Fertility concerns and fertility preservation in adolescent and adult men with cancer

<p dir="ltr">Long-term survival among young men with cancer have improved markedly in recent decades, shifting focus from life-saving treatments to long-term quality of life and reproductive health. Cancer treatments such as chemotherapy, radiotherapy, and surgery can impair spermatogenesis and fertility. Although sperm cryopreservation is the only established fertility preservation method for men, semen quality may be compromised already at diagnosis. Moreover, long-term reproductive outcomes and the psychosocial consequences of impaired fertility—such as distress and uncertainty about future parenthood—remain insufficiently understood. This thesis aimed to investigate biological and psychosocial aspects of fertility in men diagnosed with cancer, with a particular focus on patients with testicular cancer, the most common malignancy in young adult males.</p><p dir="ltr">In <b>Study I</b>, 182 men with clinical stage I testicular cancer, recruited from two Swedish oncology centers between 2001 and 2006, were prospectively followed for five years to assess sperm quality after adjuvant treatment. Semen samples were collected at baseline (post-orchiectomy but before adjuvant therapy) and at 6, 12, 24, 36, and 60 months. The adjuvant treatments included radiotherapy (25.2 Gy in 14 fractions), chemotherapy with one cycle of bleomycin, etoposide, cisplatin or one cycle of carboplatin (AUC 7). One group was managed with surveillance (i.e. no adjuvant treatment). The study found no long-term effect in sperm concentration or total sperm count between men receiving adjuvant treatment and those managed with surveillance.</p><p dir="ltr"><b>Study II</b> was an observational cohort study including 1,252 post pubertal males with either malignant or severe non-malignant diseases requiring gonadotoxic treatment, referred for sperm cryopreservation at the Reproductive Medicine Clinic, Karolinska University Hospital, between 2009 and 2020. The study compared semen parameters prior to treatment between men with malignant diagnoses and those with non-malignant conditions and comparisons were made to a reference group of known fertile men. Results showed that men with malignancies had significantly lower sperm concentration, motility, and total sperm count at referral compared to patients in the reference group. However, the men in the severe non-malignant group also had lower sperm quality than the reference group, highlighting the vulnerability of fertility potential even before treatment initiation in both groups.</p><p dir="ltr"><b>Study III</b> was a cohort study of 1,378 adolescents and young adults diagnosed with cancer referred for sperm cryopreservation to the Reproductive Medicine Centre, Karolinska University Hospital, between 1988 and 2020. Clinical data from the fertility preservation program were linked to Swedish population-based registers to evaluate long-term reproductive outcomes. The study found that a substantial proportion of men became fathers, predominantly through natural conception. For those who did not achieve pregnancy naturally, assisted reproductive technologies proved successful.</p><p dir="ltr">In <b>Study IV</b>, 193 men aged 18-39 years with testicular cancer, diagnosed between 2016 and 2017 and included in the Swedish Fertility and Sexuality Following Cancer (Fex-Can) Cohort, were investigated regarding fertility-related distress in relation to treatment intensity. Fertility-related distress was assessed using the Reproductive Concerns After Cancer (RCAC) scale at 1.5, 3, and 5 years post-diagnosis. While most men reported low levels of distress over time, a notable minority—particularly those who received more intensive treatment—experienced persistent or fluctuating distress, especially regarding the health of potential offspring. These findings highlight the need for ongoing psychosocial support for this group of survivors.</p><p dir="ltr">Together, these studies provide a comprehensive perspective on both biological and psychosocial aspects of fertility in young male cancer patients and survivors. They emphasize the importance of early fertility preservation information, and the provision of long-term psychosocial support tailored to individual needs.</p><h3>List of scientific papers</h3><p dir="ltr">I. <b>Weibring K,</b> Nord C, Ståhl O, Eberhard J, Sandberg K, Johansson H, Arver S, Giwercman A, Cohn-Cedermark G. Sperm count in Swedish clinical stage I testicular cancer patients following adjuvant treatment. Ann Oncol. 2019;30(4):604-611. <a href="https://doi.org/10.1093/annonc/mdz017" target="_blank">https://doi.org/10.1093/annonc/mdz017</a>. PMID: 30798330.</p><p dir="ltr">II. <b>Weibring K,</b> Lundberg FE, Cohn-Cedermark G, Rodriguez-Wallberg KA. Sperm quality in 1252 Adolescents and Young Adults (AYAs) Undergoing Fertility Preservation Due to Cancer or Non-malignant Diseases. J Adolesc Young Adult Oncol. 2024. <a href="https://doi.org/10.1089/jayao.2024.0068" target="_blank">https://doi.org/10.1089/jayao.2024.0068</a>. PMID: 39069896.</p><p dir="ltr">III. <b>Weibring K,</b> Lundberg FE, Cohn-Cedermark G, Rodriguez-Wallberg KA. Parenthood in a Swedish prospective cohort of 1,378 adolescents and young adults banking semen for fertility preservation at time of cancer diagnosis. Front Endocrinol. 2024; 15:1502479. <a href="https://doi.org/10.3389/fendo.2024.1502479" target="_blank">https://doi.org/10.3389/fendo.2024.1502479</a>. PMID: 39720258.</p><p dir="ltr">IV. <b>Weibring K,</b> Rodriguez-Wallberg KA, Ullemar V, Ståhl O, Wettergren L, Lampic C. Long-term impact of treatment intensity on fertility-related distress in young survivors of testicular cancer - A population-based longitudinal study. Manuscript - under review. [Submitted]</p>