Yet there are still many sad stories we hear daily of young women who will never be able to have children because of backward views of their oncologist. Many otherwise well meaning oncologists do not want to bother with referring their patients for fertility preservation for fear it would delay their cancer treatment. But freezing a young woman's ovarian tissue is a simple, minor procedure that will only delay treatment by 2 days, and will in no way hamper the cure of their cancer.

Just recently we consulted with the parents of a 17 year old girl with Hodgkin's Disease who were thrilled to save their daughter's fertility, but their oncologist actually talked them into not doing this and to only concentrate on her Hodgkin's. She will consequently never have children. Contrast that girl's sterile future to that of Amy and Melissa, who look forward in the future to having a family of their own.

Egg or Embryo Freezing

Young women with cancer can also preserve their fertility by an IVF type procedure, retrieving individual eggs and freezing the eggs (or fertilizing them, in the case of married women for example, and freezing the embryos). With this approach, the young woman with cancer can undergo hormonal stimulation for several weeks after day one of her next menstrual cycle, to mature 10 to 15 follicles and the doctors can retrieve eggs by ultrasound-guided needle aspiration, just like with IVF. If they have a permanent partner, the eggs can be fertilized and the resultant embryos (rather than just eggs) frozen. Some may prefer this approach to having ovarian tissue frozen.

The problem with this approach of egg or embryo freezing for cancer patients is that it could delay the cancer treatment by 4 to 8 weeks, or even longer, and the patient's oncologist may not be willing to wait this long before initiating cancer treatment. Furthermore, like with any IVF procedure, the pregnancy rate per cycle is usually only 30% to 50%. So if she doesn't get pregnant from these frozen eggs or embryos (derived from just this one retrieval cycle) then she has no further options because her ovaries have already been destroyed by the cancer treatment. With frozen ovary tissue, she will have hundreds of thousands of eggs frozen and many more years of opportunities for pregnancies and children. That is why for most cancer cases, it is preferable and easier on the patient to perform ovarian tissue freezing to preserve their fertility rather than simple egg freezing or IVF with embryo freezing.

The other problem with eggs or embryo freezing for many infertility centers is that the conventional freezing technologies which most IVF labs use are not reliable. With most of these conventional freezing technologies, the vast majority of eggs are damaged and as many as half the embryos are destroyed. To use this method of fertility preservation, it is absolutely critical for the IVF lab to be very experienced with "vitrification."

Freezing Eggs or Embryos by the Vitrification Process

Video Showing the Vitrification Process

The classic problem with freezing eggs used to be that as one lowered the temperature below the freezing point, the egg's genetic material would suffer damage due to ice crystals forming inside the cell. It was only possible to freeze embryos, in which the genetic material had already combined with that from the sperm, and stabilized. The classic freezing techniques (which have been known since 1983) were based on trying to extract water from the cell as the temperature drops, to minimize ice crystal damage. This has all changed now with the development of our new vitrification techniques. We no longer have to play a tenuous game of minimizing ice crystal formation -- we can now entirely avoid it -- so that there is no internal damage to the egg whatsoever.

This new technique of freezing called “vitrification” avoids the damage caused by ice forming inside the cell by not trying to pull every last molecule of water out, because it is impossible to do this 100%. In fact, 70% of the cell is water, and at best you can reduce that to 30%. So with the conventional controlled rate slow-freezing technique, there is always going to be some intra-cellular ice crystal formation, causing some damage to embryos, and severely damaging most eggs. Vitrification uses a super high concentration of antifreeze (DMSO and ethylene glycol), and drops the temperature so rapidly that the water inside the cell never becomes ice. It just instantaneously super-cools into a solid with no ice crystal formation at all.

We can now freeze and thaw, and even refreeze and rethaw, with impunity, using this new protocol from Dr. Masashige Kuwayama from the Kato Clinic in Tokyo. With conventional “slow freezing,” the temperature of the embryo goes down at precisely 0.3°C per minute. With vitrification (using four times the concentration of antifreeze, or cryoprotectant), the temperature is dropped at 23,000 degrees C° per minute, that is 70,000 times faster. At that speed of cooling, and at that concentration of antifreeze, ice crystals simply cannot form.

Of course, it is not quite as simple as it might sound. Such high concentrations of antifreeze, in a few minutes, could be toxic to cells. Therefore, the embryos (or eggs) must first be placed in lower concentrations of antifreeze (and sucrose to draw some water out), and then left in high concentrations only for less than a minute before instantaneous freezing. Then when the time comes to thaw the embryo, it must be instantaneously warmed, immediately taken out of the high concentration of antifreeze, and then placed into a solution with lower concentration, in order to avoid antifreeze toxicity. This requires more skill than conventional freezing, but it is faster, cheaper, and most importantly, avoids almost all freezing damage to either eggs or embryos. Such a reliable method of embryo freezing gives the IVF program much greater ability to safely preserve fertility.

Using this vitrification technique for freezing, we can reliably preserve eggs as well as embryos so that the pregnancy rate is no different than if the eggs or embryos had never been frozen. This allows us to preserve the fertility of young women for the future if they wish to delay childbearing, but not lose their fertility as they age. Without skill in vitrification, a clinic cannot give any assurance of the survival of any eggs or embryos they attempt to freeze to preserve the fertility of cancer patients.

Vitrification of Ovarian Tissue

Although conventional freezing of ovarian tissue has worked quite well since we began in 1996, it results in loss of half the eggs. Of course that still leaves 50,000 eggs that survive; so ovarian tissue freezing has been a robust technique for preserving fertility for well over a decade with many successful pregnancies. However, we can now use the vitrification technique of freezing also for ovarian tissue. This is truly a remarkable improvement for several reasons.

Firstly, with vitrification, we essentially LOSE NO EGGS. The frozen ovarian tissue with vitrification is no different from fresh tissue. This means that when the ovarian tissue is transplanted back (after the patient is cured of her cancer), it will have a completely normal lifetime of function. It should last twice as long as ovarian tissue that was cryopreserved with the conventional slow-freezing approach.

But there is a much more profound advantage to using the vitrification technique for freezing ovarian tissue for cancer patients. There are some cancers, like leukemia, that metastasize to all organs, including the ovary. So for leukemia patients (unlike Hodgkin's and other solid tumors), the ovarian tissue cannot be transplanted back. For these patients the maturing follicles in the ovarian tissue can be cultured in vitro and successfully fertilized for IVF. With frozen tissue there will not just be a few eggs, but literally thousands of such eggs available for IVF.

The only problem is that conventional freezing of ovarian tissue destroys all of these maturing eggs and only spares the immature primordial follicles which cannot be cultured in vitro.

But vitrification of the ovarian tissue spares all of the follicles, even the maturing follicles, the ones which can be used for IVF. Thus with vitrification of ovarian tissue, even cancer patients with leukemia can have successful preservation of their fertility.

Ultimately, it is usually better to freeze ovarian tissue to preserve fertility before undergoing otherwise sterilizing cancer chemotherapy and radiation, and vitrification is preferable to older methods of freezing.