Fertility preservation and fulfillment of parenthood after treatment of hematological malignancies: results from the ‘Aftercare in Blood Cancer Survivors’ (ABC) study

Overall survival in patients with hematological malignancies has markedly improved. In some types of aggressive disease, such as lymphoma, cure rates are high, and in indolent malignancies, long-lasting remissions can be achieved [1]. Due to a growing number of long-term survivors, patient care is increasingly being focused on the optimal management of treatment side effects.

Lasting infertility is one of the most crucial side effects of chemotherapy as it can sustainably affect a cancer survivor’s concept of life. The majority of young cancer survivors express a desire for a child [2‐5], and fear of persisting infertility causes distress and limits the quality of life [6]. Fertility preservation, such as cryopreservation of sperm, oocytes, or ovarian tissue, is a promising approach to enable post-treatment parenthood [7‐9]. Moreover, the use of fertility preservation was shown to help patients cope with their diagnosis of cancer [10]. However, fertility preservation is often insufficiently discussed [4, 11, 12], and referral rates to fertility institutes are low [4, 12‐14]. On the part of the treating oncologist, one of the main reasons accounting for this situation is fear to lose time when treatment is urgent [15‐17]. Only a few studies focus on the patterns of fertility preservation in hematological patients [13, 18].

The present report is a sub-study of the ‘Aftercare in Blood Cancer Survivors’ (ABC) study which analyzed current patterns of follow-up in patients with hematological malignancies. The core study focused on medical events, quality of life, and costs during follow-up, and the results will be presented separately. Here, we report on receipt of pre-treatment information about the risk of treatment-induced infertility, use of fertility preservation as well as wish and fulfillment of post-treatment parenthood, as reported by the patients in the retrospective part of the ABC study. We also identified patient- and disease-specific factors associated with these issues.

Support for post-treatment parenthood should begin before the start of cancer treatment. Patients must be informed about the risk of losing their fertility and the measures that can be taken to preserve it.

In our study, 72.4% of patients reported to have been informed about the risk of infertility. Compared to other studies [13, 19] the rate of informed patients was high. The improvements observed over time are encouraging and suggest rising awareness of hematologists for therapy-induced infertility. At least in part, this may be the result of guidelines published by expert associations, such as the European Society of Medical Oncology and the American Society of Clinical Oncology [20‐23].

In contrast to other studies [13, 19], only a minority of patients took steps to preserve fertility. Besides age, we found gender-specific differences to the disadvantage of women, relating both to the receipt of information about the risk of therapy-related infertility and the use of fertility preservation. This observation is in line with findings from other studies [24‐26].

Both health care professionals and patients are actively involved in the decision-making process of using fertility preservation. Health care professionals provide information and offer options to preserve fertility, while the patients decide whether they want to make use of the information provided. An important issue not addressed in our study is the question whether the costs were covered by the insurance companies or the patients themselves. Reasons for low rates of fertility preservation may, therefore, be oncologist-related, patient-related or both.

Studies focusing on the behavior of health care professionals concerning fertility issues in cancer patients revealed that oncologists preselect patients on the basis of disease- and patient-specific factors. An urgent need for treatment was one of the main reasons for neglecting fertility-related discussions [15, 16], especially in women [17]. Hematological malignancies often require immediate treatment. Thus, fear of jeopardizing the result of therapy by delaying it in favor of fertility preservation may be one explanation for our findings. This may also explain the differences observed between male and female patients. For men, cryopreservation of sperm is the method of choice, a procedure that is widely available and can be accomplished within a few days. In contrast, fertility preservation in women is more complex. Cryopreservation of embryos or unfertilized oocytes are favored procedures, while suppression of ovarian function by gonadotropin-releasing hormone analogues has shown conflicting results [21]. Harvesting oocytes, however, is a time-consuming process, requiring weeks or months. Cryopreservation of ovarian tissue appears better suited, as it can be done within a few days. In particular, women requiring rapid induction of therapy may benefit from this procedure. However, most hematological malignancies including acute leukemia carry a risk of involving the ovaries [27, 28], which limits the use of ovarian tissue cryopreservation in those who most urgently need it.

Other reasons for not undergoing fertility preservation include unavailability of fertility preservation services and high costs of the procedure that may have to be covered by the patients themselves [29, 30]. As discussed by others, not being able to pay for fertility preservation may embarrass patients, who then deny having been referred to a fertility institute. As a consequence, referral rates are reported to have been lower than they actually were [13].

More than half of our patients reported to have completed family planning by the time the hematological malignancy was diagnosed. A desire for a child after the end of treatment was expressed by only 19.3%. An association of a desire for post-treatment parenthood with young age and childlessness at the time of diagnosis has been noticed before [18, 31]. Not surprisingly, patients who decided to preserve fertility were more likely to express a desire for a child than patients not using fertility preservation. Parental status did not affect the choice to preserve fertility. This implies that patients who are already parents at the time the hematological malignancy is diagnosed refrain from planning to increase the size of their family after completion of therapy. The results of several studies are in line with this observation. While, at the time of diagnosis, patients that already had a child expressed a stronger desire for further parenthood than patients without a child, the opposite was true after the end of treatment [19]. In Hodgkin’s lymphoma, patients that already had a child at the time of diagnosis had lower post-treatment birth rates than patients without a child [32].

Unexpectedly, the desire for a child could only be fulfilled by 30% of the patients. Compared to previous studies [18, 32, 33], the rate found in our study is low. This is likely to be related to the fact that 40% of our patients underwent allogeneic stem cell transplantation, which is known to cause lasting sterility in a high proportion of patients [34‐36]. However, an unfulfilled desire for parenthood may not only originate from therapy-induced infertility. Our observation that pre- and post-treatment parenthood were positively correlated, suggests that an unfulfilled desire for a child may also be due to infertility unrelated to chemotherapy. Moreover, childlessness can be caused by infertility of the sexual partner, a possibility that was not investigated in the present study. Importantly, the rate of fulfillment of parenthood increased with increasing time since treatment termination, suggesting that fertility can be regained. Several studies reported that, depending on the gonadotoxicity of the therapy applied and the patients’ age at the time of diagnosis, gonadal function may recover [37‐40]. However, these studies also revealed that women are at high risk of premature menopause, which may hamper family planning in women receiving chemotherapy at higher age. In this group of patients, pre-treatment information about the risk of infertility and the available options for fertility preservation are particularly important to enable post-treatment parenthood.

In conclusion, in the ABC study, a large proportion of patients with hematological malignancies received adequate information about the risk of losing fertility, but only a minority decided to preserve it. Women were less likely to be informed and undergo fertility preservation than men. Moreover, childlessness at the time of diagnosis was strongly associated with a desire for post-treatment parenthood, which, however, could only be fulfilled in 30% of cases.

Our observations may gain in importance because first parenthood is increasingly being delayed to higher ages. In the future, more patients are anticipated to express a wish for parenthood after successful therapy of a hematological malignancy. Options to preserve fertility should be considered in all patients and psychosocial support should be offered not only during the time of treatment but also beyond.