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Fertility Issues

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    Although chemotherapy causes ovarian damage, there appears to be no risk of toxicity to future offspring of women treated with these agents before pregnancy.[9]

    Radiation

    When the testes are exposed to radiation, sperm count begins to decrease and, depending on the dosage, temporary or permanent sterility may result.[4] Men who receive radiation to the abdominal or pelvic region may still regain partial or full sperm production, depending on the extent of injury to the testes. Unlike the germinal epithelium, Leydig cell function may be more prone to damage from irradiation in prepubertal life than in adulthood.[3] Testicular radiation with doses higher than 20 Gy is associated with Leydig cell dysfunction in prepubertal boys, while Leydig cell function is usually preserved with doses of as much as 30 Gy in sexually mature males.[12] Exposing the testes to ionizing radiation at a dose lower than 6 Gy causes disturbances of spermatogenesis and altered spermatocytes with recovery periods dependent on dose;[4] doses higher than 6 Gy cause permanent infertility by killing off all stem cells.[13] For patients with testicular germ cell cancer, using modern radiation techniques (radiation doses to the para-aortic field <30 Gy) and testis shielding providing testis scatter radiation (<30 Gy), radiation-induced impairment of fertility is very unlikely.[11] Sperm counts are typically lowest at 4 to 6 months posttreatment; return to pretreatment levels usually occurs in 10 to 24 months, with longer periods required for recovery after higher doses.[9] Total-body irradiation (TBI) as a conditioning regimen for stem cell transplantation causes permanent gonadal failure in approximately 80% of men.[14] For men, gonadal toxicity can be evidenced by the following three measurements: testicular biopsy, serum hormone assays (levels), and semen analysis. When male infertility is the result of abnormal hormone production, the use of hormone manipulation may lead to the return of sperm production.[15]

    For women, a dose of 5 Gy to 20 Gy administered to the ovary is sufficient to completely impair gonadal function, regardless of the patient's age; a dose of 30 Gy provokes premature menopause in 60% of women younger than 26 years.[16] In a study of children and adolescents diagnosed with cancer, female 5-year survivors were significantly less likely to have ever been pregnant when compared with their siblings. Survivors who received hypothalamic/pituitary radiation doses of 30 Gy or higher or ovarian/uterine radiation doses higher than 5 Gy and those who were treated with lomustine or cyclophosphamide were less likely to have ever been pregnant.[17] Women who are older than 40 years when undergoing treatment have a smaller pool of remaining oocytes and require only 5 to 6 Gy to produce permanent ovarian failure. TBI, when used before stem cell transplantation, is associated with more than 90% permanent gonadal failure in women overall and an incidence of pregnancy less than 3%.[9] The outlook for recovery of ovarian function before puberty is more favorable, particularly if radiation is delivered in several fractions.[14] Measurement of gonadal toxicity in women is more difficult to assess due to the relative inaccessibility of the ovary to biopsy (which would require laparoscopy). Therefore, menstrual and reproductive history, measurements of serum hormone levels, and clinical evidence of ovarian function are the criteria most commonly used to determine ovarian failure. Several authors provide reviews of gonadal dysfunction in patients receiving chemotherapy [15] and the effect of cancer therapy on gonadal function.[4]

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