Clinical Review

2015 Update on fertility

OBG Manag. 2015 February;27(2):32-34,36-39

References

1. Chen C. Pregnancy after human oocyte cryopreservation. Lancet. 1986;1(8486):884–886.

2. Practice Committees of the American Society of Reproductive Medicine; Society for Assisted Reproductive Technology. Mature oocyte cryopreservation: a guideline. Fertil Steril. 2013;99(1):37–43.

3. Polge C, Smith AU, Parkes AS. Revival of spermatozoa after vitrification and dehydration at low temperatures. Nature. 1949;164(4172):666.

4. Gook D. History of oocyte cryopreservation. Reprod Biomed Online. 2011;23(3):281−289.

5. Gosden R. Cryopreservation: a cold look at technology for fertility preservation. Fertil Steril. 2011;96(2):264−268.

6. Van der Elst J. Oocyte freezing: here to stay? Hum Reprod Update. 2003;9(5):463–470.

7. Porcu E, Fabbri R, Seracchioli R, Ciotti PM, Magrini O, Flamigni C. Birth of a healthy female after intracytoplasmic sperm injection of cryopreserved human oocytes. Fertil Steril. 1997;68(4):724–726.

8. Fabbri R, Porcu E, Marsella T, Rocchetta G, Venturoli S, Flamigni C. Human oocyte cryopreservation: new perspectives regarding oocyte survival. Hum Reprod. 2001;16(3):411–416.

9. Oktay K, Cil AP, Bang H. Efficiency of oocyte cryopreservation: a meta-analysis. Fertil Steril. 2006;86(1):70–80.

10. Smith GD, Serafini PC, Fioravanti J, et al. Prospective randomized comparison of human oocyte cryopreservationwith slow-rate freezing or vitrification. Fertil Steril. 2010;94(6):2088–2095.

11. Gook DA, Edgar DH. Human oocyte cryopreservation. Hum Reprod Update. 2007;13(6):591–605.

12. Rienzi L, Cobo A, Paffoni A, et al. Consistent and predictable delivery rates after oocyte vitrification: an observational longitudinal cohort multicentric study. Hum Reprod. 2012;27(6):1606–1612.

13. Cobo A, Rubio C, Gerli S, Ruiz A, Pellicer A, Remohi J. Use of fluorescence in situ hybridization to assess the chromosomal status of embryos obtained from cryopreserved oocytes. Fertil Steril. 2001;75(2):354–360.

14. Noyes N, Porcu E, Borini A. Over 900 oocyte cryopreservation babies born with no apparent increase in congenital anomalies. Reprod Biomed Online. 2009;18(6):769–776.

15. Chian RC, Huang JY, Tan SL, et al. Obstetric and perinatal outcome in 200 infants conceived from vitrified oocytes. Reprod Biomed Online. 2008;16(5):608–610.

16. Levi Setti P, Albani E, Morenghi E, et al. Comparative analysis of fetal and neonatal outcomes of pregnancies from fresh and cryopreserved/thawed oocytes in the same group of patients. Fertil Steril. 2013;100(2):396–401.

17. Pennings G. Ethical aspects of social freezing. Gynecol Obstet Fertil. 2013;41(9):521–523.

18. Cil AP, Bang H, Oktay K. Age-specific probability of live birth with oocyte cryopreservation: an individual patient data meta-analysis. Fertil Steril. 2013;100(2):492–499.

We can freeze eggs, but when should we?
Based on media presentations and professional perspectives, it appears that many people differentiate between “medical” and “social” egg freezing.

Medical versus social freezing
Medical egg freezing is done when there is an immediate medical need to preserve fertility, such as before cancer treatment when the woman can’t reproduce now and will have reduced or no capacity later. Social freezing, on the other hand, occurs when there is no immediate need, such as when there is a desire to delay parenthood so that educational, professional, or other goals can be met. The difference is important because medical freezing is usually seen as a “need” and is therefore acceptable, whereas social freezing is elective or a “wish” and therefore is questionable.¹⁷

The labels are important for both ethical and political reasons because most people would consider medical freezing to be ethically acceptable and also worthy of societal support, perhaps even financial coverage, while some might consider social freezing to be neither ethically acceptable nor worthy of coverage.

What’s the difference?
But is the difference really all that clear? If a woman has a mother and a sister who have undergone premature menopause in their 30s and she now has signs of diminishing ovarian reserve in her late 20s, would a desire to freeze eggs be medical or social? She has no immediate need for treatment but a reasonable expectation of need later. One could argue that she should go to a sperm bank now if she has no partner, or change her life plans—but is this a reasonable expectation? If a woman is perfectly healthy but her husband has severe sperm problems and she elects IVF to treat male-factor infertility, is it medical or social? There are many situations in which it is unclear whether the reason for egg freezing would be medical or social.

Does it matter?
In any event, are social reasons to freeze eggs not legitimate? Many would argue that medical services should be used to treat diseases, not social causes. Yet we use medicine all the time to treat problems caused by social factors (obesity, depression, anxiety).

Some would argue that it is a personal decision to delay reproduction, and that health problems caused by personal decisions do not merit medical intervention. However, it is common to provide medical services to people who require the services only because of personal decisions—for instance, professional and amateur athletes who injure themselves pursuing activities for compensation or pleasure, or smokers or persons with alcoholism.

Others have argued that social freezing is inappropriate because it is only being done to avoid the consequences of aging, and that its need could be avoided by not waiting too long to get pregnant. But we treat many conditions that occur primarily as a result of aging (hypertension, dementia, poor eyesight).

Because it has become generally accepted to treat older women with diminished ovarian reserve and infertility, why is it inappropriate to treat women—when they are younger—with egg freezing to mitigate the impact of aging on reproductive performance that we know will occur later? If we could prevent or limit the impact of aging on the cardiovascular or neurologic systems by interventions earlier in a person’s life, would we not provide that medical service? Do we not provide statins and other medications to delay or limit the sequelae of aging? What is the difference with egg freezing?

Therefore, could it be discriminatory not to consider egg freezing ethical and acceptable, even if the reason for the procedure is considered social? Why should egg freezing for social reasons not be acceptable and widely available?

Who should pay for egg freezing?
Even if egg freezing performed because of social reasons is considered ethical and is supported by society, it does not necessarily follow that it will or should be paid for by society. The creation of policies determining coverage for health-care services is a complex process and is based on overall societal needs, economic capabilities, and relative social value of the services. Because infertility carries such a large personal burden and childbearing is so essential to any society, one can argue that infertility, per se, should be covered by society and, in the United States, its surrogate employers and insurance companies. This is often not the case, however. So, while it can be argued that egg freezing should be covered by insurance for both medical and social reasons, even the success of that argument does not mean it will be so in the current US health-care system.

Because egg freezing involves two major steps: (1) ovarian stimulation, egg retrieval, egg freezing, and egg storage followed at a later date by (2) egg thawing, fertilization, embryo culture, and embryo replacement in the uterus, what would be socially justified coverage of egg freezing? Society could cover just the first step or just the second, or both. Such decisions would depend on an assessment of the social benefit from coverage of these services. Such analysis is not yet available because of limited experience.

Is the cost worth it?
A major issue for women considering egg freezing for social reasons is whether a sufficient number of eggs will be retrieved to provide a reasonable chance for pregnancy later when they are used. The FIGURE illustrates the probability of a live birth after egg freezing. It should be noted that while most, but not all, eggs survive thawing after vitrification, not all eggs will become fertilized. Only about half of the fertilized eggs will grow to a day 3 embryo, and not all of those embryos will be viable. Therefore, constant reproductive loss occurs after the eggs are retrieved.

^{Source: Cil AP, et al.18 18}

Probability of a live birthRepresentative probabilities (%) of live birth for ages 25, 30, 35, and 40 based on number of oocytes thawed and embryos transferred. Source: Cil AP, et al.18

Furthermore, even after embryo replacement, pregnancy does not occur in every case, and some pregnancies are lost to miscarriage as well as other complications of pregnancy and childbirth. The FIGURE shows that a 25-year-old woman with 12 eggs frozen would have an estimated pregnancy rate much greater than 50%. However, the numbers also indicate that egg freezing is not very successful for older women who, at this time, constitute many of those considering the procedure.18

Another consideration is that a significant, but currently unknown, number of women who freeze their eggs will never use them for a variety of reasons. This is especially true of younger women, for whom many of the factors determining their eventual reproductive life might well change. They may eventually decide not to have children or they might become pregnant naturally or after fertility treatments that are cheaper than using the frozen eggs.

A $200,000 price tag?
Let’s consider the near 20% estimated pregnancy rate for age 35 in the FIGURE. If only half of the women aged 35 who freeze 6 eggs eventually use them (but, again, only about 20% have a baby), it means that only one of every 10 women who freeze their eggs eventually will have a baby as a result of the procedure. The number needed to treat (NNT) is therefore 10, and if the cost is $20,000 for the egg freezing procedure and storage over 5 to 10 years, the overall cost per baby born is about $200,000. If 12 eggs are frozen, the cost is $100,000. This clearly is a significant cost, and a greater cost than most other fertility treatments to achieve a baby, even in the older population. Therefore, the cost-effectiveness of social egg freezing is yet to be determined.

What should we do as we move forward?
Abandon the medical versus social rhetoric
It is difficult to argue against egg freezing for medical reasons, and the distinction between medical and social freezing is largely an artificial construct. In general, therefore, the differentiation between medical and social egg freezing should be abandoned, and egg freezing to preserve future fertility should be considered ethical for whatever reasons.

Consider the ideal time frame for health insurance coverage of egg freezing
That does not mean that egg freezing should always be reimbursed. The decision for coverage by employers, insurers, and other payers should be based on a cost–benefit analysis of the social benefit, individual benefit, biological chances of success, probability that the frozen eggs will be used, medical risks/sequelae, and the financial costs. Therefore, whether or not egg freezing for fertility preservation is covered will vary among countries and even within countries and among different individuals. Such an approach to coverage should apply to all medical interventions, including both medical and social egg freezing.

This approach could possibly result in findings and resulting policies that do not cover egg freezing before age 30 because too few women will return to use their eggs, or after age 38 because the chances of success are too low. Other instances of freezing should not be forbidden but would not be reimbursed by public or payer money.¹⁷

Many considerations must go into the development of social, professional, and payment policies. Policies that are seen as family-friendly that promote childbearing, especially at an earlier age, can be seen as limiting women’s academic and career opportunities and therefore women-unfriendly. Policies supporting women’s reproductive autonomy and ability to delay childbearing can be seen as women- but not family-friendly. Therefore, reproductive policies affect not only the individual woman but also society, its demographics, politics, and economics.¹⁷

The future
The new technology of egg freezing is a wonderful advance for many people. We are learning innovative ways to apply this technology for both infertile and noninfertile people. Research, better evidence, public education, informed consent, ethical practice of medicine, societal support for reproductive rights, and consideration of patient autonomy and social justice will enable us to optimize egg freezing as a treatment intervention.

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