Addressing The Male Infertility Crisis: Fertility Expert Mats Holmberg Unveils Latest Advancements in Male Infertility – From Clinical Trials To Research and Reasoning

In an interview with Mats Holmberg, a fertility expert, the significance of male infertility in today’s context is highlighted. Male infertility contributes significantly to overall infertility rates globally, with notable declines in sperm count and quality over the past four decades. Despite its prevalence, societal stigmas often discourage men from seeking help or undergoing fertility testing, exacerbating the psychological challenges associated with infertility. Mats Holmberg is the lead of the ADAM study in Sweden, which aims to evaluate an investigational treatment for idiopathic male infertility, shifting the focus towards men and addressing the gap in treatment options. By encouraging open communication, participation in clinical trials, and collaboration with research institutes across Europe, the trial seeks to normalize the conversation around male infertility, break stigmas, and advance treatments to tackle this growing problem.

1. Could you elaborate on the significance of male infertility in today’s context, particularly its contribution to overall infertility rates and the challenges it poses to couples seeking to conceive naturally?

Male infertility has increasingly been recognised as a significant factor contributing to overall infertility rates, with rates of infertility being particularly high across Central/Eastern Europe.[i] Globally, over the past 40 years, there has been a 50% reduction in sperm count and a significant decline in sperm quality.[ii] The burden of male infertility also presents unique psychological challenges.[iii] Social and cultural stigmas can lead to a reluctance amongst men to seek help or undergo fertility testing, and infertility can significantly affect mental health, self-esteem, and relationships.ⁱⁱⁱ Additionally, when couples are trying to conceive, the source of the ‘issue’ is disproportionately placed on the female partner.[iv] This bias can lead to fertility tests being prioritised for women, while potential fertility issues in the male partner may be overlooked or considered later. We need to move away from this outdated attitude and make it standard practice that both partners in a relationship undergo fertility evaluation, fostering more inclusive diagnostic and treatment approaches to achieve natural conception sooner.

2. Can you provide an overview of the ADAM trial and its objectives in evaluating an investigational treatment for idiopathic male infertility?

The ADAM trial (Assessment of Follitropin Delta Efficacy and Safety for Treatment of Men with Idiopathic Infertility) is a randomised, double-blind, placebo-controlled trial investigating the therapeutic value of rFSH (recombinant Follicle Stimulating Hormone) in the treatment of infertile men with low sperm count. We are seeking male participants, aged 18-50, who have been trying to get pregnant with their female partners, aged 18-35, for at least 6-12 months without success.

3. The narrative surrounding fertility issues often leans towards women, yet male infertility is a significant factor. Can you discuss how this trial is shifting the focus towards men and the importance of addressing this gap in treatment options?

Our knowledge around male infertility is significantly increasing, and this is due to previous clinical and research data. However, more research and clinical trials around infertility, and male infertility, is necessary, as there is still so much more we need to learn about the condition and possible treatment options. The ADAM trial is essential for several reasons. Firstly, this international clinical trial places a spotlight on male reproductive health on a global scale, strengthening conversation around male infertility and empowering men to engage more openly with their fertility issues, seek diagnosis and treatment, and participate in discussions that were once predominantly female-oriented.

Secondly, male infertility trials are instrumental in advancing our understanding of the underlying causes of male reproductive issues. By focusing on specific aspects such as sperm quality, genetic factors, and the impact of lifestyle and environmental exposures, researchers can develop more effective and targeted treatments.

4. As the lead of the ADAM study in Sweden, what are your expectations for the future of male infertility treatments, and how do you envision the role of clinical trials in shaping this landscape?

My expectations for the future of male infertility treatments are both optimistic and grounded in the potential for innovative research and technological advancements. The landscape of male infertility treatment is on the cusp of significant evolution; driven by a combination of scientific breakthroughs, an increasing understanding of male reproductive biology, and a more holistic approach to patient care. Male infertility clinical trials are at the heart of this transformation and play a crucial role in shaping the future of treatments and therapeutic strategies. Studies have shown us that many male respondents felt like there was not enough help available to them, with infertility support being mostly directed at women.[v] We can develop our understanding about male fertility, the symptoms and possible causes, and address the unmet needs directly through patients. With this data and the rapid advancements in technologies, we hope that clinical trials may soon explore targeted therapies for patients with fertility issues.

I hope that in the near future, discussing male infertility openly and without shame becomes the norm. Open communication with HCPs (healthcare professionals) is key, and equally it is essential that HCPs are more proactive in informing patients about clinical trials to encourage participation from a diverse group of candidates. My ambition is that we will one day close the gap in treatment options and have a wide choice of robust and effective treatments for male infertility, but this must start with everyone being able to talk about their fertility issues.

5. How should men and couples struggling with male infertility address the issue, and how can they benefit from participating in clinical trials like the one being conducted by Ferring Pharmaceuticals?

Firstly, couples who are trying to conceive must talk to their healthcare provider and look at all the options available to them. Knowledge is empowering and it can allow the patient to make informed decisions about their care. Participating in clinical trials ultimately helps patients to understand their health on a deeper level, and delivers valuable data that can help advance the science and ultimately lead to improved treatments to treat or cure male infertility. Moreover, having those conversations openly and participating in clinical trials will ultimately help tackle stigmas, which will then lead to improved recruitment rates in the future. In the case of the ADAM study, we hope that it may lead to better education, and drive more research and development of male infertility treatments to support people trying to build a family through natural conception.

6. What led to the collaboration between Ferring Pharmaceuticals and these 10 research institutes in Europe for this multi-center infertility study?

This is a long sought after study that no single centre could possibly manage by themselves. When the opportunity to join was presented, we were therefore eager to be one of several international sites to collaborate.

7. Traditional societal norms and perceptions often discourage men from discussing fertility issues. How does the trial’s campaign aim to break this stigma and encourage men to seek treatment for their infertility concerns?

The ADAM clinical trial is designed to help educate and normalise the conversation around male infertility – where the male is unable to cause pregnancy in a fertile female primarily due to low sperm count and mobility – and reproductive health. By its very nature, the trial shifts the stigma that infertility is solely a woman’s issue by highlighting the reality that infertility affects men and women equally; with 30-50% of all infertility cases being male related.[vi]

By providing accessible information around male infertility and the avenues of addressing the unmet needs through research, we aim to demystify the subject and dismantle misconceptions, encouraging discussions around fertility and the fact that it is a shared responsibility between partners.

8. Given the significant decline in sperm counts and quality over the past decades, how crucial are studies focusing on male infertility in advancing treatments and addressing this growing problem?

The significant decline in sperm count and quality over recent decades presents a critical public health issue, with implications not only for fertility but also for broader aspects of male health. This trend, documented in numerous studies across various populations, underscores the urgency and need for research efforts on male infertility. Studies dedicated to understanding, preventing, and treating male infertility are crucial as we tackle this growing problem.

References:

[i] Agarwal A, Mulgund A, Hamada A, et al. A unique view on male infertility around the globe. Date of publication: 2015. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424520/pdf/12958_2015_Article_32.pdf

[ii] Ravitsky V, Kimmins S. The forgotten men: rising rates of male infertility urgently require new approaches for its prevention, diagnosis and treatment. Biol Reprod. 2019 Nov; 101(5): 872–874. doi: 10.1093/biolre/ioz161

[iii]Boivin J et al. Tailored support may be required to reduce the impact of the infertility journey on mental health, relationships and daily lives of infertile patients and partners to infertile patients. Reproductive Biomedicine online. Last accessed: April 2023. DOI: https://doi.org/10.1016/j.rbmo.2022.01.015

[iv] Taebi M, Kariman N, Montazeri A, et al. Infertility Stigma: A Qualitative Study on Feelings and Experiences of Infertile Women. 2021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233927/pdf/Int-J-Fertil-Steril-15-189.pdf

[v] Fertility Family. How common is male infertility? Date of publication: June, 2021. https://www.fertilityfamily.co.uk/blog/how-common-is-male-infertility-everything-you-need-to-know/

[vi] Leslie S, Soon-Sutton T, Khan M. Male Infertility. 2024. https://pubmed.ncbi.nlm.nih.gov/32965929/