In this flourcent in situ hybridization image, human spermatozoa carrying Y chromosome (green - male) and X chromosome (red - female). Sperm nucleus is blue.

 


 

 


IVF

 

PGD can only be accomplished during In Vitro Fertilization cycle. Therefore understanding what happens during PGD requires understanding of IVF. There are many great web sites explaining IVF, however you may still find the following information useful.  

Even though infertility is defined as inability to conceive during 12 months of unprotected intercourse, there are actually not many couples who are truly infertile. However, couples do vary widely in how much time it will take for a viable pregnancy to take place, some can achieve pregnancy every ovulation, while for others it may take one-two years or even longer.  

The real question is, whether you are willing to wait and whether your age makes it feasible. If you are not willing or unable to wait, than you need an IVF whether you are fertile or not.  

Male infertility

Male infertility is one of the areas of great confusion, speculation and anxiety.

The World Health Organization guidelines refer to the semen sample as normal if:

It is at least 2 ml in volume
At least 50% sperm cells are motile
At least 40 million sperm cells per ejaculate
At least 30% of the sperm cells have normal morphology

However, a study of men undergoing vasectomy, who are proven fertile, shows a large variation, well outside normal limits.

One of the highly reputable studies into the subject suggests that anything above 5 million total motile sperm cells in ejaculate does not make any difference for fertility.

Moreover, even sperm count below 1 million motile sperm cells does not preclude pregnancy in some couples.

On the other hand, paradoxically, an apparently normal sperm sample may fail to fertilize an egg during an IVF in about 5% of the cases, motivating some programs to use ICSI irrespective of sperm characteristics to assure fertilization.

Only about 10% of males with infertility are carriers of chromosomal errors.  Usually those are cases with severe forms of infertility where no live sperm cells are present in ejaculate.

As far as chromosomal aberrations detectable by PGD, sperm contributes less than 1% of errors in most cases. Errors in eggs and embryos contribute the remaining 99%.

Female infertility

A woman’s ovaries contains thousands of eggs. Those eggs may look similar but they differ greatly in their ability to become a baby once fertilized: some of them are good, while others are not.

There is no woman who has only good eggs or only bad eggs, but certainly even in the same age group some woman have a relatively high proportion of good eggs, while others relatively low. Both can be considered a variation of normal.

During a menstrual cycle, a women's body randomly chooses an egg, which can be good or bad. This egg ovulates, becoming available for fertilization.

Because a woman with a lot of good eggs has a higher chance of ovulating with a good egg, she will become pregnant quicker. Woman with fewer good eggs will also become pregnant, although it will probably take her longer.

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. 

Preimplantation Genetics Diagnosis