The best treatment option for patients with recurrent implantation failure

One of the most frustrating group of patients for IVF specialists are those with recurrent implantation failure. These are patients for whom we’ve done multiple IVF cycles , but who still do not get pregnant. These patients as labeled as having repeated IVF failure ; or recurrent implantation failure , which is actually just a waste paper basket diagnosis which means we really do not know why the embryos we transfer do not implant for these women.

On an intellectual level , we understand that there are broadly only two groups of reasons for failure of implantation. One could be that the embryos are not of good quality; while the other is that there is a problem with endometrial receptivity .

Unfortunately, because it is still very difficult for us to pinpoint what the problem is in an individual patient, there is a lot of hocus-pocus and mystery surrounding the treatment options for these patients . They are emotionally very vulnerable and very desperate . They will often keep on changing doctors , and each new doctor will offer his own particular flavor of some magic potion in order to solve the problem. This could range from using intravenous Intralipids; to doing PGD for comprehensive chromosomal screening; to using immunotherapy for treating NK ( natural killer ) cells .

A lot of this is extremely speculative stuff ; and I feel a better treatment option would be one which is based on sound science. This would be to grow all the embryos to blastocyst stage; freeze all of them; and then transfer them in the next cycle. While this may seem to be a lot of hard work, there is a sound scientific basis to this approach.

Growing embryos to blastocyst stage ( rather than transferring them on Day 2 or 3) is the best way we have today of ensuring that the embryos are competent. While it’s true that not all blastocysts are genetically normal , which is why not all of them will implant , given the state of the technology available today, this is the best approach we have for making sure that the embryos are viable. If the embryos do not grow upto the blastocyst stage in the incubator in vitro (assuming that the IVF lab is experienced and competent ), this means that means the problem for recurrent implantation failure is quite likely to be an embryo problem. This is especially true when patients with recurrent implantation failure have had multiple failed IVF cycles with only Day 2 or Day 3 transfers ; and the earlier IVF clinic has not tried to grow their embryos to the blastocyst stage.

While the fact that their embryos have arrested in vitro; and have failed to develop to blastocysts ( which means they will not have any embryos to transfer at all) can break their heart , at least this way they know where the problem lies , so they can then approach their next treatment cycle armed with more intelligence . This approach provides valuable information, rather than leave patients groping in the dark.

Why not transfer the fresh blastocysts ? This is because endometrial receptivity may be suboptimal in a super ovulation cycle , because of all the hormones which have been injected. Because the thrust of superovulation is to focus on growing good-quality eggs , sometimes we may not be able to optimize endometrial receptivity at the time at which the eggs are ready for retrieval. Once we have frozen all the blastocysts, we can then focus all our energies in the next cycle on improving endometrial receptivity. This approach allows us maximize the chances of implantation, because we are transferring good-quality blastocysts into an optimally prepared endometrium.

This approach allows us to use sound scientific principles , without resorting to a lot of expensive hocus-pocus , to maximize chances of success in this group of heartsink patients . Only very skilled IVF labs can offer this kind of service, because it needs a lot of expertise and experience to do this successfully.

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15 Responses to The best treatment option for patients with recurrent implantation failure

  1. Moises says:

    Since Fall 2007, I’ve had two myomectomies (w/ a caeeclnd engagement in between), a couple of bouts with ovarian cysts, two “suspicious” mammograms and a biopsy and four failed IUIs, so I completely understand how you feel. Spent the holidays in a very depressed state, and used that time to reassess things. As a consequence I made some very crucial decisions that have put me on my current path, and I feel optimistic that things are going to work out in my favor. Wishing you the best, and confident that you and Joey will continue to be happy regardless of where this decision leads you.

  2. Valerie says:

    We had “RIF.” After 4 years, 3 IVF clinics in 3 states and 45 negative pregnancy tests, we finally got pregnant. The 3rd clinic tested us for autoimmune/thrombophilia issues and discovered Antithrombin and MTHFR. After adding blood thinners to our protocol, we finally had success with a 5-day blast retrieved at age 43 with FSH at 56 during a natural cycle. The first two clinics dismissed us due to age because I did not stim well. We did obtain 7 5-day blasts from 9 natural IVF cycles. To think we may have been able to conceive on our own simply with blood thinners and without 4 years of heartache and expense is beyond words. In my opinion, all implantation patients should be advised they can have the full miscarriage panel of testing. Why is it not offered BEFORE an IVF cycle to confirm individual protocol treatment and ensure the highest chance of success during IVF?

    • Hi Valerie!
      Congratulations! I applaud your persistence and am delighted that you are finally pregnant.

      I hope you do realize that you are indeed very lucky. To get pregnant at age 43 with an FSH of 56 is indeed like winning the lottery!

      The current recommendation for thrombophilia testing is that it be offered only to patients with a history or a family history of blood clots. In fact, thrombophilia testing is considered experimental and currently is NOT recommended as a routine test for patients with recurrent miscarriages.

      As far as testing for antiphospholipid antibody syndrome, studies have shown that these tests do not predict outcome. Denis et al. from Saint Barnabas Hospital in New Jersey analyzed blood from more than 600 IVF patients and showed no correlation between the immune test results and who got pregnant, who miscarried and who delivered a baby.

      There are no data supporting routine testing and these tests are fairly expensive.

      Once again Congratulations! and I hope I have answered your excellent question fully.

      Sincerely
      Dr V Karande

  3. Commenter says:

    What about RIF with 5 day frozen blastocysts? I am 32, husband is 39; all tests are ok. We tried natural for 5 years and then started IUI and IVF procedures, ran so far 3 IVF cycles, in each we had very good quality 5 day embryos (around 9 blstocysts per cycle), we transferred both fresh and frozen. With different protocols (includive endometrial injuries, prednison medication, or with no additional medication support). Yet, implantation failure occurs recurrently, irrespective of what we do. There are very few articles and researches on RIF with 5 days blastocysts for patients diagnozed with infertility without cause. What is your opinion on this? thank you.

    • First of all, I would like to commend you for your persistence. Its indeed been a long road for you and your husband.

      The question is, why have your 3 IVF cycles failed? Is it egg, sperm or both? uterine lining?

      You may have to consider using other options including using a gestational carrier, donor egg or donor sperm, adoption.
      I do not have enough information to give you specific advice.

      Please get a formal second opinion from a Board Certified Reproductive Endocrinologist.

      Sincerely
      Dr V Karande

      • Commenter says:

        apparently neither egg, nor sperm nor the lining. no cause, whatsoever.
        anyway, thank you for your answer, much appreciated.

  4. Commenter says:

    Hi Dr. Malpani and Dr. Karande,
    I have had two cycles of Frozen Embryo Transfers using 3 of my embryos. All 3 embryos were 5 day blasts, graded 4AA. I have yet to become pregnant. I was told everything looked perfect, including my lining that was 11.5, 6 days prior to transfer (both cycles). I’ve been put on Estrace at the start of my menstrual cycle and I start crinone 6 days before transfer. We have been diagnosed with “unexplained infertility” as there have been no issues found with sperm, egg, uterus, ovulation… etc. They cannot find one thing wrong. What you do in this case of implantation failure? We are at a loss. Thanks for your input.

    • I am sorry your FETs have been unsuccessful.
      I do no have all the details to give you specific advice as to the next step.
      It is possible you need to try again.
      Please get a formal second opinion from a Board Certified REI.
      Sincerely
      Dr V Karande

  5. Anonymous says:

    If I’ve had multiple IVF failures ( the last with donor eggs), all of which indicated no implantation (HCG levels less than 5.0 mIU) would you just recommend we keep trying? It feels like something MUST be wrong to never have implantation of multiple grade 4AA blasts?

    • I do not have enough information to give you specific advice.
      Please get a formal second opinion.
      We would welcome you as a patient at InVia.
      Some patients in your situation end up being successful with a gestational carrier.
      Sincerely
      Dr V Karande

  6. Kim says:

    If I’ve had multiple IVF failures ( the last with donor eggs), all of which indicated no implantation (HCG levels less than 5.0 mIU) would you just recommend we keep trying? It feels like something MUST be wrong to never have implantation of multiple grade 4AA blasts?

  7. Anonymous says:

    I agree with the above but I do not understand the following?
    ‘This approach allows us to use sound scientific principles , without resorting to a lot of expensive hocus-pocus , to maximize chances of success in this group of heartsink patients .’
    Ok, so let’s say we have grown our embryos to blactocyst and we use them on the next cycle and they fail- we hope the embryos are good so what ‘scientific principles ‘ are used to aid the correct growth of the endometrial lining and uterus habitat?
    I am now at this stage and need to now what to investigate next as I have been looking at nk cells, immune testing, endometrial biopsy etc etc- but what are the scientific things to try ?

    Thank for any guidance

    • Hi Ms. Rebecca Hawkins
      He did not use the word “heartsink” in his blog!!!!
      I agree with Dr Malpani that tests for NK cells and the use of IVIG or intralipids is experimental and unproven.
      You need specific guidance, something which is not possible in a blog.
      Please consult with a Board Certified REI.
      We would welcome you as a patient at InVia.
      Sincerely
      Dr V Karande

  8. Anonymous says:

    Any solution for this

    • I believe this is your question
      “I have done 1 ivf which failed in 2011. but i was diagnosed to have high ana titre and positive for antithrombin. would these affect my ivf success and implantation?”
      I do not have enough information to give you specific advice.
      Why did your IVF cycle fail? Did you respond normally? Number of eggs? embryos? etc
      Why were these tests done? Have you had recurrent miscarriages?
      In some patients, we treat these abnormalities with Lovenox or Heparin and baby aspirin.
      Please consult with a Board Certified REI.
      We would welcome you as a patient at InVia.
      Sincerely
      Dr V Karande

About draniruddhamalpani

Dr. Aniruddha Malpani is an IVF specialist with a brilliant career with numerous awards, educational distinctions and prizes. Dr. Malpani completed his postgraduate degree in Gynecology from the University of Bombay in 1986. He received further training in IVF from UCSF, San Francisco, and U.S.A. As a medical student, he studied at Harvard, Johns Hopkins and Yale. He practices in Mumbai, India along with his wife Anjali. He can be contacted at info@drmalpani.com

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