“Immature, Mature and Post-Mature Eggs” – Confusing and Misleading Terminology

08 Mar
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Within 38-42 hours of the onset of the spontaneous LH surge in normally ovulating women as well as after the administration of human chorionic gonadotropin (hCG) to women undergoing ovarian stimulation with fertility drugs, the 46 chromosomes in the human egg begin to segregate to divide in two. This process, known as meiosis or maturational division is designed to leave the mature egg (MII) with precisely 23 chromosomes in its egg nucleus. The remaining 23 are expelled from the egg nucleus (enveloped on a thin membrane) and come to lie in the viteline space (located between the outer membrane of the egg (the oolema) and the egg’s outer shell (envelopment) or zona pellucida. The purpose of the expulsion of this so called first polar body (PB-1) is to ensure that following fertilization by a mature spematazoon (whose chromosome number has also been reduced from 46 to 23), the resulting embryo so propagated would have regain the full quota of 46 chromosomes that makes up the human genome.

Thus the detection by microscopy, of a PB-1 situated immediately under the zona pellucida, indicates that maturational division (meiosis) has been completed. However, it does NOT confirm that chromosome segregation has take place evenly, i.e. that precisely 23 chromosomes remain in the egg nucleus (i.e. that the egg is “euploid”). The presence in the MII egg of one or more chromosomes above or below 23 in number, is referred to as “aneuploidy”, a condition that almost always inevitably in failed embryo development, failed implantation, miscarriage or a chromosomal birth defect such as Down’s syndrome.

As it turns out, even in younger women a half to one two thirds of MII eggs are aneuploid and this incidence increases rapidly with advancement in age beyond 35 years.

It follows therefore that the absence of a PB-1 on microscopic evaluation (i.e. an MI egg) clearly indicates that the egg had not completed meiosis, and thus “is aneuploid” and “incompetent” (i.e. is incapable of propagating a viable, healthy embryo. On the other hand, the detection of a PB-1 under the zona pellucida (an MII egg) while confirming that meiosis has been completed, offers no assurance that the egg is in fact “euploid” and thus is potentially “competent”. Quite to the contrary most MII eggs are in fact “aneuploid” and thus totally ‘incompetent”.

It is by and large the chromosomal integrity of the egg, rather than the sperm that determines embryo “competency”. Thus egg “competency” is an essential prerequisite for the propagation of a viable embryo and a healthy baby.

Another interesting fact is that in more than 90% of cases, an embryo that fails to reach the blastocyst stage (>100 cells), will be aneuploid, “incompetent” and thus are doomed from the get go. On the other hand, although not invariably the case, embryos that do make it to the blastocyst stage are much more likely to be euploid and thus “competent.” In fact, even in young women, at least 50% of blastocysts are aneuploid and thus “incompetent.” This percentage increases progressively with advancing age. While age is the main determinant of what percentage of eggs are aneuploid, the protocol used for ovarian stimulation as well as the timing of the hCG “trigger” can also influence the incidence of chromosomal abnormalities. When the hCG trigger is administered too early or too late, the egg might not be developmentally positioned to undergo orderly meiosis and either 1) be unable to expel half its chromosomes as a PB-1 and thus remain an M-I egg, or 2) the PB-1 may be expelled, but could contain an irregular number of chromosomes. In the latter case, the egg would have a visible PB-1 and would thus be labeled as a “mature” (MII) egg, though it would be aneuploid and “incompetent.” The terms “immature” and “post-mature” as applied to eggs, are often interpreted as meaning that the eggs were either harvested (retrieved) too early or too late, and that performing the egg retrieval a day or two earlier or later would have prevented this from happening. This infers that an MI egg was harvested before it was developmentally ready to enter meiosis and that egg post-maturity results from waiting too long before the hCG trigger. This inference is completely erroneous. In fact, an M1 egg could just as easily have resulted from delaying the hCG trigger shot, as it could from administering it too early. Likewise a “postmature” egg can result just as readily from administering hCG too early as too late. For these reasons, the terms “immature” and “post-mature,” as applied to eggs, should be supplanted by the term “dysmature” which simply means that the M-1 or M-2 egg in question is maldeveloped, aneuploid and “incompetent”.

86 Comments

  • 2NKN2 says:

    I’ve had three IVF cycles that have resulted in large amounts of immature eggs. The first cycle, conducted when I was 37, they retrieved about 25 eggs, half of which were immature. (I still have a Grade B blastocyst from that cycle.) The following year, they retrieved 16 eggs and only 6 to 8 were mature. Eight embryos at first, then two arrested and the other six didn’t make it to blast. They were Grade A on day 3, but none made it to blast. (I later found out my husband had high estrogen levels and borderline sperm DNA fragmentation results. He was put on Arimidex to balance his hormones and had a TESE procedure. Not sure what role that might have played in first two cycles). Doc blamed the failed cycle on me being 38. Just last week I had a third retrieval at age 39. 15 eggs were retrieved but just two were mature–my worst result yet! I started stimming exactly 3 months after a Lupron injection following a laparoscopy for fibroids/mild endo and was still having hot flashes. I’m worried Lupron may have affected the results. Also, this doctor gave me double the dose of Menopur I used in the other cycles (with different docs). With the first two, I had one vial of Menopur. Rather than consider any possible way to help me get more mature eggs, the doctor suggested I have a genetic defect and will have to use donor eggs, even though my AMH is 2.23. In all of these cycles I’ve had eggs mature in the lab and be fertilized with IVF and ICSI. This last cycle three grew in the lab to give me a total of five embryos, although on day 3 they were ranked fair and poor, my worst graded embryos ever. They have been frozen. This cycle was done just 10 months after the 2nd second cycle, so confused as to why it went so badly. Do you think it’s likely that I am the extremely rare woman with a genetic egg defect and will need donor eggs, as this doctor implied? The doctor doesn’t want me to attempt IVF again. I am quite worried. Thank you.

    • Geoffrey Sher says:

      My website has changed. The new site is at http://www.sherIVF.com where I host and populate new and updated blog articles . The blog can also be accessed directly by going to http://goo.gl/4hvjoP. I now only respond to posts on this new site.

      To find and follow updated and new blog articles and to post questions or comments, please use this new venue. I promise to respond promptly.

      In the interim, please re-post this question or comment on my new website-blog.

      Geoff Sher

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