Dr. Schlegel reports updates on male infertility clinical guideline

Peter N. Schlegel, MD, FACS

The American Urological Association (AUA) and the American Society for Reproductive Medicine (ASRM) created an official guide for the diagnosis and treatment of infertility in men so that urologists can have a uniform approach to evaluating and managing male infertility.

Senior author Peter N. Schlegel, MD, FACS, recently presented updates to this guideline at the 2021 American Urological Association Annual Meeting.^1,2 Schlegel is a professor of urology and reproductive medicine at Weill Cornell Medicine, New York, New York.

Please provide some background on the importance of having a male infertility clinical guideline for urologists.

Management of male infertility has changed substantially over the last 10 or 20 years. It’s actually been 20 years since a joint guideline between the ASRM and the AUA has been put together. Some updates have occurred in the meantime, but it was clearly time to relook at the data and come up with new information, particularly information as it relates to the health consequences of a man having fertility problems as well as the management of men who are being treated for cancer. And similarly, we have more information about treating some of the most severe cases of male infertility, specifically men with non-obstructive azoospermia.

Please briefly describe how the guideline was created.

The guideline is very evidence based. It follows the PICO format, which is to look at questions involving a patient, intervention, comparator, and outcome. Essentially, it looks at an entire series of clinical questions for patient evaluation and management. That is the framework for the ECRI team to search published data behind to determine the value of an intervention and what the level of evidence is behind it. It was supported by the two ECRI investigators, as well as members from the ASRM and members from the AUA, having both a female infertility and male infertility perspective as well as the patient perspective, a unique component of this guideline.

What are some key takeaways from the guideline for the practicing urologist?

There are over 52 guidleine statements, so I won't go over very many of them, but part of the guideline restated and validated the idea that evaluation of the male should be done in parallel with evaluation of the female. It also looked at varicoceles in men with infertility and confirmed that varicocele repair has substantial benefits for these men, both in terms of improving sperm numbers, but far more importantly, in terms of initiating pregnancies. It also looked at the right varicocele. Many of us were trained to believe that if you have a right varicocele, you should have imaging of the abdomen, such as CAT scan or ultrasound. The data that now exist does not support it. Unless there is a fixed large or new right varicocele, abdominal imaging is not required just because of the presence of a right varicocele.

It also looked at some of the limitations we have in our evidence in terms of correcting lifestyle issues, using empiric medical therapy, and adjunctive treatments for non-obstructive azoospermia such as medical therapy or varicocele repair.In these settings, we just don't have enough data—particularly controlled trials—to indicate whether adjunctive treatments help in treatment of these men.

One of the quirks of this guideline in the way that evidence is put together.For example, the statistical analysis for empiric medical therapy such as clomiphene, or injectable FSH in idiopathic infertility, indicates benefits of treatment. But it's also important to remember that the magnitude of that benefit is extremely small. So, for example, you might take a pregnancy rate of 9% and increase it up to 18% with clomiphene. Similarly, with FSH, you may take a natural pregnancy rate of 1% in controls and increase it to 10%. But obviously, those benefits are extremely small, so even though "evidence" statistically supports the treatment, the magnitude of benefit really has to be considered together with the other options, such as management with assisted reproduction for clinical relevance of these data.We have included such discussion in the guidelines.

In the area of management of men who have cancer, important concepts like sperm banking prior to treatment, which could be gonadotoxic or affect sperm transport, is important. Similarly, how we evaluate those men, meaning after gonadotoxic chemotherapy when you reevaluate them, is also important. At least 1 year, preferably at 2 years after treatment is when you should consider getting a semen analysis. And further, the guidelines provide guidance, even though the data is not perfect, to indicate that couples should not try to conceive within the year after a man received gonadotoxic chemotherapy because of the increased risk of sperm chromosome abnormalities and/or birth defects in offspring. These are key points and takeaways that now we have available as part of a guideline, as well as dozens of other points that I would encourage everybody to read in this 2-part guideline that was published.

Is there anything else you feel our audience should know about the guideline?

The guidelines are published in both Fertility and Sterility, as well as the Journal of Urology. They're freely available on the AUA website. I think it's important to remember that some of these data are evolving. We know, for example, issues that affect lifestyle and how male factors, including male obesity and lifestyle issues can affect the outcomes of in vitro fertilization. But these data are developing rapidly, and awareness of where we stand right now is provided by the guidelines as well as the potential that ongoing future evolution of our knowledge will be important for the practicing urologist.

References

1. Schlegel PN, Sigman M, Collura B. Diagnosis and treatment of infertility in men: AUA/ASRM Guideline Part I. J Urol. 2021;205(1):36-43. doi:10.1097/JU.0000000000001521

2. Schlegel PN, Sigman M, Collura B. Diagnosis and treatment of infertility in men: AUA/ASRM Guideline PART II. J Urol. 2021;205(1):44-51. doi:10.1097/JU.0000000000001520