An ever increasing number of American women first seek IVF treatment in their late 30’s or early 40’s.This trend is in large part due to the fact that more and more women are choosing to defer childbearing until they have fulfilled their career aspirations. While such deliberate deferment is understandable, it nevertheless poses significant problems, because women in their late 30’s and early 40’s have about one half the chance of having a baby following IVF than do women in their early to mid-30’s. There are two primary reasons for this:
First is the fact that advancing age beyond 35 years is accompanied by an inevitable and progressive increase in numerical chromosomal egg abnormalities (aneuploidy) that lead to “incompetent” embryos that cannot propagate viable pregnancies. That is why we see a profound and steady decline in IVF success rates as well as an increase in chromosomal miscarriages and birth defects such as Down’s syndrome with advancing maternal age.
Second, as women get older, there occurs a progressive decline in their ovarian egg supply, referred to a diminished ovarian reserve (DOR) which manifests with a declining response to fertility drugs, an elevated basal blood FSH level and a falling blood AMH concentration” When it comes to IVF, DOR results in less eggs being accessible at egg retrieval and consequentially, fewer “competent” embryos available for transfer to the uterus.
Most women/couples would like to have more than one child. This desire is no less prevalent in older women. However, by the time the older woman decides to do IVF, goes through the process successfully, has a baby, completes breastfeeding, and thereupon re-establishes regular menstruation in order to try for another IVF baby, a period of 2-3 years will have elapsed. While such a hiatus would usually be of little consequence to a young woman, for an older woman such a delay could seriously impact her “biological clock” so as to drastically reduce her chance of having another baby with her own eggs.
The concept of Embryo Banking/Stockpiling: Embryo Banking offers a potential alternative to IVF with egg donation, for older women and those with DOR who wish to minimize the relentless effect of the “biological clock”. The process involves undergoing several IVF stimulation/egg retrieval procedures in relatively quick succession, biopsying them for preimplantation genetic sampling (PGS) and then freezing/banking all those that survive to the blastocyst stage (day 5-6 post-fertilization) embryos for future dispensation, rather than having them transferred to the uterus immediately .Once enough biopsied embryos (usually 4-8) have been stockpiled, all biopsied material derived from those embryos that reached the blastocyst stage are dispatched for PGS testing by generation gene sequencing-(NGS) . Those embryos found to have a normal number of chromosomes (euploid) are held for subsequent transfer to the uterus in a later FET cycle (i.e. “staggered” embryo transfer). ”Such embryo banking/stockpiling” literally stops the biological clock in its tracks, allowing for the subsequent elective thawing of one or two frozen embryos at a time in future frozen embryo transfer (FET) cycles. This process would avert the risk of progressive declining egg/embryo “competency” over time.
Embryo banking/stockpiling would not have been feasible a decade ago since it was not until quite recently that we became able to reliably identify chromosomally normal (“competent”) embryos for selective banking. Embryo freezing technology has also evolved dramatically over that time. Just a few years ago, the freezing process took a serious toll on embryos, severely damaging up to 50% of them in the freeze/thaw process. But that was then…Today, through embryo karyotyping with NGS for the selection of euploid embryos we are able to much better identify “competent” embryos for banking and stockpiling. In addition, the recent introduction of much improved egg/embryo freezing through ultra-rapid cryopreservation (or possibly even improved) eliminates most of the potential damage incurred to “competent” embryos during the freezing and thawing process. In fact, in IVF centers of excellence, the frozen embryo transfer (FET) process using vitrified/thawed embryos now yields at least the same IVF success rate as when fresh embryos are transferred!
These innovations (PGS and blastocyst Vitrification) have not only made embryo banking/stockpiling feasible, but have rendered the approach a most appealing option for older women and women with DOR who seek to undergo IVF using their own eggs.
This having been said, PGS is not an indispensable part of embryo banking. The process can be done without it. But, given the inevitability of an age-related increase in the incidence of chromosomal abnormalities in the egg/embryo, it would be impossible for patients to know whether they have stored the most “competent” embryos and thus which ones to transfer to the uterus for the best chance of success when the time comes.
I want to emphasize that PGS does not improve embryo quality. It is merely an efficiency tool that allows us to select the most “competent” embryos for transfer and thereby significantly improve the baby rate per embryo transferred. It is also well to bear in mind that embryo aneuploidy not only reduces the chance of a successful pregnancy but it is also the commonest cause of miscarriages and certain birth defects (e.g. Down’s syndrome). Thus PGS embryo selection not only improves IVF success (per embryo transferred),reduces the risk of miscarriages and birth defects but by identifying the most “competent” embryos it also reduces the incentive to transfer multiple embryos at a time, thereby dramatically reducing the occurrence of high-order multiple pregnancies (triplets or greater).
Proudly, Levent Keskintepe and I were the first to introduce PGS embryo selection into the clinical IVF arena. We initially used a PGS method known as comparative metaphase genomic hybridization (mCGH) but now have largely switched to NGS (an improved method). Since introducing clinical PGS for IVF we have reported hundreds of successes using this approach, which has since gained wide acceptance in throughout the IVF field. It is against this background that we now provide selective embryo banking/stockpiling to an ever increasing number of older women and women with DOR.