**6. Trends in embryo storage**

Worldwide, 1.5 million ART cycles are performed each year and this number continues to rise [133]. Up to a third of patients who undergo IVF have supernumerary embryos that are cryogenically stored. A case is made for the perpetually increasing reserve of embryos and more importantly those of patients lost to follow up. For reasons undescribed here, these embryos are termed "abandoned".

At least in the USA, estimates provide that there are up to 1.4 million abandoned embryos [134] and though unknown it is safe to assume this number dwarfs the combined worldwide total. Even with permitting signed patient consents, clinics are hesitant to act and discard unclaimed embryos, largely because of the lack of regulatory guidance [135], leaving clinics vulnerable to unanticipated legal ramifications. Recently, several solutions have been proposed.

Consideration of imposing strict time limits on storage, outlining relevant responsibilities of fertility clinics and patients, and clarifying absolute guidelines related to unrestricted utility of embryos in terms of donation for third party, teaching or research use must be defined within a strict legal framework. Above all adequate long-term storage facilities are lacking.

A somewhat limited solution supporting non-fertile couples in conception and familial continuity is embryo donation. It is noteworthy to mention that cryopreservation has indirectly found a place in a larger market in terms of the transport and exchange of all types of biological samples. Initial concern over the sensitivity of microscopic volumes employed in vitrification to potentially shifting conditions during shipment has largely been overcome by advanced vapor shipping dewars, temperature monitoring, and precautionary handling.

Specific to embryo donation, ethical and genetic consequences of donation to related and unrelated parties, including offspring, must be carefully considered. In addition, given lack of restrictions on storage time limits, decades old donated embryos, thus far, may provide relatively antiquated genetics which ultimately interfere with the natural evolution of the population.

Similarly, in the case of multiple embryos donated to different parties, even a marginal risk of unsuspecting, related siblings, procreating by chance may have devastating consequences for the developing fetus. This is even more likely if embryos are donated to a clinic within the same geographical region. As such, advanced screening methods prior to procreation and/or pre-natal testing may be of benefit.

Contrary to this line of thought, in a separate context, in animal and cell line research laboratory settings, recessive gene expression and cell line mutations confer an advantage for study purposes and cryopreservation provides cell line stability against undesired changes induced by adverse events or long-term culture [136].
