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What is Male Factor?
One third of all cases of infertility are the result of a problem in the male partner. Another third is due to a combination of male and female problems. In the male partner, the inability to produce or ejaculate (release) sperm can be the reason for infertility. Sperm quality is also important and traditionally is determined by the amount, the movement and the shape of sperm. Other medical problems can also affect a man’s ability to produce normal amounts or normal quality sperm. Men with diabetes, for instance, might have trouble ejaculating. Men with cystic fibrosis might have a blockage that prevents the sperm from being ejaculated. Overweight men, those who smoke, or men who use recreational drugs such as marijuana are more likely to have problems with their sperm.

Why mature sperm?
It´s pretty simple, Hyaluronan (HA), a naturally occurring substance found on the outside of the human egg cell, allows only fully mature sperm carrying receptors for HA to bind. This means that only sperm that have completed the last crucial stages of spermatogenesis have developed receptors for HA, and only they can bind to the egg and initiate fertilization.

Immature sperm are found to have higher rates of DNA fragmentation and often carry an abnormal number of chromosomes. However, these damaged sperm do not have receptors for HA and hence cannot bind and fertilize the egg. Immature sperm can however still show normal motility and morphology.

Traditionally, the criteria for selecting sperm for intracytoplasmic sperm injection (ICSI) is just motility and morphology. We now know that unfit sperm with compromised development and DNA fragmentation can still look normal and healthy, but if picked for fertilization can lead to poor embryo quality and possible pregnancy loss.v1

1. Parmigiani et al., (2010) Fertility and Sterility 2010; vol 93, no 2.

What is DNA Fragmentation?
DNA is the hereditary material in humans and other organisms. It consists of two long chains of simple units with backbones — DNA strands — made of sugars and phosphate. The information in DNA is stored as a code made up of four types of molecules called bases, which are attached to the DNA strands. The order, or sequence, of these bases determines the information available for building and maintaining an organism.

DNA fragmentation occurs when there is an alteration to the bases or a physical break in one or both of the DNA strands.

What are some causes of DNA Fragmentation?
Oxidative stress — stress on the body that is caused by the cumulative damage of free radicals that is not adequately neutralized by antioxidants — is a main contributor to sperm DNA fragmentation. Sperm DNA fragmentation is associated with infections, drug use, cigarette smoking, exposure to environmental and occupational pollutants, advanced age, varicocele, illnesses with high fevers, elevated testicular temperature (laptop computers, hot tubs), chronic diseases such as diabetes, cancer and cancer treatment, and poor diet.

The genetic integrity of the spermatozoan is essential for normal embryo development. A high level of DNA fragmentation in sperm cells may represent a cause of male infertility that conventional examinations – sperm concentration, motility analysis, morphology assessment – cannot detect.

  • High sperm DNA fragmentation does not appear to affect fertilization or the first or second embryo cleavage stages (day 1 or day 2)
  • High sperm DNA fragmentation can affect embryo cleavage once the paternal genome is switched on, and subsequent blastocyst development (day 5)
  • DNA fragmentation levels are closely correlated with IUI, IVF and ICSI miscarriage and pregnancy rates
  • Men with poor semen parameters are more likely to have high DNA fragmentation
  • High sperm DNA fragmentation is also found in men with normal semen parameters