Abstract
Purpose:
This study aimed to characterize associations between male childhood cancer survivors’ perception of infertility risk and objective fertility status, and to identify factors contributing to risk perception.
Methods:
Participants were from SJLIFE, exposed to alkylating agents but not radiation, completed a Men’s Health Questionnaire (MHQ) and semen analysis. Samples were obtained following the 2010 World Health Organization Guidelines, and classified as azoospermic (0 sperm), oligospermic (> 0 and < 15 million sperm/ml), or normospermic (≥ 15 million sperm/ml). Participants were classified as at minimally or high/significantly increased risk for infertility according to the Pediatric Initiative Network (PIN) criteria. Perception of infertility risk was assessed via self-report where survivors indicated: 1) more risk than peers without cancer history, 2) less risk, or 3) equal risk, as well as factors contextualizing perceived risk. Chi-squared tests or Fishers’ exact tests assessed differences in variables of interest.
Results:
Among 238 participants (age 27±6 years, 85% NH White, 47% survivors of leukemia), 58% perceived increased infertility risk than peers without cancer history, 29% equal risk, and 13% less risk. A larger proportion of survivors with azoospermia perceived higher risk than other groups (74%) (p=0.01). No differences were observed in risk perception by PIN criteria. No differences were observed by sperm concentration category or PIN criteria in factors contextualizing perceived risk.
Conclusions:
Male survivors not exposed to radiation in the SJLIFE cohort are generally aware of their infertility risk.
Implications for Survivors:
Male survivors should seek continued follow-up care regarding fertility and information on risk from reputable sources.
Keywords: infertility risk perception, semen analysis, Pediatric Initiative Network (PIN) criteria, male childhood cancer survivors
Introduction
The number of 5-year survivors of childhood cancer (survivors) has increased in recent decades due to improved diagnostic and treatment modalities.[1] However, survivors face increased risk for adverse health outcomes compared to peers due in part to cancer and its treatment.[2–4] Among these adverse health outcomes is infertility, which is a primary concern to many survivors.[5] In the Childhood Cancer Survivor Study where self-report of partner pregnancies was used as a proxy for fertility, 46% of male survivors reported infertility[6], as well as decreased likelihood to sire a pregnancy compared to peers (hazard ratio, 0.56; 95% CI, 0.49–0.63)[7]. In a previous report from the St. Jude Lifetime (SJLIFE) Cohort that employed objective measures of fertility, 53% of males who received risk-based fertility screening did not have optimal sperm count in semen sample (n=214, median age 29.0 years (95% CI 18.4–56.1) at assessment, median of 21.0 years (10.5–41.6) since diagnosis, 25% azoo-, 28% oligo-, and 48% normo-spermic).[8] Studies have demonstrated that patients who underwent abdominopelvic surgery, radiation exposing gonadal tissue or the hypothalamus, and gonadotoxic chemotherapeutic agents (most commonly alkylating agents and heavy metals) have increased risk for infertility.[9, 10]
Guidelines have been created to assist practitioners in identifying survivors at increased infertility risk who may benefit from closer follow-up and intervention. These survivors could then be referred to reproductive specialists to address ongoing concerns about family planning. One guideline, established by The Pediatric Initiative Network, provides chemotherapy and radiation specific dose-related risk stratification for both male and female survivors[11], with specific exposures identified for each biological sex group. However, adherence to surveillance guidelines has been shown to be suboptimal in survivors as they transition into adulthood (>18 years)[12], even if engaged in interventions to improve patient adherence to surveillance.[13] Lack of adherence to screening guidelines for fertility risk may result from lack of awareness of exposures, exposure dose thresholds, and host factors that confer or increase magnitude of risk. Knowledge gaps may contribute to misperceptions about risk; for example, misperception of fertility could lead to suboptimal contraception use in males, and increased unplanned pregnancies. Conversely, misperception of fertility could also lead to lost opportunities to mitigate risk and optimize opportunities for family building.
Previous studies describing perception of infertility risk among male survivors demonstrate that while survivors are not accurate in their assessment of fertility risk related to treatment exposures[14–17], which could be due to a variety of factors (i.e., lack of knowledge and fertility education, etc.). Additionally, survivors endorse lack of recall of discussions throughout treatment and follow-up of reproductive health risks with health care providers or parents.[18, 19] These findings underscore the importance of counseling at diagnosis and during follow-up to assure that male survivors’ perceptions of infertility risk align with available evidence and realistic expectations of family planning as they age into adulthood. In addition, determining where and when survivors seek and find this information could be beneficial to development of relevant targets for risk information dissemination. Therefore, the purpose of this study is to 1) characterize the relationship between perception of infertility risk and objective fertility status, 2) characterize the relationship between perception of infertility risk and PIN criteria risk stratification, and 3) identify trends in factors contributing to risk perception development.
Methods
Participants
Participants in this study were selected from the larger St. Jude Lifetime (SJLIFE) cohort study, who are survivors at least 5 years from diagnosis of childhood cancer between 1962–2012 who were also treated at St. Jude.[20] For this cohort study, participants travel to St. Jude Children’s Research Hospital for comprehensive evaluations, which include survey data collection (on topics such as health history, sociodemographics, and psychosexual health), medical assessment, and neuromuscular assessment. This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of St. Jude Children’s Research Hospital (Institutional Review Board #00000029 FWA00004775). Males from this cohort who were exposed to alkylating agents but not radiation therapy, had provided a semen sample, and had completed the SJLIFE survey were eligible for this study. Those without complete treatment records or those who were treated with radiation therapy, who had received bilateral orchiectomy or vasectomy and were currently using androgen therapy (assessed via self-report) were excluded. Informed consent was obtained from all participants prior to participation.
Measures
Infertility Risk Perceptions
Risk for infertility was assessed via self-report as part of the larger SJLIFE study survey battery, which is completed before the larger study visit or upon arrival to campus. Participants were asked to indicate their perceived risk for infertility compared to peers who had never had cancer on a scale of 1 (much less) to 5 (much more), with 3 indicating neutral risk (about the same). Those who indicated values below 3 were classified as perceiving lower risk for infertility. Those who indicated 3 were classified as perceiving the same amount of risk for infertility. Those who indicated values above 3 were classified as perceiving higher risk for infertility.
Among those who indicated higher risk, further questions were asked to determine 1) which cancer-related factors participants believed influenced risk for infertility, 2) by what method (i.e., from a medical professional, an oncologist, family, or the internet) did they learn of increased risk for infertility, and 3) when they received information about increased risk of infertility if they did receive this information from a medical professional. For analysis purposes, responses to question one were categorized as either chemotherapy only or other cancer-related factors (i.e.- radiation, surgery, etc.). Responses to question two were categorized as from an oncologist and/or medical professional or any other source. Responses to question three were categorized as at time of diagnosis and treatment, after diagnosis and treatment, both at time of diagnosis and after diagnosis, and neither or at no time.
Sperm Concentration
Sperm concentration was used as the assessment of infertility risk. Semen analyses were offered to males in the SJLIFE determined to be at risk for poor fertility outcomes based on treatment exposures. Samples were collected as part of the comprehensive evaluation during the SJLIFE study visit, and were from the same visit as the completion of questions related to infertility risk perception. Samples were collected via masturbation in a private location at the fertility clinic after a planned minimum of two days and a maximum of seven days without ejaculation and were processed within 30 minutes of collection.[21] Specimens that were evaluated in raw form, found to be without sperm, centrifuged, concentrated, and again found to be without sperm were classified as azoospermic. Specimens that contained > 0 and < 15 million sperm/ml were classified as oligospermic and those with ≥ 15 million/ml were classified as normospermic. A repeat semen analysis was requested of men with abnormal semen parameters who had a history of fever over 102° F during the preceding three months, any hormonal medication use, or recent genitourinary tract infection or injury.
Pediatric Initiative Network (PIN) Risk Stratification
Based on cumulative exposures of potentially gonadotoxic agents, each participant was assigned a risk level for infertility according to the Pediatric Initiative Network (PIN) risk stratification.[11] Participants who had received <4 CED gm/m2 of alkylating agents, <=500 mg/m2 of cisplatin and/or carboplatin were classified as minimally increased risk. Participants who had received > 500 mg/m2 cisplatin and retroperitoneal lymph node dissection (RPLND) surgery were classified as significantly increased risk. Participants who had received >= 4 CED gm/m2 of alkylating agents were classified as high level of increased risk. While the PIN criteria also include radiation parameters, these participants were not exposed to radiation and therefore those criteria were not utilized for risk strata in these analyses. For analyses, significantly increased and high level of increased risk groups were combined due to a low number of participants meeting significantly increased criteria compared to minimally increased and high level of increased risk.
Partner Pregnancies
Partner pregnancy information was obtained via self-report as part of the larger SJLIFE battery. Participants were asked about pregnancy attempts and outcomes. Those who responded “no” to attempt of a pregnancy were classified as never trying to impregnate a partner. Those who responded “yes” to attempt of a pregnancy and reported “no” to achieving pregnancy were classified as attempting and not impregnating a partner. Those who responded “yes” to attempt of a pregnancy and reported “yes” to achieving pregnancy were classified as impregnating a partner. These categories were used in analyses. Use of assisted reproductive technologies was assessed but not included in these analyses due to a low number of those who reported use (n=5) as well as a low number of pregnancies sired from use (n=1).
Demographic and Clinical Characteristics
Demographic and clinical data were evaluated during the SJLIFE visit. Race and ethnicity were self-reported. Cancer diagnosis and treatment data were abstracted from medical records.
Analyses
Demographic and clinical characteristics of participants were summarized using descriptive statistics. Chi-squared or Fishers’ exact tests were used to describe differences in distributions among variables of interest. All analyses were conducted using SAS 9.4 (Statistical Analysis System (RRID:SCR_008567) ver. 9.4, Cary, NC).
Results
A total of 529 males from the SJLIFE cohort were identified as being exposed to alkylating agents but not radiation therapy and were offered a semen analysis. One-hundred and forty-seven of those males declined (~28%). An additional 144 did not complete survey questions pertaining to perceived risk. Among 238 participants in this study, median age at assessment was 26.2 (range 18.7–64.9) years. Participants were a median of 17.7 (range 7.2–47.8) years from diagnosis. Most participants identified as non-Hispanic White (84.9%). The most common primary cancer diagnosis was leukemia (47.1%), followed by lymphoma (21.4%), non-CNS solid tumor (14.3%), embryonal solid tumor (11.8%), and other malignancies (5.5%). Over half of the sample (66.8%) had not attempted to impregnate a partner at the time of assessment. (Table I)
Table I.
Demographic Characteristics (n=238)
| Characteristic | Med. (Range) | No. (%) |
|---|---|---|
| Age at assessment (years) | 26.2 (18.7–64.9) | |
| Age at diagnosis (years) | 7.6 (0–21.3) | |
| Time since diagnosis (years) | 17.7 (7.2–47.8) | |
| Race/Ethnicity | ||
| NH White | 202 (84.9) | |
| NH Black | 18 (7.6) | |
| Hispanic | 11 (4.6) | |
| NH Other | 7 (2.9) | |
| Primary Diagnosis Group | ||
| Leukemia | 112 (47.1) | |
| Lymphoma | 51 (21.4) | |
| Non-CNS solid tumor | 34 (14.3) | |
| Embryonal tumor | 28 (11.8) | |
| Other | 13 (5.5) | |
| Total chemotherapy dose (mg/m2) | ||
| Alkylating agents (cyclophosphamide equivalent dose, CED) | 5206.7 (12.1–55043.5) | |
| Antimetabolites | 413.0 (7.6–155829.8) | |
| Anthracyclines (doxorubicin isotoxic equivalents) | 121.7 (0–613.6) | |
| Anti-tumor antibiotics | 13.6 (2.8–113.6) | |
| Corticosteroids | 1119 (6.6–9880.4) | |
| Asparaginase | 123235.3 (4326.3–724101.56) | |
| Vinca Alkaloids | 37.2 (1.0–531.3) | |
| Epipodophyllotoxins | 5645.2 (149.1–19294.2) | |
| Educational Atttainment Level | ||
| High school graduate or less | 56 (23.5) | |
| Some post-high school training or some college | 87 (36.6) | |
| College graduate | 69 (29.0) | |
| Other/Unknown | 26 (10.9) | |
| Marital Status | ||
| Single/Never married | 118 (49.6) | |
| Married | 96 (40.3) | |
| Widowed/Divorced/Separated | 18 (7.6) | |
| Unknown/Missing | 6 (2.5) | |
| Partner Pregnancy History | ||
| Has attempted and impregnated a partner | 51 (22.5) | |
| Has attempted and not impregnated a partner | 24 (10.1) | |
| Has not attempted to impregnate a partner | 159 (66.8) | |
| Unknown/Missing | 4 (1.7) | |
| Infertility Risk Perception | ||
| Increased risk | 138 (57.9) | |
| Neutral risk | 68 (28.6) | |
| Less risk | 32 (13.5) | |
| Sperm Concentration Category | ||
| Azoospermic | 51 (21.4) | |
| Oligospermic | 61 (25.6) | |
| Normospermic | 126 (52.9) |
Over half of the survivors in this sample (57.9%) perceived themselves to be at increased risk while 13.5% perceived themslves at lower risk for infertility compared to peers who had not had cancer. A quarter of the sample (25.6%) were oligospermic while 21.4% were azoospermic. According to PIN criteria for risk stratification, 77.3% of the sample were at high or significantly increased risk for infertility. (Table I) In distributions of sperm concentration category by PIN criteria for risk stratification, a larger proportion of those who were normospermic fell into the minimally increased risk stratification than high and significantly increased risk stratification (77.8 vs. 45.7%, respectively). (Table II)
Table II.
Sperm Concentration Categorization by Pediatric Initiative Network (PIN) Risk Stratification (n=238)
| Pediatric Initiative Network (PIN) Risk Stratification | |||
|---|---|---|---|
| Sperm Concentration Category | High and Significantly Increased Risk No. (%) | Minimally Increased Risk No. (%) | P value |
|
| |||
| Azoospermic | 50 (27.2) | 1 (1.9) | <0.0001* |
| Oligospermic | 50 (27.2) | 11 (20.4) | |
| Normospermic | 84 (45.7) | 42 (77.8) | |
significant at alpha=0.05
Differences in distribution of risk perception by sperm concentration category were observed, such that a larger proportion of those who were azoo- (74.5%) or oligo- (60.7%) spermic endorsed increased perceived risk of infertility than those who were normospermic (50.0%) (p=0.0147). Among those who reported partner pregnancy history (n=238), those who were normospermic were more likely to have reported attempting and impregnating a partner (31.5%) compared to those who were azoo- (3.9%) and oligo- (16.9%) spermic (p=<0.0001). Similar trends were observed in those who endorsed increased perceived risk for infertility (n=135), with those who were normospermic being more likely to have reported attempting and impregnating a partner (29.5%) compared to those who were azoo- (5.3%) and oligo- (19.4%) spermic (p=0.0041). Among those who endorsed increased percieved risk (57.9%), no differences were observed in 1) source of information regarding increased risk of infertility, 2) cancer or treatment related reasons for perceived increased risk for infertility, or 3) timepoint at which infertility information was received by sperm concentration category. (Table III)
Table III.
Characteristics by Sperm Concentration Category (n=238)
| Characteristic (n) | Azoospermic No. (%) | Oligospermic No. (%) | Normospermic No. (%) | P value |
|---|---|---|---|---|
|
| ||||
| Infertility Risk Perception (n=238) | 0.0147* | |||
| Increased risk | 38 (74.5) | 37 (60.7) | 63 (50.0) | |
| Neutral risk | 7 (13.7) | 14(23.0) | 47 (37.3) | |
| Less risk | 6 (11.8) | 10 (16.4) | 16 (12.7) | |
| Partner Pregnancy History (n=234) | <0.0001* | |||
| Has attempted and impregnated a partner | 2 (3.9) | 10 (16.9) | 39 (31.5) | |
| Has attempted and not impregnated a partner | 12 (23.5) | 3 (5.1) | 9 (7.3) | |
| Has not attempted to impregnate a partner | 37 (72.5) | 46 (78.0) | 76 (61.3) | |
| Partner Pregnancy History in those with Increased | ||||
| Perceived Risk (n=138) | 0.0041* | |||
| Has attempted and impregnated a partner | 2 (5.3) | 7 (19.4) | 18 (29.5) | |
| Has attempted and not impregnated a partner | 10 (26.3) | 2 (5.6) | 5 (8.2) | |
| Has not attempted to impregnate a partner | 26 (68.4) | 27 (75.0) | 38 (62.3) | |
| Infertility Risk Information Source in those with | ||||
| Increased Perceived Risk (n=138) | 0.71 | |||
| Oncologist/medical professional | 28 (73.7) | 24 (64.9) | 44 (69.8) | |
| Other sources (family, internet) | 10 (26.3) | 13 (35.1) | 19 (30.2) | |
| Cancer or Treatment-Related Reasons for Increased | ||||
| Risk Perception in those with Increased Perceived | ||||
| Risk (n=138) | 0.91 | |||
| Any chemotherapy | 32 (84.2) | 30 (81.1) | 53 (84.1) | |
| Other cancer or treatment-related causes | 6 (15.8) | 7 (18.9) | 10 (15.9) | |
| Timepoint at Which Information Regarding Risk | ||||
| Was Related in those with Increased Perceived Risk | ||||
| (n=138) | 0.86 | |||
| At time of diagnosis and treatment | 7 (18.9) | 7 (20.0) | 15 (24.6) | |
| After diagnosis and treatment | 21 (56.8) | 21 (60.0) | 30 (49.2) | |
| Both at time of diagnosis and after | 5 (13.5) | 2 (5.7) | 6 (9.8) | |
| Neither timepoint | 4 (10.8) | 5 (14.3) | 10 (16.4) | |
significant at alpha=0.05
When observing differences in distributions by PIN risk strata, a greater proportion of those who were in the minimally increased risk strata had attempted and impregnated a partner (27.5%) than the high and significantly increased risk strata (20.2%) (p=0.0065). No differences were observed in any other measured characteristic. (Table IV)
Table IV.
Characteristics by Pediatric Initiative Network (PIN) Risk Stratification
| Characteristic (n) | High and Significantly Increased Risk No. (%) | Minimally Increased Risk No. (%) | P value |
|---|---|---|---|
|
| |||
| Infertility Risk Perception (n=238) | 0.31 | ||
| Increased risk | 111 (60.3) | 27 (50.0) | |
| Neutral risk | 51 (27.7) | 17 (31.5) | |
| Less risk | 22 (12.0) | 10 (18.5) | |
| Partner Pregnancy History (n=234) | 0.0065* | ||
| Has attempted and impregnated a partner | 37 (20.2) | 14 (27.5) | |
| Has attempted and not impregnated a partner | 24 (13.1) | 0 (0.0) | |
| Has not attempted to impregnate a partner | 122 (66.7) | 37 (72.5) | |
| Partner Pregnancy History in those with Increased | |||
| Perceived Risk (n=135) | 0.06 | ||
| Has attempted and impregnated a partner | 20 (18.0) | 7 (29.2) | |
| Has attempted and not impregnated a partner | 17 (15.3) | 0 (0.0) | |
| Has not attempted to impregnate a partner | 74 (66.7) | 17 (70.8) | |
| Infertility Risk Information Source in those with | |||
| Increased Perceived Risk (n=138) | 0.92 | ||
| Oncologist/medical professional | 77 (69.4) | 19 (70.4) | |
| Other sources (family, internet) | 34 (30.6) | 8 (29.6) | |
| Cancer or Treatment-Related Reasons for Increased | |||
| Risk Perception in those with Increased Perceived | |||
| Risk (n=138) | 0.29 | ||
| Any chemotherapy | 91 (82.0) | 24 (88.9) | |
| Other cancer or treatment-related causes | 20 (18.0) | 3 (11.1) | |
| Timepoint at Which Information Regarding Risk | |||
| Was Related in those with Increased Perceived Risk | |||
| (n=133) | 0.88 | ||
| At time of diagnosis and treatment | 23 (21.7) | 6 (22.2) | |
| After diagnosis and treatment | 58 (54.7) | 14 (51.9) | |
| Both at time of diagnosis and after | 11 (10.4) | 2 (7.4) | |
| Neither timepoint | 14 (13.2) | 5 (18.5) | |
significant at alpha=0.05
An analysis restricted to respondents younger than 25 years of age was performed to address any potential participation bias with respect to inferences made about fertility due to siring pregnancies. In distributions of sperm concentration category by PIN criteria for risk stratification, a larger proportion of those who were normospermic fell into the minimally increased risk stratification compared to the high and significantly increased risk stratification (70.4 vs. 44.9%, respectively) (Supplemental table I). These results also indicated no difference in perception of infertility risk by sperm concentration category as well as PIN risk stratification (Supplemental table II). Differences were observed in distributions of pregnancy history by both sperm concentration category as well as PIN Risk (Supplemental tables II–III). Differences were also observed in timepoint at which infertility information was received among those who endorsed increased perceived risk by PIN criteria, indicating that a larger proportion of those in the high and significantly increased risk strata received information after diagnosis and treatment only compared to the minimally increased risk strata (78.4 vs. 53.9%, respectively) (Supplemental table III).
Because SJLIFE visit components do not always occur in a regulated order (i.e., surveys could be completed before or after being on campus for comprehensive evaluation), a sensitivity analysis was conducted to determine any effect of previous knowledge (i.e., receiving semen analysis results prior to the survey completion) on the present results pertaining to risk perception and sperm concentration category. Because PIN risk is defined clinically, these analyses were restricted to sperm concentration category. Of the 238 participants, 47 (~20%) had given a semen sample prior to the completion of their survey. After removal of those 47 participants, differences in distribution of risk perception by sperm concentration category were observed, such that a larger proportion of those who were azoo- (75.6%) or oligo- (58.3%) spermic endorsed increased perceived risk of infertility than those who were normospermic (49.0%) (p=0.02). (Supplemental table IV)
The sample was also stratified by age at diagnosis (0–5 years of age, 5–10 years of age, 10–15 years of age, and > 15 years of age) and analyses were performed to further understand the potential impact of age at diagnosis on associations between risk peception and fertility status. Differences were observed in distributions of risk perception by sperm concentration category in those diagnosed between 0 and 5 years of age and 10 to 15 years of age. Among those diagnosed between 0 and 5 years of age (n=92), a larger proportion of those who were azoo- (69.6%) or oligo- (67.9%) spermic endorsed increased perceived risk of infertility than those who were normospermic (31.7%) (p=0.01). Among those diagnosed between 10 and 15 years of age (n=58), a larger proportion of those who were azoospermic (80.0%) endorsed increased perceived risk of infertility than those who were oligo- (54.6%) or normospermic (59.4%) (p=0.04). (Supplemental table V).
Discussion
The results of this study describe infertility risk perception in adult male survivors of childhood cancer treated with potentially gonadotoxic therapies, but not radiation therapy. When risk perception was assessed by semen analysis results, men who were azoo- and oligo- spermic were more likely to perceive themselves to be at higher risk for infertility compared to peers. However, the result was not replicated when risk perception was assessed by PIN criteria. Further studies should consider observing risk perception vs. objective risk in larger samples with diverse treatment exposures. In addition, these results highlight the importance of definitive testing to estimate infertility risk as opposed to history of exposures to estimate risk. Results of early and definitive testing could better inform survivors of infertility risk and aid in making informed decisions about family planning.
The finding pertaining to risk perception by semen analysis result is not in line with the conclusions regarding risk and treatment-related exposure in survivors in the extant literature.[14–17] SJLIFE study procedures include risk-based screenings to help inform survivors of health status.[20] This sample, because of participation in a study like SJLIFE in which risk-based screenings are performed, could be generally more informed of the potential impact of childhood cancer treatment on fertility, which could be why consistencies in perception and objective fertility status were observed. Evidence from a study of 6,462 men demonstrated white men to be more likely to seek and follow through with fertility evaluation than other racial and ethnic groups.[22] The present results could be influenced by the larger proportion of NH White males in the study sample. Further studies are necessary to describe associations between perceived infertility risk and objective fertility status in samples that are diverse.
Most participants who believed themselves to be at higher risk for infertility received this information from oncologists or other medical professionals, believed chemotherapy to be a cancer-related reason for infertility risk, and reported that information about infertility was provided after diagnosis and treatment. No differences were observed by semen analysis results or PIN criteria regarding source of infertility information, perception of cancer-related reasons for increased infertility risk, or timepoint at which information was obtained. These results indicate that, across risk strata, 1) survivors in this sample seem to be informed by reputable sources after completing treatment, 2) survivors in this sample understand the role of chemotherapy in their fertility status, and 3) can recall what time this information was relayed. While this result is encouraging, it should be considered in light of previous discussion of possible bias in the SJLIFE study sample because of their engagement in long-term follow-up. One other study of information regarding infertility found that 39% of survivors self-reported receiving information at the end of therapy, 72% reported receiving information at long-term follow-up, and an oncologist was the preferred deliverer of this information regardless of timing.[23] Limited studies focus on survivors’ experiences about fertility counseling, which are invaluable to understanding the experiences that shape fertility risk perception in survivors. Future studies are needed to better characterize these factors and their association with risk perception. These results also underscore the need for communication between oncologist and patient prior to treatment administration, so sperm banking can be presented as a viable option to retain family planning options.
In the general population, pregnancies are heavily-relied upon as a metric of fertility.[24] In our study, more pregnancies were reported by those who were normospermic and in the minimally increased risk PIN strata, which is to be expected. This finding reflects confirmation bias in information processing, in which humans interpret evidence in support of existing beliefs[25] (i.e., previous pregnancy indicates no potential threat to fertility). However, the majority of the study sample (~67%) reported not attempting to impregnate a partner at time of assessment, and median age indicates that these survivors, in general, were younger men (~26 years of age). The analyses performed in the 25 years and younger group indicate differences in pregnancy occurrence as well. It is possible that this SJLIFE testing was the only fertility screening or testing received by these men. Lack of action with regards to fertility screening could be reflective of lack of the influence of education about risk[26] or fear of discovering abnormal results[27] on risk perception. Efforts to inform younger survivors about fertility and promote fertility screening are imperative to ensure male survivors’ reproductive health and psychosexual wellbeing throughout the lifespan.[28] Strategies, such as the BETTER model[29], have been developed to encourage effective communication about sexual health between oncologists and patients.
The results of this study should be interpreted in light of several limitations. This sample was obtained from the larger SJLIFE cohort, who receive access to care and resources that are not universally available. Some semen analysis participants could have become uncomfortable with answering questions regarding their own perception of fertility, potentially biasing the present sample. The perception of the impact of non-cancer-related factors, such as lifestyle[30], on fertility was not explored in the present study. Future studies should consider asking survivors about these contributors in relation to fertility. While these analyses explored potential sources of information regarding infertility risk, attitudes informing infertility risk or attitudes about seeking infertility resources were not explored. Future studies should seek to further contextualize the results of this study by exploring attitudes about infertility and how those attitudes affect seeking resources; these data could be useful for understanding survivors’ willingness to engage in further action (i.e., screening for infertility risk). Finally, it is possible that these survivors engaged in previous screening that could influence their perception of infertility risk.
Conclusions
In this small sample of males from the SJLIFE cohort, infertility risk perception was in line with risk as assessed by semen analysis. The majority who believed themselves to be at higher risk for infertility received this information from oncologists or other medical professionals, believed chemotherapy to be a cancer-related reason for infertility risk, and reported that information about infertility was provided after diagnosis and treatment. The latter suggests an important missed opportunity for fertility preservation in patients who may be candidates for sperm cryopreservation prior to cancer therapy. Further studies should consider contextualizing these results by examining perceptions in more diverse groups, exploring non-cancer-related factors contributing to increased risk for infertility, and attitudes about the timing of receiving this information and resources for fertility in survivors.
Supplementary Material
Funding
This work has been supported by the following: National Institutes of Health, National Cancer Institute, Cancer Center Support Grant from the National Cancer Institute, and the American Lebanese-Syrian Associated Charities (ALSAC).
Footnotes
Competing Interests
Dr. Kirsten Ness is a deputy editor of this journal. Dr. Melissa Hudson is on the editorial board of this journal.
Data Availability
Data utilized in these analyses will be made available to the public via Zenodo link.
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This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Data utilized in these analyses will be made available to the public via Zenodo link.