Posted under Fertility Treatment by Dr. Rajeev Agarwal

How DNA Fragmentation and Microfluidics are changing how we assess Sperm Quality?

Classical semen analysis is based mainly on sperm count, the number, ability of the sperm to swim and the shape or morphology of the sperm. Although Semen analyses test is used as a gold standard to different fertile men from infertile men, it doesn’t provide any information on the genetic constitution of the sperm.

Natural selection Filters Sperm DNA damage but ART doesn’t:

Sperms with DNA damage are less motile.

This is nature’s way of ensuring that sperms with DNA damage don’t reach the egg. Only one on 300 million sperms fertilize the egg. Body’s natural selection mechanism promotes surplus production of sperms and allows a race in which only the fittest are able to reach the egg.

ICSI bypasses the natural selection mechanism of the body that stops Sperms with DNA damage from fertilization.

ICSI allows direct selection of a single sperm and injection into the egg. A semen sample with normal semen parameters indicated in semen analysis may still carry DNA damage. If such a sperm is injected into the egg, the resulting embryo will be less viable and of poor quality.

How does DNA Fragmentation effect ART Treatment outcome?

  • Evidence suggests that in the field of ART, DNA damage in sperms can be passed on to the embryo and result in cell degeneration and gene mutations, leading to arrested embryo development, miscarriage, abnormalities in the offspring and an increased susceptibility to childhood cancers.
  • Embryos derived from sperm whose DNA is highly fragmented have a poor prognosis and may result in implantation failure or miscarriage or birth defects.
  • High sperm DNA fragmentation is more likely to affect embryos from day two of development once the paternal genome is switched on and it impairs subsequent blastocyst development.

Thus, the current era of assisted reproductive technology demands more sophisticated diagnostic and predictive tools in the management of male infertility that can assess the extent of DNA damage in sperms.

 

DNA Fragmentation is High in DNA damage is caused by
 
Who May Benefit from DNA fragmentation tests
  • Infertile men
  • Low Sperm Motility
  • Poor Sperm Parameters
  • Men with Normal Sperm parameters but unexplained
  • Infertility
  • Infection
  • Leucocytospermia
  • High Fever
  • Elevated Testicular Temperature
  • Varicocoele
  • Advanced Age
  • Obesity
  • Poor Diet
  • Drug Use
  • Cigarette Smoking
  • Exposure to Environmental and Occupational Pollutants and Heat
  • Unexplained Infertility
  • Arrested Embryo Development
  • Poor Blastocyst Development
  • Multiple Failed IVF/ICSI Treatment
  • Recurrent Miscarriage in Partner
  • Advanced Age
  • Varicocoele
  • Poor Semen Parameters
  • Exposure to Harmful Substances

 

Fertility centers are therefore turning their attention to this area of fertility research which focusses on assessment of Sperm quality based on DNA damage.

Clinics are now adopting advanced techniques like DNA fragmentation tests and Microfluidics in an attempt to identify and reduce the possibility of using sperms with DNA damage in IVF.

Measuring Sperm DNA damage using DNA Fragmentation Tests:

These tests indicate the DNA fragmentation Index of an individual, which is reported as the percentage of sperms having fragmented DNA. It helps doctors to check if the DNA damage is high, investigate the cause and to decide the appropriate treatment outcome which may be:

  • Varicocoele Surgery.
  • Reversing or reducing DNA damage caused by Reactive Oxygen Species by means of medicines, anti-oxidant supplements, diet and lifestyle changes.
  • Treatment of infection with antibiotics.
  • Sperm Donation if the extent of fragmentation is very high or can’t be treated.

Sorting Normal sperms without DNA damage via Microfluidics Sperm Sorting Technology (MSSQ):

MSSQ makes it very easy to sort sperms based on their motility using microfluidics and is currently the most favored tool in Andrology laboratories for sorting sperms with DNA damage. This is because Sperms with DNA damage have lower motility whereas sperms with higher motility are very less likely to have a poor DNA damage score.

The MSSQ is an ingenious device with four chambers connected via paralleled channels. Media is added to three of the chambers. Differences in gradients in media between the chambers are used to establish two parallel laminar flow channels between the three chambers. This laminar flow is used to sort motile sperms from immotile sperms.

To Understand how the Microfluidics Sperm Sorter sorts Normal sperms from DNA damaged sperms click here.


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