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

      Dr. Geoffrey Sher Recommends

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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”).

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

      1. Kristin says:
        December 21, 2012 at 11:51 am

        Hi Dr Sher, I am 38 and have undergone surgery performed by Dr Camran Nezhat in 2011 for ovarian cysts and severe endometriosis. I am currently doing egg banking with Dr Christo Zouves in Foster City, CA. We have done two egg retrievals, received 6 eggs each time and out of the 6 , each time, there were 3 mature eggs, which are now frozen. We plan to do a third and final retrieval in February and then fertilize the eggs. My husbands sperm is better than average for Motility and morphology, though he is 49. I am now concerned that we should do CGH not PGD, on our embryos, in order to maximize success. I had never heard of CGH until I read your site. Dr Zouves uses PGD and so do you think that is not worth doing it if it can damage the embryos then why would doctors use it? And am I a better candidate for CGH? I hope you can help clarify for me. Thank you! Kristin

        Reply
        • Geoffrey Sher says:
          December 21, 2012 at 2:07 pm

          It will NOT damage ermbryos if done expertly.Please go to http://www.IVFauthority.com and when you get to the home page find the “search bar” in the right hand column. Type in the following subjects into the bar and it will take you to all the relevant articles I posted there.

           “CGH embryo testing”
           “Staggered IVF”
           “Embryo Banking”

          Geoff Sher

          Reply
      2. Tanya says:
        January 11, 2013 at 8:11 am

        Hi Dr.Sher,

        I’ve just turned 41 and have had 3 IUI’s and 3 IVF’s with one miscarriage. I have a DOR and recently met with a new specialist that gave us the 2 options of either:ED or multiple IVF’s to bank/freeze the eggs with the genetic testing. I fear spending a tremendous(to us)amount of money and risking not getting any competent embryos and then not having the funds to do ED. This could be my one last shot due to finances. I’ve only been able to get 1-2 eggs each IVF. 1st IVF: 2 average implanted then miscarried at 6 weeks. 2nd IVF: was supposed to have 2 but, the doctor retrieved 1 egg which fertilized abnormally so no transfer was done. 3rd IVF: was told both embryos were the best quality and graded at a 1 but, neither implanted. I wanted to know what the success rates have been with women at age 41 with DOR doing the banking of the eggs and realistically getting competent embryos? As you can imagine I’m having a tough time making this decision to have a chance at success. Also, are there any “free” study trials offered for women of age 41?
        Thank you!
        Tanya

        Reply
        • Geoffrey Sher says:
          January 11, 2013 at 10:39 am

          The success with embryo banking would depend on there being CGH -normal blastocysts for transfer and how many as well as the exclusion of implantation dysfunction well in advance of the cycle (see below). The quality of the embryos would be a function of your age (about 1:5 blastocysts would be CGH-normal) and the protocol of ovarian stimulation used (see below). The baby rate per transferred embryo under such conditions should be as good as with ED. However, the egg donor, being younger will likely produce many more blastocysts than you would, per cycle.

          Please go to the home page on this blog (www.IVFauthority.com) . When you get to home page, 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 I 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. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)

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

          8. “IVF success: Factors that influence outcome”

          9. “Staggered IVF”

          10.“Embryo Banking”

          11. “Egg Donation”

          Consider calling 800-780-7437 or 702-699-7437 to arrange a telephone or 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.. While an audiovisual (Skype) interaction is much more personable and preferable than a discussion by telephone, either will suffice.

          Geoff Sher

          Reply
      3. Reshma says:
        February 25, 2013 at 10:25 am

        Dear Sir,
        Please can you help to understand the quality of embryos that I have trasferred last month. According to the embryologist, the transferred embryos grades (day 5) are : 1 CC, 2 BC. And she said that 12 discarded on day 6. Is the transferred embryos are of good quality.

        Reply
      4. Janice Alers-Garcia says:
        March 14, 2013 at 6:38 am

        Dr. Sher,
        I stumbled across your site while trying to find information on the advantages/disadvantages to a day 3 embryo biopsy + CGH+ day 5 embryo transfer vs. day 5 embryo biopsy+CGH+FET.
        I am 42 years old and have seeking medical help with infertility for the past 3 years. I was diagnosed with PCOS in my early 20’s and usually had 1-3 menstrual cycles per year. At age 39, a couple of years after trying to conceive without success I stated seeing a RE. Given my PCOs diagnosis, I was placed on Metformin which help me cycle within a month. At that point the ER decided to add Clomid and I went through 3 closely monitoring cycles (blood tests and sonograms) of Metformin+Clomid+timed intercourse. It turned out that the ovulation predictions based on the blood tests and the sonogram were accurate only once and we were unable to get pregnant. At that point the ER recommended we switch to IVF as it was a more accurate and perhaps effective method. After getting appropriate medical coverage and getting our finances in place, we went through 2 failed IVFs.
        On the first cycle we had 16 eggs and 12 embryos that made it to blastula (3 embryos were transferred, 3 stopped dividing and were discarded, and 6 were frozen). My RE mentioned that the response I showed (number of eggs, embryos that made it to blastula) was not typical for someone with PCOS or my age and thought that the IVF failure might be related to a problem with my uterine lining rather than embryo quality. At that point we discussed 3 options: 1) going for a ‘test run” of what ratio of estrogen and progesterone would support a healthy uterine lining for a pregnancy (doing some endometrial biopsies throughout it) followed by FET, 2) going through and IVF with PGD, and 3) just going for another IVF. Given age vs. eggs quality concerns (already 41yrs. old) and the the fact that many IVFs fail the first time around, and the good number of embryos that had made it to blastula in my previous cycle I decided to go for another IVF . Considering that I needed Cabergoline during my first IVF, my RE lowered my doses of Follistim for the second IVF and I ended with 8 eggs and a 5 embryo transfer on day 3. This time around I felt great, I had some vaginal bleeding whose timing was compatible with pre-implantation bleeding, but I did not get pregnant. A month after this cycle –while going for the follow up evaluation- I mentioned to my RE that I felt ovulation-like symptoms the day before. After following up with 2 rounds of blood tests (the first set was inconclusive) the RE concluded I had ovulated and regardless of timed intercourse we did not get pregnant (I had some bleeding six days after ovulation). After the results of my second IVF my RE major concern became that the failure to get pregnant might be the genetic quality of the embryos and we discussed the following alternatives as a way to explore whether this might be the case: 1) a day 3 embryo biopsy + CGH+ day 5 embryo transfer , 2)a day 5 embryo biopsy+CGH+FET. It still not clear to me why he thinks might be genetics instead of a lining issue. I just had 12 eggs retrieved yesterday, and I was told that they will be biopsied on day 3 and that we can transfer any “genetic competent ones” on day 5. I received a call from my nurse today saying that my RE would call us tomorrow to discuss the alternatives of a day 3 embryo biopsy + CGH+ day 5 embryo transfer vs. a day 5 embryo biopsy+CGH+FET. Up to know I thought a day 3 embryo biopsy + CGH+ day 5 embryo transfer yielded accurate results and was possible. However, while searching for information on your website and other sites, it seems that CGH takes longer that 2 days and that’s the main reason that day 5 embryo transfer it is not possible. Do you know whether a reliable/accurate CGH can be done in 48 hours or less? Can day six embryos be transferred (I only found a website mentioning this, all other agree that 5 days is the longest most embryos will make in vitro)? What are the advantages of a biopsy and CGH on a 3 day embryo vs. a 5 day embryo? Can you explain mosaicism to me? Finally, I was thinking if a day 5 embryo can be biopsied and CGH done (while freezing the embryos-hopefully through vitrification), while the initially suggested “dry run” is used to set up the upcoming FET wouldn’t that take care of all the potential factors -genetic and lining issues simultaneously? Is there any way to determine whether I am likely to have a lining issue? I read your blog in thin uterine lining and the use of vaginal Viagra and realized my RE has never discussed my lining thickness prior to the trigger shot with me? Are there any other factors that might point to a lining issue that I should bring to his consideration?
        I would really, really appreciate your input since it looks like we would have this discussion tomorrow and should take a decision by Friday!

        Reply
        • Alice says:
          April 18, 2013 at 1:51 pm

          Dear Dr Sher,
          I turned 44 last month. My husband is 58 years old.
          We live in Europe and we followed an embryo banking program in Kiev, Ukraine. I did 3 IVF’s in the last 6 months. Diphereline in the 19th day of my period and after 18-20 days start stimulation for 12 days. The first stimulation was with Gonal F 150 and Menopur 150 and I got 14 eggs, 5 fertilised , only 1 embryo 3BB. Second and third IVF was with Pergoverice 300 and I got 11 eggs with 2 embryos 4AA both and 8 eggs with 4 embryos (4AB,3AB,3AC,3BB). They also did ICSI and IMCI with the last 2 stimulations.
          From all 7 embryos none was competent.
          Could you please give me an advise what to do next?

          Reply
          • Geoffrey Sher says:
            April 18, 2013 at 2:48 pm

            Hi Alice,

            At 44 the chance of IVF success with own eggs is VERY low. You should be considering egg donation preferentially. However, if that is not an option then embryo banking of CGH-tested normal blastocysts is your only other rational choice. See below.

            Please go to the home page of 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 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 702-699-7437 to arrange a Skype consultation with me so we can discuss your case in detail

            Geoff Sher

            Reply
        • Alice says:
          May 16, 2013 at 12:44 am

          Hello Dr Sher,
          I would like to ask for your opinion on mitochondrial DNA transfer.
          Is this an available treatment in this moment, anywhere arownd the world?
          Thank you

          Reply
          • Geoffrey Sher says:
            May 16, 2013 at 7:40 am

            No…not to my knowledge. But read the article in this blog on “Nuclear-Cytoplasmic transfer”.

            Geoff Sher

            Reply
      5. ColoradoGirl says:
        April 18, 2013 at 5:31 pm

        Hello Dr. Sher. I love your informative website. My RE tends to not be so informative, which requires me to do a lot of research on my own.

        I am a 39 y/o with great “numbers” who responds well to IVF meds. They just retrieved 21 eggs from me.

        We were planning a fresh cycle, but due to my high E2, we are now (within the last 24 hours) looking at a frozen. We are glad to be waiting, actually, since my body is close to OHSS.

        My RE has suggested CCS testing.

        My main fertility issue is uterus-based – fibroids specifically – and completely blocked tubes. I have had two operative hysteroscopies in the last six months to remove fibroids that would impact implantation and my doctior is concerned they could grow back, which is why we were aiming at a fresh ET. He was initially asking for a laparotomy myomectomy for removal of the fibroids outside the uterus.

        We are asked to make a decision on CCS testing in a period just over 24 hours, when they decided no fresh, now freeze-all. I’ve never been pregnant (completely blocked tubes!), this is our first IVF. My spouse has no issues with sperm.

        I am hestitant to go through CCS (it is $7k) and would rather just see what we get this first cycle and move into an FET to see how my uterus does. I am worried that $7k may be spent on analyzing embryos (assuming we get some that make it to freeze!) when my uterus may not be receptive.

        Can you shed some light on points I should consider when making a decision? I have read several white papers on the biology/ studies behind CCS, but would like to consider your opinion as well.

        Thanks!

        Reply
        • Geoffrey Sher says:
          April 18, 2013 at 8:12 pm

          I cannot disagree that full embryo karyotyping is a good idea at +/-40Y. This is really the only way to identify the most “competent” embryos for transfer.

          Good luck!

          Geoff Sher

          Reply
      6. Bev Vanamburg says:
        May 8, 2013 at 6:56 pm

        Hi Dr. Sher.. i just had ivf with you and am now 4 months pregnant after over 2 years of failures at clinic here in canada. I now have a g/f who i want to see you who was told she is hopeless to have a baby as she is 36 and had an AMH reading of 1.8. Her average day 3 (FSH is 6). (LH 5.64), (E2 280) (PRL 20) n (TSH 0.804), she has had 5 iui’s all failed. Her fertility doc told her to go on DHEA for 3 months and see if that helps improve her AMH level. I only trust your opinion and wondering what advise you may have for her. I want her to come see you and I think this other doc has her feeling hopeless….is she?

        Reply
        • Geoffrey Sher says:
          May 8, 2013 at 8:43 pm

          Congratulations Bev! I am glad I could help you. Of course, please have your friend call 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 her case in detail

          Geoff Sher

          Reply
      7. Maia says:
        May 9, 2013 at 2:00 am

        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?

        Reply
        • Geoffrey Sher says:
          May 9, 2013 at 5:05 am

          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

          Reply

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      Wennerlinds
      Karmann and Ryan – Nine Miscarriages, Then Hope!
      In observation of National Infertility Awareness Week (NIAW), I wanted to share the touching story of a couple that I first met last year – after they had already experienced 8 years of heartbreak and frustration.  Their story is representativ... more
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      IVF in a Same-Sex Male Couple: A Case Study
      Background: About two years ago, I received a call from a gentleman that I will call “John”. John was a movie producer who stated that he and his partner “Brian” had been in a monogamous same-sex relationship for 7 years and each wanted to si... more
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      Recurrent Molar Pregnancy Treated By “IVF Genetic Chess”
      Background: Maria (fictitious name), a childless 34-year-old Hispanic lady, presented with a history of having had five (5) successive spontaneous pregnancy losses at 7 weeks gestation, all due to hydatidiform moles. Four (4) of these losses were ... more
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      Case Study: Donor Egg IVF in a Post Menopausal Woman
      Mary (fictitious name), a 54 year menopausal woman, presented at SIRM-Las Vegas for IVF using an egg donor. She had been menopausal for 7-plus years and had NOT been on any hormone replacement therapy. Mary gave a history of having undergone IVF with... more
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      Case Study: Endometriosis Presenting as “Unexplained Infertility”
      I consulted with a 36 year old lady (whom I will refer to as “Sandra”) and her partner, about 18 months ago. She and her husband of 5 years had been having regular unprotected intercourse throughout this time and had been unable to conceive. Sand... more
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      Case Study: Pelvic Tuberculosis, Hypothyroidism, and Immune Implantation Dysfunction
      About 18 months ago I saw an Asian Indian couple who presented with a very interesting history. The female partner (whom I will refer to as DB) had regular menstrual cycles and normal ovarian reserve, was ovulating regularly and had a fertile male pa... more
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      Dear Dr. Sher: A Healthy Baby Followed by Multiple Miscarriages
      This is the second in a series of posts taken from questions that have been submitted to me via email, website, or discussion boards.  This question is from a patient who had a healthy baby from her first pregnancy, but then went through a period of... more
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      Karmann and Ryan’s Journey – My Approach to Their Treatment
       Please refer to last week’s blog post, where Karmann tells in her own words her struggles with recurrent miscarriage – nine miscarriages to be exact – and her long journey  of heartbreak, disappointment, and finally – hope.... more
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      Why Did My IVF Fail? Part 2 – Uterine Receptivity and Transfer Technique
      This is the second part of a two-part post on IVF failure. In my January 22nd post, I discussed what I often refer to as the “seed” variable in the “seed/soil” relationship – the embryo. This week’s post will address the “soil” variab... more
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      My IVF Cycle Failed – What Went Wrong? Question #19: Why Do I Keep Having Chemical Pregnancies and Miscarrying?
      This is the 19th in a series of answers to common questions about failed IVF. Early pregnancy loss – whether due to miscarriage or chemical pregnancy – is due to two major factors. In more than 70-80% of cases the cause is attributable to... more
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      My IVF Cycle Failed – What Went Wrong? Question #18: My Fertility Clinic Reports a High Success Rate – How Could I Have 2 Failed Cycles In A Row?
      This is no. 18 in a series of answers to common questions about failed IVF. While it is true that IVF failure can be due to preventable factors, it is as important to understand that optimal medical care does not always equate with an optimal outcome... more
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      My IVF Cycle Failed – What Went Wrong? Question #17: Why Didn’t I Get Pregnant When I Used a Young Egg Donor and Had Good Quality Embryos?
      This is #17 in a series of answers to common questions about failed IVF. For women whose advancing age and/or ovarian resistance make having a baby with their own eggs unfeasible or unlikely, IVF using donated eggs from a young donor (under 35 years)... more
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      My IVF Cycle Failed – What Went Wrong? Question #16: Why did my hCG levels stop rising properly?
      This is the 16th in a series of answers to common questions about failed IVF. Immediately following implantation, the root system (trophoblast) of the embryo begins to release the pregnancyhormone, human chorionic gonadotropin (hCG) into the surround... more
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      My IVF Cycle Failed – What Went Wrong? Question #15: Might My Mental State Have Played a Role?
      This is the 15th in a series of responses to common questions about failed IVF There is little doubt that stress and emotional lability plays a role in the normal physiological/hormonal regulation of the menstrual cycle.After all, Eskimos often stopp... more
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      My IVF Cycle Failed – What Went Wrong? Question #14: Could it Have Been Due to Inadequate Hormonal Support After the Egg Retrieval & Embryo Transfer?
      This is the 14th in a series of answers to common questions about failed IVF. In vitro fertilization establishes an abnormal hormonal environment in the uterus.In some cases (especially older women and those with a diminished ovarian reserve), high o... more
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      My IVF Cycle Failed – What Went Wrong? Question #13: Did the Number of Embryos I Had Transferred Play a Role?
      This is the 13th in a series of answers to common questions about failed IVF. Virtually everyone recognizes that pregnancy with multiples (especially triplets or greater) is associated with a high incidence of premature delivery that has serious cons... more
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      My IVF Cycle Failed – What Went Wrong? Question #12: Might the Timing of Embryo Transfer – Day 2-3 (Cleaved) vs. Day 5-6 (Blastocyst) Play a Role?
      This is the 12th in a series of answers to common questions about failed IVF. (Note: I’ll be hosting a live video chat on Aug. 2 on the topic of Failed IVF where I’ll discuss the issues addressed in this series of posts and take your ques... more
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