Testicular function after non-cytotoxic and immunotherapy drug treatment.

BACKGROUND: The effects of novel non-cytotoxic and immunotherapy drugs for cancer treatment on human testicular function have not been studied systematically. OBJECTIVES: The present study aimed to characterize effects of non-cytotoxic and immunotherapy drugs in patients with cancers who had not been previously treated with gonadotoxic chemo- or radiotherapy. MATERIALS AND METHODS: This study involved 34 men, not previously treated with gonadotoxic regimens, in a mixed longitudinal (Cohort 1: 19 men about to start and approximately 1 year on non-cytotoxic and immunotherapy treatment) and cross-sectional (Cohort 2: 15 men already on non-cytotoxic and immunotherapy treatment) study using data modeling to estimate within-person time-course changes in testicular exocrine and endocrine functions. Cohort 1 provided 45 paired semen and blood samples (34 prior to and nine during treatment) and Cohort 2 provided 45 sets of samples (15 pre-treatment, 30 on treatment), including six men in Cohort 2 who had pre-treatment spermatozoa cryostorage prior to the study. Men on non-cytotoxic and immunotherapy treatment had undergone a median of 33.5 months long-term treatment. RESULTS: Spermatozoa output and concentration were reduced by about 50%, with corresponding increases in serum follicle-stimulating hormone and decreases in serum inhibin B. Serum testosterone, luteinizing hormone, and sex hormone-binding globulin were unaffected by non-cytotoxic and immunotherapy treatment. CONCLUSION: Within limits of the present study of sample size and duration of on-non-cytotoxic and immunotherapy treatment, non-cytotoxic and immunotherapy drugs have a modest effects on testicular exocrine function (sperm production) or its hormonal correlates (follicle-stimulating hormone, inhibin B), with minimal impact on testicular endocrine (testosterone, luteinizing hormone) function.

Oncofertility Information Available for Recently Approved Novel Non Cytotoxic and Immunotherapy Oncology Drugs.

We reviewed the available animal and human reproductive function studies of recently approved noncytotoxic oncology drugs. We reviewed the oncofertility information in the prescribing information for the US Food and Drug Administration (FDA)-approved products and/or the product information and consumer medicine information for Therapeutic Goods Administration (TGA)-approved drugs of 32 novel oncology drugs approved between 2014 and 2018 in the United States and/or Australia supplemented by a literature review for additional reproductive effects. No human studies were available on the reproductive effects of all 32 drugs. A systematic literature review of animal reproductive toxicity studies provided only very limited data with nine drugs displaying impaired male fertility, three impaired female fertility, and nine producing impaired fertility in both male and female animals. Two drugs in the study are reported to have no demonstrable impact on fertility in animal reproductive toxicity studies and nine are reported to have unknown effects on fertility. Of the 32 newly listed drugs, only 4 had recommendations regarding potential human fertility risks and accordingly advised clinicians about fertility preservation procedures for patients. The lack of human data and limited animal reproductive toxicity data raises concerns about the potential impact of these novel oncology drugs on human fertility and reproductive function. Consequently, adequate oncofertility recommendations, including for fertility preservation procedures, counselling for psychological or cost implications, and future prognosis for fertility are hindered by this paucity of relevant data. More data on human reproductive effects of novel oncology drugs is urgently required to facilitate effective use of the growing array of oncofertility care options available.

Fatherhood Following Treatment for Testicular Cancer: A Systematic Review and Meta-Analyses.

Purpose: Testicular cancer (TC) is considered the most commonly diagnosed malignancy in males between 15 and 34 years of age. The objective of this study is to systematically review and meta-analyze studies on fatherhood following treatment for TC. Methods: We reviewed studies reporting on fatherhood following TC from Medline and Embase search engines by developing search strategies. Only studies including patients with TC and at least one reproductive variable were considered as part of the analysis. Estimate of heterogeneity was calculated using the I2 statistic. Meta-analyses employing a fixed effects model were also applied as an additional measure of sensitivity. Results: A total of 27 studies were included which reported on fatherhood after treatment for TC. A meta-analysis of included studies with subgroup analysis was conducted. Subgroup analysis, for the combined studies, indicated an overall pooled pregnancy rate of 22% (95% confidence intervals [CI]: 0.21-0.23; I2 = 98.1%) for couples who conceived after TC. Of those couples that became pregnant, 11% (95% CI: 0.07-0.16; I2 = 8.5%) experienced a miscarriage. Fatherhood was experienced by 37% (95% CI: 0.35-0.39; I2 = 98.1%) of males following treatment for TC. Conclusions: Male cancer patients should be offered discussions, information, and counseling regarding the impact that TC treatment can have on fertility. Furthermore, sperm banking must be recommended to all patients before starting treatment.