自然周期冻融胚胎移植使用绒促性素诱发排卵后不同胚胎移植时间临床结局比较

目的:比较自然周期冻融胚胎移植(FET)使用绒促性素(HCG)诱发排卵后不同胚胎移植时间的临床结局,探讨自然周期FET时机。方法:回顾性分析2014年1月至2018年7月于河南省人民医院生殖中心行自然周期使用HCG诱导排卵的FET周期,根据移植胚胎的不同分为卵裂期胚胎(n=522)和囊胚期胚胎(n=251)共773个周期。根据移植日距HCG注射日天数进行分组,以HCG注射日为D0,HCG注射后第3天移植卵裂期胚胎为D3-3组;HCG注射后第4天移植卵裂期胚胎为D4-3组;HCG注射后第5天移植卵裂期胚胎为D5-3组。HCG注射后第5天移植囊胚为D5-5组;HCG注射后第6天移植囊胚为D6-5组;HCG注射后第7天移植囊胚为D7-5组。比较各组一般情况和妊娠结局相关指标,并对妊娠结局指标进行多元Logistic回归分析。结果:移植卵裂期胚胎的D4-3组移植日子宫内膜厚度高于D3-3组与D5-3组,差异有统计学意义(P0.05);移植囊胚期胚胎的D7-5组优胚移植周期率显著低于D5-5组与D6-5组,差异有统计学意义(P0.05);将患者体质量指数(BMI)、年龄、移植胚胎数、优胚移植周期率、移植日子宫内膜厚度作为可能对妊娠结局产生影响的混杂因素进行调整后,移植卵裂期胚胎的D3-3组、D4-3组、D5-3组相比较,移植囊胚期胚胎的D5-5组、D6-5组、D7-5组相比较,胚胎种植率、临床妊娠率、异位妊娠率、持续妊娠率、早期流产率差异无统计学意义(P0.05)。结论:在HCG诱导排卵的自然周期FET中,HCG注射后3～5天移植卵裂期胚胎,5～7天移植囊胚期胚胎均可取得相似的临床结局。     

非优质胚胎囊胚培养应用价值研究

目的探讨非优质胚胎囊胚培养是否为高效利用非优质胚胎的最佳选择,为制定更利于患者的助孕方案提供参考。方法选择2015年12月至2016年12月在中国医科大学附属盛京医院辅助生殖中心接受体外受精-胚胎移植(IVF-ET)或卵胞浆内单精子显微注射-胚胎移植(ICSI-ET)的不孕患者308例。第3天无优质胚胎形成,按患者意愿分为两组:卵裂期移植组(196例)及囊胚培养组(112例)。比较两组累积临床妊娠率、种植率、流产率、治疗成本、移植周期。结果卵裂期移植组与囊胚培养组的种植率(26.4%vs.44.3%)、周期数[每例患者(1.12±0.37)个vs.(0.86±0.45)个]、治疗成本[每例患者(4433.67±2027.10)元vs.(4750.97±2067.06)元]比较,差异均有统计学意义(P0.05)。累积临床妊娠率(49.5%vs.44.6%)、流产率(4.1%vs.2.0%)比较,差异均无统计学意义(P0.05)。囊胚培养组具有较高的周期取消率。卵裂期移植组第3天胚胎数≥5枚的累积临床妊娠率显著高于囊胚培养组(81.6%vs.53.6%),差异有统计学意义(P0.05)。结论囊胚培养并不是高效利用非优质胚胎的最佳选择;卵裂期胚胎形态学评估预测胚胎植入潜能作用有限。     

薄型子宫内膜新鲜胚胎和冻融胚胎移植妊娠结局比较

目的探讨在薄型子宫内膜患者中新鲜胚胎移植与冻融胚胎移植(FET)妊娠结局的差异。方法回顾性分析接受体外受精/卵胞质内单精子显微注射-胚胎移植(IVF/ICSI-ET)治疗采用长方案胚胎移植h CG注射日与冻融周期胚胎移植内膜转化日的内膜厚度≤7 mm的患者共592个周期的临床资料。将移植周期按胚胎是否冻融分为新鲜胚胎移植组(n=173)和FET组(n=419)。比较组间的胚胎种植率、临床妊娠率、流产率、多胎率和异位妊娠率有无差异。结果新鲜胚胎移植组患者平均移植胚胎(2.1±0.4)枚,与FET组患者平均移植胚胎(2.1±0.5)枚比较,组间有统计学差异(P0.05);按照移植胚胎数分为3个亚组,新鲜胚胎移植组1枚胚胎者,妊娠率为7.7%,2枚者为30.2%,3枚者为23.8%;FET组1枚胚胎者15.6%,2枚者为34.9%,3枚者为41.6%,新鲜胚胎移植组与FET组间差异均无统计学意义(P0.05)。组间着床率、流产率、异位妊娠率等结果也均无统计学差异(P0.05)。移植3枚胚胎新鲜组多胎率(80.0%)高于FET组(29.7%)(P0.05)。新鲜胚胎移植组多胎率3个亚组间有统计学差异(P0.05),FET组妊娠率和流产率3个亚组间均有统计学差异(P0.05)。将移植胚胎数作为协变量,纳入Logistics回归模型对结果变量进行分析,说明周期类型与临床妊娠率间无显著相关性(OR=0.726,95%CI=0.504~1.104)。结论子宫内膜厚度≤7 mm的薄型内膜患者新鲜胚胎移植和FET妊娠结局相似,选择新鲜周期移植不影响妊娠结局并可缩短治疗周期,降低总费用。     

融合期胚胎和囊胚移植的探讨

目的：探讨融合期胚胎和囊胚单胚胎移植的可行性.方法：选取苏北人民医院生殖医学中心冷冻胚胎解冻移植231个周期的患者为研究对象,比较卵裂期胚胎移植组、融合期胚胎移植组和囊胚移植组的胚胎种植率、临床妊娠率以及多胎的发生率.结果：融合期胚胎移植组平均移植胚胎数低于卵裂期胚胎移植组,差异有统计学意义[（1.35±0.50） 个vs.（1.73±0.59） 个,t=-4.902,P＜0.001],但其胚胎种植率和临床妊娠率高于卵裂期胚胎移植组,差异均有统计学意义（49.58% vs.23.00%,χ2=24.567,P＜0.001;53.41% vs.34.15%,χ2=7.805,P=0.005）;囊胚移植组胚胎种植率高于卵裂期胚胎移植组,差异有统计学意义（46.88% vs.23.00%,χ2=8.214,P=0.004）;3组间多胎发生率差异无统计学意义（χ2=2.231,P=0.328）.结论：进行融合期胚胎或囊胚移植可获得较高的胚胎种植率和周期移植妊娠率,降低多胎率,尤其应用于单胚胎移植有重要意义.     

卵子玻璃化冷冻在辅助生殖技术治疗中的临床应用

目的探讨卵子冷冻以及冻卵冻胚(卵裂胚及囊胚)双次冷冻在辅助生殖技术(ART)中临床应用的安全性和可行性。方法回顾性分析2014年1月—2017年12月期间行卵子玻璃化冷冻,随后解冻并后续培养移植共164个周期,其中新鲜胚胎移植组解冻卵88个周期,冻融胚胎移植卵裂胚组冻卵冻胚40个周期,冻融胚胎移植囊胚组冻卵冻囊胚36个周期,并分别以同期未行卵子冷冻的新鲜胚胎(n=1 480)、解冻胚胎(n=246)、解冻囊胚(n=304)移植作为对照,比较卵子受精率、卵裂率及可利用胚胎率,以及各组的复苏率、后续的着床率、临床妊娠率、早期流产率、活产率等指标。结果解冻卵复苏存活率为[94.00%(999/1 063)]。解冻卵受精率[84.00%(838/999)]优于新鲜卵子受精率[72.67%(10 703/14 729)],组间差异有统计学意义(P=0.00),第3日可利用胚胎率、冻融后存活率、着床率、临床妊娠率、早期流产率、活产率差异均无统计学意义(P0.05)。结论卵子冷冻不会降低卵子的发育潜能,冷冻后可获得比较满意的复苏效果,行卵胞质内单精子显微注射(ICSI)仍可获得较好的妊娠和活产结局,对于需要保存生育力的女性来说卵子冷冻是一种较为安全有效的方法。     

体外受精-胚胎移植周期中不同天数和发育阶段囊胚移植妊娠结局的比较

目的:寻找体外受精-胚胎移植(IVF-ET)治疗中选择合适时期和高质量囊胚进行移植的依据。方法:回顾性分析行囊胚移植的4 237例患者的临床资料,其中新鲜单囊胚移植1 574例,冻融单囊胚移植854例,新鲜双囊胚移植135例,冻融双囊胚移植1 674例。根据囊胚发育天数和发育阶段分为第5日(D5)早期组、D5扩张组、第6日(D6)早期组和D6扩张组。比较各组临床妊娠率、种植率、妊娠结局和新生儿情况等各项指标。结果:①单囊胚移植:新鲜周期D5扩张组临床妊娠率和种植率显著高于其它组,其活产率显著高于D6早期组和D6扩张组,流产率明显低于D6扩张组(P0.05);冻融周期D5扩张组具有较高的复苏率、临床妊娠率和种植率显著高于D5早期组和D6早期组(P0.05);②双囊胚移植:D5移植2枚扩张期囊胚的种植率显著高于D5移植2枚早期囊胚,其他各组间差异无统计学意义(P0.05);冻融周期D5扩张组移植2枚囊胚种植率最高,且临床妊娠率显著高于D5早期组,而流产率明显低于后者,差异有统计学意义(P0.05)。结论:对于单囊胚移植和双囊胚移植,无论新鲜周期或冻融周期,D5扩张组囊胚妊娠结局最佳。     

PCOS患者移植冻融胚胎后妊娠结局

目的:探讨多囊卵巢综合征(PCOS)患者在优质冻融胚胎移植(FET)后是否有更高的妊娠丢失率。方法:回顾性分析诊断为PCOS并初次接受体外受精-胚胎移植(IVF-ET)或卵胞质内单精子注射(ICSI)FET的患者,选择移植冻融胚胎中含有卵裂期优质胚胎且生化妊娠阳性的157个周期的临床资料为PCOS组,同期年龄、体质量指数(BMI)、不孕年限与PCOS组匹配的、因单纯输卵管因素接受IVF-ET助孕治疗并生化妊娠阳性的389个FET周期的临床资料为对照组,比较组间的生化妊娠丢失率、早期流产率、晚期流产率、活产率。结果:在接受优质卵裂期FET的PCOS患者妊娠后,生化妊娠丢失率、早期流产率、晚期流产率、活产率与对照组相比(8.28%vs 5.14%、7.64%vs 8.13%、6.94%vs 5.15%、79.86%vs 84.28%),差异无统计学意义(P0.05)。结论:在固定胚胎质量这个重要的影响妊娠早期丢失的影响因子的基础上,排除年龄、BMI、自然流产次数、是否多胎妊娠、移植日内膜厚度等影响因素的干扰,患PCOS并不增加IVF/ICSI的生化妊娠丢失率和临床妊娠流产率。     

玻璃化冻融人卵裂期胚胎移植结局的影响因素分析

目的:探讨玻璃化冻融人第3天卵裂期胚胎移植结局的影响因素。方法:回顾分析977例1301个冻融胚胎移植周期,根据患者年龄、新鲜周期结局、移植胚胎质量等因素分组,比较各分组的胚胎植入率、临床妊娠率。结果:复苏3598个胚胎,存活3462个。周期临床妊娠率24.1%,出生婴儿291个。新鲜周期结局、移植胚胎质量组间胚胎着床率、临床妊娠率的差异有统计学意义(P<0.01)。子宫内膜准备方案、胚胎的复苏程度组间差异无统计学意义(P>0.05)。不同年龄组相同不孕年限亚组间的胚胎着床率、临床妊娠率的差异有统计学意义(P<0.05)。移植日子宫内膜厚度>12.0mm组与其他两组相比,胚胎着床率、临床妊娠率较高(P<0.05);不同FET次数组间,1次组的胚胎着床率、临床妊娠率明显高于其他两组(P<0.01)。非条件逐步logistic回归分析表明年龄(P<0.01,OR=0.43)、FET次数(2次组P<0.01,OR=0.30;3次组P<0.01,OR=0.19)、新鲜周期结局(P<0.01,OR=9.01)、移植胚胎质量(P<0.01,OR=3.52)与移植结局相关。结论:年龄、新鲜周期结局、移植胚胎质量等是影响冻融胚胎移植结局的重要因素。     

桑葚期胚胎玻璃化冷冻在体外受精-胚胎移植中的应用

目的:探讨用玻璃化冷冻法冷冻桑葚期胚胎的可行性.方法:选择2010年6月至2012年9月在河北医科大学第二医院生殖医学门诊行体外受精-胚胎移植患者784例(829个周期)为研究对象,对照组(606例)为前期采用玻璃化冷冻法冷冻第3天卵裂期胚胎637个周期;研究组A(145例)采用玻璃化冷冻法冷冻第4天桑葚期胚胎159个周期;研究组B(33例)为前期采用玻璃化冷冻法冷冻胚胎在第3天评分较差,介于冷冻和非冷冻之间的胚胎,通过继续培养至第4天采用玻璃化冷冻法冷冻桑葚期胚胎33个周期.3组均解冻以后行冻融胚胎移植,比较3组复活周期的胚胎完整率、周期临床妊娠率、种植率以及流产率.结果:①研究组A的完整胚胎存活率、周期临床妊娠率和流产率高于对照组,但差异无统计学意义(P＞0.05).而研究组A的胚胎种植率(33.2％)高于对照组(27.0％),差异有统计学意义(P＜0.05);②研究组B和对照组比较,完整胚胎存活率、种植率、周期临床妊娠率和流产率方面,差异均无统计学意义(P＞0.05).结论:桑葚期胚胎较原核期胚胎和早期卵裂期胚胎处于胚胎发育的更晚阶段,是胚胎的进一步选择,其玻璃化冷冻是可行的,能获得较好的妊娠率和种植率,值得临床推广应用.     

冻融囊胚移植降低重复性异位妊娠发生

目的:探讨重复性异位妊娠的发生与移植日胚胎发育天数的关系。方法:回顾性分析741个冻融胚胎移植(FET)周期且有明确异位妊娠病史患者的临床资料。按胚胎体外培养时间分为卵裂组,复融第3日胚胎(n=458);囊胚组,复融第5或第6日囊胚(n=283)。比较组间患者的一般情况及治疗情况。结果:组间患者的平均年龄、平均不孕年限、既往异位妊娠病史、输卵管手术史、内膜准备方案、内膜厚度等差异无统计学意义(P0.05),囊胚组平均移植胚胎数低于卵裂组(1.9±1.3 vs 2.0±0.5,P0.05),临床妊娠率、双胎妊娠率囊胚组高于卵裂组(75.97%vs 42.36%,57.20%vs 31.40%,P0.05),流产率、重复异位妊娠率囊胚组低于卵裂组(6.97%vs 16.49%,0.82%vs 5.15%,P0.05)。结论:有异位妊娠病史的患者,囊胚移植可降低重复异位妊娠的发生风险。     

Transfers of fresh blastocysts and blastocysts cultured from thawed cleavage embryos are associated with fewer miscarriages

The literature shows an inconsistent relationship between miscarriage and assisted reproduction treatment factors. This study assessed the association between miscarriage and transfer of fresh or thawed embryos at cleavage/blastocyst stages. A population study included 52,874 pregnancies following autologous cycles. The miscarriage rate was compared by groups of transferred embryos (fresh cleavage embryo, fresh blastocyst, thawed cleavage embryo, blastocyst from thawed cleavage embryo, thawed blastocyst), IVF/intracytoplasmic sperm injection procedures, number of embryos transferred and woman's demographics. The overall miscarriage rate was 18.7%. Women aged 35-39 years and ≥40 years had a 51% and 177% increased hazard of miscarriage, respectively, compared with women <35 years. Women with history of miscarriage had 1.22 times hazard of miscarriage compared with those without previous miscarriage. Singleton pregnancies following fresh double-embryo transfer had 1.43 times higher rate of miscarriage than fresh single-embryo transfer. Fresh blastocyst transfer was associated with 8% less hazard of miscarriage than fresh cleavage-embryo transfer. Compared with pregnancies following thawed cleavage-embryo transfers, thawed blastocyst transfers were at 14% higher hazard of miscarriage. This study suggests that a practice model that includes transferring blastocysts and freezing cleavage embryos in fresh cycles would result in better outcomes.     

MicroRNAs and ovarian function

Objectives

This study sought to evaluate the outcome of fresh and vitrified-warmed cleavage-stage and blastocyst-stage embryo transfers in patients undergoing ART treatment within an ethnic Chinese population.

Study design

We compared the clinical results of embryo transfer on the 3rd (cleavage stage) or 5th (blastocyst stage) day after oocyte retrieval, including clinical pregnancy rates, implantation rates and multiple pregnancy rates.

Results

Our data showed that blastocyst transfer on day 5 did not significantly increase clinical pregnancy rate (41.07% vs 47.08%, p>0.05) and implantation rate (31.8% vs 31.2%, p>0.05) in patients under 35 years of age, in comparison with day 3 cleavage stage embryo transfer. In patients older than 35 years of age, the clinical pregnancy rate after blastocyst transfer was slightly decreased compared with cleavage stage embryo transfer (33.33% vs 42.31%, p>0.05). Unexpectedly, It was found that vitrified-warmed blastocyst transfer resulted in significantly higher clinical pregnancy rate (56.8%) and implantation rate (47%) compared with fresh blastocyst transfer in controlled stimulation cycles (41.07% and 31.8%, respectively). For patients under 35 years of age, the cumulative clinical pregnancy rate combining fresh and vitrified-warmed blastocyst transfer cycles were significantly higher compared to just cleavage-stage embryo transfer (70.1% versus 51.8%, p<0.05). However, the cumulative multiple pregnancy rates showed no significant difference between the two groups.

Conclusions

In an ethnic Chinese patient population, fresh blastocyst transfer does not significantly increase clinical pregnancy rate. However, subsequent vitrified-warmed blastocyst transfer in a non-controlled ovarian hyperstimulation cycle dramatically improves clinical outcomes. Therefore, blastocyst culture in tandem with vitrified-warmed blastocyst transfer is recommended as a favourable and promising protocol in human ART treatment, particularly for ethnic Chinese patients.     

Ongoing and cumulative pregnancy rate after cleavage-stage versus blastocyst-stage embryo transfer using vitrification for cryopreservation: Impact of age on the results

Purpose

To determine if blastocyst transfer increases the ongoing and cumulative pregnancy rates, compared with day 3 embryo transfer, in women of all ages when at least 4 zygotes are obtained.

Methods

Prospective study including patients undergoing a first IVF/ICSI treatment and assigned to cleavage stage (n = 46) or blastocyst (n = 58) embryo transfer. Supernumerary embryos were vitrified and patients failing to achieve an ongoing pregnancy after fresh embryo transfer would go through cryopreserved cycles. The main outcome measure was the ongoing pregnancy rate after the fresh IVF/ICSI transfer and the cumulative ongoing pregnancy rate. Results were also analyzed according to age (under 35 and 35 or older).

Results

A majority of patients (96.6 %) had a blastocyst transfer when at least 4 zygotes were obtained. The ongoing pregnancy rate was significantly higher in the day-5 group compared with the day-3 group (43.1 % vs. 24 %, p = 0.041). The cumulative ongoing pregnancy rate was higher (but not significantly) with blastocyst than with cleavage stage embryos (56.8 % vs. 43.4 %, p = 0.174). When analysed by age, patients 35 or older showed significantly higher ongoing pregnancy rate (48.4 % vs. 19.3 %, p = 0.016) and cumulative ongoing pregnancy rate (58 % vs. 25.8 %, p = 0.01) in the day-5 group compared to the day-3 group, while no such differences were observed in women under 35.

Conclusions

Blastocyst transfer can be suggested whenever there are at least 4 zygotes. While there are no differences in women under 35, the benefit of this option over cleavage stage transfer could be significant in women 35 or older.     

Outcome of blastocyst transfer according to availability of excess blastocysts suitable for cryopreservation

The purpose of this study was to assess the outcome of blastocyst transfer in relation to the presence or absence of excess blastocysts available for cryopreservation. The study was designed as a retrospective case series in a tertiary care private hospital. The study group consisted of 450 blastocyst stage embryo transfer cycles. In 139 cycles there were excess freezeable blastocysts (group 1), in 78 cycles there were excess but unfreezeable blastocysts (group 2), and in 233 cycles there were no excess blastocysts (group 3). A mean of three blastocysts was replaced in all groups. Treatment cycle characteristics, implantation and pregnancy rates following fresh and cryopreserved blastocyst transfer were assessed in each group. More embryos reached the blastocyst stage in group 1 and more blastocysts were of good quality. In group 1, clinical pregnancy and implantation rates (71 and 41%) were significantly higher compared with groups 2 (56 and 27%) and 3 (43 and 19%). Embryos that were selected for transfer among a cohort of good quality blastocysts yielded the highest implantation and pregnancy rates. Given a clinical pregnancy rate of 71%, an implantation rate per embryo of 41%, and a multiple pregnancy rate of 58%, serious consideration should be given to a single blastocyst transfer in these patients.     

辅助生殖技术中影响异位妊娠发生的相关危险因素分析

目的:探讨辅助生殖技术(assisted reproductive technology,ART)后发生异位妊娠的危险因素。方法:收集2014年1月至2016年1月在本院生殖中心行ART治疗并获得临床妊娠的8548例患者的临床资料,包括女方年龄、体质量指数(BMI)、不孕原因、异位妊娠史、冻融胚胎移植内膜准备方式、胚胎移植类型、数目和期别。采用单因素及多因素Logistic回归分析不同因素对于ART后异位妊娠发生的影响。结果:8548例患者中,异位妊娠196例,异位妊娠率为2.29%。单因素分析结果显示,异位妊娠组盆腔输卵管因素、非男方因素、既往异位妊娠史、新鲜胚胎和D3胚胎移植比例均高于非异位妊娠组(P0.05)。将以上因素纳入多因素Logistic回归分析,结果显示,盆腔输卵管因素(OR=1.524,95%CI 1.100~2.111,P=0.011)和D3胚胎移植是行ART后异位妊娠发生的独立危险因素。且移植D6胚胎要比移植D5胚胎发生异位妊娠的风险低。进一步对盆腔输卵管因素进行分层分析,表明移植D5或D6胚胎异位妊娠发生率显著降低(P0.01)。结论:盆腔输卵管因素以及D3胚胎移植可导致ART后异位妊娠发生增加。囊胚移植,尤其是D6囊胚移植有利于降低异位妊娠发生的风险。     

Blastocyst culture and cryopreservation to optimize clinical outcomes of warming cycles

Surplus embryos available for cryopreservation in fresh cycles are considered as having good potential for future use. However, the optimal stage of embryo cryopreservation remains unclear. In this study, 1190 patients with surplus embryos on day 3 were divided into two groups: cleavage-stage embryo cryopreservation (control group) and blastocyst cryopreservation (blastocyst group). The clinical outcomes of the subsequent warming cycles were evaluated. The proportion of cycles with blastocyst formation was 73.8% in the blastocyst group. Although in the blastocyst group, the cancellation rate of blastocyst transfer was increased due to lack of blastocysts available for cryopreservation, the blastocyst group achieved significantly higher rates of clinical pregnancy/cycle (43.2% versus 34.9%; P = 0.003), pregnancy/transfer (59.5% versus 35.4%; P < 0.001) and implantation (46.5% versus 22.2%; P < 0.001) from the first warming cycle compared with the control group. In an embryo-number classified analysis, the clinical pregnancy rate was also higher in the blastocyst group. However, the cumulative pregnancy was similar between the two groups. Blastocyst culture as an embryo selection tool will not improve embryo viability but it will help patients to achieve pregnancy more quickly. Extended culture of surplus embryos to the blastocyst stage for cryopreservation optimizes the clinical outcomes.Surplus embryos available for cryopreservation in fresh cycles have been considered as having good potential for future use. However, it remains unclear whether cleavage-stage embryo cryopreservation on day 3 or further extended culture with blastocyst cryopreservation on day 5 or 6 is of most benefit to patients. This prospective study was undertaken to evaluate the clinical outcomes of vitrified–warmed embryo transfer cycles according to cryopreservation of embryos at different stages. The study enrolled 1190 patients with surplus embryos on day 3, who were divided into two groups: cleavage-stage embryo cryopreservation (control group) and blastocyst cryopreservation (blastocyst group). The proportion of cycles with blastocyst formation in the blastocyst group was 73.8%. Although the cancellation rate of blastocyst transfer in the blastocyst group was increased due to lack of blastocysts available for cryopreservation, the blastocyst group achieved significantly higher rates of clinical pregnancy/cycle (43.2% versus 34.9%; P = 0.003), clinical pregnancy/transfer (59.5% versus 35.4%; P < 0.001) and implantation (46.5% versus 22.2%; P < 0.001) from the first warming cycle as compared with the control group. In an embryo-number classified analysis, the clinical pregnancy rate was also higher in the blastocyst group. However, the cumulative pregnancy was similar between the two groups. In conclusion, blastocyst culture as an embryo selection tool will not improve embryo viability but it will help patients to achieve pregnancy more quickly. Extended culture of surplus embryos to the blastocyst stage for cryopreservation optimizes the clinical outcomes of the subsequent warming cycles.     

Factors related to early spontaneous miscarriage during IVF/ICSI treatment: an analysis of 21,485 clinical pregnancies

Research questionWhich factors are related to early spontaneous miscarriage in IVF-conceived clinical pregnancies?DesignA total of 21,485 clinical pregnancies were included in the analysis. First, early spontaneous miscarriage rates were compared among different groups according to female age, body mass index (BMI), number of previous miscarriages, infertility diagnosis and type and cycle characteristics. Then, the spontaneous miscarriage rate in patients with polycystic ovary syndrome (PCOS), uterus malformation and endometriosis was compared with that in patients with male factor infertility alone. Last, logistic regression was used to analyse factors affecting the early spontaneous miscarriage rate.ResultsOf the 21,485 cycles, 2703 cycles (12.58%) resulted in early spontaneous miscarriage. In patients <35 years old, those with uterus malformation or PCOS experienced significantly higher spontaneous miscarriage rates (14.44% versus 9.47%, P = 0.027; 11.43% versus 9.47%; P = 0.003) compared with controls (male factor only). In multivariate logistic regression analysis, the spontaneous miscarriage rate increased in frozen embryo transfer cycles in patients <35 years old (odds ratio [OR] 1.449, 95% confidence interval [CI] 1.303–1.611, P = 0.000), but decreased in patients ≥35 years old (OR 0.794, 95% CI 0.671–0.939, P = 0.007) compared with fresh cycles.ConclusionsFemale age, number of previous miscarriages and endometrial thickness on the day of embryo transfer were independent factors associated with early spontaneous miscarriage. PCOS, uterus malformation and frozen embryo transfer significantly increased spontaneous miscarriage rate in patients <35 years old compared with male factor alone controls. However, frozen embryo transfer decreased the spontaneous miscarriage rate in patients ≥35 years old compared with fresh cycles.     

Freeze-all: enhanced outcomes with cryopreservation at the blastocyst stage versus pronuclear stage using slow-freeze techniques

This retrospective cohort study compared outcomes from transfer of embryos cryopreserved at the pronuclear versus blastocyst stage following ‘freeze-all’ IVF cycles without fresh transfer for 87 consecutive IVF patients <40 years, who underwent cryopreservation of all viable embryos followed by at least one subsequent frozen embryo transfer (FET) between January 2003 and July 2007. Cryopreservation of all embryos from one oocyte retrieval was performed at either the pronuclear (1.5 mol/l propanediol and 0.1 mol/l sucrose) (group A) or blastocyst (10% glycerol) (group B) stage. Main outcome measures included survival, live birth and implantation rates. A total of 110 FET cycles were analysed. Live birth and implantation rates observed after the first FET were significantly higher (P = 0.025 and P = 0.002) in group B (67.7% and 40.8%) than in group A (41.1% and 21.5%) despite a higher survival rate in group A. After two FET cycles, 32.1% of group A had not conceived despite thaw of all available embryos, compared with 6.5% of group B. When freeze-all is necessary, blastocyst cryopreservation leads to higher implantation and live birth rates compared with pronuclear-stage cryopreservation despite lower survival rates. Prolonged embryo culture may allow for more optimal embryo selection.     

Early cleavage of human embryos to the two-cell stage. A simple,effective indicator of implantation and pregnancy in intracytoplasmic sperm injection

OBJECTIVE: To evaluate the relationship between embryo cleavage time and implantation and pregnancy rates in women undergoing intracytoplasmic sperm injection (ICSI) for male factor infertility. STUDY DESIGN: A total of 78 patients undergoing their first ICSI cycle were evaluated prospectively. Embryos were assessed for early cleavage to the two-cell stage 27 hours after injection. RESULTS: Early cleavage of at least one embryo was observed in 48 cycles (group I). None of the embryos cleaved early in the remaining 30 cycles (group II). There was no difference regarding mean patient age, duration of ovarian stimulation, number of gonadotropin ampules used, number of oocytes retrieved, fertilization, cleavage rates and embryo quality between the two groups. Implantation and clinical pregnancy rates were significantly higher in group I than II (17.9% and 45.8% vs. 5.1% and 16.7%, respectively; P < .05). Furthermore, progression to the blastocyst stage in excess embryos was significantly higher in group I than II (56.7% vs. 25.0%, P < .05). CONCLUSION: Pregnancy and implantation rates were higher in patients who have early cleaving embryos; absence of early cleavage was associated with a poor outcome.     

Comparing the effect of sequential embryo transfer versus double blastocyst embryo transfer on pregnancy outcomes in intracytoplasmic sperm injection (ICSI) cycles in patients with repeated implantation failure: A randomized controlled trial

ObjectiveRecurrent implantation failure (RIF) is the main challenge in assisted reproductive technology (ART) practice. Sequential embryo transfer, in which both, cleavage-stage embryo on day 3 and blastocyst on day 5, are sequentially transferred in the same cycle, has been suggested for increasing embryo implantation in RIF patients. The aim of the present study was to compare the effect of sequential embryo transfer versus double blastocyst embryo transfer on pregnancy outcomes in intracytoplasmic sperm injection (ICSI)/frozen embryo transfer (FET) cycles in RIF patients.Materials and methodsThis prospective study was enrolled 224 RIF patients undergoing ICSI/FET cycles and randomly divided to sequential and control groups. In sequential group, embryo transfer was conducted on day 3 (cleavage stage) and day 5 (blastocyst stage). In control group, two top-quality blastocysts were transferred on day 5.ResultsTwo hundred and two couples accomplished the trial, and their data were analyzed. Results demonstrated that sequential embryo transfer on day 3 and day 5 compared to double blastocyst transfer on day 5 significantly increased implantation rate, clinical pregnancy rate and ongoing pregnancy rate in RIF patients (p-value = 0.0142, p-value = 0.0154, p-value = 0.0201, respectively). However, there were no significant differences in terms of chemical pregnancy rate, multiple pregnancy rate, miscarriage rate and ectopic pregnancy rate in the studied groups.ConclusionSequential embryo transfer is associated with improved pregnancy outcomes in RIF patients. Further prospective studies with larger sample sizes are required to validate these results.