Why egg quality can be even more important than embryo quality

Good-quality embryos from poor-quality eggs don’t have the same IVF outcomes as embryos from good-quality eggs

Every IVF program in the world carefully assesses in every cycle the “quality” of obtained embryos. Whether the plan is to transfer those embryos at cleavage stage (day-3 after fertilization) or blastocyst stage (days 5-6), following different classification schemes which all in principle classify embryos as “good,” “mediocre” or “poor,” the goal is to select the “best” embryos from among the cycle cohort for the initial embryo transfer.

Though in principle a valid concept in that 100 “good” embryos will result in more pregnancies and deliveries than 100 “mediocre” embryos (most IVF centers do not transfer “poor” quality embryos), it is only a statistical parameter that holds up when it comes to large cycle numbers. Yet, transfers of many “good” embryos will still fail, while a good number of mediocre embryos will result in normal pregnancies and healthy deliveries. In other words, embryo selection has significant limitations. Yet embryo selection has been a “holy grail” of embryology since the inception of IVF.

Within this context it is important to remember that the embryo is the ultimate downstream product of a long physiological process, which starts with recruitment of a follicle from the primordial follicle pool a woman is born with. This follicle then undergoes a 3-4 months of maturation before becoming responsive to the fertility medications used in an IVF cycle to stimulate follicle growth. This so-called gonadotropin-dependent phase of follicle maturation lasts ca. two weeks and ends with ovulation of one egg in a natural cycle and with retrieval of usually multiple eggs in an IVF cycle, where eggs are fertilized with sperm and embryos are created. For this to be achieved the sperm penetrates the egg; in other words, spermatozoa enter the environment of eggs, which is reflective of the physiological fact that the egg dominates ca. 95% of embryo quality.

The embryo that is graded, therefore, is the end product of this months-long series of events, during which time much can, and does, happen that will influence the quality of the embryo. CHR investigators, therefore, concluded a number of years ago that closer attention to egg quality may, indeed, help in improving embryo selection. As previously discussed in the VOICE, a number of studies confirmed this hypothesis, demonstrating that, assuming everything else is equal, egg quality becomes an important predictor of pregnancy success, often outperforming standard embryo assessments.

In CHR’s weekly conference, where every failed IVF cycle is dissected into all of its individual components and reanalyzed, egg quality assessments have, therefore, become a very important factor in adjusting treatments for future cycles. With special attention given to egg quality, it has become quite obvious that not infrequently embryos appear to have the ability to correct poor egg quality and, based on standard morphological criteria, present themselves as very “good” quality embryos on day-3; yet, their pregnancy chances are quite poor. Assessment of egg quality, therefore, has at CHR become as important as standard assessments of embryo quality have been for decades.

This is a part of the December 2018 CHR VOICE.

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned reproductive endocrinologist, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.