NEWS: Deselection of Physiologically Abnormal Spermatozoa Before ICSI Reduces Birth Defects and Improves Clinical Results

Sperm morphology plays a vital role in determining fertility and is associated with fertilization and pregnancy rates in spontaneous as well as induced pregnancy. Highlighting the importance of the selection of morphologically normal spermatozoa for ART treatment, a recent prospective population-based study demonstrated that major birth defects were significantly higher in standard ICSI than intracytoplasmic injection of morphologically selected spermatozoa (IMSI). The study findings, published in Reproductive BioMedicine Online, further reiterated the need for long term follow up and research to estimate the prevalence and risk of specific IMSI-based birth defects.

Nino Guy Cassuto, Head of the Drouot Laboratory, Paris, France, and co-workers, studied the major malformations in a cohort of 1028 infants, among whom 578 were born after ICSI and 450 following IMSI. The women above 39 years and who were pregnant were not included in the study. Spermatozoa obtained after selection in a bilayer gradient were assessed for their morphology using high magnification, according to the Cassuto–Barak sperm classification protocol.

The two groups were also matched based on the parents’ age, ovulation induction treatment, number of oocytes retrieved, days of transfer, gestational age, and birth weight. The study revealed that the incidence of major malformations were significantly higher in children born after ICSI (3.80%) than those following IMSI (1.33%) (adjusted odds ratio (OR)=0.35, 95% CI=0.14–0.87, P=0.014).

Although there was no difference with respect to the gender ratio (0.92 versus 0.84) in the ICSI group, the major malformations were found to be more in boys than the girls in both the ICSI (16 vs. 6) and IMSI (4 vs. 2) groups (adjusted OR=2.84; 95% CI=1.24–6.53, P=0.009). It was also observed that the fertilization rate in the ICSI group (77.7%) was significantly lesser compared to IMSI (80.6%). This may be attributed to the deselection of the spermatozoa with one or more vacuoles or any abnormalities in the head or base shape in IMSI method.

An earlier study by Berkovitz et al (Human Reproduction, 2006) reported that nuclear vacuoles in spermatozoa with normal nuclear shapes do not affect the development of the embryos at an early stage. However, it negatively affects the survival of the embryos at a later stage. There is still insufficient knowledge on the biological mechanism underlying the impact of large vacuole in the spermatozoa on later embryonic development. The study found that the presence of vacuoles in the nuclei of motile spermatozoa significantly decreases the pregnancy rate per ICSI cycle and increases abortion rate per pregnancy as compared to sperms with normal nuclear shape. On the contrary, Tanaka et al (Fertility and Sterility, 2012) demonstrated that human sperm head with vacuoles do not influence the fertilization rate and blastocyst formation in ICSI cycles.

IMSI, based on motile sperm organelle morphology examination (MSOME) under high magnification (>6000x), is known to have a theoretical potential of improving ART outcomes since it helps in selecting the best sperm. In order to compare the safety and effectiveness of IMSI with standard ICSI, a Cochrane review by Teixeira et al (Cochrane Database Syst Rev, 2013) shortlisted nine randomized controlled trials that involved 2014 infertile couples. The review did not observe any incidence of congenital abnormalities following ICSI or IMSI and concluded on the lack of significant evidence to support the use of IMSI in routine clinical practice.


  • Cassuto NG, Hazout A, Bouret D, et al. Low birth defects by deselecting abnormal spermatozoa before ICSI. Reprod Biomed Online. 2014 Jan;28(1):47-53.
  • Lo Monte G, Murisier F, Piva I, Germond M, Marci R. Focus on intracytoplasmic morphologically selected sperm injection (IMSI): a mini-review. Asian J Androl. 2013 Sep;15(5):608-15.
  • Berkovitz A, Eltes F, Ellenbogen A, Peer S, Feldberg D, Bartoov B. Does the presence of nuclear vacuoles in human sperm selected for ICSI affect pregnancy outcome? Hum Reprod. 2006 Jul;21(7):1787-90.
  • Tanaka A, Nagayoshi M, Tanaka I, Kusunoki H. Human sperm head vacuoles are physiological structures formed during the sperm development and maturation process. Fertil Steril. 2012 Aug;98(2):315-20.
  • Teixeira DM, Barbosa MA, Ferriani RA, Navarro PA, Raine-Fenning N, Nastri CO, Martins WP. Regular (ICSI) versus ultra-high magnification (IMSI) sperm selection for assisted reproduction. Cochrane Database Syst Rev. 2013 Jul 25;7:CD010167.

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