The best treatment option for recurrent implantation failure

Share on FacebookShare on Google+Tweet about this on TwitterEmail this to someoneShare on StumbleUponShare this article

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 to 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 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.

Download free infographic

Did you like this? Share it:

Leave a Comment!

37 Responses to The best treatment option for 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.

      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.

      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.
      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.
      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.
      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.
      Dr V Karande

      • Commenter says:

        I have had 7 cycles of IVF. 5 with my own eggs and my husband’s sperm the results were negative.4th cycle I got pregnant but was miscarried in 8th week. 6th cycle with donor egg and husband’s sperm again it was a failure. 7th cycle we had donor embryo and again it was a failure. Doctor sent my husand’s sperm for DFI test and it was poor. He has very low morphology 99% abnormal morphology and my AMH levels are less than 0.3. Can you suggest me what else can I do to achieve succesful pregnancy? I just knew that my last cycle also did not work. We are devastated and don’t know what to do next. Can you please help?

        • I am so sorry you have not achieved pregnancy after what appears to be a long and arduous journey.
          Please get a formal second opinion from a Board certified REI.
          I would begin by carefully analyzing your failed cycles.
          Your husband should see an urologist specializing in male infertility. A course of anti-oxidants (Co-Q 10) may help.

          Your uterine cavity should be rechecked.
          I am unable to give you more specific advice at this time as I do not have your specifics (your age for starters).
          We would welcome you as a patient at InVia.
          Dr V Karande

  9. Commenter says:


    • Commenter says:

      I have had 6 cycles of IVF and no success so far. In all my cycles I have at least 2 or 3 normal blasts and even though I had PGS for all cycles I faced BFN in the fresh transfers and in the FETs I got BFP but miscarried (at 7 weeks after seeing a HB for one and at 5 weeks in another). In the last attempts dr. added lovenox, dexamethasone and intralipids but it didn’t work either.

      I have no idea what else to do. Did all the tests for RPL and everything came back clear. Also, I have 2 kids from previous marriage, that I had no issue to conceive or during pregnancy. I’m in a total loss. Don’t know if it’s time to give up or if there’s something else that I could try. Any advice?

      • How old are you?
        What do you mean by “BFN” and “BFP”?
        What are the success rates at the Center you have been seeing?
        Please get a formal second opinion.
        We would welcome you as a patient at InVia.
        Dr V Karande

        • Commenter says:

          I’m 35.
          BFN–> big fat negative (negative beta)
          BFP –> big fat positive (positive beta)

          I cycled in two centers. They have good rates in my region for my age.

  10. Commenter says:

    I was 29 when i went for my 1st IVF which was successful with twins. Unfortuantely the pregnancy lasted for 6 months then had premature babies. They survied for a month then passed on. Since 2005 – 2014 we have been trying to get pregnant. So far we have done more than 10 infertility procedures ( long and short protocols) without any success. We have also tried both sperm and egg donor. Egg donor twice and sperm donor once. The last was only egg donor which resulted in 6 healthy embryos, 3 were put back,but no implantation took place. 3 is now frozen. I am now 39 years. Is there any hope?

    • I am so sorry the twins did not make it.
      Hats off to you for your persistence and tenacity.
      Your situation is too complex for me to give you a definite answer as part of a blog.
      I would need to review all your treatment cycles in detail before giving you an opinion.
      I am presuming you have tried at more than one Center and the ones you have used have excellent pregnancy rates.
      If you would like a formal second opinion, we would welcome you as a patient at InVia.
      There is a new test for endometrial receptivity call ERA. The researchers are very reputable. However, we have not tried it yet at InVia. Here is a link
      Dr V Karande

  11. Commenter says:

    Hi, you’re missing ‘to’ in the last sentence of your second last paragraph. Sack the proof-reader!

  12. Commenter says:

    Dear Doctor, I am 40 years old and have had 3 failed IVF cycles. All 3 day transfer. The last cycle I had two 6 cell which the doctor were very positive about. For each cycle there has been no implantation. My doctor is suggesting that on the next cycle we freeze the eggs and transfer on a natural cycle. What are your views?

  13. Commenter says:

    Hello Doctor. I am 42, my husband 43! Over the past 5 years I have had 3 fresh cycles and one IVF. First fresh: chemical pregnancy. IVF: 18 eggs, all fertilized, 4 transfers, 1st with three fresh, next three with the rest frozen, three each time, all good quality 3-day embryos, one miscarriage (week 7). I had a left hydrosalpinx and have removed it after the first fresh cycle and the two first IVF transfers. The other salpinx is partially open. But still no implantation. The center I am currently at has suggested the two fresh cycles, since the doctor (considered an IVF guru in Greece) sees I am ovulating normally and with good eggs. FSH about 7 and Anti-Mullerian Hormone 11. My endometrium is thick and perfect, as all doctors have said. My uterus is also fine. No health issues. The sperm is fine. I am a smoker for 25 years but a light one (social smoker) and I have quit altogether as of this last cycle. After the fresh transfers I am on progesterone, estrogen and an injectable blood thinner (Innohep). Do you think it is normal to not have succeeded yet because of my age? What do you think is more appropriate as a next step? Pre-implantation embryo check for chromosome abnormalities? Killer cell checking? Blastocysts? Please advise, I just got my last negative beta today and I am at my lowest…Thank you.

    • Since you produce a good number of eggs, you fall in the “good prognosis” category. At the same time, I would like to acknowledge the courage and tenacity you have displayed in persisting after so many failed attempts.
      Using pre-implantation genetic screening of the the embryos is a reasonable next step. In fact, I would strongly recommend it.
      If the embryos are all abnormal, it may help you make a decision regarding the use of donor eggs.
      Dr V Karande

  14. Commenter says:

    and when PGD testing has been done and implantation failure still occurs? what then?

    • Excellent question.
      Preimplantation genetic diagnosis (PGD) or screening (PGS) checks for chromosomally normal embryos. 30 – 70% of human embryos are chromosomally abnormal. In older patients 100% of the embryos can be abnormal. So by screening the embryos for chromosomal abnormalities, we are eliminating a significant cause of IVF failure. We are currently getting the same pregnancy rates with a single euploid (normal) embryo that we used to previously get with multiple embryos. Even so, the pregnancy rate is not 100%
      So, what to do if PGS fails to result in a pregnancy?
      There are several reasons why IVF fails. These include genetic abnormalities, problems with the cytoplasm (mitochondrial) errors and issues with the embryo transfer or uterine lining.
      In most cases, you just need to try again.
      Good luck!
      Dr V Karande

  15. Commenter says:

    Dear Doctor,
    I am 34 years old and undergone 3 cycles till now. first cycle: I was pregnent but was a biochemical pregnancy and lasted for 6 weeks. Second and third cycle : implantation failure with second cycle- day 5 blastocyst (frozen) transfer and third cycle Day 2 stimuated cycle transfer.
    Will I be categorised into RIF group of patients? My AMH is 1.2.
    No antiphosholpid antibodies, no factor 5 abnormality. I ve autoimmune thyoiditis with mildly elevated TPO Ab. I am planning to undergo next cycle soon. Should embryo pooling with transfer of blastocysts ( forzen) in a natural cycle be a better option for me? With my thyroid problem, should I receive additional medication for improving endometrial receptivity:High dose IVI g intralipids or corticosteroids help?

    • My recommendation would be for you to consider pre-implantation genetic screening of your embryos.
      We call it SMART IVF as it is the smart thing to do.
      The commonest reason for miscarriage is a chromosomal abnormality in the fetus. By transferring a chromsomally normal (euploid) embryo, you will be (practically) eliminating this cause for miscarriage.
      I have no experience with intralipids and have stopped using corticosteroids many years ago as they do not help with implantation failure.
      Dr. V Karande

      • Commenter says:

        Dear Dr Karande,
        Many thanks for your quick reply. PGD was never done till now. I would certainly request my Doctor to do it this time.
        As my AMH has been on the lower side, I underwent 1 self and 2 donor egg cycles(fresh and frozen) and all failed. I am more keen to do a self cycle with pooling this time.Will this affect the embryo quality and cause another failure? I dont know .. but when self and donor both ve failed in the past I want to try self cycle blastocyst (with a PGD) this attempt. Am I thinking on correct lines? please advise. Also, can morphological abnormality in sperm (teratozoospermia 2%) , despite selecting good ones by IMSI technique, be responsible for chromosomal abnormality in the embryo? thanks again for your valuable advice.

        • I do not have any experience with IMSI.
          Pooling cycles + PGD is a reasonable option as long as you are aware of the commitment (time + money + courage) and get a fair idea of success from your physician.
          Dr. V Karande

          • Commenter says:

            Thanks Dr Karande.
            You are absolutely right. The most difficult part is “Courage” to keep yourself going despite repeated failures. I really appreciate your gesture to help and advice.

About Dr. Aniruddha Malpani

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

View all posts by Dr. Aniruddha Malpani →

Chicago Area Fertility ClinicsArlington Heights Crystal Lake Hoffman Estates Northbrook

Entire Website © 2003 - 2016 Karande and Associates d/b/a InVia Fertility Specialists / By visiting this website, you agree to our Terms Of Use | Sitemap
Web Design by NETRIX, LLC