For fertility preservationists, effective and reliable egg freezing is the Holy Grail of the field and--like that fabled chalice—it seemed just as elusive. Over the last three-plus decades, researchers avidly pursued egg cryopreservation, spurred by the possibility of liberating women from the twin tyrannies of fertility-compromising diseases and, significantly, the biological clock.

With promise that big, the search drew legions of talented scientists who persisted with each taste of slow yet measurable progress. To date, there have been reports of more than 400 children born via frozen eggs since the first baby in 1986. A substantial achievement but still too limited to engender unalloyed faith in the procedure.

The problem seemed to reside in the freezing technique itself, which so severely damaged most of the delicate eggs that the method represented little more than dashed hopes. Experts homed in on the problem and in the last couple of years developed a rapid-freezing process, called vitrification. Vitrification is so fast that it minimizes the formation of ice crystals in the egg, assumed to be the culprit spoiling the results.

Indeed, vitrification does protect the eggs from ice damage. It turns out, though, that the obstacles to egg cryopreservation are considerably more complex and they reside in the ova themselves.

The research scientists at the Sher Institute for Reproductive Medicine (SIRM) have discovered that the majority of eggs—even in young women -- are destined for failure by aneuploidy, an abnormal number of chromosomes. This last point is critical to understanding why, despite vastly enhanced freezing techniques, the birth rate at most IVF centers continues, and will continue to be disappointing. It is also essential to understanding why SIRM has achieved a level of confidence in a proprietary process that involves full chromosomal analysis and ultra-rapid freezing technique that finally allows for sound and dependable egg cryopreservation.

Cryopreservation Works, Doesn't it?

The answer to that one is yes, it does. Just not well enough as practiced by most specialists in the field.

Positive outcomes measured in successful pregnancies and deliveries have been few and far between. The lack of consistent results, despite enhanced freezing methods, prompted the American Society for Reproductive Medicine (ASRM) to slap the "experimental" label on egg freezing last year and issued a detailed guide to informed consent for women seeking “elective” fertility preservation.

Based on available, peer-reviewed literature, ASRM noted that there's an approximate overall 2% live-birth rate per ovum thawed after conventional slow freezing. Using high-speed vitrification that jumps to roughly 3- 4% live birth rate per thawed oocyte. ASRM also observed that since most of the results reported are based on the experience of women under 35 and those who are over that age could expect a precipitous decline in success rates.

Not a good statistical landscape. Certainly not one into which women could put their faith and bank on the future by banking their eggs.

The Numbers Game: Counting Chromosomes

So if vitrification went a long way to limiting oocyte damage during the freezing process, then there must be some other reason why failure was the dominant cryopreservation theme.

It remained a frustrating mystery until SIRM researchers uncovered the fundamental problem: Most of the eggs humans produce are aneuploid; that is, they contain an abnormal complement of chromosomes.

Our research tells us that in order for a mature (M2) egg to be "competent" – capable of developing into a healthy "competent" embryo that, in turn, can develop in to a healthy, normal baby-- it must have 23 chromosomes (half the normal human component of 46), no more and no less! In other words, it must be euploid.

By the time it's ripe and ready for fertilization, the mature ovulated egg (M2), has gone through a ripening process called meiosis, a complicated dance within the cell during which half the usual 46 chromosomes split into two identical strips. One strip of chromosomes is expelled out of the egg into the first polar body. That leaves the ripe egg with 23 chromosomes ready to pair with the paternal set of 23 chromosomes. The healthy embryo will have 46. It is during the specialized choreography of meiosis where things can go wrong. And most often, in most humans, they do.

In women under the age of 35 in their peak reproductive years, a mere 40% of their eggs are euploid. For women 35-40, the number drops to one in four to six. We're not quite sure, but based on our understanding of the natural degradation of oocytes during the normal aging process, we estimate that at 40 it's only about one in seven or eight. For women over the age of 45, we believe that the number of euploid eggs plunges to approximately one in 15-20.

As if that wasn't enough of a procreative challenge, the incidence of aneuploidy is random. One 36 year old woman yielded 11 eggs after stimulation and not one was normal. With her second identical hormonal stimulation cycle, she yielded 12 eggs and seven of them were euploid.

Moreover, studies at SIRM have illustrated that, in the absence of male infertility, it's the egg, rather than the sperm, that is most responsible for determining the chromosomal integrity of the embryo. We have established that when a “competent” embryo is transferred to a healthy, receptive uterine environment the odds are in favor of a viable pregnancy.

The Implications for Egg Freezing

Put it all together and you get a clear insight into why egg freezing has been a myth to date. Most cryopreserved eggs are an undifferentiated lot, with fertility centers needing at least 20 mature frozen oocytes (M2) from each patient before they’re comfortable predicting they have a good shot at success. Even then, the ASRM numbers are a compelling indication of the shortcomings.

That's all about to change.

Freezing The Chromosomally Sound Egg:

In a study published last year in the prestigious journal, "Fertility and Sterility", SIRM reported on the use of a genetic analytical technique called Comparative Genomic Hybridization (CGH) to test the DNA of mature (M2) eggs. CGH allowed the researchers to determine whether or not a mature oocyte has the full, normal complement of chromosomes. With that study the SIRM investigators were able to illustrate that in the vast majority of cases, “competent” eggs made for “competent” embryos and that the transfer of a single "competent" embryo to a receptive uterine environment produced a baby more than 60% of the time.

The key thing here is that using a euploid (chromosomally normal) oocyte in the In Vitro Fertilization process dramatically increases the efficiency of IVF itself.

In a more recent study published in "Reproductive BioMedicine Online", SIRM researchers demonstrated that upon thawing and fertilizing each vitrified euploid egg produced a live birth 26%-to-27% of the time. That is about 7 times greater than the 3%-to-4% that is the field’s norm. The study also reported that the transfer of one or two embryos per woman resulted in 17 live births, (i.e. a 75% success rate). This leap was only possible because using CGH those eggs having the best chance of yielding competent embryos were identifiable upfront…and they were the ones selectively banked, fertilized and then transferred to the uterus.

In plain language it means that a woman needs only a single CGH-normal egg to have a baby with seven times more confidence than with one unscreened vitrified egg. Aside from SIRM, few (if any) IVF centers that offer egg freezing require CGH screening to selectively freeze only euploid eggs. In fact, most egg freezing programs require that at least 20 unscreened cryobanked mature (M2) eggs per woman be available before they feel reasonably confident of a subsequent successful outcome. It also serves to explain why, in an attempt to improve success, such IVF programs advocate the transfer of numerous embryos (at a time).

Thus, when euploid (CGH-normal) eggs are selectively frozen and banked, there is a vast improvement in baby rate per frozen egg …..bringing us much closer to meaningful fertility preservation than ever before.

The tag-team technique of CGH and vitrification also knocks out the imperative to transfer greater numbers of embryos to maximize the chances of success. Accordingly, the process represents an important milestone in reducing the incidence of twins and higher order multiples and with that, reducing the risk of all the associated medical problems.

These advances in egg freezing bring us one giant step closer to the goal of ART " one healthy baby at a time.

The Future is Now, When Biology and Social Realities Merge

Women have long struggled under the double yoke of the social pressure to become educated and economically self-sufficient and the competing biological imperative to reproduce while still young. The choice comes with high costs no matter which route is chosen. It is unrealistic to expect young women to choose a mate simply because she’s at her reproductive peak, assuming there are partners available to her. On top of that, there are penalties suffered by working women who do take maternity leave when they are in their earning prime. Fertility preservation via egg freezing is the one path that levels the playing field. It preserves a woman's right to have her own biogenetic children if and when she's ready, financially able to undertake the expensive task of raising a child.

These advanced technologies also give hope to the cancer survivor who now has the chance to continue her family line. By harvesting a patient's eggs before radiation or chemotherapy treatments and freezing only the competent eggs, the reproductive endocrinologist can rescue a cancer patient’s fertility. This is the first time we are able to offer women a realistic expectation of successfully having a biogenetic child.

Our obligation is to make sure that women understand the reproductive facts of life, and to let them know that at last, the promise of fertility preservation has been realized. Is it the insurance policy against age-related infertility that some centers claim? Is it an iron-clad guarantee that a cancer survivor will have her own sons and daughters? No! But, if they can produce chromosomally normal, competent eggs, we can offer decent odds that will only get better. Now that’s a proposal worth making.

To learn more about egg freezing call the SIRM Information Center at 866 428 3222