Insights into Oncofertility

Introduction
The need
The scope
Ethical concerns
Preserving fertility potential
Contraception in cancer survivors
Conclusion
References
Further Reading

Introduction

Oncofertility is a new term describing an area of medicine that helps cancer survivors have their own children after chemotherapy, radiation therapy, or surgery that could leave them infertile. Such patients are of all ages, but those up to the age of 39 years are subjects of this branch of reproductive medicine.

It is devastating to know that due to the treatment of one deadly disease, another crucial bit of one’s life has been endangered. Moreover, the loss of the hormones produced in these tissues can often cause other chronic medical or subclinical loss of health. Yet, cancer care and fertility preservation were divorced for a long time.

The lack of urgency is understandable since cancer is such a malignant condition, with the focus being on surviving the disease rather than on long-term health management. However, over the last 15 years, the discipline of oncofertility was evolved to offer help to these patients for future fertility and reproductive health.

The need

Over the last few decades, diagnostic and therapeutic advances have made it possible for 80% of young cancer patients to survive. This means it is now essential to think about how best to address potential cardiac, endocrine, reproductive, and neurological issues that could arise due to treatment.

Female childhood cancer patients could suffer ovarian damage due to gonadotoxic therapies, causing premature ovarian failure in up to one in ten of them. Approximately a third will suffer gonadal dysfunction, which could mean a potential for impaired ovarian function in about 100 million women.

The mechanisms by which this occurs include chemotherapy-induced activation of the primordial follicles on a large scale, inhibition of DNA replication and cell division, atresia of the ovarian stroma, and impaired ovarian vascularity. Radiation therapy, meanwhile, induces the destruction of 50% of primordial follicles.

Especially after high doses of alkylating agents and other chemotherapeutic agents, or pelvic radiation, ovarian failure, premature menopause, and male infertility are more common. More research is urgently needed to understand the varying risk with the hundreds of cancer treatment protocols in use today and the wide range of ages and health statuses of the patients undergoing such treatments.

A large study of childhood cancer survivors found a 13% risk of female infertility, slightly higher than the 10% in their siblings.

The scope

Oncofertility includes several areas: developing novel options to preserve sperm and ova before the start of cancer treatment; a multidisciplinary approach to preserving fertility, helping with having children and managing sex hormone levels in the cancer survivor; and promoting research and communication in oncofertility. 

Apart from fertility preservation, there is a need to develop strategies that reduce the off-target effects of cancer therapies on oocyte function to prevent significant endocrine impairment and thereby, one day, avoid the need for oncofertility altogether. Multidisciplinary approaches are being worked out to better handle the development of better tools, with knowledge sharing on an active and ongoing basis between scientists in different centers and countries.

Patient-friendly web portals to allow patients to explore available technologies and fertility preservation options, as well as similar tools for healthcare providers to go through this process with their patients, are now online. Networks of oncofertility providers have been set up to make things easier for both patients and providers. Several societies have also developed professional guidelines.

Ethical concerns

Researchers have long explored the technological side of assisted reproductive technologies (ART), but the ethical aspects are equally worthy of exploration. Several religious traditions contribute to the actual responses of individuals to the use of ART within the area of oncofertility, as in other areas.

Many different viewpoints exist, ranging in their impact from refusing non-genetically related gametes or embryos, refusing non-spousal surrogates, refusing non-biological children the rights of inheritance, and viewing ART as important only if the family determines that its mission involves having children.

Each cultural and religious tradition contributes to and diversifies the dialogue around ART. They could be used to explore the dynamic relationships occurring between parents, children, and other family members. This could help understand how individuals view these techniques in the context of oncofertility.

Preserving fertility potential

To preserve female fertility, embryo banking is the best-known and most-tried procedure. It cannot be carried out in girls or women before puberty, nor with those with hormone-sensitive cancers and those who cannot find a donor to contribute the sperm. It involves oocyte banking after retrieval from the patient, but the need for hormonal stimulation makes this unviable for a subset of patients.

Another option for these patients is ovarian tissue cryopreservation. Further research is on to support now-experimental techniques like ovarian tissue transplants and in vitro follicle maturation. However, the cost and time lag involved in these protocols are obstacles to rapid research. Some have suggested using multiple models to cut down the time required to translate animal experiment results into humans.

In vitro follicle growth is promising but still in the experimental stage, as there is a need to identify the right conditions and the right type of follicle for preservation.

In males, things have been easier because of the ability to cryopreserve sperms once puberty is over. In pre-pubertal males, however, giant challenges remain. Testicular sperm extraction and testicular tissue cryopreservation are being studied as possible solutions, especially as such specimens can be thawed and transplanted back following completion of gonadotoxic treatments or by the maturation of spermatocytes in vitro, or by using an immunodeficient rodent model for xenotransplantation. The potential for the reintroduction of cancer cells must be held in mind.

Communication with such patients is key, especially with younger males who are psychologically immature when such procedures need to be considered. Guidance will be needed for them, in consultation with their families, to help them make the best decisions for their future fertility potential.

Contraception in cancer survivors

Cancer survivors often refuse contraception for fear of taking more medications, especially hormones. Yet, they will be faced with decisions on fertility and contraception because of the higher risk of pregnancy-related complications, including miscarriage, low-birth-weight and preterm births, which would make planned pregnancies a better choice for some survivors.

Ironically, some studies indicate that this group uses emergency contraception at higher rates than the general population of reproductive-age women in the USA. Researchers have found that cancer survivors think of themselves as infertile, a perception linked to their refusal of effective contraception. Another potent factor is the perceived adverse impact of hormones, which leads to the non-acceptance of hormonal contraception.

Oncofertility specialists should therefore provide a patient-specific rather than generic assessment of the risk to fertility following cancer treatments to avoid unplanned and high-risk pregnancies.

Conclusion

Many providers may not know precisely the level of risk posed by different procedures and protocols or about fertility preservation technologies in detail. Busyness leads to a shortage of time with each patient, and personal opinions may also come into play.

Also, the great difficulty of introducing fertility discussions into the treatment paradigm of aggressive cancer could mean suggesting a non-feasible postponement of the commencement of treatment often operated as a constraint. Yet, patients often deeply regret not having had the information to make such decisions at a time when intervention might have been possible.

As one expert says, “New technologies to more precisely target drugs and radiation, as well as biologics that are specific to the disease, are on the horizon. By coupling these technological advancements with a concerted effort to identify the triggers of cancer and refocus our efforts on preventive measures that will either reduce the incidence of disease or diagnose it earlier, we will achieve better outcomes for patients. All of these advances will make it possible to address cancer without affecting future reproductive health, making the word oncofertility and its practice obsolete.”

References

• Wairney, K. E. et al. Future Directions in Oncofertility and Fertility Preservation: A Report from the 2011 Oncofertility Consortium Conference. Journal of Adolescent and Young Adult Oncology. https://dx.doi.org/10.1089%2Fjayao.2012.0035. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604786/
• Hadnoff, T. N. et al. (2018). Perceived Infertility and Contraceptive Use in the Female, Reproductive Age Cancer Survivor. Fertility and Sterility. https://dx.doi.org/10.1016%2Fj.fertnstert.2018.12.016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446574/
• Zoloth, L. et al. (2011). Bioethics and Oncofertility: Arguments and Insights from Religious Traditions. Cancer Treatment Resources. https://dx.doi.org/10.1007%2F978-1-4419-6518-9_20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086485/
• Woodruff, T. K. (2015). Oncofertility: A Grand Collaboration Between Reproductive Medicine And Oncology. Reproduction. https://doi.org/10.1530/REP-15-0163. https://rep.bioscientifica.com/view/journals/rep/150/3/S1.xml
• Speller, B. et al. (2019). An Evaluation of Oncofertility Decision Support Resources Among Breast Cancer Patients and Health Care Providers. BMC Health Services Research. https://doi.org/10.1186/s12913-019-3901-z. https://bmchealthservres.biomedcentral.com/articles/10.1186/s12913-019-3901-z
• Covelli, A. et al. (2019). Clinicians’ Perspectives on Barriers to Discussing Infertility and Fertility Preservation with Young Women with Cancer. JAMA Network. doi:10.1001/jamanetworkopen.2019.14511. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2753979

Further Reading

• All Cancer Content
• What is Cancer?
• What Causes Cancer?
• Cancer Glossary
• Cancer Classification

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.