Assessing Male Infertility to Help the Childless Conceive

Assessing Male Infertility to Help the Childless Conceive

Probing the enigma of male infertility, Prof. Haim Breitbart is developing a test kit that will identify cases where it is possible to prod nature along its course and minimize costly artificial intervention.


Translated and adapted from the Hebrew article by Avi Blizovsky, published in Galileo, Vol. 134


Approximately 15% of all couples in western countries suffer from fertility problems. Pollution, drugs, chemical food preservatives, radiation therapy, and, of course, the trend to delay parenthood – all these are common causes cited in contemporary medical literature. And yet, there are many cases of infertility which elude explanation.


Among 50% of barren couples, men are the source of the infertility," notes BIU life scientist, Prof. Haim Breitbart, who has studied male fertility for three decades. In June 2009, he and Prof. Arie Raziel of Assaf Harofe Medical Center presented their findings at the European Society of Human Reproduction and Embryology (ESHRE) in the Netherlands, considered to be one of the most prestigious international conferences on the subject.


In couples where infertile males suffer from known conditions such as low sperm count, treatment may be in the form of expensive intra-cytoplasm sperm injection (ICSI), which entails injecting a solitary sperm cell into an egg. Another widely used method is in vitro fertilization (IVF), which works conversely: one egg is incubated with many sperm cells, allowing the most viable sperm cell to penetrate the egg on its own. In ICSI, the physician selects what he believes to be the best sperm cell and injects it directly into the egg. In other words, with ICSI, nature’s contest is bypassed: A sperm does not penetrate the egg independently, so it’s not certain that the best sperm cell has indeed been chosen.


Moreover, in approximately 15% of male infertility cases, the source of the problem is unknown, so these methods provide a potential solution without addressing the root cause. "In my opinion, it is desirable to intervene as little as possible,” says Prof. Breitbart. “Therefore, the IVF system, in which sperm and eggs are combined in a test tube and allowed to proceed naturally, is preferable. However, in many cases physicians prefer to use ICSI, because fertilization is accomplished through the mechanical penetration of a single sperm cell into an egg.”


Ideally, physicians would be required to treat infertility by trial and error, meaning first attempting IVF, and if that process proved unsuccessful, only then proceeding to ICSI. However, according to Breitbart, some laboratories perform 95% of artificial insemination procedures using ICSI.


In response, Breitbart and his team have been working on ways to identify which cases are most likely to succeed with IVF, so that ICSI won’t always be used by default. Their research focuses on a process known as capacitation, which has been identified as a weak point in reproduction. Despite what animated films showed us in high school biology, a sperm cell that enters the female system is not able to fertilize an egg immediately.


Although it does reach its target quickly, it takes three hours for a sperm to connect to, penetrate, and fertilize an egg. During these three hours, the sperm undergoes the biochemical changes of capacitation. Professor Breitbart speculates that in some cases of unexplained infertility, the cause may be the result of a malfunction during these changes.


Professor Breitbart has identified two elements of this process that can be tested to assess the sperm’s capacitation abilities. The first element is actin polymerization. During capacitation, monomers of the protein actin bind together to form polymers and after binding to the egg these polymers are broken down and the "acrosome reaction" occurs. This reaction allows the sperm to penetrate into the egg. But if the acrosome reaction happens before the sperm cell touches the egg, the sperm can’t fertilize the egg. Secondly, the development of sperm cell’s circular or “hyperactive” movement, which helps sperm progress through the fallopian tubes toward the egg, can be measured.


In the lab, Breitbart’s team tested several dozen cases for the correlation between a sperm cell’s ability to manufacture actin filaments, the development of hyperactive motion and the ability of cells to undergo the acrosome reaction (the three biochemical-morphological stages of the capacitation process), in addition to the ability to fertilize an egg with IVF. “We discovered a connection between IVF failure and lower levels of manufactured of actin filaments, along with a decreased ability to develop hyperactive motion,” Professor Breitbart notes.


“These two parameters make the success of the IVF process nearly 100% predictable. If the process predicts a less than 30% chance of success, it is then worthwhile to choose ICSI. If the results are better, meaning the chances are greater than 30% that the eggs will be fertilized, it is beneficial to try the IVF process first.”


A Male Fertility Test Kit

Bar-Ilan University, in cooperation with an investor, is establishing a company that will continue developing this diagnostic method, and eventually convert it into a kit that will be available in the future to fertility clinics around the world. Initially, the kit will be intended exclusively for use in hospitals or private clinics. The kit will include all the requisite chemical components and instructions, so that any laboratory will be able to use the test with relative ease and without highly skilled personnel. “After the system becomes routine in fertility laboratories, we will develop a kit for home testing,” relays Professor Breitbart. “The method we have developed works excellently in a research laboratory, but in order to be accepted in hospital laboratories and clinics, it must be easy and accessible. Once we have completed the kit, and hospitals understand its importance, we will then see its wide distribution.”

And why isn’t capacitation ability being tested today? “The prevailing attitude of most laboratories is that since ICSI is available, there is no need to check the capacitation process since it is possible to implant the sperm directly into the egg,” says Professor Breitbart. “However, this excludes the many cases in which it would be possible to bypass complex and expensive procedures.”


Not Just Diagnosis – but Treatment Too

The knowledge and findings compiled by Professor Breitbart’s laboratory is not just limited to diagnosis. “Following our biochemical work, we were able to understand, to some extent, the process of manufacturing actin filaments and we are now offering a treatment solution to those men whose sperm cells are unable to manufacture actin filaments.


The intention is to achieve a situation in which men with this condition will provide sperm samples to undergo treatment that imitates the natural capacitation process. The treated sperm will then be injected directly into the partner's womb, or used for IVF if artificial insemination is unsuccessful. This will also reduce the need to remove eggs from a woman’s body, a process that is very complicated, dangerous and difficult for the woman. Obviously, it also bypasses the need to implant embryos, a process which only has a 15-20% success rate.”


By focusing on causation and treatment, Professor Breitbart and his team hope their work will bear fruit, resulting in more effective solutions that are also financially accessible for couples facing the heartbreaking consequences of infertility.


Last modified: 05/07/2010








                Prof. Haim Breitbart

The ICSI System makes it possible to
inject a sperm cell directly into the egg.
Photo courtesy of Prof. Haim Breitbart.