This is the 10th in a series of answers to common questions about failed IVF.

The most important determinant of IVF outcome is embryo “competence” (i.e., the ability of an embryo to propagate a pregnancy in a receptive uterus). Since egg quality at the time of retrieval that is the most important determinant of embryo “competence”, it follows that the factors that influence the process of egg develoment and post ER egg processing ovogenesis will feature centrally as possible causes of IVF failure or success. These include the following:

1. The genetic potential of eggs as they begin their developmental process (i.e., immediately prior to the initiation of the cycle).
2. The intra-ovarian environment in which eggs develop (ovogenesis) during controlled ovarian stimulation (COS).
3. The technical expertise in the embryology lab.

Unfortunately, there is nothing that anyone can do with regard to #1. Eggs are genetically recruited about four months in advance of their availability for use in an IVF cycle and it is thus preordained as to which of them will be chromosomally normal when they arrive at the “starting gates” of any IVF cycle.

Item #2 above is another matter altogether. There can be little doubt that the environment in which eggs develop prior to egg retrieval or ovulation, can and does profoundly influence their potential to make “competent” embryos upon fertilization. This influence is most pronounced in older women and/or those with diminished ovarian reserve, where implementation of COS protocols that result in ovarian overexposure to Luteinizing Hormone (LH) are used (e.g., clomiphene citrate, Lupron “flare” protocols and/or administration of a large dosage of gonadotropins that have a high LH-like component, such as Menopur). In such cases, overexposure to LH could provoke excessive ovarian testosterone production, which in turn can compromise follicle growth and egg development. This can set the stage for egg aneuploidy (an irregular number of chromosomes) and thus ultimately also for embryo “incompetence.”

In spite of the above, when IVF fails to result in a viable pregnancy, a finger of suspicion is often directed at the most vulnerable part of the IVF team…the embryologists. This is usually completely unjustified. In fact, IVF embryologists tend to be far more committed to quality control and adherence to established protocols and procedures than are most RE’s, who often randomly modify established protocols and procedures at a whim. This does not mean to imply that embryologists are never to blame for embryos being compromised…. They sometimes are, but this is not usually the case. Remember, no embryologist is capable of generating a chromosomally normal (“competent”) embryo from an aneuploid egg. And since the chromosomal integrity of the egg is primarily genetically determined and influenced by the protocol of ovarian stimulation(see #1 and #2 above), it follows that embryo “incompetence” will rarely be due to the laboratory error.

Of course adequate technical laboratory expertise is required for the performance of procedures such as egg/embryo biopsy for PGD, which if inexpertly performed, can prejudice embryo quality and outcome. Likewise, procedures such as ICSI and assisted hatching (AH) also require significant dexterity…but most well trained embryologists have such expertise. Thus, what it all boils down to is that in the final analysis, the responsibility falls on the RE to craft individualized protocols of COS that will promote the best possible ovarian environment for mature (MII), chromosomally normal eggs which upon ER will be available to the embryology lab for optimal processing, fertilization, and culturing.