Recurrent failure of pronucleus formation after intracytoplasmic sperm injection

We report on a couple with complete fertilization failure in three consecutive trials of intracytoplasmic sperm injection. Some of the unfertilized oocytes were fixed and decondensed sperm heads were found in all of them. It is not clear whether specific defects of the oocyte, abnormalities of sperm chromatin, or a combination of factors are responsible for the observed failure to develop pronuclei. Received: 22 August 1998 / Accepted: 22 September 1998     

Intracytoplasmic sperm injection overcomes previous fertilization failure with conventional in vitro fertilization

Objective: To evaluate the outcome of intracytoplasmic sperm injection (ICSI) in patients with previous idiopathic fertilization failure (≤20% fertilization rate) after conventional IVF.

Design: Retrospective analysis.

Setting: IVF program at a university medical center.

Patient(s): Twenty-five patients who underwent 38 ICSI cycles after experiencing unexplained fertilization failure with conventional IVF (group A) and 87 patients who underwent 118 ICSI cycles for male factor indications during the same period (group B).

Intervention(s): Intracytoplasmic sperm injection was performed in a subsequent cycle after fertilization failure with conventional IVF.

Main Outcome Measure(s): Outcomes of IVF were compared between groups A and B.

Result(s): Fertilization was achieved with ICSI in all patients with previous fertilization failure. The mean (±SD) fertilization rate (68% ± 21% vs. 64% ± 22%), implantation rate per embryo (22.6% vs. 20%), and delivery rate per cycle (47.3% vs. 49.1%) did not differ significantly between groups A and B. Overall, 72% of patients with previous unexplained fertilization failure had a successful pregnancy after ICSI.

Conclusion(s): Intracytoplasmic sperm injection can overcome unexplained fertilization failure caused by a potentially occult gamete abnormality, with the same fertilization, implantation, and pregnancy rates as are seen in patients with abnormal sperm parameters.     

Overview Analysis of Outcomes with Intracytoplasmic Sperm Injection

The study of male factor infertility only recently has begun to receive increasing attention because there are now more therapeutic options. This situation has become possible because of the availability of assisted fertilization techniques, particularly intracytoplasmic sperm injection (ICSI) which has resulted in high fertilization and pregnancy rates. Although the sperm for ICSI have been used mainly from ejaculated specimens, it is now possible to use sperm from epididymal and testicular sources. Factors that affect the pregnancy rate with ICSI include female age, the number of embryos transferred, and oocyte morphology. The small follow up studies of children born after ICSI provide reassurance that the technique appears to be safe.     

Effect of sperm selection using hyaluronan on fertilization and quality of cleavage-stage embryos in intracytoplasmic sperm injection (ICSI) cycles of couples with severe teratozoospermia

Abstract

This study aimed to evaluate the effect of hyaluronan-selected/physiological intracytoplasmic sperm injection (PICSI) on fertilization and quality of cleavage-stage embryos in infertile couples with ≤1% of spermatozoa with normal strict morphology (severe teratozoospermia). Seventy-seven couples underwent PICSI between October 2017 and December 2018 (PICSI group), while 75 couples underwent conventional intracytoplasmic sperm injection (ICSI) between January 2016 and September 2017 (ICSI group). Good quality embryos (GQEs) were evaluated based on morphology. Patient and cycle characteristics were comparable between the PICSI and ICSI groups, except for age and anti-Müllerian hormone (AMH) level (38.4?±?3.9?years vs. 36.3?±?4.3?years, p?=?.002 and 2.06?±?1.99?ng/mL vs. 2.97?±?3.25?ng/mL, p?=?.040). The fertilization rate per oocyte inseminated and GQE rate were significantly higher in the PICSI group than in the ICSI group (82.7% vs. 71.7%, p ? .001 and 52.8% vs. 34.0%, p ? .001). Furthermore, the absence of GQEs was found to be lower in the PICSI group (13.0% vs. 30.7%, p?=?.008). Multivariate analysis adjusted for age and AMH level identified PICSI as an unfavorable and independent factor for the absence of GQEs (adjusted odds ratio, 0.333; 95% confidence interval, 0.125–0.890). PICSI seems to be superior to ICSI in terms of fertilization and embryo quality in couples with severe teratozoospermia.     

Use of hyaluronic acid for sperm immobilisation and selection before intracytoplasmic sperm injection: A systematic review and meta-analysis

AIM: To appraise critically the published randomised controlled trials (RCTs) reporting on the effectiveness of using hyaluronic acid (HA) for sperm immobilisation and selection before intracytoplasmic sperm injection (ICSI). METHODS: Two authors used the PICO Method in order to perform a comprehensive literature search of the standard medical databases in June 2015. Data from the included studies was extracted independently by two authors using a predefined pro-forma. Review Manager (RevMan) was used to calculate the combined outcomes where multiple studies contributed with their results. Risk ratio (RR) with a 95%CI using the Mantel-Haenszel method was calculated for binary data variables. Heterogeneity was measured using the χ² test and quantified using I². In case of substantial heterogeneity (P < 0.10 for χ² test or I² > 50%) the combined outcome was calculated using the random effects model. The results from the meta-analysis were displayed as forest plots. The guideline of the Cochrane Collaboration was used to assess the risk of bias and it was illustrated as a risk of bias graph. RESULTS: The systematic literature search identified 166 different studies related to sperm immobilisation and selection for ICSI. Eleven RCTs involving 13719 oocyte intracytoplasmatic injections with sperm immobilised and selected using HA or polyvinylpyrrolidone (PVP) were included in this systematic review and meta-analysis. There was low heterogeneity among the included trials (χ² = 16.86, df = 11, P = 0.11; I² = 35%). There was no statistical difference between HA and PVP groups in terms of fertilisation rate (RR = 1.01; 95%CI: 0.99-1.03; z = 0.75; P = 0.45), good embryos rate (RR = 1.01; 95%CI: 0.96-1.06; z = 0.30; P = 0.76), live birth rate (RR = 1.15; 95%CI: 0.86-1.54; z = 0.92; P = 0.36), clinical pregnancy rate (RR = 1.04; 95%CI: 0.92-1.17; z = 0.62; P = 0.53) and implantation rate (RR = 1.17; 95%CI: 0.94-1.46; z = 0.40; P = 0.16). The quality of most of the included studies was moderate to poor because of unclear randomisation technique, inadequate allocation concealment and blinding. CONCLUSION: This systematic review and meta-analysis provides evidence of similar efficiency between using HA or PVP for sperm immobilisation and selection before ICSI.     

IMSI和ICSI来源胚胎PGT-A结局的回顾性研究

目的:通过植入前胚胎遗传学检测技术,初步研究胞浆内形态选择精子注射(IMSI)来源胚胎的遗传学安全性.方法:回顾分析2016年5月至2017年5月于大连市妇女儿童医疗中心接受植入前遗传学检测的83个周期患者,按受精方式不同分为IM-SI组(n=48)和ICSI组(n=35),IMSI组、ICSI组成功活检囊胚144个和...     

The development of surgical sperm extraction and new challenges to improve the outcome

Surgical sperm extraction with intracytoplasmic sperm injection has become widespread worldwide and is regarded as the sole option for patients with azoospermia. However, the sperm retrieval rate remains unsatisfactorily low, particularly for men with non-obstructive azoospermia (NOA). Therefore, the technical challenges associated with improving the sperm retrieval rate for men with NOA are being addressed. The most successful method developed to date is microdissection testicular sperm extraction (micro-TESE), which is rapidly becoming recognized as a useful technique due to its relatively high sperm retrieval rate and low complication rate. However, even with micro-TESE, the sperm retrieval rate for men with NOA remains at 30–60 %, with an even lower birth rate. The technical challenges associated with improving the outcomes of surgical sperm extraction are being approached through the use of ultrasound and optimal surgical devices such as narrow band imaging, multiphoton microscopy, and optical coherent tomography. In addition to the difficulties related to searching for sperm, medical treatments that induce spermatogenesis remain controversial. For example, varicocele repair prior to surgical sperm extraction and hormonal therapy before and after TESE have been extensively examined. We herein briefly summarized the development process in surgical sperm extraction up to the present and technical challenges to improve the outcomes of surgical sperm extraction.     

常规体外受精与卵胞浆单精子注射技术妊娠及分娩结果比较

目的通过比较接受常规体外受精技术(IVF)及卵胞浆单精子注射技术(ICSI)治疗后妊娠的病例,分析临床资料、妊娠及产科结局,从而评估其安全性。方法对中山大学附属第一医院1998年1月至1999年12月接受体外受精-胚胎移植治疗后妊娠的533例临床资料进行回顾性分析。结果ICSI组受精率明显高于IVF组,IVF和ICSI两组早期胚胎发育情况、产科结局、围生情况及出生后婴儿的健康情况差异无显著性意义。结论与常规IVF相比,ICSI并不增加胎儿畸形率及新生儿并发症,但仍需要长期的大量的随访以排除可能的危险性。     

不同精子参数及来源与ICSI结局的相关性研究

目的:探讨不同精子参数及来源与单精子卵胞浆内注射(ICSI)治疗结局的相关性.方法:回顾分析2010年6月至2011年12月在武汉大学人民医院生殖医学中心行ICSI助孕治疗的413个周期,根据精子质量及来源分为4组,非严重少弱的新鲜射出精子组(A1组,244个周期)、严重少弱的新鲜射出精子组(A2组,61个周期)、睾丸精子组(B组,86个周期)、冻融的射出精子组(C组,22个周期).比较4组的ICSI治疗结局.结果:4组患者的受精率、正常受精率、卵裂率、优胚率、临床妊娠率、胚胎种植率和早期流产率均无显著差异(P＞0.05).结论:精子的质量及来源不影响ICSI治疗的受精及早期妊娠结局.     

Rate of aneuploidy in miscarriages following in vitro fertilization and intracytoplasmic sperm injection

OBJECTIVE: To evaluate the incidence of aneuploidy in miscarriages after IVF and intracytoplasmic sperm injection (ICSI) procedures. DESIGN: Retrospective study. SETTING: University IVF program. PATIENT(S): All IVF patients with missed abortions undergoing uterine curettage. INTERVENTION(S): Cytogenetic analysis of products of conception (POC). MAIN OUTCOME MEASURE(S): Incidence of aneuploidy in POC. RESULT(S): Thirty-two of 59 specimens (54%) reviewed were abnormal. The patients with ICSI were more likely to have aneuploidy identified in their POC than conventional IVF, 76% vs. 41%. The average ages in these groups were similar: 37.1 vs. 37.8 years. There was a trend toward decreased aneuploidy with day 5 compared to day 3 embryo transfers; 38% vs. 63%. CONCLUSION(S): We found a significantly higher aneuploidy rate in the abortuses of patients who conceived with ICSI. It is possible that this increased incidence is due to abnormalities in the sperm of patients with ICSI, but could also be partially related to the technique itself.     

Clinical outcome of magnetic activated cell sorting of non-apoptotic spermatozoa before density gradient centrifugation for assisted reproduction

PURPOSE: Magnetic activated cell sorting (MACS) eliminates apoptotic spermatozoa based on the presence of externalized phosphatidylserine residues. We evaluated the outcome of male fertility treatment when intracytoplasmic sperm injection (ICSI) into human oocytes was performed with non-apoptotic MACS-selected spermatozoa. METHODS: 196 couples were treated by ICSI following spermatozoa preparation by MACS (study group; 122 couples) or density gradient centrifugation (DGC) (control group; 74 couples). Fertilization, cleavage, pregnancy, and implantation rates were analyzed. RESULTS: The percentage of sperm with normal morphology after MACS selection was improved. Cleavage and pregnancy rates were higher, respectively, in the study group than in control. A slightly higher implantation rate was also observed in the study group. CONCLUSIONS: MACS selection of human spermatozoa increased cleavage and pregnancy rates in oligoasthenozoospermic ART cases. This novel method for selecting non-apoptotic spermatozoa for ICSI is safe and reliable, and may improve the assisted reproduction outcome.     

早期补救卵胞浆内单精子显微注射在完全受精失败周期的临床结局分析

目的:评估短时受精联合早期补救卵胞浆内单精子显微注射(R-ICSI)在完全受精失败周期的临床价值。方法:2009年1月～2010年6月我中心试管婴儿助孕治疗709例,其中短时受精完全失败行早期R-ICSI周期82例,卵胞浆内单精子显微注射(IC-SI)周期627例,比较两组正常受精率、异常受精率、优质胚胎率、胚胎种植率、临床妊娠率及流产率。结果:两组正常受精率、优质胚胎率、胚胎种植率、临床妊娠率及流产率无统计学差异,R-ICSI组异常受精率(5.0%)显著高于ICSI组(3.0%)(P<0.05)。结论:短时受精联合早期R-ICSI可及早发现受精失败并及时补救,获得较好的临床结局。     

Y-chromosome microdeletions and cytogenetic findings in unselected ICSI candidates at a Danish fertility clinic

Purpose : To determine the frequency and type of microdeletions on the Y chromosome, and to evaluate cytogenetic findings in unselected ICSI candidates at a Danish Fertility Clinic. Methods : Genomic DNA was extracted from blood samples, which were collected prospectively from 400 ICSI candidates attending the Fertility Clinic at Aarhus University Hospital, Denmark. Twenty-five sequence tagged sites (STSs) spanning the azoospermia factor (AZF) regions of the Y chromosome were amplified in 5 multiplex sets to investigate Y microdeletions. Semen analysis, karyotype analysis, and histological evaluation of testicular biopsies were also performed. Results : Y microdeletions were detected in 3 (0.75%) of 400 unselected ICSI candidates. The frequency of Y microdeletions was found higher in azoospermic men (2%) than in oligozoospermic men (0.6%). Two patients having oligozoospermia had Y microdeletions in the AZFc region only, whereas the patient having azoospermia had Y microdeletions spanning the AZFb and AZFc regions. No microdeletion was detected in the AZFa region. Chromosomal anomalies were found in 6.1% of azoospermic men and in 2.7% of oligozoospermic men. A high frequency of cytogenetic abnormalities was found in normozoospermic men with fertilization failure (7.4%). Conclusions : The frequency of Y microdeletions both in the unselected ICSI candidates and subgroups classified as azoospermic and oligozoospermic seems rather low compared to results of previous studies, which have been quite varying. It is possible that in addition to patient selection criteria, ethnical and geographical differences may contribute to these variations. Cytogenetic evaluation of normozoospermic men with fertilization failure seems indicated because of a high frequency of cytogenetic abnormalities.     

Comparison of embryo quality between intracytoplasmic sperm injection and in vitro fertilization in sibling oocytes

Background The aim of the present study was to compare the quality of embryos derived from sibling oocytes by in vitro fertilization (IVF) or ICSI. Methods Consecutive patients with a less than 40% fertilization rate in a previous standard IVF cycle or with relative male factor infertility were recruited for the study. The oocytes retrieved from each patient were divided into two groups for either conventional insemination (group A) or ICSI (group B). Power analysis showed that to detect a 25% difference in the rate of high-quality embryos between the groups with a power of 0.8, at least 1,200 oocytes were needed in each group. Results One hundred seventy-seven patients were included in the study. Group A was comprised of 1,526 oocytes and group B of 1,480 sibling oocytes. As expected, the fertilization rate was significantly higher in group B than group A (67.1 vs. 43.6%, p < 0.001). No significant between-group differences were observed in cleavage rate (92.7 and 89.7%, respectively) and the rate of either grade A embryos (22.6 and 23.9%, respectively) or grade A₁ embryos (37.3 and 33.5%, respectively). However, in the subgroup of patients with relative male-factor infertility (n = 36), the rate of grade A₁ embryos was significantly higher in the IVF than the ICSI group (46.4 vs. 29.0%, respectively, p = 0.02). Conclusions Embryo quality does not seem to be influenced by the mode of fertilization (IVF or ICSI). We assume that embryo quality depends on intrinsic factors of the gametes involved rather than on the fertilization process per se. Capsule Embryo quality does not seem to be influenced by the mode of fertilization but depends on intrinsic factors of the gametes involved.     

Relationship between first polar body morphology before intracytoplasmic sperm injection and fertilization rate, cleavage rate, and embryo quality

Objectives

To evaluate the influence of the morphology of the first polar body (PB) on intracytoplasmic sperm injection (ICSI) outcomes.

Methods

The morphology of the first PB was assessed in 3177 metaphase II oocytes and classified as: intact and normal size, fragmented, or enlarged size. The rates of fertilization, cleavage, and embryo quality were evaluated on day 2.

Results

The rates of fertilization, cleavage, and formation of good quality embryos resulting from the insemination of oocytes with an enlarged first PB (20.7%, 18.7%, and 5.0%, respectively) were significantly lower than those for oocytes with an intact first PB of normal size (70.8%, 62.5%, and 19%, respectively) or a fragmented first PB (69.7%, 60.5%, and 17.1%, respectively). Rates did not differ significantly between oocytes with an intact first PB of normal size and oocytes with a fragmented first PB (P > 0.05).

Conclusions

The presence of an enlarged PB is related to poorer rates of fertilization, cleavage, and top quality embryos. However, identification of first PB fragmentation does not seem to interfere with ICSI outcomes.     

ICSI outcome is significantly better with testicular spermatozoa in patients with necrozoospermia: a retrospective study

Objective: To determine whether intracytoplasmic sperm injection (ICSI) outcome with testicular sperm is superior to that of ejaculated sperm in men with incomplete necrozoospermia, defined as sperm viability ≥5 to ≤45%.

Study design: Retrospective study at a Reproductive Medicine Center of a tertiary referral hospital. A total of 231 couples with male infertility due to incomplete necrozoospermia underwent 342 ICSI cycles with freshly ejaculated sperm (ICSI-ejaculated) and 182 cycles with testicular sperm (ICSI-TESE).

Results: Overall 1624 MII oocytes were injected in the ICSI-ejaculated group with a fertilisation rate of 60.8%, while in ICSI- TESE cycles the fertilisation rate was 59.6% in 874 MII oocytes. The cleavage rate was higher in ICSI-ejaculated cycles than in ICSI-TESE cycles (96.3% versus 92.9%; p?=?0.004). However, the pregnancy and implantation rates per cycle were significantly higher in the ICSI-TESE group (67/182, 36.8% versus 68/342, 19.9% (p?=?0.0001); and 23.7% versus 12.7% (p?=?0.0001), respectively). The miscarriage rate was similar (ICSI-ejaculated 26.5% versus ICSI-TESE 17.9%, p?=?0.301). Live birth rate per cycle in the ICSI-ejaculated group was significantly lower than in the ICSI-TESE (13.7% versus 28.6%, p?=?0.0001).

Conclusions: In cases of persistent necrozoospermia, testicular sperm should be favoured over ejaculated sperm. These data call for more research to understand the pathophysiology of refractory necrozoospermia.     

Does the genetic and familial background of males undertaking ICSI affect the outcome?

Purpose  To investigate whether the success rate of ICSI is (1) related to the etiology of infertility or (2) adversely affected by a family history of potential genetic disorders. Methods  All men with an ICSI indication in our hospital between 1994 and 2005 were included in our cohort study. Data on the ICSI process, etiology of infertility, and family history were collected. ICSI success rates of infertility subgroups and a subgroup with a positive family history were compared to a group with unknown etiology and a negative family history. Results  There was no significant difference in clinical pregnancy or delivery rates between the subgroups. Couples achieving a pregnancy underwent significantly more ICSI cycles compared to couples not achieving a pregnancy. Conclusion  Our results suggest that the success rate of ICSI treatment is not related to the cause of infertility or a family history positive for potential genetic disorders. Capsule ICSI success rate is neither related to the cause of infertility nor adversely affected by a family history positive for potential genetic disorders.     

The predictive value of high-magnification sperm morphology examination on ICSI outcomes in the presence of oocyte dysmorphisms

Purpose

To evaluate the relationship between oocyte dysmorphisms and IMSI outcomes

Methods

Data of IMSI cycles performed in 332 patients were included in this study. Patients were included only if presented more than four and less than 30 oocytes upon oocyte retrieval. Patients who underwent IMSI were matched, concerning female age and sperm parameters, with patients who underwent ICSI in the same period (n = 332). The two groups (ICSI and IMSI) were compared with regard to treatment outcomes. The influence of IMSI on fertilization and embryo quality on D3 and D5, when oocyte dysmorphisms were present was analyzed.

Results

A total of 6444 oocytes were morphologically evaluated and injected. Regardless of the oocyte quality, IMSI performance was a determinant of the increased odds of development to high quality embryo on D3 (OR: 1.98; CI: 1.54–2.56) and D5 (OR: 3.27; CI: 1.61–6.66).

Conclusions

The selection of a morphologically normal spermatozoon under high-magnification is associated with increased embryo quality, regardless of the oocyte morphology. The injection of a spermatozoon, selected under high-magnification, into a morphologically normal oocyte leads to the highest probability of developing high quality embryos.     

冻融后小鼠卵母细胞培养时间对ICSI结果的影响及受精失败辅助激活的结果

目的:研究冻存后的小鼠成熟卵母细胞复苏后培养不同时间对ICSI结果的影响,观察Ca2+载体霉素联合嘌呤霉素对ICSI受精失败的卵母细胞补救激活的有效性。方法:采用慢冻-快融程序化冷冻方法冻融小鼠成熟卵母细胞,复苏后卵母细胞分别培养不同时间(1h、2h、3h、4h、5h)后行ICSI,比较其受精和胚胎发育情况。冻融后受精失败的卵母细胞分为两组(A组:辅助激活,B组:不采取辅助激活),另外获取ICSI受精失败的新鲜卵母细胞(C组)采用和A组同样方法辅助激活,观察3组激活效果。结果:复苏的卵母细胞ICSI前培养3~4h后正常受精率、囊胚形成率明显高于培养1h、2h和5h实验组;A组激活率与B组相比,有明显差异(30.4%vs 6.7%,P<0.05);A组激活率和2PN2PB比例明显低于C组(30.4%vs 75.6%,P<0.05;21.4%vs 47.1%,P<0.05);A、C两组之间1PN2PB比例相比无统计学差异。结论:复苏的成熟卵母细胞ICSI前培养3~4 h后有助于卵母细胞结构的恢复,提高正常受精率和后期发育潜能。辅助激活在一定程度上可以挽救ICSI受精失败的卵母细胞;由于冻融损伤,复苏后ICSI受精失败的卵母细胞被辅助激活的能力明显下降。