Egg Quality and Fertility Treatment Success

Egg Quality and Fertility Treatment Success

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What does egg quality means?

Good quality eggs are mature eggs that are able to fertilize, develop into normal embryos that are able to implant and progress to a healthy baby. Good quality eggs have normal chromosomes. A normal egg contains 23 chromosomes and when fertilized with a sperm produce a zygote that has 46 chromosomes.

How is egg quality tested?

Two methods

  1. Non invasive: asking a woman about her age. Age is the most important determinant of fertility. All women have abnormal eggs and well as normal ones. With advance in age the proportion of normal eggs decrease because the ovary ovulates the healthier eggs earlier in life. Older women have less eggs and more abnormal eggs. Apart from age and ovarian reserve testing there are no other noninvasive methods to test for egg quality. Couples may present with unexplained infertility, minor abnormalities or repeated unsuccessful fertility treatment. Other indicators of lower egg quality are recurrent early first trimester pregnancy loss (biochemical pregnancy), pregnancy loss in the first trimester when chromosome analysis of products of conception is abnormal. Ectopic pregnancies are more common with chromosomally abnormal embryos.
  2. Invasive method: the eggs can be retrieved and DNA analyzed via PGD, before or after fertilization to detect the number and structure of chromosomes. This is usually done during actual fertility treatment.
Advance in maternal age is associated with lower chance for conception due to lower number of eggs with normal chromosomes

Advance in maternal age is associated with lower chance for conception due to lower number of eggs with normal chromosomes

 

How can we improve egg quality during fertility treatment?

Strategies employed to improve egg quality during fertility treatment include

  1. Random increase in the number of eggs produced: Ovarian stimulation can increase the number of eggs produced increasing the odds that one or more of those eggs have normal chromosomes. This random increase in the number of eggs is employed in IUI and IVF cycles. We do not know if any of the eggs are normal but generally the more eggs you make the higher the likelihood that one or more are normal.
    Human eggs retrieved after ovarian stimulation

    Human eggs retrieved after ovarian stimulation

  2. Tweaking of ovarian stimulation protocol: Many changes to the stimulation protocol can improve response and egg quality including, choosing an agonist or antagonist based protocol, the addition of an oral agents like clomid or letrozole, reducing the dose of gonadotropins, changing the timing for the trigger shot hCG.
  3. Embryo selection using morphology: Healthy embryos divide and double the number of cells every 24 hours or less (8 to 10 cells on day 3). Healthy embryos have equal cells and each has a single nucleus. Healthy embryos are not fragmented (due to cell breakdown). These embryos are identified under the microscope. The problem with morphology is that many unhealthy embryos are good looking. the prediction ability of morphology in detecting chromosomally normal embryos is probably 60% or less. Morphology, however is non invasive and cheep. Extended vulture is used to push embryos to day 5 to observe which embryo will reach the blastocyst stage and select it for transfer. Blstocysts have generally higher implantation rates than day 3 embryos because of the ability to select the better embryos. Extended culture is employed when many embryos are available on day 3 (usually five or more).
  4. Genetic analysis of eggs or embryos: The most important point to know about genetic analysis of eggs and embryos is that PGD does not create a new potential or improve the overall success for fertility treatment for a given stimulation cycle. It just detects fairly accurately (not 100% accurate) the chromosome makeup of eggs or embryos. The potential advantage of PGD is to directly select the embryo, out of available cohort, that is most likely to implant instead of selecting based on morphology. Thus it maybe helpful for women with large number of embryos available on day 3 and day 5. In other words if you have two embryos available on day 3 and you are transferring two embryos, there is no point in testing them. On the other hand if you have eight embryos on day 3 and you will only transfer 1-2 embryos, then PGD may makes sense to go directly to the embryos most likely to work.

The potential disadvantages of PGD are the need for embryo biopsy that potentially may harm the embryo. PGD assumes that the cell obtained represents the whole embryo while sometimes that cell chromosomes maybe different than the embryo. The method for analysis used is not 100% accurate. In other words the method may misdiagnose a healthy embryo as abnormal or vice versa or on occasions fail to diagnose the embryo at all. PGD is expensive requiring embryo biopsy and embryo genetic analysis.

So far no large scientific studies are available and reproduced by many centers indicating increase in fertility potential of IVF. Because of all these factors, PGD is selectively applied to select patients and not a universal step in all IVF cycles.

Other methods suggested as supplements as well experimental methods as mitochondrial transfer still lack scientific evidence that they work.

 

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