The first study to report on a ‘national landscape’ of elective fertility preservation – based on SART data in the USA - finds that most eggs ‘remain frozen’ despite a steady uptake in the number of cryopreservation cycles.
In some countries, the concept of cryopreserving oocytes for later personal use – known familiarly as elective or social egg freezing – hardly exists. The practice may be of little public interest, or restricted by law. Indeed, it was only in July this year that the French Parliament approved a bill extending IVF rights to single and lesbian women and allowing egg freezing for non-medical reasons.(1)
Yet in its most recent report on trends in UK fertility treatment, the HFEA noted that egg freezing (for medical and non-medical indications) has increased tenfold in the past ten years, from just under 230 cycles in 2009 to almost 2400 cycles in 2019. ‘It is likely that demand for egg freezing will continue to increase in the future,’ reported the HFEA with some understatement.(2) Indeed, a statutory change in the UK has just seen the gamete storage limit extended from ten years (to 55), which, says the HFEA, will give the public even greater ‘reproductive choices’.(3)
Yet these UK numbers seem somewhat negligible when seen alongside those in the USA – although the annual rates of increase are not too different. A new study, said to be the first to include all oocyte cryopreservation cycles performed from 2012-2018 (and based on SART data), puts total treatment cycles at more than 54,000, for which 5400 transfers were performed.(4) However, despite these numbers and the hype behind social egg freezing in the USA, the authors note that the number of transfers after the cryopreservation cycle is still ‘relatively low’, accounting for just 11% of the cryo-cycles completed within the study period.
Such figures in the speculative world of egg freezing have remained ‘unpublished’, say the authors, leaving clinics offering a service reliant on limited studies – and the promise of ‘false hope’ – in counselling their prospective patients. However, to them, say the authors, the appeal of such treatment ‘is to increase the likelihood of future conception with the use of autologous gametes, because live birth rates with the use of conventional IVF depend primarily on female age at the time of oocyte retrieval’. As registry figures show time and time again in egg donation, it’s the age of the donor which determines outcome, not the age of the recipient.(5)
So with this first real-world analysis of what’s going on in egg freezing – at least in the USA – what did we learn?
* In absolute terms, the patient numbers are not as high as some might imagine – a rise in egg freezers from 2719 in 2012 to 13,824 in 2018, and a rise in thawers from 348 to 1810.
* Age at the time of egg freezing remained consistent throughout the study period at 35.4 years; however, age at the time of thaw did increase, from 36 to 38.5 years. This was reflected in an increase in the duration of cryopreservation from 15.7 to 29.4 months.
* Most of those who received embryos from their thawed oocytes had a normal BMI, although around one-third appeared to have a diminished ovarian reserve.
* And we now have some real-life data on the correlation of success rates with age at the time of freezing. Among those who actually thawed eggs and went on to embryo transfer, LBR as expected decreased markedly with increasing age at the time of freezing - from 42.8% at 35 years to under 10.8% at over 42 years. Because some patients ended up with no transfer, LBR was unsurprisingly higher when calculated per transfer than per thaw cycle.
As seems to be a persistent challenge for clinics (and their patients), the number of oocytes needed for a successful live birth is not precise but is closely correlated with the patient’s age at time of freezing. Thus, the average number of oocytes retrieved (in thawed cycles) in women under 35 was 17.6, while this fell to 11.5 in 38-40s and to 6.9 in over 42s. However, the average number of oocytes thawed per treatment remained fairly consistent, at around ten (although falling to six in over 42s), with a commensurate number of embryos available for transfer.
As is evident in routine IVF, the rate of attrition from oocyte to embryo rose with increasing age at the time of freezing, such that each resulting embryo had a lower chance of implantation and a higher chance of miscarriage. ‘The concordance of a larger study population over a longer period of time with national fresh IVF outcomes and with previous studies is reassuring,’ the authors write.
They also show some confidence that this study, unlike previous ‘center-specific studies’, describes a broad ‘national landscape’, though adding as their first conclusion that most cryopreserved oocytes ‘remain frozen’. This too is the situation reported from the few centres previously presenting data.(6)
One study, however, based on a population of patients at Harvard Medical School (including egg donors), has tried to develop an evidence-based model to predict the probability of a woman having at least one, two or three live birth(s) based on her age at egg retrieval and the number of mature oocytes frozen.(7) This age specific model, said the authors, would provide a counselling tool to help inform those considering elective egg freezing of their likelihood of live birth(s), how many cycles to have, and when additional cycles would bring diminishing returns.
The strong patient message from this latest study is the effect of age at the time of freezing. ‘The striking increase in the number of oocytes needed to achieve one live birth in women of increasing age should be publicized,’ insist the authors, ‘because the degree to which frozen oocytes serve as an “insurance plan” correlates directly with age at the time of cryopreservation.’ The recent systematic review cited above also notes that ‘clinicians should properly inform women about the safety, efficacy, benefits, usage rate, risks, and costs of the procedure and offer them real expectations’.(5)
The new US study offers no comment on vitrification and how its widespread uptake has made egg banking possible, nor on a distinction in outcome between oocytes cryopreserved for medical and non-medical indications. A comparison was previously made in data from the IVI group, which found a significantly lower implantation rate in their onco-fertility patients, but no proven impact of the disease per se.(8) But again, this study was hindered by a small number of patients thawing their eggs and going on to transfer – and again the emphatic message was that ‘patients should be counselled according to their age and number of available oocytes’.
1. See https://www.focusonreproduction.eu/article/News-in-Reproduction-Legislation-in-France
2. See https://www.hfea.gov.uk/about-us/news-and-press-releases/2021-news-and-press-releases/hfea-responds-to-new-gamete-storage-limit/
3. See https://www.hfea.gov.uk/about-us/publications/research-and-data/fertility-treatment-2019-trends-and-figures/#Section6
4. Kawwass JF, Crawford S, Hipp HS. Frozen eggs: national autologous oocyte thaw outcomes. Fertil Steril 2021;
6. Varlas VN, Bors RG, Albu D, et al. Social freezing: Pressing pause on fertility. Int J Environ Res Public Health 2021; 18: 8088. doi.org/10.3390/ ijerph18158088
7. Goldman RH, Racowski C, Farland LV, et al. Predicting the likelihood of live birth for elective oocyte cryopreservation: a counseling tool for physicians and patients. Hum Reprod 2017; 32: 853-859. doi.org/10.1093/humrep/dex008
8. Cobo A, Garcia-Velasco J, Domingo J, et al. Hum Reprod 2018; 33: 2222-2231. doi.org/10.1093/humrep/dey321