Cancer incidences have an increasing trend worldwide causing a global burden. Currently, many cancer patients are achieving long-term survival due to early detection and improvements in treatments.
Intense chemotherapy and/or radiotherapy has increased the cancer survival rate but at the expense of reproductive ability, most of the time.
Therefore, oncofertility is becoming an important aspect of cancer supportive care. Thus, it is necessary to consider fertility preservation (FP) in children, adolescents, and young adults with cancer and explain the importance of this matter to their parents or guardians. It is better to be aware of clinical practice guidelines (CPG) that have been adopted by several societies working on oncofertility around the world.
This article is an update of a previous article published in 2016. It aims to provide details on oncofertility care to the Sri Lankan community and to increase the awareness related to FP options available and CPG for patients taking anti- cancer treatments.
According to the national cancer control program, 28, 967 Sri Lankans were diagnosed with cancer in 2015. Overall cancer incidence rate has increased from 83.7 per 100,000 population (17482) in 2011 to 138.1 per 100,000 population in 2015 (National cancer control program). The crude incidence rate of 31.6 was reported among the reproductively viable age group (10-39 years old) giving a percentage of 10.6. Among them, 66.8 percent were females and 33.2 percent were males.
There are some methods to treat cancer; surgery, chemotherapy, radiation therapy, target therapy and immunotherapy to name a few and some of those are still under experimental conditions.
Chemotherapy, radiotherapy and bone marrow transplantation can cure most patients if detected and treated at early stages. However, intense chemotherapy/radiotherapy can damage sex glands, leading to loss of fertility in most cases. Currently, cancer treatments are not only focusing on extending life but providing quality of life. Therefore, oncofertility is becoming an important aspect of cancer treatments.
Oncofertility is a medical field that bridges the specialties of oncology and reproductive medicine with the purpose of maximising the reproductive potential of cancer patients and survivors.
It is achieved through fertility preservation, which is the process of saving or protecting eggs, sperms, or reproductive tissues so that a person can use them to have their own children in the future.
It is useful for patients who require medical treatment that may cause reduction or loss of reproductive ability. Reproduction is the essence of life and it is important for the continuity of a nation and it is a right of every individual as well.
Cryopreservation of gametes or tissues prior to chemotherapy and/or radiation is the principal way of preserving fertility.
Cryopreservation, commonly known as freezing, is a process where cells or tissues are preserved by cooling to sub-zero temperatures through controlled (slow/rapid freezing) or uncontrolled (Vitrification) mechanisms and stored in liquid nitrogen at -196 oC.
Several options are currently available for female cancer patients to preserve fertility such as cryopreservation of immature or mature oocytes (egg freezing), embryos or ovarian tissues.
For male patients, general practice is to freeze ejaculated sperms (sperm banking) and other options are to preserve sperms residing inside the epididymis or testicular tissues (experimental). By preserving reproductive cells or tissues, it gives a great chance for patients to become parents when they overcome their disease.
Egg freezing (Cryopreservation of oocytes)
It is a simple and well-established strategy to preserve female fertility, as it does not require surgery. The first birth after human oocyte cryopreservation was recorded in 1986. The frozen eggs are thawed and combine with sperm either by IVF (In Vitro Fertilisation; the egg is allowed to be fertilised by a sperm outside the female body) or ICSI (Intra Cytoplasmic Sperm Injection; single sperm is injected directly into an egg).
Egg freezing can be used by married women as well as by unmarried women if they are willing to do so. This option is well suited for women who have religious or ethical objections to embryo cryopreservation.
This procedure requires time (depending on the woman’s menstrual cycle) for ovarian stimulation. However, menstrual cycle independent ovarian stimulation methods (Random start method) have been developed recently. Moreover, aromatase-inhibitor-based stimulation methods for estrogen-sensitive malignancies have also been formulated.
Embryo freezing (Cryopreservation of embryos)
It is an established FP method and is considered the best option for married patients. It has been available since the 1980s and has routinely been used for storing extra embryos after IVF/ICSI.
Fertilised oocyte is culture in an incubator until the embryo stage. Then the embryo is frozen and store in liquid nitrogen until the woman is ready for implantation. Embryo freezing among partners who are not married is neither ethical nor legal. Since the embryos belong to both partners, legal issues should be considered upon separation, divorce or death of the couple.
Ovarian tissues freezing (Cryopreservation of ovarian tissues)
It does not require sexual maturity and hence may be the only method available for children and girls who have not reached puberty yet.
It is useful for unmarried women with cultural backgrounds as well. Since it does not require ovarian stimulation and can be performed immediately, it is also suitable for women who cannot delay the start of chemotherapy and for young cancer patients who have recently been exposed to chemotherapy treatments.
More than 100 births have been reported worldwide from the transplantation of frozen ovarian tissue and it has demonstrated the clinical success of this method. However, in some countries, it remains experimental and some others it is not experimental anymore.
The method involves removing pieces of ovarian tissues (from the cortex, i.e. outer layer) before chemotherapy/radiotherapy and re-implanting them on the remaining ovary or close to it or in the uterine environment (an orthotopic site) or outside the peritoneal cavity (heterotopic site). However, it is important to analyse the risk of transferring malignant cells with transplanted frozen-thawed ovarian tissues.
Sperm banking (Sperm cryopreservation)
It is the simplest, effective, and established FP method for boys/men who have already reached puberty. Usually, fresh semen is collected by masturbation, electro ejaculation, or surgical method (MESA – micro epididymal sperm aspiration or TESE – testicular sperm extraction) and analysed for quality parameters. Then sperms are cryopreserved in a storage device and store in liquid nitrogen. Later it can be used for artificial insemination (AI, if the sample is enough), IVF or ICSI.
Testicular tissue freezing (Cryopreservation of testicular tissue)
It is an emerging fertility preservation technique. Although it is still experimental, it might be the only option for boys who have not reached puberty yet. This method involves surgically removing testicular tissue pieces and freezing them in liquid nitrogen at -196oC. For, post pubertal boys and men, thawed tissues can be transplanted later.
Similar to the ovarian tissues in women, it is important to analyse the risk of reseeding malignant cells with transplanted frozen-thawed testicular tissues.
Societies associated with FP and CPG
The American Society of Clinical Oncology (ASCO) has published the CPG for FP for the first time in 2006. In addition, the European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NAAN), Oncofertility Consortium, Fertiprotekt, International Society for Fertility Preservation (ISFP), and Japan Society of Clinical Oncology (JSCO) have published and updated CPGs.
The Asian Society for Fertility Preservation (ASFP) has already been established and many countries such as Japan, Hong Kong, India, Singapore, Korea, Taiwan, Thailand, Philippines, China, and Pakistan have joined the society. Some countries such as Indonesia, Malaysia, Vietnam, and Iran have started practicing FP.
Clinical practice guidelines
The major point in any CPG is “Oncofertility counseling is recommended at the earliest opportunity and prior to cancer treatment, to help patients make informed decisions on pursuing fertility preservation”.
CPG are published by some of the above societies every once in a while. Following are the main recommendations given in the CPGs published by ASCO in 2018.
Health care providers should; Address the possibility of infertility as a potential risk of therapy and discuss available fertility preservation approaches as early as possible before treatment starts. The discussion can ultimately reduce distress and improve quality of life.
Refer patients who express an interest in fertility preservation (and those who are ambivalent) to reproductive specialists.
Refer patients to psychosocial providers when they are distressed about potential infertility.
Suggest established methods of fertility preservation for post pubertal children, with patient assent and parent or guardian consent.
Encourage patients to participate in registries and clinical studies.
FP will have a social, economic, ethical, and psychological impact on society. A lack of information is the most common reason for failing to practise these methods. Good coordination between different disciplines and providing an environment that allows patients to make decisions through careful counseling is important.
Guidelines need to be optimised according to the local policies, social decorum, economical factors, cultural and religious background of the country.
What about Sri Lanka? To the best of my knowledge, FP is currently practised as an infertility treatment in Sri Lanka but not as a routine FP method for cancer patients. Money matters.
However, one centralised FP centre for the whole island might make a big difference in the post-cancer care system. A proper system should be built up to connect different sectors to act regarding FP.
It is the time to bring oncologists, gynecologists, urologists, radiologists, and pediatricians, and so on to one table, discuss, share the knowledge and make the mindset to advise young cancer patients on fertility issues and take action. It will bring hope to young cancer patients who wish to become a parent after surviving the battle.
The writer is currently attached with the Okayama University, Okayama, Japan