This is the 11th in a series of answers to common questions about failed IVF.

(Note: I’ll be hosting a live video chat on Aug. 2 on the topic of Failed IVF where I’ll discuss the questions addressed in this series of posts and take your questions. For more information on this live IVF chat, click here.)

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One of the commonest questions asked by patients undergoing IVF relates to the likelihood of their eggs fertilizing and the likely “quality” of their embryos. This is also one of the most difficult questions to answer.

On one hand, many factors that profoundly influence egg quality such as the genetic recruitment of eggs for use in an upcoming cycle, the woman’s age, and her ovarian reserve, are outside of our control. On the other hand, the protocol for controlled ovarian stimulation (COS) can also profoundly influence egg/embryo development, and this indeed is dictated by the treating physician.

First: it should be understood that the most important determinant of fertilization potential, embryo development and blastocyst generation is the numerical chromosomal integrity of the egg. While sperm quality does play a role, in the absence of moderate to severe sperm dysfunction this is a relatively small one. Human eggs have the highest rate of numerical chromosomal irregularities (aneuploidy) of all mammals. In fact only about half the eggs of women in their twenties or early thirties have the proper number of chromosomes (euploid), without which they cannot make a normal pregnancy. As the woman advances into and beyond her mid-thirties, the percentage of euploid/normal eggs declines progressively such that by the age of 40 years, only about one out of seven or eight are likely to be chromosomally normal. By the time she reaches her mid-forties, less than one in ten of her eggs will be euploid.

Second: embryos that fail to develop into blastocysts are almost always aneuploid (abnormal) and not worthy of being transferred to the uterus because they will either fail to implant, miscarry, or even result in a chromosomally abnormal baby (e.g. Down syndrome). However, it is incorrect to assume that all embryos reaching the blastocyst stage are euploid (“competent”). It is true that many aneuploid embryos are lost during development, and that those that survive to the blastocyst stage are far more likely to be competent than are earlier (cleaved) embryos. It is also true that the older the woman who produced the eggs, the less likely it is that a given blastocyst will be “competent.” As an example, a morphologically pristine (good looking) blastocyst derived from the egg of a 30-year-old woman would have about a 50:50 chance of being euploid and a 35%-40% chance of propagating a healthy, normal baby, while a microscopically comparable appearing blastocyst derived through fertilization of the eggs from a 40-year-old would be about half as likely to be euploid and/or propagate a healthy baby.

While the inherent potential of human eggs to be euploid at ovulation is genetically preordained and nothing we do can alter this equation, there is unfortunately a lot that the RE (often unwittingly) can do to worsen the situation by selecting a suboptimal protocol of controlled ovarian stimulation (COS). This will, by creating an adverse intra-ovarian hormonal environment, often disrupt normal egg development and lead to a higher incidence of egg aneuploidy than otherwise might have occurred. Older women, those with diminished ovarian reserve (DOR), and those with polycystic ovarian syndrome (PCOS) are especially vulnerable in this regard.

During the normal ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone) are produced by the tissue surrounding the ovarian follicles (stroma) during the pre-ovulatory phase of the cycle to enhance late follicle development, estrogen production by the granulosa cells (that line the inner walls of follicles), and egg maturation. However, over-production of testosterone can adversely influence the same processes. It follows that COS protocols should be individualized and geared toward optimizing follicle growth and development time while avoiding excessive ovarian androgen (testosterone) production, and that the hCG “trigger shot” should be carefully timed.

In summary it is important to understand the influence that species, the age of the woman, and the effect of the COS protocol have on egg/embryo quality, and thus on IVF outcome. The selection of an individualized protocol for ovarian stimulation is one of the most important decisions that the RE has to make. This becomes even more relevant when dealing with older women, those with DOR, and women with PCOS. Such factors will in large part determine fertilization potential, the rate of blastocyst generation, and indeed IVF outcome.