Fertility Preservation: Should we Reconsider the Terminology?

Michaël Grynberg; Nathalie Sermondade

Disclosures

Hum Reprod. 2019;34(10):1855-1857. 

In This Article

Reasoned Opinion

From Sperm Freezing to Oocyte Vitrification

Becoming a parent represents a crucial issue for most human beings. Indeed, reproductive health is considered by the World Health Organization as a part of health, defined by a state of complete physical, mental and social wellbeing (Preamble to the Constitution of World Health Organization, 1946). Ideally, having children implies for both parents the transmission of their own genetics and for women the capacity of carrying a pregnancy. Thus, medicine has sought either to help the conception or to maintain the capacities of conceiving both in the female and male. Before the emergence of ART, preservation of these abilities was only based on minimally invasive surgical techniques. The development of ART in the late 1970s has made it possible to help infertile couples, resulting in the birth of >8 million children. Advances in embryo and gamete freezing processes improved the efficiency of ART, but also launched this discipline in the field of preventive medicine by offering solutions in case of treatment at risk of impairing fertility. The first live birth after sperm freezing was obtained in 1953 (Bunge and Sherman, 1953), and the mastery of this process has led clinicians to routinely propose cryopreservation of spermatozoa for men, young adults or pubertal adolescents in whom the fertility potential might be altered as a result of a disease and/or its treatment (Oktay et al., 2018).

However, the situation was much more complex for women. The difficulties for cryopreserving oocytes with slow freezing protocols led during the 1990s to the proposal of embryo cryopreservation for women in a couple (Oktay et al., 2018). In parallel, ovarian tissue cryopreservation for further transplantation was also developed (Oktay and Karlikaya, 2000; Oktay et al., 2001). After a first live birth obtained in 1999 (Kuleshova et al., 1999), the development of oocyte vitrification during the 2000s represented an important technical improvement that brought about major changes. It was then possible to finally consider oocyte cryopreservation as an efficient and reliable solution for women having to face gonadotoxic treatments (Oktay et al., 2018). Since then, other indications for oocyte cryopreservation have emerged such as endometriosis, gynecologic benign diseases and even healthy women seeking a strategy against the negative impact of ovarian ageing.

A Limited Efficiency

The results of these so-called 'fertility preservation' techniques in terms of live births remain difficult to establish. Although the relevance of this label is discussed (Donnez et al., 2015; Forman, 2018; Oktay et al., 2019; Gornet et al. 2019), ovarian tissue cryopreservation is still widely considered as an experimental technique, allowing the birth of only about 150 children worldwide (Donnez and Dolmans, 2018). Live birth rate after transplantation remains quite poorly known, or even unknown when dealing with ovarian tissue frozen before puberty. Concerning oocyte vitrification, following the delivery of >900 babies, the experimental label was dropped in 2013 (Practice Committee of American Society for Reproductive Medicine, 2013). It is now currently admitted, at least for donated oocytes from young females, that biological outcomes, live birth rates and perinatal outcomes are similar between vitrified and fresh oocytes (Cobo et al., 2014).

Nevertheless, oocyte cryopreservation usually concerns a limited number of samples and requires the use of IVF, a technique that is, unfortunately, far from guaranteeing success. Therefore, the overall efficiency of the procedure is very difficult to predict with certainty, even though the number of frozen oocytes and the age at egg retrieval constitute the two most important keys to success. Thus, Cobo et al. (2014) reported an only 15% live birth rate in women having five oocytes vitrified before the age of 35 years, this rate dropping to 5% when cryopreservation was performed above 35 years.

From 'Fertility Preservation' to 'Gamete Cryopreservation'?

In this context, and since we are still missing reliable markers of oocyte competence and more generally of female fertility, it is noteworthy and surprising that the term 'fertility preservation' is routinely used and seems currently well accepted for describing those techniques. Interestingly, this expression was hardly ever used for men as long as the techniques concerned only 'sperm cryopreservation'. The first appearances in scientific articles concerned surgical techniques that were meant to preserve (to spare) the ability to produce offspring by conservative interventions (Feng, 1983). The expression 'fertility preservation' remained relatively unused, and dedicated to these surgical techniques, with a few exceptions (Abir et al., 1998). Then an exponential growth was observed from 2008 to 2010, in parallel with the mastery of oocyte vitrification/devitrification processes. Gradually, this term became essential, not only when dealing with oocyte cryopreservation, but also with gonadal tissue (Bahadur and Ralph, 1999; Janson, 2000), and even sperm cryopreservation (Gosden and Nagano, 2002).

Nevertheless, we believe that 'fertility preservation' is a very ambiguous term for patients and even doctors. It contributes to false hopes about the real chances of truly preserving fertility, meaning to be able to have the number of children one would dream if (s)he did not have to face the disease and its treatments. In order to limit confusion, unambiguous and realistic terms should be allocated. To this end, qualifying the term 'fertility preservation' and even preferring 'gamete or gonadal tissue cryopreservation' may be discussed (Table I).

'Gamete Cryopreservation': A Segment of a Global Process?

One could argue that the term 'gamete cryopreservation' would only capture a piece of the 'fertility preservation' process. Indeed, it involves a multi-step strategy, from identifying the candidates, counselling them, possibly performing gamete or gonadal tissue cryopreservation techniques, evaluating post-treatment fertility potential and, when necessary, using the stored materials to achieve conception.

Another point in favour of the term 'fertility preservation' lies in the existence of options other than techniques strictly based on gamete or gonadal tissue cryopreservation. Although their usefulness for fertility preservation purposes remains controversial, these include ovarian suppression (Lambertini et al., 2019), or ovarian transposition (Arian et al., 2017).

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