Background Patients with recurrent implantation failure (RIF) may have more uterine contractions. Several observational studies suggested that atosiban administration around embryo transfer resulted in higher pregnancy rates in RIF patients. This study aimed to evaluate the effect of atosiban given before fresh embryo transfer on pregnancy outcomes of women with RIF. Methods A prospective, randomized, double-blind controlled clinical trial was performed in IVF center of Shanghai First Maternity and Infant Hospital. According to a computer-generated randomization list, 194 infertile women with RIF received fresh embryo transfer between July 2017 and December 2019 were randomly allocated into the atosiban ( n = 97) and the placebo ( n = 97) groups. Women in the treatment group received atosiban intravenously about 30 min before embryo transfer with a bolus dose of 6.75 mg over one minute. Those in the placebo group received only normal saline infusion for the same duration. Results There was no significant difference in the live birth rate between the atosiban and placebo groups (42.3% vs 35.1%, P = 0.302, RR = 1.206 (0.844–1.723)). No significant differences were found between the two groups in the positive pregnancy test, clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy and implantation rates. Similar results were found when stratified by the number of embryos previously transferred, number of previous failed embryo transfers, frequency of endometrial peristalsis on embryo transfer day (≥ 3 waves/min) or serum estradiol (E 2 ) on the day of hCG above the median level. And, there was no correlation between the serum E 2 level on the day of hCG and the frequency of endometrial peristalsis on embryo transfer day. The frequency of endometrial peristalsis on embryo transfer day, total FSH/HMG dosage and duration were the significant factors which independently predicted the likelihood of a live birth. Conclusions These results suggested that atosiban treatment before fresh embryo transfer might not improve the live birth rate in RIF patients. Trial registration The study had been approved by the Institutional Review Board of the hospital (2017 ethics No.43) and was registered under Clinicaltrials.gov with an identifier NCT02893722.

Endoplasmic reticulum (ER) stress, with adaptive unfolded protein response (UPR), is a key link between obesity, insulin resistance and type 2 diabetes, all of which are often present in the most common endocrine-metabolic disorder in women of reproductive age, polycystic ovary syndrome (PCOS), which is characterized with hyperandrogenism. However, the link between excess androgen and endoplasmic reticulum (ER) stress/insulin resistance in patients with polycystic ovary syndrome (PCOS) is unknown. An unexpected role of kisspeptin was reported in the regulation of UPR pathways and its involvement in the androgen-induced ER stress in hypothalamic neuronal cells. To evaluate the relationship of kisspeptin and ER stress, we detected kisspeptin and other factors in blood plasm of PCOS patients, rat models and hypothalamic neuronal cells. We detected higher testosterone and lower kisspeptin levels in the plasma of PCOS than that in non-PCOS women. We established a PCOS rat model by dihydrotestosterone (DHT) chronic exposure, and observed significantly downregulated kisspeptin expression and activated UPR pathways in PCOS rat hypothalamus compared to that in controls. Inhibition or knockdown of kisspeptin completely mimicked the enhancing effect of DHT on UPR pathways in a hypothalamic neuronal cell line, GT1-7. Kp10, the most potent peptide of kisspeptin, effectively reversed or suppressed the activated UPR pathways induced by DHT or thapsigargin, an ER stress activator, in GT1-7 cells, as well as in the hypothalamus in PCOS rats. Similarly, kisspeptin attenuated thapsigargin-induced Ca2+ response and the DHT- induced insulin resistance in GT1-7 cells. Collectively, the present study has revealed an unexpected protective role of kisspeptin against ER stress and insulin resistance in the hypothalamus and has provided a new treatment strategy targeting hypothalamic ER stress and insulin resistance with kisspeptin as a potential therapeutic agent.

Objective: The present study focused on the clinical pregnancy and cumulative live birth rate (CLBR) of female patients with X chromosome mosaicism (XM) after the first in-vitro-fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment, and the possible impact of different mosaic subtypes. Design: Retrospective cohort study Setting: Single Center study Population: Infertility couples Methods: In total, 76 couples with XM female partners and normal male partners were included (2014–2019) as the X group, with another 76 couples with normal karyotype included as the control group. Subgroup X1 included 41 45,X/46,XX cases, Subgroup X2 included 22 47,XXX/46,XX cases, and Subgroup X3 included 12 45,X/47,XXX/46,XX cases. Main Outcome Measures: The ovarian stimulation, embryo results and pregnancy outcomes were analyzed. Results: The X group presented similar CLBR but required a higher total gonadotropin (Gn) dosage than the control group (1800 IU vs. 1612 IU). Following subgroup analysis, the number of follicles during oocyte retrieval and average number of fertilized oocytes was lower in subgroup X1 than in X3. The clinical pregnancy rate and CLBR were similar in all groups. Conclusion: Females with XM may present a similar CLBR until one year after oocyte retrieval, but may require a higher total Gn dosage. Females with 45,X cells may recover fewer follicles during oocyte retrieval, resulting in fewer embryos. A higher 45,X cell ratio (over 5%) may lead to a lower CBLR. Funding: This study was supported by the Ministry of Science and Technology of China (2016YFC1000602). Keywords X chromosome mosaicism, IVF/ICSI outcome, cumulative live birth rate

BACKGROUND:This study focused on the outcomes of patients with pericentric inversion of chromosome 9 who underwent IVF/ICSI and fresh day 2 or day 3 embryo transfer and the possible impacts of carrier gender and chromosome karyotype on pregnancy outcomes.METHODS:A total of 214 couples (107 couples with one pericentric inversion of chromosome 9 in one partner [Group 1], 107 couples with normal karyotypes [Group 2]) underwent their first IVF/ICSI treatment and were included in this study. Oocyte number, normal fertilization rates, abnormal fertilization rates, cleavage rates, embryo utilization rates, fresh embryo transfer rates, clinical pregnancy rates (CPR), implantation rates, miscarriage rates, and live birth rates per embryo transfer (LBR) were compared between groups.RESULTS:Group 1 did not show any disadvantage when compared with Group 2. The CPR and LBR were similar between all groups. The female carrier group had a higher normal fertilization rate and higher utilization rate than the male carrier group. Cases with inv(9)(p12;q13) had a lower utilization rate but a higher implantation rate than the remaining karyotypes.CONCLUSION:In the first IVF or ICSI cycle, couples with one pericentric inversion of chromosome 9 in one partner had satisfactory outcomes. The subgroup analysis showed a tendency of better prognosis for the female carrier and inv(9)(p12;q13) type.

OBJECTIVE:To measure blood and follicular antimüllerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) undergoing assisted reproductive technologies (ART) and to examine the direct action of insulin on AMH expression in human granulosa cells. DESIGN:Prospective clinical and experimental study. SETTING:University Hospital-based laboratory. PATIENT(S):Women with (n = 86) and without (n = 172) PCOS in ART. INTERVENTION(S):Blood, follicular fluid, and luteinized granulosa cells were collected from PCOS and non-PCOS women in ART. MAIN OUTCOME MEASURE(S):Hormone levels in blood and fluid, and gene expression in granulosa cells. RESULT(S):Serum levels of AMH were elevated and inversely correlated with embryo cleavage rate in PCOS women in ART. Significant higher levels of AMH were also found in small and large follicles collected from PCOS women compared with non-PCOS women. Luteinized granulosa cells from PCOS women showed higher expression of AMH and its receptor AMHR2. Direct effect of insulin in increasing the expression of AMH in the isolated luteinized granulosa cells was observed, with the PCOS granulosa cells responding to a high dose of insulin. Cotreatment with AMH attenuated insulin-induced aromatase expression in the luteinized granulosa cells. CONCLUSION(S):These results suggest that insulin may contribute to AMH elevation in PCOS and that AMH counteracts insulin-promoted aromatase expression in granulosa cells.

首要排查染色体风险 一般来说,只要没有染色体方面的问题,高龄女性孕育的宝宝跟年轻女性孕育的宝宝在身体素质上并无差别.大龄备孕女性在备孕期可以先做些简单的自查,如基础体温测定等,观察排卵情况.如果有月经异常、内分泌异常等问题造成妊娠困难的情况,及时到医院全面检查,争取尽快解决问题.

Objective To investigate the effect of appropriate starting time of gonadotropin (Gn) in modified prolonged protocol on outcomes of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) in women with endometriosis (EMS).Methods A total of 98 cycles from infertile patients who underwent IVF/ICSI were retrospectively analyzed.The patients were divided into group A (modified prolonged protocol,EMS,n=44),group B (modified prolonged protocol,non-EMS,n=21) and group C (regular prolonged protocol,EMS,n=33).The difference of clinic outcomes was compared and analyzed among the different groups.Results 1) The total dosage of Gn used was lower and the fertilization rate was higher in group A [(2 330.4 ± 747.8) IU,77.6％]than in group B [(3 338.7 ± 1 341.5) IU,65.8％],the differences were statistically significant (P＜0.05).No statistically significant difference was observed in the number of oocytes retrieved and the clinical pregnancy rate between group A and group B (P＞0.05).2) The initial dosage and total dosage of Gn used in group A [(192.0±35.3) IU,(2 330.4 ± 747.8) IU] was higher than that in group C [(228.8 ± 48.9) IU,(2 828.5 ± 1 129.0) IU],the difference was statistically significant (P＜0.05).The number of retrieved oocytes in group A (8.8 ± 4.7) was higher than that in group C (6.1 ± 3.9),the difference was statistically significant (P＜0.05).No statistically significant difference was found m the fertilization rate,high-quality embryos rate,clinical pregnancy rate between group A and group C (P＞0.05).Conclusion It is a cost-effective controlled ovarian hyperstimulation (COH)protocol for infertile patients with EMS,because the modified prolonged protocol can reduce the dosage of Gn used without affecting the clinical results through monitoring E2 level.

Objective:To analyze the influencing factor of the in vitro fertilization and embryo transfer failure.Methods:The clinical data of 4 886 patients were collected.The patients with assisted pregnancy success at the first time(1 420 cases),324 success cycles and 365 failure cycles patients with assisted pregnancy success at two times and more than two times were divided into group A,B and C,respectively.The related factors of in vitro fertilization and embryo transfer failure were analyzed.Results:The age and infertile time in group A were significantly less and shorter than those in group B,respectively(P<0.01).The assisted reproductive technology(ART) results showed that long protocol in ovulation was often implemented in group A compared with group B,the mini-stimulation and antagonist protocol were often used in group B compared with group C,and the proportion of ICSI in group B was higher than that in group A and group C(P<0.01).The results of IVF also showed that the number of embryo transplantation in group B was more than that in group A,the total number of oocyte retrieval,fertilization rate,high quality embryo rate,number of available embryo,number of frozen embryo and implanting rate in group B were lower compared with group A(P<0.01),and the total number of oocyte retrieval,fertilization rate,cleavagerate rate,high quality embryo rate,number of available embryo,number of frozen embryo and implanting rate in group B were higher compared with group C(P<0.05 to P<0.01).Conclusions:The patients with older age,longer duration of infertility,less retrieved oocyte,less available embryo and poorer quality embryo are easy to lead to the in vitro fertilization and embryo transfer failure.

赠卵试管婴儿使原本无法怀孕的妇女获得了做母亲的权利,其成败的核心是子宫内膜的准备,生殖内分泌学和女性激素制剂进展为其提供了保证.本文从卵子捐赠指征、受卵者及其黄体支持等研究,综述相关临床孕激素的应用研究.

目的:通过回顾卵巢过度刺激综合征(OHSS)患者的情况,分析OHSS患者在控制性超促排卵(COH)过程中存在的危险因素及早发型和晚发型OHSS的差异.方法:选择2002年6月-2010年8月在本院行体外受精(IVF)治疗因中、重度OHSS住院患者36例(OHSS组),其中早发型OHSS 25例,晚发型OHSS 11例.选取因OHSS倾向行全胚冷冻或单胚移植而未发生OHSS的患者76例为高危组.另选取同期移植≥2个胚胎,与OHSS组基本情况相近,未发生OHSS者61例为对照组.记录注射人绒毛膜促性腺激素(hCG)日血清雌二醇(E2)水平、穿刺卵泡数及获卵数等.结果:①早发型OHSS患者hCG日E2水平高于晚发型(P＜0.05).②OHSS组和高危组的hCG日E2值,卵泡数均高于对照组(P＜0.05).③3组获卵数差异有统计学意义(P＜0.05),OHSS组的获卵数少于高危组(P＜0.05).结论:①hCG日E2值升高可作为OHSS发生的参考指标.②卵泡数及获卵数是预测OHSS敏感的指标.③中、小卵泡较多时更易导致OHSS.

目的:探讨辅助生殖技术(ART)后发生异位妊娠(EP)的类型及危险因素.方法:收集2008年1月至2013年6月在本中心行ART后发生EP及同期宫内妊娠(IUP)各97例患者的临床资料,分别作为EP组和IUP组,观察发生EP的类型,并对其危险因素进行单因素及多因素Logistic回归分析.结果:97例EP中输卵管妊娠85例(87.63％),宫角妊娠5例(5.15％),宫内外同时妊娠4例(4.12％).单因素分析结果显示,EP组继发不孕的比例明显高于IUP组(x2=8.25,P＜0.1),既往有人工流产史和输卵管手术史患者的比例高于对照组(x2 =2.72,P ＜0.1;x2=12.44,P＜0.1),HCG日子宫内膜厚度比IUP组薄(x2=3.61,P＜0.1).将单因素分析有差异的因素纳入多因素Logistic回归分析,结果显示,继发不孕(OR=2.072,95％CI 1.129～3.804,P＜0.05),输卵管手术史(OR=3.770,95％CI 1.684 ～ 8.438,P＜0.05),HCG日子宫内膜厚度(OR=0.496,95％CI0.285 ～0.862,P＜0.05)为行ART后发生EP的独立危险因素.结论:ART后特殊部位EP有所增加.继发不孕、有输卵管手术史或HCG日子宫内膜较薄的患者在行ART后发生EP的风险显著增加.

Women with polycystic ovary syndrome (PCOS) undergoing IVF-embryo transfer based-assisted reproductive technology (ART) treatment show variable ovarian responses to exogenous FSH administration. For better understanding and control of PCOS ovarian responses in ART, the present study was carried out to compare the follicular hormones and the expression of granulosa cell genes between PCOS and non-PCOS women during ART treatment as well as their IVF outcomes. Overall, 138 PCOS and 78 non-PCOS women were recruited for the present study. Follicular fluid collected from PCOS women showed high levels of testosterone. The expression of aromatase was found significantly reduced in luteinized granulosa cells from PCOS women. In cultured luteinized granulosa cells isolated from non-PCOS women, their exposure to testosterone at a level that was observed in PCOS follicles could decrease both mRNA and protein levels of aromatase in vitro. The inhibitory effect of testosterone was abolished by androgen receptor antagonist, flutamide. These results suggest that the hyperandrogenic follicular environment may be a key hazardous factor leading to the down-regulation of aromatase in PCOS.

目的 研究在体外授精(in vitro fertilization,IVF)治疗过程中多囊卵巢综合征患者(polycystic ovarian syndrome,PCOS)与非多囊卵巢综合征患者的对照组促排卵后内分泌的差别,胚胎质量和妊娠结局的差异,探讨内分泌情况以及卵泡微环境对PCOS患者在IVF治疗中卵泡发育以及妊娠结局的影响.方法 将自2011年12月-2013年3月在上海市第一妇婴保健院生殖中心行IVF助孕的患者分成对照组和PCOS组.比较两组的一般情况,内分泌以及卵泡液中激素水平改变,以及胚胎质量和IVF妊娠结局等.结果 两组一般情况无明显区别,PCOS的获卵率明显低于对照组,而受精数,卵裂数,妊娠率等无明显差别.PCOS组中卵泡液睾酮(T)水平高于对照组.结论 PCOS患者内分泌紊乱尤其是高水平的卵泡液睾酮会影响卵子发育成熟,降低成熟卵子的获得率,但是卵子及胚胎质量并未受到影响,临床在促排卵前应注重改善PCOS微环境,提高成熟卵子获得率.

目的 本研究将基于已经建立的三维小鼠体外胚胎着床模型,将整个培养环境的氧浓度调整为2％,从而探究缺氧环境对胚胎着床的作用和影响.方法 将已经建立的小鼠体外着床模型分为两组,其中一组置于氧浓度2％的密封箱内进行培养.另外一组为对照组,直接置于培养箱中,按照原先的大气氧浓度进行培养.观察对比这两组之间胚胎与内膜的黏着率.并对着床胚胎及内膜进行组织切片,观察组织的形态学变化,检测其中细胞凋亡的情况.结果 小鼠囊胚在2％的氧浓度及大气氧浓度下的胚胎黏着率分别为41.4％及53.2％;这两组的胚胎黏着率比较,差异无统计学意义.两种情况下的小鼠胚胎均已经黏附于体外共培养的子宫内膜上皮层表面,未见明显形态学异常.但在2％氧浓度下,子宫内膜组织中很多间质细胞发生了细胞凋亡.结论 2％的氧浓度在三维体外胚胎着床模型的运用中,虽然没有导体外胚胎黏着率的显著降低,但却诱导了体外培养子宫内膜组织中细胞的凋亡.

目的 讨论子宫内膜异位症对体外受精-胚胎移植过程的影响.方法 对生殖中心自2008年1月至2011年-1月共63例子宫内膜异位症合并不孕患者(内异症组)的体外受精-胚胎移植结局等进行回顾性分析;并选取同期136例输卵管因素不孕患者(对照组)作为对照组,从促排卵药物总量、用药时间、HCG日雌二醇(estrogen,E2)、孕酮、促黄体生成素水平、获卵数、受精率、卵裂率、优质胚胎率、冷冻胚胎数、妊娠率、种植率、流产率、异位妊娠率等方面进行比较分析.结果 内异症组用药总量显著高于对照组(P＜0.01),内异症组HCG日E2水平、获卵数、卵裂率、优质胚胎率、冷冻胚胎数明显低于对照组(P＜0.05).结论 子宫内膜异位症患者卵巢储备能力下降,同时其卵子及胚胎质量亦下降.

目的 运用已有的小鼠体外三维着床模型观察LIF抑制状态下对胚胎着床这一过程中的影响以及其转导通路中下游STAT3和pSTAT3蛋白表达水平的变化,从而探究LIF及其转导通路在胚胎着床中的功能.方法 将小鼠内膜组织置于有不同浓度LIF抗体(0.1和1.0μg/ml)及正常IgG对照和阴性对照的培养基中预培养0.5h.然后进行内膜组织和囊胚的共培养,观察比较胚胎与内膜的黏着率的不同,并对抗体处理后的内膜进行STAT3及pSTAT3的免疫组化染色.结果 运用1.0％抗体预处理组的黏着率与正常IgG对照组及阴性对照组之间均有统计学差异.pSTAT3的表达在经LIF抗体预处理的内膜中明显高于对照组.结论 LIF在小鼠胚胎着床中起着非常重要的作用,通过LIF表达的降调节可以显著降低胚胎黏着率.LIF对胚胎黏着的作用可能是通过JAK/STAT通路中STAT3的磷酸化活化而实现的.

目的:比较玻璃化法与慢速程序法对人卵裂期胚胎冷冻复苏的效果.方法:将接受体外受精-胚胎移植患者的取卵周期移植后剩余的胚胎,分别进行玻璃化法或慢速程序法冷冻,比较两组胚胎解冻后的复苏率、胚胎完整率、胚胎种植率、临床妊娠率及观察非当日移植的复苏胚胎的发育潜能等指标.结果:玻璃化冷冻组的活产率均显著高于慢速程序化冷冻;玻璃化冷冻后的胚胎复苏率和胚胎完整率显著高于慢速程序化冷冻;复苏周期移植取消率显著低于慢速程序化冷冻;而临床妊娠率和种植率的差异无统计学意义.结论:玻璃化冷冻和慢速程序化冷冻相比有更高的复苏率和胚胎利用率.

目的:通过总结IVF-ET中多囊卵巢综合征(PCOS)患者应用控制性超促排卵(COH)后发生卵巢过度刺激综合征(OHSS)的特点,提出防止中、重度OHSS发生的有效措施.方法:将IVF/ICSI治疗时出现中、重度OHSS的患者根据有无PCOS史分成PCOS组和对照组.比较分析PCOS组和对照组在COH中的雌激素水平、卵泡数、取卵数及发生中、重度OHSS的时间等临床资料；分析妊娠对OHSS的影响.结果:PCOS组的Gn用药总量及hCG注射日的血清E2水平比对照组低,其总卵泡数、中小卵泡数明显高于对照组,发生中、重度OHSS的时间早,妊娠可能加重OHSS病情发展.结论:卵泡总数、中小卵泡数可作为PCOS患者预测中、重度OHSS独立的重要指标,建议即使取卵前E2水平不高、获卵数不多也考虑行全胚冷冻,以阻止严重的OHSS发生.