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    • Fertility Preservation (FP) Through Egg Freezing

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      Female fertility preservation (FP) refers to the process whereby a woman’s eggs are frozen (cryopreserved) and banked for future use. Until very recently, FP by egg freezing was by and large confined to cases where young women faced chemotherapy or were suffering from illnesses that might make them infertile. More recently, indications have expanded to include individual lifestyle choices. It has been determined that the potential demand for FP using frozen eggs could far exceed that for conventional IVF (by a factor of 8).

      For more than a quarter century, medical scientists have attempted to defy the biological clock by freezing a woman’s eggs to preserve her fertility. Until recently, almost all such efforts have yielded very poor results. This is why, since the birth of the 1st “frozen egg baby” in the mid 1980’s, fewer than 1500 such births have been reported worldwide. Compare this to the more than 3-4 million IVF babies born in the same time period and the approximately 25,000 IVF births per year resulting from 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. Typically, it takes at least one cycle of fertility drug administration to harvest about 12 to 15 eggs.

      Until quite recently, the reported statistical chance of each frozen and thawed egg ultimately resulting in a baby has been under 5%. This is due to several reasons:

      The first reason is that traditional freezing techniques were very damaging to the egg. This is because eggs contain a lot of water and, as a result, ice crystals can form that may damage their structure, damaging them to the point that a high percentage did not survive the freezing and/or thawing process. Those that did were usually so compromised that they were rendered “incompetent”. The recent introduction of a new freezing method called vitrification avoids this effect, because it freezes the eggs so fast (about 600 times faster than older methods), that ice crystals will not form. Vitrification uses a cryoprotectant formula that helps dehydrate the eggs so that they can be safely frozen without forming damaging ice crystals. When, at a later date the woman is ready to use her eggs, a thawing formulation reverses the process, rehydrating the eggs back to their original state. Thus, vitrification has opened the door to safe freezing and banking of eggs over an indefinite period of time.

      The second reason why in the past egg freezing has been such a dismal failure, is the inability to accurately identify eggs that are chromosomally normal (“competent”) and thus likely to propagate a baby once they were fertilized and transferred to the uterus. This is particularly important because even in young women, less than half of eggs are “incompetent.” The incidence rises rapidly with advancing age, such that by the mid forties, less than 10% of human eggs are chromosomally normal. Thus, the safe and successful banking of eggs for FP largely hinges on the ability to successfully identify and then freeze-store (cryobank) only the “competent” ones for future dispensation.

      The above mentioned factors serve to explain why most IVF programs that offer egg freezing for FP currently insist that in order to have a reasonable chance of pregnancy a woman should have 16-20 eggs cryobanked. To reach this target often requires that she undergo more than one cycle of hormonal stimulation with egg retrieval.

      In October 2008, we at SIRM were the first to report (in the Journal, “Reproductive Biomedicine Online”) on a process that dramatically improves the baby rate per egg frozen by 7-8 fold. It involves first identifying chromosomally normal eggs using a genetic test known as Comparative Genomic Hybridization (CGH), and then selectively freezing (by vitrification) only these eggs. The process of combining CGH testing with selective egg vitrification, and then banking only chromosomally normal eggs promises to provide a far better success rate with egg freezing for FP, thereby allowing women to have relative confidence that once about 5 such “competent” eggs have been safely cryobanked the subsequent transfer of embryos derived from such eggs would afford an excellent (better than 60%) chance of a baby.

      There are several advantages to selectively cryopreserving (vitrifying) only chromosomally normal (“competent”) eggs:

      First, each CGH-normal egg, upon being thawed is about 7 times more likely to result in a live birth (going from around 4% per frozen egg to about 28%).

      Second, given the resulting improvement in the competency and viability of cryobanked eggs, pregnancies resulting from such embryos would be about 4 times less likely to miscarry than would embryos that are derived from non-CGH selected eggs.

      Third, because more than 80% of embryos derived from CGH-normal eggs are likely to be chromosomally normal, the baby rate per embryo derived from a CGH-normal egg is about 60%. Thus there would seldom be a need to transfer more than 2 such embryos at one time, thereby virtually eliminating the risk of high order multiple pregnancies (triplets or greater)
      Fourth and finally, given that embryos were derived from “competent” eggs, the chance of chromosomal birth defects such as Down’s syndrome would be dramatically reduced.

      Who might benefit from Fertility Preservation through Egg Freezing?

      1. Women who face the prospect of losing ovarian function – either because of surgical removal of the ovaries, or exposure to radiation therapy and/or chemotherapy,
      2. 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.
      3. Couples undergoing in vitro fertilization who are opposed to embryo freezing on moral, ethical or religious grounds.

      There is little doubt that the demand for FP will grow as emerging technology allows egg freezing to become more readily available, safer and more reliable. The advent of CGH and other methods for fully evaluating the chromosomal integrity of eggs is a giant step in the right direction, but we still have a long way to go.

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