Hypoosmotic swelling test in the prediction of male fertility

The hypoosmotic swelling test (HOS) is a simple test to measure the functional competence of human sperm membranes. The question is, does a relationship exist between this competence and the fertilization potential of human spermatozoa? In this study the strongest correlation (r = 0.76) was obtained between sperm swelling and sperm viability (supravital staining). Only a moderate correlation (r = 0.50) was obtained with normal sperm morphology; weaker correlations were also obtained with the sperm penetration assay (r = 0.42) and human IVF (r = 0.24). The results, therefore, indicate that the HOS test has a limited predictive value. Notwithstanding this low concordance between sperm swelling and fertilizing potential, a less than 50% HOS test threshold was seen to be a definite indicator of a male factor.     

精子形态变化对体外受精率的影响

目的:通过对ICSI和IVF受精率的统计,比较精子形态中的精子正常形态率、头部畸形率、畸形精子指数(TZI)和精子畸形指数(SDI)对受精结果的影响。方法:用Krger's严格标准法分别计算每组样本的精子正常形态率、头部畸形率、TZI和SDI值,与受精率进行比较。结果:①IVF组和ICSI组的受精率,与精子正常形态率、头部畸形率、TZI、SDI均无相关性。②IVF组和ICSI组中SDI>1.6和SDI<1.6的受精率、优质胚胎率和临床妊娠率差异均无统计学意义(P>0.05)。③IVF组和ICSI组中精子正常形态率≤15%与精子正常形态率>15%的二组间受精率、优质胚胎率和临床妊娠率的差异均无统计学意义(P>0.05)。结论:精子形态在体外受精时对受精率无影响,不能用精子形态来直接评价体外受精的结果。     

Abnormal sperm morphology and other semen parameters related to the outcome of the hamster oocyte human sperm penetration assay

A new method for evaluation of sperm morphology using strict criteria is currently used in the andrology laboratory at the Eastern Virginia Medical School. A prospective study was designed to evaluate the following semen parameters in samples of all patients over a set period of time: sperm concentration and motility, and normal sperm morphology. These factors were correlated with results of the hamster zona-free oocyte/human sperm penetration assay (SPA). One hundred patients with a sperm concentration ranging from 2 to 219 X 10(6)/ml, a motile sperm fraction ranging from 6.9 to 87%, and normal sperm morphology ranging from 1 to 39%, were evaluated. The statistical analysis system general linear model was used to judge the influence of the different variables. There was a statistically significant relationship between the per cent of sperm with normal morphology and penetration rate in the SPA (P = 0.001). Outcome of the SPA was also correlated with in vitro fertilization, retrospectively, in 84 patients. Thirty-eight patients had an SPA less than 10%, with no fertilization in vitro in 13 patients (33.3%) and fertilization in 25 (66.7%). Forty-five had an SPA greater than 10% with fertilization in 37 (82.2%) and no fertilization in eight (17.8%) patients.     

Relationship between human sperm lipid peroxidation, comprehensive quality parameters and IVF outcome

The membranes of human spermatozoa contain an extremely high concentration of polyunsaturated fatty acids and are therefore susceptible to lipid peroxidation damage. The aim of this study was to retrospectively determine the association between the lipid peroxidation levels of washed spermatozoa, as indicated by thiobarbituric-acid-reactive substance concentration, and: (a) semen quality evaluated by basic routine, biochemical, cytological and quantitative ultramorphological analyses; (b) IVF fertilization rate. Semen samples from 45 male partners of couples who had been referred for IVF treatment due to a female infertility factor were evaluated for quality as well as for thiobarbituric-acid-reactive substance concentrations. The latter were found to have a negative correlation with total sperm count, semen volume, zinc/fructose ratio, and the integrity of sperm acrosome and axonema. It was suggested that lipid peroxidation has a deleterious effect on the ultramorphological status of the sperm cells and, thereby, on the male fertilization potential. The content of the seminal fluid, about 30% of which is produced by the prostate, may protect spermatozoa from this destructive process. A negative correlation was also found between thiobarbituric-acid-reactive substance concentrations and IVF fertilization rate. When the patients were subdivided into fertilizing (fertilization rate > 0%) and nonfertilizing (fertilization rate = 0%) subgroups (n = 33 and n = 12, respectively), the former exhibited significantly lower thiobarbituric-acid-reactive substance concentrations than the latter. A new IVF fertilization index based on the lipid peroxidation level was established. This index had a predictive power of 93% (94% sensitivity and 92% specificity). The clinical value of this index should be further verified.     

精子功能指标在辅助生殖助孕方式选择中的作用

目的 评估精子功能参数对精子常规体外受精能力的预测价值,探寻有效选择受精方式的新指标.方法 回顾性分析2017年1月至2019年12月于我院首次行体外受精-胚胎移植(IVF-ET)短时受精的429个周期的临床资料,根据受精结局不同分为2组:受精失败或受精率＜30％的患者为早补救卵胞浆内单精子注射(R-ICSI)组(n=...     

精子功能检测与男性不育诊治的新进展

传统的精液常规分析是用于判断男性生育力的最基本临床指标,但是,只依靠精液分析的结果来预测男性生育状况仍是很不准确的。精子功能正常与否,对临床选择IVF还是ICSI治疗不育症极为重要。因为IVF需要功能完全正常的精子才能受精,而ICSI的受精只需要精子的正常核DNA,不需要其它的精子功能。在发明ICSI以前,患者IVF受精失败或低下(<30%)发生率很高(20%~35%)。研究证明,这些IVF受精失败的患者主要与精子功能障碍有关。常见的是少精子症,弱精子症和畸形精子症。但是有很多患者,精液分析结果仍正常。为了提高临床对精子功能测定的准确性,文献里有很多新的精子功能试验的研究报导,比如丫啶橙(AO)测定精子DNA、精子与透明带结合和穿透、顶体诱发精子顶体反应和精子与透明质酸结合试验。精子形态测定是常规精液分析中最重要的临床指标之一。但精子形态又是最难测定准确和稳定。IVF/ICSI受精失败的人卵可以用来测定精子功能。人卵透明带选择性地与正常形态和顶体完整的精子结合,透明带诱发的顶体反应与精子穿透明带的能力有很强的相关性。在不明原因的男性不育患者中,由于透明带诱发顶体反应障碍所导致的不育症占25%左右。少精子症(精子计数<2×106/ml)和严重精子形态畸形症(严格正常形态<5%)的男性不育患者,精子-透明带结合反应缺陷的发生率很高(>70%)。这类患者用IVF治疗受精率会很低,因此只能用ICSI治疗。精子与透明质酸结合试验与精子活力和形态有很强的相关性,但它不是很有用的精子功能试验。AO测定精子DNA对预测ART的受精和妊娠率的临床意义目前还没有肯定的结论,需要进一步研究。总之,在常规精液分析时,增加一些新的精子功能试验,在临床ART中对男性不育患者的诊治会有很大的帮助。     

Correlation between sperm morphology, acrosin, and fertilization in an IVF program

Acrosin, a neutral proteinase, is located within the acrosome. The aim of this study was to evaluate acrosin concentrations in patients with severe damage of the sperm head and to determine whether acrosin concentration could predict the chances of fertilization in an IVF program. Sixty patients were accepted into this study, prospectively. The patients were divided into two groups, those with a normal morphology of less than 14% (group I, n = 33) and those with normal morphology less than 14% (group II, n = 27). All patients had a sperm concentration of less than 20 million sperm/ml and less than 30% progressively motile sperm. The acrosin assays were performed on the semen sample obtained on the day of IVF. Routine IVF insemination procedures were used, and only mature oocytes were considered. The only factor that showed a significant correlation of fertilization was normal morphology (p less that 0.01). The mean acrosin level was 73.4 /+- 38.6 mED/10 million sperm in group I and 70.9 /+- 42.7 mIU/10 million sperm in group II (no significant difference). The fertilization rate in group I was 45.4% and in group II, 77.7% p less than 0.002). Acrosin levels were not significantly different in patients with and without fertilization (72.0 /+- 42.1 and 73.6 /+- mIU/10 million sperm, respectively).     

Computer-assisted assessment of sperm morphology: comparison with conventional techniques

The aim of the present study was to compare conventional and computer-assisted morphology assessment of spermatozoa. Sixty-two semen samples from patients undergoing in vitro fertilization (IVF) and 40 samples from patients undergoing an intracytoplasmic sperm injection (ICSI) were studied using both techniques. The percentage of normal spermatozoa found was closely correlated between the techniques (r=0.788, p < 0.0001). The intra-operator variation was low for both techniques but the inter-operator variation was much higher with the conventional than with the computer-assisted method (coefficient of variation = 0.43 vs. 0.08, respectively, for conventional and computer-assisted assessments). The percentage of spermatozoa with normal morphology, as well as sperm motility, was significantly enhanced after PureSperm preparation, whatever the method used for assessment. In the IVF study, fertilization rate was poorly correlated with sperm morphology using both methods. However, combined with motility, morphology assessed with the computer allowed discrimination of two groups of patients with significantly different fertilization rates (30.5 +/- 5.4% vs. 63.1 +/- 5.4%, p < 0.0001). In contrast, the fertilization rate in ICSI was influenced neither by sperm morphology nor by motility. In conclusion, computer-assisted assessment of sperm morphology has a slightly better predictive value for ART than conventional assessment, but above all is much more reproducible, allowing standardization.     

异常形态精子对植入前胚胎发育和妊娠结局的影响

目的探讨异常形态精子(畸形率≥98%)对植入前胚胎发育及妊娠结局的影响。方法采用回顾性队列研究,分析2017年1~12月在唐都医院妇产科生殖医学中心行ART助孕的2419例患者临床资料,根据异常形态精子分为3组,即IVF对照组(畸形率≤96%,n=2129)、IVF实验组(畸形率≥98%,n=90)和ICSI实验组(畸形率≥98%,n=200)。比较3组间植入前受精失败率(受精率<30%)、正常受精率、可用胚胎率等胚胎发育参数和着床率、临床妊娠率、流产率及活产率等妊娠结局的差异。结果(1)胚胎发育结果:组间比较,IVF实验组受精失败率显著高于IVF对照组(P<0.05),ICSI实验组的受精失败率为0;ICSI实验组正常受精率显著高于IVF对照组和IVF实验组(P<0.05);IVF实验组可用胚胎率显著低于IVF对照组和ICSI实验组(P<0.05)。(2)妊娠结局:单因素分析结果显示,与IVF对照组、ICSI实验组相比,IVF实验组的着床率、临床妊娠率、流产发生率和活产率差异均有统计学意义(P<0.05);IVF对照组和ICSI实验组组间妊娠结局指标比较均无显著性差异(P>0.05)。(3)Logistic多因素分析显示:IVF实验组的受精失败风险显著高于IVF对照组(P=0.002),可用胚胎率、活产率显著低于IVF对照组(P=0.002);ICSI实验组的正常受精率显著高于IVF对照组(P=0.05)。结论对于活力正常、但异常形态精子率≥98%的患者,采用ICSI授精方式,能降低受精失败风险,提高正常受精率和可用胚胎率,同时提高妊娠率和活产率并降低流产发生率。     

The human sperm head: a key for successful fertilization

In order to examine the predictive value of determining the sperm head shape, the acrosomal size, the presence of acrosomal vacuoles, and the challenged acrosome reaction (AR) on the outcome of a standard in vitro fertilization (IVF) program, a prospective study was conducted that included 75 couples undergoing IVF treatment. An assessment of sperm morphology was performed using the Hobson Sperm Tracker (Hobson Tracker Limited, Sheffield, United Kingdom). The assessment of the AR was performed before and after adding pooled undiluted human follicular fluid (FF). The outcome measure was an IVF rate of inseminated oocytes. A positive correlation was found between the fertilization rate (FR%) and the proportion of the sperm with a normal (oval) head shape (P <.001), the sperm exhibiting acrosomal vacuoles (P <.003), the sperm with a normal acrosomal size (40%-70% of total head area, P <.025), and the sperm undergoing AR after adding FF (P <.001). Multiple logistic regression analysis revealed that by incorporating the above 4 parameters, the sensitivity of prediction of IVF FR% values was 79%, and the specificity was 93%, with a positive predictive value of 96%. This study shows that the multiparametric assessment of the sperm head is useful in predicting the FR% values of a standard IVF treatment. The automated analysis used in this study is shown to maintain a level of precision and accuracy acceptable for application in a routine semen analysis situation.     

Predictive value of selected sperm parameters for classical in vitro fertilization procedure of oocyte fertilization

A proportion of fertilized oocytes during classical in vitro fertilization (IVF) procedure was analysed depending on the following factors: number of mature oocytes, seminological criteria such as sperm morphology in raw semen and after its selection in a density gradient (six structural defects of a male gamete were taken into consideration), sperm concentration, motility parameters according to World Health Organization criteria and the functional tests: hypo-osmotic swelling assay and acrosomal reaction induced by calcium ionophore. Evaluation of DNA content in sperm by image cytometry and determination of malonyldialdehydes in seminal plasma were also performed. Seventy-nine semen samples from patients undergoing IVF were assessed. Apart from significant correlations obtained for selected semen parameters and proportion of fertilized eggs, logistic regression analysis showed that the best predictive factors for oocyte fertilization were normal morphology of sperm before and after gradient selection, grade B and C of sperm movement in raw semen, and DNA content after density gradient centrifugation, which all accounted for 76.7% of fertilization predictive value.     

Efficacy of zona-free hamster egg sperm penetration assay as a predictor of in vitro fertilization

The efficacy of the zona-free hamster egg sperm penetration assay (SPA) as a predictor of in vitro fertilization (IVF) is studied. Indications for IVF were tubal factors in 35 couples and male factors in 24 couples. The diagnostic characteristics of SPA in reference to IVF for the whole group (n = 59) were reasonably reliable. Sensitivity was 74%, specificity was 84%, and diagnostic accuracy was 81%. However in patients with male factors, SPA was less reliable in terms of sensitivity (70%), specificity (57%), and diagnostic accuracy (63%), than in patients with tubal factors where the indicators were 80%, 97%, and 94%, respectively. Semen from patients with male infertility shared notable variations in terms of sperm density and motility which may account for the low SPA predictivity. SPA seems to be a useful screening test for prediction of IVF outcome. However other semen variables should be considered before interpretation, especially in male infertility where the diagnostic accuracy is low.     

A retrospective comparison of pregnancy outcome following conventional oocyte insemination vs intracytoplasmic sperm injection for isolated abnormalities in sperm morphology using strict criteria

Initial in vitro fertilization (IVF)-embryo transfer studies found poor fertilization and pregnancy rates following conventional fertilization of oocytes when using sperm with <4% normal morphology using strict criteria. Some consider today that sperm with only < or =5% normal morphology using strict criteria are associated with infertility. However, other studies have disputed the diagnostic potential of low strict morphology in identifying subnormal male fertility. Based on the original studies most IVF centers perform intracytoplasmic sperm injection (ICSI) when the sperm shows low morphology using strict criteria to allow selection of normal sperm. However, ICSI adds extra time for the embryologist and extra expense for the infertile couple. The present study retrospectively compared fertilization, pregnancy, and implantation rates according to the 2 methods of oocyte fertilization with sperm having normal morphology using strict criteria of < or =5% in women < or =39 years. All fresh embryo transfers were performed on day 3. There was a significantly higher fertilization rate with ICSI. However, there were significantly higher clinical and delivered pregnancy and implantation rates following conventional insemination. The rate of canceled transfers due to no available embryo was 1.9% with conventional insemination vs 1.5% for ICSI in women with adequate egg reserve. Hopefully, this retrospective study will generate interest in a prospective study.     

Seminal elastase-inhibitor complex, a marker of genital tract inflammation, and negative IVF outcome measures: role for a silent inflammation?

There is no consensus on whether and how male genital tract inflammation affects sperm fertilizing potential. The aims of this prospective study were to evaluate the elastase-inhibitor complex in seminal plasma (s-EI) level, a marker of male genital tract inflammation, in men undergoing in vitro fertilization (IVF) having no clinical signs of inflammation, and its association with semen characteristics, and the predictive role of s-EI for the outcome of IVF in terms of fertilization, embryo development to the blastocyst stage and pregnancy. The study involved 104 male partners of infertile couples with normal spermiogram undergoing IVF. On the day of oocyte retrieval, spermiogram and s-EI assessment using homogeneous immunoassay were performed. The outcome of IVF according to the s-EI level was assessed in 85 cycles with two or more oocytes. In 67 cycles embryos were cultured to the blastocyst stage. Spearman's and Pearson's correlation tests, chi-square test, and multiple linear and logistic regression analyses were used for statistical evaluation. Increased s-EI level (> or =250 microg/L) was detected in semen of 32% of men, and in 24% of men without leucocytospermia. We found an association between the s-EI level and semen leucocytes (r = 0.49, p = 0.004) but not with classical sperm characteristics. No correlation between the s-EI level and fertilization was observed. Increased s-EI levels were associated with a poorer blastocyst development rate (p = 0.03) and a higher number of arrested embryos (p = 0.04). Extended embryo culture to the blastocyst stage shows a negative effect of clinically silent male genital tract inflammation on embryo developmental potential.     

The relationship between critical evaluation of sperm morphology and the TYB-optimized zona free hamster oocyte sperm penetration assay

The objective of this study was to analyse the relationship between the percentage of spermatozoa in semen with normal morphology, assessed using the Tygerberg criteria, and sperm fertilizing ability assessed using the TYB-optimized zona free hamster oocyte sperm penetration assay (TYB-optimized SPA), to evaluate the predictive value of strict morphology on outcome of the SPA. In a retrospective study, 56 samples were analysed. In addition to routine semen parameters, the percentage of spermatozoa with normal morphology (A forms) and the average number of penetrations per oocyte (Sperm Capacitation Index) was evaluated in all cases. Using a multiple linear regression analysis with all semen parameters, sperm morphology was the best predictor (p = 0.001) of the SPA score. The agreement between the percentage of A forms and the Sperm Capacitation Index beyond chance (kappa coefficient) was 0.5842. Twenty-two specimens had abnormal SPA scores, with 21 exhibiting abnormal sperm morphology (Sensitivity = 96%). The remaining 34 samples had normal Sperm Capacitation Index values; of these, 23 had normal sperm morphology in semen (Specificity = 68%). The positive predictive value was 96%, and the negative predictive value was 66%. All semen samples from control donors had normal semen parameters and Sperm Capacitation Index values. In conclusion, the percentage of spermatozoa with normal morphology assessed using Tygerberg criteria (> 14% A forms) are predictive of the results in the TYB-optimized SPA. However, sperm morphology appears to be a better predictor when it is normal than when it is abnormal.     

精子CMA3阳性率与IVF受精率的相关性研究

目的探讨精子色素酶A3(CMA3)阳性率与IVF受精率之间的相关性。方法收集2015年4月至2016年7月因单纯输卵管性不孕在我院生殖医学科行常规IVF助孕的156个周期,以受精率<25%为低受精,根据受精率不同分为正常受精组(134个周期)和低受精组(22个周期)。取卵日,将授精后剩余的洗涤精液行精子浓度和活动率分析,并将精子进行CMA3染色。比较两组优选后的精子参数,分析IVF受精率与精子参数及CMA3阳性率的关系。结果与正常受精组比较,低受精组精子CMA3阳性率显著升高[(20.0±4.2)%vs.(30.7±2.3)%],优选后前向运动精子的百分率显著降低[(90.4±4.8)%vs.(74.3±3.4)%](P<0.05);两组精子浓度比较无显著性差异(P>0.05)。IVF受精率与优选后的前向运动精子百分率呈正相关(r=0.76,P<0.01)。精子CMA3阳性率与优选后前向运动精子百分率(r=-0.82,P<0.01)及IVF受精率(r=-0.83,P<0.01)呈显著负相关,与精子浓度则无显著相关性(P>0.05)。结论精子CMA3阳性率与IVF受精率负相关,但其具体机制尚需进一步研究探讨。     

Prediction of unexpectedly poor fertilization and pregnancy outcome using the strict criteria for sperm morphology before and after sperm separation in IVF-ET

This study was performed to investigate if unexpectedly poor fertilization and in-vitro fertilization (IVF) outcome could be predicted using sperm morphology as diagnosed by the strict criteria. Sperm morphology was assessed in 137 IVF-ET cycles with at least three oocytes collected. The lowest amount of normal forms was 5% in 137 samples, indicating there were no patients belonging to 'poor prognosis' (<5% normal forms). Treatment using intracytoplasmic sperm injection (ICSI) was also excluded. Before sperm separation by the swim-up method, sperm morphology demonstrated a significant correlation with the fertilization rate (p < 0.0001). The fertilization rate (80.5%) in 110 'normal' samples (>14% normal forms) was significantly higher (p < 0.01) than that (55.4%) in 27 samples with 'good prognosis' (those with 5--14% normal forms). No embryo was available for transfer (ET) in 4 (3.6%) of 110 'normal' cycles and in 3 (11.1%) of 27 'good prognosis' cycles (not significant). Fresh ET was intentionally cancelled to avoid severe ovarian hyperstimulation syndrome (OHSS) in six of 110 'normal' cycles as well as in one of 27 'good prognosis' cycles. The pregnancy rate per ET was 31.0% (31/100) in the former group, while it was 26.1% (6/23) in the latter group. There was no difference between the two groups. In the post swim-up evaluation of sperm characteristics, morphology was significantly correlated with the fertilization rate in IVF-ET (p < 0.05) while other sperm parameters were not. When the cut off level for the post swim-up sperm morphology was set at 25%, there was a significant difference in the fertilization rates between patients (78.6%) with post-swim-up >25% and those (55.0%) with post-swim-up < or =25% (p < 0.01). Taken together, a relative indication for ICSI using sperm morphology before and after swim-up was established. Category A includes < or =14% normal forms in the ejaculate and post-swim-up < or =25%, while Category B includes < or =14% in the ejaculate and post-swim-up >25%. There was a significant difference in the fertilization rates between patients (47.2%) in Category A and those (60.2%) in Category B (p < 0.05). The clinical pregnancy rate was 11.1% for patients in Category A compared with 35.7% for patients in Category B. However, there was no significant difference between the two categories. These results indicate that the strict criteria provide a reliable estimation of the fertilizing ability of human spermatozoa. ICSI might be considered in Category A patients to avoid poor fertilization and pregnancy outcome.     

Teratozoospermia and its effect on male fertility potential

Teratozoospermia and its significance for male fertility problems is discussed. Different points of view and available information concerning the phenomenon of teratozoospermia have been presented. Ongoing debate about the influence of sperm morphology on male infertility and IVF results emphasizes the fact that when sperm morphology is evaluated using strict criteria, this parameter is thought to have an excellent predictive value and shows a significant positive correlation with successful fertilization. Selective abilities of zona pellucida to differentiate between morphologically normal and abnormal spermatozoa, the superior role of acrosomal morphology assessment in the prediction of IVF outcome, and the involvement of cell surface molecules in the adhesion of spermatozoa to oocytes are described. The usefulness of the hamster oocyte penetration assay (HOPA), which is important not only because of its predictive value of sperm function, but also because of its role as a tool for visualizing sperm chromosomes, was found to be questionable in cases of teratozoospermia. Cytogenetic findings related to teratozoospermia are controversial as classical methodology of visualizing sperm chromosomes (through HOPA) may cause selection of sperm metaphases which can be obtained only from good-penetrating spermatozoa. There are few reports presenting chromosome complements of abnormal sperm visualized with the help of micromanipulation. There is clear evidence that a variety of genetic defects can affect spermatogenesis. The possible genetic background of teratozoospermia is discussed.     

Does computerized image analysis of sperm movement enhance the predictive value of semen analysis for in-vitro fertilization results?

The influence of semen quality on fertilization rates in an in-vitro fertilization (IVF) programme was studied by analysing both conventional semen parameters and computerized movement characteristics. The study was based on 407 inseminated oocytes which were obtained from 50 patients in 113 laparoscopies. Sperm concentration did not correlate strongly with the fertilization rate. Sperm motility and morphology were the most meaningful parameters in predicting fertilization success. A drop in fertilization rate was found when sperm motility or normal morphology were below 40%. Sperm velocity measured in semen was the only sperm movement parameter which correlated with the fertilization rate, albeit weakly. The latter was reduced when average sperm velocity in semen was less than 50 microns/sec. Conventional semen parameters seem to be more predictive of the fertilizing potential of an ejaculate than movement characteristics obtained by computerized image analysis.     

Comparison of sibling oocyte outcomes after intracytoplasmic sperm injection and in vitro fertilization in severe teratozoospermic patients in the first cycle

To follow up the outcome of sibling oocytes subjected to both conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in the first cycles of severe teratozoospermic patients with normal sperm morphology (NSM)or=6 cell embryos on day 3 and blastocyst formation on days 5 and 6, did not differ significantly between the two groups. There was a trend towards a high pregnancy rate cycle in mixed ICSI/IVF embryo transfer (ET) (49.1%). In conclusion, this study showed that in couples with only severe teratozoospermia, there was a benefit in subjecting sibling oocytes to both IVF and ICSI in the first cycle because 24 (28.2%) cycles of total fertilization failure were avoided. Furthermore, despite initially significant higher fertilization rates in ICSI than IVF oocytes, subsequent rates of development from >or=6 cells up to blastocyst stage were the same suggesting that ICSI should be used with caution, as after day 3, ICSI-derived embryo development was compromised compared with IVF.