In the article, “Phthalates In Males Reduce Blastocyst Quality,” that I posted in January of this year, I was so excited to be reporting on some infertility research that was focused on the male factor. After all, as far as I know, anyone trying to conceive is going to need at least one good sperm at some point! 😉
In that article, I described some frustrations I have had over the years feeling like we all focus too much on the female factor in the world of infertility care, forgetting that it is statistically just as likely that a delay in conception or difficulty in staying pregnant is related to a male factor. This fact is one I have tried to help seep into the consciousness of my patients in the clinic as well as through this blog. A fact that has been harder to communicate, but no less true is this: a “good” or “normal” semen analysis does NOT mean there is not a male factor at the root or a contributing force to a couple’s difficulty becoming or staying pregnant.
While at the Integrative Fertility Symposium this year, I was really excited to learn about the advances being made in the study of male factor fertility and even more excited to learn that this new research has resulted in a lab test that may help couples understand if a male factor, even in men with normal semen parameters may be what is slowing them down from starting or expanding their families. (It is even available in the Twin Cities, I just checked!) These test results may help couples decide what assistive reproductive technologies they are more likely to have success with. And, I will admit, even with all of my frustrations regarding what I consider to be an over-emphasis on female factor, listening to this presentation caused me to have a big aha moment. It clicked for me that one of the implications of this research is for couples who have exhausted all options using their own gametes with many tries at IVF. At this point, we shouldn’t necessarily be jumping to donor egg without also considering donor sperm, another potential use for this testing. Moving on to donor options is a big decision whether it is sperm or egg, but to have some information in regards to which is more likely to result in success is hugely valuable, and something we need to be pressing our RE’s to discuss with us.
Now for a little more on the research, which was presented by Alan Horsager, Ph.D in neuroscience. Dr. Horsager was involved in the research and development of this new male factor test. The scientists including Dr. Horsager set out to determine if they could predict male infertility or poor embryo quality by looking for abnormal DNA methylation in male sperm, which is another way of saying they were looking to assess the role of epigenetics in male factor fertility. Epigenetics is the study of chemical reactions that influence gene expression, by activating or deactivating them. These changes are normal and natural, but they may also be influenced by our environment and our lifestyles. These changes may lead to adverse effects that can cause diseases. Epigenetic changes have been linked to diseases such as cancer and cardiovascular disease, and more recently infertility and embryo development.
This knowledge has been around for around 15 years, but Dr. Horsager and his team were looking to see if they could use it to help patients better understand the cause of their infertility and what to do about it.
One process known to begin and sustain epigenetic modification is DNA methylation. The researchers set out to answer 2 questions: could they discriminate between a fertile male and an infertile male and could they predict the production of a good quality or poor quality embryo based on the DNA profile of the sperm, specifically by looking for abnormal methylation occurring in the sperm. After testing the samples of 127 infertile men undergoing IVF compared to 36 fertile men, they came to the conclusion that yes, you can discriminate between fertile and infertile as well as predict which men would produce good quality or poor quality sperm by looking at which genes in the sperm were showing abnormal methylation.
The lab test for male fertility that was developed after this “proof of concept” study was completed looks at specific genes with known roles in fertility. For example, if abnormal methylation is found at gene ID3, the couple faces a 47% increased risk for producing poor quality embryos. Other examples include genes involved in the sperm’s ability to find the egg or to penetrate an egg. This type of information could be hugely helpful to a couple deciding between pooling their resources for a few rounds of IUI or going straight to IVF. This type of information could be just as important as knowing if the female’s tubes are open or not, as in, can things get to where they need to go. And again this type of information is NOT found in a traditional semen analysis, and having a normal semen analysis does NOT take you off the hook.
Beyond the availability of this testing, which I am obviously pretty excited about, is that we have reason to believe, just as we do in the issue of phthalates affecting embryo development, that a lot of these epigenetic changes can be reversed, and maybe even pretty quickly. As mentioned above, epigenetic changes as a result of abnormal methylation are influenced by your environment and lifestyle. Losing weight, quitting smoking, cutting out alcohol, eating clean whole foods, and taking some antioxidants may be enough to reverse whatever abnormalities exist in your individual genes.