Evidence of uterine inadequacy to egg implantation in stimulated in vitro fertilization cycles

From 104 IVF cycles 166 embryos were immediately transferred (63 embryo transfers, ET), whereas 151 embryos were frozen until later transfer (77 embryo transfers). There were 8 (12.7%) or 19 (24.7%) pregnancies after fresh or frozen-thawed ET, respectively. Sixteen pregnancies (29.1%) originated from 55 ETs of frozen-thawed embryos coming from IVF cycles in which pregnancy was not induced by fresh ET. The pregnancy rate after fresh ET (10.5%) was lower than that obtained when the same patients received frozen-thawed embryos (27.1%, P less than 0.02). It is concluded that a normal pregnancy rate may result if the embryos originating from an unsuccessful IVF-ET cycle are transferred in a favorable uterus.     

剖宫产手术史对体外受精-胚胎移植患者临床结局的影响

目的探讨剖宫产手术史对体外受精-胚胎移植(IVF-ET)患者临床结局的影响。方法回顾性分析2013年1月—2015年12月行IVF-ET且有剖宫产手术史的144例患者的助孕情况、妊娠及分娩结局,对照组为同期行IVF-ET且既往仅有阴道分娩史的166例患者。结果与对照组比较,剖宫产史组基础卵泡刺激素水平(b FSH)、人绒毛膜促性腺激素(h CG)注射日雌二醇(E2)水平、子宫内膜厚度、促性腺激素(Gn)用量、G n刺激时间,获卵率、受精率、卵裂率、优质胚胎率、胚胎移植数、多胎妊娠率、流产率、异位妊娠率差异均无统计学意义(P0.05);但剖宫产手术史组胚胎移植困难比例(6.25%)高于阴道分娩史组(0.00%),胚胎种植率(24.01%)及临床妊娠率(40.28%)明显低于阴道分娩史组(分别为34.98%和54.82%),差异均有统计学意义(P0.05);剖宫产史组双胎妊娠者较对照组双胎妊娠发生前置胎盘、产后出血比例增加(P0.05);无论是剖宫产手术史组还是阴道分娩史组,双胎分娩较单胎分娩新生儿出生孕周、体质量明显降低(P0.01)。结论剖宫产手术史可能降低IVF-ET患者的胚胎种植率和临床妊娠率,增加胚胎移植难度。对疤痕子宫妇女应严格控制移植胚胎数目,妊娠后加强孕期监管。     

Efficacy of blastocyst transfer after implantation failure

Clinicians who treat unsuccessful couples despite repeated transfers of good quality embryos face a challenge. Among the various strategies that have been described, embryo transfer at the blastocyst stage has been postulated to improve implantation. A prospective non-randomized analysis was performed in 276 IVF patients who failed to conceive after at least two early embryo transfers of at least two grade 1-2 embryos per cycle. For the next attempt, couples chose between day 2 embryo transfer (D2 group; n = 147) and day 5/6 blastocyst transfer (D5/D6 group; n = 129) before starting the following attempt. Embryo quality was assessed and results were expressed as clinical pregnancy, live birth and implantation rates per cycle. Embryo grade 1 number was similar between both groups, whereas mean embryo score of the whole cohort was slightly higher in the D2 group. The live birth rates per cycle (27.9 versus 19.7%) and implantation rates per cycle (25.4 versus 12.4%) were higher in the D5/D6 group compared with the D2 group. Improved embryo selection and uterine receptivity may explain the additional benefit of embryo transfer at the blastocyst stage for couples with repeated implantation failures.     

超长方案在卵巢储备良好前次IVF/ICSI-ET失败患者中的应用分析

目的:评估超长降调节方案在卵巢储备良好前次IVF/ICSI-ET失败患者中的应用效果。方法:回顾分析246例卵巢储备功能良好前次IVF/ICSI-ET常规长方案失败再次行助孕治疗的患者,其中超长方案治疗52例为研究组,常规长方案治疗194例为对照组。结果:研究组Gn时间及获卵数均高于对照组(P<0.01);但优质胚胎数、Gn量、注射HCG日孕酮水平、移植日子宫内膜厚度、中-重度OHSS发生率与对照组比较均无明显统计学差异(P>0.05);研究组HCG阳性率、临床妊娠率均明显高于对照组,分别是:79.1%vs 61.1%,P=0.03;69.8%vs 54.9%,P=0.048,胚胎种植率有上升趋势(39.5%vs 31.5%,P=0.18)。结论:在前次卵巢反应良好IVF/ICSI-ET失败患者中超长方案较长方案子宫内膜容受性可能更好,妊娠结局明显改善,是值得推荐的治疗方案。     

ICSI and day 5 embryo transfers: higher implantation rates and lower rate of multiple pregnancy with prolonged culture

This retrospective review study, carried out in a private IVF clinic, compared pregnancy and implantation rates with day 3 versus day 5 embryo transfers in a selected group of patients. Participants were patients who failed to achieve pregnancy in at least one previous attempt with embryo transfer on days 2 or 3, and had more than five oocytes fertilized. A total of 296 patients who had undergone day 3 (group A) transfers were compared with 154 who had undergone day 5 transfers (group B). Interventions were intracytoplasmic sperm injection (ICSI), day 3 and day 5 embryo transfer. Outcome measures were pregnancy, implantation, multiple gestation and blastocyst formation rates. Overall, 86.4% of embryos were at the six- to eight-cell stage at 72 h and 30% developed to blastocyst by day 5. The mean number of embryos transferred was 4.0 on day 3 and 3.0 on day 5. Pregnancy and implantation rates were 34.8 and 11.5% in group A, versus 45.3 and 18.5% in group B. Multiple gestation rate was 47.1% in group A and 28.5% in group B. Prolonging embryo culture in vitro to day 5 improved embryo selection and implantation rates. A significant decrease in high order gestations was achieved by reducing the number of embryos transferred, without compromising the pregnancy rates.     

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。     

机械刺激子宫内膜对内膜形态不良者IVF-ET临床结局的影响

目的:探讨机械刺激子宫内膜对临床结局的影响及机制。方法:选取行体外受精-胚胎移植(IVF-ET)且其自然月经周期卵泡晚期超声提示子宫内膜形态不良的不育患者63例,随机分为研究组(n=30)和对照组(n=33)。研究组在胚胎移植前1～2周对子宫内膜行机械刺激,对照组未行机械刺激为,统计分析IVF-ET的临床结局。结果:Gn用量、hCG注射日P/E2值、平均获卵数、受精率及移植优质胚胎数组间无统计学差异(P>0.05);研究组子宫内膜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及临床妊娠率明显高于对照组(P<0.01),早期流产率明显降低(P<0.01)。结论:机械刺激子宫内膜可能是通过改善子宫内膜形态及子宫内膜和内膜下血流,从而提高胚胎种植率及临床妊娠率,降低早期流产率。     

Blastocyst culture after repeated failure of cleavage-stage embryo transfers: a comparison of day 5 and day 6 transfers

OBJECTIVE: To evaluate the efficacy of blastocyst transfer among patients with at least three previous cleavage-stage embryo transfer failures and to compare pregnancy and implantation rates of blastocysts according to the day of embryo transfer (day 5 or day 6 after oocyte retrieval). DESIGN: Retrospective clinical study. SETTING: Private ART center. PATIENT(S): One hundred forty-eight patients (with at least three failed cleavage-stage embryo transfers) undergoing blastocyst-stage embryo transfer. INTERVENTION(S): Embryos were grown for up to 6 days and only blastocyst-stage (cavitating) embryos were transferred on either day 5 or day 6 after oocyte retrieval. MAIN OUTCOME MEASURE(S): Clinical pregnancy and implantation rates. RESULT(S): Blastocysts transferred on day 5 implanted almost five times the rate of those transferred on day 6 (23% vs. 5%). Pregnancy rates were triple as high among the 73 day 5 patients compared to the 63 day 6 transfer patients (38% vs. 11%). The number of blastocysts formed and per embryo rates of blastocyst formation were both significantly higher for patients undergoing day 5 transfers: more blastocysts developed (3.0 vs. 2.1) and more were transferred (3.0 vs. 1.9). In addition, blastocyst formation rates were 46% and 33%, respectively, for both groups of patients. CONCLUSION(S): Blastocyst transfer (preferably on day 5 after retrieval) appears to be a successful and improved alternative for patients with multiple failed IVF attempts. Moreover, with blastocyst transfer there should be a reduction in multiple pregnancy risk, because fewer embryos have to be transferred.     

Successful treatment of cervical stenosis with hysteroscopic canalization before embryo transfer in patients undergoing IVF: a case series

The course of the transfer catheter through the cervical canal is one of the most important issues for a successful embryo transfer (ET) during in vitro fertilization (IVF) cycles. Technically difficult ETs due to cervical stenosis are associated with reduced chance of pregnancy after assisted reproductive procedures. In the current case series, we report on three patients with cervical stenosis who underwent IVF-ET cycles. These three patients, in whom ET was classified as "difficult," failed to conceive with previous ET attempts. An intervention to create a cervical tract was performed with operative hysteroscopy under general anesthesia before transcervical ET. After the hysteroscopic shaving procedure, we observed quite an improvement in access to the endometrial cavity during ET procedure. These patients had significantly easier ET procedures compared with previous attempts and achieved clinical pregnancies. Hysteroscopic revision of the cervical canal results in easier ET and improves pregnancy rates in patients with cervical stenosis and histories of difficult ET.     

Linking back-to-back stimulation cycles with oral contraceptives or progestins in women undergoing embryo accumulation for preimplantation genetic testing,a retrospective study

Abstract

The purpose of this study was to determine the pregnancy rate in the double sequential transfer of embryos on both day 3 and day 5 compared to day 5 alone, in in vitro fertilization-embryo transfer (IVF/ET) in patients with the three repeated consecutive IVF failures. In this controlled trial, women scheduled for IVF/ET with the three repeated consecutive IVF failures were randomized to either sequential transfer of embryos on day 2 and on day 5 after ovum pick-up (group 1, n = 60) or blastocyst ET on day 5 (group 2, n = 60) as a control group. The primary outcome measures were the chemical and clinical pregnancy rate. Baseline and cycle characteristics were comparable in both groups. Chemical and clinical pregnancy rate was similar in the sequential ET group (40%) compared to the day 5 of ET group (38.3%) (p value = .85). It seems that the double ET does not increase the chance of pregnancy rate compared to blastocyst ET on day 5 in the patients with the three repeated IVF-ET failures.     

Factors influencing the success rate of human embryo freezing in an in vitro fertilization and embryo transfer program

Certain factors influencing the success of embryo cryopreservation were analyzed from 124 cycles of in vitro fertilization and embryo transfer (IVF-ET) program in which 193 1- or 2-day embryos were frozen and had already been thawed. There were 100 transfers of one or two surviving embryos from which 26 pregnancies were initiated. Several factors significantly influenced embryo survival after thawing. They were: the developmental stage of frozen embryos; the appearance of the embryo at the time of freezing; and the mode of ovarian stimulation in the IVF cycle. The pregnancy rate after frozen-thawed embryo transfer was higher with 4-cell frozen embryos than with embryos at all other stages combined. There were also tendencies for the pregnancy rate to be higher if a spontaneous luteinizing hormone surge occurred in the transfer cycle or if the duration of embryo storage did not exceed 1 to 2 months. The results obtained support a new policy in IVF-ET programs: it should be advantageous for the sterile couple if the immediate fresh embryo transfer is only performed with the categories of embryos that demonstrate a poor aptitude for survival following cryopreservation procedures.     

Endometrial preparation in oocyte recipients

Oocyte donation is offered to patients with premature ovarian failure to achieve pregnancy when no other assisted reproductive technology is possible. Some clinical and biological factors have been identified for influencing the outcome of oocyte donation cycles. Embryo implantation depends on embryo quality, method for the embryo transfer, and endometrial differentiation. In our center, the oocyte recipients receive for the endometrial preparatory cycle the same treatment that for the patients undergoing frozen embryos transfers, with good clinical pregnancy rates, about 35% per transfer. Estrogen and progesterone supplementation with GnRH agonist down regulation are used in synchronized protocols or for frozen embryos transfers. The synchronization between recipient's endometrium and donor's ovarian stimulation is very restrictive. Nowadays, the oocytes vitrification lithens the oocyte donation process: the endometrial preparation has a limited duration and is well controlled, and embryos that are transferred are all fresh embryos.     

Uterine cavity findings and hysteroscopic interventions in patients undergoing in vitro fertilization-embryo transfer who repeatedly cannot conceive

OBJECTIVE: To assess hysteroscopic findings in patients undergoing IVF-ET who repeatedly failed to conceive despite transfer of good-quality embryos. DESIGN: Prospective, observational study. SETTING: Clinical research unit for reproductive medicine in a private clinic. PATIENT(S): Fifty-five patients with a normal uterine cavity on hysterosalpingography before the initial IVF-ET cycle and two previous failed IVF-ET attempts despite transfer of a minimum of two good-quality embryos on each occasion. INTERVENTION(S): Standard transvaginal ultrasonography and diagnostic and therapeutic hysteroscopy. MAIN OUTCOME MEASURE(S): Endometrial findings on transvaginal ultrasonography and hysteroscopy and outcome of the cycles after surgical hysteroscopy and antibiotic therapy. RESULT(S): Twenty-five (45%) patients had abnormal endometrial findings and underwent treatment to correct the lesions. All patients underwent a third IVF-ET cycle. Pregnancy (50% vs. 20%) and implantation (19% vs. 5.5%) rates were significantly higher in patients who were treated for uterine abnormalities than in patients who had normal uterine cavities on hysteroscopy. CONCLUSION(S): The incidence of pathologic findings on hysteroscopy is high in patients with repeated failures of IVF-ET. Evaluation of endometrial integrity by hysteroscopy is highly valuable and should be applied to all such cases.     

Autologous endometrial coculture in patients with IVF failure: outcome of the first 1,030 cases

OBJECTIVE: To analyze the effectiveness of autologous endometrial coculture (AECC) in improving embryo quality and pregnancy rates in 1,030 consecutive cycles of in vitro fertilization-embryo transfer (IVF-ET) utilizing AECC from January 1996 to December 2001. STUDY DESIGN: Embryos from each of 1,030 patients allocated to growth on AECC were analyzed for outcome. All patients had previously undergone failed IVF cycles. During a luteal phase biopsy (5-12 days after the luteinizing hormone surge) performed prior to the treatment cycle, glandular (G) and stromal (S) endometrial cells were isolated by enzymatic digestion and separated based on differential sedimentation rates. These cells were cryopreserved, then plated as a 50%/50% combination of G and S cells prior to embryo exposure. The conditioned medium was changed every 2 days. Embryos were randomly grown on endometrial coculture (ECC) or conventional media if > 6 oocytes were normally fertilized. Otherwise, all embryos were grown on AECC. RESULTS: The patients' mean age was 36.9 (+/-3.1) years. The patients had on average a history of 3.1 (+/- 1.7) failed prior attempts. When comparing a previous cycle (same institution only), the cleaved embryos on day 3 were of an improved quality (6.8+/-1.2 vs. 5.5+/-1.0 blastomeres and 14.6% +/- 9.3 vs. 27.2% +/- 9.8 fragmentation, P <.05). Twenty-two (2.13%) patients did not undergo ET secondary to poor embryonic development. Overall positive and clinical pregnancy rates of 49.8% and 41.5% were noted, respectively. Age remained the most important predictor of outcome. CONCLUSION: We demonstrated a significant improvement in embryo quality with ECC. We also demonstrated that patients with a poor prognosis secondary to prior IVF failures can have a good outcome when utilizing AECC.     

Embryo transfer is equally effective at cleavage stage and blastocyst stage: a randomized prospective study

OBJECTIVE: To compare the implantation and pregnancy rates after cleavage stage embryo transfer (ET) with transfer of blastocyst-stage (days 5-6) embryos. STUDY DESIGN: Prospective randomized trial at an assisted reproduction unit in a university hospital. Women with six or more follicles at the last ultrasound scan before oocyte aspiration were randomized for transfer of a maximum of two embryos after 2-3 days (n = 80) or after 5-6 days (n = 64) of culture. Embryo quality, implantation and pregnancy rates were evaluated. Statistical significance was tested with the Chi-square test and Fisher's exact test. RESULT(S): No significant difference was observed in implantation rates (21.1% versus 20.9%, respectively) and clinical pregnancy rates (36.7% versus 32.5% respectively) after blastocyst and cleavage stage transfers for the two groups. The pregnancy rate among subjects who had at least one good quality embryo transferred was 37.5% per day 2-3 ET and 60% per day 5-6 ET. CONCLUSION(S): The overall implantation and pregnancy rates after embryo transfer at cleavage stage and at blastocyst stage transfer were not statistically different. Women who had at least one good quality blastocyst (n = 25) had a high pregnancy rate (60% per ET). Blastocyst transfer is a good alternative for couples with many good quality embryos on day 2 after insemination.     

Endometrial thickness significantly affects clinical pregnancy and live birth rates in frozen-thawed embryo transfer cycles

In order to explore the relationship between endometrial thickness on the day of embryo transfer and pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles, we retrospectively analyzed data from 2997 patients undergoing their first FET cycles from January 2010 to December 2012. All patients were divided into three groups (Group A, ≤8?mm; Group B, 9–13?mm; Group C, ≥14?mm) according to the endometrial thickness on embryo transfer day. Compared with patients in the other two groups, patients with thin endometrial thickness in Group A had significantly lower clinical pregnancy rate (33.4%, 41.3% and 45.4%, p?p?p?p?相似文献   

Embryo implantation rates in oocyte donation: a prospective comparison of tubal versus uterine transfers.

OBJECTIVE: To compare pregnancy and implantation rates in tubal and uterine transfers during a hormonal replacement cycle in an oocyte donation program. DESIGN: Prospective randomized. PATIENTS: Forty-two consecutive patients who entered an oocyte donation program. INTERVENTIONS: Twenty-two patients were assigned for uterine transfer and 20 for tubal embryo transfer (ET). RESULTS: Twenty-three pregnancies were achieved, 12 (54.5%) after uterine transfers and 11 (57.9%) after tubal transfers. Implantation rates in both groups are not significantly different (17.4% uterine transfers versus 21.5% tubal ETs). CONCLUSIONS: Our results suggest that in hormonal replacement cycles (uniform endometrial stimulation) there is no advantage in transferring embryos to the fallopian tube. Furthermore, embryo quality and endometrial receptivity appear to be significantly more important than the time of entrance of an embryo to the uterine cavity in determining its chances of implantation.     

Suboptimal laboratory conditions can affect pregnancy outcome after embryo transfer on day 1 or 2 after insemination in vitro

We have demonstrated that the replacement of pronuclear stage human embryos on the day after insemination in IVF-ET results in a pregnancy rate as good as, if not better than, the rate after ET on day 2. The pregnancy rate appears to be influenced by the culture environment used for the gametes. We would recommend that ET be undertaken as soon as possible after insemination on day 1 so that if suboptimal culture conditions are present, they do not have sufficient time to affect the viability of the embryos and reduce the subsequent chance of pregnancy after replacement. If culture conditions have been optimized there is no difference in pregnancy rate after embryo transfer on day 1 or day 2 and one can then replace embryos on either day and expect the pregnancy rate obtained in either case to be similar.     

黄体中期补充戊酸雌二醇对IVF-ET结局的影响

目的:探讨黄体中期补充戊酸雌二醇对体外受精-胚胎移植(IVF-ET)妊娠结局的影响。方法:采用回顾分析研究,选择2009年1月至11月及2010年1月至11月共772个黄体期长效促性腺激素释放激素激动剂(GnRHa)降调节后的常规IVF或卵胞浆内单精子注射(ICSI)周期(标准长方案),其中2009年399个周期于黄体中期不补充戊酸雌二醇作为对照组,2010年373个周期于黄体中期均补充戊酸雌二醇3～6mg作为实验组,再分别根据ET第7日与HCG日血清雌激素水平的比值分为4亚组(A,B,C,D组),比较4亚组周期的临床妊娠率、流产率。结果:各组妊娠率差异无统计学意义(P>0.05);ET第7日与HCG日血清雌激素水平的比值位于30%以下的组别(实验组的C,D亚组)于黄体中期补充戊酸雌二醇,其流产率较不补充戊酸雌二醇者明显降低(P<0.01)。结论:黄体中期补充戊酸雌二醇对IVF-ET结局无提高妊娠率的作用,但可降低流产风险。     

What is the optimal timing of embryo transfer when there are only one or two embryos at cleavage stage?

Today, most IVF programs have moved to blastocyst transfer but there is still uncertainty regarding when to transfer if there are only one or two embryos at the cleavage stage. The aim of this study was to compare the pregnancy rate of day 3 transfers vs. blastocyst stage transfers in patients who had only one or two embryos on day 3. We conducted a retrospective study of 102 patients with one or two cleavage stage embryos that had their embryos transferred on day 3 and 429 patients had their embryos cultured to day 5 for transfer. The number of mature oocytes (4.0 vs 4.6, p?=?NS) and number of cleavage stage embryos on day 3 was similar in the two groups (1.3 vs. 1.5, p?= NS). The clinical pregnancy rate per retrieval (22% vs. 24.6%, p= NS) and the ongoing pregnancy rate per retrieval (20% vs. 20.2%, p?=?NS) was comparable between the groups. Fifty seven (13.2%) of the patients had cleavage embryo arrest and did not have an embryo to transfer on day 5. We conclude that the cumulative pregnancy rate is the same for patients with 1–2 cleavage stage embryos regardless of whether the embryo is transferred on day 3 or day 5.