Source of chromosomal errors

About 75% of preimplantation (in vitro) embryos are chromosomally abnormal. By the time they reach a blastocyst stage, about 40% of all surviving embryos are chromosomally abnormal. On average, oocytes contribute about 27% of numerical errors, sperm about 7% and the remaining about 3 % appear as an embryo divides (the numbers for sperm, oocyte, and embryo errors are probabilistic and can’t simply be added together to get 100%). With age, an oocyte’s relative contribution to overall chromosomal errors increases. 

Chromosomal errors in oocytes

It is very important to keep in mind that ALL immature oocytes in the ovary, at any age, are chromosomally normal. An oocyte remains chromosomally normal until after a natural LH surge or an artificial trigger is administered. It is only at this moment that chromosomal errors begin to take place. More than half of all errors happen at this time. Most of the remaining errors take place after fertilization before pronuclei are formed in a zygote.

The percentage of mature oocytes with numerical chromosomal errors can be estimated in two ways. An indirect approach, based on the number of chromosomal errors in sperm and embryos, gives an expected percentage of chromosomally equal to 27%. This is in astonishingly close concordance with a direct method of observing chromosomal errors in oocytes – 26.5%

Chromosomal errors in sperm 

There are only 3 publications that exist directly evaluate the rate of chromosomal errors in individual human spermatozoa by injecting them into mouse oocytes. They evaluated both, numerical and structural aberrations in sperm chromosomes. Because we cannot be certain that the fidelity of replication in mouse oocytes for human chromosomes is 100%, the number of structural aberrations may be higher than in reality. However, the number of numerical aberrations can be accepted without any reservations. 

My friend and colleague Dr. Andrew Rybouchkin was the first to use this experimental model for evaluating chromosomes of human spermatozoa.  He has also shown that so-called globospermia, when sperm cells are lacking acrosome and have round heads) do not have any increase in the number of chromosomal aberrations, compared to sperm donors. 

Dr. Lee( from Dr. Yanagimachi) group has demonstrated using the same approach that the rate of numerical chromosomal aberrations in sperm is low, 1.3%.  They also show that in grossly chromosomally abnormal sperm cells the rate of aberrations can be as high as 26%. It is very important to keep in mind that the criteria they used to classify a sperm cell as “abnormal” are very different from those used in standard sperm morphology. First, they were judged as abnormal using the inverted microscope, live, without any fixation and staining. Second, they were truly grossly abnormal and clearly represent an outlier of extremely poor morphology, which contributes only a tiny percentage point to morphologically abnormal sperm cells as judged after fixation and staining using conventional techniques.  

From the above studies, we can conclude that no more than 7% of the sperm cells are chromosomally abnormal. 

Chromosomal errors during first cell divisions

When the zygote cleaves for the first time, and even less often with subsequent divisions, additional chromosomal errors may take place. Those errors combined,  contribute less than oocytes or sperm to overall chromosomal errors. 

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