Purpose Long-term survivors of successfully treated Hodgkin’s lymphoma (HL) are at risk for late complications. Among these, infertility for female patients is of major importance. The subject of this analysis is to evaluate the menstrual status after HL therapy. Patients and Methods From 1994 to 1998, the German Hodgkin’s Lymphoma Study Group conducted clinical trials for early-, intermediate-, and advanced-stage HL (trials HD7 to HD9) involving a total of 3,186 patients. A survey was carried out to evaluate the menstrual status after therapy. The following factors were assessed concerning their influence on amenorrhea: age, treatment, stage, and the use of oral contraceptives during chemotherapy. Results A total of 405 women aged younger than 40 years answered the study questions. After a median follow-up of 3.2 years, 51.4% of the women receiving eight cycles of dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) had continuous amenorr...

Secondary Amenorrhea After Hodgkin’s Lymphoma Is Influenced by Age at Treatment, Stage of Disease, Chemotherapy Regimen, and the Use of Oral Contraceptives During Therapy: A Report From the German Hodgkin’s Lymphoma Study Group

Gonadal dysfunction and fertility problems are adverse effects of cancer treatment or may be associated with specific malignancies. This review focuses on these problems in the young cancer survivors, where methods of protecting or restoring endocrine function and fertility need to be considered. In females, treatment adverse effects can result in infertility, but premature ovarian failure (POF) is probably relevant for more female cancer survivors, affecting also those who do not wish post-treatment parenthood. POF affects present and future health, especially through oestrogen deficiency symptoms and an increased risk of developing osteoporosis. A lower risk of developing POF has been considered in young females than in older due to a larger pool of oocytes. However, a recent long-term follow-up study reported a prevalence of POF in young females with Hodgkin's lymphoma of 37% showing that young age at time of treatment only delays the development of POF. In male gonads, germ cells are much more sensitive to irradiation and chemotherapy than Leydig cells. Thus, infertility is a more common adverse effect than hypogonadism. Some malignancies are particular relevant. Persistent azoospermia was formerly common after treatment for Hodgkin's lymphoma, but currently, most patients recover spermatogenesis. Modern treatment of childhood acute lymphoblastic leukemia is also unlikely to cause infertility. Norwegian testicular cancer survivors diagnosed in 1980-1994 who attempted conception had an overall 15-year actuarial post-treatment paternity rate of 71% (range 48-92% depending on the treatment). However, the rate was significantly higher among men diagnosed in1989-1994 (over 80%) than in 1980-1988 (about 63%). Patients at risk for hypogonadism and infertility should be defined prior to treatment, and available methods for gonadal preservation should maximally be utilised. During follow-up, oncologists should routinely address these issues.

https://www.tandfonline.com/doi/pdf/10.1080/02841860601166958

Gonadal dysfunction and fertility problems in cancer survivors.

In the past, cancer survivors tended to be most concerned about disease recurrence and treatment side effects. As survival rates have increased, however, patients are now also concerned about quality-of-life issues such as preserving fertility potential. It is well known that cancer treatment adversely affects male fertility via direct effects on the testis and/or through the endocrine glands. Evidence also suggests that the disease process itself may affect a man's fertility by influencing spermatogenesis. However, the causes of poor semen quality in cancer patients are not well understood. Multiple factors are likely involved, including preexisting defects in germ cells, systemic effects of cancer, and endocrine and immunological disturbances. This paper will summarize available evidence on different factors involved in impaired spermatogenesis in patients with various cancers with emphasis on testicular cancer and Hodgkin lymphoma. Cryopreservation of spermatozoa is a simple and practical approach available to all patients with cancer who wish to preserve their fertilizing potential before cancer therapy.

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Disruption of Spermatogenesis by the Cancer Disease Process

Purpose To evaluate fertility in male patients with osteosarcoma after chemotherapy including high doses of alkylating agents. Patients and methods Postchemotherapy fertility was evaluated in 96 male patients who received chemotherapy at the authors' institution from 1976 to 1996 for localized bone osteosarcoma of the extremities. Four drugs were administrated (doxorubicin, cisplatin, methotrexate, ifosfamide) at different doses according to six different protocols. Eleven patients were prepubertal and 85 were postpubertal at the time of chemotherapy. The median age of these patients at the time of chemotherapy was 17 years (range 10-42), the median age at the time of the interview was 27 years (range 19-53), and the median follow-up from the end of chemotherapy was 9 years (range 4-17). Results Of the 96 patients, 26 underwent sperm analysis and 20 showed oligo- or azoospermia. Patients who received high-dose ifosfamide showed a higher incidence of azoospermia. Six patients were normospermic and received no ifosfamide or lower doses of ifosfamide. Eight patients fathered a total of 12 children. No birth defects or congenital anomalies were observed in their offspring. Conclusions The rate of sterility was related to ifosfamide dosage. It appears that pubertal maturation is not affected by chemotherapy. No congenital malformations were seen in the children of the few patients who fathered children.

Fertility in male patients treated with neoadjuvant chemotherapy for osteosarcoma.

This systematic review of the literature reports on the use and effectiveness of sperm banking programmes for cancer patients. Thirty studies with 11798 patients were included. The aggregated rate of use of cryopreserved semen was 8% (95% CI 8 to 9%). A statistically significant correlation emerged between the mean and median duration of follow-up and the rate of use (R(2) = 0.46; P = 0.03). The rate of patients discarding their frozen sample was reported in 11 studies. The aggregated rate was 16% (95% CI 15 to 17%). The rate of patients who used their frozen semen and achieved parenthood was reported in 19 papers. The aggregated rate was 49% (95% CI 44 to 53%). The rate of patients achieving parenthood with the use of frozen sperm is low and, from an economical perspective, the effectiveness of programmes of sperm banking might therefore be questioned. On the other hand, the low rate of patients discarding their frozen samples and the correlation between rate of use and duration of follow-up suggest that the calculated 8% rate of use may be an under-estimation and that cumulative rate of use may be substantially higher. Specific studies are, however, required to clarify this issue.

B. Hcerni

Papers

Semen analysis and cryoconservation before treatment in Hodgkin's disease.