© Springer International Publishing Switzerland 2017Teresa K. Woodruff and Yasmin C. Gosiengfiao (eds.)Pediatric and Adolescent Oncofertility10.1007/978-3-319-32973-4_19
19. Optimizing the Decision-Making Process About Fertility Preservation in Young Female Cancer Patients: The Experience of the Portuguese Centre for Fertility Preservation
Faculty of Psychology and Educational Sciences, University of Coimbra, Rua do Colégio Novo, Apartado 6153, 3001-802 Coimbra, Portugal
Unit of Psychological Intervention, Maternity Dr. Daniel de Matos, Coimbra Hospital and University Centre, Coimbra, Portugal
Faculty of Medicine, University of Coimbra, Coimbra, Portugal
Portuguese Centre for Fertility Preservation, Reproductive Medicine Department, Coimbra Hospital and University Centre, Coimbra, Portugal
KeywordsOncofertilityCancerFertility preservationDecision-makingSurvivorshipReproductive decisions
Currently, cancer is no longer synonymous with death. Despite the increasing number of new cases of cancer per year in the last decades, the survival rates have also been increasing steadily . Specifically in Portugal, in 2009, the cancer incidence rate was 426.5 cases per 100,000 individuals, which was the highest value ever registered . However, Portugal is reported to be one of the European countries with the highest 5-year survival rates for several types of cancer (e.g., melanoma and colon cancer; ). The intervention in oncology therefore needs to be focused not only on the life preservation of patients but also on the promotion of their quality of life after the completion of cancer treatment . Specifically, the patients’ reproductive future needs to be taken into account by health professionals during the process of cancer diagnosis, mainly due to the risk of infertility and the duration of cancer treatments as well as the current characteristics of cancer patients.
Over the past years, there have been major advances in cancer treatment protocols. Currently, there are more aggressive regimens that are more effective against malignancies. However, these regimens also have more side effects, including the risk of fertility impairment . Specifically in female patients, the treatment of some types of cancer comprises hormonal therapy that can last for at least 5 years . Given the normal ovarian reserve decline that registers significantly after the age of 32 , the combination of the impact of gonadotoxic cancer treatments and the postponement to later ages of attempts to become pregnant due to hormonal treatments may have a serious negative impact on female cancer patients’ reproductive future .
Another important aspect to bear in mind is the characteristics of cancer patients at the present time. It is increasingly common to find cancer patients of reproductive age whose parental projects are not fully completed, mainly due to the increasing incidence of some types of tumors at young ages  and the current social trend of delaying childbearing until older ages . This means that the reproductive future of many newly diagnosed cancer patients who are young and childless is at risk. However, despite the gonadotoxicity of cancer treatments, the possibility for these patients to have a biological child after surviving cancer is now a reality, mainly due to advances in fertility preservation (FP) methods. The decision-making process about FP is particularly demanding for female cancer patients for several reasons that are presented below.
The main aim of the present article was to describe the experience of the Portuguese Centre for Fertility Preservation in terms of the provision of support for the reproductive choices of young female cancer patients. To our knowledge, this is the first proposal of a prospective intervention model to counsel and support these patients with regard to their reproductive future.
Brief Notes on Female Fertility Preservation Methods
Retrospective data indicate that pregnancy after cancer can be safe for survivors and their offspring . Research indicates that there does not seem to be an additional risk of death in survivors during subsequent pregnancies. The literature also suggests that the infants of cancer survivors do not have an increased risk of low birth weight, malformations , or cancer (in the absence of a genetic cancer syndrome)  when compared to the general population. However, pregnancy monitoring by a “high-risk obstetric service” (, p. 32) is recommended to supervise potential cancer treatment-related risks that are specifically associated with hormone-dependent tumors.
Taking into account the risk of future cancer-related infertility, both female and male FP techniques have been developed to attempt to ensure the possibility of cancer patients having biological children in the future. These methods comprise the cryopreservation of gametes before possibly gonadotoxic cancer treatments (e.g., chemo- or radiotherapy, surgery) and their subsequent use, after the recovery of the patient from the oncological disease, in case of fertility impairment .
Female FP methods consist of the cryopreservation of embryos, oocytes, or ovarian tissue.
Embryo cryopreservation comprises, first, the collection of oocytes from the female cancer patient (after an ovarian stimulation that can last 2 weeks) and, second, the in vitro fertilization (IVF) of these oocytes with sperm from the patient’s partner. The obtained embryos are then stored. After cancer treatments, if the female patient is not able to conceive naturally, the patient and her partner can use their embryos to try to have a child. The cryopreservation of embryos is a well-established technique , and data have shown good success rates (i.e., the clinical pregnancy rate per transfer of frozen embryos is 22.3 % on average; ). However, this method has drawbacks that should be considered. First, ovarian stimulation may imply the postponement of the beginning of cancer treatments and may have an impact on the growth of hormonal tumors, a risk that remains unclear in the research . Second, this method does not maintain the reproductive autonomy of the female patient because it can only be performed in female patients who are married or in civil unions, and only the couple can use the previously cryopreserved embryos. It is important to note that in Portugal, since July 2015, embryo cryopreservation has been considered an unviable FP method given the related ethical, moral, and legal issues.
Cryopreservation of oocytes also involves ovarian stimulation and its disadvantages, as previously described. However, in this procedure, the collected oocytes are stored without being fertilized. After cancer treatments, if the female’s reproductive function is affected, it is possible to collect sperm from her partner and perform an IVF with the previously cryopreserved oocytes . Since 2013, this has been considered a well-established technique  due to the increasing number of live births resulting from oocyte cryopreservation (i.e., there have been more than 1000 children born through IVF with frozen oocytes; ).
Cryopreservation of ovarian tissue comprises the extraction of an ovary (partially or totally) through laparoscopy and the subsequent dissection and freezing of the ovarian cortex into small fragments. To reestablish the reproductive function of the female patient after the cancer treatments, the ovarian tissue slices are implanted, one by one, in the remaining ovary in the patient’s uterus. It is hoped that this transplantation can restore the activity of the ovary that was subjected to the impact of the oncological treatment. This is a recent and still experimental technique , but clinical and research results have been improving in recent years (i.e., there are now more than 40 babies born through transplantation of frozen ovarian tissue; ). Despite its experimental label, this FP method has some cons that should be considered. This procedure does not require as much time as ovarian stimulation does, so it can be performed in patients who need to begin their cancer treatments as soon as possible. Moreover, in the case of a successful ovarian tissue transplant, there is no need to perform IVF and embryo transplant in the future to achieve pregnancy .
In conclusion, reproductive medicine now provides techniques that attempt to ensure the biological parenthood of cancer patients who plan to undergo treatments that may threaten their fertility. In this context, oncofertility is rising as an imperative research and clinical field that involves an “integrated network of clinical resources [to] focus on developing methods to spare or restore reproductive function in patients diagnosed with cancer” (, p. 2).
The Decision-Making Process About Female FP
The decision-making process about FP is complex in female cancer patients for two main reasons. First, and according to the description in the previous section, female FP techniques are invasive, and one of these techniques is still considered experimental. Second, in the decision-making process about female FP, it is necessary to consider several clinical (e.g., type of cancer, time until the beginning of cancer treatments, ovarian reserve), sociodemographic (e.g., age, marital status), and FP technique-related (e.g., success rates, medical procedures, risks, duration of the techniques, maintenance of the reproductive autonomy) variables. Often, there is little time to consider these variables [10, 25].
Although this may be a difficult and emotionally overwhelming process for recently diagnosed young adult female cancer patients , some data in the literature suggest the importance of this decision in these women’s lives.
Research with Female Cancer Patients
Young female cancer patients seem to value the opportunity to make a decision about FP [33, 36]. These patients report the desire to receive as much information about fertility treatments and FP interventions as possible around the time of the diagnosis so they can play an active role regarding this decision . This is particularly important because studies reveal that more informed patients who have the opportunity to make a decision about FP together with health professionals have lower decisional-conflict levels [24, 33], make higher-quality decisions , have greater satisfaction with their care after the decision , and have better psychological adjustment to the diagnosis  than patients who are less informed and do not have the opportunity to be part of this decision-making process. A study by Peate and colleagues  that evaluated women with breast cancer of reproductive age (21–40 years old) reported that a lack of information increases anxiety and negatively influences the quality of the decision-making experience. However, this study also revealed that the presence of anxiety levels in female breast cancer patients do not appear to be correlated with their fertility knowledge or with their desire for information, suggesting that fertility-related information should be provided to all women regardless of their emotional well-being.
Research with Female Cancer Survivors
Results on the motivations for parenthood among female cancer survivors and the impact of cancer-related infertility and of the FP decision in these women’s psychological adaptation in survivorship suggest the key role of the FP decision before cancer treatment in these women’s lives.
Research reveals that female cancer survivors have more positive motivations for childbirth than healthy women do (e.g., ). Despite the fear of a cancer recurrence after a pregnancy, these survivors associate having a child with happiness and a fulfilling life , value the family, and feel very competent to educate a child . Through a systematic literature review, Gonçalves et al.  reported that childbearing seems to be an important issue for young female breast cancer survivors, even for those who are against having children after cancer due to the potential risks associated with some types of tumors.
The diagnosis of cancer-related infertility has been shown to have a negative impact on the individual adaptation of these survivors in terms of the experience of high levels of anxiety [28, 41], depression , sexual dysfunction [9, 37], disruptions to intimate relationships , and feelings of loss and anger [37, 40]. Moreover, infertile survivors also must address menopausal symptoms, such as vaginal dryness and hot flashes, which can have a negative impact on their quality of life . Some female cancer survivors even describe the experience of being infertile as being as painful as the cancer diagnosis itself . According to results reported by Canada and Schover , social parenting (i.e., adoption) does not completely resolve this distress.
Young adult female cancer survivors evaluate the opportunity to make a decision about FP before the cancer treatments as important because this experience can make them feel positive, peaceful, happy, and hopeful and can give them a reason to live [20, 47]. Many survivors report that one good thing about FP is that it is one of the few decisions that they can make themselves; it allows them to feel in control of an uncontrollable situation . Furthermore, this decision-making process seems to have a positive impact on the adaptation of these female patients in survivorship. Letourneau and colleagues  preformed a retrospective study with 1041 female cancer survivors of reproductive age (18–40 years old) who had previously submitted to fertility-threatening treatments and found higher levels of life satisfaction and quality of life and lower levels of regret in relation to the FP decision in women who were counseled by a specialist in reproductive medicine about FP before cancer treatments than in women who did not receive this consultation. These results were found regardless of the decision of the female patients about FP.
Despite the importance that the decision-making process about FP seems to have for young female cancer patients, these women note significant gaps in the information provided by their oncologists about the risks of a pregnancy in survivorship, the infertility risk associated with cancer treatments and possibilities to spare their fertility . Moreover, the literature reveals a lack of or delayed referral of these patients to a fertility specialist consultation to make a decision about the preservation of their fertility (e.g., ). These two factors can prevent these patients from having a choice in this matter  because these cancer patients cite their oncologists as a critical source of support and information in the cancer diagnosis and treatment process . The literature has also reported the key role of written information and web-based tools in the improvement of FP decision-making outcomes [34, 42].
Taking this situation into account, the guidelines for intervention of several oncology societies around the world (e.g., the American Society of Clinical Oncology, Clinical Oncology Society of Australia [COSA], European Society for Medical Oncology, the European Society of Breast Cancer Specialists) emphasize the responsibility of all health professionals in oncology to inform all cancer patients about the risk of cancer treatment-related fertility and to refer them in a timely manner to a specialist in reproductive medicine to make a decision about FP [7, 12, 27, 35]. Specifically in Portugal, updated and general guidelines for intervention in oncology, with recommendations for the discussion with young adult cancer patients about their reproductive future, are needed (i.e., the existing guidelines are from 2009 and are specific to breast cancer patients; ).
The Prospective Intervention Model of the Portuguese Centre for Fertility Preservation
The PCFP of the Reproductive Medicine Department of the Coimbra Hospital and University Centre is the sole public center in Portugal that provides all the available FP options (i.e., cryopreservation of sperm, embryos, oocytes, and ovarian tissue) to patients facing treatments that may threaten their reproductive function. It was officially created in 2010 to meet the reproductive needs of patients whose fertility is at risk. Despite the availability since the 1990s of male FP in several Portuguese public institutions, female FP techniques were not previously available in Portuguese public practice. Thus, it is clearly important to attempt to ensure the potential for biological parenthood among female patients.
In the present day, the PCFP team is constituted by seven doctors, two embryologists, a psychologist, and a pharmacist. Its main goal is to support informed reproductive decisions through the life course of female cancer patients who are risk of cancer treatment-related infertility. To achieve this aim, in the last 4 years, the team has worked through different but complementary pathways that are described below.
The PCFP provides reproductive monitoring and counseling to female cancer patients from all over the country who are planning to undergo treatments that may threaten their fertility.
These patients can be referred to the PCFP by their oncologists or can ask for a consultation. Regardless of the situation, the first appointment at the center is scheduled in the 24–48 h following the request.
In their first visit to the PCFP, female cancer patients are supported in making a decision about FP. They undergo (1) a medical appointment with a specialist in reproductive medicine, where they are informed about the available FP options in terms of medical procedures involved, costs, risks, and success rates, and the adequacy of each method to each situation is discussed, taking into account sociodemographic, clinical, and reproductive variables; (2) medical exams to assess their baseline reproductive function; and (3) an appointment with the psychologist. The psychologist plays an important role in this process because this health professional assesses the psychological adaptation of the patient to the recent cancer diagnosis, the patient’s attitudes toward the risk of future infertility, and their understandings and expectations of FP and discusses the pros and cons of each FP option (this appointment is also important to identify information that needs to be better clarified by the oncologist or the specialist in reproductive medicine). This process is always performed in collaboration with the patient’s oncologist, which is essential to ensure that the decision about FP does not interfere with the cancer treatments. In this first visit to the center, the amount of time the patient has to make the final decision is defined, taking into account several variables, such as the date provided by the oncologist for the beginning of the gonadotoxic cancer treatments.
If the patient, together with the health professionals involved, decides to preserve her fertility, the next step is to perform the chosen technique. It is important to note that throughout the medical procedures involved, medical and psychological support is provided to patients according to their needs.
After this process, all patients are followed up regardless of whether they preserve their fertility. First, during the cancer treatments, the patients’ follow-up is performed by phone calls made by the psychologist of the team every 6 months. These are important opportunities for the PCFP team to stay updated about the clinical situation of the patients and for the patients to maintain contact with the team that is available to support their reproductive decisions in the future. These phone calls are also important to provide emotional support and to identify patients in need of regular appointments with a psycho-oncologist. Second, after the completion of the cancer treatments, the patients are followed through visits to the PCFP every 6 months. As in the first visit to the center, in these follow-up visits, the patients undergo (1) a medical appointment where they are counseled about their reproductive health and decisions (e.g., the possibility of becoming pregnant naturally, the use of cryopreserved material in case of previous FP, implementation of assisted reproduction techniques [ART]); (2) medical exams to monitor their reproductive function after the cancer treatments and to assess the impact of the cancer treatments in ovarian function, taking into account the baseline assessment of the first visit to the PCFP; and (3) an appointment with the psychologist. The psychologist plays an important role in this process because this health professional assesses the patients’ psychological adaptation to survivorship, their understandings and attitudes toward survivorship, and their expectations and plans about their parental project, provides emotional support in case of an infertility diagnosis, and supports decisions regarding the use of the cryopreserved material to achieve pregnancy (in case of previous FP) and attitudes about ART and even third-party techniques and adoption. It is important to note that the goals of each medical and psychological appointment in the follow-up phase are variable according to each patient, taking into account the patient’s sociodemographic, reproductive, and clinical variables.