“At 45 years of age the incidence of
aneuploidy is likely to be nine in ten.”
Several weeks ago, I posted an article about endometrial receptivity and its effect on IVF success. This, as I noted, was the “Soil” component of the “Seed/Soil” equation. I turn now to the “seed” component of the equation – the embryo.
This will be the first of three posts outlining the factors that contribute to embryo “competence” (the ability of an embryo to make a healthy baby), and the current methods of genetic testing in the IVF setting.
Today’s post will discuss the intrinsic factors that contribute to (or detract from) embryo competence.
First, a brief background discussion….
If an embryo reaching the endometrial cavity either fails to implant or is lost soon after implantation (i.e., a chemical pregnancy or miscarriage) it will, in the vast majority of cases (about 80%), be due to an inherent defect that has rendered it incapable of propagating a viable conceptus – a condition we term “embryo incompetence”. In only about one of five such reproductive losses would the cause be attributable to “poor endometrial receptivity”.
What is important to bear in mind is that it is primarily the genetic/chromosomal integrity of the egg (rather than the sperm) which determines embryo competence. Given the fact that egg numerical chromosomal integrity declines with advancing maternal age, it is hardly surprising that embryo competence also deteriorates in lock step with advancing age. Research has shown that about half of all embryos derived through fertilization of the eggs of a young woman (under 35 years) are likely to be incompetent, while at 45 years of age the incidence is likely to be nine in ten. This serves to underscore and explain why both spontaneous pregnancy and IVF success rates plummet, and miscarriage rates virtually treble, by the time the woman reaches her mid-forties.
It is thus important that the following intrinsic factors which control embryo competence be considered:
- The relative influence of egg versus sperm: In order for an embryo to be “competent” it must have its full component of 46 chromosomes (i.e., euploid). Any irregularity in the numerical chromosomal integrity (i.e. aneuploidy) of the embryo will inevitably result in “reproductive failure”, manifesting as failure to conceive, miscarriage, or an aneuploidy- birth defect such as Down Syndrome. While it is the chromosomal integrity (karyotype) of the egg which exerts the predominant influence on embryo’s karyotype and thus its “competency”, the chromosomal integrity of the sperm also plays a role, albeit a far lesser one when the man is fertile. However, in cases of sperm dysfunction, this influence can be significantly greater.
- The influence of the chromosomal structure of the egg and sperm: The structural chromosomal integrity of the embryo also influences its “competency”. In some cases, part of one or more of the embryo’s chromosomes may be missing (a “deletion”). Sometimes during fertilization, parts of one or more chromosomes detach and reattach to another chromosome (a “translocation”). Such structural changes can emanate from a sperm and/or an egg defect, but the degree to which either gamete contributes, and what role paternal or maternal age, environmental, or genetic factors may play in its genesis are presently poorly understood. Unless specifically looked for at the time of preimplantation genetic sampling (PGS) of the embryo, such structural chromosomal aberrations might go undetected.
- The role of genetic and metabolic factors: There can be little doubt that genetic and metabolic factors also impact embryo competency, but how and to what extent such influence is exerted remains poorly understood. To make matters worse, they are, by and large, neither identifiable nor quantifiable through any currently available diagnostic methodologies. This having been said, the potential exists for the future application of human genomics to embryo evaluation, and with it will likely come a new-found ability improve to better evaluate “embryo competency”
NEXT: Check back next week, when my post will focus on clinical considerations – what your RE can do to optimize embryo competence.