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 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
Low Sperm Motility
Poor Sperm Parameters
Men with Normal Sperm parameters but unexplained infertility
DNA damage is caused by
Elevated testicular temperature
Exposure to environmental and occupational pollutants and heat
Who May Benefit from DNA fragmentation tests
Arrested embryo development
Poor blastocyst development
Multiple failed IVF/ICSI treatment
Recurrent miscarriage in partner
Poor semen parameters
Exposure to harmful substances
Fertility centres 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.
DNA fragmentation Tests:
These tests indicates 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:
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 of Sperms based on DNA damage made possible by Microfluidics:
Microfluidics Sperm Sorting Technology can help filter sperms that are more likely to carry DNA damage from normal sperms. This technique works on the principle that Sperms with lower motility have higher DNA damage and motile sperms are less like to carry DNA damage.
Microfluidic sperm sorter separates morphologically normal sperms with high motility. Sperm selection in this method is done by two gravity driven laminar flows within a central microfluidic channels.
The Microfluidic Sperm Sorter Qualis (MSSQ) contains 4 chambers A, B, C and D connected by two parallel channels A – D and B - C. Media is added in chambers B, C, D and Laminar flow channels are allowed to form between the chambers. Sperm sample is added to Chamber A. After some time, only motile sperms would collect in chamber C while immotile sperms would collect in chamber D.