Taking Sides: Elective egg freezing: Is 40 too old?

No. Outcomes data argue for higher age cutoffs

Micah J Hill, DO, FACOG, LTC, MC, USA, and Eric D Levens, MD, FACOG

Dr Hill is REI Assistant Division Director, OBGYN Residency Assistant Program Director, Walter Reed & NIH REI Fellowship, and Associate Professor, Obstetrics and Gynecology, Uniformed Services University, Bethesda, Maryland. He has no conflicts of interest to report in respect to the content of this article.

Dr Levens is Director of Research at Shady Grove Fertility Science Center, Rockville, Maryland. He has no conflicts of interest to report in respect to the content of this article.

The views expressed in this manuscript are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the US Government.

Egg freezing is a common and effective treatment for loss of fertility secondary to cancer and other medical conditions. Elective egg freezing to delay child bearing for “social indications” is also becoming more common. Whether there should be an age limit for elective egg freezing is controversial.

The first question is if a reasonable number of eggs can be obtained from patients older than age 40 to justify egg freezing. Patients aged 41–44 produce on average 6–9 eggs suitable for freezing per stimulation cycle and require 2 cycles to bank 16 eggs.¹ This is not much reduced from patients aged 37–40, who produce on average 8–10 eggs suitable for freezing per cycle and require 2 cycles to bank 16 eggs.¹ So it is clear that there is not a dramatic drop in egg yield after age 40 to make this age a discriminator.

The second question is if a reasonable live birth rate can be obtained from frozen eggs in women over 40. While the number of eggs frozen might be acceptable, the decline in egg quality with age could make live birth unlikely. Age-specific egg freezing outcomes have been evaluated in a meta-analysis by Cil et al.² Live birth rates ranged from 5% to 17% in patients over age 40, varying by the number of eggs and embryos available. Live birth rates in patients ages 41 to 42 were as high as 14% when 3 embryos were transferred and 17% when 6 oocytes were available for insemination. The live birth rates in patients ages 41–42 were only 2%–3% lower than patients ages 37–40.² Overall, this study demonstrated successful live births in patients up to age 44 when vitrification was used for egg freezing and the authors recommended this age as a cutoff for elective treatment.

At our facility it is not uncommon for us to offer fertility treatment to women with a prognosis for success below 10%. Women over age 40 who desire elective egg freezing appear to have a prognosis at or above this value and should not be excluded from treatment. With egg freezing, women over 40 have a prognosis for live birth that is only 2%–3% lower than that of women aged 37–40. Thus an age cutoff of 40 does not seem to be justified from an outcomes perspective.

Recent studies have demonstrated that elective egg freezing before the age of 34–36 maximizes live birth and before the age of 37–38 is most cost effective.^1-3 Patients should be clearly counseled that these younger ages are ideal for elective age freezing. However, older patients still have a reasonable chance of live birth. A patient over age 40 who is well counseled and understands the costs and realistic chances of success should not be excluded from egg freezing.

References

1. Devine K, Mumford SL, Goldman KN, et al. Baby budgeting: oocyte cryopreservation in women delaying reproduction can reduce cost per live birth. Fertil Steril. 2015;103:1446–1453.

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

3. Mesen TB, Mersereau JE, Kane JB, Steiner AZ. Optimal time for elective egg freezing. Fertil Steril. 2015;103:1551–1556.

Next: Yes. The likelihood of success is too low and the cost is too high >>

Yes. The likelihood of success is too low and cost too high

Alice Rhoton-Vlasak, MD

Dr Rhoton-Vlasak is Associate Professor, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville. She has no conflicts of interest to report in respect to the content of this article.

I advocate an age restriction of 40 for elective oocyte cryopreservation. In 2013, the American Society for Reproductive Medicine first endorsed oocyte cryopreservation as non-experimental.¹ Egg freezing typically works best for women in their 20s–30s, and is not generally recommended for women older than 38 years.² Proposed applications of this technology included preserving fertility in patients receiving gonadotoxic therapies for cancer or other diseases, in certain genetic conditions, in situations in which there is a failure to obtain sperm for IVF, for couples who cannot or do not want to cryopreserve excess embryos that are not transferred in a fresh cycle, and for elective oocyte cryopreservation to defer or protect child-bearing potential (ie, for “social indications”).

Recent European Society of Human Reproduction and Embryology committee statements concluded that oocyte cryopreservation to improve prospects of future childbearing should be available for nonmedical reasons.³ “Social” egg freezing has gained significant accessibility as more women desire to delay parenthood to pursue their educational, professional, and other goals. Two of the country’s largest technology firms, Apple and Facebook, have announced that they will provide a $20,000 employee benefit to fund oocyte cryopreservation.⁴ Oocyte cryopreservation may offer a viable option for single women or career-oriented women wanting to protect against the age-related decline in fertility. However, this advanced technology will not protect against the natural age-related decline in fertility.

Egg freezing typically works best for women in their 20s to 30s, and is not generally recommended for women older than 38 years.² The biological clock cannot be reversed by oocyte cryopreservation in women older than 40. Women older than 40 can freeze eggs but because of the low-to-nearly-absent chances of a resulting pregnancy, this policy does little for fertility preservation or to assist the patient’s future reproductive goals. An age cutoff of 40 should be advised because increasing age markedly increases the likelihood of chromosomal abnormalities in oocytes thus reducing the chance of pregnancy and increasing the risk of miscarriage and birth defects in offspring. A recent study by Mesen et al. found that oocyte cryopreservation can be of great benefit to specific women and has the highest chance of success when performed at an earlier age. This study concluded that at age 37, oocyte cryopreservation has the largest benefit over no action and is the most cost effective.⁵ Several studies have observed decreased success with oocyte vitrification in women of advanced age, with success rates for oocyte cryopreservation via vitrification declining with maternal age consistent with the clinical experience with fresh oocytes.¹

Allowing oocyte cryopreservation in women older than 40 has emotional, financial, and societal consequences. Generally, women will require higher doses of fertility medicines for an adequate stimulation, therefore increasing the costs of oocyte cryopreservation cycles. Given the markedly lowered success rates, this will provide little hope or significant benefit. The 2013 Society for Assisted Reproductive Technology data from the United States show that for fresh embryos from non-donor oocytes, the percentage of cycles resulting in live births drops from 21% at ages 38–40 to 11% at ages 41–42, with a further decline to 4.5% over age 42. This reduction exists despite an increased number of embryos transferred per transfer over age 40.⁶  Healthcare policy should be based on the Hippocratic principal of “primum non nocere” instead of “how can I grow my practice this quarter.”

Women should have access to elective egg freezing, but I advocate an age limit of 40 based on very low pregnancy rates with increased costs, similar surgical risk, and wanting to avoid giving patients false hope. There are limits and contraindications for everything that is done in medicine and we clearly need to define an age limit somewhere for oocyte cryopreservation. When patients seek our advice, it makes sense to have some guidelines. When the risk:benefit ratio approaches zero, “primum non nocere” takes over as our best guiding principle.

References

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

2. American Society for Reproductive Medicine Fact Sheet 2014. Can I freeze my edds to use later if I'm not sick? http://www.sart.org/uploadedFiles/ASRM_Content/Resources/Patient_Resources/Fact_Sheets_and_Info_Booklets/Can_I_freeze_my_eggs_to_use_later_if_Im_not_sick-FINAL_8-13-14.pdf. Accessed August 28, 2015.

3. Dondorp W, de Wert G, Pennings G, et al, ESHRE Task Force on Ethics and Law. Oocyte cryopreservation for age-related fertility loss. Hum Reprod. 2012;27:1231–1237.

4. McGregor J. The new Silicon Valley perk? Freezing your eggs. Washingtonpost.com. https://www.washingtonpost.com/news/on-leadership/wp/2014/10/14/the-new-silicon-valley-perk-freezing-your-eggs/. October 14, 2014. Accessed August 28, 2015.

5. Mesen T, Mersereau J, Kane J, Steiner A. Optimal timing for elective egg freezing. Fertil Steril. 2015;103:1551–1556.

6. Society for Assisted Reproductive Technology. Clinic summary report: All SART member clinics. https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0. Accessed August 28, 2015.