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Tuesday, October 16, 2012

A comparison of CCRM's publication about blastocyst tranfer and blastocyst transfer after Comprehensive Chromosome Screening - are they biased?

I found two different publications of CCRM, one from the year 2000 and it talks about the importance of blastocyst transfer over day 3 embryo transfer. The other publication is a very recent one (2010) where they talk about the supremacy of comprehensive chromosome screening (CCS). Their published implantation rate caught my attention. They showed that when blastocyst transfer was performed they obtained an implantation rate of 70% (in 2000) in their patients and when blastocyst transfer was performed after CCS testing (in 2010) (that is transferring only euploid embryos) they obtained an implantation rate of 68.9%. But in control group where no CCS testing was performed they got only an implantation rate of 44.8% (in 2010). This means CCRM is able to get the same high implantation rate using blastocyst transfer (without performing CCS on them, that is, without selecting for euploid embryos) almost 10 years ago. But in 2010 when they performed blastocyst transfer without CCS (control group) they got only an implantation rate of 44.8%! I hope people get my point!!! So I decided to compare patient selection criteria used in both the studies and found not much difference.
2000, CCRM,  PMID: 10856474 ( publication on blastocyst transfer)
Patient selection criteria
FSH ≤ 15 mIU/ml,
age ≤ 45 years
atleast  10 follicles ≥ 12 mm on the day of HCG administration
Mean age
34 years
Age range
Mean number of blastocysts on day 5
Implantation Rate
No of blastocysts transferred

2010, CCRM,  PMID: 19939370
( publication on CCS)
Patient selection criteria
FSH  7.3-7.6 mIU/ml , patients with  AMA, RPL and RIA
Mean age
37.7 years
Age range
Mean number of blastocysts on day 5 (CCS group)
Implantation Rate (control group)
Implantation Rate (CCS group)
No of blastocysts transferred
2 .7 (control group)
2 (CCS group)

In their 2000 publication they used blastocysts scored using morphological appearance (no selection for chromosomally normal embryos). There is not much information about the patient characteristics (like whether there are patients who underwent recurrent pregnancy loss (RPL) and implantation failure). But definitely there are patients with Advanced Maternal Age (AMA) as evidenced by the age range of patients given in the publication. But nowhere had they mentioned that the above said patients are first time IVFers! So naturally there would have been patients with previous IVF failures. 68 patients underwent 2 blastocyst transfers (top scoring blastocyst).

In 2010 publication where they applied CCS using aCGH to screen embryos, they say they have included patients with AMA, patients who underwent RPL and patients with recurrent IVF failure (RIF) (more than 2 failed IVF cycles!). They had 48 patients in CCS group and their control group consisted of 113 patients undergoing blastocyst transfer in the same center. They say that the patients were matched for age, day 3 FSH, previous unsuccessful attempt etc. But there is no mention whether there are patients with RPL in control group! It must be noted that the day 3 FSH in two groups is very less when compared to day 3 FSH of patients from 2000 paper. They said the selection criteria for including patients for blastocyst transfer (2000 publication) is day 3 FSH 15 mIU/ml. It does imply that they used patients who had FSH upto 15 mIU/ml.

If this is the case how come they got an implantation rate (with fetal heart tone) of 70% in 2000 (the same group and the same author too!) with the transfer of 2 good quality blastocyst and when they performed 3 blastocyst transfer (2.7 mean) in control group in 2010 they are able to achieve only an implantation rate (with fetal heart tone) of only 44.8%. In the CCS group they got an implantation rate of 68.9%. 

Even if they argue that they have included only the difficult patients (as per AMA, RPL and RIF) – the FSH level in patients and the blastocyst formation rate do not show much difference between the patients selected in 2000 and in 2010. Actually in 2010 paper the day 3 FSH level of patients seems to be lower than in 2000! 

The only question in my mind after comparing both their publications is - ARE THEY BIASED? 


  1. Would love to hear more lay-man discussion on this topic. If there was higher implantation rate 12yrs back without CCS testing What necessitates it to be done now? Should I infer that such research publications are mostly biased to direct public / medical opinion to certain factors which the research group desires?

  2. You have caught the point exactly : )

    "If there was higher implantation rate 12yrs back without CCS testing What necessitates it to be done now?"- This is my question too!

    YES, that is what I think too! But we have to wait and watch how the field of CCS develops and people should not get carried away by such super positive publications.

  3. Lol, Manju, I see you are pulling your hair out like I do so often, trying to discern whether there was a difference in methodology between two different research documents which exhibit counterdictory results. It would seem to make sense that CCS would positively influence outcomes, but I'm wondering too whether it's a good idea to conduct CCS if you only have, say, 2 mature blastocysts. After all, if you only have 2 to implant both anyway, it shouldn't really matter.

    Also, I was curious, do you know how much CCS costs? During our first cycle, my wife and I didn't have CCS available to us.

  4. Dana, are you with CCRM ? How old is your wife ? With 2 blastocysts I do not think there is a need for CCS. I don't think it will help in anyway. If they do CCS on the two blasties and in the most unfortunate scenario find that both are not genetically normal, you won't be going in for an ET. But, do all genetically abnormal embryos (as labelled by CCS) fail to develop into a normal baby ? Or do all CCS normal embryos will implant and result in a live birth ? So, why to bother about CCS ?

  5. Manju, no, we're not with CCRM. We're down in the southern U.S. and we're using a South Florida Clinic that has yielded pretty good results. My wife is 31.

    I'm curious about CCS because we may have more embryos in our next cycle than we did in our last cycle. Our previous cycle only yielded two, 3-day embryos because of egg quality issues. We didn't wait for blastocycsts. However, after a rigorous weight loss and exercise regiment and some new meds, our numbers look substantially better than they did before, so we suspect we might end up with some additional embryos if we're lucky. Our first cycle yielded a pregnancy, but we miscarried in the first trimester (likely due to aneuploidy).

    So yeah, if you only have two embryos, it seems to me like it doesn't matter, especially if you have already paid for the embryo transfer. Sure, it's aggravating to have to deal with the "fog of war," but with only two embryos, having that knowledge doesn't seem to influence the outcome very much.

  6. I am sorry that you people had to go through the dreadful miscarriage. Miscarriage after IVF is even horrible. You wife is young and I am sure you will find success soon. Good Luck !

    If you have more than 5 blastocyts then I will think about CCS. But Dana, to be very truthful, I will rather freeze the embryos and transfer them sequentially instead of doing CCS !


  7. Yeah, the miscarriage was kind of a disorienting experience. Rani and I have never been romanticists when it came to human gestation. We're excited about the long term elements of parenthood, not so much about the few years in which our child would be in its "larval state."

    But oddly, the miscarriage came down on us harder than we expected it could. Not so much because we anthropomorphized the embryo, but because we felt like our chance was slipping away. Our numbers were pretty bad for the first cycle with pretty poor odds, but that seems like it might be turning around, now.

    Thanks, always, for all of the advice!

  8. There is a huge factor here...age. 25 year olds have a 10x higher rate than the 40 year olds


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