By Beatrice Acheson
Graphic design by Jeah Kim
Infertility, like many other reproductive health topics, tends to centre around female issues, but recent statistics compel us to think otherwise. Infertility affects around 15 to 20% of couples, and male factors account for nearly a third of these cases.1 Despite the prevalence of male infertility, it is often neglected, with most resources directed toward female treatments, leaving men underdiagnosed and undertreated. Dr. Keith Jarvi, a clinician scientist at Mount Sinai Hospital and professor at the Institute of Medical Science, has devoted his career to addressing this disparity by developing male-focused diagnostics and treatments while also uncovering how infertility may serve as an indicator of overall health.
Photo credit: Susan Lau
“There are a vast number of resources for women with infertility, and large numbers of clinics, but there are fewer doctors offering fertility care for men,” says Dr. Jarvi. “Care for infertility is skewed toward female treatments.” This skew has prompted the development of male-focused fertility programs. In collaboration with urologists Dr. Kirk Lo and Dr. Ethan Grober, Dr. Jarvi directs The Murray Koffler Urologic Wellness Centre. The centre, which operates between Mount Sinai and Women’s College Hospital in Toronto, provides nearly all services available for the diagnosis and treatment of male infertility.
Dr. Jarvi is not only working to improve access to care; he is transforming the way infertility is diagnosed and treated in male patients. He describes the current treatment landscape, explaining that there are two avenues available: “you can treat the men with infertility, or you can manage the couple’s infertility,” Dr. Jarvi says. Treatments, such as corrective surgeries or hormonal therapies, address the root cause of male infertility in hopes of improving sperm quality or other parameters. Management, in contrast, focuses on helping couples conceive through assisted reproductive technologies like in vitro fertilization and sperm banking.2
Choosing between “treating” or “managing” male infertility depends largely on its underlying cause, which is not always easy to identify. Male infertility may result from acquired factors, like testicular trauma, infection, and exposure to toxins; or, it may be attributable to congenital factors, including developmental alterations, genetic abnormalities, and hormonal imbalances.3 Adding to the complexity, acquired and congenital factors do not produce uniform changes across individuals, and may have variable effects on sperm parameters like motility, morphology, or number.4
Dr. Jarvi is working with this heterogeneity, rather than against it, to develop personalized treatment paradigms. Dr. Jarvi has identified testicular proteins in semen that may predict the underlying cause of male infertility, simplifying diagnoses and eliminating the need for invasive procedures like testicular biopsies.5 With collaborators at the Cleveland Clinic, Dr. Jarvi developed a model to predict changes in semen parameters following surgical repair of varicocele, an enlarged vein in the scrotum affecting sperm production.6 The tool is now widely used in clinics and helps determine which patients will benefit from surgical intervention, meaning fewer invasive procedures and more hopeful outcomes. Dr. Jarvi is committed to shifting the treatment and diagnostic landscape for male infertility toward personalized approaches.
Dr. Jarvi isn’t stopping there; he intends to build on his work with biomarkers and propel the field of male infertility into a new era of precision medicine. To do so, he is studying the genetic contributions underlying male infertility. Like many conditions, male infertility is attributable to both environmental and genetic factors. Further elucidating the genetic underpinnings of male infertility will provide opportunities for more precise diagnoses, personalized treatment options, and predictive medicine aiding in early intervention and preventive health planning.
Dr. Jarvi’s fascination with the genetic etiology of male infertility began over 20 years ago, when Dr. Lap-Chee Tsui, discoverer of the genetic defect that causes cystic fibrosis (CF), asked Dr. Jarvi to examine his patients for a missing vas deferens—the duct that transports sperm to the urethra. Its absence is an irreversible cause of male infertility. Dr. Jarvi agreed on the condition that Dr. Tsui also sequence the genes of his patients, suspecting his patients with no vas deferens may be carriers of the CF mutation. An unlikely collaboration was born. In 1998, they published an article demonstrating the association between CF mutations and the absence of the vas deferens. The findings transformed clinical practice and prompted increased genetic screening and counseling for men with infertility.7 For the first time, infertility was used as a window into broader implications for men’s health.
CF is not the only genetic condition related to male infertility. Dr. Jarvi and others have identified potential associations between male infertility and other common men’s health problems, including prostate cancer, colon cancer, and melanomas.8-10 In his latest project, Dr. Jarvi is collaborating with geneticists Dr. Steve Scherer and Dr. Christian Marshall to uncover the genetic link underlying these associations. By integrating seminal biomarker data with genetic analysis, Dr. Jarvi hopes to identify predictors of infertility and related hereditary conditions, like cancer.
According to Dr. Jarvi, “examining genetic predisposition is probably the best shot we have at understanding the long-term risks of infertility… [and] the other health risks that men with infertility or their children may experience.” Dr. Jarvi is harnessing his own expertise and the expertise of his collaborators to promote a more comprehensive approach to treating male infertility and the diseases that often arise with it.
The benefits of understanding the genetic link between male infertility and other conditions are two-fold. First, the knowledge will enhance our current understanding of the pathways and mechanisms that underly male infertility, potentially unlocking novel pharmacological strategies for treatment and management. Second, it will provide crucial insight that may reshape the current standard of care for male infertility and related health issues. Through decoding the relationships between male infertility and other hereditary conditions, Dr. Jarvi is laying the groundwork for precision medicine that extends beyond reproduction. To do so, he is leveraging his expertise and capitalizing on his propensity for collaboration, thereby ushering in a more informed and holistic approach to treating male infertility and related conditions.
References:
1. Witherspoon L, Flannigan R. Male factor infertility: Initial workup and diagnosis in primary care. Can Fam Physician. 2021;67(4):248–54.
2. Agarwal A, Baskaran S, Parekh N, et al. Male infertility. The Lancet. 2021;397(10271):319–33.
3. Brannigan RE, Hermanson L, Kaczmarek J, Kim SK, Kirkby E, Tanrikut C. Updates to Male Infertility: AUA/ASRM Guideline (2024). J Urol. 2024 Dec;212(6):789–99.
4. Eisenberg ML, Esteves SC, Lamb DJ, et al. Male infertility. Nat Rev Dis Primer. 2023;9(1):1–22.
5. Drabovich AP, Jarvi K, Diamandis EP. Verification of male infertility biomarkers in seminal plasma by multiplex selected reaction monitoring assay. Mol Cell Proteomics MCP. 2011;10(12):M110.004127.
6. Samplaski MK, Yu C, Kattan MW, et al. Nomograms for predicting changes in semen parameters in infertile men after varicocele repair. Fertil Steril. 2014;102(1):68–74.
7. Jarvi K, McCallum S, Zielenski J, Durie P, Tullis E, Wilchanski M, et al. Heterogeneity of reproductive tract abnormalities in men with absence of the vas deferens: role of cystic fibrosis transmembrane conductance regulator gene mutations. Fertility and Sterility. 1998 Oct 1;70(4):724–8.
8. Eisenberg ML, Li S, Brooks JD, et al. Increased Risk of Cancer in Infertile Men: Analysis of U.S. Claims Data. J Urol. 2015;193(5):1596–601.
9. Walsh TJ, Croughan MS, Schembri M, et al. Increased Risk of Testicular Germ Cell Cancer Among Infertile Men. Arch Intern Med. 2009;169(4):351–6.
10. Walsh TJ, Schembri M, Turek PJ, et al. Increased risk of high-grade prostate cancer among infertile men. Cancer. 2010;116(9):2140–7.
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