MD Steven Mansell about semen analysis: This has always bothered me, as it implies that the diagnosis of male infertility is binary. Either there is an issue or there isn’t

wawa is speaking to MD Steven Mansell from Medicus about the way we do semen analysis today and what are we missing with the currunt method of semen analysis

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wawa

16. juli - 2022


Interview with Steven Mansell, Medicus

Please tell us a bit about your expertise?

I received my PhD in human reproduction from the University of Dundee school of Medicine in 2013 under the supervision of Professor Christopher Barratt. My project was aimed at assessing the electrical activity of individual human sperm from healthy donors and male patients attending the infertility clinic. The goal was to characterize how this electrical activity correlates with normal sperm function, as well as identifying how this differs in men with male infertility. Once these could be distinguished, I worked on finding compounds that both inhibit sperm function for male contraceptive purposes and enhanced sperm function for improving male fertility. After receiving my PhD, I was offered a Post-Doctoral fellowship position at the University of California Berkeley where I continued my research to better understand the inner workings of the human sperm cell and how these are altered in men with male factor infertility. I am currently the laboratory Manager for Medicus Oslo where I have over 6 years’ experience in the field of clinical embryology. However, it was only when I started practicing clinical embryology that I realized all my years of research did not actually prepare me for what I now experience on a daily basis. Furthermore, it became very apparent that the “treatment and diagnosis”, for men experiencing male infertility has not changed significantly in over 30 years. I am currently working on introducing better diagnostic tests for male infertility, educating doctors and embryologists on the importance of sperm quality when it comes to improving treatment outcomes, and trying to provide advice to men undergoing infertility treatment to take control of their fertility.

What do you think of the way we do semen analysis today?

A basic semen analysis is the cornerstone of the male infertility work up and forms the basis of treatment options in the clinics. For example, low sperm count and/or motility would indicate ICSI while normal semen parameter, IUI or IVF. It also provides some insight into a man’s risk of having issues fathering a child naturally. This has always bothered me, as it implies that the diagnosis of male infertility is binary. Either there is an issue or there isn’t. I have noticed that many men taking a semen analysis also have this impression. “So I’m fertile?”, is often the response I get. Unfortunately, the answer to that question is never that simple and I think men should keep that in mind. This is where we start distinguishing between sperm quantity vs sperm quality. If we break it down, in order for a sperm cell to successfully fertilized an egg and create a viable embryo it needs to overcome a large number of critical processes. Firstly, it needs to have the right motility and shape to transverse the female reproductive tract. This is where basic semen analysis comes into play. Next it needs to find the egg, attach to the outer layers of the egg, create a hole in the egg shell and alter its motility to have enough power to make its way through the shell. Once through the shell it still needs to successfully bind to the surface of the egg, be taken into the egg, activate the egg and successfully release its genetic material. Lastly the genetic material needs to be intact and capable to providing 50% of the genetic code for making a child. A semen analysis, as performed today, does not provide this information. What is apparent is that there are many pieces to the story we are missing, and these pieces provide inside into the sperm quality. This is also not a new concept, numerous studies have questioned the diagnostic and prognostic value of a semen analysis especially for couples under going fertility treatment 1–4. As support of this, roughly 30% of couples are diagnosed with idiopathic infertility. This means that based on our current standard tests no cause of infertility can be identified. Personally, this is the worst diagnosis any couple can receive as it basically means there is no reason they can not to have a child naturally, or we don´t know why you have abnormal semen parameters. In my experience these couples often have lower success rates when undergoing treatment, which I feel is because we haven’t identified a cause to formulate an effective treatment plan.

There are also many inconsistencies between clinics on how many times a man should produce a sample to have a proper representation of his semen parameters, as well the correct abstinence period between sample production. It is relatively common practice to only produce one sample after 2-7 days of abstinence. However, this can lead to inaccuracies in the result. A single sample is only a representation of sperm production during that round of spermatogenesis (the process of sperm production). A man’s sperm count can vary significantly from month to month which is well documented and even stated on page 9 of the world health organization (WHO) laboratory manual for the examination and processing of human semen 5. This section of the document shows the sperm concentration of five healthy men over the course of half a year. All five men showed variations in total sperm count and sperm concentration over the course of the study. With all five men fluctuating between normal and abnormal results. This means that based on when a man takes a semen analysis they could have a completely different result. I have even experienced this with men who I have examined. Some men even think that it was because the clinic must have made a mistake while carrying out the test.

Abstinence can also play a part in the result of a semen analysis. The WHO recommends 3-7 days of abstinence before taking the test. However, this is a broad range and the optimal abstinence period isn’t well documented. In short, for longer abstinence periods there is typically an increase in sperm count and a slight reduction in sperm motility. This might sound somewhat beneficial but longer periods of abstinence will result in a larger population of dead and dying sperm. Thereby potentially lowering the chance of successful pregnancy.

I think there are currently many flaws in how we do semen analysis today without even mentioning how embryologist and andrologists are trained to carry out the test6. However, it is still an important part of the diagnostic work up for men. What we as clinical workers should keep in mind is that it is not an accurate test and the results should not be interpreted as such. Instead the results from a semen analysis should be used as one piece of the puzzle in how to best identify, treat and provide advice for men seeking to have a child.

There is a big focus on morphology, motility and concentration. What are we missing here?

There is a multitude of parameters we are missing, but in my opinion the one parameter that shows the most promise is sperm DNA quality. Assessing the level of sperm DNA damage and its impact on male fertility is a concept that has been around for many years. Numerous studies have suggested a link between increased sperm DNA damage and adverse fertilization rates, embryo quality, pregnancy rates and miscarriage rates. Logically and scientifically this makes a lot of sense as the sperm contributes 50% of the genetic material to the development embryo and child. Therefore, if the sperm DNA is damaged this could impact how that embryo develops. However, the role of sperm DNA quality in male infertility has been controversial due to the variations in the assessment of sperm DNA quality and the usefulness of the test in how to treat these men. The reproductive community has taken a step closure to recognizing the role of sperm DNA damage testing for diagnostic purposes. In the latest addition of the WHO semen analysis manual the editors stated that sperm DNA damage testing, “could represent an important addition in the work-up of male infertility, becoming one of the most discussed and promising biomarkers in basic and clinical andrology”. In my daily practice I see the benefit of sperm DNA damaging testing, especially in couples with idiopathic infertility. In many cases the identification of sperm DNA damage as a cause of infertility provides an answer to many couples who have had many failed previous cycles. The good news this that in many cases sperm DNA damage is treatable and once treated this can improve the chances of success.

How do you see sperm as a good marker of overall health?

Basic semen analysis results as well as sperm DNA damage results are closely linked to a man’s overall health. For example, obesity, diabetes, excess alcohol consumption, smoking, stress, use of recreational drugs and poor diet all negatively impact sperm quality and quantity. There is also growing evidence that male fertility, overall health, prevalence of comorbidities, morbidity and mortality are interconnected7–11.  Although further research is required, assessing both sperm quality and quantity could provide an indication of a man’s overall health status, potential underlying conditions and risk of developing health issues in the future.

How can this help reduce the risk of male infertility?

This is all about educating young men about taking ownership of their fertility. There needs to be more openness around the topic of male reproductive health and highlighting how our lifestyle choices impacts our sperm. I personally think this should take place in high school as part of sex education or biology class. In high school the primary focus usually focuses on contraception as we all believed that if we had unprotected sex it would result in a child. Considering the estimated prevalence of infertility globally, roughly 13% of the men in the class will experience infertility issues with their partner in the future. In addition, roughly 50% of those men will either be the sole cause or contributing cause of the issue. By educating young men to take control of their fertility through their lifestyle choices, being more open about infertility, identifying changes in their body and providing sources for seeking help, this could potentially lead to a reduction in men having to undergo fertility treatment for preventable causes.

Anything else we are missing here?

Firstly, in an ideal world there would be a specialist male reproductive Urologist in every fertility clinic. What we are desperately missing are highly specialized male reproductive professionals to carry out necessary investigations and treatments for men attending the fertility clinic. The industry is dominated by gynecologists who are expertly trained in female reproductive medicine, however as a consequence the male partner has often been inadvertently neglected, boiled down to the results of whatever is produced in a collection cup. This is by no means pointing blame at gynecologists who do an amazing job every day by helping couples realize their dream of having a family. What I am highlighting is that we need to provide equally as much expert advice to both partners from specialists dealing with each side of the fertility story. Only by doing this can we offer men the same level of treatment and advice as their partner.

Secondly, there needs to be more discussion around male reproductive age and infertility. For a long time, it has been stated that men can continue having children as long as they can produce sperm. Well, yes, but there are studies showing that success rates from couples where the male is older are significantly lower compared to younger men.12,13 What is more worrying is that recent studies are identifying links between children born from older fathers and increased risk of psychological issues such as autism and schizophrenia and certain types of cancers14. Although more research is needed to confirm these links we should be keep in mind when carrying out infertility investigation in older men.

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