Live birth and miscarriage rate following intracytoplasmic morphologically selected sperm injection vs intracytoplasmic sperm injection: An updated systematic review and meta-analysis.

INTRODUCTION: Intracytoplasmic morphologically selected sperm injection (IMSI) is one of the sperm selection techniques used for assisted reproduction which has been applied for a variety of indications including previously failed fertilization with intracytoplasmic sperm injection (ICSI). A Cochrane review1 found no difference in outcomes between either modality of sperm selection. Since the Cochrane review was published there have been a further two randomized controlled trials comparing IMSI and ICSI. This systematic review and meta-analysis aims to compare IMSI with ICSI as insemination methods regarding live birth rate and miscarriage rate. MATERIAL AND METHODS: Systematic review of randomized controlled trials, observational studies and similar reviews in electronic databases published before January 2018. RESULTS: We found nine randomized controlled trials, evaluating 1610 cycles of in vitro fertilization and 15 observational studies evaluating 1243 cycles of in vitro fertilization. Meta-analysis of the included randomized controlled trials showed no difference in the live birth rate or miscarriage rate between the ICSI and IMSI groups. Meta-analysis of five observational studies showed a significantly higher number of live births in the IMSI group than ICSI group (live birth rate odds ratio 1.47, 95% confidence interval 1.16-4.07), with a moderate degree of heterogeneity (I2  = 41%). Additionally, from six observational studies, a significantly lower miscarriage rate was observed in the IMSI group than in the ICSI group (odds ratio 0.51, 95% confidence interval 0.37-0.70, I2  = 0%). CONCLUSIONS: Meta-analysis of randomized studies comparing IMSI to ICSI has not shown any difference in live birth rate and miscarriage rate. Meta-analysis of observational studies, which must be interpreted with caution, revealed an increased live birth rate and decreased miscarriage rate with IMSI vs ICSI.

Impact of high magnification sperm selection on neonatal outcomes: a retrospective study.

PURPOSE: The aim of this study was to compare the effect of the deselection of spermatozoa presenting vacuole-like structures using IMSI (intracytoplasmic morphologically selected sperm injection) with ICSI (intracytoplasmic sperm injection) by means of neonatal outcomes. METHODS: In a retrospective two-center analysis, a total of 848 successful IMSI or ICSI cycles ending with a live birth, induced abortion, or intrauterine fetal death (IUFD) were included. RESULTS: The IMSI and ICSI groups included 332 and 655 babies or fetuses, respectively. The parents were older in the IMSI group than in the ICSI group (mothers were 35.1 vs 32.9 years, and fathers were 39.1 vs 36.2 years). The multiple pregnancy rate was higher in the IMSI group. The mean pregnancy duration and mean birth weight were almost identical in both groups. There was no significant difference in major congenital malformations between the two groups. However, this rate was decreased in the IMSI group compared to that in the ICSI group (1.8 vs 3.2%), the difference being mainly found in singletons (1.4 vs 3.3%). Boys were more often affected than girls in both groups. The percentages of chromosomal abnormalities did not differ between the IMSI and ICSI groups (0.6 and 0.8%). The reported congenital malformations mainly affected the heart, urogenital, and musculoskeletal systems. CONCLUSIONS: In the present study, the malformation rates observed in the IMSI and ICSI groups were not significantly different, even if slightly lower after IMSI. However, the observed difference followed the same trends observed in previous reports, indicating the possible impact of IMSI on decreasing congenital malformation occurrences. This highlights the necessity to prospectively evaluate the impact of IMSI on neonatal outcome after IVF treatment.

[IMSI versus ICSI for male factor infertility: A meta-analysis].

OBJECTIVE: To evaluate the efficacy and safety of intracytoplasmic morphologically selected sperm injection (IMSI) versus intracytoplasmic sperm injection (ICSI) in in vitro fertilization (IVF) for couples with male factor infertility. METHODS: Using the Cochrane system evaluation method, we searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and SinoMed and manually searched the reference lists of the included studies and relevant reviews for randomized controlled trials (RCT) comparing ICSI and IMSI published from 1992 to July 2017. We performed a meta-analysis on the included literature with the RevMan 5.3 software and subgroup analyses due to the prominent clinical heterogeneity of the patients. RESULTS: Of the 280 articles retrieved, 8 RCTs were included, involving 1 741 IVF cycles (842 cycles of IMSI versus 899 cycles of ICSI). There was no evidence for any significant difference between IMSI and ICSI in the live birth rate in the subgroup of infertility induced by pure male factors (RR = 1.31, 95% CI: 0.68－2.51; very low quality evidence from 1 RCT with 77 cycles) but an association of IMSI with an increased clinical pregnancy rate (RR = 1.46, 95% CI: 1.02－2.07; low quality evidence from 4 RCTs with 813 cycles), nor was there any evidence for that in the live birth rate (RR = 0.88, 95% CI: 0.60－1.31; low quality evidence from 1 RCT with 255 cycles) or clinical pregnancy rate (RR = 1.03, 95% CI: 0.86－1.23; moderate quality evidence from 3 RCTs with 851 cycles) in the subgroup of infertility caused by accompanying male factors. CONCLUSIONS: The evidence is of low quality for the association of IMSI with an increased rate of clinical pregnancy and is not sufficient to support the routine use of IMSI in IVF for male factor infertility.

Laser-Guided Sperm Selection: Optimizing the Reproductive Success Rate in Assisted Reproductive Technology.

Assisted reproductive technologies (ART) enable these patient's spermatozoa to fertilize the oocyte and create viable and healthy offspring, but the effectiveness of the various procedures still has room to increase. In the field of assisted reproductive technology, the need to improve fertility results has led to the development of novel sperm selection strategies. Laser-assisted selection of immotile sperm (LAISS) appears to be a promising strategy, harnessing the power of modern optical instruments to better the selection process and, ultimately, maximize the probability of successful fertilization. This technology takes advantage of sperm cells' distinctive features, such as shape, form, and motility patterns, that can be sensitively changed by laser forces. Using precision laser manipulation, spermatozoa with desirable features can be precisely targeted, improving the overall quality and viability of the sperm population. The existence of an elevated percentage of DNA-damaged sperm in a patient's ejaculation may be one of the key factors decreasing ART outcomes. As a result, one of the most difficult tasks in reproductive medicine is ensuring the best quality of spermatozoa utilized in ART, particularly with regard to genetic integrity. The most recent approaches for preparing and selecting human spermatozoa by LAISS techniques are covered here, with an emphasis on those that have been shown to improve.

IMSI-Guidelines for Sperm Quality Assessment.

Intracytoplasmic sperm injection (ICSI) is a widely used and accepted treatment of choice for oocyte fertilization. However, the quality of sperm selection depends on the accurate visualization of the morphology, which can be achieved with a high image resolution. We aim to correct the conviction, shown in a myriad of publications, that an ultra-high magnification in the range of 6000×-10,000× can be achieved with an optical microscope. The goal of observing sperm under the microscope is not to simply get a larger image, but rather to obtain more detail-therefore, we indicate that the optical system's resolution is what should be primarily considered. We provide specific microscope system setup recommendations sufficient for most clinical cases that are based on our experience showing that the optical resolution of 0.5 µm allows appropriate visualization of sperm defects. Last but not least, we suggest that mixed research results regarding the clinical value of IMSI, comparing to ICSI, can stem from a lack of standardization of microscopy techniques used for both ICSI and IMSI.

Impact of Intracytoplasmic Morphologically Selected Sperm Injection (IMSI) on Birth Defects: A Systematic Review and Meta-Analysis.

OBJECTIVE: It is generally accepted that the incidence of birth defects in spontaneously conceived children ranges between 2.0-4.0%. However, several studies have shown that babies born after assisted reproductive technology (ART) procedures tend to present more congenital malformations than naturally conceived children, with 6.5% of the children born after intracytoplasmic sperm injection (ICSI) presenting birth defects. The use of high magnification sperm selection before ICSI was introduced in the early 2000s to allow the identification of spermatozoa with low risk of sperm DNA damage. Intracytoplasmic morphologically selected sperm injection (IMSI) is expected to change the incidence of congenital malformations, although data on the incidence of birth defects in children conceived after IMSI are still scarce. METHODS: A systematic review based on searches performed in electronic databases (PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane Central Register of Controlled Trials) including articles published by February 2021 was conducted to identify trials comparing the neonatal outcomes of ICSI and IMSI. The outcome measured was the rate of birth defects in children born after ICSI or IMSI. Three trials were included as targets for data extraction and meta-analysis. RESULTS: Our meta-analysis included 3907 children conceived after IMSI (1280) or ICSI (2627). The incidence of birth defects was statistically different, with 2.5% (32/1280) in IMSI and 4.5% (119/2627) in ICSI (RR=0.59; 95% CI=0.40-0.87; p=0.007). The results demonstrated that IMSI decreased the incidence of structural defects compared to ICSI - 2.2% (18/830) vs. 3.8% (78/2049) - in a statistically significant manner (RR=0.58; 95%CI=0.35-0.96; p=0.04). No significant difference was observed in chromosomal abnormalities (Trisomy 13; 18; 21 and Triple X) between children conceived after IMSI (8/830) or ICSI (19/2049) (RR=1.07; 95%CI=0.47-2.43; p=0.87). CONCLUSIONS: IMSI seems to be an effective tool at reducing the incidence of structural defects compared to ICSI. However, IMSI does not change the incidence of chromosomal abnormalities.

Which semen analysis correlates with favorable Intracytoplasmic morphologically selected sperm injection (IMSI) outcomes?

OBJECTIVE: To assess whether a correlation exists between different sperm pathologies and Intracytoplasmic morphologically selected sperm injection (IMSI) outcomes. STUDY DESIGN: A retrospective cohort study which included couples with recurrent implantation failures (2 or more unsuccessful IVF-ICSI cycles) undergoing their first IVF-IMSI cycle in Hebrew-University Hadassah Medical Center between January 2008 and May 2017. RESULTS: A total of 170 couples with at least two IVF failures attempting their first IVF-IMSI cycle were included, of them 56 (32.9%) achieved a clinical pregnancy. No correlation was found between clinical pregnancy and a specific abnormal semen parameter. However, a positive correlation with clinical pregnancy was demonstrated when all three semen parameters were abnormal (OR-3.33, p = 0.015). CONCLUSIONS: Our findings suggest that IMSI procedure may be more efficient in severe compound sperm pathologies than in patients with one abnormal sperm parameter. Future prospective trials are required to reinforce these findings and allow formation of clear indications for IMSI.

Can intracytoplasmic Morphologically Selected Spermatozoa Injection be Used as First Choice of Treatment for Severe Male Factor Infertility Patients?

AIM: This study was carried out to assess the outcome of the intracytoplasmic morphologically selected sperm injection (IMSI) technique compared with the previous failed intracytoplasmic sperm injection (ICSI) attempts in oligoasthenoteratozoospermia (OAT)/severe OAT (SOAT)/teratozoospermia patients. SETTING: Institution-based, in vitro fertilization center. STUDY DESIGN: It was a nonrandomized prospective study including 57 couples who had previous one or two ICSI failures (failure due to no implantation as embryos were transferred in these cycles and had no pregnancy) due to male factor. There was no case of total fertilization failure. IMSI was carried out in these couples and the results were compared with their previously failed ICSI attempts. MATERIALS AND METHODS: Real-time selection of sperms was done using IMSI as it allows the assessment of fine nuclear morphology and vacuoles in the sperm head at a high magnification (>6000×) with differential interference contrast optics. Therefore, IMSI was applied in couples having OAT, SOAT or teratozoospermia as male factor and the results were compared with their previous failed ICSI attempts. Statistical analysis was carried out using GraphPad Prism. RESULTS AND CONCLUSION: Data analysis demonstrated significant difference in the fertilization rate between IMSI and previous ICSI attempts of these patients (30.0% vs. 52.0%; P < 0.05). The embryo quality, implantation and pregnancy rates with IMSI were also significantly higher than those of their previous ICSI cycles (32% vs. 56.4%; 30.2% vs. 68.5%; 0.0% vs. 62.4%; P < 0.05). Our conclusion is that the IMSI procedure improved embryo development and the clinical outcomes in the same infertile couples with male infertility and poor embryo development over their previous ICSI attempts and can be taken up as the treatment of choice in cases of severe male factor infertility.

Role of sperm DNA fragmentation in male factor infertility: A systematic review.

OBJECTIVE: To summarise the latest evidence on the role of sperm DNA fragmentation (SDF) in male factor infertility, as SDF has been emerging as a valuable tool for male infertility evaluation. METHODS: A search of PubMed was conducted using the keywords 'sperm DNA fragmentation' and 'male infertility'. Studies in languages other than English were excluded. All identified studies were screened and clinical studies in humans were included. RESULTS: In all, 150 articles were included for analysis. Current evidence supports the association between high SDF and poor reproductive outcomes for natural conception and intrauterine insemination. Although the relationship between high SDF and in vitro fertilisation and intracytoplasmic sperm injection is less clear, the negative implication of high SDF on pregnancy loss is evident. Various treatment strategies have been attempted with varying success. The predictive value of SDF testing on outcomes of natural pregnancy and assisted reproduction illustrates its value in clinical practice. CONCLUSION: The significant role of SDF in male factor infertility is supported by current evidence. The beneficial role of SDF testing in selection of varicocelectomy candidates, evaluation of patients with unexplained infertility and recurrent pregnancy loss, selection of the most appropriate assisted reproductive technique with highest success rate for infertile couples, and assessment of infertile men with modifiable lifestyle factors or gonadotoxin exposure has been recently proposed.

An effective method for improving outcomes in patients with a fertilization defect.

The effect of artificial oocyte activation (AOA) with a calcium ionophore on intracytoplasmic morphologically selected sperm injection (IMSI) was examined in patients with histories of repeated failed implantation attempts. Four singleton pregnancies and one twin pregnancy were obtained after embryos transfer (5/14, 35.7%). Therefore, AOA combined with IMSI can be considered an option for cycles with a fertilization defect and recurrent implantation failures.

Comparison between intracytoplasmic sperm injection and intracytoplasmic morphologically selected sperm injection in oligo-astheno-teratozoospermia patients.

OBJECTIVE: The aim of this study was to evaluate the efficiency of the intracytoplasmic morphologically selected sperm injection (IMSI) technique compared with conventional ICSI and previous ICSI attempts in oligo-astheno-teratozoospermia (OAT) patients. METHODS: The sperms were selected under high magnification (6,600×) and used to induce fertilization in previous ICSI patients by IMSI. These results were compared with previous conventional ICSI cycles in patients with OAT infertility. RESULTS: These results demonstrated no significant difference in the fertilization rate between IMSI and previous ICSI cycles (67.7% vs. 65.0%). However, the pregnancy and implantation rates with IMSI were significantly higher than those of the ICSI cycles (33.3% vs. 12.5% and 14.6% vs. 5.4%, respectively; p<0.05). The miscarriage rate among pregnant patients (18.2% vs. 37.5%) showed no statistically significant difference between groups. CONCLUSION: Compared to conventional ICSI, this study found that IMSI increased the IVF-ET success rates in patients with OAT.

Epigenetic heterogeneity of developmentally important genes in human sperm: implications for assisted reproduction outcome.

The molecular basis of male infertility is poorly understood, the majority of cases remaining unsolved. The association of aberrant sperm DNA methylation patterns and compromised semen parameters suggests that disturbances in male germline epigenetic reprogramming contribute to this problem. So far there are only few data on the epigenetic heterogeneity of sperm within a given sample and how to select the best sperm for successful infertility treatment. Limiting dilution bisulfite sequencing of small pools of sperm from fertile donors did not reveal significant differences in the occurrence of abnormal methylation imprints between sperm with and without morphological abnormalities. Intracytoplasmic morphologically selected sperm injection was not associated with an improved epigenetic quality, compared to standard intracytoplasmatic sperm injection. Deep bisulfite sequencing (DBS) of 2 imprinted and 2 pluripotency genes in sperm from men attending a fertility center showed that in both samples with normozoospermia and oligoasthenoteratozoospermia (OAT) the vast majority of sperm alleles was normally (de)methylated and the percentage of epimutations (allele methylation errors) was generally low (<1%). However, DBS allowed one to identify and quantify these rare epimutations with high accuracy. Sperm samples not leading to a pregnancy, in particular in the OAT group, had significantly more epimutations in the paternally methylated GTL2 gene than samples leading to a live birth. All 13 normozoospermic and 13 OAT samples leading to a child had <1% GTL2 epimutations, whereas one (7%) of 14 normozoospermic and 7 (50%) of 14 OAT samples without pregnancy displayed 1-14% GTL2 epimutations.

Is intracytoplasmic morphologically selected sperm injection (IMSI) beneficial in the first ART cycle? a multicentric randomized controlled trial.

Intracytoplasmic morphologically selected sperm injection (IMSI), by selecting spermatozoa at high magnification improves the outcome of intracytoplasmic sperm injection (ICSI) mainly after several failures. However, only few monocentric randomized studies are available and they do not analyse results as a function of sperm characteristics. In 255 couples attempting their first assisted reproductive technology (ART) attempt for male infertility (motile sperm count <1×106 after sperm selection, but at least 3×106 spermatozoa per ejaculate to allow a detailed analysis of sperm characteristics), a prospective randomized trial was performed to compare the clinical outcomes of IMSI and ICSI and to evaluate the influence of sperm characteristics on these outcomes. IMSI did not provide any significant improvement in the clinical outcomes compared with ICSI neither for implantation (24% vs. 23%), nor clinical pregnancy (31% vs. 33%) nor live birth rates (27% vs. 30%). Moreover, the results of IMSI were similar to the ICSI ones whatever the degree of sperm DNA fragmentation, nuclear immaturity and sperm morphology. These results show that IMSI instead of ICSI has no advantage in the first ART attempts. However, this does not rule out IMSI completely and more randomized trials must be performed especially regarding patients carrying severe teratozoospermia, or high sperm DNA fragmentation levels or having previous ICSI failures.