Blastocyst Transfer: The Preferred Approach!

06 Dec
Ask Dr. Sher A Question

The issue of whether it is better to transfer early cleaved embryos rather than blastocysts continues to rage. I have previously written in this blog on this important topic. Here, I once again wish to refocus on the reasons why I personally strongly favor transferring blastocysts.

What we do know is that cleaved embryos (day 2-4, post-fertilization) that fail to develop into blastocysts are with few exceptions “incompetent” (unable to propagate a viable pregnancy in a “receptive ” uterine environment). So had they been transferred in the “cleaved” state, they almost certainly would not have developed to blastocysts and thus could not propagate a pregnancy anyway.

Simply stated, there is no difference in pregnancy potential by doing an earlier transfer of pre-blastocyst (cleaved) embryos versus forgoing an embryo transfer because none of the embryos developed into blastocysts. There is no validity to the often-stated opinion that an embryo would develop better and have a greater chance of propagating a baby by being inside the uterus earlier, than it would by being allowed to develop into a blastocyst in an incubator.

Don’t get me wrong – I am not saying that there is no place for doing earlier pre-blastocyst transfers! Indeed, if it were possible to determine with confidence, by microscopic grading alone, which embryos would develop into blastocysts by day 5-6 post fertilization (and this is currently not possible), then in terms of outcome, it would not matter whether such embryos were transferred sooner or later. What we now do know for certain (and have reported on) is that if a day-3 embryo is found to have its full quota of 46 chromosomes (i.e. it is “euploid”) as assessed by day-3 metaphase CGH, then, regardless of the age of the egg provider, more than 90% of such embryos will develop into a blastocysts by day 5-6 post fertilization.

By comparison, in the absence of CGH testing, about 40% of embryos derived from the fertilization of eggs extracted from a woman under 35 years, (and +/-10% in women in their mid 40’s) will subsequently develop into blastocysts. Certainly, chromosomal integrity of the embryo is not the sole determinant of “competency” (epigenetic and metabolomic factors also play a role) but, it is by far the most important variable.

Given the following facts:

  • The odds are relatively poor that embryos determined to be of a “High Grade”, microscopically, will turn out to be euploid (chromosomally normal)
  • The likelihood of aneuploid (chromosomally abnormal) eggs increases as the age of the egg provider increases.

It is my opinion that there is nothing wrong with transferring up to three (3) such early (day-3), untested embryos to women under 39 years and/or no more than four (4) to women over 40 years, especially if they would agree to pregnancy reduction to twins in the unlikely event of a high order multiple pregnancy (triplets or greater) where the risk to mother and offspring would be greatest.

The strong arguments in favor of blastocyst transfer are:

1) By waiting to day 5-6 many unworthy, aneuploid and “incompetent” embryos can be culled out, thereby providing “relative” confidence that you will not end up with a high order gestation. This allows for the transfer of fewer embryos, minimizing the risk of high order multiple pregnancies.

2) Waiting until day 5-6 post-fertilization affords important diagnostic benefits:

a) Failure of the expected number of cleaved embryos to advance to this stage of development suggests either inherent embryo “incompetence” (which is usually a function of the age of the egg provider…the effect of the ‘biological clock”), and/or may be due to the wrong protocol of ovarian stimulation being applied. (For expansion on this important concept, I urge read the article “An Individualized Approach to Ovarian Stimulation for IVF“)

b) It facilitates the performance of CGH to identify and then selectively transfer only the most “competent” (euploid) blastocysts. In such cases, the transfer of a single blastocyst (SBT) should yield a 60-70% baby rate per embryo transferred to the uterus, provided there is no underlying uterine implantation dysfunction.

Of course, after everything IVF patients go through, it is much easier and far less stressful on the treating physician not have to have to confront patient(s) with the heartbreaking news that they have no surviving embryos to transfer. Undoubtedly, this is one of the main reasons why IVF practitioners still prefer to transfer cleaved embryos rather than blastocysts. But as far as I am concerned, this is not justification to do what ultimately might not be in the in the patents’ best interest. Rather, it is about doing what serves patients best and what they choose after being fully informed regarding associated risks and benefits.

13 Comments

  • TinaP says:

    If I have severe endometriosis should I transfer 2 blasts or 1 blast? What are my chances of twins if 2 are transfered.

    • Geoffrey Sher says:

      I usually transfer 2 blastocysts. Success , in my opinion dpends on 2) the chromosomal integrity of the embryos, b) technical skill in performing the ET and c) whether or not you have a coexisting immunologic implantation dysfunction (IID).

      Patients with endometriosis have immunologic abnormalities. The most significant of these involve the presence of harmful antibodies known as antiphospholipid antibodies (APA) which are in the bloodstream of about 66 percent of women with endometriosis. In about half such cases (i.e. about 1/3 of all cases of endometriosis…regardless of severity) the immunologic implantation is profoundly aggravated by the presence of activated (i.e “toxic”) Natural Killer cells (Nka) in the uterine lining (endometrium). These NKa attack the invading trophoblast cells (developing “root system” of the embryo/early conceptus) as soon as it tries to gain attachment to the uterine wall. In most cases, this results in death of the embryo even before the pregnancy is diagnosed and sometimes, in a chemical pregnancy or even an early miscarriage. . As such, many women with endometriosis, rather than being infertile, in the strict sense of the word, often actually experience repeated undetected “mini-miscarriages”. Treatment requires prior and specific identification of all 18 sub-types and their gammaglobulin isotypes. Unfortunately, only a handful of Laboratories in the United States are capable of adequately testing for APAs. But it probably not APAs that cause infertility in endometriosis patients. Rather it is the co-existence of toxic or activated NK cells (as measured by the K-562 target cell test) that attack the early embryo’s root system as soon as it tries to attach to the uterine wall that causes the problem. Women who test positive for Nka require intravenous Intralipid (IL) plussteroid (dexamethasone, prednisolone or prednisone) therapy.

      Geoff Sher
      702-699-7437

      • TinaP says:

        If I have very good grade blastocysts as well I will be taking intrallipids the day of the transfer would you a) still recommend 2 blasts be transferred and b) do you recommend taking intralipids only the day of FET or even earlier ?

        • Geoffrey Sher says:

          If you have an autoimmune implantation dysfunction the 2 blastocysts transferred would be fine provided IL/steroids are started 10-14 days prior to ET. If it is a partial alloimmune implantation dysfunction, then in my opinion only one embryo should be transferred under IL/Steroid cover.

          To determine the etiology, your blood should be tested for NK cell activation (using the K-562 target cell test) and your and your husband’s blood should be matched for DQ alpha and HLA genetic similarities.

          Please go to the home page of 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.

          Important Announcement:

          Dr Al Peters (Medical Director at SIRM-New Jersey), and I ,recently established the “SIRM Reproductive Immunology Forum(SRIF) which will provide a venue where you can address and hopefully find solutions to problems relating to Immunologic Implantation dysfunction (IID) that often manifest with “Unexplained” infertility, IVF Failure and Recurrent Pregnancy Loss (RPL..

          To this end we established http://www.InfertilityImmunology.com , a dedicated website where you can:
          • Register with SIRF
          • Request and receive (free of charge) a PDF copy of our book: “Unexplained” Infertility and Miscarriage : The Immunologic Link”
          • Be kept abreast of what is current in the IID arena
          • Post questions for Dr Peters and I to respond to and,
          • Interact with other patients on a separate discussion board dedicated to this.

          We look forward to hearing from you!

  • Stacie says:

    Dr. Sher, In this article, you quote “Failure of the expected number of cleaved embryos to advance to this stage of development suggests either inherent embryo “incompetence” (which is usually a function of the age of the egg provider…the effect of the ‘biological clock”), and/or may be due to the wrong protocol of ovarian stimulation being applied.” Does this imply that ovarian stimulation protocol can influence the ability of an embryo to develop a competent embryo vs incompetent embryo? Can you elaborate on this?

    So if in an IVF cycle, you have an abundance (>10) of appropriate embryos on day 3, most of which arrest between day 3-5, and deteriorate therafter (suggesting incompetent embryos), are there ways to alter that embryo quality/competence by changing pre-retrieval conditions?

    Thanks!

    • Geoffrey Sher says:

      The protocol used for ovarian stimulation, by affecting the hormonal environment in which eggs develop, can have a profound impact on the ability of the egg to go through orderly meiosis (chromosomal segregation) following the hCG trigger…resulting in egg aneuploidy (irregular number of chromosomes) which is the primary cause of “embryo aneuploidy” and incompetence.

      Geoff Sher

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