Egg Freezing: Is it Right for You?

By Carlene W. Elsner, M.D., Z. Peter Nagy, M.D., Ph.D., and Amy E. Jones M.S.

Cryopreservation or freezing of human eggs is a technique intended to preserve a woman’s eggs for later use by herself or a designated recipient to create embryos and subsequent pregnancies. There are several groups of women who may be potential candidates for cryopreservation of eggs.

1. Young unmarried women facing chemotherapy or irradiation for treatment of life-threatening disease, i.e. cancer, may be rendered sterile by the treatment of their disease. For these women the option to freeze some eggs, making it possible for them to have children later when their disease is cured, may be very important.
2. Women who, because of impaired ovarian reserve or poor egg quality, require donor egg to conceive may consider the use of cryopreserved donor eggs in an egg bank because it would substantially lower the cost of treatment. Stimulation of one donor may produce enough eggs to supply several recipients, potentially lowering the cost of this technology to an individual.
3. Women undergoing IVF in countries that prohibit the freezing of embryos may choose to have excess eggs cryopreserved for additional attempts to conceive without another stimulation cycle, effectively lowering the cost of additional treatment cycles.
4. Women who for professional or family reasons desire to extend their ability to conceive past their normal reproductive lifetime may be interested in having some eggs frozen for later use. Most commonly women requesting these services are older and frequently already have impaired ovarian reserve, making them suboptimal candidates for this technology.

Ideally, all women should create their own egg bank before the age of 30 for 2 possible reasons. First, even if they have children, they may want additional children later in life (divorce and remarriage or death of child). Secondly, one’s own oocytes may be useful to assist in treating some disease that may develop in oneself anytime later in life (through stem cell therapy).

BACKGROUND

Frozen banked human sperm has been in use for many years for the treatment of male factor infertility. However, the human egg is much more sensitive to the freeze thaw process than is sperm.  The egg, because of its very nature, is definitely different from the sperm. It contains not only the genetic material necessary for the development of a new individual, but also a myriad of intracellular organelles and the meiotic spindle all of which may be damaged by the freeze thaw process. Damage to these structures may result in uneven separation of chromosome pairs leading to aneuploidy (an abnormal number of chromosomes within the cell), disruption of metabolic pathways, and even cell death. Early work proceeded slowly because of concerns about efficacy and potential risk of aneuploidy.

It was not until 1986 that Chen reported the first child born from an egg that had been frozen and thawed prior to fertilization. Since that time, a number of groups around the world have reported pregnancies and births of normal children using cryopreserved eggs and yet this technology has still not become commonplace. Initially, many eggs did not survive the freeze thaw process; fertilization rates were low because the zona pellucida (the coating around the egg) hardens from the freeze thaw process resulting in decreased sperm penetration; subsequent embryo development and implantation rates were poor; and pregnancy loss rates were high. However, there have been no reports of abnormalities in the children born following oocyte cryopreservation,       

In the past several years, significant progress has been made in the field of cryopreservation of eggs. Outcomes are improving, making this technology a realistic option for some women.

THE STATE OF THE ART

Currently most eggs are frozen as MII oocytes using one of two methods. The slow freeze rapid thaw method has been favored by European investigators, while their Asian counterparts favor a rapid freeze and rapid thaw technique called vitrification. Both procedures have resulted in acceptable pregnancy rates in small numbers of patients.  Freezing and thawing of eggs results in hardening of the zona pellucida making sperm penetration of the egg more difficult. For this reason, ICSI (intracytoplasmic sperm injection) is required with both techniques to achieve optimal fertilization rates. In order to achieve a live birth with egg cryopreservation, 1) the egg must survive the freeze and thaw, 2) fertilize normally 3) implant, 4) and the resultant pregnancy must continue until a live birth occurs. Using eggs from 7 young donors (age 18-25),  Fosas et al. reported 90% oocyte survival, 73% fertilization rate, and 57% (4/7) pregnancy rate with the slow freeze rapid thaw method plus ICSI. Five normal children were born to 4 recipients.

Quintans et al. used a slow freeze rapid thaw process with ICSI in 12 women (average age 33). He reported 63% oocyte survival, 59% fertilization rate, and 50% pregnancy rate per transfer. From the 6 pregnancies established, 2 children were born to women aged 29& 30 respectively.

Yoon et al. used virtification plus ICSI in 34 patients (average age 32.4) to produce 69% oocyte survival, 72% fertilization rate, and 21% (6/28) pregnancy rate. Seven normal children were born to 6 women.

The common thread here is that if eggs of young women are frozen, outcomes are acceptable. Therefore, cryopreservation of eggs for young women who need chemotherapy or irradiation makes sense provided the outcome of therapy is not adversely affected by the gonadotropins used and the necessary time delay to recover mature eggs. Cryopreservation of eggs is already available in countries where embryo cryopreservation is prohibited by law. The technology of egg cryopreservation has now progressed to the point that we will soon see the development of egg banks for storage of donor eggs which recipients can then order as needed.

OOCYTE CRYOPRESERVATION FOR WOMEN OVER 35

The age of the egg is the single most important determinant of the outcome of an IVF cycle. Women have all the eggs they will ever have when they are born and are most fertile in their late teens and early 20’s. With advancing age of the egg, per cycle pregnancy rates decline and miscarriage rates rise. Both of these occur because of meiotic spindle abnormalities common in aging eggs. These spindle abnormalities lead to aneuploidy (extra or absent chromosomes).  Battaglia et al. studied the aneuploidy rate in eggs of women of various ages and found in women 25 years of age or younger, 17% of eggs were aneuploid. However in women over 40, 79% of eggs were aneuploid. Aneuploid embryos usually either fail to implant or they are lost in early miscarriage, thus, aneuploidy explains both the fall in the pregnancy rate and the rise in the miscarriage rate that occurs with advancing age.  Aneuploidy causes most of the first trimester losses in older women. (see article on PGD)

As a woman ages, ovarian reserve diminishes. Therefore, fewer and poorer quality eggs are produced in each stimulation cycle. One stimulation cycle may produce 15 or more mature eggs in a woman under 35 while a woman over the age of 40 may produce fewer than 5. Over 50% of all embryos produced by women 40 and older are chromosomally abnormal. The results reported by Porcu et al. of 112 cycles of oocyte cryopreservation and ICSI are as follows: 1502 eggs were thawed; 16 pregnancies were established; and 9 women delivered 11 children (2 sets of twins). More than 100 eggs were required to produce 1 child in this large series. The sheer numbers of eggs required to give an older woman a reasonable chance to have a child from cryopreservation of her own eggs makes this technology impractical for women over the age of 35 at the present time. Further research may lead to improved outcomes in the future.

SUMMARY

Oocyte cryopreservation is a rapidly advancing technology that deserves ongoing attention. Over 100 babies have been born to date worldwide. As far as we know all the children are normal. Not all articles reporting live births from this technology report the age of the eggs in successful patients. When they do, the eggs used to successfully create babies were almost always from women under the age of 32.  For women over 35, oocyte cryopreservation does not yet provide the answer to advancing maternal age and impaired ovarian reserve.

Carlene W. Elsner, M.D. is a reproductive endocrinologist  at Reproductive Biology  Associates in Atlanta Georgia.
Phone: 404-843-3064 or Toll Free 1-888-RBA-4IVF

Email: rba-online@rba-online.com

Website: http://www.rba-online.com 

Z. Peter Nagy, M.D., Ph.D. is the scientific and laboratory director and Amy E. Jones M.S. is the laboratory supervisor at Reproductive Biology Associates.

REFERENCES

Battaglia, D. E., Goodwin, P., Klein , N.A., and Soules, M. R.. Influence of maternal age on meiotic spindle assembly in oocytes from naturally cycling women. Hum. Reprod., 11, 2217-2222. 1996.

Chen, C..  Pregnancy after human oocyte cryopreservation. Lancet 1, 884-886. 1986.

Fosas, N., Marina, F., Torres,  P., Jove, I., Martin, P., Perez,N., Arnedo, N., and Marina, S.. The births of five Spanish babies from cryopreserved donated oocytes. Hum. Reprod. 18[7], 1417-1421. 2003.

Quintans, C., Donaldson, M., Bertolino, M., and  Pasqualini, R..Birth of two babies using oocytes that were cryopreserved in a choline-based freezing medium. Hum. Reprod. 17[12], 3149-3152. 2002.

Yoon, T., Kim, T., Park, S., Hong, S., Ko, J., Chung, H., Cha, K.. Live births after vitrification of oocytes in a stimulated in vitro fertilization-embryo transfer program. Fertil. Steril. 79[6], 1323-1326. 2003.