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Parenthood after Hodgkin's Disease Treatment
Abstract & Commentary
By William B. Ershler, MD, Editor, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.
Synopsis: There is now a growing literature describing various medical issues in long term survivors of Hodgkin's disease. One of these is infertility. In the current report, an analysis of success of achieving parenthood after treatment in a cohort of female and male patients treated between 1971 and 1998. Approximately 50% attempted pregnancy and between 60% (males) and 75% (females) were successful. Those who received radiation alone or low gonadotoxic chemotherapy were most successful.
Source: Kiserud CE, et al. Post-treatment parenthood in Hodgkin's lymphoma survivors. Br J Cancer. 2007;96:1442-1449.
Attempted and achieved post-treatment parenthood remain issues of concern for many survivors of Hodgkin's disease. Kiserud and colleagues from the University of Oslo examined this question in a large series of patients who were registered in a national lymphoma registry between the years 1971 and 1998. In the study, investigators addressed the success of achieving post-treatment parenthood by twice (in 2002 and 2005) surveying those female patients younger than 50 years and male patients younger than 65 years regarding the issue of post treatment parenthood. Of the 1557 Hodgkin's lymphoma patients who were registered in that database during the period, 602 were eligible for the present study and were contacted by mail. Seventy-five percent responded to the surveys. Of all the responders, 86% were younger than 40 years at the time of diagnosis. The median observation time from the last treatment to the survey was 15 years (range 3 to 34 years) with 62% of the patients diagnosed before 1989. Of those treated before 1989, 61% had received both radiotherapy and chemotherapy. For the whole group, 46% had at least one child at the time of diagnosis of Hodgkin's disease.
Of the females, 50% of females and 45% of males had attempted post treatment parenthood. All of these patients were under the age of 40 years at the time of diagnosis. By both univariate and multivariate analysis, low age and prior childlessness at diagnosis were the only variables associated with post treatment attempts at parenting. Of these, 68 females (75%) and 76 males (63%) who had attempted post treatment parenthood were successful without the use of assisted reproduction techniques. The 10-year probability of post treatment parenthood was 59% in females and 56% in males. In patients who were childless at the time of diagnosis, the 10-year probabilities of post treatment parenthood were 58% in females and 54% in males. Females aged below 30 years at diagnosis were significantly more likely to achieve post treatment parenthood compared to older females.
In both males and females, achievement of post treatment parenthood was associated with the treatment modality and dose. The type and intensity of chemotherapy was most important in this regard. Individuals (males and females) who received radiation alone or low gonadotoxic chemotherapy were most likely to conceive in the 10 years following treatment whereas those who received high gonadotoxic chemotherapy such as MOPP or high dose cyclophosphamide were less likely. Cryopreserved sperm was used for fertilization by 13 males and this was successful in ten.
Although fertility has long been an issue for those cured of Hodgkin's disease, this study is the first to investigate long-term post treatment success at achieving parenthood in a large series of consecutive Hodgkin's disease survivors. About 47% of those in the study had attempted post treatment parenthood. Young age and childlessness at the time of diagnosis were factors associated with attempting to parent. Of those who made the attempt, 68% became parents spontaneously and another 10 (males) became fathers with the use of pretreatment cryopreserved semen. Multivariate analysis confirmed the long-held notion that type of treatment is significantly associated with success, and this, for both genders. Patients who had received radiotherapy alone or low gonadotoxic chemotherapy enjoyed the greatest success.
This report adds significantly to our understanding, primarily based upon the careful methodology employed, the large data base and the choice of the highly relevant primary outcome: the first post treatment childbirth. Prior studies had relied on semen analysis in men and the development of amenorrhea in women as predictors of infertility. Nonetheless, the current study may overestimate the actual success of achieving parenthood. For one thing, patients were excluded from analysis if they relapsed, even if there had been a significant remission duration. It is unclear whether this group had attempted parenthood and whether they were successful. Furthermore, it was not clear to what extent individuals attempted to achieve parenthood. Certainly, a number of psychological factors might come to play in responding to questionnaires on an issue such as this. Nonetheless, it is gratifying to see the relatively high rate of achieved pregnancy in these long-term survivors of Hodgkin's disease.
Although it appears the optimal success was observed in those receiving radiation alone, it was not strikingly different from those receiving low gonadotoxic chemotherapy such as ABVD. In light of the risk of long-term complications from radiation in excess of that of ABVD, issues regarding parenthood might be considered minor. Finally, females aged above 30 years at the time of diagnosis are at particularly high risk of becoming infertile. They constitute a subgroup for which cryopreservation of ovarian tissue should be considered. Males, on the other hand, have the opportunity for pretreatment cryopreservation of semen and as spermatogenesis recovers in the great majority, their potential infertility after treatment is a problem of less magnitude.