Question About Embryo Crowding
3 Replies
oldgal - October 8

I just finished my 1st v cycle. I am 44 and had 11 eggs retrieved, 8 fertilized. 6 of the 8 were excellent grade- 8 cell /or 8+ cell (2 early compacting) on Day 3 with little or no frag. One was a grade 1 - but 4 cell with no frag, and 1 was a 5 cell grade 3 - with 50% frag. RE transferred 5 embies on day 3. 3 others lost arrested between day 4 & day 5.

I tested postive - on 9dp3dt - beta 5; 2nd beta 12 dp3pt - 31; 3rd beta - 16p3pt- 24. Classified as chemical pregnancy.

The good news in my opinion was that I stimmed well, fert rate was goot and embie quality was good. Bad of course, it that our utlimate goal is to seek out and find that "one or two" good eggs that are euploid.


Can you give me any opinion on the concept of Embryo Crowding? I have found differing trains of thought as it relates to this concept. The idea is that transfer of more than 5 embryos does not result in increaed pregnancy rates, due to the potential competition for implantation that can occur between normal vs abnormal embryos. With that said, the thought is that good embryos could compete with abnormal ones, which could throw off "free radicals" and adversely affect the implantation of good embryos?

Have you every hear of this> Can you tell me how this works as an embryologist?

P.S.- I know so many people, including you, Dr Smith would recommend 5- day blast a one of the best methods of identifying and selecting the "best embryos" for transfer. But,I respectfully am not inclined to follow this protocal. I prefer 3 day transfers, and if at all possible, would like to consider transferring higher multiples of embryos on day 3 to offset the high %s of anueploidy, knowing that appearance, alignment, blast culture, or other morphological indicators cannot clearly predict which embryo will or wont be euploid.

Thank you so much in advance for for your thoughts or experiencce on the embryo crowding concept


Dr Smith - October 10

The embryo crowding concept comes from animal science and was studied in regard to how many embryos to transfer back in cows to maximize the chance of implantation without "overcrowding". However, there is at least one major distinction between cows and women (tounge firmly in cheek); the developmental potential of the embryos. In the bovine model, the vast majority of the embryos are developmentaly compentent (i.e. they reach the blastocyst stage). The opposite is true in humans. The embryos must develop to the blastocyst stage to attain the capacity for attachment and implantation. Embryos that fail to reach the blastocyst stage are not competing with anything. They're dead. So, transferring several Day 3 embryos of which a very few will make it to the blastocyst stage will not result in competition for implantation sites. This is paticularly true in your case, becasue you are 44 and very few of your embryos will develop to the blastocyst stage (in vitro or in vivo).

As far as dying embryos releasing free radicals (and other toxic chemcials), the point is moot. There is an abudant number of free radical scavenging molecules in uterine fluid. Let's stop and think for a moment. What happens to all the left over sperm after "the one" sperm (played by Keanu Reeves) makes it to the egg and fertilizes it. The sperm die. All over the place. And they release free radicals and a bunch of other toxic dying cell stuff into the uterine fluid. The uterine fluid is capable of taking care of this (clean up on aisle 3) and making it a habitable place for embryo implantation. No worries there.

Transferring high numbers of embryos does not result in higher "pregnancy rates" becasue pregnancy is an all-or-none outcome measure. For example, transferring 3-4 embryos in a 32 year old patient will not increase her chances of pregnancy as measured as an all-or-none outcome (she has a good prognosis anyway). HOWEVER, it will increase her chances of conceiving twins, triplets, etc. Multiple gestation is a incremental outcome measure (i.e. 1 or 2 or 3, etc.). If the outcome of a 3-4 embryo transfer is measured as an incremental outcome, transferring 3-4 embryos in a young patient is simply bad medicine.

As you pointed out, blastocyst transfer is not for everyone. Something to consider: Chemical pregnancies can be caused by a few things, but a low number of stem cells in the blastocyst stage embryo is a major cause. Your chemical pregnancy may have been avoided by evalauting the adequacey of the stem cell population in the blastocyst prior to transfer. Just a thought...


oldgal - October 11

Hi dr Smith

Thank you so very much for your response. It gave me much greater insight into how this works. I am very appreciative.

In so far as your comments relating to chemiccal pregnancies, I have a few follow-up queries:

1) how would one go about testing for the adequacy of the stem cell population? is this done thru PGD or thru some other type of testing?

2) I have read that testing for the polar body1 can provide an indication of anueploidy. Is this done on the egg or on the embryo?

Thanks again.


Dr Smith - October 12

A1. The stem cell population (the inner cell mass) is clearly visible inside the expanded blastocyst stage embryo. The adequacy of the stem cell population is evaluated visually by a trained embryologist. There are a variety of grading systems: ABC, 123, etc. In general terms, A or B, 1 or 2, are considered adequate. C and 3 are considered inadequate and should not be transferred because if they do attach and intiate implantation, they will result in chemical or emty sac pregnancies. In the final analysis, there are two grades of stem cell populations: baby grade or non-baby grade.

A2. Genetic testing on the 1st polar body is performed on the egg immediately prior to ICSI. Anaylsis of the 2nd polar body is performed on the 1-celled embryo (zygote) shortly after fertilization. Although great in theory, genetic testing of 1st and 2nd polar bodies is not very reliable and usually requires follow up testing on the 4 to 8 cell stage embryo anyway. So what was the point of subjecting the embryos to multiple biopsies? Good question. Accordingly, polar body analysis has been, for the most part, abandoned in favor of cell stage biopsies.



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