The clinical guidelines of American Society of Clinical Oncology (ASCO) have outlined the key discussion elements between cancer patient and physician regarding referral and fertility preservation methods.1
Fertility preservation options are dependent on several factors, including age, type of treatment, diagnosis, presence or absence of a partner, time availability and the potential for metastasis of the primary cancer to the ovaries.2,12,13
According to ASCO guidelines, embryo freezing is the most established method of fertility preservation when there is a partner available.1
Evidence has been accumulating that oocyte freezing success and safety may be similar to embryo freezing.14-16
At least two weeks are required to complete an ovarian stimulation cycle. Because ovarian stimulation is begun with the onset of menstruation, the delay before cancer treatment can be as long as 5-6 weeks depending on when in the cycle a patient is referred. In a typical adjuvant chemotherapy setting this time period is available in women with breast cancer, while such a delay may not be acceptable in other settings. When time is insufficient to allow embryo or oocyte freezing, ovarian tissue freezing is the only option, as it does not require pre-treatment. The latter is the most experimental of all three. Thus early referral also favors more established fertility preservation procedures.
Oncologists play a key role in understanding the patients’ concerns regarding fertility. Despite our encouraging data indicating increased referral for FP, most recent studies indicate that still less than half of physicians routinely refer cancer patients of childbearing age to reproductive specialists.17
Another recent study reported that most oncologists recognize the importance of discussing infertility risks after cancer treatment, but few actually bring up FP with their patients.18
Primary importance may be placed on discussing issues regarding immediate or life-threatening complications instead of discussing possible infertility issues in the patient-physician setting. Additionally emotional discomfort regarding fertility issue discussions by physicians may be problematic.19
The importance of fertility to cancer survivors may go unrecognized by some oncologists.20
Our results suggested several factors favoring early referrals. Older age affects early referral, perhaps because these women are perceived as more likely to have ovarian failure post-chemotherapy. Early stage cancer also favors early referral to FP. A possible explanation for the latter finding is that in early stage breast cancer, oncologists may be more open to delaying chemotherapy or any perceived risks of undergoing fertility treatments. Receiving academic center cancer also increases the likelihood of referral to FP. It is possible that the oncologists at academic centers may be better informed about FP options and may have easier access to investigation of fertility preservation protocols.
A family history of breast cancer is another factor influencing early referral to FP. Patients with a family history of breast cancer may be more aware of fertility issues associated with chemotherapy because of personal involvement in the subject. It is also possible that because younger women are more likely to have BRCA mutations, and impending decision for risk-reducing salpingo-oophorectomy might have influenced favorable decision towards FP. Another possible explanation is that, those who are BRCA–positive are more likely to be childless, as we have recently shown that some women with those mutations may have compromised ovarian function.12
Nevertheless, our database did not suggest a significant influence of parity on the referrals. We also did not have sufficient information on the BRCA status to test this hypothesis from this database.
From the analysis of our database, we did not find any impact of distance from patient’s residence to the center, type of occupation, race, ethnicity or household income. These data suggest that fertility preservation is important among people regardless of their distance to the specialists, occupation, race, ethnicity and family income. Notably, given the racial mix in our area, non-whites were under-represented in FP referrals. Gravida, parity, abortion, childbearing, and infertility treatment history did not affect the referral pattern. However, the study size might have limited the detection of possible subtle differences between categories.
To our knowledge this is the first and largest study that provides detailed information on early referral to FP compared to delayed referral to PCART. The insight gained from our data may help us improve patient access to FP. Nevertheless, a secondary analysis of a database poses some limitations. As a retrospective study, some data such as the socioeconomic status, educational level, and medical insurance information were not available. Fertility preservation procedures are in general excluded under the infertility coverage as these patients do not meet the classical definition of infertility. Because we did not have precise information on socioeconomic status (SES), we could not directly analyze the impact of SES on access to FP. Instead, we examined as a surrogate for SES, an indirect measure of the median household income based on the postal code of the patients’ residence. Based on this indirect assessment, income had no significant influence on referral patterns.
Our data suggests that younger patients may experience further delay in referral presumably because of the belief that their fertility may not be affected by cancer treatments. Further research on the impact of cancer treatments on young cancer patients are needed, and some are under way.21-22
However, the concept of chemotherapy-induced diminished reserve must be better conveyed to patients as many will experience early menopause. Given that information and especially if the patient desires a large family, even the youngest women with cancer may consider FP before chemotherapy.12
The importance of early referral to FP cannot be overstated. In a recent study we quantified the benefit of early referral.3
We found that those who were referred late in the process were less likely to cryopreserve as many oocytes and embryos, and would experience 3-4 weeks of delay in the initiation of chemotherapy. The current study identified some important factors influencing delay in access to FP, which can be used to improve the delivery of the care.