Exploring the perspectives of female cancer patients on the donation of reproductive cells for fertility preservation and research purposes

Introduction

Cancer morbidity and mortality in Poland have been on the increase since 2010 and are 15% higher than the European Union average [1]. Apart from such common risk factors as alcohol, smoking, unhealthy diet, and family history of cancer, high rates of cancer in women are also caused by the postponement of motherhood from between 20–30 years to approximately 40 years, genetic predisposition (especially the BRCA1 or BRCA2 genes), genetic anomalies of reproductive cells, no history of pregnancy or menstrual issues, use of contraceptives, hormone replacement therapy, and human papillomavirus (HPV) infection [2–4].

However, people’s fertility is also affected by the use of anti-cancer therapies, e.g. radio-chemotherapy, which not only destroys diseased cells but also has a damaging effect on healthy tissue and reproductive cells, leading to the disruption of reproductive functions [5]. Many chemotherapy drugs, especially those with high gonadotoxicity and radiotherapy, also deplete the ovarian reserve and destroy the growing population of ovarian follicles, which results in premature ovarian insufficiency [5–9]. Resumption of the menstrual cycle after completion of treatment indicates the maintenance of some ovarian function but does not guarantee fertility [5].

In Poland, following the recommendations of the Working Group on the Preservation of Fertility in Oncological Patients of the Polish Oncological Society in 2017, the cryopreservation of ovarian tissue should be used only in centres with appropriate experience by protocols approved by the Bioethics Committee [10]. There are currently 138 centres of medically assisted reproduction and banks of reproductive cells and embryos throughout the country, and they examine the causes of infertility, supporting fertility and preventing the loss of reproductive capacities [11]. Biomedical procedures such as the freezing of reproductive cells and tissues (ovarian tissues and unfertilised oocytes, testicular tissue and sperm, embryos) are used as fertility preservation methods in patients before oncological and gonadotoxic treatment [3, 12] because they help prevent the loss of fertility as a side effect of anti-cancer therapies.

The storage of eggs, sperm, and embryos in Poland is regulated by the Infertility Treatment Act and the Regulation of the Minister of Health of 15 October 2015, which state that human biological samples may be collected, stored, and distributed in biorepositories only as a part of a medically assisted procreation procedure. Simultaneously, while reproductive tissues cannot be transferred for other purposes (art. 45), on the donor’s request, surplus reproductive cells may be used for research purposes (art. 19) [13, 14]. At the same time, although these regulations protect donors and their biological material, they contain no detailed ethical or legal regulations regarding such vital issues as the transfer of reproductive material (cells and tissues) for research purposes and their preservation for reproductive purposes. This study, therefore, explores the attitudes of female cancer patients on the donation of cancer and reproductive cells for scientific and fertility research.

Material and methods

Results

The patients’ ages ranged from 19 to 78 years, the median age was 50, and the mean age was 50.8 (Table 1). The level of education varied, with the majority (56%) having completed higher education. Respondents were scattered across various urban areas, with the most significant percentage living in areas with up to 10,000 inhabitants (28.7). While 81.8% declared having children, 13.1% said they were planning to have children. The distribution of tumour stages varied, with the majority being stages 1 and 2 (28.7% and 25.7%, respectively). 24.4% considered religion important in their lives, and 17.2% thought it unimportant. 68.1% of women reported cancer history in their families.

73.4% of respondents favoured allowing the donation of reproductive cells for scientific purposes, and 62.5% believed that these issues should be regulated by Polish law (Table 2). Whereas 87.9% of respondents declared the will to share their tumour sample collected during a test or procedure for fertility research, 82.3% would not donate their reproductive cells for research purposes. Similarly, 88.2% of women expressed a negative attitude towards donating embryos that remain after in vitro treatment for research purposes.

Simultaneously, while 57.1% were willing to freeze fertilised eggs before beginning cancer treatment, only 15.8% would refuse. Moreover, 74% believed that the National Health Fund (NHF) should reimburse the freezing of eggs and sperm in cancer patients, 3.2% disagreed, and 22% were unsure.

Table 3 presents OR, 95% CI, and p-values for factors influencing women’s views on the legal regulation of reproductive cell research in Poland. The findings indicate that the most important factors associated with female cancer patients’ support for reproductive cell donation were education and religiosity. Respondents with higher education were more eager to support the donation of reproductive cells (OR = 1.976, 95% CI: 1.239–3.155, p < 0.01) and its legal regulation (OR = 2.287, 95% CI: 1.489–3.513, p < 0.001). Similarly, patients with higher education (OR = 1.809, 95% CI: 1.126–2.905, p < 0.05) and those declaring as non-religious (OR = 2.534, 95% CI: 1.535–4.183, p < 0.001) were more willing to support the reimbursement for egg and sperm freezing by the National Health Fund. The stage of the disease does not significantly impact female cancer patients’ opinions on the legal regulation of reproductive cell research in Poland.

Table 4 presents OR, 95% CI, and p-values for factors influencing women’s views on donating reproductive cells for research and fertility preservation. The findings demonstrate that female cancer patients’ opinions were associated with age, education, family planning, and religiosity. Patients who were more willing to freeze fertilised eggs before cancer treatment were younger (OR = 0.516, 95% CI: 0.340–0.782, p < 0.01), more highly educated (OR = 2.132, 95% CI: 1.400–3.248, p < 0.001), non-religious (OR = 1.968, 95% CI: 1.292–2.996, p < 0.01), and planned future offspring (OR = 2.284, 95% CI: 1.168–4.468, p < 0.05). Similarly, female cancer patients who planned future offspring (OR = 5.780, 95% CI: 1.368–24.390, p < 0.01) and declared themselves as non-religious (OR = 2.040, 95% CI: 1.185–3.510, p < 0.01) were more willing to donate reproductive cells for research purposes. Finally, younger patients declared the will to donate embryos left after in vitro treatment more often (OR = 0.470, 95% CI: 0.240–0.918, p < 0.05). The stage of disease did not significantly impact female cancer patients’ opinions on donating reproductive cells for research or fertility preservation.

Discussion

Most countries in the European Union have introduced legal regulations that require covering partial or complete financing of procedures for the use of assisted reproduction techniques, along with the possibility for oncological patients to store reproductive cells in biorepositories [18]. The Polish Parliament passed such regulation on 1 June 2024 with an amendment to the act on financing in vitro fertilisation (IVF) from the state budget on 29 November 2023, and people who have cancer are covered by this programme [19].

This research shows that although most women were in favour of donating reproductive cells for research purposes (73.4%), its legal regulation (62.5%), and the transfer of collected cancer samples for fertility research (87.9%), still 88.2% did not approve the use of embryos remaining after the IVF treatment for research purposes. These results are comparable with studies from the United Kingdom [20] showing that while respondents declared themselves willing to donate their cancer samples collected during the study (90%), less than half of the participants were willing to donate spare eggs (women only, 48%) or spare embryos remaining after in IVF treatment (44%) for scientific and research purposes. According to respondents, such research is ethically questionable because there are no detailed legal regulations regarding the embryo being considered spare and intended only for biomedical purposes.

Even documents such as the Human Fertilisation and Embryology (HFE) Act of 1990 and the amended HFE Act of 2008 lack clear regulations on this subject [21, 22]. As other research conducted by Kirkman has shown, donating eggs for research purposes is a more significant ethical challenge for women than donating sperm for men. One possible reason may be the limited number of eggs a woman has, and the more significant effort and risk required to make them available ex vivo, resulting in a more cautious approach to their use. Women, for example, may prefer to retain excess eggs after IVF for future use rather than donate them to research [23].

This research also showed that if reproductive cells were to be used for reproductive purposes, the ethical objections from cancer patients would be lower. More than half of the respondents claimed they would like to freeze fertilised eggs before beginning cancer treatment (57.1%), and 74% believed this medical procedure should be reimbursed by the NHF in Poland. Education and the role of religion in the respondents’ lives and age also greatly impacted women’s points of view.

Guaranteeing patients’ universal access to fertility preservation methods is a task that researchers and doctors might seek to implement [24]. According to another study that was conducted among 92 women with breast cancer aged 18–40 years, most patients stated that they had not received fertility preservation treatment (87.2%), 50.6% of women received no advice regarding fertility preservation, and 49.3% of patients informed about these options made no such decision because they were advised against getting pregnant. Young women with cancer rarely receive information about the possibility of preserving fertility and are often discouraged from making such a decision. Subsequent studies also confirm these conclusions. Although 90% of oncologists considered it essential to refer cancer patients to an infertility specialist for advice, as many as 86.4% of healthcare professionals failed to do so because, according to 50.5% of respondents, the urgent need to begin therapy was more important, and 34.5% justified the decision by stating that they feared for the health of any future children. Almost half of the respondents (45.6%) were unaware of any possibilities for preserving fertility in women [25]. Another study conducted in the Netherlands among 96 physicians (gynaecologists, oncologists, surgeons, radiotherapists, and haematologists) showed that although 62% of respondents took measures to protect ovarian function before or during gonadotoxic therapy, approximately one-third of oncologists failed to discuss fertility issues with women suffering from cancer due to poor prognosis for their health or the need to begin treatment immediately [26].

The intention among doctors to discuss the effects of gonadotoxic therapy on fertility appeared to be more common in the Netherlands than in the United Kingdom, as shown by the results of research by Anderson et al. Although the impact of cancer treatment on fertility was presented to 63% of younger patients, in practice, methods of fertility protection were used only in 4 girls out of 38 patients who underwent methods of fertility preservation such as oophoropexy, ovarian tissue cryopreservation, oocyte cryopreservation, embryo cryopreservation, and hormone protection were only discussed. In contrast, in 421 patients, this topic was not discussed at all. The most common reason for the lack of discussion was the fact that, in the opinion of the clinician, the remaining patients were too young (pre-pubertal), the disease was at an advanced stage of development, or, according to the respondents, there was no confirmation of the effectiveness of the techniques of fertility preservation used [27].

This last argument also appeared in the research results of other researchers. According to Rabah, Abu-Rafea, and Arafa, 80% of clinicians believe that cryopreservation is a complicated process and neglect to offer it to their patients [25]. According to Mazur-Roszak et al., cryopreservation of ovarian tissues and oocytes rather than embryos is an innovative, experimental, and invasive method [28].

In addition, the above methods of fertility preservation are also offered to patients with a specific type of cancer, but with certain reservations. According to research carried out by Dolmans et al., in the case of some diseases, such as myeloid leukaemia and acute lymphoblastic leukaemia, there is a 33% and 70% risk, respectively, of metastases to the ovaries, so the decision to cryopreserve ovarian tissue with its repeated autograft after the patients’ treatment is considered risky because it may lead to a recurrence of the disease. The researchers, therefore, believe that after thawing the collected biological material, the autotransplantation of ovarian cortical fragments should be abandoned, and in vitro, maturation of primordial follicles should be used, or isolated primordial follicles should be transplanted [29, 30].

One of the latest studies has also shown that in women who are carriers of the BRCA1 mutation, the risk of developing ovarian cancer is between 39% and 46%. In carriers of the BRCA2 mutation, the lifetime risk is between 12–20%, so it is not only recommended that regular screening tests for the diagnosis of ovarian cancer with the CA 125 marker and transvaginal ultrasound be used but also that women who are yet to have children are also offered first hormonal stimulation to collect a more significant number of oocytes, before resection of the ovaries and fallopian tubes and fertility preservation procedures [5, 31].

In addition, patients perceive oncologists as the best specialists who have the most extensive knowledge base about cancer, which is why they would like the information they receive to include fertility preservation issues. However, a recent study conducted in Poland showed that as many as 57% of patients admitted that the oncologist did not inform them about the latest infertility treatment methods. Additionally, only 19% were referred to a specialist for infertility treatment, and of this number, 17% decided to use fertility preservation methods [32]. Similar results were found by Hoffman et al., who showed that only 12% of women with cancer remember a discussion with a physician about preserving fertility [33]. Other studies have also shown that many female cancer patients do not feel adequately supported in making fertility decisions before starting treatment and, therefore, find it stressful [34].

Physicians understand the needs of their patients, but their views on fertility protection largely depend on factors such as the level of knowledge about the effectiveness of fertility protection methods, the patient’s cancer development, and access to infrastructure providing infertility treatment services in a given area/country. For example, a study conducted among British oncologists demonstrated that although 70% of respondents did not perceive the country’s existing infrastructure of fertility services as a primary barrier, 81% feared the effectiveness of fertility preservation methods [35]. A study by Alshamsan et al. also confirmed that 86% of Canadian oncologists were willing to discuss fertility preservation methods with patients. However, their decision to talk depended on the development of the patients’ oncological disease. If it was not advanced, 92.8–100% of doctors declared that they provide their patients with knowledge about fertility preservation methods [36]. However, research conducted in Oman showed that although 78% of oncologists believed that a discussion of the impact of treatment on fertility should be presented along with information about the diagnosis of cancer, and many physicians declared feeling comfortable raising this topic in conversations with their patients, as many as 82% of respondents said that the main obstacle to starting a discussion was the awareness of the lack of access to facilities providing infertility treatment services in the country. In addition, 53% of physicians expressed concerns about having the latest knowledge about effective fertility preservation methods [37].

It is also worth noting that over the last decade, the number of women referred for fertility preservation tests before starting anticancer treatment has been gradually increasing. A recent study conducted among approximately 7000 American oncology patients showed that women received advice on fertility preservation methods more often than men (56% vs. 32%) [38]. This result is similar to the conclusions presented by researchers from Japan, who showed that 48% of teenagers and young women received information about the impact of anticancer therapy on the health of the reproductive organs [39].

The data shows that oncologists from various regions of the world increasingly express the need to develop knowledge in the field of fertility preservation and learn new effective methods of communication with patients because they want to avoid misunderstandings and unnecessary stress, as well as to provide factual information about methods to protect patients’ fertility before they start treatment. Secondly, they call for better access to fertility protection counselling. Therefore, they expect a clear strategy and new programs to facilitate cooperation between oncologists and reproductive specialists. The concept of cooperation with physicians from highly specialised clinics would offer not only faster access to clinical trials but also highly specialised care, informing patients about the risk of infertility related to chemotherapy and radiotherapy and the selection of an appropriate method to protect fertility, especially in young patients who are in their reproductive years and would like to have offspring in the future.

Conclusions

This research shows that most cancer patients believe that research using reproductive cells should be legally regulated in Poland. Moreover, while the majority expressed the will to donate their reproductive cells for reproductive purposes, they also believed that the State should reimburse medical costs of fertility preservation. Additionally, most patients supported donating cancer tissues left after surgery for research purposes.

Simultaneously, while most respondents expressed the wish for fertility preservation and the planning of children after their cancer treatment is over, there is an urgent need for legal regulation of the surplus embryos that remain after in vitro treatment and their use for research purposes. The following guidelines should, therefore, also be implemented: