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      • Embryo Quality & Embryo “Competence” – Part One: Planting a Good Seed

      Dr. Geoffrey Sher Recommends

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      Phone:
      702-892-9696

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      702-892-9666

      “At 45 years of age the incidence of
      aneuploidy       is likely to be nine in ten.”

      Several weeks ago, I posted an article about endometrial receptivity and its effect on IVF success. This, as I noted, was the “Soil” component of the “Seed/Soil” equation. I turn now to the “seed” component of the equation – the embryo.

      This will be the first of three posts outlining the factors that contribute to embryo “competence” (the ability of an embryo to make a healthy baby), and the current methods of genetic testing in the IVF setting.

      Today’s post will discuss the intrinsic factors that contribute to (or detract from) embryo competence.

      First, a brief background discussion….

      If an embryo reaching the endometrial cavity either fails to implant or is lost soon after implantation (i.e., a chemical pregnancy or miscarriage) it will, in the vast majority of cases (about 80%), be due to an inherent defect that has rendered it incapable of propagating a viable conceptus – a condition we term “embryo incompetence”.  In only about one of five such reproductive losses would the cause be attributable to “poor endometrial receptivity”.

      What is important to bear in mind is that it is primarily the genetic/chromosomal integrity of the egg (rather than the sperm) which determines embryo competence. Given the fact that egg numerical chromosomal integrity declines with advancing maternal age, it is hardly surprising that embryo competence also deteriorates in lock step with advancing age. Research has shown that about half of all embryos derived through fertilization of the eggs of a young woman (under 35 years) are likely to be incompetent, while at 45 years of age the incidence is likely to be nine in ten. This serves to underscore and explain why both spontaneous pregnancy and IVF success rates plummet, and miscarriage rates virtually treble, by the time the woman reaches her mid-forties.

      It is thus important that the following intrinsic factors which control embryo competence be considered:

      1. The relative influence of egg versus sperm: In order for an embryo to be “competent” it must have its full component of 46 chromosomes (i.e., euploid). Any irregularity in the numerical chromosomal integrity (i.e. aneuploidy) of the embryo will inevitably result in “reproductive failure”, manifesting as failure to conceive, miscarriage, or an aneuploidy- birth defect such as Down Syndrome. While it is the chromosomal integrity (karyotype) of the egg which exerts the predominant influence on embryo’s karyotype and thus its “competency”, the chromosomal integrity of the sperm also plays a role, albeit a far lesser one when the man is fertile. However, in cases of sperm dysfunction, this influence can be significantly greater.
      2. The influence of the chromosomal structure of the egg and sperm: The structural chromosomal integrity of the embryo also influences its “competency”.  In some cases, part of one or more of the embryo’s chromosomes may be missing (a “deletion”). Sometimes during fertilization, parts of one or more chromosomes detach and reattach to another chromosome (a “translocation”).  Such structural changes can emanate from a sperm and/or an egg defect, but the degree to which either gamete contributes, and what role paternal or maternal age, environmental, or genetic factors may play in its genesis are presently poorly understood. Unless specifically looked for at the time of preimplantation genetic sampling (PGS) of the embryo, such structural chromosomal aberrations might go undetected.
      3. The role of genetic and metabolic factors: There can be little doubt that genetic and metabolic factors also impact embryo competency, but how and to what extent such influence is exerted remains poorly understood. To make matters worse, they are, by and large, neither identifiable nor quantifiable through any currently available diagnostic methodologies. This having been said, the potential exists for the future application of human genomics to embryo evaluation, and with it will likely come a new-found ability improve to better evaluate “embryo competency”

      NEXT: Check back next week, when my post will focus on clinical considerations – what your RE can do to optimize embryo competence.

      18 Responses to “Embryo Quality & Embryo “Competence” – Part One: Planting a Good Seed”

      1. liz says:
        September 21, 2012 at 7:01 am

        I am 50 now, and am looking for an IVF clinic in this country that would do donor egg for me, will be 51 in december. Do you have any knowledge of clinic that treat up to age 55?

        thx

        Reply
        • Geoffrey Sher says:
          September 21, 2012 at 7:42 pm

          As long as you meet the required physical (medical) criteria, we would be willing to consider this. Please call 702-892-9696 and set up a video conference call or telephone consultation with me ASAP.

          Might I recommend that you go to the home page on this site, find a “search bar” in the upper right hand column and type in the following subjects into the bar and it will take you to all the relevant articles I posted there.

           “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)
           “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)
           “A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
           “IVF success: Factors that influence outcome”
           “Egg Donation”

          Geoff Sher

          Reply
      2. Tara says:
        September 22, 2012 at 6:42 am

        I am 41 for a few more months. Initial workup yielded an FSH of 5.4, Estradiol of 63, AMH of <.3, and 11 antral folicles. All ultrasounds, HSGs, etc., were normal. With the exception of very low AMH, primary issue is male factor infertility due to a now reversed vasectomy. Stimulation protocol that was chosen for me involved oral contraceptives, beginning on day 4 of my cycle for ~17 days, then a baseline ultrasound, stimulation was to begin 3 days later with Bravelle and Menopur leading upto a trigger shot of HCG and so on. After 7 ultrasounds in the past year and no known history with cysts, my baseline ultrasound (after the oral contraceptives) showed a large cyst on one ovary, and bloodwork showed an estrogen level of 74. I was told to stop oral contraceptives and return in a week for another ultrasound. As one can imagine the cyst is still there. There is now discussion of switching me to a Lupron flare protocol – but the docs are unequivocal leaving the decision to be based on what meds have already been paid for. I have read your articles on individualized protocols for patients based on their unique situation – which is what one would expect from medical practitioners. I am concerned that Im on an expensive, emotionally charged wild goose chase.Any input would be appreciated.

        Reply
        • Geoffrey Sher says:
          September 24, 2012 at 11:05 am

          First off…with your low AMH (regardless of the AFC and FSH), it is likely that you have diminishing ovarian reserve (DOR)> This, in conjunction with your age, would in my opinion, mean that you are not a good candidate for a “microflare-lupron stimulation”. Also I would not take you directly off a BCP on to a stimulation (see the article elsewhere on this blog that deals with “use of the BCP in IVF”. I would use a BCP but only with a long protocol. Here I probably would choose an agonist/antagonist conversion protocol-A/AQCP (read up on this topic as well …on this blog) and I would personally would not use Bravelle ( which is a urinary-derived gonadotropin). I would use purified recombinant DNA-FSH (e.g. Folistim or Gonal F)

          Feel free to call 800-780-7437 to set up a free video conference call with me to discuss in more detail.

          Geoff Sher (

          Reply
      3. Celina Dawson says:
        October 30, 2012 at 1:47 pm

        I’m 40 with FSH 7.2 and AMH <0.16 ng/mL. First round of IVF produced 5 retrievable follicles. Through ICSI we got two embryos: a 2-cell and an 11-cell. The IVF failed and it is now recommended that I take 75 mg DHEA and Resveratrol 500 mg twice daily for 4 months until the next IVF to enhance the egg quality and then try again. Heres' the question(s): can I really improve my egg quality? and could it be that I should just go for egg donation because of my low AMH levels? THanks!

        Reply
        • Geoffrey Sher says:
          October 31, 2012 at 10:03 pm

          Respectfully, in my opinion, these treatments will NOT improve egg quality. Because of age and diminished ovarian reserve, you either need to consider embryo banking with CGH embryos selection before time runs out for you or go directly to using an egg donor (Please see below)

          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.

           “An Individualized Approach to Ovarian stimulation” (posted on November 22nd, 2010)
           “Ovarian Stimulation in IVF: Why is it important to down-regulate LH?”
           “Agonist/Antagonist Conversion Protocol”
           “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.
           “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)
           “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)
           “A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
           “IVF success: Factors that influence outcome”
           “Staggered IVF”
           “Embryo Banking”
           “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). While an audiovisual (Skype) interaction is much more personable and preferable than a discussion by telephone, either will suffice.

          Geoff Sher

          Reply
        • zahra maravandi says:
          March 12, 2013 at 4:24 am

          Hi
          my name is zahra and i get married 4 years ago.
          we try to have baby,But unfortunately it is imposible beacuse we do icsi 4 times but it did not answer,here,The doctors did a thorough check-up and they said: i hadn’t any problem and problem is about my husband.Experiments show that concentration of spermatozoa is low,in addition,their physical shape have problem beacuse heads and their tails are separated.so we do icsi but it Was not successful.(grade of Fetal was e)
          i heard that Quality,Instruments,…. are important.Even in city – to city of my country(iran).
          i have question:
          can you help us please?
          is it imposible come there for Treatment?
          if yes,What should I do?

          thanks a lot

          Reply
      4. sharon wilson says:
        January 13, 2013 at 9:53 am

        My wife and I have been trying to have a baby for about two years now doing the iui. We will be trying again in a month or so this time with ivf. What should we look forward too as far as how the size of the eggs? While the egg get transferred back to her body what should we do to make sure they stay in their.

        Reply
        • Geoffrey Sher says:
          January 13, 2013 at 1:07 pm

          I cannot answer that question because there are tgoo many variables at play and without knowing much more about your history I am unable to be specific.

          Howewer, please go to the home page of this blog, (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. “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”

          If you wish, call 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
      5. Ruth says:
        March 6, 2013 at 3:27 am

        Hi doc, my 1st IVF-ICSI on last Feb failed. I’m 33 yo, my obgyn said I have mild PCO, I have many antral follicles but my period has been regular. Hormones LH 3.6, FSH 3.7, Prolactin 13.87, Estradiol 30.45, AMH 7.03. My husband’s 36yo, has oligoteratozoospermia, only 1 testicle (the other one is undescended), last SA concentration 3 mill/ml; motility : fast progressive 0%, slow progressive 30%, non progressive 20%, immotile 50%; normal morph 23%.

        I was stimulated using Gonal-F, 150iU for 7days, decreased to75iU for 1day, then 37.5iU for another day (total 9days). Cetrotide from the 5th day of stim. At trigger day my E2 was 4760, P4 0.99. Triggered with Ovidrel.

        20 eggs was collected, of that 5 were immature, 2 were abnormal. Did ICSI on the 13 eggs, 10 were fertilised. At the 3rd day after collection, we had only 4 embryos : two 10-cells, one 8-cells, one 7-cells. Transfered 2, one 10-cells and one 8-cells, the other 2 were frozen. The remaining 6 were cultured further but finally at the 5th day the lab said they all didn’t make it.

        After transfer, I was prescribed for Crinone pressary (once daily), Ascardia (once daily), and Utrogestan (twice daily).

        2 days after transfer, I got checked for estradiol, result was 1690. The doctor said I didn’t need to get Gonasi because my estradiol were above 1500.

        At the time of bHCG test,my result was less than 1.

        Based on above information, what do you think cause the failure? Are there things that can be changed to improve my chance in the future IVF cycle (change in protocol, medications, etc)? And also, are there additional tests that should be done to check for undiagnosed factors?

        Regarding the 2 frozen embryos we still have, do you have any suggestions for the FET (protocol, medications, additional test before FET)?

        Thank you.

        Reply
        • Geoffrey Sher says:
          March 6, 2013 at 9:25 am

          It could be one or more of the following:

          1. Bad luck
          2. Male factor
          3.That a different stimulation protocol in readiness for coasting, is needed
          4. An undiagnosed implantation dysfunction.

          Please go to the home page of this blog, (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. “PCOS”

          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. “Prolonged coasting”

          10. Male Factor Infertility”

          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
      6. sara swan says:
        April 24, 2013 at 2:53 pm

        Hi, I am a mother of a four year old child (naturally conceived, very easily). I just turned 43 yesterday, and have endured two miscarraiges at 42 years old. One was in October ( natural conception) and the other was a month ago after IUI with a fertility clinic in Dublin, Ireland. They encouraged me to go for IUI rather than IVF, and I went ahead with their advice, not realising at the time that the success rates with IUI (especially in this clinic!) for women over forty were so low.My AMH is 10.4, my antral follicular count is ten. I had my FSH tested a year ago and it was 8.3 My period has not returned yet so obviously I have not been able to get retested for FSH. However, I had a regular 28 day cycle, and I ovulated every month without fail.
        Anyway, I would love your opinion, as the clinic have advised me strongly, since early April, to go on DHEA for three months to improve my egg quality. I don’t trust them anymore, so I am reluctant to take their advice and am reluctuant to take such a strong drug anyway with all my body and mind have been through. I am very sceptical of their claims that it will help me. Having said that, the clinic tested my liver and testosterone function a few weeks ago, and it all came back normal. Can you advise me please? Many thanks.

        Reply
        • Geoffrey Sher says:
          April 24, 2013 at 9:26 pm

          I would definitely not advise DHEA. It is an androgen and is metabolized to testosterone in the ovaries. Too much ovarian testosterone is not good for egg/embryo quality…especially in older women and women with diminished ovarian reserve.

          The most important factor for you is selection of the ideal protocol for ovarian stimulation (see below).

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

          5. “Nutritional supplements in IVF”

          6. “Staggered IVF”

          7. “Embryo Banking”

          8. “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
        • Geoffrey Sher says:
          April 25, 2013 at 5:48 pm

          I responded to you directly by email Sara.

          Good luck!

          Geoff Sher

          Reply
      7. sara swan says:
        April 24, 2013 at 3:08 pm

        Hi again,

        I forgot to mention, in this same clinic, one consulant advised that I stay off the chinese herbs prescribed to me by my acupuncturist (they are called Ba Zhen Wan, she swears by them to prevent miscarraige)if I go on DHEA, but another consultantfrom the same clinic said its fine to take the herbs along with them! I would really appreciate your thoughts on this issue as well, many thanks.

        Reply

      Leave a Reply

       
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      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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