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This JCO Podcast provides observations and commentary on the JCO article Gonadal Functioning and Perceptions of Infertility Risk among Adult Survivors of Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study\\xa0by Lehmann et al. My name is Leslie Schover, and I am retired from the faculty of MD Anderson Cancer Center and currently Founder of Will2Love.com a digital health company in Houston, Texas. My oncologic specialty is cancer-related problems with reproductive health, i.e. sexual function and fertility.

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Damaged fertility is unfortunately quite common in survivors of childhood cancer. A variety of chemotherapy drugs, as well as surgery affecting parts of the reproductive system or radiation therapy focused on the pelvis or brain, can damage spermatogenesis, reduce ovarian reserve, or interfere with uterine function. In general, males are more at risk than females for cancer-related infertility. Some survivors do not undergo puberty without hormonal support. For others, fertility may recover over time. However, many young women who have menstrual cycles in their teens or twenties are at risk for premature ovarian failure, leaving a narrowed window of time to become pregnant. Men do not know whether they have normal sperm counts, motility, or form unless they have had a recent semen analysis. People diagnosed with cancer before puberty may never have been counseled about fertility. Even survivors treated as teens or young adults typically do not know their fertility status unless they have consulted an expert in reproductive endocrinology or andrology. Surveys of young survivors suggest that the majority want to have children, particularly those who are childless.

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A number of studies have documented markers of infertility or reduced rates of offspring in survivors of cancer, but little has been known about their perceptions of their fertility status. In the paper that accompanies this podcast, Lehmann and colleagues present novel data about the risk perceptions for infertility compared to indicators of actual gonadal function in over a thousand long-term survivors of childhood cancer participating in the St. Jude Lifetime Cohort. None of the participants already had children or a previous pregnancy. The mean age of the sample was 29, with a mean follow-up of 22 years since cancer diagnosis. 85% were white and 32% had at least a 4-year college degree. 52% were married or in a relationship. Only 10% of men and 16% of women had been tested for infertility outside of the study.

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Gonadal function was measured by a semen analysis in 56% of men and by a panel of hormones in the others. In women under age 40, status as fertile vs. sub-fertile was assigned by chart review based on menstruation, diagnosed premature ovarian failure, or hormonal assays. Perception of risk for infertility was based on one question with a Likert scale of 5 response options, comparing one\\u2019s own fertility to that of peers who had not had cancer. Answers were dichotomized into two categories: perceived at risk for fertility or perceived normal fertility.

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62% did perceive themselves as at risk for infertility. Those who perceived their fertility as damaged had characteristics that would indicate potentially more knowledge about cancer and fertility, including being older, white, in a relationship, having a college education, a history of gonadotoxic treatment, having tried unsuccessfully to conceive, or having sexual dysfunction.

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In actuality, 24% of women and 56% of men had evidence of impaired gonadal function. However, actual medical status had no significant relationship to perceptions of risk. The most common discordance was that the survivor believed him or herself to have damaged fertility when medical tests appeared normal. This included 20% of men and 44% of women. Inaccurate perceptions were more common in respondents who were white, had more education, had more gonadotoxic cancer therapy, were very concerned about their fertility, and had sexual dysfunction. In contrast only 16% of men and 5% of women overestimated their fertility potential.

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In terms of clinical implications, it is common for young survivors to overestimate their risk of infertility. Such beliefs can diminish quality of life. A young person who feels like \\u201cdamaged goods\\u201d may be distressed about the future and perhaps reluctant to date or to enter into a committed relationship. For women, risky drinking was another factor associated with overestimating fertility risk. Risky drinking, and the notion that pregnancy is impossible, may contribute to findings in other studies of excess rates of unintended pregnancies and failure to use consistent contraception in young adult female survivors. Those unaware of their damaged fertility maybe in for distress and disappointment if they try for a pregnancy. Clearly a greater effort should be made to inform young survivors about risks to fertility and to refer them for testing at intervals of fertility status.

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It appears that women are much more likely than men to perceive themselves as potentially infertile, despite the fact that men are more likely to be infertile. However, the measures of gonadal function used in women were not sensitive enough to predict the likelihood of diminished ovarian reserve in the future. Many young survivors of cancer can conceive in their teens or twenties, yet have a steeper than normal drop-off in ovarian reserve with aging, so that their menopause occurs far before the average age of 51. In fact, women\\u2019s fears in this study that they will have trouble getting pregnant in the future may be more accurate than they appear. Age at first pregnancy has steadily increased in our society, with women postponing childbearing until they have completed educational goals or established a working life. More cancer survivors are likely to run out of time before they are ready to have a child. One solution may be commercial egg banking before age 25-30, if fertility preservation was not accomplished before starting cancer treatment. Egg banking is expensive, however, and does not guarantee a future pregnancy.

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This survey adds to our knowledge of the informational needs of survivors of cancer in childhood or teen years. Both medical and counseling support should be more readily available. Survivors with lower health literacy would be particularly good targets for such services.

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This concludes this JCO Podcast. Thank you for listening.