Advancements in cancer diagnosis and treatment have a significant impact on cancer survival rates. Therefore, quality-of-life issues, such as fertility preservation, have become paramount in the lives of reproductive-age women who are battling malignancies and an integral component in cancer management. Moreover, women are increasingly postponing childbearing to later in life for social or financial reasons, and the incidence of most cancers increases with age.

In female patients, the risk of menopause-related complication and infertility at a young age due to cancer treatment may be devastating and be considered a loss of their essential femininity[13]. A recent study showed that undergoing fertility preservation improves the patients’ subjective experience of cancer treatments[14]. However, only a small fraction of patients at risk of premature ovarian failure are referred to specialists to discuss fertility preservation options. Studies have shown that oncologists infrequently discuss fertility preservation options with their patients or refer their patients to infertility specialists[8,15,16]. The priority of the oncologists is to treat the malignancy, and they are reluctant to introduce this issue that could add stress to the patients, especially if the prognosis is uncertain. The patients themselves may be very hesitant to delay treatment for any reason.

Recent research on young adult female cancer survivors indicates that there are many barriers to fertility preservation[17] In particular, a significantly higher prevalence of high decisional conflict was observed in participants who were not referred for fertility consultation and in participants who reported that the cost of fertility preservation services was prohibitive[18]. Moreover, religious, cultural, and ethical barriers may prevent fertility preservation options from being discussed with the patients. In addition to those factors, for many physicians there is a lack of training in fertility-sparing procedures or awareness of the new emerging options for fertility preservation[19].

Oncofertility is a new interdisciplinary field that involves gynecologic oncologists, reproductive medicine gynecologists, biologists, general oncologists, psychologists, and endocrinologists in a common objective to provide fertility preservation options for cancer patients[20,21]. In this study, we reported our 3-year experience of fertility preservation at the San Raffaele Hospital. Several meetings in hospitals have been organized to explain fertility preservation strategies, the selection criteria, and the role of the Oncofertility Unit at our hospital. The number of patients referred to our Oncofertility Unit for evaluation has increased over time. More interestingly, the number of patients who were not referred for fertility preservation technique decreased over time, showing an improvement in referrals to the Oncofertility Unit and in the patients’ counseling and understanding. The higher rate of oncofertility procedures since the beginning of our experience is most likely linked to both more appropriate referrals and more directive counseling.

The cooperation between specialists is important to evaluate the best option for the patients. The diagnosis of cancer in a young woman represents a reproductive urgency: the first evaluation should be dispatched in a few days, possibly one day. A short waiting time helps to overcome the patients’ fear of delaying treatment, which is the first cause of rejection of fertility preservation techniques. Oocyte cryopreservation is an option if chemotherapy can be delayed, giving patients with cancer the hope of a successful pregnancy when they have overcome their disease. This method required 2–6 weeks of ovarian stimulation depending on the menstrual phase. Fortunately, newer random-start stimulation protocols can be initiated in the follicular or luteal phase, reducing the length of time to oocyte retrieval and minimizing treatment delay[22].

In this study, these young women exhibited a weaker response to controlled ovarian stimulation than expected for their age (a mean of 7.5 cryopreserved oocytes), showing a possible adverse association between the disease and the response to ovarian stimulation. In a recent meta-analysis conducted on 7 retrospective studies, women with malignancies had fewer total oocytes retrieved after controlled ovarian stimulation for fertility preservation compared with healthy age-matched patients (11.7 ± 7.5 versus 13.5 ± 8.4, P = 0.002)[23].

So far, 30 term pregnancies have been reported after reimplantation of cryopreserved ovarian tissue[24]. Although still considered experimental, ovarian tissue banking is indicated when there is no time to delay for chemotherapy or for prepubertal girls. Using minimally invasive techniques, a small amount of cortical ovarian tissue is retrieved, frozen, and preserved for future use[25].

For our patients who were referred for oocyte cryopreservation, the mean time from the counseling for oocyte cryopreservation to oocyte retrieval was 15 days; for patients referred for ovarian tissue preservation, the mean time from surgery for ovarian biopsy to the beginning of radiotherapy/chemotherapy was only 4 days. The fertility preservation treatment does not affect the oncologic treatment, and this aspect should be stressed during the counseling. Patients who refuse or are excluded from fertility preservation strategies received ovarian protection by medical therapy. Controversy exists regarding benefit of gonadotrophin-releasing hormone agonist (GnRH-a) or combined oral contraceptives administered at the time of cancer therapy in preventing premature ovarian failure in women, and the available data from both human and animal studies have been mixed. However, more evidence is necessary to offer the routine use of GnRH-a for women as a plan for gonadotoxic therapy[26] We offer oral contraceptives because of the psychological role: women do not experience amenorrhea or hormonal deficit and avoid pregnancies during oncologic treatment.

Fertility preservation in the setting of cancer can positively influence a patient’s overall feeling of wellbeing by reducing the stress of potential fertility loss. An effective multidisciplinary team ensures that fertility preservation is accomplished efficiently and safely while optimizing the time from consultation to treatment; moreover, fertility preservation strategies could be evaluated even after the end of the treatment in patients at risk of premature ovarian failure. Recently, we have reported oocyte cryopreservation as an option in the unique setting of patients affected by malignant ovarian germ cell tumors after the end of treatment[27]