Fertility Issues Following Hematopoietic Stem Cell Transplantation

André Tichelli; Alicia Rovó


Expert Rev Hematol. 2013;6(4):375-388. 

In This Article

Ethical & Legal Considerations

The practice of offering fertility preservation to patients treated with HSCT raises a number of ethical issues, which may be inconsistent with one another. The principle of self-termination and autonomy (right to produce) could compete with the principle of non-maleficence (doing no harm), raising concerns about the health of the patients and the risk for the offspring. The principle of justice also belongs to an ethical consideration, referring to the question of equal access to the fertility preservation methods.[85]

The issue whether a child of a cancer survivor would be at increased risk of cancer cannot be supported as a justification for not advising fertility preservation using assisted reproduction. The consideration about a possible premature death of a cancer survivor that would leave a child bereft of one parent could raise more concern. However, the Ethics Committee of the American Society of Reproductive Medicine concludes that the risks to children to be raised by a single parent are not a sufficient reason to deny cancer patients assistance in reproducing.[84] This issue becomes more contentious for cancer survivors who are single parents, and who would leave the child orphaned.

A common debate on fertility preservation in cancer patients concerns resource allocation and the access to care. For long, the right to produce was considered a 'negative right', meaning the state should not interfere with the ability of a person to reproduce or to deny access to fertility treatment. In cancer patients the question arises about a 'positive right'.[86] Should the community or the state provide resources to enable an otherwise infertile individual to procreate? This would mean that centers for reproductive medicine should become available for all transplanted patients, and by extension, that the cost for fertility preservation should be covered either by insurance companies or by the national health care system.[68,87]

Ethical issues inherent with the development assisted reproductive technology, concern safety of tissue harvesting, its subsequent use, possible implications for progeny and ownership of the tissue. Of particular relevance is the increasing number of embryos stored IVF clinics and the fate of surplus embryos after successful treatment. In some cases religious beliefs and cultural values may preclude assisted reproductive technology. Ethical concerns involving assisted reproductive technology often lead to changes in legal regulations.

The most important legal considerations in respect of fertility preservation in general and assisted fertilization technology in particular involve consent and assent in minors, preimplantation genetic diagnosis, gestational surrogacy and disposition of stored gametes (who is the owner, leftover stored tissue and posthumous use). Since national legislation is promulgated by the government of a country, it is not surprising that a great diversity may be observed between countries.

Countries can be classified according to their technique of surveillance: countries with national legislation; countries that have guidelines only, usually provided by a national medical group; countries that have neither legislation nor voluntary guideline. However, the events in the field of medically assisted procreation are developing quickly both from a scientific point of view and in term of development of legal framework for its practical application. Therefore, surveillance and legislations may change quickly. In terms of legislation of assisted reproductive technology, some countries have a permissive approach, while others are very restrictive. The International Federation of Fertility Societies summarized regularly the various laws, regulation and guidelines established in nations from the whole world to regulate the medical practice of assisted reproductive technology.[81,88]

The consent and assent to store gametes in minor patients must be made at the time of cancer diagnosis or at least before HSCT. At that time minor patients are too young to make decision by their own, and therefore consent and assent have to be made by the parents of the child. The fertility preservation procedure in prepubertal children represent a greater than minimal risk, according to the guidelines for ethical study in children published from the American Academy of Pediatrics. However, experimental procedures in children involving greater than minimal risk are permissible as long as the risks are justified by the anticipated benefits: the anticipated benefit is at least as favorable as that provided by alternatives; appropriate permission (agreement of a parent to participation of their child in research); and assent has been obtained.[89]

Preimplantation genetic diagnosis permits to select embryos of particular genotype prior to implantation and is mostly used to avoid severe genetic disorders. Preimplantation genetic diagnosis, which implies IVF, involves creation and destruction of embryos and is therefore linked to ethical and legal considerations. Access to preimplantation genetic diagnosis is determined by the way it is regulated and available in a given country.[90] For most survivors transplanted for malignant disease pretransplant genetic diagnosis is not an issue. Theoretically it may become a relevant consideration for survivors treated for a serious genetic disorder.

Gestational surrogacy is when a woman carries a child for the transplanted woman who is unable to carry a baby. Treatment by IVF surrogacy remains a controversial issue worldwide. Of 71 countries, only 17 state that they actually practice gestational surrogacy. However, there are a number of countries in which surrogacy is being offered to couples travelling from other countries.[81]

Several legal issues concern disposition of gametes. Who has the authority to decide the fate of unused embryos and gametes in case of disagreement or subsequent to the death of the cancer survivor? Excepting cases of planned gamete donation, sperm and eggs remain the sole possession of the person from whom they were moved. An embryo however belongs to both the egg and the sperm donor. Without going into details, there is some legal ambiguity on question of how embryos should be managed if the parties refuse to pay storage fee, disagree on future use, die or divorce. Therefore, when embryos provided from a coupled relationship are cryopreserved, the couple should make an advance decision on the fate of the embryos in case that the embryos have not been used for any reason, including the death of the patient. Considering these issues and making such decision can be particularly difficult for a cancer patient who has been recently diagnosed with a life-threatening disease and has to face a long treatment.[28,84,85] Once IVF performed, patients or couples have to decide what should be done with the leftover embryos. Depending on the national legislation the options are to discard the embryos, donate them for research or use them for third party donation.

The use of an individual's gametes after his death is called posthumous reproduction. Key questions on posthumous assisted reproduction concern rights to unused material, autonomy of the patients (had the deceased person consented to posthumous use of his stored tissue or gametes), and welfare of future posthumously conceived children.[85] As for other issues of IVF, there is a great diversity in laws between different countries, varying from complete prohibition to permissive rules. There is neither a consensus among the different religions on posthumous reproduction. In a population-based study performed in the USA of attitudes toward posthumous reproduction, almost 50% among questioned individuals between the age of 18 and 75 years support posthumous reproduction in men and women. However, the majority favor prior consent from the deceased.[91] According to the most recent opinion from the Ethics Committee of the American Society for Reproductive Medicine, posthumous reproduction is ethically justifiable if written documentation from the deceased authorizing the procure is available. In the absence of written documentation from the decedent, this type of reproduction should only be considered when such request is initiated by the surviving spouse or life partner.[92]