Oocyte Cryopreservation and Ovarian Tissue Freezing
Cancer in young women of reproductive age is fortunately overall a rare event, yet, still occurs more frequently than often believed. Despite improving cure rates, and maybe exactly because of them, the experience can be devastating. The reason is that the same treatments which potentially cure the malignancy, frequently, at the same time, obliterate ovarian function. Young women, therefore, fortunately survive at ever increasing rates but, concomitantly, are rendered sterile, unless they are willing to conceive with (third party) donated eggs.
Complete loss of ovarian function is usually due to either chemo-, radiotherapy or both. In recent years, modern medical care has started to make some early inroads when attempting to maintain at least some ovarian function after cancer treatment. Various ideas and technologies have been attempted. None has, so far, proven universally successful, though steady progress is being made.
Egg Freezing & Fertility Preservation for Cancer Patients
Dr. Norbert Gleicher on CHR's fertility preservation programs.
While it remains important to understand that all currently available treatments should, as of this point, still be considered experimental, their use in a clinical situation, where the alternative is functional sterility, makes sense as long as patients understand the experimental nature of these treatments and accept the fact that none of them can guarantee fertility in the future. CHR offers all of the below described methods of fertility preservation but requires that patients acknowledge their experimental nature by signing an appropriate “experimental” informed consent.
What unifies all of the currently available treatments is the need for quick and proactive treatment once the initial cancer diagnosis has been made. Since most cancer specialists urge rapid therapeutic responses, the time to act is usually very limited. Affected patients are, therefore, well advised to consult fertility experts who can react quickly. In addition, close cooperation and coordination between fertility and cancer experts is of absolutely crucial importance.
Gonadotropin Releasing Agonist Treatment
Mostly based on the work of an Israeli group, we know that the devastating effects of, at least some, chemotherapeutic agents can be partially mitigated by pre-treating affected women with a hormone, called gonadotropin releasing agonist (GnRH-a). This medication puts the ovaries into a “rest” stage and, in doing so, can diminish the toxic effects of the chemotherapy on the eggs within the ovary. This medication works, however, only in conjunction with certain chemotherapies.
Egg (Oocyte) Freezing
A considerable, by many in the profession believed to be an excessive, amount of publicity has recently surrounded the concept of egg freezing. Indeed, some fertility centers, and specially created commercial enterprises, have, in our opinion, greatly oversold the concept. CHR has been offering egg freezing as a clinical service for over one and a half years. Yet, we have been offering the service only as an experimental procedure, with appropriate informed consent.
Egg freezing, as much as our techniques have improved, still lags behind embryo freezing. Paradoxically, a “simple” egg freezes (and thaws) much less reliably than the more “complex” embryo. Consequently, we can not predict the outcome from egg freezing with similar accuracy to embryo freezing. In other words, when we have a certain number of embryos cryo-preserved, we have a pretty decent idea what their pregnancy chance will be, once thawed and transferred into a uterus. This, in turn, allows us a rather accurate calculation as to how many embryos a patients needs to freeze if she wished to establish a certain likelihood of pregnancy from these cryo-preserved embryos. Our predictive abilities in regards to egg freezing are not as good yet and, therefore, our ability to advise patients is much more limited.
The freezing of egg (oocytes) requires a full IVF cycle. This usually means, even when shortened cycle stimulation is used, a delay of at least one month in cancer therapy. It is also important to remember that one cycle of IVF will result in only a limited numbers of eggs which, given what we discussed above, may offer only a very limited pregnancy chance in the future.
This represents probably the most experimental treatment discussed here as, so far, only two pregnancies have been reported world-wide, utilizing the concept of re-implanting ovarian tissue. Here is how it is supposed to work: A young woman, who wishes to preserve her ovarian function prior to cancer treatment, undergoes surgery in which (at least) one of her ovaries is removed. The removed ovary is dissected and the portion where the follicles are housed is cut into thin slices which are frozen. Months to years later, when the patient is considered cured from her cancer, and if her ovarian function has, indeed, not returned in the ovary (usually) left behind, one or more of the frozen ovarian “slices” are re-implanted into her body. Different locations and techniques have been reported for this re-implantation procedure and it currently appears that the best techniques involve re-implantation into the ovarian capsule left behind during the first surgery. Indeed, both reported successes, involving, re-implantation of ovarian tissue, have followed such surgical techniques.
The world wide experience with ovarian freezing is obviously still very small. The concept, however, appears promising and CHR is, therefore, offering ovarian freezing on an experimental basis. The emphasis here is, however, still, as well, on “experimental” because success rates remain to be defined and, at least one paper from Israel, reported metastatic cancer cells in a removed ovary, thus creating, at least theoretically, the risk that the re-implantation of ovarian fragments could re-introduce cancer into a previously cured patient.
We, therefore, cannot overemphasize the importance of explaining to patients the experimental nature of all of these treatments. The American Society for Reproductive Medicine concurs with this assessment and, only recently, in a published opinion reemphasized this point.
When patients are diagnosed with cancer, they are at their most vulnerable. We consider it an absolute ethical obligation to advise them, under such circumstance, with passion but, at the same time, openly and without hype. The clinical options for preserving fertility are increasingly promising, but still far from perfect. As long as this is understood, expectations, down the road, will be met. If expectations are, however, allowed, or encouraged, to become unrealistic, patients will feel victimized for a second time when those expectations, months or years later, cannot be met. We, therefore, always make it a point to stress that, even under the worst of all circumstances, when none of the here described methods of fertility preservation turns out to be successful, we always have the wonderful option of egg donation left. In such cases, by the time most patients give birth, they usually have forgotten where the egg came from that produced their baby!
Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.