Increasing the odds with IVF.
In IVF, the number and quality of eggs are the main factors determining success. More specifically, until the age of about 38, the number of eggs almost exclusively defines the chance of pregnancy, while after 38, both egg number and their quality (mainly chromosomal errors), determine success. We cannot control egg quality, however, modern ovarian stimulation protocols can increase the number of eggs. Here is how it works: Every natural menstrual cycle 5 to 15 follicles containing eggs beginning to grow. Those follicles are recruited by ovaries randomly in a mysterious, hormone-independent way which physicians cannot control. After a couple of days it becomes apparent that one of the follicles in the growing cohort is clearly larger than others. From this moment on, this follicle, now called – dominant (it may or may not contain a good egg), – is the only one that will continue to develop. It will ovulate around the mid of the menstrual cycle, while all sibling follicles will degenerate. IVF medications, primarily FSH, will rescue those sibling follicles and most of them will come to the finish line together with the dominant follicle. As a result, your chance of pregnancy in a single IVF cycle is multiplied roughly by the number of eggs that were retrieved during follicular aspiration. For example, if you have 5 matured eggs harvested during an IVF, your chances would be multiplied by 5. During an IVF attempt, there will still be a variation in pregnancy chance between women with more or less good eggs in their ovaries, but this difference will become smaller than during a natural cycle, provided that several eggs are retrieved. For example, one woman has 10% good eggs while another woman has 50% of good eggs in their ovaries. During a natural cycle, at any given time, the woman with 50% of good eggs is 5 times more likely to get pregnant than the other. Let's assume that in an IVF cycle the women have 10 eggs retrieved each. In theory, out of those 10 eggs, one woman will have 1 good egg and another 5. However, since each woman needs only one good egg to get pregnant, their chances of taking a baby home will be the same. The above calculations is a simplification that assumes we can identify that one good egg (or an embryo developing from it), which unfortunately remains an illusive task. In fact, identifying the best egg or embryo (embryo selection) is the most important research goal in IVF and PGD is considered one of the tools to achieve this goal.
Embryo selection
Today we have several available tools to select the best embryo, by evaluating embryo morphology, blastocyst culture, measurement of metabolic activity and PGD.
Embryo morphology (appearance)
Embryo morphology (appearance) on day 2 or 3 of in vitro development is the most common way to select viable embryos. It generally works well. However, the goal of modern IVF is a singleton pregnancy and anything else is coming to be considered a failure because of the risk associated with multiple gestations. This goal cannot be accomplished by embryo morphology assessment alone.
Blastocyst culture
Using extended embryo culture is becoming one of the most common ways of embryo selection. This type of selection is based on a simple idea that embryos that are able to survive in vitro for 5 days and develop into the blastocyst are the strongest. Even though that is generally true, there are no doubts that blastocyst culture also eliminates some of the embryos that would become babies if they were transferred earlier (on day 3). This is because in vitro culture is not equal in quality to the uterine environment (fallopian tubes would be even more natural at that stage). Indeed, some studies indicate that there are patients who benefit from transferring embryos as soon as possible, even as earlier as right after fertilization (day 1). Besides, we do not know what we are really selecting with extended culture. Perhaps those embryos that survive to the blastocyst stage in vitro are future line backers, and those that do not are rocket scientists, doctors and lawyers. Furthermore, despite helping to narrow down the choice, blastocyst culture still does not allow selection of the single best embryo, and in most cases 2 blastocysts are transferred. Prospective randomized trial has demonstrated no advantages of blastocyst transfer. To summarize, even though our ability to culture embryos in vitro to the blastocyst stage has improved greatly over the last 5 years, this is still not an option for every couple. In some cases it may result in the loss of otherwise viable embryos.
Metabolic activity
Finding metabolic markers is one of the areas where progress is being made. This research is extremely important because chromosomal errors that can now be detected by PGD are essentially a collateral damage of errors in metabolism. Having metabolic markers available would allow a non-invasive technique for comprehensive assessment of not only an embryo but also of an egg.