Embryo Quality & Embryo “Competence” – Part III – Testing the Seed

04 Oct
Biochemistry research
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This is the third and final post in three part series on embryo quality. In the prior two posts, I outlined the intrinsic/physiological factors and the clinical factors that can impact embryo “competence”.  In this post, I will discuss the role, indications, and benefits of genetic/chromosomal testing of embryos.


The role of Embryo Chromosomal Testing (Karyotyping)
Elsewhere on this blog I have described embryo chromosomal tests that can accurately count all the chromosomes in eggs and embryos. Such testing involves the use of comparative genomic hybridization (CGH), which we first introduced into the IVF clinical setting about 6 years ago. Hitherto, fluorescence in situ hybridization (FISH) had been used, but this method lacked reliability. This having been said, it is important to recognize that CGH cannot improve embryo competence, it can only identify those embryos that are most likely to be competent.

We have previously reported on the fact that the transfer of up to two CGH-normal, advanced embryos (blastocyst) into a “receptive” uterus, results in about a 60% chance of a live birth and at the same time significantly reduces the chance of chromosomal birth defects. However, it does not consistently and reliably identify all structural chromosomal anomalies and is not capable of identifying non-chromosomal (genetic/metabolomic) causes of “embryo incompetence”.

Finally, we do not know the extent to which maternal and/or paternal age and/or exposure to extrinsic (outside) and environmental affect impact genetic (non-chromosomal) “embryo competence” and whether or to what degree such factors increase with maternal or paternal age. If they do, then one would expect CGH-normal embryos derived from older women’s/men’s gametes to be less “competent” than those derived from the gametes of younger parents. So while, CGH-embryo normality is indeed likely to be most of the “embryo competency” story, it might well not be the “entire story”.

Who should have their embryos CGH tested?
As stated above, older women and those with DOR are at increased risk of producing incompetent, aneuploid embryos. However, CGH testing, while improving the efficiency of IVF, does not improve embryo quality. Thus it should never be mandated in all such cases. There is, however, one notable exception, and this applies in cases where “Embryo Banking” is done in order to try and stockpile competent embryos for future dispensation. Here, by selectively stockpiling CGH-normal embryos it is possible to increase the reproductive options available to women who otherwise would clearly be running out of time on the “biological clock”.

Diagnostic benefits of CGH testing
The following are examples of where CGH embryo testing can identifying whether numerical chromosomal factors are contributing to the reproductive failure while at the same time can select only the most “competent embryos” for transfer to the uterus:
o Unexplained infertility
o Unexplained/recurrent IVF failure
o Recurrent pregnancy loss (RPL)
o Differentiating between egg and embryo aneuploidy as a cause of failed fertilization, poor embryo quality or failed IVF (egg and embryo CGH testing).

Notwithstanding the fact that “embryo competence” is certainly the most important factor contributing to reproductive failure, it is essential that possible causes of implantation dysfunction (anatomical or immunologic)be identified and if detected, be addressed when it comes to cases of “unexplained” infertility, recurrent pregnancy loss, or repeated IVF failure. This becomes even more critical in cases where IVF failure has occurred in spite of CGH-normal embryos having been transferred. After all, even a “good seed “ (i.e., a “competent embryo”) will fail to thrive if planted in a “poor soil” (“non-receptive uterus”).

19 Comments

  • Layla says:

    Background – I am currently 39 yo. In 2005 diagnosed with a unicornate uterus, only developed one functioning fallopian tube which was damaged (hydrosalphinx) and had to be removed. No fallopian tubes to be able to conceive naturally – started IVF. First cycle, transferred one embryo which did not result in a pregnancy. 3 Frozen embryos remained from that cycle. One embryo did not survive the thaw and was subsequently discarded. Two embryos were transferred in January 2006 and resulted in the uncomplicated pregnancy and full term birth of my son. We returned to the IVF clinic in 2011 and have had these cycles to try and conceive again:
    Cycle #1
    Retrieval Date – 11/10/11
    13 eggs retrieved, 9 fertilized
    Transfer two blastocysts on 11/16/11– No pregnancy resulted
    Two frozen transferred 1/11/11 – No pregnancy resulted

    Cycle #2
    Retrieval Date 6/22/12
    26 eggs retrieved, 16 fertilized
    Transfer of two blastocysts on 6/28/11 – no pregnancy resulted
    No frozen embryos

    Cycle #3
    Retrieval Date – 12/13/12
    12 eggs retrieved , 8 fertilized
    Transferred 3 embryos at Day 3 on 12/16/12 – Pregnancy resulted in a miscarriage at approximately 8 weeks due to chromosomal abnormality

    Cycle #4
    Retrieval Date – 9/5/13
    22 eggs retrieved, 15 fertilized, 7 blastocysts were CGH tested – 4 embryos were reported normal and frozen for FET cycles

    Transfer (FET) of one genetically normal embryo on 10/23/13 – no pregnancy
    Transfer (FET) of one genetically normal embryo on 12/16/13 – no pregnancy

    Immune tests are normal.
    Hysteroscopy is normal other than confirming a unicornate uterus.

    Total Number of embryos transferred – 13
    Total Number of Pregnancies – 2
    Total Number of Miscarriages – 1
    Total Number of Live Births – 1

    Any other tests or treatments that you would recommend prior to transferring our last two normal embryos? Any assistance you can provide would be greatly appreciated.

    • Geoffrey Sher says:

      This sounds typical of an implantation dysfunction (immunologic or anatomical). know you said the immune tests were normal. However, you must do the correct tests at the appropriate Reproductive immunology reference laboratory. I recommend Reprosource in Boston, MA. Call tina to get their contact information (702-699-7437). The test you need to order are : a) ON YOUR BLOOD: NKa, APA, ATA, immunophenotype, ANA, ATA and tests for DQ alpha and HLA genotypes. ON HUSBAND’S BLOOD: DQa and HLA genotypes.

      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 column. Then type in the following subjects into the bar, click and this will take you to all the relevant articles I posted there.
      1. “An Individualized Approach to Ovarian stimulation” (posted on November 22nd, 2010)

      2. Ovarian Stimulation for IVF: The most important determinant of IVF Outcome” (Nov. 2103)

      3. “Agonist/Antagonist Conversion Protocol”

      4. “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.

      5. “Thyroid Autoimmune Disease and IVF”

      6. “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)

      7. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)

      8.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)

      9. “IVF success: Factors that influence outcome”

      10. “Use of the Birth Control Pill in IVF”

      Consider calling 800-780-7437 or 702-699-7437 to arrange a Skype with me so we can discuss your case in detail.

      Finally, perhaps you would be interested in accessing my new book (recently released). It is the 4th edition (and a re-write) of “In Vitro Fertilization, the ART of Making Babies”. The book is available through “Amazon.com” as a down-load or in book form. It can also be obtained from most bookstores.

      Geoff Sher

      P.S: Please go to http://www.youtube.com/watch?v=Vp3GYuqn2eM&feature=youtu.be
      To view a video-tutorial by Linda Vignapiano RN, Clinical Manager at SIRM-Las Vegas.

      Also your uterine lining response (US) and the regularity of your uterine cavity (sonohysterogram)needs to be reassessed.

  • Maia says:

    Hi Doctor,
    I am 38 and had 4 failed IVFs so far. I have endometriosis and had a chocolate cyst removed. We had 6 eggs from our previous 2 IVFs and 4 eggs in the 3rd and 2 eggs in the 4th. In the 2nd IVF, out of 6 eggs, 4 were fertilized and 2 survived for transfer on the 3rd day. After 7 weeks, test showed implantation but is a blighted ovum. On the 3rd IVF we had 4 eggs and 2 fertilized and we decided for a 5 day transfer. On the 5th day, the blastocyst failed to progress in growth. On our 4th IVF, we had 2 eggs, 1 fertilized and transferred on the 3rd day. Tests showed implantation but embryo failed to grow. What is the likely cause and what tests should we try to have?

    • Geoffrey Sher says:

      The issues relate to endometriosis and the fact that if there are severe adhesions it could be compromising ovarian reserve by cutting off blood supply to the ovaries. I would need to see your day 3 FSH and E2 blood levels and your AMH. With this information at hand, a very individualized protocol for ovarian stimulation would be needed (see below). Then given the relationship between endometriosis and implantation dysfunction you would need immune testing, among other things…for NK cell activation.

      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. “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.

      5. “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)

      6. “Endometriosis and IVF”

      7.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)

      8. “IVF success: Factors that influence outcome”

      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

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