For more than a thirty years, attempts by medical scientists to freeze and bank (cryobank) a woman’s eggs have yielded limited success. In fact, to date, since the birth of the 1st “frozen egg baby” in the mid 1980’s, fewer than 2,000 births resulting from the fertilization of thawed eggs have been reported worldwide. Compare this to > 4 million IVF babies born worldwide in the same time period, and approximately 1,000,000 babies resulting from the transfer of frozen embryos.
Harvesting eggs for freezing typically involves giving a woman fertility drugs to stimulate her ovaries to produce multiple eggs, and then harvesting those eggs from her ovaries using ultrasound guided needle aspiration. In general, it takes at least one cycle of fertility drug administration to harvest about 10 to 15 eggs.
Presently, the statistical chance of each frozen and thawed egg ultimately resulting in a baby is at best 7% and based upon the May 2013 data meta-analysis study published in Fertility and Sterility, using ultra rapid freezing by way of a technique known as ‘vitrification’ women younger than 30y had a 13.2% success rate per completed embryo transfer procedure. The same study indicated that women older than 36Y experienced a significantly reduced chance of success. While success rates following the transfer of embryos derived from frozen eggs have indeed improved substantially over the last 4-5 years, they are still significantly lower than when embryos derived through fertilization of fresh (not frozen) eggs are transferred,
The ability to accurately identify eggs that are numerically chromosomally normal (“euploid”) and are thus the ones that are most likely to propagate a baby once they were fertilized and transferred to the uterus is particularly important. For the reason that, even in young women, less than half of eggs are euploid and by their mid-forties, that percentage drops to below <10%. It follows that an ability to identify and selectively vitrify only euploid eggs would markedly improve success per frozen egg. In fact, safe and successful banking of eggs largely hinges on the ability to successfully identify and then freeze-store (cryobank) only the “competent” ones for future dispensation.
In October 2008, Levent Keskintepe PhD and I became the first to report (in the Journal, “Reproductive Biomedicine Online”) on a process that dramatically improves the baby rate per egg frozen several fold. It involved first identifying chromosomally normal eggs using a preimplantation genetic sampling (PGS) method known as Comparative Genomic Hybridization (CGH), and then selectively freezing (by vitrification) only the euploid eggs. The process of combining such PGS testing with selective egg vitrification, and then banking only chromosomally normal eggs provided a 60% success following the transfer of up to two embryos derived from the fertilization of thawed “euploid” eggs.
There are several clinical applications of this technology which benefits two different group of women falling into the following categories:
- FERTILITY PRESERVATION (FP)
Female fertility preservation (FP) refers to the process whereby a woman’s eggs are frozen (cryopreserved) and banked for future use. It has been estimated that the potential demand for FP using frozen eggs could far exceed that for conventional IVF by a factor of 6 to 8. This need covers several categories of women/couples.
- Women who face the looming prospect of losing their ovarian function – either because a pending surgical removal of their ovaries, and/or exposure to radiation therapy and/or chemotherapy,
- Women who anticipate delaying or deferring childbearing, for a) financial reasons, b) because they do not feel ready to commit to a permanent relationship c) because they do not feel secure in their existing relationship or d) because they feel that by waiting, the ever advancing biological clock might render them unable to conceive later on.
- Women/couples undergoing in vitro fertilization who are opposed to embryo freezing on moral, ethical or religious grounds.
The demand for FP will no doubt grow as emerging technology allows egg freezing to become more readily available, safer and more reliable. In addition, the improved potential of cryobanked euploid eggs, upon being thawed, fertilized and transferred to the uterus, to develop into healthy babies will enable consumers to make better decisions as to when to discontinue the egg stockpiling process.
The recent introduction of a new PGS methodology known as Next Generation Gene Sequencing (NGS) that has surpassed CGH in assessing embryo chromosomal integrity, promises to soon supplant CGH in the realm of egg testing as well.
- BANKING EGGS FOR DONOR EGG-IVF:
In this scenario, viable eggs are stored and subsequently made commercially available for IVF and embryo transfer to women for whom egg donor-IVF provides the only means by which they can go from infertility to family.
It has been estimated that in the United States, more than 15,000 IVF procedures involving the transfer to the uterus of embryos (fertilized eggs) derived from donor eggs are performed annually. In addition, a growing number of IVF/egg donation seeking couples are traveling abroad in search of lower cost treatment. Numerous frozen egg banks have been established in this country and more and more egg donor agencies are offering banked, vitrified (cryobanked) eggs as an alternative to the simultaneous coordination of the egg donor and recipients for fresh egg donor-IVF.
The standard approaches involving traditional/conventional, egg donor-IVF using fresh/non-frozen eggs), aside from being costly is also stressful and emotionally draining. The process involves trying to match egg donors with recipients, the simultaneous coordination of the egg donor and recipients, and then ultimately having to deal with an ever present uncertainty regarding the subsequent performance of donors in terms of egg production and quality. It starts with the chosen egg donor undergoing medical and psychological screening followed by ovarian stimulation with fertility drugs to promote egg development. Synchronously, the embryo recipient (i.e. the patient) receives injections and other hormones to prepare her uterus in order to maximize the chances of successful embryo implantation. This process is painstaking, requiring exquisite timing and coordination with the recipient’s cycle and in the final analysis will at best provide a 45% chance of success.
The current cost of undergoing a single cycle of conventional egg donor IVF in the United States is about $25,000-$30,000 per cycle (the highest in the world). This is why more and more women/ couples travel abroad for lower cost treatment. Such “medical tourism” is fast becoming a significant industry in Europe, Asia, Africa, Australia and South America. In the United States, much of the cost of donor egg IVF relates to the amount paid as donor stipends. This helps explain why there is presently a real need for an improved process by which prospective clients seeking access to IVF with donor eggs can gain access to euploid (“competent”) donated eggs. The fact is that the process involved in using cryobanked eggs, is far less complex and stressful than when traditional fresh egg donor-IVF is undertaken. This is why an ever increasing number of candidates for egg donor-IVF are choosing the former over the latter approach
While it is presently indisputable that using fresh egg donation is more successful than when cryobanked eggs are used, the difference is not that large (roughly, 40% versus 30% per completed embryo transfer procedure). However, this statistic is misleading because it does not take into account the fact that for a variety of reasons, the egg freeze/thaw process renders many frozen eggs incapable of developing into viable, transferable embryos. In fact, the baby rate per (non-genetically tested) mature (M2) egg frozen, is at best, 7% as compared with 15- 20% per “fresh” egg. This serves to explain why in an effort to improve the chance of success per completed embryo transfer procedure, most commercial donor egg banks, require that their clients purchase at least six (6) eggs at a time, at a cost of about $3,000 per egg. When one adds to this the cost of the actual IVF procedure itself, the overall out of pocket cost for a cycle of IVF using banked donor eggs currently runs at $25,000 to $30,000 per treatment cycle (roughly the same as the cost for conventional Donor Egg IVF treatment using unfrozen, “fresh” eggs.)
The required shift in the paradigm, from conventional fresh donor egg IVF egg cryobanking requires identifying a way to enhance the success rate per frozen egg and at the same time bring down the current cost associated with using the services of commercial egg banks. The only way this can be accomplished is through the selective banking of euploid eggs. This would provide consumers with the ability to selectively purchase only euploid frozen eggs from a commercial egg bank.
The process of genetically testing eggs and then selectively vitrifying and banking those that are found through PGS to be euploid has definite and decisive benefits.
Patients who seek access to frozen donor eggs-IVF deserve to have direct and on-line access, to an egg bank that provides them with an inventory of euploid eggs and with an ability to purchase such eggs at their convenience. This would immediately, substantially lower (by at least 25%) the current industry standard cost for either IVF egg donation with non-genetically tested frozen banked eggs or with conventional IVF utilizing fresh (non-frozen) donated eggs.
By accessing only genetically eggs for purchase, patients would not need to purchase more than 2-3 eggs (at a cost of about $3,500 per egg) for a total cost of $7,000-$11,500. Each genetically normal egg would likely yield a 28% baby rate (i.e. at least a 4-fold improvement over non-genetically tested eggs and the pregnancy rate following the transfer of even one (1) advanced embryo (blastocyst).
The advantages of using genetically tested euploid eggs cannot be understated. It would improve the baby rate per frozen egg at least 4- fold (i.e. from 7% to almost 30%), yield a birth rate of >50% when up to 2 embryos are transferred. With such a high baby rate per egg, patients would not typically need to purchase more than 2 to 4 eggs at a cost of $3,500 per egg to gain reasonable assurance that there would be a high likelihood of the process culminating with the birth of a healthy baby.
Finally, I propose that an immediate effort be launched to insure that going forward, predominantly euploid eggs be cryobanked for commercial availability. This would maximize convenience, reduce cost and minimize the complexity and stress associated with IVF/egg donation. It is a sad statement that presently not a single such facility exists anywhere.