Egg Freezing 2010 A Practical Update on the State of the Art by Carlene Elsner, M.D.

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Egg Freezing 2010 A Practical Update on the State of the Art

by Carlene Elsner, MD

 

 

Background                         

Interest in freezing and storing gametes (sperm and eggs) for later use is nothing new. By the 1960’s the technology to freeze sperm was reliable enough, in terms of freeze thaw survival rates, to make the development of sperm banks reasonable for long term storage of donor sperm to be used by couples who needed donor sperm to conceive, and also for sperm storage for men before treatment for certain cancers, where treatment would render them infertile. Banking of sperm makes it possible to quarantine sperm for months before use, allowing for retesting of donors for sexually transmitted disease prior to thawing and use of the specimen. Initially, the per cycle pregnancy rates for the use of fresh sperm in insemination cycles were better than in cycles when frozen sperm was used. By the 1980’s sperm freezing techniques had improved such that pregnancy rates using fresh or frozen sperm were very much the same. At that time the use of frozen banked sperm began to replace the use of fresh sperm for insemination because of the increased margin of safety with its use. At the present we take the use of frozen banked sperm for granted as the state of the art when donor sperm is needed.

Until 1978 with the birth of the first IVF baby, Louise Brown, human eggs were not available to researchers in the laboratory at all for study. The first possibility to consider egg freezing did not come until controlled ovarian hyperstimulation for IVF became commonplace and there were extra eggs available that could either be inseminated to create extra embryos that could then be frozen for later use or could be frozen as eggs. It soon became apparent that with techniques available at the time, freezing embryos worked much better than freezing eggs.

Freezing sperm and freezing eggs are totally different in terms of degree of difficulty so the technology for freezing eggs did not develop as rapidly as it did for freezing sperm. The human egg is physically much larger than a sperm. The sperm is small and compact consisting largely of DNA. The larger egg contains DNA in its nucleus, but also in its cytoplasm it contains a large number and variety of intracellular organelles that are necessary for cell viability and protein synthesis. Very importantly, as opposed to the sperm, the cytoplasm of the egg largely consists of water. During early attempts at egg freezing, the slow freeze techniques in use at that time resulted in the formation of ice crystals in the cytoplasm of the egg. These ice crystals damaged the intracellular organelles resulting in frequent cell death, so freeze thaw survival rates for frozen eggs were poor. Even if the egg did not die, the spindle in the egg is particularly sensitive to damage from intracellular ice crystal formation. Damage to the spindle of the egg causes uneven sorting of chromosomes during cell division resulting in aneuploidy (abnormal embryos). The embryos derived from frozen eggs at that time were poorer in quality than embryos derived from fresh eggs. With continued work, freezing techniques improved so that by the late 1990’s pregnancy could be achieved in the human using previously frozen eggs. We, at RBA reported in 1997 two of the first successful births in the world of children derived from the use of frozen thawed eggs. At that time egg freezing was an inefficient process. It took about 100 eggs to achieve a successful pregnancy, so the technology was not practical for common usage.

More recently, with expanded use of IVF throughout the world for treatment of infertility, many governments have enacted laws limiting or prohibiting the use of certain techniques in their respective countries. These laws vary from country to country. For instance, many countries limit the number of embryos that can be transferred, Germany forbids PGD (the chromosomal testing of embryos prior to transfer), and in Italy, freezing embryos is forbidden, only three eggs may be inseminated because all embryos produced must be transferred and cannot be frozen. In Italy if a woman produces a large number of eggs still only three can be inseminated, therefore the excess eggs must be discarded, donated to another woman, or used for research. Many of these eggs in Italy have been used to improve egg freezing using the slow freeze method. In the late 1990’s almost simultaneously, a few reports of successful egg freezing from vitrification in Asia began to appear in the literature. 

 

 

Egg Freezing Technology

As of 2009, when eggs are frozen one of these two techniques are used; either the slow freeze rapid thaw method popularized in Europe or the vitrification method first used in Asia. Only mature eggs (MII oocytes) may be frozen. The slow freeze rapid thaw method is more time consuming but less difficult technically and requires less equipment in the laboratory than does the vitrification method. What this means from a practical standpoint is that centers with relatively little experience with egg freezing can have success using the slow freeze rapid thaw method. Vitrification is much less forgiving, meaning that even minor deviations from protocol can have disastrous results. Not surprisingly, most of the centers in the world that currently offer egg freezing are using the slow freeze rapid thaw technique.

In the slow freeze method, the eggs to be frozen are placed in a media containing a cryoprotectant. The concentration of the cryoprotectant is gradually increased in a stepwise fashion to draw water out of the cell to prevent ice crystal formation in the cytoplasm of the egg as the temperature is gradually lowered to freeze the eggs. Vitrification involves flash freezing of eggs where the temperature is lowered so rapidly that a glass is formed because there is no time for ice crystals to form in the freezing process. This formation of a glass does not damage the intracellular organelles in the cytoplasm of the egg like ice crystal formation does if it occurs in the slow freeze method. In labs experienced in the use of vitrification, freeze thaw survival rates of eggs as well as post thaw egg and embryo quality, per embryo implantation rates, and ongoing pregnancy rates are better with vitrified eggs than with slow frozen eggs. At the moment only a few labs in the United States routinely use vitrification for eggs freezing.

 

Results

When the ongoing pregnancy rates from the use of previously frozen eggs began to approach the success rates from the use of frozen embryos, we at RBA felt that egg freezing deserved further evaluation. We did a study to compare outcomes with vitrification and slow freezing in 2006. Briefly, we froze eggs obtained from 10 young donors. Twenty couples needing donor egg received free cycles in which some eggs were thawed for each couple and inseminated using ICSI. The average fertilization rate was 87%. Early embryo development was observed in the laboratory and 2 to 3 embryos were transferred on day 5. Fifteen of the 20 women were pregnant from the initial transfer. Of the 5 not pregnant, some had extra embryos frozen that had been derived from frozen eggs. Two women returned for thaw and replacement of these extra embryos. Both conceived, so a total of 17 of the 20 women became pregnant from egg freezing. These women delivered 28 children, all of which were healthy. These data were reported at the ASRM in Washington, DC in October 2007 (full article F&S Aug 2009).

These results were so encouraging to us that we began routinely freezing and banking eggs from donors. We opened an egg bank in December 2007. Results from the use of previously frozen eggs continue to exceed expectations. As of December 2009, we have had more that 100 babies born and there are many ongoing pregnancies. Ongoing pregnancy rates continue to be 65% or higher. Most of the women who come to us for donor egg are now preferring to use the egg bank for several reasons; 1) it reduces the price of egg donation by approximately 50%, 2) there is no wait time (over 1000 eggs from more than 70 donors are available at this writing, with constant turnover, meaning more become availably every week), 3) the intended parents can choose their own donor from the website with complete profiles and baby pictures of the donors, and 4) the results are as good as if fresh donor eggs were used.

 

Other uses of egg freezing

After the initial successes from the egg bank, we began to evaluate egg freezing in women older than those in our donor pool (21-30 years of age). Although the numbers are still small, it appears that ongoing pregnancy rates using frozen eggs are age appropriate; that is that pregnancy rates are similar for women using their own frozen eggs to the rates they could expect if they used their own fresh eggs. With vitrification, the freeze thaw process does not seem to damage the egg. This fact allows us to extend the use of egg freezing to other groups including 1) women who desire fertility preservation if ovarian reserve is good, 2) prior to treatment for women who require sterilizing surgery, radiation or chemotherapy for cancer, 3) women who require IVF for infertility treatment but do not wish to create a large number of embryos to freeze that may be potentially unused.

 

The future

The recent improvements in egg freezing hold great promise for the future. It has the potential to revolutionize family planning in much the same way as the birth control pill did in the last century. Imagine being able to plan the perfect time to have a child without having to worry about the reproductive time bomb of advancing age.

Dr. Elsner also wrote an earlier article on egg freezing in 2003.

 

 

Carlene W. Elsner, M.D. has worked in the field of infertility for over 20 years. She was the first board certified reproductive endocrinologist in Atlanta and joined Drs. Kort and Massey at RBA in 1984. Before coming to Atlanta Dr. Elsner was on faculty at Bowman Gray School of Medicine at Wake Forest University. She completed fellowships in reproductive biology at the University of Pennsylvania and in reproductive endocrinology at the Harbor UCLA Medical Center. A Georgia native, Dr. Elsner received her MD from the Medical College of Georgia. She completed a four year residency in obstetrics and gynecology at the University of Florida. 

Dr. Elsner is an INCIID Professional Member. Read her biography here.

 

Reproductive Biology Associates
1150 Lake Hearn Dr. Suite 400
Atlanta, GA 30342
Phone: 404-250-6848
Fax: 404-256-6999

 

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