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The dilemma of social oocyte freezing: usage rate is too low to make it cost-effective

      Abstract

      Delayed childbearing in affluent countries and the financial crisis of the Y-generation have contributed to the dramatic decline in birth rate. Social oocyte freezing (SOF) has fuelled the imagination of patients and doctors to offer it as a solution to single, presumably fertile, women to preserve their fertility potential by egg banking at an early age. Some are calling on governments to support large-scale ‘fertility preservation’, but is it cost-effective? Social oocyte freezing is effectively expensive insurance, where future utilization is unknown. Theoretical studies have suggested that SOF is only cost-effective with a usage rate of 50% or over, and when getting married is not set as a condition. Maximal possible utilization of frozen eggs, however, is much lower. Recent studies have found usage rates of 3.1–9.3%, which sets the cost of each extra live birth between $600,000 and 1,000,000. As IVF is being privatized and business-driven, it is hard for experts to decipher scientific- from business-oriented claims. The cost-effectiveness of SOF for individuals or society unclear. These facts place the burden of responsibility on the treating physician, who should inform patients about the true likelihood of using their eggs, the age at which to freeze and possible alternatives.

      KEYWORDS

      Key message
      Social freezing is promoted to single women as a way of preserving their fertility potential. Recent studies have found usage rates of 3.1–9.3%, setting the cost of each extra live birth at between $600,000 and 1,000,000. Women should be informed about the true chance of using the eggs, the age to freeze them and possible alternatives.

      Introduction

      Delayed marriage, late childbearing especially among the affluent countries and the financial crisis of the Y-generation, in some countries, have led to a dramatic decline in birth rate and population. Nothing has changed in women's physiology that allows deliberate postponement of childbearing. Pregnancies and deliveries should ideally be completed before a woman reaches the age of 35 years, at which point fertility tends to drop at a faster rate. Fertility drops annually: 1–4% before the age of 35 years, 15% after the age of 35 years and 35% after the age of 40 years (
      • Malchau SS
      • Henningsen AA
      • Rasmussen LS
      • Forman J
      • Nyboe Andersen A
      • Pinborg A
      The long-term prognosis for live birth in couples initiating fertility treatmentsHum.
      ). At the age of 35 years, about 35–40% of women will face difficulties in conceiving, increasing after 40 years to over 60% of women. The reasons for this decrease in fertility are numerous. The first and most important reason is the ‘ageing ovary’: a sharp drop in the number of oocytes in the ovary with increasing age. Incidence of the so-called ‘mechanical infertility’, pelvic adhesions or blocked tubes owing to previous pelvic infections, pelvic operations, cystectomy or endometriosis is also increasing. Uterine fibroids and the surgery to remove them can also potentially damage the uterine, tubal or pelvic architecture. Male factor infertility, which can be responsible for, or exists concomitantly with female infertility, affects almost one-half of cases and increases with age.
      As physicians, we cannot influence the trend of delayed marriage nor solve the financial problems of youth, which require governmental reform. We also cannot influence, beyond providing education, the delay in childbearing, which is related, among other factors, to a longer life expectancy. Women are usually aware of the risks of delayed childbearing, but they have a subjective sense of security amidst popular publications that advocate fertility treatments and IVF, even in older age, and recently that egg banking as the ultimate solution, so that frozen eggs can be used in the future when the right partner comes along. Reports show that women decide on egg banking at a mean age of over 37 years, which is older than the medical community suggests. But a relevant question is how many women ever use their frozen eggs (
      • Cobo A.
      • García-Velasco J.A.
      • Coello A.
      • Domingo J.
      • Pellicer A.
      • Remohí J
      Oocyte vitrification as an efficient option for elective fertility preservation.
      ,
      • Hammarberg K
      • Kirkman M
      • Pritchard N
      • Hickey M
      • Peate M
      • McBain J
      • Agresta F
      • Bayly C
      • Fisher J
      Reproductive experiences of women who cryopreserved oocytes for non-medical reasons.
      ). Have we, the physicians, in our eagerness to provide a perfect, albeit a costly solution, missed something in the perceived ‘crowd wisdom’? Maybe.
      Infertility treatments, particularly IVF, can help in achieving pregnancy, with success in most cases dependent on age. In some cases, however, IVF often fails. The most challenging indication for IVF is poor ovarian reserve and the age-related decrease in fertility, which is associated with a low number of poor-quality eggs, chromosomal abnormalities and higher incidence of miscarriages. The possible evolutional explanation for these processes, which limits fertility several years before menopause (which coincides with life expectancy of our ancestors) is maybe to allow the mother time to rear the last child to puberty. This ‘protective mechanism’ becomes an obstacle when it occurs early, in women who wish to delay motherhood. Until recently, the only way to offset the consequences of ovarian ageing was reverting to egg donation.

      High success with oocyte freezing was proven

      In the past decade, an extension of the oncology-related procedures of ‘fertility preservation’ and the increasing efficacy of oocyte vitrification have fuelled the imagination of patients and doctors to think that it is also the solution for all young fertile women or women with unproven fertility who delay marriage and childbearing to the fourth or fifth decade of life. Studies have proven that vitrified–warmed oocytes can be fertilized at a high percentage, implant and achieve normal pregnancies and offspring after a relatively ‘short period’ of freezing (
      • Rienzi L.
      • Cobo A.
      • Paffoni A.
      • Scarduelli C.
      • Capalbo A.
      • Vajta G.
      • Remohı J.
      • Ragni G.
      • Ubaldi F.M.
      Consistent and predictable delivery rates after oocyte vitrification: an observational longitudinal cohort multicentric study.
      ,
      • Cobo A.
      • Garcia-Velasco J.A.
      • Domingo J.
      • Remohí J.
      • Pellicer A.
      Is vitrification of oocytes useful for fertility preservation for age-related fertility decline and in cancer patients?.
      ,
      • Cobo A.
      • Serra V.
      • Garrido N.
      • Olmo I.
      • Pellicer A.
      • Remohí J.
      Obstetric and perinatal outcome of babies born from vitrified oocytes.
      ,
      • Cobo A.
      • Garrido N.
      • Pellicer A.
      • Remohi J.
      Six years' experience in egg banking.
      ,
      • De Munck N.
      • Belva F.
      • Van de Velde H.
      • Verheyen G.
      • Stoop D.
      Closed oocyte vitrification and storage in an oocyte donation programme: obstetric and neonatal outcome.
      ). Although it is yet to be proven that oocytes cryopreserved for a decade or more remain highly viable and effective, today's knowledge (
      • Goldman KN
      • Kramer Y
      • Hodes-Wertz B
      • Noyes N
      • McCaffrey C
      • Grifo JA
      Long-term cryopreservation of human oocytes does not increase embryonic aneuploidy.
      ) suggests that it will probably be the case even if the methods are still being refined in many clinics to reach the level of published experience.
      Superficially, the issue seems straightforward. If carried out in a timely manner ‘social oocyte freezing’ (SOF) can offer an efficient solution for women who opt to delay childbearing and can freeze the potential to conceive for a later age (Lockwood et al., 2011). A young woman who freezes her eggs before the age of 35 years will freeze her potential to conceive during her fourth and fifth decades, preserving her potential at the age of freezing. No studies have supported the cost-effectiveness of this practice, which is essentially offered to ‘fertile’, or at most to women of ‘unproven fertility’, who must undergo costly, taxing, and somewhat risky oocyte retrieval procedures to preserve their potential. This is a new and potentially profitable market for IVF clinics, which has stimulated reservations and condemnation (
      American Society for Reproductive Medicine (ASRM)
      ASRM Practice Committee response to Rybak and Lieman: elective self-donation of oocytes.
      ). Others (Radon et al., 2015) have expressed concerns that the procedure will encourage patients to further delay childbearing. Doubts have also been raised about the high efficacy of freezing (
      • Kushnir VA
      • Barad DA
      • Albetinin DA
      • Darmon SK
      • Gleicher N
      outcome of fresh and cryopreserved oocyte donation.
      ), as live birth rate in donated eggs after freezing is lower compared with fresh.

      What is the controversy?

      Fertility preservation for social reasons is probably here to stay based on its inherent logic, but also because of powerful marketing and interest among patients and doctors. The offer to use freezing for social motives, however, is gaining ground worldwide, marketing a new indication that increases the request for IVF to the domain of fertile women. Nevertheless, SOF leaves many questions unanswered; apart from the need to frequently reassess the strengths, weaknesses and opportunities of the procedure, we need to redefine indication, and to evaluate the true cost effectiveness to the individual and to the society.
      As discussed, SOF is a sort of insurance, where the full cost of the procedure must be paid upfront. Only those who have ‘bought’ the full insurance ‘not too early and not too late’ will have a chance of benefitting from its potential at a better cost. Early freezing is associated with higher success but lower usage percentage and lower cost-effectiveness and vice versa. Also, differences in social practices, such as women who attempt pregnancy only if married or after finding a known partner, might be a barrier as age advances. From a medical perspective, the woman ‘buys’ time and a sense of security; statistics shows that at an advanced age, the chances of marriage are slim (
      • Mesen T.B
      • Mersereau J.E.
      • Kane J.B.
      • Steiner A.Z.
      Optimal timing for elective egg freezing.
      ). Hence, egg freezing and waiting to get married are somewhat contradictory, and such delay proves detrimental to the chances of ever using the eggs, thus decreasing the cost-effectiveness of the procedure. Understandably, some have dubbed SOF as a ‘lottery’.

      A procedure without indication with slim chances of usage

      Social oocyte freezing is a procedure without indication. The target population is all single women, at almost all age groups, and certainly between the ages of 30 and 40 years. The users are affluent women for whom the cost might not be a prime issue; otherwise, going through repeated cycles of egg banking might be too costly for most patients. Women who are trapped between the hammer of social changes and the anvil of ageing ovaries are the target of aggressive marketing of this procedure by public and private clinics. Many are calling on governments or insurers to support large-scale ‘fertility preservation’ to offset the natural decrease in fertility, as well as to give a second chance to women who delay childbearing as if it is already a fully proven cost-effective procedure. It is not surprising, therefore, that major global corporations such as Apple and Facebook (www.washingtonpost.com, accessed 15 October, 2014) have stepped in and have offered SOF as a ‘work benefit’, which can allow young women to dedicate their prime years to their careers and delay motherhood without ‘worrying’ about their future fertility. This highly publicized move came early during the course of events and is perceived as endorsement of the technology by the ‘leaders of technology’, as well as indicating it to be the right move for young childless women. This endorsement has added to the conviction that egg freezing is the right move for young affluent women, and came before the medical community had the chance to fully appraise the procedure. In theory, however, a woman who freezes her eggs at the ages of 32–34 years and gets married at the age of 35 years and starts trying to conceive, will most probably not use her frozen eggs initially. She will first attempt to achieve a spontaneous pregnancy, then attempt with treatments and, only if these fail, which is less than 5% of all women at that age (table 1), will she use the frozen eggs; therefore, a woman freezing her eggs at this age should know that she is paying the full cost with slim chances of utilization.
      Table 1 Theoretical calculation of the maximal ‘usage percentage’ expected for each age group using the results from Malchou et al. (
      • Malchau SS
      • Henningsen AA
      • Rasmussen LS
      • Forman J
      • Nyboe Andersen A
      • Pinborg A
      The long-term prognosis for live birth in couples initiating fertility treatmentsHum.
      )
      Age (years)Adjusted odds ratio
      Adjusted odds ratio: annual decrease in adjusted odds ratio for live birth rate with age.
      (%)
      Infertile (%)Pregnant spontaneously (%)Pregnant with treatment (%)Cumulative pregnant (%)Overall infertile women pregnant (%)Overall not pregnant (%)
      Calculation of the maximal possible usage rate expected if entire age group freezes eggs and all opt to use the banked eggs after treatment failure.
      26–35415166480123
      35–3915401050602416
      >40336011162716.245
      a Adjusted odds ratio: annual decrease in adjusted odds ratio for live birth rate with age.
      b Calculation of the maximal possible usage rate expected if entire age group freezes eggs and all opt to use the banked eggs after treatment failure.
      The number of eggs needed to freeze at each age to give a fair chance of success differs and determines the cost. Statistics show that, in general, only one out of 20–25 eggs collected (4–5%) will result in the delivery of a baby (
      • Doyle JO
      • Richter KS
      • Lim J
      • Stillman RJ
      • Graham JR
      • Tucker MJ
      Successful elective and medically indicated oocyte vitrification and warming for autologous in vitro fertilization, with predicted birth probabilities for fertility preservation according to number of cryopreserved oocytes and age at retrieval.
      ). The mean number of eggs collected in a single cycle is eight to 12, which means that freezing of 20–25 mature eggs requires two to four cycles at a cost of 6–15,000 US$ per cycle plus variable yearly storage cost. Between 20 and 25 eggs gives an 80–85% chance of having a baby (
      • Cobo A.
      • Garrido N.
      • Pellicer A.
      • Remohi J.
      Six years' experience in egg banking.
      ); after the age of 35 years, however, a larger number of eggs are required to secure such a high success rate, owing to the decline in egg quality and quantity. Obviously, these figures are dependent on the male partner's health and sperm quality, which is unknown at the time of freezing. Therefore, the total financial commitment, be it for the individual or for the governmental budget, is enormous.

      Cost-effectiveness considerations

      Few theoretical studies have looked at usage rate to address cost-effectivenesss.
      • van Loendersloot L.L.
      • Moolenaar L.M.
      • Mol B.W.
      • Repping S.
      • van der Veen F.
      • Goddijn M
      Expanding reproductive lifespan: a cost-effectiveness study on oocyte freezing.
      concluded that oocyte freezing is more cost-effective than no freezing if at least 61% of women return to use their frozen eggs and are willing to pay 19,560 (cost of 6.5 cycles) Euro per live birth. The investigators did not specify if the goal of 61% usage rate is at all achievable.
      Others (
      • Devine K.
      • Mumford S.L.
      • Goldman K.N.
      • Hodes-Wertz B.
      • Druckenmiller S.
      • Propst A.M.
      • Noyes N.
      Baby budgeting: oocyte cryopreservation in women delaying reproduction can reduce cost per live birth.
      ) have concluded that oocyte cryopreservation remains cost effective as long as it is carried out before the age of 38 years, and if more than 49% of those women not achieving a live birth spontaneously returned to use their oocytes. These authors also stressed that ‘per cent usage’ is a major factor in determining cost–benefit calculations, but did not mention if such a high usage rate (49%) is realistic and achievable.
      • Devine K.
      • Mumford S.L.
      • Goldman K.N.
      • Hodes-Wertz B.
      • Druckenmiller S.
      • Propst A.M.
      • Noyes N.
      Baby budgeting: oocyte cryopreservation in women delaying reproduction can reduce cost per live birth.
      have set the age higher at younger than 38 years rather than the clinical suggestion of 30–35 years and similar to real-life results (
      • Cobo A.
      • García-Velasco J.A.
      • Coello A.
      • Domingo J.
      • Pellicer A.
      • Remohí J
      Oocyte vitrification as an efficient option for elective fertility preservation.
      ,
      • Hammarberg K
      • Kirkman M
      • Pritchard N
      • Hickey M
      • Peate M
      • McBain J
      • Agresta F
      • Bayly C
      • Fisher J
      Reproductive experiences of women who cryopreserved oocytes for non-medical reasons.
      ). Also, as the cost of IVF varies widely (two- to six-fold) between countries and between the studies that originated in the USA and Europe, prices should be compared as multiples of the cost of single IVF cycle for each country.
      Hirschfeld-Cytron et al. (
      • Hirshfeld-Cytron J
      • Grobman WA
      • Milad MP
      Fertility preservation for social indications: a cost-based decision analysis.
      ) used three different strategies to examine cost per live birth: freezing at 25 years; using frozen eggs or frozen ovarian tissue at 40 years after six cycles of conventional treatment; and waiting. Both freezing strategies did not seem to be cost-effective compared with the waiting strategy.
      • Mesen T.B
      • Mersereau J.E.
      • Kane J.B.
      • Steiner A.Z.
      Optimal timing for elective egg freezing.
      constructed a theoretical model for women aged 25–40 years attempting conception 3, 5 and 7 years after freezing with or without electing to marry before usage. They found that oocyte cryopreservation was most cost-effective at age 37 years, at a cost of $28,759 per each additional live birth. Little benefit over no action was seen at ages 25–30 years (2.6–7.1% increase). Moreover, if the probability of getting married was factored-in, as many women are only willing to use their eggs if they married, cryopreservation resulted in no improvement in live birth rates. The societal cost for additional live birth between the ages of 25–30 years in such cases will increase to $366,824–$698,722, casting doubts over an early freezing strategy for the individual and surely for the society.
      If the societal cost is dependent on usage rate, what is the maximal usage rate that can be expected? Can we reach the threshold of approximately 50% needed to make SOF cost effective? To answer these questions, data from a recent large study (
      • Malchau SS
      • Henningsen AA
      • Rasmussen LS
      • Forman J
      • Nyboe Andersen A
      • Pinborg A
      The long-term prognosis for live birth in couples initiating fertility treatmentsHum.
      ) on 19,884 women were analysed to assess the realistic usage rate possible in each age group (table 1). It is widely accepted that about 10–15% of all couples between the ages of 25 and 35 years are infertile, gradually growing to 35–40% after the age of 35 years, and reaching over 50–60% infertility after the age of 40 years.
      • Malchau SS
      • Henningsen AA
      • Rasmussen LS
      • Forman J
      • Nyboe Andersen A
      • Pinborg A
      The long-term prognosis for live birth in couples initiating fertility treatmentsHum.
      have shown that the cumulative delivery rate (treatment dependent and independent) of 80%, 60% and 27%, respectively, was achieved within 5 years in these three age groups, respectively, despite an annual fertility rate decrease at each age group of 4% in women younger than 35 years, about 15% between the ages of 35 and 39 years, and 33% in women over 40 years, respectively. When these two sets of numbers are combined, the usage rate of approximately 50%, required for cost-effectiveness, is unachievable (table 1). Of the maximal 15% infertile women under the age of 35 years, 80% will achieve pregnancy with or without treatment, leaving only 3% infertile. This represents the maximal ‘usage rate’ for this age group if the entire group freezes their eggs, a figure which is extremely non-cost effective. At the age group of 35–39 years, of the maximal 40% infertile women, 60% according to
      • Malchau SS
      • Henningsen AA
      • Rasmussen LS
      • Forman J
      • Nyboe Andersen A
      • Pinborg A
      The long-term prognosis for live birth in couples initiating fertility treatmentsHum.
      are expected to succeed (24%), leaving only 16% infertile, which also represents the maximal expected usage rate in this age group if all the women freeze their eggs and are ready to use them. Among women aged over 40 years (an age at which most doctors will not suggest freezing) with an approximate 60% infertility rate, only 27% are expected to be successful (16.2%), with 43.8% remaining infertile.
      As the mean age for egg banking is above 37 years, and the actual utilization rate would be less than the maximum theoretical rate, even without factoring in the women who opt to wait to marry first, which would further decrease the usage rate, the utilization rate of 50% would not be achieved.

      Results of new publications substantiates the doubts

      Unexpected support for this calculation was recently provided by real-life studies evaluating the usage percentage and the age at egg banking (Table 2). The first study (
      • Cobo A.
      • García-Velasco J.A.
      • Coello A.
      • Domingo J.
      • Pellicer A.
      • Remohí J
      Oocyte vitrification as an efficient option for elective fertility preservation.
      ) shows that, from 1468 women freezing their eggs between 2007 and 2015, at a mean age of 37.7 years (CI 36.5 to 37.9), only 137 (9.3%) returned to use their oocytes and only 40 babies were born (2.7% per patient), which concurs with the theoretical estimation (Table 1) and is far lower than the minimum usage of 50–60% that was calculated to be cost-effective. If we put a modest tag price of $8000 per cycle and considering only two such cycles for egg collection and storage, then the cost for each baby born in this study reaches about $600,000 (1468 × 8000 × 2 ÷ 40). According to the second study (
      • Hammarberg K
      • Kirkman M
      • Pritchard N
      • Hickey M
      • Peate M
      • McBain J
      • Agresta F
      • Bayly C
      • Fisher J
      Reproductive experiences of women who cryopreserved oocytes for non-medical reasons.
      ), of 193 women who stored their eggs between 1999 and 2014, the mean age at the time of freezing was 37.1 years (range: 27–42 years), as in the study by
      • Cobo A.
      • García-Velasco J.A.
      • Coello A.
      • Domingo J.
      • Pellicer A.
      • Remohí J
      Oocyte vitrification as an efficient option for elective fertility preservation.
      , and the average number of oocytes stored was 14.2. A total of 18 patients conceived spontaneously or with treatment, only six women (3.1%) returned to use the frozen eggs and three (1.6%) patients achieved pregnancy. Assuming again a cost of $8000 per cycle and two cycles per patient, the societal cost per live birth was over $1,000,000. In this study, one in three women achieved a pregnancy at some stage without the frozen eggs; the main reason stated for not using stored oocytes was not wanting to be a single parent.
      Table 2– Cost per baby, assuming cost per egg retrieval plus storage of $8000, and assuming only one or two cycles of oocyte freezing per patient following egg banking
      StudyCycle cost ($)YearsNumber of women freezing eggsMean age (years)Women using frozen eggs n (%)Pregnancies from frozen oocytes n (%)Cost per baby ($)
      • Cobo A.
      • García-Velasco J.A.
      • Coello A.
      • Domingo J.
      • Pellicer A.
      • Remohí J
      Oocyte vitrification as an efficient option for elective fertility preservation.
      One cycle: 80002007–2015146837.7137 (9.3)40 (2.7%)293,600
      Two cycles: 16,000587,200
      Hammarberg, 2017One cycle: 80001999–201419337.16 (3.1)3 (1.6%)514,666
      Two cycles: 16,0001,029,332
      The low usage rate commensurate with our calculation and the high societal price per live birth (of about $600,000–1000,000) is probably an underestimate, as many women will need more than three cycles and the cost of treatment plus storage in many countries might be higher.
      In both studies, age at freezing was over 37 years, which is contrary to the advice of most physicians, of freezing eggs at an earlier age when chances are better (
      • Cobo A.
      • García-Velasco J.A.
      • Coello A.
      • Domingo J.
      • Pellicer A.
      • Remohí J
      Oocyte vitrification as an efficient option for elective fertility preservation.
      ,
      • Hammarberg K
      • Kirkman M
      • Pritchard N
      • Hickey M
      • Peate M
      • McBain J
      • Agresta F
      • Bayly C
      • Fisher J
      Reproductive experiences of women who cryopreserved oocytes for non-medical reasons.
      ). This trend is not surprising given the high cost of the procedure and the need for many eggs, the hope of succeeding without medical help and the low overall usefulness of egg banking. In fact, according to
      • Mesen T.B
      • Mersereau J.E.
      • Kane J.B.
      • Steiner A.Z.
      Optimal timing for elective egg freezing.
      , cost-effectiveness is slightly improved in women aged over 37 years (
      • Mesen T.B
      • Mersereau J.E.
      • Kane J.B.
      • Steiner A.Z.
      Optimal timing for elective egg freezing.
      ), and the success rate is still low (not more than 30% with 10 metaphase II oocytes, which translates to over 30 eggs for 85–90% success rate, which usually means several costly retrievals. On this basis, some investigators have suggested that patients should opt for egg freezing at an earlier age (
      • Cobo A.
      • García-Velasco J.A.
      • Coello A.
      • Domingo J.
      • Pellicer A.
      • Remohí J
      Oocyte vitrification as an efficient option for elective fertility preservation.
      ), when efficiency is better; however, this will only make SOF less cost-effective.
      To increase the chances of future usage of frozen eggs and make the procedure more cost effective, stricter indications are needed, which will decrease the denominator; however, SOF has no clear indication. For example, women who are destined to be poor responders and who have up to 100-fold fewer eggs at any given age than other women could have been the prime indication. These women are the first to pay the price of the current social practice to delay childbearing. If we could identify them before they become low responders, we could offer them a thorough consultation, including SOF, to protect their fertility or allow them time to better space childbearing. Currently used tests, however, such as antral follicular count, anti-Müllerian hormone and FSH levels, can identify poor ovarian reserve only when it has started (
      • Broekmans F.J.
      • Kwee J.
      • Hendriks D.J.
      • Mol B.W.
      • Lambalk C.B.
      A systematic review of tests predicting ovarian reserve and IVF outcome.
      ) and the patients are already low producers of eggs. The lack of tests capable of predicting low response ahead of time is a great limitation in our ability to serve these patients with egg banking when the cost and effectiveness can be higher.
      Another possible target group are women with endometriosis who undergo surgery for endometrioma. It is well recognized that such an operation may decrease the ovarian reserve and, therefore, must be delayed if possible. If such an operation is deemed necessary, however, it is important to consider freezing eggs before the operation in case the patient loses ovarian potential and becomes a low responder (
      • Somigliana E.
      • Viganò P.
      • Filippi F.
      • Papaleo E.
      • Benaglia L.
      • Candiani M.
      • Vercellini P.
      Fertility preservation in women with endometriosis: for all, for some, for none?.
      ).
      • Malchau SS
      • Henningsen AA
      • Rasmussen LS
      • Forman J
      • Nyboe Andersen A
      • Pinborg A
      The long-term prognosis for live birth in couples initiating fertility treatmentsHum.
      have indicated that the decrease in adjusted annual odds ratio for birth in smokers and women with a body mass index of over 30 may be 7%, faster than the usual annual rate of 1–4%; if confirmed, SOF may be offered earlier on the basis of these indications. Other rare genetic or chromosomal anomalies that are associated with premature menopause, i.e., Mosaic Turner Syndrome or fragile X or BRCA carrier that might need early oophorectomy, are legitimate candidates for early egg banking, but do not fall under this discussion.

      Conclusion

      As IVF treatments move from the public sectors to private hands, it is not easy, even for the expert, to decipher scientific claims from business-oriented claims. The fact that the sales agents of SOF are the same doctors who carry out the procedure and benefit financially carries a potential conflict of interest.
      Social oocyte freezing is a new option offered by IVF units to supposedly perfectly fertile women who are offered to ‘hedge’ fertility by diversifying their future options. The procedure is growing in popularity; however, research on the true effectiveness of this procedure is only now starting to accumulate, and it seems too low to make it cost-effective for society. Moreover, for the individuals who are to bear the full costs, freezing might not be a panacea. Despite being urged to freeze at a young age, patients probably perceive the contradiction between egg banking at early age, when the success might be high but utilization and cost effectiveness is expected to be low, and freezing at later age and so the mean age of freezing is above 37 years, which seems suboptimal but, counterintuitively, the results can be slightly more cost-effective (
      • Mesen T.B
      • Mersereau J.E.
      • Kane J.B.
      • Steiner A.Z.
      Optimal timing for elective egg freezing.
      ).
      The pregnancy rates in these studies for the few women who returned to use their eggs was high, but the overall usage rate was extremely low (
      • Cobo A.
      • García-Velasco J.A.
      • Coello A.
      • Domingo J.
      • Pellicer A.
      • Remohí J
      Oocyte vitrification as an efficient option for elective fertility preservation.
      ,
      • Hammarberg K
      • Kirkman M
      • Pritchard N
      • Hickey M
      • Peate M
      • McBain J
      • Agresta F
      • Bayly C
      • Fisher J
      Reproductive experiences of women who cryopreserved oocytes for non-medical reasons.
      ), and the cost per viable birth becomes disturbingly high, reaching a level that might deter even affluent individuals if consulted properly. One of the leading reasons of the low usage is the high chances of success in achieving a live birth spontaneously or by various treatments, including IVF, before the age of 39 years (
      • Malchau SS
      • Henningsen AA
      • Rasmussen LS
      • Forman J
      • Nyboe Andersen A
      • Pinborg A
      The long-term prognosis for live birth in couples initiating fertility treatmentsHum.
      ). Most women who opt for single parent family with sperm donation have a high chance of achieving motherhood between the ages of 35 and 39 years without freezing eggs. Obviously, women who accept to use sperm donation can try as soon as possible and need not freeze their eggs. If the patient had frozen eggs early and decided to conceive, she will exhaust other treatments before she uses the stored eggs, hence usage will be low. On the contrary, women who are planning to use the stored eggs only if they find a partner should know that the chances of achieving this second condition is low and, accordingly, the chances of using the eggs are very low, which makes freezing non-cost-effective (
      • Mesen T.B
      • Mersereau J.E.
      • Kane J.B.
      • Steiner A.Z.
      Optimal timing for elective egg freezing.
      ,
      • Hammarberg K
      • Kirkman M
      • Pritchard N
      • Hickey M
      • Peate M
      • McBain J
      • Agresta F
      • Bayly C
      • Fisher J
      Reproductive experiences of women who cryopreserved oocytes for non-medical reasons.
      ).
      In summary, except for few rare genetic associated indications, we are lacking real indications and reliable methods to predict who will benefit from cost-effective SOF later in life. Nevertheless, it is important to frequently refresh the cost–benefit and cost–efficacy calculations based on real results and present to the patients and the public clear and trustworthy information, including the low numbers returning to use the eggs and the reasons why. Presenting the correct statistics and the alternative options is in everyone's interest. Women should know about the decrease in fertility after the age of 39 years, about the low statistical chances to find a partner after that age, about the chances to conceive spontaneously or with treatments before using the frozen eggs and about the advantages and disadvantages of SOF, including the chance that frozen eggs may never be used, and the option of egg donation as a cost-effective alternative. A recent suggestion (
      • Andersen C.Y.
      • Kristensen S.G.
      Novel use of the ovarian follicular pool to postpone menopause and delay osteoporosis.
      ) that preservation of autologous ovarian tissue and re-implantation at later age can be the ‘HRT of the future’, should be met with similar criticism that was raised here.

      Declaration

      The author reports no financial or commercial conflicts of interest.

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      Biography

      Zion Ben-Rafael Board certified in Israel and USA. 84-87, NIH Fellow in Reproductive Endocrinology, HUP, Philadelphia. Associate (1990), Full Professor, (1993), Incumbent Tarnesby Chair of Fertility regulation Tel-Aviv university, Previously: 1991 Chairmen of both Departments of OBGYN Hasharon and (1997) Rabin Med Center. Publications: Over 380 articles, 2 books written, 12 edited. Founder, Co-Chairman, COGI congresses.