Selecting the "Good" Sperm for Human Assisted Reproduction

The spermatozoa of all placental mammals, including humans, are in a protective state at ejaculation and are incapable of fertilization. Spermatozoa must undergo a subsequent period of final maturation termed capacitation and spermatozoa in the ejaculate are prevented from undergoing capacitation by some factors that are present in the seminal plasma ¹. This final maturation of the mammalian spermatozoa can be evaluated in three steps; capacitation, hyperactivated motility, and acrosome reaction.

As a common sense, sperm preparation prior to assisted reproduction has three basic advantages:

1- Sperm preparation and wash procedures remove the seminal plasma and help the sperm cells to prepare for capacitation.

2- Sperm preparation methods help to eliminate immotile, dead and morphologically abnormal spermatozoa and non-reproductive cells, which are the main causes of ROS in the ejaculate.

3-Sperm washing and selection techniques can be used to purify the sperm cells from pathogenic microorganisms.

The oocyte makes the choice in selecting the best sperm to win the race in natural conception and conventional insemination protocols like intra uterine insemination (IUI) and in vitro fertilization (IVF), therefore the contribution of the healthy paternal genome to embryo development, implantation and conception are the main problems to be solved in sperm preparation for intracytoplasmic sperm injection (ICSI).

In the era of human assisted reproduction where the main choice of treatment for the severe male infertility is ICSI, quality of gametes is one of the factors that help to determine the success.

With the innovation of strict Tygerberg criteria a consensus regarding the importance of sperm morphology assessment in human assisted reproduction seems to be reached. After the breakthrough in human assisted reproduction by ICSI, the raised question about the future need of extended sperm analysis as well as sperm function tests evoked ^2,3.

Infertile men with poor sperm motility and morphology were found to have increased sperm DNA fragmentation compared with individuals with normal semen parameters ⁴. Men with normal semen analysis may also have a high degree of sperm DNA fragmentation, which can be a major cause of unexplained infertility, and sperm DNA fragmentation may result from aberrant
chromatin packaging during spermatogenesis ⁵, defective apoptosis before ejaculation ⁶, or excessive production of reactive oxygen species (ROS) in the ejaculate ⁷. Exposures to environmental or industrial toxins ⁸, genetics ⁹ or life style ¹⁰ are also known factors that may cause sperm DNA fragmentation and infertility.

Although the factors present in the paternal genome that may have an impact on poor reproductive outcome are still not well defined, there is accumulating evidence linking sperm nuclear DNA abnormalities to poor reproductive outcome and one of the most suspected organelle is the sperm nucleus. Studies reveal that severe teratozoospermia results in high preimplantation embryo aneuploidy ^11,12 and the interchromosomal effect is related to impaired semen parameters ¹³. Studies have also shown that immature sperm have increased rates of lipid peroxidation and bear poor morphometric and morphological attributes, zona pellucid-binding properties and fertility ¹⁴. The ROS induced lipid peroxidation is involved in the mechanisms by which spermatozoa are damaged in many cases of male infertility. Studies show a significant correlation between sperm morphology attributes and the expressed apoptotic markers like caspases-3 activation and mitochondrial membrane potential integrity ¹⁵.

The sperm nucleus, as the carrier of paternal DNA to the oocyte, remains as the greatest contributor to the potential success of reproductive outcome, where, sperm nuclear DNA strand breaks, DNA repair mechanisms, apoptosis and DNA remodeling processes are the main factors to be considered ¹⁶. Table 1 shows common characteristics of a good sperm.

Table 1

Common characteristics of a “good” sperm for ICSI

 Memorial Antalya Hospital, Center for Reproductive Medicine

 Antalya, Turkey

Referances

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5. Manicardi GC, Bianchi PG, Pantano S, et al; Presence of endogenous nicks in DNA of ejaculated human spermatozoa and its relationship to chromomycin A3 accessibility. Biol Reprod. 1995;52:864-867.

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10. Agarwal A, Desai N, Makker K, et al; Effects of radiofrequency electromagnetic waves (FR-EMV) from cellular phones on human ejaculated semen: an in vitro pilot study. Fertil Steril. 2009;92(4): 1318-1325.

11. Cinar C, Yazici C, Ergünsu S, et al; Genetic diagnosis in infertile men with numerical and constitutional sperm abnormalities. Genet Test. 2008;12(2):195-202.

12. Dubey A, Dayal MB, Frankfurter D, et al; The influence of sperm morphology on preimplantation genetic diagnosis cycles outcome. Fertil Steril. 2008;89(6):1665-1669.

13. Kirkpatrick G, Ferguson KA, Gao H, et al; A comparison of sperm aneuploidy rates between infertile men with normal and abnormal karyotypes. Hum Reprod. 2008;23(7):1679-1683.

14. Huzsar G, Vigue L; Correlation between the rate of lipid peroxidation and cellular maturity as measured by creatine kinase activity in human spermatozoa. J Androl. 1994;15:71-77.

15. Aziz N, Said T, Paasch U, et al; The relationship between human sperm apoptosis, morphology and the sperm deformity index. Hum Reprod. 2007;22(5):1413-1419.

16. Sakkas D, Seli E; Sperm DNA and embryo development. In: Elder K, Cohen J, eds; Human preimplantation embryo selection. London: Informa Healthcare; 2007:325-335.