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Sperm damage and fertility problem due to COVID-19

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Many couples initially deferred attempts at pregnancy or delayed fertility care due to concerns about coronavirus disease 2019 (COVID-19). One significant fear during the COVID-19 pandemic was the possibility of sexual transmission. Many couples have since resumed fertility care while accepting the various uncertainties associated with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2), including the evolving knowledge related to male reproductive health. Significant research has been conducted exploring viral shedding, tropism, sexual transmission, the impact of male reproductive hormones, and possible implications to semen quality. However, to date, limited definitive evidence exists regarding many of these aspects, creating a challenging landscape for both patients and physicians to obtain and provide the best clinical care.

According to a new study, which looked at sperm quality in patients who suffered symptomatic coronavirus (COVID-19) infections, showed that it could impact fertility for weeks after recovery from the virus. The data showed 60% COVID-19 infected men had reduction in sperm motility and 37% had drop in sperm count, but, 2 months after recovery from COVID-19 the value came down to 28% and 6% respectively. The researchers also of the view that COVID-19 could not be sexually transmitted through semen after a person had recovered from illness. Patients with mild and severe cases of COVID-19 showed similar rate of drop in sperm quality. But further work is required to establish whether or not COVID-19 could have a longer-term impact on fertility. The estimated recovery time is three months, but further follow-up studies are still required to confirm this and to determine if permanent damage occurred in a minority of men.

Some viruses like influenza are already known to damage sperm mainly by increasing body temperature. But in the case of COVID-19, the researchers found no link between the presence or severity of fever and sperm quality. Tests showed that higher concentrations of specific COVID-19 antibodies in patients’ blood serum were strongly correlated with reduced sperm function. So, it was believed the sperm quality reduction cause could be linked to the body’s immune response to the virus. While the study showed that there was no COVID-19 RNA present in the semen of patients who had got over the virus, the fact that antibodies were attacking sperm suggests the virus may cross the blood-testis barrier during the peak of an infection.

It was found in a previous report that SARS-CoV-2 can be present in the semen of patients with COVID-19, and SARS-CoV-2 may still be detected in the semen of recovering patients. Due to imperfect blood-testes/deferens/epididymis barriers, SARS-CoV-2 might be seeded to the male reproductive tract, especially in the presence of systemic local inflammation. Even if the virus cannot replicate in the male reproductive system, it may persist, possibly resulting from the privileged immunity of testes.

If it could be proved that SARS-CoV-2 can be transmitted sexually in future studies, sexual transmission might be a critical part of the prevention of transmission, especially considering the fact that SARS-CoV-2 was detected in the semen of recovering patients. Abstinence or condom use might be considered as preventive means for these patients. In addition, it is worth noting that there is a need for studies monitoring fetal development. Therefore, to avoid contact with the patient’s saliva and blood may not be enough, since the survival of SARS-CoV-2 in a recovering patient’s semen maintains the likelihood to infect others. But further studies are required with respect to the detailed information about virus shedding, survival time, and concentration in semen.

References:

https://www.euronews.com/next/2021/12/21/covid-can-damage-sperm-for-months-making-it-harder-to-conceive-a-baby-a-new-study-finds

https://www.fertstert.org/article/S0015-0282(20)32780-1/fulltext

https://www.fertstertreviews.org/article/S2666-5719(21)00004-9/fulltext

https://www.fertstertscience.org/article/S2666-335X(21)00064-1/fulltext

https://www.fertstert.org/article/S0015-0282(21)02156-7/fulltext

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2765654/

https://www.fertstert.org/article/S0015-0282(21)01398-4/fulltext

https://www.euronews.com/next/2021/08/27/do-covid-vaccines-affect-pregnancy-fertility-or-periods-we-asked-the-world-health-organiza

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Infertility has been primarily treated as a female predicament but around one-half of infertility cases can be tracked to male factors. Clinically, male infertility is typically determined using measures of semen quality recommended by World Health Organization (WHO). A major limitation, however, is that standard semen analyses are relatively poor predictors of reproductive capacity and success. Despite major advances in understanding the molecular and cellular functions in sperm over the last several decades, semen analyses remain the primary method to assess male fecundity and fertility.

Chronological age is a significant determinant of human fecundity and fertility. The disease burden of infertility is likely to continue to rise as parental age at the time of conception has been steadily increasing. While the emphasis has been on the effects of advanced maternal age on adverse reproductive and offspring health, new evidence suggests that, irrespective of maternal age, higher male age contributes to longer time-to-conception, poor pregnancy outcomes and adverse health of the offspring in later life. The effect of chronological age on the genomic landscape of DNA methylation is profound and likely occurs through the accumulation of maintenance errors of DNA methylation over the lifespan, which have been originally described as epigenetic drift.

In recent years, the strong relation between age and DNA methylation profiles has enabled the development of statistical models to estimate biological age in most somatic tissue via different epigenetic ‘clock’ metrics, such as DNA methylation age and epigenetic age acceleration, which describe the degree to which predicted biological age deviates from chronological age. In turn, these epigenetic clock metrics have emerged as novel biomarkers of a host of phenotypes such as allergy and asthma in children, early menopause, increased incidence of cancer types and cardiovascular-related diseases, frailty and cognitive decline in adults. They also display good predictive ability for cancer, cardiovascular and all-cause mortality.

Epigenetic clock metrics are powerful tools to better understand the aging process in somatic tissue as well as their associations with adverse disease outcomes and mortality. Only a few studies have constructed epigenetic clocks specific to male germ cells and only one study reported that smokers trended toward an increased epigenetic age compared to non-smokers. These results indicate that sperm epigenetic clocks hold promise as a novel biomarker for reproductive health and/or environmental exposures. However, the relation between sperm epigenetic clocks and reproductive outcomes has not been examined.

There is a critical need for new measures of male fecundity for assessing overall reproductive success among couples in the general population. Data shows that sperm epigenetic clocks may fulfill this need as a novel biomarker that predicts pregnancy success among couples not seeking fertility treatment. Such a summary measure of sperm biological age is of clinical importance as it allows couples in the general population to realize their probability of achieving pregnancy during natural intercourse, thereby informing and expediting potential infertility treatment decisions. With the ability to customize high throughput DNA methylation arrays and capture sequencing approaches, the integration of the epigenetic clocks as part of standard clinical care can enhance our understanding of idiopathic infertility and the paternal contribution to reproductive success and offspring health.

References:

https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deac084/6583111?login=false

https://pubmed.ncbi.nlm.nih.gov/33317634/

https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-019-0656-7

https://pubmed.ncbi.nlm.nih.gov/19319879/

https://pubmed.ncbi.nlm.nih.gov/31901222/

https://pubmed.ncbi.nlm.nih.gov/25928123/

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A Genetic Switch to Control Female Sexual Behavior, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

In an African cichlid fish, Astatotilapia burtoni, fertile females select a mate and perform a stereotyped spawning / mating routine, offering quantifiable behavioral outputs of neural circuits. A male fish attracts a fertile female by rapidly quivering his brightly colored body. If she chooses him, he guides her back to his territory, where he quivers some more as she pecks at fish egg–colored spots on his anal fin. Next, she lays eggs and quickly scoops them up in her mouth. With a mouthful of eggs, she continues pecking at the male’s spots, “believing” them to be eggs to be collected. As she does, he releases sperm from near his anal fin, which she also gathers. This fertilizes the eggs, and she carries the embryos in her mouth for two weeks as they develop.

 

But, the question was how these females can time their reproduction to coincide with when they are fertile. The female fish will not approach or choose males until they are ready to reproduce, so there must be something in their brains that signals when sexual behavior will be required. The scientists began by considering signaling molecules previously associated with sexual behavior and reproduction, and showed that PGF2α injection activates a naturalistic pattern of sexual behavior in female Astatotilapia burtoni. They would engage in mating behavior even if they were non-fertile, doing the quiver dance with males, but wouldn’t actually lay eggs since they had none.

 

The scientists also identified cells in the brain that transduce the prostaglandin signal to mate and showed that the gonadal steroid 17α, 20β-dihydroxyprogesterone modulates mRNA levels of the putative receptor for PGF2α. The scientists keyed in on a receptor for PGF2α in the preoptic area (POA) within the hypothalamus of the brain, a region involved in sexual behavior across animals. They suspected that when PGF2α levels elevated in the fish, the molecule attaches to this receptor and triggers sexual behavior. Then they used CRISPR/Cas9 to generate PGF2α receptor knockout fish. This gene deletion or knockout uncoupled the sexual behavior from fertility status to prove that the receptor of PGF2α is necessary for the initiation of sexual behavior.

 

The finding has parallels across all vertebrates, and might influence the understanding of social behavior in humans. The next steps for this work will involve understanding other behaviors that are regulated by this receptor, and the finding provides insight into both the evolution of reproduction and sexual behaviors. In mammals and other vertebrates, PGF2α promotes the onset of labor and motherly behaviors, and this present research, coupled with other studies, suggests that PGF2α signaling has a common ancestral function associated with birth and its related behaviors.

 

References:

 

http://www.ncbi.nlm.nih.gov/pubmed/26996507

 

http://news.stanford.edu/news/2016/march/fish-mating-behavior-031716.html

 

 

http://www.academia.edu/676252/The_Genetics_of_Female_Sexual_Behaviour

 

https://scifeeds.com/news/scientists-identify-genetic-switch-for-female-sexual-behavior/

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A Magnetically controlled Mechanical Propeller for Immotile Sperm

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Researchers from the Institute for Integrative Nanosciences, IFW Dresden, Germany and Material Systems for Nanoelectronics, Chemnitz University of Technology, Germany have developed something known as the spermbot, a remotely controlled sperm movement controlling robot that could help create babies of the future. It is a magnetically powered robotic “suit” that can strap itself to individual sperm and help guide it faster towards the egg. According to the inventors all the initial tests with the spermbot have delivered promising results.

The purpose of the spermbot is to solve one of the widely talked about causes of infertility in men which is poor motility of sperm. Low sperm motility, or otherwise healthy sperm that just can’t swim, can be a big factor in infertility. While the development of the spermbot is in its early stages, this is already being talked about as a promising alternative to existing popular techniques that are expensive and come with a high failure rate. These include methods like in-vitro fertilization and artificial insemination. Only 30 percent of the traditional “spray-and-pray” approach ends up with success, which warranted the need for an alternative procedure like the spermbot. According to the report, initial experiments show a marked increase in the probability of the spermbot-assisted sperm to reach its intended destination. The process of fertilization can be completed inside the body or in the lab, inside a petri-dish.

The spermbot is a coat of microscopic metal polymers shaped into a helix. It can attach itself to the tail of the spermatozoid, and then, using a hybrid micromotor, it can help propel the sperm faster towards the egg. The direction the sperm needs to take is controlled using a rotating magnetic field. In fact, even the motion of the sperm can be remote-controlled by simply adjusting this magnetic field. Once the spermbot propels the sperm towards the egg and the sperm manages to implant itself into the egg, the bionic part of the spermbot detaches itself from the tail.

While the initial experiments look promising, there is still some way to go before the spermbot technique is regularly used. To start off, scientists have very few sample size to correctly evaluate the results, and unless more comprehensive tests are carried out, it would not be possible to start using them on human subjects. Another major stumbling block is that there is currently no way to film the spermbot in action while it is moving inside the body. This also means that doctors would not be able to correctly direct it towards the egg. Another concern is the response of the body’s own immune system to the spermbot. The use of the spermbot could trigger a reaction from the body’s immune system, the results of which cannot be predicted without comprehensive clinical trials. The idea of the spermbot looks promising right now, but it is still too early to call it a replacement to the tried and tested methods like in-vitro fertilization and artificial insemination. In fact, it would take a few years for the procedure to be made available to patients if clinical trials are successfully completed.

References:

http://pubs.acs.org/doi/abs/10.1021/acs.nanolett.5b04221

http://www.acs.org/content/acs/en/pressroom/presspacs/2016/acs-presspac-january-13-2016/spermbots-could-help-women-trying-to-conceive-video.html

http://www.inquisitr.com/2711435/spermbot-robot-sperm-infertility-treatment/#utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+google%2FyDYq+%28The+Inquisitr+-+News%29

http://www.slate.com/articles/video/video/2016/01/spermbot_attached_to_sperm_and_delivers_it_quickly_to_an_egg_video.html

http://www.sciencemag.org/news/2016/01/video-motorized-spermbot-helps-sperm-reach-egg

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Lifelong Contraceptive Device for Men: Mechanical Switch to Control Fertility on Wish

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

There aren’t many options for long-term birth control for men. The most common kinds of male contraception include

  • condoms,
  • withdrawal / pulling out,
  • outercourse, and
  • vasectomy.

But, other than vasectomy none of the processes are fully secured, comfortable and user friendly. Another solution may be

  • RISUG (Reversible Inhibition of Sperm Under Guidance, or Vasalgel)

which is said to last for ten years and no birth control pill for men is available till date.

VIEW VIDEO

http://www.mdtmag.com/blog/2016/01/implanted-sperm-switch-turns-mens-fertility-and?et_cid=5050638&et_rid=461755519&type=cta

Recently a German inventor, Clemens Bimek, developed a novel, reversible, hormone free, uncomplicated and lifelong contraceptive device for controlling male fertility. His invention is named as Bimek SLV, which is basically a valve that stops the flow of sperm through the vas deferens with the literal flip of a mechanical switch inside the scortum, rendering its user temporarily sterile. Toggled through the skin of the scrotum, the device stays closed for three months to prevent accidental switching. Moreover, the switch can’t open on its own. The tiny valves are less than an inch long and weigh is less than a tenth of an ounce. They are surgically implanted on the vas deferens, the ducts which carry sperm from the testicles, through a simple half-hour operation.

The valves are made of PEEK OPTIMA, a medical-grade polymer that has long been employed as a material for implants. The device is patented back in 2000 and is scheduled to undergo clinical trials at the beginning of this year. The inventor claims that Bimek SLV’s efficacy is similar to that of vasectomy, it does not impact the ability to gain and maintain an erection and ejaculation will be normal devoid of the sperm cells. The valve’s design enables sperm to exit the side of the vas deferens when it’s closed without any semen blockage. Leaked sperm cells will be broken down by the immune system. The switch to stop sperm flow can be kept working for three months or 30 ejaculations. After switching on the sperm flow the inventor suggested consulting urologist to ensure that all the blocked sperms are cleared off the device. The recovery time after switching on the sperm flow is only one day, according to Bimek SLV. However, men are encouraged to wait one week before resuming sexual activities.

Before the patented technology can be brought to market, it must undergo a rigorous series of clinical trials. Bimek and his business partners are currently looking for men interested in testing the device. If the clinical trials are successful then this will be the first invention of its kind that gives men the ability to control their fertility and obviously this method will be preferred over vasectomy.

 

References:

 

https://www.bimek.com/this-is-how-the-bimek-slv-works/

 

http://www.mdtmag.com/blog/2016/01/implanted-sperm-switch-turns-mens-fertility-and?et_cid=5050638&et_rid=461755519&type=cta

 

http://www.telegraph.co.uk/news/worldnews/europe/germany/12083673/German-carpenter-invents-on-off-contraception-switch-for-sperm.html

 

http://www.discovery.com/dscovrd/tech/you-can-now-turn-off-your-sperm-flow-with-the-flip-of-a-switch/

 

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Meiosis plays a crucial role in generating haploid gametes for sexual reproduction. In most organisms, the presence of crossovers between homologous chromosomes, in combination with connections between sister chromatids, creates a physical connection that ensures regular segregation of homologs at the first of the two meiotic divisions.

Abnormality in generating crossovers is the leading cause of miscarriage and birth defects. Crossovers also create new combinations of alleles, thus contributing to genetic diversity and evolution. Recent linkage disequilibrium and pedigree studies have shown that the distribution of recombination is highly uneven across the human genome, as in all studied organisms. Substantial recombination active regions are not conserved between humans and chimpanzees or among different human populations, suggesting that these regions are quickly evolving and might even be individual-specific. However, such variation in the human population would be masked by the population average, and resolution of this variation would require comparison of recombination genome-wide among many single genomes.

Whole-genome amplification (WGA) of single sperm cells was proposed decades ago to facilitate mapping recombination at the individual level. With the development of highthroughput genotyping technologies, wholegenome mapping of recombination events in single gametes of an individual is achievable and was recently demonstrated by performing WGA by multiple displacement amplification (MDA) on single sperm cells, followed by genotyping with DNA microarrays recently demonstrated by Wang et al.. However, due to the amplification bias and, consequently, insufficient marker density, the resolution of crossover locations has been limited to ~150 kb thus far. In addition, in their recent work, Wang et al. relied on prior knowledge of the chromosome-level haplotype information of the analyzed individual, which is experimentally inconvenient to obtain and is currently available for only a few individuals.

Meiotic recombination creates genetic diversity and ensures segregation of homologous chromosomes. Previous population analyses yielded results averaged among individuals and affected by evolutionary pressures. In this study 99 sperm from an Asian male was sequenced by using the newly developed amplification method—multiple annealing and looping-based amplification cycles—to phase the personal genome and map recombination events at high resolution, which are non-uniformly distributed across the genome in the absence of selection pressure. The paucity of recombination near transcription start sites observed in individual sperm indicates that such a phenomenon is intrinsic to the molecular mechanism of meiosis. Interestingly, a decreased crossover frequency combined with an increase of autosomal aneuploidy is observable on a global per-sperm basis.

Source References:

http://www.ncbi.nlm.nih.gov/pubmed/23258895

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

An estimated 10 to 15% of couples suffer from infertility, and many treatment decisions rely on trial and error. A team of international scientists has found a common genetic variant which may explain why some men with normal sperm counts and good quality sperm are affected by infertility.

The study findings suggested that men with a variation in a gene which codes for a sperm-coating protein called beta defensin 126 (DEFB126) have a reduction in the protein coat on the outside of the sperm which makes it difficult for the sperm to ‘swim’ to the egg.

Dr Edward Hollox of the University of Leicester and co-author of the study said: ‘If you’ve got this gene variant you should allow that little bit longer if your partner’s planning to get pregnant’. The researchers, including scientists from the University of California and the Anhui Medical University in China, carried out the study on over 500 newly-wed Chinese couples who were trying for a baby.

They found that when men’s sperm lacked a coat of the DEFB126 protein, their wives were significantly less likely than expected to become pregnant.

Previous studies have shown that two copies of the genetic variant may be found in up to one quarter of men around the world, with about half of all men having one copy. The DEFB126 protein coat helps sperm to swim through cervical mucus and evade the woman’s immune system, as well as enabling it to attach to the walls of fallopian tubes.

The study showed, however, that men with two copies of the variant produced sperm that were less able to swim through a substitute to cervical mucus, hyaluronic acid gel. In macaques, it has already been shown that this protein is important in evading the immune system and the researchers believe the protein coat plays the same role in humans. Commenting on the study, Dr Allan Pacey, senior lecturer in Andrology at the University of Sheffield, said: ‘We actually understand very little about the subtle molecular events which occur in sperm as they make their journey through the woman’s body to fertilise an egg’. The research was published in the journal Science Translational Medicine. If replicated in future studies, these findings promise to guide choices about the timing and type of assisted reproduction interventions—and further hint at the possibility of treating sperm from del/del homozygotes to promote fertility.

A gene which helps sperm bind to an egg has been identified by scientists. Sperm-to-egg binding is an essential process during fertilization and although the preliminary studies were performed on mice, the gene may represent a new target for infertility treatments. Sperm from mice that had the gene switched off were only able to fertilise eggs from female mice three percent of the time compared to 80 percent fertilisation success in normal mice.

The gene codes for a protein called PDILT which helps another gene product to form and assemble correctly and then to reach the surface of a sperm. Once this happens the sperm is able to navigate the uterus and oviduct and penetrate the sticky outer layers of an egg. The study, which is published in PNAS (Proceedings of the National Academy of Sciences), also demonstrates the importance of cumulus cells, a cluster of cells that surround and protect the egg, as their presence allows sperm to bind to their target. Sperm from mice that had their PDILT gene switched off would not bind to a bare egg, but would bind to an egg surrounded by cumulus cells.

Co-author Dr Adam Benham from Durham University in the UK said that the PDILT protein is ‘an essential part of the navigation system of sperm. Like any navigation system, you have to programme where it is that you want to go and this protein plays an essential role in getting sperm to the right destination, in good shape, and in good time’. A question now for the scientists is whether the PDILT gene has as much importance in human fertility as it does in mice. ‘Mutations in the gene may be responsible for unexplained male fertility problems and further research may aid more effective IVF treatment‘, said Dr Benham.

Source References:

http://stm.sciencemag.org/content/3/92/92ps31.abstract

http://www.bionews.org.uk/page_142955.asp

http://www.itv.com/news/update/2012-05-01/scientists-discover-new-gene-key-to-fertility/

http://www.bionews.org.uk/page_102705.asp

 

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Reporter: Sudipta Saha, Ph.D.

Laboratory testing is an integral component of the evaluation of the infertile men. This testing must be appropriate and specific for the individual couple. As there are many tests that evaluate various aspects of infertility, the urologist have to decide what information the tests can offer as well as the limitations of each assay. The semen analysis remains the cornerstone of the evaluation but is not a functional assay. Other assays such as sperm-cervical mucus tests, hemizona assays, and the sperm-penetration assay are functional tests. Through the appropriate use of these and other tests, the urologist will be capable of better and more accurately counseling the infertile couple (http://www.springerlink.com/content/t518435632851834/).

5.3 million American couples of reproductive age (9%) are affected by infertility, among which male factors account for up to 50% of cases, which necessitates the identification of parameters defining sperm quality, including sperm count and motility. In vitro fertilization (IVF) with or without intra cytoplasmic sperm injection (ICSI) has become the most widely used assisted reproductive technology (ART) in modern clinical practice to overcome male infertility challenges. One of the obstacles of IVF and ICSI lies in identifying and isolating the most motile and presumably healthiest sperm from semen samples that have low sperm counts (oligozoospermia) and/or low sperm motility (oligospermaesthenia). Microfluidic systems have shown potential to sort sperm with flow systems. However, the small field of view (FOV) of conventional microscopes commonly used to image sperm motion presents challenges in tracking a large number of sperm cells simultaneously. To address this challenge, Zhang et. al. at Harvard Medical School and MIT integrated a lensless charge-coupled device (CCD) with a microfluidic chip to enable wide FOV and automatic recording as the sperm move inside a microfluidic channel. The integrated system enables the sorting and tracking of a population of sperm that have been placed in a microfluidic channel. This channel can be monitored in both horizontal and vertical configuration similar to a swim up column method used clinically. Sperm motilities can be quantified by tracing the shadow paths for individual sperm. Moreover, as the sperm are sorted by swimming from the inlet towards the outlet of a microfluidic channel, motile sperm that reach the outlet can be extracted from the channel at the end of the process. This technology can lead to methods to evaluate each sperm individually in terms of motility response in a wide field of view, which could prove especially useful, when working with oligozoospermic or oligospermaesthenic samples, in which the most motile sperm need to be isolated from a pool of small number of sperm (http://mit.edu/bammlabs/Lensless_Imaging.pdf).

There are also some new kit based methods developed to analyze male fertility at home. There is no need to count hundreds of sperm in these methods. They are user-friendly, quite affordable (between 40 and 100 dollars) and quick. One of the pioneers on the market is FertilMARQ Home Diagnostic Screening Test, which works by staining the cells in the sperm sample to produce a color. The intensity of this color is then compared to a color reference on the FertilMARQ test cassette providing results with an overall accuracy of 78 percent. Another popular home kit is Spermcheck fertility, known to be 97 percent accurate. This test is based on the detection of SP-10, a protein compound found on the surface of the head of a sperm cell and which concentrations are directly related to the sperm count number (http://howto.wired.com/wiki/Check_a_Man’s_Sperm_Count).

Techniques such as Vasectomy Reversal and Tubal Ligation Reversal, In vitro fertilization (IVF), Intra-cytoplasmic sperm injection (ICSI) have also improved with respect to the instrumentation used. Dr. Sherman J. Silber, M.D. and his Japanese collaborators have recently developed a new “mini-IVF” technique that saves money, eliminates complications of IVF, and is useful for older women and women with low ovarian reserve. (http://www.infertile.com/).

The pioneer company in making the most sophisticated and most popular sperm analysis instrument is Hamilton Thorne (http://www.hamiltonthorne.com/products/casa/systems-index.htm) and their website may be reviewed for more knowledge on modern sperm analysis.

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