评估和改善子宫内膜容受性治疗反复种植失败的研究进展

反复种植失败(RIF)是困扰辅助生殖技术(ART)发展的难题,子宫内膜容受性是体外受精-胚胎移植(IVF-ET)成功的关键因素。如何提高RIF患者的子宫内膜容受性日益受到生殖医学界的关注。本文从子宫内膜容受性评价常用临床方法到宫腔镜治疗宫腔结构异常、子宫内膜机械性损伤、调节母-胎免疫容受性、药物抑制子宫收缩、改善子宫内膜厚度、改善子宫内膜血流等方面,对RIF的治疗方法进行了阐述与总结,以期为未来的科学研究及临床治疗提供参考。     

促性腺激素释放激素激动剂降调节方案对子宫内膜容受性的研究进展

辅助生殖技术(ART)中,子宫内膜容受性(ER)是影响女性妊娠成功与否的重要因素。促性腺激素释放激素激动剂(GnRHa)在控制性卵巢刺激(COS)过程中得到广泛应用,GnRHa一方面解决了单纯促排卵导致的早发黄体生成激素(LH)峰造成卵子质量下降、周期取消率高的问题,另一方面能够通过调控激素及生物活性分子(雌、孕激素及其受体、整合素、转化生长因子等)的分泌、胞饮突的数量、HOXAl0等基因的表达影响ER,本文总结了GnRHa调节ER的机理,综述了不同的GnRHa降调节方案(GnRHa超长方案、GnRHa长方案、GnRHa短方案、GnRHa超短方案)对ER的影响,为临床上制定合理、科学的个体化GnRHa降调节方案提供参考。     

宫腔镜子宫内膜微刺激术后再次冻融胚胎移植的临床结局

目的探讨宫腔镜子宫内膜微刺激术对再次移植冻融胚胎患者临床结局的影响。方法选取2015年1月—2016年8月在本院行体外受精(IVF)助孕首次移植治疗失败的患者共281例,随机分为研究组(A组)和对照组(B组)。A组129例,月经干净后第3~7日进行宫腔镜子宫内膜微刺激术;B组152例,第2次移植前未行手术。统计分析冻融胚胎移植(FET)的妊娠结局。结果 (1)A、B两组间患者年龄、不孕年限、基础性激素、体质量指数、黄体酮转化日内膜厚度、移植胚胎数、优质胚胎率、异位妊娠率、多胎率、早期流产率相比较,差异无统计学意义(P0.05)。(2)A组的临床妊娠率和着床率分别是58.1%、34.0%,显著高于B组(47.4%、27.6%)(P0.05)。进一步运用多因素Logistic回归分析显示,宫腔镜子宫内膜微刺激术能够显著增加临床妊娠的几率(OR=1.50,95%CI=1.12~2.43),而对异位妊娠、多胎妊娠及早期流产的发生无明显影响。结论宫腔镜子宫内膜微刺激术属微创手术、并发症少,手术方便快捷,能更直观评价患者的宫腔内情况,并且通过对子宫内膜局部轻微刺激,改善内膜容受性,提高着床率、妊娠率,故宫腔镜子宫内膜微刺激术值得推广。     

彩色多普勒超声监测子宫内膜和内膜下血流对IVF患者子宫容受性的预测价值

目的:评价彩色多普勒超声监测子宫内膜和内膜下血流在IVF-ET中对子宫内膜容受性的预测价值。方法:选择第一次进行IVF/ICSI-ET治疗的不孕症患者119例,根据注射hCG日子宫内膜和内膜下血流状况分为A组(n=8):子宫内膜和内膜下血流≤2支;B组(n=50):子宫内膜和内膜下血流3-4支;C组(n=61):子宫内膜和内膜下血流≥5支。各组患者均移植1-3个胚胎。比较各组的临床特征、卵巢反应、内膜情况和妊娠结局。结果:各组的临床特征、卵巢反应、内膜情况均无统计学差异,A组妊娠率低于B组(P<0.05)和C组(P<0.01)。A组着床率低于C组(P<0.01),B组和C组的妊娠率和着床率均无明显差异(P>0.05)。结论:子宫内膜和内膜下血流在IVF-ET中对子宫内膜容受性有一定预测价值。IVF-ET周期中内膜和内膜下血流≤2支者建议当月不做胚胎移植,可待血流改善后再行胚胎移植术。     

子宫内膜异位症与辅助生殖技术

子宫内膜异位症(EMs)的发病率逐年增长,是造成不孕的重要原因,但其发病机理以及导致不孕的机制尚不清楚。传统治疗包括药物、手术治疗。随着辅助生殖技术近几年来的发展,对EMs的治疗上升到一个新的高度。本文重点讨论EMs与辅助生殖技术(ART)的关系,为提高临床辅助生殖技术的成功率提供一些新的思路。     

超促排卵与胚胎着床前期子宫内膜容受性的关系

目的：探讨体外受精-胚胎移植（IVF—ET）中超促排卵与胚胎着床前期子宫内膜容受性的关系。方法：选择行长方案IVF-ET患者70例,检测自然周期排卵后第3天和超促排卵周期取卵后第3天（即ET日）的子宫内膜厚度和血流状态。按子宫内膜穿支血流显示情况分为3级：I级,内膜穿支血流≤2支;II级,内膜穿支血流为3—5支;Ⅲ级,内膜穿支血流≥6支。随访IVF-ET结局,分为妊娠组（24例）和非妊娠组（46例）。结果：妊娠组自然周期内膜穿支血流情况与未妊娠组间差异有统计意义（P〈0．05）,而2组间超促排卵周期内膜穿支血流情况差异无统计意义（P〉0．05）。妊娠组自然周期和超促排卵周期子宫内膜穿支血流情况均较为丰富,差异无统计意义（P〉0．05）;而未妊娠组超促排卵周期子宫内膜穿支血流情况较自然周期丰富,差异有统计意义（P〈0．01）。自然周期和超促排卵周期子宫内膜血流参数和子宫内膜厚度差异均无统计学意义（均P〉0．05）。结论：自然周期内膜穿支血流丰富可能提示较高妊娠率,可作为子宫内膜容受性的参考指标之一。超促排卵可能改变胚胎着床前期子宫内膜容受性,但尚无影响子宫内膜厚度及血流参数的相关证据。     

三维超声测定子宫内膜容积预测IVF-ET结局

目的评价三维(3D)超声测定子宫内膜容积在预测体外受精-胚胎移植(ⅣF-ET)结局中的作用.方法对124例行ⅣF-ET的患者在HCG注射当天进行超声测定子宫内膜的厚度和容积.结果妊娠组(48例)和未妊娠组(76例)在HCG注射当天测得的子宫内膜厚度、内膜容积、子宫容积两组间无统计学差异(P＞0.05).子宫内膜容积和厚度的ROC曲线下面积分别为0.532和0.523.子宫内膜容积＜2.0ml的5例患者,无一例发生妊娠.结论子宫内膜容积和子宫内膜厚度不能预测ⅣF-ET结局.但子宫内膜容积测定可指导是否行ET.     

超促排卵与胚胎着床前期子宫内膜容受性的关系

目的：探讨体外受精-胚胎移植（IVF-ET）中超促排卵与胚胎着床前期子宫内膜容受性的关系。方法：选择行长方案IVF-ET患者70例,检测自然周期排卵后第3天和超促排卵周期取卵后第3天（即ET日）的子宫内膜厚度和血流状态。按子宫内膜穿支血流显示情况分为3级：Ⅰ级,内膜穿支血流≤2支;Ⅱ级,内膜穿支血流为3~5支;Ⅲ级,内膜穿支血流≥6支。随访IVF-ET结局,分为妊娠组（24例）和非妊娠组（46例）。结果：妊娠组自然周期内膜穿支血流情况与未妊娠组间差异有统计意义（P ＜0.05）,而2组间超促排卵周期内膜穿支血流情况差异无统计意义（P ＞0.05）。妊娠组自然周期和超促排卵周期子宫内膜穿支血流情况均较为丰富,差异无统计意义（P ＞0.05）;而未妊娠组超促排卵周期子宫内膜穿支血流情况较自然周期丰富,差异有统计意义（P ＜0.01）。自然周期和超促排卵周期子宫内膜血流参数和子宫内膜厚度差异均无统计学意义（均P ＞0.05）。结论：自然周期内膜穿支血流丰富可能提示较高妊娠率,可作为子宫内膜容受性的参考指标之一。超促排卵可能改变胚胎着床前期子宫内膜容受性,但尚无影响子宫内膜厚度及血流参数的相关证据。     

Glycodelin-A与IVF-ET的子宫内膜容受性及妊娠结局的关系

目的 探讨Glycodelin-A表达与体外受精-胚胎移植(IVF-ET)的子宫内膜容受性及妊娠结局的关系.方法 回顾性选择2016年8月至2018年1月武汉市第一医院生殖医学中心接诊的拟行IVF-ET治疗患者71例,分析人绒毛膜促性腺激素(human chorionic gonadotropin,hCG)日抽血检测性...     

子宫内膜异位症患者IVF促排卵不同降调节方案的比较

目的:探讨子宫内膜异位症(EMs)患者合适的降调节方案。方法:收集因中-重度EMs接受IVF-ET治疗的139例不孕患者的资料,按不同的降调节方案分为超长方案(A组)、GnRHa长方案(B组)、GnRHa短方案(C组)3组,回顾性比较分析3组患者的治疗结局。结果:A组的促性腺激素(gonadotropic hormone,Gn)用量(尤其是hMG)显著多于B组和C组,差异有统计学意义(P<0.05);而冷冻周期率、临床妊娠率与种植率显著高于C组(P<0.05),与B组比较有上升趋势,但差异无统计学意义(P>0.05)。结论:EMs患者接受IVF/ICSI-ET治疗时,建议采用超长方案和常规长方案诱导排卵,以提高患者的临床妊娠率。     

促排卵周期围着床期宫腔分泌物细胞因子表达与妊娠结局的关系初探

目的:探索体外受精促排卵周期围着床期宫腔分泌物细胞因子表达与妊娠结局的关系。方法:促排卵周期胚胎移植前宫腔分泌物63例(试验组),同时选取同年促排卵后直接行胚胎移植的171例作为对照组,以排除胚胎移植前取宫腔分泌物对妊娠结局的影响。采用多重免疫分析方法检测宫腔分泌物中与胚胎种植有关17种调节因子(IL-1β、IL-2、IL-4、IL-5、IL-6、IL-7、IL-8、IL-10、IL-12(p70)、IL-13、Il-17、G-CSF、GM-CSF、IFN-γ、MCP-1、MIP-1β、TNF-α)的表达。试验组再根据妊娠结局进行分组,比较妊娠组和非妊娠组17种调节因子的表达谱。结果:患者的一般情况、促排卵数据及妊娠结局,试验组和对照组间均无统计学差异(P>0.05)。妊娠组IL-13(9.76±5.04 pg/ml)、IFN-γ(7.50±2.62 pg/ml)、MCP-1(17.5±9.63 pg/ml)水平均低于未妊娠组(分别为18.37±17.82 pg/ml、8.87±2.39 pg/ml和49.97±85.95 pg/ml),差异具有统计学意义(P<0.05),余各因子妊娠组与非妊娠组间均无统计学差异(P>0.05)。结论:胚胎移植前微量取样宫腔分泌物不影响临床结局;围种植窗期宫腔分泌物IL-13、IFN-γ以及MCP-1表达水平升高可能不利于妊娠。     

The Effects of E2 Supplementation from the Early Proliferative Phase to the Late Secretory Phase of the Endometrium in hMG-Stimulated IVF-ET

Purpose: Our purpose was to determine if pregnancy rates(PRs) for hMG (human menopausalgonadotropin)-stimulated IVF-ET (in vitro ferilization-embryo transfer) can beincreased by estradiol (E₂) supplementation from the earlyproliferative phase to the late secretory phase of theendometrium. Method: Eighty-one infertile women with pure tubal factorwere randomized into two groups. One group received noE₂ supplementation (control group) and the other receivedoral E₂ supplementation (2 mg two times daily) from theearly proliferative phase starting on the third day of themenstrual cycle to the late secretory phase of theendometrium, with hMG stimulation for ovulation induction startingon the sixth day of the menstrual cycle. Results: In 85 cycles, at least one embryo was transferred.Compared with the control group (n = 27 cycles), the E₂supplementation group (n = 58 cycles) had a significantlyhigher PR (control, 25.9%, versus E₂ supplementation,48.3%) and IR per ET (control, 10%, versus E₂supplementation, 26%), but FRs per retrieved oocytes were notstatistically different between the two groups (control, 74%, versusE₂ supplementation group, 73%). Four spontaneousabortions occurred in the E₂ supplementation group, and onecase in the control group. Ectopic pregnancy occurred inone case in the control group. Conclusions: Clinical PRs and IRs in the E₂supplementation group were significantly higher than in the controlgroup, while FRs in the control group did not differstatistically from the E₂ supplementation group. This suggests thatE₂ supplementation from the early proliferative phase to thelate secretory phase of the endometrium in hMG-stimulatedIVF-ET increases the receptivity of the endometrium fortransferred embryos and clinical PRs.     

An IVF fallacy: Multiple pregnancy risk is lower for older women

Introduction: Multiple pregnancy is one of the most important and preventable complications of in vitro fertilization (IVF) and embryo transfer. The general clinical practice in many IVF clinics is to transfer four or five embryos to older women if available, since pregnancy rates are lower in women older than 35 years of age. However, it is not clear whether the risk for multiple pregnancy is also lower. Objective: Our objective was to investigate whether transferring a higher number of embryos actually improves pregnancy outcome in older women, without increasing the risk for multiple pregnancy and to investigate other factors that may affect the occurrence of multiple pregnancy. Setting: The setting was university-based IVF program at The Toronto Hospital. Design: The design was a retrospective case series. Patients and Methods: The outcome of 1116 IVF cycles between January 1992 and December 1993 was investigated according to different age groups. Main Outcome Measure: The main outcome measure was multiple pregnancies. Results: Seventy multiple pregnancies resulted from a total of 242 pregnancies. Overall pregnancy and multiple pregnancy rates were inversely correlated with age. However, when the data were adjusted for the number of embryos transferred, this trend disappeared. The result of multiple regression analysis showed that the multiple pregnancy rate was higher without improving the pregnancy rate when the number of embryos transferred exceeded three, regardless of the age of the patients, especially when more embryos were available than the number of transferred ones. Conclusions: The number of embryos transferred should be limited to a maximum of three regardless of the age of patients, to reduce the high frequency of multiple gestations in an IVF program.     

补佳乐联合复方氨维胶囊对薄型子宫内膜不孕症者妊娠结局的改善

目的:探讨补佳乐联合复方氨维胶囊对子宫内膜厚度及妊娠率的影响。方法:经B超监测有排卵发生但子宫内膜厚度<7 mm的不孕患者,随机分为补佳乐组(月经第7日给予补佳乐至排卵后2周)、氨基酸组(以复方氨维胶囊代替补佳乐)及联合用药(同时服用补佳乐和复方氨维胶囊)组,观察内膜生长情况及妊娠率。结果:共纳入患者142例,补佳乐组46例,氨基酸组48例,联合用药组48例,3组患者用药后子宫内膜厚度均较服药前增加(6.11±0.62 mmvs 8.03±1.34 mm、6.09±0.57 mm vs 7.94±1.28 mm、6.08±0.76 mm vs 8.93±1.47 mm),差异均显著(P<0.05)。联合用药组服药前、后的子宫内膜增加幅度及妊娠率均高于补佳乐组及氨基酸组,差异显著(P<0.05)。结论:复方氨维胶囊联合补佳乐可一定程度提高子宫内膜厚度,有助于胚胎着床,增加妊娠率,从而改善妊娠结局。     

卵巢肿瘤经保守性手术后进行IVF/ICSI治疗的安全性及有效性探讨——附23例病例分析与总结

目的:探讨不孕症合并卵巢肿瘤手术史患者的IVF/ICSI-ET治疗的妊娠结局及安全性。方法:回顾性分析23例卵巢肿瘤保守性手术后行IVF/ICSI-ET治疗患者的临床结局及随访资料。结果:23例患者共35个新鲜移植周期,8个冷冻胚胎移植周期;平均基础FSH和E2分别为6.26±1.87 IU/L,41.9±24.7 pg/ml;平均Gn启动剂量165±59 IU,平均Gn使用总量1 516±866 IU,平均Gn使用天数8±3 d;hCG注射日E2峰值平均水平1 202±976 pg/ml;平均获卵数6.0±5.3个,平均成熟卵子数5.2±4.8个,受精率83.5%,平均可移植胚胎数3.1±2.7个,平均优质胚胎数2.8±2.8个,平均胚胎移植数1.8±0.7个;新鲜周期着床率29.0%,临床妊娠率28.6%;冻融胚胎周期着床率25.0%,临床妊娠率25.0%;平均随访时间(即首次IVF启动时间至末次随访日)为23个月,经IVF治疗后仅有1例复发,没有与卵巢肿瘤相关的死亡。结论:卵巢良性及交界性肿瘤经保守性手术治疗后合并不孕的患者,IVF-ET治疗有效且安全。     

子宫内膜单胺氧化酶A（MAO-A）在反复IVF-ET失败患者种植窗口期的表达及其意义

目的：探讨子宫内膜单胺氧化酶A（MAO—A）在评估子宫内膜容受性中的作用。方法：应用实时荧光定量PCR和免疫组织化学技术,检测3次IvF-ET失败患者fA组,n=39）、2次IVF-ET失败,第3次获得临床妊娠患者（B组,行=8）、首次IVF—ET获得临床妊娠患者（C组,n=21）在子宫内膜种植窗口期子宫内膜MAO-AmRNA的表达和MAO-A蛋白的表达及定位,同时扫描电子显微镜观察子宫内膜的胞饮突数量及发育情况,探讨子宫内膜MAO—A在评估子宫内膜容受性中的作用。结果：反复IVF-ET失败患者在子宫内膜种植窗口期子宫内膜MAO-A的表达低于首次IvF-ET获得临床妊娠的患者（P〈0．05）。结论：子宫内膜MAO-A可以作为子宫内膜容受性的预测指标。     

生长激素在IVF-ET周期子宫内膜发育不良患者中的应用

目的:探讨生长激素(growth hormone,GH)在体外受精-胚胎移植(in vitro fertilization-em-bryo transfer,IVF-ET)治疗中对子宫内膜发育不良者子宫内膜及临床结局的影响。方法:IVF-ET患者共67例,均由于子宫内膜发育不良而致IVF-ET种植失败,再次行IVF-ET治疗时随机分为研究组(加用GH治疗,32例)和对照组(未使用GH治疗,35例),统计分析患者的临床结局。结果:患者Gn用量、平均获卵数、受精率、优质胚胎率组间无统计学差异(P>0.05);研究组子宫内膜厚度、形态及子宫内膜和内膜下血流均较对照组有明显改善(P<0.01);研究组的胚胎种植率(31.4%)及临床妊娠率(39.5%)明显高于对照组(15.7%和19.8%)(P<0.01),早期流产率明显减低(14.6%vs 21.4%)(P<0.01)。结论:对内膜发育不良的患者进行IVF-ET治疗时加用GH可能是通过改善子宫内膜对胚胎的容受性,从而提高胚胎种植率及临床妊娠率,降低早期流产率。     

Impact of a second insemination on the results of an in vitro fertilization-embryo transfer (IVF-ET) program

In an attempt to increase the fertilization and pregnancy rates in our program, a second insemination was carried out when the first insemination yielded fewer than two fertilized oocytes. One hundred eighty consecutive patients were studied retrospectively and thirty-four required second insemination, 35% of them by donor-semen. Fifty-five and nine-tenths percent of the patients had at least one fertilized oocyte for embryo transfer, but only 21.9% of the oocytes exposed to a second insemination were fertilized. No pregnancy resulted from the transfer of oocytes fertilized by the second insemination. There were no significant correlations between the success of fertilization after a second insemination and the number of oocytes retrieved, the protocol for the induction of superovulation, or the age of the female patient. Considering that the first insemination was done at a variable time after oocyte retrieval to allow oocyte maturation, we expected all oocytes to be mature at the time of first insemination and we considered the possibility of delayed fertilization as negligible since second insemination was done at least 24–30 hr after oocyte retrieval. Even though a second insemination provides further hope for the patient, by yielding additional fertilized oocytes for embryo transfer, its main value is that it may provide additional information about male fertility.