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Embryo & Blastocyst Grading: Which to Transfer, Which to Discard

Dr. Geoffrey Sher Recommends

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Currently, when it comes to embryo/blastocyst grading, there is no standard method practiced universally across all IVF centers. There are a variety of systems used in different embryology laboratories; some are orthodox and proven, while others are not. This often leads to confusion when it comes to patients trying to interpret a recommendation to freeze, transfer or discard embryos based upon their microscopic appearance or “grade.” Consider the following:

Some IVF programs freeze embryos on day 2 post-fertilization, prior to division or cleavage (i.e. at the pronucleate stage) , while others freeze on day 3 (cleaved embryos). However, more and more IVF programs are starting to recommend that only embryos that make it to the blastocyst stage be frozen.
Some programs freeze and transfer embryos regardless of their grade, while others selectively freeze only embryos that are deemed to be viable.
Some embryologists (usually, those less experienced) are less courageous in making the important determination of whether an embryo is potentially viable and err on the side of extreme caution by recommending the transfer of all grades of embryos.
The poorer the quality of an embryo the less likely it is to propagate a baby even if freshly transferred. Also, the poorer the quality, the less likely it is that the embryo will even survive the freeze/thaw.
There comes a point where the quality of an embryo is so poor that it won’t survive the freeze/thaw and if transferred fresh, would NOT propagate a pregnancy.
Most embryos that are allowed to develop to blastocyst reach their maximum potential by day 5 post-fertilization. Some take 6 days (and incidentally, there is no indication that these later developing blastocysts necessarily have poorer implantation potential).
Those embryos that fail to expand by the 6th day AND do not have a demonstrable inner cell mass from which the baby develops (i.e. grade 3), are without exception non-viable.
Some embryologists base their blastocyst grading on morphology as determined on day 5 post-fertilization while others allow blastocysts that have not developed well by day 5 (grade 3 blastocysts) to go to day 6 by which time the grade might improve.
Some IVF programs still freeze embryos slowly (“conventional freezing”), while others have adopted ultra-rapid freezing (“vitrification“). Conventional freezing is associated with a much higher rate of freeze/thaw attrition and a much lower baby rate per frozen embryo.

Now to SIRM policy and why we take this position: I conferred with our Executive Director of Embryology, Levent Keskintepe, PhD in formulating the response below:

Our published as well as yet unpublished data shows that while embryos that develop into Grade 1-2 blastocysts by day 5- 6 post fertilization are not always chromosomally normal, those that do NOT reach this stage of development are almost invariably “incompetent” (non-viable). Thus, the often quoted assumption that an embryo would be better off transferred earlier into the “natural” uterine environment to develop is inaccurate. In fact, it is preferable to allow embryos a chance to prove their potential by reaching the Grade 1-2 blastocyst stage in the laboratory before deciding which ones to transfer or vitrify (freeze/store) for future dispensation. At SIRM, we do transfer cleaved embryos in some cases – generally only those involving women who end up having very few or no other embryos for transfer. As such, they have little risk of a “high order multiple” (triplets or greater) pregnancy. The same would apply to a patient/couple who, in spite of our recommendation to the contrary, still insists on having cleaved embryos (or for that matter even Grade 3 blastocysts) transferred (or frozen).

Dr Keskintepe has imposed a “uniform embryo grading system” throughout all 7 SIRM embryology laboratories. All of our Laboratory heads are thoroughly trained in the use of this system. Dr Keskintepe informs me that using this rigid system, (in many thousands of cases) our experience is that if an embryo fails to attain Grade 1-2 status by the sixth (6th) post-fertilization day, it will not propagate a viable pregnancy. This has been the case without exception. Furthermore, our CGH embryo karyotyping data shows that those embryos that fail to make it to grade 1-2 blastocysts by day 6, with very few exceptions, are chromosomally abnormal (aneuploid), thereby validating our policy.

There is little doubt that for a variety of reasons (several of which are cited above) some will find fault with this SIRM policy. However, we are confident that using our approach best serves those patients who entrust us with their care and who deserve our best advice based upon our own unique but substantial experience in the field.

Tags: Blastocyst Transfer, embryo competence, Embryo Grading, IVF Authority, Vitrification

12 Responses to “Embryo & Blastocyst Grading: Which to Transfer, Which to Discard”

myraviveash says:

December 23, 2010 at 12:16 pm

Not sure if you are still answering questions on this post…

I have had 3 failed fresh IVF cycles (neg. BETA) over the past 1.5 years. The clinics I used only freeze blastocysts. I never had any blastocysts that were able to be frozen because the ICM was not large enough. The first cycle, my transfer was a day 6 1AB blast (grade given by Shady Grove); the second was day 3 (5 and 6 cell, both fair quality, or 3 on a scale of 1-5); the third was day 3 (two 8-cell compacting embryos).

Since I never had a blast frozen, is it likely that all of my embryos are abnormal / non-viable? I'm now 34 (32-33) at time of cycles, never pos. pregnancy test, trying 3+ years, no male factor (great SAs and excellent SCSA).

Was considering CGH, but perhaps it would not be helpful in my case?

Reply
Geoffrey Sher, MD says:

March 31, 2011 at 5:48 pm

I would strongly recommend CGH. Also do immunologic implantation tests.

Feel free to call 800-780-7437 so that we might interact one on one.

Geoff Sher

Reply
Lisa says:

April 6, 2013 at 2:02 pm

Good day Dr Sher
I just had a failed FET cycle where 2 grade 1 embryos were transferred. The cycle ended with a chemical pregnancy. I did PGD for beta thal minor. We had no eggs to freeze. I had 23 at retrieval and we did ICSI. In the end there were a few aneuploidy and only 2 made it ” normally” to day 5. I also did the 22 I believe aneuploidy screen.. I am 34. I am planning to start the next ivf in June. I was placed on the menopur, gonal, ganirelix, hcg – antagonist protocol. This time my RE wants to do the baby aspirin and a double trigger with Lupron. He also wants to stim me an extra day in hope of getting more competent eggs, for a lack of a better way of putting it. He also wants to use bravelle instead of gonal. Do you believe this is a plausible change? For the FET itself I was only on vivelle patches and endometrin. This FET he wants to add pio. Do you believe these for good changes in hopes of having a greater chance of success. Thank you… Lisa

Reply
- Geoffrey Sher says:
  
  April 6, 2013 at 4:26 pm
  
  I do not think at your age, that the protocol used is the issue (even though I do not use the Lupron as a “trigger”). At your age and the fact that you have good ovarian reserve makes you less vulnerable to protocol variations. You seem to have had several “chromosomally normal embryos transferred but did not conceive. This makes an implantation dysfunction a strong possibility. This needs to be evaluated, in my opinion.
  
  Please go to the home page of this blog, http://www.IVFauthority.com . When you get there, look for a “search bar” in the upper right hand corner. Type the following subjects into the bar, click on it and it will take you to all the relevant articles posted there.
  
  1. “An Individualized Approach to Ovarian stimulation” (posted on November 22nd, 2010)
  
  2. “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)
  
  3. “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.
  
  4. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)
  
  5.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
  
  6. “IVF success: Factors that influence outcome”
  
  7. “FET”
  
  Consider calling 800-780-7437 or 702-699-7437 to arrange a Skype consultation (free of charge to those who reside in the United States or Canada) with me so we can discuss your case in detail
  
  Geoff Sher
  
  Reply
Lisa says:

April 7, 2013 at 2:07 am

Thank you do very much Dr Sher for taking time to answer. You are indeed awesome. I forgot to mention that prior to knowing about the beta thal minor, I had a miscarriage at 7 weeks. I did not know I was pregnant. Blighted ovum was the dx. Do u still perceive that implantation dysfunction is still an issue?

Reply
- Geoffrey Sher says:
  
  April 7, 2013 at 9:12 am
  
  Absolutely! A blighted ovum can also be due to implantation dysfunction.
  
  Geoff Sher
  
  Reply
Charlotte says:

April 9, 2013 at 9:05 am

HI Geoff I had IVF and had 2 blast put back that where top quality. My hcg has been 1100 at 4 weeks pregnant and over 9000 at 5 weeks pregnant. I have no bleeding or cramps but I am worried about Blighted Ovum. Is there any signs I should watch out for? I have a scan this week but I have just read about Blighted Ovum and I am worried when I have my scan I won’t see a baby and just wondered what signs there are for this? thank you

Reply
- Geoffrey Sher says:
  
  April 9, 2013 at 11:25 am
  
  Hi Charlotte,
  
  I am afraid there is no way of knowing except for US.
  
  Good luck!
  
  Geoff Sher
  
  Reply
Misty says:

April 25, 2013 at 9:35 pm

Hi,
I am looking for more information on doing a natural cycle FET. I did IVF in 2008 at Yale and was blessed with a beautiful boy. We had put back two blastocysts. Just over a year later we got pregnant on our own and unfortunately that pregnancy resulted in a blighted ovum. Four months later we were thrilled to find out we were pregnant with twins, mono mono twins. They are now two and doing amazing. We have 7 frozen expanded blastocyst (one hatched). We would like to try a natural cycle FET. I have contacted Red rock fertility and today had a consult with LV fertility. The price seems as high as doing full cycle IVF. We would be transfering our embryos from Connecticut. Do you have long term storage available? Would I need to undergo most of the diagnostic testing again (this is why the cost would be so high at LV Fertility)? I would love more information! Thank you for your time!!
Misty

Reply
- Geoffrey Sher says:
  
  April 26, 2013 at 10:31 am
  
  Absolutely we do long term storage in LV and could arrange the transfer of the embryos here. We would be able to do NC-FET but in my opinion, it is the lesser choice.Set up a consultation to discuss the merrit of NC, FET versus hormonally prepared cycle with me.
  
  Geoff Sher
  
  Reply
Jessica H says:

May 8, 2013 at 6:21 pm

I am at a loss and would really like some advice. My husband and I are carriers for SMA (oldest daughter affected-naturally conceived) we have done 3 rounds of ivf all unsuccessful. I am 31 all fsh and lab work
Is normal husbands sperm is normal. Dr said it could be an egg quality issue. First round was ant. Protocol and yielded 3 eggs none making it to day 5 for biopsy. Second round was long Lupron yielded 1 egg not mature. Third round was micro flare and yielded 10 eggs 7 fertilized 1 is 7 cell on day 3. What is going on? Where do I go from here? Do I give up on ivf?

Thanks!
Jessica

Reply
- Geoffrey Sher says:
  
  May 8, 2013 at 8:41 pm
  
  Spinal muscular atrophy (SMA), an autosomal recessive disease is caused by a genetic defect in the SMN1 gene that codes SMN. It is not a chromosomal issue. Thus it has nothing to do with egg quality which is adversely affected by chromosomal irregularities. The issue of egg quality is related to age, ovarian reserve and the protocol used for ovarian stimulation.
  
  Please go to the home page of this blog, http://www.IVFauthority.com. When you get there, look for a “search bar” in the upper right hand corner. Type the following subjects into the bar, click on it and it will take you to all the relevant articles posted there.
  
  1. “An Individualized Approach to Ovarian stimulation” (posted on November 22nd, 2010)
  
  2. “Ovarian Stimulation in IVF: Why is it important to down-regulate LH?”
  
  3. “Agonist/Antagonist Conversion Protocol”
  
  4. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)
  
  5.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
  
  6. “IVF success: Factors that influence outcome”
  
  7. “Staggered IVF”
  
  8.“Embryo Banking”
  
  9. “Egg Donation”
  
  Consider calling 800-780-7437 or 702-699-7437 to arrange a Skype consultation (free of charge to those who reside in the United States or Canada) with me so we can discuss your case in detail
  
  Geoff Sher
  
  Reply

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