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Closing discussion by Dr Richard Marrs

Closing discussion by Dr Richard Marrs D r R ichard M arrs (Closing statement), Los Angeles, Calif. Dr Paulson asked whether the reliability of the embryo's score was based on the individual doing it or was there a single individual who scores. Actually, in our laboratory, Dr Stone scores every embryo every day. He is the only person who will do the numerical scoring on a day-to-day basis. Occasionally, if he is not there, which is rare, Jodi will do the scoring, but 99.9% of the time, every embryo gets its numerical score from Dr Stone. What is the predictability of implantation based on this scoring or fragmentation type analysis? It is very difficult to answer that question because, as we all know, we are not yet doing single-embryo transfers. Because of the issues of having 2 or 3 embryos in a group of embryos transferred, I tried to look at the best type of fragmentation score in a group of embryos and gave you those data, and that is as close as I can get right now as far as what the impact of the scoring is on implantation rates. However, if you assume, and you have to take this leap of faith, that the best scored embryo or the embryo with the least fragmentation is probably the most likely embryo to implant if we can make that assumption. In the graph that I showed you, there was kind of a stairstep down as fragmentation increased based on the best embryo in the group. I think we are very close to the point now that we will be transferring 1 or 2 embryos with high scores as the choice for patients to reduce multiple pregnancy rates if we continue with the day 3 transfer. Going to blastocyst transfer has not helped multiple pregnancy rates in this country because people who primarily use blastocyst transfers will transfer more than 1 blastocyst. If you are going to do a blastocyst transfer, transfer 1 embryo. Most centers that primarily do blastocyst transfer will still transfer 2 or 3 blastocysts; thus, twin and triplet rates are higher than what you see on day-3 embryo transfers. Did we stratify between donor and patient? We did not. We looked at this group solely on the basis of the embryo appearance, and then we stratified as to age. We just looked at every embryo transfer done with the embryo as the issue, not whether it was donor or so on. Dr Paulson also asked a question that I have been interested in for 15 years: “Have we seen a change in embryo quality (ie, fragmentation types, fragmentation scores), and have we seen improvement?” The answer is “yes,” I think we have. If we look at the new in vitro culture media that we are using, the sequential media that we use, and the conditions in the laboratory, we have seen improved embryos. I did not focus on it very much, but if you look at the implantation and live birth rates that we saw in our group from age 40 to 44 years (23%), that is a number we have not seen in the past and reflects on the culture conditions and embryo quality as well as how we stimulate. You can totally affect embryo fragmentation type and amount by how you stimulate the follicle before you get the egg out. There is a clear correlation with aggressive high-stimulation protocols creating more fragmented embryos, and Mitch Schiewe and I showed that probably 10 to 12 years ago. Dr Adamson asked about whether we would change our cryopreservation criteria based on what we are seeing. Yes, we probably should because of the number of embryos that were 4 cells had very minimal or no fragmentation. Almost 30% of those went to blastocyst. We would like to freeze earlier, but we have to look at that, and I think we are going to reanalyze those data. The issue of developing a scoring system with multiple regression analysis is very difficult. First of all, you are using subjective criteria, and if you have got 3 embryologists in your laboratory and all 3 are scoring, there are inherent problems. If you have, like we do, a single viewer every day, then you can look at cell number, age of the patient, and score of the embryo, and we may be able to determine a system whereby we can transfer 1 or 2 embryos and have the same high pregnancy rate that we get with 3 or 4 embryos but reduce the multiple pregnancy rate. That is what we are looking at right now. Dr Gamberdella asked whether the embryos that have increased fragmentation could be utilized for stem cell development. If you look at what we are seeing with those embryos on day 2 with type 2 fragmentation or type 3 fragmentation, some of those embryos will create a blastocele cavity, but they do not create what we would consider a usable blastocyst. We would not freeze them, we would not use them, but they may be the potential for the future of stem cell research because they will begin to form intercell mass, and, therefore, stem cell development might take place. Dr Henderson, I totally agree. We feel that embryos that advance beyond the 8-cell stage are probably not your best-quality embryos on day 3. We used to think, “Oh my God, we have a 10-cell embryo, here a 12-cell embryo; let's just transfer just 1 embryo—this is a slam dunk.” Well, that is wrong. They are probably worse quality as far as implantation outcome than your 6- and 8-cell development on day 3.</P> http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Obstetrics and Gynecology Wolters Kluwer Health

Closing discussion by Dr Richard Marrs

American Journal of Obstetrics and Gynecology , Volume 192 (6) – Jun 1, 2005
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Publisher
Wolters Kluwer Health
Copyright
Copyright © 2005 Elsevier Inc.
ISSN
0002-9378
DOI
10.1016/j.ajog.2005.03.028
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Abstract

D r R ichard M arrs (Closing statement), Los Angeles, Calif. Dr Paulson asked whether the reliability of the embryo's score was based on the individual doing it or was there a single individual who scores. Actually, in our laboratory, Dr Stone scores every embryo every day. He is the only person who will do the numerical scoring on a day-to-day basis. Occasionally, if he is not there, which is rare, Jodi will do the scoring, but 99.9% of the time, every embryo gets its numerical score from Dr Stone. What is the predictability of implantation based on this scoring or fragmentation type analysis? It is very difficult to answer that question because, as we all know, we are not yet doing single-embryo transfers. Because of the issues of having 2 or 3 embryos in a group of embryos transferred, I tried to look at the best type of fragmentation score in a group of embryos and gave you those data, and that is as close as I can get right now as far as what the impact of the scoring is on implantation rates. However, if you assume, and you have to take this leap of faith, that the best scored embryo or the embryo with the least fragmentation is probably the most likely embryo to implant if we can make that assumption. In the graph that I showed you, there was kind of a stairstep down as fragmentation increased based on the best embryo in the group. I think we are very close to the point now that we will be transferring 1 or 2 embryos with high scores as the choice for patients to reduce multiple pregnancy rates if we continue with the day 3 transfer. Going to blastocyst transfer has not helped multiple pregnancy rates in this country because people who primarily use blastocyst transfers will transfer more than 1 blastocyst. If you are going to do a blastocyst transfer, transfer 1 embryo. Most centers that primarily do blastocyst transfer will still transfer 2 or 3 blastocysts; thus, twin and triplet rates are higher than what you see on day-3 embryo transfers. Did we stratify between donor and patient? We did not. We looked at this group solely on the basis of the embryo appearance, and then we stratified as to age. We just looked at every embryo transfer done with the embryo as the issue, not whether it was donor or so on. Dr Paulson also asked a question that I have been interested in for 15 years: “Have we seen a change in embryo quality (ie, fragmentation types, fragmentation scores), and have we seen improvement?” The answer is “yes,” I think we have. If we look at the new in vitro culture media that we are using, the sequential media that we use, and the conditions in the laboratory, we have seen improved embryos. I did not focus on it very much, but if you look at the implantation and live birth rates that we saw in our group from age 40 to 44 years (23%), that is a number we have not seen in the past and reflects on the culture conditions and embryo quality as well as how we stimulate. You can totally affect embryo fragmentation type and amount by how you stimulate the follicle before you get the egg out. There is a clear correlation with aggressive high-stimulation protocols creating more fragmented embryos, and Mitch Schiewe and I showed that probably 10 to 12 years ago. Dr Adamson asked about whether we would change our cryopreservation criteria based on what we are seeing. Yes, we probably should because of the number of embryos that were 4 cells had very minimal or no fragmentation. Almost 30% of those went to blastocyst. We would like to freeze earlier, but we have to look at that, and I think we are going to reanalyze those data. The issue of developing a scoring system with multiple regression analysis is very difficult. First of all, you are using subjective criteria, and if you have got 3 embryologists in your laboratory and all 3 are scoring, there are inherent problems. If you have, like we do, a single viewer every day, then you can look at cell number, age of the patient, and score of the embryo, and we may be able to determine a system whereby we can transfer 1 or 2 embryos and have the same high pregnancy rate that we get with 3 or 4 embryos but reduce the multiple pregnancy rate. That is what we are looking at right now. Dr Gamberdella asked whether the embryos that have increased fragmentation could be utilized for stem cell development. If you look at what we are seeing with those embryos on day 2 with type 2 fragmentation or type 3 fragmentation, some of those embryos will create a blastocele cavity, but they do not create what we would consider a usable blastocyst. We would not freeze them, we would not use them, but they may be the potential for the future of stem cell research because they will begin to form intercell mass, and, therefore, stem cell development might take place. Dr Henderson, I totally agree. We feel that embryos that advance beyond the 8-cell stage are probably not your best-quality embryos on day 3. We used to think, “Oh my God, we have a 10-cell embryo, here a 12-cell embryo; let's just transfer just 1 embryo—this is a slam dunk.” Well, that is wrong. They are probably worse quality as far as implantation outcome than your 6- and 8-cell development on day 3.</P>

Journal

American Journal of Obstetrics and Gynecology – Wolters Kluwer Health

Published: Jun 1, 2005

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