Egg Freezing: You’ve come a long way baby

August 15, 2010Carole No Comments »

You might have seen the recent articles about the first baby born in Hawaii from an egg that was previously vitrified, stored, warmed and  fertilized using ICSI.  Although exciting, especially for the proud parents and perhaps Hawaii, this birth is not the first baby born from a previously frozen egg.

You might be surprised to learn that sperm was frozen decades before embryos, and embryos  were frozen successfully years before clinical egg freezing, which is only now entering routine clinical practice.  An Australian IVF team (Trounson and Mohr 1983, Nature 305, 707) reported the first pregnancy from a frozen embryo in 1983, but sadly, the pregnancy did not result in a live birth. California was the site of the first US baby born from a slow frozen embryo transferred in 1986. In 1990, the first pregnancy and successful delivery from a human cleavage-stage embryo frozen by a new technique called vitrification was reported (Gordts et al., 1990, Fertil Steril 53, 469).

The first report of  a birth (twins)  from frozen eggs was reported in  the Lancet by a Chinese scientist in 1986 (Chen C. (1986) “Pregnancy after human oocyte cryopreservation”. Lancet 1 (8486): 884-886), but this achievement was not immediately followed by widespread clinical success.  More than a decade later, Dr. Elanore Porcu and her Italian IVF team reported births from frozen eggs in 1997. Part of their breakthrough was in discovering that eggs that were previously frozen underwent a hardening of the shell surrounding the egg so that sperm injection or ICSI was often necessary to achieve fertilization.  Earlier successes using frozen eggs to establish IVF pregnancies were few and far between.

Another factor that slowed the clinical adoption of egg freezing was that the original slow-freezing technique was not very successful- at least compared to using fresh eggs or even using frozen embryos. Pregnancies from frozen eggs remained anecdotal and relatively rare. Doctors Raffaella Fabbri and Eleanora Porcu in Italy were one of the few clinical teams that consistently reported very respectable pregnancy rates using the slow-freezing method for eggs. Their pioneering efforts in egg freezing were driven by Italy’s legal prohibition against embryo freezing, arising from the strong Catholic political influence. Because freezing embryos is illegal, Italian clinics were expected to fertilize only as many eggs as they were prepared to transfer and so egg freezing was put into widespread clinical use in Italian IVF clinics to preserve excess eggs from the fresh cycle.

The slow-freezing method was the original method used to freeze embryos and was later adapted for egg freezing. It is still used by many clinics today because it is a fairly simple protocol that uses an extension of technical skills already in use to perform IVF.  Slow-freezing is less technically demanding than vitrification but requires expensive freezing equipment that is prone to sticky valves and equipment failures. Having personally experienced the loss of frozen embryos due to mechanical failure, I was more than ready to adopt vitrification which eliminated the need for sometimes unreliable freezing equipment. Another advantage from the lab’s perspective is that preparation for vitrification is performed in less than 30 minutes and the actual vitrification occurs in seconds instead of requiring a three hour freezing period.

Although many clinics still employ slow-freezing methods, vitrification for egg cryopreservation is steadily gaining in popularity as more clinics realize that once they master the vitrification technique, they can get better pregnancy results with vitrification. The problem with slow freezing, especially applied to eggs,  is that it never seemed to deliver pregnancy rates “as good as fresh” when used by most clinics.  Except for a few clinics, most clinics reported much lower pregnancy rates with slow-frozen eggs ( 1% to 20%)  compared to what was being achieved with fresh eggs (30% to 50%).

Because pregnancies from egg freezing were more anecdotal than routine, the earliest egg banking commercial efforts were often rightly criticized for raising a woman’s hopes with false expectations of the probability of success with frozen eggs. This 2002 Times article describes the dismal early results with slow freezing of eggs. Even today, buyer beware when it comes to egg freezing. This interview with Dr. Michael Tucker discusses the trend toward vitrification and how vitrification is paving the road toward making egg freezing a reliable clinical procedure.

There are many differences between the two cryopreservation methods but both methods are based on the principle that ice crystal formation must be avoided at all costs as the intracellular temperature is lowered. Ice crystals, when they form inside the cell, shred cell membranes and quickly kill the cell. The advantage of ultra-rapid vitrification is that residual water in the cell is immediately converted to a glass-like stage, bypassing ice crystal formation entirely. The cell is dehydrated in cryoprotectant solution, then covered only in a thin film of cryoprotectant, is plunged directly into liquid nitrogen, achieving ultrarapid cell freezing rates as fast as  -3000 degrees per minute! This method may be better suited to eggs which have an exceptionally large volume of cellular water, compared to embryos or sperm, and may be more difficult to adequately dehydrate before freezing.

A Japanese scientist, Dr Masashige Kuwayama, of the Kato Ladies Clinic in Tokyo was the first to publish routine and reproducible clinical pregnancies using egg vitrification. Until Dr. Kuwayama and his team demonstrated the feasibility of vitrification for clinical use, this technique had been largely relegated to research studies in animals. Currently, more and more clinics are reporting pregnancy rates from vitrified eggs to be almost as good as those achieved with fresh eggs. Many (most?) donor egg banks have adopted vitrification as the preferred cryopreservation method as well.

Why is successful egg freezing such a significant clinical achievement?

1). Women with a cancer diagnosis can choose to freeze eggs in anticipation of survival and future parenthood. Men have had this option through sperm freezing for decades.

2.) Women can choose to freeze eggs in the prime of their reproductive years- usually in their twenties- and postpone parenthood until they are ready. The uterus is able to support implantation for years after menopause, long after the ovaries have ceased to produce healthy eggs.  So eggs frozen in their twenties can be thawed and used with IVF decades later, allowing women the same option to delay parenthood that men have always had.

Having just pointed out the obvious gender parity that egg freezing permits,  I also feel compelled to add that going through pregnancy and birth at older ages is one thing but having the stamina (emotional and physical) to parent a kid for 20+ years is an entirely different thing.

Like every technical advancement in reproductive medicine, egg freezing has created a firestorm of public opinion, pro and con. Even the original egg freezing pioneers Fabbri and Porcu are on two different sides of this ethical divide. This fascinating Newsweek account by Rachel Lehmann-Haupt about “Why I froze my eggs”, includes an interview with Eleanor Porcu, who unlike her colleague Raffaella Fabbri, does not support egg freezing to extend fertility.

Dr. Porcu’s argument is that society should be more supportive of  women so they can have babies when they are younger and pursue careers later. Her argument has two flaws. First, that Utopian society she envisions isn’t coming to the US any time soon. Second, even a social environment supportive of women having children now and careers later doesn’t address the problem for women who don’t want to parent alone but haven’t found the right mate yet. Simply having the social support to have children at a younger age isn’t the only issue that affects when a woman decides to have children.

If you are considering egg freezing, you need to carefully scrutinize the clinic or egg freezing bank you plan to use. ASRM still considers egg freezing an experimental protocol, and in some clinics, it is much more experimental than others!! Unlike IVF outcomes, the CDC does not track pregnancies from frozen eggs. Before selecting a clinic, read ASRM’s practice committee report on the minimal information that women considering egg banking should be informed of before giving informed consent.  This provides a nice template of questions you can ask.

Be very careful of overblown promises. Realize that a typical egg freeze might be ten eggs which may only give you one shot at parenthood. Egg freezing is still not comparable to freezing sperm (by the hundreds, thousands or millions) and needing only one to fertilize an egg with ICSI. Although we are well on the way to routine egg freezing,  not every clinic is equally proficient with stellar results. You need to know what percentage of the freezing clinic’s patients have actually returned to use their eggs and have had a baby.  The 2008 ASRM report cites that expectations for egg freezing births should be a 2% live birth rate per oocyte thawed for slow -freezing and a 4% birth rate per oocyte thawed for vitrified oocytes.  Put another way, the best clinics/banks report pregnancy rates from freezing eggs approaching those using fresh, but this is not a widespread success rate. The age of the egg still matters. Like IVF, donor eggs from younger women will freeze better and produce higher pregnancy rates than those from a older infertility patient. So if clinics are quoting you only donor egg freezing rates, be aware your prognosis may not be as rosy.

© 2010 – 2015, Carole. All rights reserved.

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