Fertility Preservation Counseling for Pediatric and Adolescent Cancer Patients

Materials and Methods

After approval from the Investigational Review Board, a cross-sectional study was performed from May 26, 2014, to August 26, 2014. An online survey through Survey Monkey was created and emailed to the members of the Children's Oncology Group (COG). COG is the largest clinical trials organization comprised of clinicians and investigators dedicated to pediatric cancer research. The survey addressed demographics, specifically physician sex, provider credentials, years in practice, practice location, and patient population, counseling patterns of physicians regarding fertility preservation, and number of physicians that are referring patients to a specialist for fertility preservation (Appendix A). Questions were asked concerning specific fertility preservation options that are offered and the barriers that are preventing physicians from providing fertility preservation counseling. The primary outcome was the number of physicians who provided their patients with fertility preservation counseling. The secondary outcomes addressed prescribing and counseling patterns in comparison to the new ASCO guidelines, as well as limitations to providing counseling. The statistical analysis used descriptive proportions, and was calculated with GraphPad Prism.

Results

Discussion

Fertility preservation has become a cancer survivorship concern. Decreased fecundity with diminished ovarian reserve and decreased sperm production can occur in cancer survivors. ⁷ As the updated fertility preservation guidelines have been published through ASCO, assessing the rates of compliance with the new guidelines is essential so that steps can be instituted to ensure future compliance and make sure patients gain access to fertility preservation options.

There have been two recent small studies that reported practice trends in pediatric oncology counseling for fertility preservation. Terenziani et al. issued a 21-question questionnaire to pediatric onco-hematology institutions across Europe. Sixty-eight (34%) institutional representatives responded noting that pre-treatment fertility counseling was offered by 64 (94%) institutions surveyed. ⁸ The present study strived to assess if individual practitioners had read and implemented the ASCO guidelines into their practices, and overall it had a higher number of responses. Similarly, Overbeek et al. reported that 37 (97%) pediatric oncologist surveyed in the Netherlands discussed fertility preservation with their patients. ⁹ The present study reviewed 234 surveys identifying 226 (95%) of COG providers responding that they provided fertility preservation counseling in their practice. These results reveal consistency with previous published reports, and suggest that fertility preservation counseling is being performed in most settings.

The present study revealed possible limitations in the content of information provided to patients during counseling. The findings suggest that provider education should be promoted, as only a third of the providers responded that they were familiar with the ASCO fertility preservation guidelines, and 39% of responses listed lack of knowledge as a barrier. As the guidelines for fertility preservation evolve, it is important that oncologists and their patients have a basic understanding of current practices that are being offered. Future education could be offered within training programs via published literature and through conferences or webinars to reinforce new practice recommendations.

The most common barrier to fertility preservation counseling identified was that the patient could not afford the treatment. This finding is consistent with a recent publication stating that patients lacking private insurance were less likely to receive counseling. ¹⁰ It is recognized that this is difficult to interpret, as the provider should make the referral and leave it to the patient to decide whether cost is actually the barrier.

The perceived poor success rate of fertility preservation was listed as a barrier by 35% of responses. In a young patient, the rate of success in the established methods of fertility preservation is reassuring. Oktay et al in a recent publication showed that embryo cryopreservation in women with breast cancer results in pregnancy rates comparable to a non-cancer population. ¹¹ A cancer patient with a poor prognosis is unfortunately one of the considerations for not offering fertility preservation, which must occur because the cancer treatment is of utmost importance. Social limitations in partner availability was an identified barrier and does make counseling more difficult, but a referral to a reproductive endocrinologist would be appropriate to counsel the patient about his/her options. One of the most challenging parts of counseling adolescent patients is helping them consider the future beyond their diagnosis. So in this patient population, it is important to involve the family. ¹² Surprisingly, lack of time was only listed by 12% of providers in the survey, which is less than previously stated in the literature. ¹³ This may represent a rise in perceived importance of this subject matter to oncologists faced with a newly diagnosed patient.

The majority of current practice patterns provide ASCO-endorsed options for fertility preservation. However, it is important when counseling on fertility preservation that the types of methods offered are understood. For embryo and oocyte cryopreservation, the female patient has to undergo at least a 2-week period of monitoring for the in vitro fertilization process. From the present survey, established methods for women of embryo and oocyte cryopreservation (8%) are being offered less than experimental methods such as gonadotropin suppression or ovarian tissue cryopreservation (15%). Since the previous ASCO guidelines were published, oocyte cryopreservation moved from experimental to established. This method is more applicable to the younger female patients without a partner than embryo cryopreservation where sperm is needed. The ASCO guidelines and American Society for Reproductive Medicine Fertility Preservation committee opinion addressed the children and adolescent population options, specifically mentioning oocyte cryopreservation and ovarian tissue cryopreservation.^1,14 Ovarian tissue is still experimental, and patients must undergo a surgery to remove some of their ovarian tissue, which makes this option less desirable for some.

Males are being offered fertility preservation more than females (57% vs. 28%). This anecdotally may be true in practice, but one limitation of the present survey is that patient sex was not specifically delineated. Males being offered more counseling is consistent with a recent paper by Shnorhavorian that also addressed fertility preservation counseling rates provided to AYAs with cancer. ¹⁰ For the male patient, sperm banking is a short time commitment in that it often does not delay treatment protocol and is less invasive than oocyte and embryo cryopreservation. Thus, it is easier to counsel male patients at the time of diagnosis.

The ASCO fertility preservation guidelines state that gonadotropin suppression is still considered experimental. Currently, the number of physicians prescribing it for this function is unknown, and more research is needed. ¹ Despite still being considered experimental, 28% of surveyed providers are prescribing a gonadotropin-releasing hormone analog in their practice. However, when counseling on fertility preservation, it is important that patients understand the details, timelines, and logistics of the methods that are available to them based on their cancer treatment plan. The data on ovarian suppression with gonadotropin-releasing hormone are controversial. However, many of the recent studies report improving fertility in the adult population.^15,16

As previously discussed, this study's response rate is an obvious limitation, but it is consistent with the findings of other previous published reports.^12,17,18 Compensation may be a future strategy to improve response rates. Another limitation includes survey study bias, since the providers who responded are more likely to have a favorable opinion on the subject. However, if survey study bias is assumed, it would still highlight the need for more education in the area of fertility preservation in the pediatric oncology community. Considering selection bias of only the providers who counsel on fertility preservation answering our survey, these reported percentages are likely lower estimates of the pediatric oncology practice. The decision was made not to develop a validated survey for time constraints and brevity of this study. Improvements to the survey in the future could also address if any patient handouts were provided.

In the authors' academic practice, adjacent to their cancer center, pediatric oncologists have ready access to RE specialists. The RE specialist will see the patients as inpatients at the time of diagnosis or on an outpatient basis, time permitting. Oncofertility clinics allow for a collaborative effort, and assist the oncology and survivorship patients in gaining access to fertility preservation care. Programs such as the LIVESTRONG Foundation help provide more affordable care for patients to overcome the barriers of cost to fertility preservation. Additional resources for oncologists that are user friendly include the ASCO University Focus Under Forty Course and the oncofertility university site. Combined educational activities facilitate discussion of fertility preservation options with oncology colleagues, while multimodal cancer treatment options and late effects are reviewed with REs. The authors' experience suggests that a collaborative practice between REs and oncologists is important to overcome many of the barriers to access of care. Pediatric oncology providers should also be encouraged to become more familiar with the new ASCO fertility preservation guidelines and incorporate REs early on in patient care.

As survivorship increases, late effects from cancer treatments have become a mounting concern for cancer survivors. ¹⁹ Treating cancer is the most important role of the pediatric oncologist. However, addressing fertility preservation in patients may improve the survivors' quality of life and ultimately patient satisfaction.