arterial perfusion sequence,TRAPS)是单绒毛膜双胎妊娠(单绒双胎)的严重并发症,较为罕见,是由于双胎妊娠中胎儿胎盘间血管异常吻合所致,特征表现为其中一胎心脏缺如或心脏结构失去正常发育形态。报告南通大学附属南通妇幼保健院收治的1例发生于辅助生殖技术助孕后三胎妊娠中的TRAPS。患者移植2枚卵裂期冻融胚胎,其中1枚胚胎在分裂过程中发育为单绒双胎。患者孕8+5周早孕B超及时诊断单绒双胎为TRAPS,但因个人因素未行干预,单绒双胎TRAPS之泵血胎儿死亡。另一单胎发育正常至足月分娩。TRAPS如果需要治疗,射频消融术通常是阻断无心胎儿血流供应技术的首选方法,但干预的最佳时机仍存在争议。

ART中影响新生儿性别比的相关因素分析

辅助生殖技术(assisted reproductive technology,ART)在给广大不孕不育患者带来福音的同时,也带来了男女出生性别比的失衡,相关影响因素有待研究分析。通过收集并分析2013年1月至2014年12月于广州医科大学附属第三医院接受ART治疗并成功分娩4 635个新生儿的3 462个周期患者的临床资料发现,ICSI组与IVF组比较,活产男婴比例没有统计学差异(P=0.07),但PESA/TESA-ICSI组出生男婴比例较IVF组显著降低(P=0.036);同时,移植囊胚期胚胎出生的男婴比例要显著高于移植卵裂期胚胎的男婴比例(P=0.005)。进一步的分层卡方检验结果显示,除去授精方式的影响,移植胚胎期别仍然可以影响出生婴儿的性别比(P=0.021)。但多因素logistic回归分析提示,以上因素均不能构成独立预测因素。上述结果表明在体外受精-胚胎移植周期中,移植囊胚期胚胎可显著增加男婴出生比例,而PESA/TESA-ICSI授精方式则会显著降低男婴出生比例。

小柴胡汤治疗不孕症的研究进展

小柴胡汤是《伤寒论》中著名方剂,具有和解少阳、疏肝解郁、调和气血等功效,可以用来治疗外感、内伤杂病、妇人病等疾病,疗效良好。中医学认为不孕症的病机与肾精亏虚、肝气郁结等因素有关,针对“肝气郁结”这一病机,结合张机“但见一证便是,不必悉具”之宗旨,小柴胡汤常被临床用于治疗不孕症及其相关疾病。

ART知情同意的困境与对策

由于受到千百年来传统家庭观念及患者认知能力的影响,同时,由于辅助生殖技术(ART)的专业性、复杂性,ART技术应用的局限性、结果的不确定性以及诊治周期长、费用高等因素的存在,ART知情同意过程面临着困境。ART伦理管理落实真实知情同意的体现在对患者进行充分、全面、如实的信息告知,取得其配偶的同意和支持,完善的、个案化的文书签定,是ART伦理管理落实真实知情同意的体现。

卵巢过度刺激综合征的发病机制及预防药物研究进展

卵巢过度刺激综合征(OHSS)是辅助生殖技术中常见的并发症之一,其发生机制尚未完全明确,内源性或外源性人绒毛膜促性腺激素(HCG)刺激卵巢释放大量的血管活性物质被认为是OHSS发病的核心环节。目前临床对OHSS的预防方法包括药物、个体化控制性促排卵、全胚冷冻、滑行疗法及未成熟卵母细胞体外成熟等手段,但仍未能完全预防OHSS的发生,且中重度OHSS对患者的生理及心理健康产生不利影响。因此,阐明OHSS的发病机制,发现可靠的预防方法,降低患者周期取消率及经济负担至关重要。本文将就OHSS的发病机制及预防药物研究进展进行综述,以期为OHSS的预防及治疗提供临床参考。