Morphologically poor blastocysts could affect the implantation rate of a morphologically good blastocyst during a double‐blastocyst transfer for patients who have experienced repeated implantation failures

Purpose

Increasing the number of transferred blastocysts sometimes is selected for patients with repeated implantation failure (RIF). To confirm this strategy, the pregnancy rates (PRs) were compared among the groups who had transferred either a single morphologically good blastocyst (MGB group), double blastocysts with both a MGB and a morphologically poor blastocyst (MGB + MPB group), or a double‐BT with 2 MGBs (two‐MGB group).

Methods

This study was performed between April, 2009 and September, 2014, including 634 cycles for 354 patients with RIF. All the patients received cryopreserved blastocysts in either hormone replacement or natural ovulatory cycles. The included MGBs were at more than the Gardner grade 3BB stage. The PR and implantation rates (IRs) among the three groups were statistically evaluated by the chi‐square test. Statistical significance was set at P < .01.

Results

Although the PRs were similar in these three groups, the IR in the MGB + MPB group was significantly lower than that of the MGB group. The rate in the two‐MGB group also was significantly lower than that of the MGB group.

Conclusion

A double‐BT with a MGB and a MPB does not increase the pregnancy rate, compared with a single‐BT with a MGB among patients with RIF.     

Comparison of zygote intrafallopian tube transfer and transcervical uterine embryo transfer in patients with repeated implantation failure

OBJECTIVE: This study was designed to evaluate the role of zygote intrafallopian transfer (ZIFT) procedure in patients with repeated failure of implantation. STUDY DESIGN: A total of 141 ZIFT cycles of 132 women and 145 embryo transfer (ET) cycles of 97 women in whom five or more embryos were transferred were included in this study. Transcervical uterine embryo transfer and ZIFT cycle outcome in patients with five or more previous implantation failure were compared. Embryos were transferred by laparoscopy into the fallopian tube 24-27 h following oocytes retrieval in the ZIFT group. In the ET group, embryos were transferred transcervically on the third day following oocytes retrieval. RESULTS: The mean age was 34+/-4.9 and 34.9+/-5.0 years in ZIFT and ET group, respectively. No difference was determined between the two groups regarding the basal FSH, E2 value on the day of HCG injection and the number of oocytes retrieved or fertilized. The implantation rate was 6.5% versus 7.2%, clinical pregnancy rate was 22.7% versus 24.8% and live birth rate was 21.2% versus 16.5% in ZIFT and ET groups, respectively. CONCLUSIONS: Implementation of ZIFT procedure in patients with repeated implantation failure is not superior to transcervical uterine embryo transfer.     

Frozen-thawed blastocyst transfer in natural cycle increase implantation rates compared artificial cycle

Abstract

Objective: To analyze global outcomes in frozen-thawed embryo transfer according to endometrial preparation with natural cycle and artificial cycle taking into account the developmental stage of the embryo.

Methods: Retrospective cohort study, held in a tertiary-care university hospital with 1265 cycles for frozen-thawed embryo transfer of 860 patients, performed between January 2014 and December 2017. A total of 1097 embryo transfers were performed: 163 transfers in natural cycle (N), 531 in artificial cycle: transdermal estrogens and 403 with oral estrogens.

Results: Demographical factors were similar in the three groups studied. When comparing the number of embryos transferred, the quality and the stage of embryos within the three groups there were no differences. Implantation rates were significantly higher in natural cycle. When adjusted depending on the developmental stage, blastocyst embryos transferred in natural cycle preparation had the highest implantation rate. Multiple pregnancies were also higher in natural cycle preparation. There were no significant difference between the groups in the clinical pregnancy rate, ongoing pregnancy, live birth, and miscarriages.

Conclusions: Our results suggest that a natural cycle endometrial preparation assessing the disappearance of the dominant follicle by ultrasound increases implantation rates, especially when transferring blastocysts.     

Integration of blastocyst transfer for all patients

OBJECTIVE: To evaluate the efficacy of using day-5 embryo transfer (ET) for all patients. DESIGN: Retrospective, non-randomized comparison of day-3 ET versus day-5 ET. SETTING: Private practice. PATIENT(S): Women having in vitro fertilization and receiving either day-3 ET or day-5 ET. INTERVENTION(S): Extended embryo culture through embryonic genome activation to select those embryos with higher implantation potential. MAIN OUTCOME MEASURE(S): The following parameters were compared for day-3 ET and day-5 ET: clinical and ongoing pregnancy rates, implantation rates, patients having cryopreservation, and liveborn rates. RESULT(S): Blastocyst embryo transfer (day-5 ET) increased the clinical and ongoing pregnancy rate for patients <35 years of age and for the total program. The risk of high order multiple pregnancy was reduced by a decrease in the number of embryos transferred (2.0 vs. 2.7; day-5 ET vs. day-3 ET, respectively). However, the multiple pregnancy rate was not different due to an increase in the implantation rate (day-5 ET 43% vs. day-3 ET 27%). There was no difference in the percent of patients not having an ET (day-5 ET 2.8%; day-3 ET 1.3%). CONCLUSION(S): Blastocyst ET increased the clinical and ongoing pregnancy rate for patients <35 years of age and for the total program, with a concomitant decrease in the number of embryos transferred. However, the decrease in the number of embryos transferred did not decrease the multiple rate, but did reduce the incidence of high order multiples. Most patients (97%) had an embryo transfer. Therefore, culturing embryos an additional 48 hours through embryonic genome activation allows for selection of the most viable embryos without compromising the patient's opportunity to become pregnant.     

Zygote intrafallopian transfer among patients with repeated implantation failure

ObjectiveTo summarize the experience of a single center with laparoscopic zygote intrafallopian transfer (ZIFT) performed exclusively among patients with high-order repeated implantation failure (RIF) following in vitro fertilization-embryo transfer (IVF-ET).MethodsA retrospective cohort study was performed at the Edith Wolfson Medical Center, a tertiary referral university hospital located in Holon, Israel. A group of 176 patients with 8.15 ± 3.9 previously failed IVF-ET cycles underwent 280 ZIFT procedures between 1995 and 2010. The main outcome measure was the live birth rate per patient treated.ResultsIn all, there were 274 fresh and 6 frozen ZIFT cycles recorded in the study cohort, resulting in 96 clinical pregnancies per attempt (34.3%) and 72 live births (25.7%). The live birth rate per patient was 39.8%.ConclusionThe use of ZIFT remains a powerful tool in the clinical management of selected patients with high-order RIF. This procedure should be kept in mind when all other measures fail among patients with at least 1 unobstructed fallopian tube.     

Zona-free versus laser zona-assisted hatching blastocyst transfer: a comparison of outcomes

In unselected IVF patients, zona-free and laser zona-assisted hatching produced a comparable effect on blastocyst transfer.     

An 18-month survey of infertility treatment by in vitro fertilization,gamete and zygote intrafallopian transfer,and replacement of frozen-thawed embryos

An 18-month survey of infertility treatment by in vitro fertilization (IVF) and related procedures at the Centre for Reproductive Medicine of the Vrije Universiteit Brussel is described. During this period, 1326 treatment cycles were started in patients with long-standing infertility and 1135 oocyte retrievals were performed in 771 different patients. IVF and embryo transfer (ET) after laparoscopic (N=793) or ultrasonically guided (N=342) ovum pickup, gamete intrafallopian transfer (GIFT;N=284), or zygote intrafallopian transfer (ZIFT;N=15) combined with IVF as well as the replacement of cryopreserved embryos yielded an overall pregnancy rate of 21.8% per started cycle. Echographic and laparoscopic oocyte retrieval gave similar results except for a higher fertilization rate after echographic-guided retrieval. For in vitro fertilization and embryo transfer an overall pregnancy rate of 26% per transfer was obtained. For GIFT and ZIFT the pregnancy rates were, respectively, 27.8 and 46.7% per replacement. For each procedure onethird of the pregnancies aborted. After the replacement of frozen and thawed embryos, during a natural cycle, a significantly lower fetal loss was observed.     

Elective single embryo transfer: Comparison of blastocyst and cleavage-stage embryo transfer

Objective:   Blastocysts are reportedly suitable for preventing multiple pregnancies as a result of the high implantation rate per embryo. The present study compared clinical results for elective single embryo transfer (ET) between blastocysts and cleavage-stage embryos in order to ascertain the usefulness of blastocyst culturing in single ET.
Methods:   Between January 2002 and December 2004, conventional in vitro fertilization ET and/or intracytoplasmic sperm injection was carried out for single ET in 86 cycles, to prevent multiple pregnancies (for medical reasons or because of patient wishes).
Results:   Among the 80 cycles in which a fresh embryo was transferred, pregnancy/implantation rates per ET were 35.3% for day 2/3 ET and 50.0% for day 5 ET, and pregnancy/implantation rates per oocyte retrieval were 35.3% for day 2/3 ET and 44.2% for day 5 ET. Ongoing pregnancy/delivery rates per oocyte retrieval were 32.4% for day 2/3 ET and 38.5% for day 5 ET. Monozygotic twinning occurred in one case of day 5 ET.
Conclusions:   Pregnancy rates per single ET tended to be higher for day 5 ET than for day 2/3 ET. However, no marked differences were identified in ongoing pregnancy/delivery rates per oocyte retrieval between groups. (Reprod Med Biol 2005; 4 : 197–201)     

Obstetric and perinatal outcomes of pregnancy in patients with repeated implantation failure

ObjectiveDespite the great advance of assisted reproductive technology (ART) in recent decades, many IVF patients failed to achieve a pregnancy even after multiple IVF-ET attempts. These patients are considered to have repeated implantation failure (RIF). While exhausting efforts have been devoted to the improvement of pregnancy rate in RIF patients, it is not clear whether RIF patients have aberrant obstetric or perinatal outcomes after they eventually achieved a pregnancy.Materials and methodsTaking advantage of a relatively large database of IVF-ET cycles at the Chang Gung Memorial Hospital, we compared obstetric and perinatal outcomes of RIF patients who have a successful pregnancy after IVF-ET treatment(s) to those of control IVF-ET patients.ResultsBecause multiple pregnancies are associated with a high risk of obstetric complications, we restricted the analysis to patients who had singleton pregnancies. Analysis of a total of 596 control and 46 RIF cases showed the rates of almost all obstetric and perinatal outcomes investigated are not different between the two groups. However, the rate of placental abruption in the RIF group (4.35%) appeared to be significantly higher than that of controls (0.50%; OR = 8.99). This difference is still statistically significant after adjustment with the age (adjusted OR = 8.2).ConclusionWhile the rates of a spectrum of obstetric and perinatal outcomes are normal in RIF patients, these patients could have an enhanced risk of placental abruption. However, investigations with a large sample size are needed to substantiate this inference.     

Introduction of blastocyst culture and transfer for all patients in an in vitro fertilization program

Objective: To evaluate the nonselective application of extended embryo culture on the outcome of IVF.

Design: Retrospective analysis.

Setting: Private practice assisted reproductive technology center.

Patient(s): Seven hundred ninety nonselected patients undergoing IVF with controlled ovarian stimulation.

Intervention(s): For day 3 ET, multicell embryos were cultured in human tubal fluid medium and 12% synthetic serum substitute. For day 5 ET, embryos were cultured for 48 hours in S1 medium and then for 48 hours in S2 medium.

Main Outcome Measure(s): Implantation rate (determined by total no. of visualized gestational sacs), ongoing pregnancy rate, and number of embryos available for ET.

Result(s): Respective day 3 and day 5 implantation rates for patients aged <35 years (29.5% and 38.9%), patients aged 35–39 years (20.7% and 28.2%), and all patients combined (23.3% and 32.4%) were statistically significantly different. Significantly more embryos were transferred on day 3 than on day 5 for patients aged <35 years (2.9 vs 2.4), patients aged 35–39 years (3.1 vs 2.6), and all patients combined (3.0 vs 2.5). The difference in ongoing pregnancy rates per retrieval was statistically significant for day 3 compared with day 5 transfers for all patients combined (35.9% vs 43.8%). Cancellation rates for transfer after retrieval increased significantly for day 3 compared with day 5 transfer (2.9% vs 6.7%).

Conclusion(s): These results demonstrate the feasibility of using extended embryo culture in a nonselective manner for couples undergoing IVF. Overall, extended embryo culture was associated with a significant increase in pregnancy rates and implantation rates and a significant decrease in the number of embryos transferred. The rate of multiple implantation among patients aged <35 years warrants consideration of single blastocyst transfers for this group.     

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.     

降调节联合激素替代冻融胚胎移植周期中不同内膜转化时间对反复种植失败患者临床结局的影响

目的:探讨反复种植失败(RIF)患者冻融胚胎移植(FET)周期移植时机的选择及对临床结局的影响。方法:选择采用Gn RH-a降调节激素替代方案准备子宫内膜进行FET的RIF患者106例,随机分为A组(常规法)53个周期,即孕酮作用内膜3 d后移植第3日胚胎;B组(改良法)53个周期,即延迟内膜扳机和黄体支持用药,比较组间血清性激素水平、临床妊娠率、早期流产率等相关指标。结果:患者的基本情况组间具有可比性(P0.05);移植日雌二醇(E_2)、孕酮(P)、E_2/P、临床妊娠率组间均有统计学差异(P0.05);移植前1日血清P水平组间差异有统计学意义(P0.05)。结论:对于RIF患者,在降调节联合激素替代-FET周期中,延长雌、孕激素用药时间可刺激内膜达到理想状态,进而获得满意的妊娠结局。     

宫腔灌注绒毛膜促性腺激素对反复着床失败后冻融胚胎移植妊娠结局的作用

目的:探讨胚胎反复着床失败(RIF)后冻融胚胎移植(FET)时行宫腔内灌注基因重组人绒毛膜促性腺激素(rh CG)对妊娠结局的影响。方法:选择既往胚胎RIF再次行FET的208个周期的患者资料进行回顾性分析。将其中FET日宫腔内灌注rh CG为研究组,另按1∶1选择匹配(年龄、既往ET失败次数、不孕类型)对照组。分析比较着床率、自然流产率、生化妊娠率、临床妊娠率、多胎妊娠率。结果:研究组着床率(22.92%)、生化妊娠率(5.77%)、自然流产率(17.78%)均略高于对照组(分别为16.88%、1.92%、16.13%),多胎妊娠率略低于对照组(15.56%vs 19.35%),但差异均无统计学意义(P0.05)。研究组和对照组均未观察到异位妊娠病例,研究组临床妊娠率显著高于对照组(43.27%vs 29.82%),差异有统计学意义(P0.05)。结论:FET日行宫腔内灌注rh CG可以提高RIF患者的临床妊娠率。     

Comparison of the sex ratio with blastocyst transfer and cleavage stage transfer

Purpose : To evaluate the sex ratio in births conceived with blastocyst transfer compared to day 3-ET. Methods : A retrospective analysis of IVF patients who became pregnant after blastocyst or cleavage stage transfer at Stanford University Hospital and a literature review were performed. Result(s) : In the day 3-ET group, the male-to-female (M/F) ratio was 157/139 (53%/47%) compared to 97/66 (59.5%/40.5%) in the blastocyst group (P = 0.18). Similar trends have been found in individual studies in the literature but reached statistical significance in only one out of six reports reviewed. The combined data from our study and the literature show a male-to-female ratio of 797/594 (57.3%/42.7%) in blastocyst transfer compared to 977/932 (51.2%/48.8%) in day 3-ET (P = 0.001). Conclusion(s) : Although individual studies may lack power to show an altered sex ratio with blastocyst transfer, the combined data presented in this report do suggest that the M/F ratio is higher with blastocyst transfer compared to cleavage stage transfer.