Abstract
Study question
What is the cause of semen quality impairment in oncological patients during fertility preservation programs? The cancer type and stadiation or the resulting inflammatory state?
Summary answer
The inflammatory state seems to be related to the decrease of sperm concentration, motility, morphology and viability due to the worsening of oxidative stress microenvironment.
What is known already
Fertility preservation acquired a great importance in the last decades due to increase survival of oncological patients, boost of diagnosis under 40 years and postponement of paternal age. At the time of cryopreservation, only one third of these males are normozoospermic. Tumor itself or other factors, added to psychological reasons, may be involved but there is no clear evidence. An imbalance of ROS (reactive oxygen species) in semen can compromise its quality. However, the correlation between cancer-related generalized stress state and fertility is poorly investigated. Inflammatory conditions induced by infections and pathologies, including cancer, increase ROS.
Study design, size, duration
Retrospective observational analysis was performed on 45 patients (29.0 ± 6.9 yrs) recruited during their fertility preservation program between 2016 and 2019 with written consent on use of their clinical data for research purpose. Patients presented several oncological diagnoses. Semen samples obtained from multiple collections (N = 58) were analyzed before applying standard freezing protocol. Data on semen parameters, inflammatory indices, hematological values and type/stage of tumors were collected. No exclusion criteria were applied.
Participants/materials, setting, methods
Routine semen analysis was performed according to the WHO standards. Sperm concentration and motility were evaluated on Makler Chamber, whereas eosin stain and Diff-quick slides were used for viability and morphology, respectively. Lymphoma was present in 72% of cases, leukemia in 8%, seminoma in 7% and other cancers in 13%. Correlations (Pearson/Spearman tests) among principal semen parameters and hematological values (leukocytes, erythrocytes, hemoglobin, RDW, albumin, etc.) were calculated with a P-value <0.05 considered statistically significant.
Main results and the role of chance
The majority of semen samples showed a severe impairment, with one or more parameters under lower reference limits (WHO): 48.3% had sperm concentration under 15 millions/ml, 43.1% had a progressive motility under 32%, 41.4% had viability under 58% and 91.4% had abnormal morphology (under 4%). The role of potential inflammatory state was analyzed by correlating semen parameters and some hematological values. No correlation was found with cancer type. Negative association resulted between progressive motility (%PR) and leukocytes (p = 0.041) or RDW% (p = 0.015), but positive one with albumin (p = 0.012). Even sperm count, total motility (%PR+NP) and morphology were significantly correlated to RDW% (p = 0.003, p = 0.032, p = 0.034, respectively). These findings suggest a possible role of inflammation and ROS related generation in semen quality impairment. Indeed, albumin exerts a protective action, but leukocytes are known to cause ROS increase. Cancer-induced oxidative stress state may alter red blood cells homeostasis and vitality and increase erythrocytes turnover resulting in high RDW values. It is likely semen is worse when blood values indicate more severe cancer-induced inflammatory condition.
Limitations, reasons for caution
Significant correlations with type/stage of cancer were not found due to small number of each diagnosis, in spite our study considered 3 years of patients inclusion. Moreover, we lack to analyze the same patient before the cancer onset to avoid the influence of inflammatory state generated by the tumor itself.
Wider implications of the findings: Understanding the influence of cancer-induced inflammatory state on semen quality could increase the awareness that clinicians should direct patient to the fertility preservation as soon as possible, even if diagnosis is still ongoing. It should be evaluated whether offering specific treatments may reduce oxidative stress conditions.
Trial registration number
Not applicable
Fertility Preservation in Childhood Cancer: Endocrine Activity in Prepubertal Human Testis Xenografts Exposed to a Pubertal Hormone Environment