With the increasing changes in lifestyle, there has been a growing ignorance about the factors that lead to infertility and how one can tackle it. However, the notion that infertility or the inability to have children, is a condition that can be medically treated is gradually being accepted in the Indian society today. The advancements in Assisted Reproductive Technology (ART) have proved to be greatly helpful in treating the problems of infertility both in men and women.
In the last decade, there has been a steady increase in the incidence of infertility in India. Studies indicate that one in every 10-12 couples in the country suffers from some form of infertility. In today’s world however, it is still difficult to accept that infertility affects both men and women equally. Male infertility is on the rise and it is rampant in cities where people are prone to stressful lifestyle.
According to internal reports, male factor is found in 40-45 per cent of infertile couples in India. Many male fertility problems often go undiagnosed and untreated because of various reasons, the main one being the misconception that infertility is a female problem. Unlike gynaecologists for women, there is not much awareness about the male infertility specialists, also called andrologists.
Often there may not be a particular symptom of male infertility, apart from the inability to get pregnant when a couple is trying. A thorough medical and urologic history that includes duration of infertility, timing of puberty, childhood urologic disorders or surgical procedures, acute or chronic medical illnesses, sexual history, testicular tumour and treatment, medications, spinal cord injury, etc. are to be considered for the diagnosis of male infertility.
Abnormalities of sperms have significantly increased these days. It is observed that the some of the factors that increase oxidative stress include pollution, cigarette smoking, lack of essential minerals and vitamins in daily diet, disturbed circadian rhythm of sleep, lack of exercise, reduced exposure to sunlight and ozone free oxygen in the early mornings, psychological depression, etc. Exposure to radiation is noted to be one of the most important causes of abnormal sperm parameters. Such exposure can happen due to excessive use of mobiles, laptops and televisions. In fact, it is said that “Cell phone is the modern age Cigarette”.
Sometimes there could be physical problems like varicocele where the veins around the testes are swollen and increase the local temperature, thereby reducing the semen parameters. After three months of antioxidants with changes in the lifestyle, some of these men demonstrate improved results with better sperm parameters. In others, varicocele surgery may help. In those cases of male infertility where the problem is either idiopathic or irreversible, Magnetic-Activated Cell Sorting (MACS) comes as a rescue.
One of the important factors determining the outcome of an ART procedure is the quality of the sperms. Sometimes men are able to produce sperms in sufficient quantity, however the quality is poor, causing difficulties in conception. For fertilization to take place, sperm must be able to reach the egg and then penetrate it. Sperms that don't move well or are abnormally shaped may be unable to do this. MACS comes in handy as an efficient technology that helps in the preparation of motile, viable and morphologically normal sperms.
Suboptimal success rates with Assisted Reproductive Technology calls for an ideal sperm preparation technique. Conventional sperm preparation methods are based on sedimentation or migration, on the motility or the density of the sperm and not on the basis of apoptosis, which may play a major role in the fertilisation and implantation rates. Apoptosis refers to the natural death of cells that enables controlled growth of an organism. In male reproductive system, apoptosis plays a very important role in controlling over production of sperms.
Apoptosis is characterised by changes like cell shrinkage, plasma membrane disruption, phosphatidylserine externalization, nuclear chromatin condensation and DNA fragmentation. These characters are noted in the ejaculated sperms which may be one of the reasons for the reduced pregnancy rates even with ART. Of all the changes representing apoptosis, externalisation of phosphatidylserine is one of the earliest changes.
The principle of magnetic-activated cell sorting revolves around the concept of filtering out the apoptotic sperms using externalised phosphatidylserine (phospholipid membrane component that has high affinity for Annexin V) that binds with Annexin V (calcium-dependent phospholipid-binding proteins). The apoptotic sperms bind to the paramagnetic beads and gets separated out while they pass through the magnetic field. So this pool will have intact membrane and non-apoptotic sperms.
After preparing the sperms by DDG (double density gradient), 100 micro litre paramagnetic beads are used for every 10 million sperms. After incubation this suspension is passed through a separation chamber which is surrounded by 0.5 T magnetic fields. The sperms labelled with microbeads are retained within the chamber and the unbound sperms which represent the non-apoptotic pool pass through.
There are many advantages that this technology possess. Firstly, it helps in segregating the non-apoptotic sperms which is its primary function. Secondly, it mainly enhances improved sperm deformity index which is a measure of the average number of deformities per sperm assessed in the process. Apart with these, this method ensures lesser DNA fragmentation, results in better motile sperms and much improved ART outcomes.
On the whole, MACS is a sperm separation technique that is technically easy, quick and reproducible. MACS is also known to significantly improve the pregnancy rates. A systematic meta-analysis revealed that the pregnancy rates of MACS separated were about 45 per cent whereas that of controls was 24.69 per cent which was statistically significant. Studies have proved that Annexin V negative sperms chosen by MACS had better cryosurvival rate of sperms (76 per cent) and retained higher motility (76 per cent) and viability (82 per cent). Using zona free hamster oocyte, it has been shown that Annexin negative sperms chosen by MACS have better ability to penetrate the oocyte than the Annexin positive sperms.
In conclusion, Magnetic-Activated Cell Sorting is a revolutionary technology which helps fertility specialists segregate sperms with normal morphology and better fertilisation capacity so as to ensure the best pregnancy results with either Intra-Cytoplasmic Sperm Injection (ICSI) or even IUI. MACS is a boon for men that improves the pregnancy rates after ICSI while reducing the abortion rates and risks of fertilisation failure or embryo degeneration.
(Author is with Nova IVI Fertility, Bengaluru)