Morphokinetics of embryos after IMSI versus ICSI in couples with sub-optimal sperm quality: A time-lapse study
A retrospective cohort study was conducted to investigate the influence of IMSI (intra-cytoplasmic morphologically selected sperm injection) and ICSI (intra-cytoplasmic sperm injection) techniques on the yield of euploid embryos and morphokinetics.
Unlike conventional ICSI using 200x magnification, IMSI enables detailed morphological observation of individual sperm by increasing the optical resolution to 6000x magnification, however the potential benefits of IMSI remain inconclusive.
A total of 84 couples, who attended the Morula IVF clinic (Indonesia) for treatment participated in this study. Included males had sub-optimal sperm profiles (teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia, severe oligoasthenoteratozoospermia) while males with cryptozoospermia, testicular sperm extraction (TESE) or percutaneous sperm aspiration (PESA) were excluded. Similarly female partners older than 43 or diagnosed with severe endometriosis were also excluded to minimise confounding factors.
Controlled ovarian stimulation commenced on day 2 or 3 utilising the gonadotropin-releasing hormone antagonist protocol. Once 3 or more follicles reached 18µm in size, a hCG trigger was administered and oocytes collected the following day.
Semen samples were prepared using either density gradient, if sperm count was 5 to 15 million/ml and motility ≤20%, or the swim-up method, when sperm count was >15 million/ml or in cases of teratozoospermia. The best looking sperm was then selected as per each methods (ICSI / IMSI) magnification technique. Where the number of normal spermatozoa was insufficient, the second best quality spermatozoa was selected using the Cassuto and Barack criteria.
Following insemination embryos were cultured in a MIRI® Time Lapse incubator to record embryo morphokinetics and dynamic development data. Top-quality blastocysts was defined as grade 3–5 with a combined score of both ICM and trophoblast cells (AA, AB, BA). On day 5, top-quality blastocysts from both groups underwent pre-implantation genetic testing for aneuploidy (PGT-A), followed up by statistical analysis of all the data.
Of the 84 couples, 33 went through ICSI and 51 IMSI. A total of 628 embryos were retrieved, resulting in 83 top quality blastocysts from the ICSI group and 149 in the IMSI group. Among the 84 males, asthenoteratozoospermia was most prevalent featuring in 66 men (78.6%), with mean age, progressive sperm motility (A+B) count, median semen volume, sperm concentration and normal morphology all comparable. Likewise baseline and clinical characteristics of the female partners was also similar between the two groups.
Initial analysis of the results found that the number of oocytes retrieved, number of injected mature oocytes and number of top-quality blastocysts obtained was not significantly different between the IMSI and ICSI groups. However sperm selection using IMSI did result in a significantly higher median number of fertilised oocytes compared to ICSI (80.37% vs 76.37%).
Morphokinetics analysis of top-quality blastocysts observed that T7, TEB and CC3 parameters among the IMSI embryos was significantly shorter than the ICSI group, while all other morphokinetic variables remained similar. (T7, time of two to seven cells cleavage; TEB, initiation time of expanded blastulation; CC3, duration of third cell cycles).
Further analysis of dynamic developmental parameters found the incidence of multinucleation in top-quality blastocysts was significantly lower in the IMSI group compared to ICSI, with a low (adjusted) relative risk (RR = 0.243). This difference was only found in chromosomally aneuploid embryo population.
Interestingly neither euploid or aneuploid blastocysts from either group showed any differences in the prolonged S2 and CC2 parameters which are commonly used to predict implantation potential in other time-lapse studies.
Overall neither sperm selection method (ICSI or IMSI) had any significant influence on the yield of chromosomally normal euploid embryos (51.3% vs 44.2% respectively) leading to comparable clinical pregnancy rates (p = 0.736).
SUMMARY: IS IMSI BETTER THAN ICSI
In this study, IMSI did not perform better than ICSI in the yield of chromosomally normal euploid embryos (44.2% vs 51.3% respectively), even though the median fertilisation rate was better among the IMSI group (80.37% vs 76.37%), resulting in similar clinical pregnancy rates (p = 0.736).
- Use of different culture media manufacturers
- Inadequate diagnostic precision of trophectoderm biopsy for euploidy
- Embryos can acquire a DNA-breakage repair mechanism from spermatozoa confounding results
Mangoli E, et al. (2020). Association between early embryo morphokinetics plus transcript levels of sperm apoptotic genes and clinical outcomes in IMSI and ICSI cycles of male factor patients. https://doi.org/10.1007/s10815-020-01910-7
Sacha C R, et al. (2020). The impact of male factor infertility on early and late morphokinetic parameters: A retrospective analysis of 4126 time-lapse monitored embryos. https://doi.org/10.1093/humrep/dez251
Mangoli E, et al. (2019). IMSI procedure improves clinical outcomes and embryo morphokinetics in patients with different aetiologies of male infertility. https://doi.org/10.1111/and.13340
Balakier H, et al. (2016). Impact of multinucleated blastomeres on embryo developmental competence, morphokinetics, and aneuploidy. https://doi.org/10.1016/j.fertnstert.2016.04.041
Keskintepe L, et al. (2016). Intracytoplasmic morphologically selected sperm injection (IMSI) does not improve clinical outcomes and embryo ploidy in assisted reproductive cycles. https://doi.org/10.1016/j.fertnstert.2016.07.480
Luna D, et al. (2015). The IMSI procedure improves laboratory and clinical outcomes without compromising the aneuploidy rate when compared to the classical ICSI procedure. https://doi.org/10.4137/cmrh.s33032
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