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Thursday, August 14, 2014

My embryos fail to implant repeatedly – Recurrent Implantation Failure in IVF !

“My doctor said that my embryos looked picture-perfect, yet they failed to implant – why did this happen? “

This is the question in the minds of women who undergo IVF failure and this becomes a particularly nagging doubt when they face multiple IVF failures. Many women naturally think that their uterus is defective or their body is not good enough to accept the embryo and hence the transferred embryo is getting rejected by their uterus , or it is being killed by their own body. After all, fertilization happened in the lab , the embryo grew well in vitro , and they even saw their embryo (remember, you must always see your embryos and ask for photos  before embryo transfer !) The embryologist assured them that they looked perfect, , and they’ve read lots of IVF success stories of women who got pregnant with such good embryos. As a result, they naturally come to the conclusion that good embryos  are meant to implant – and if they didn’t, this clearly means there’s a problem with their uterus or their body. Because they have low self-esteem because of their infertility, it’s easy for them to jump to this conclusion and beat up on themselves. A bad situation is often made worse by relatives telling them that their embryo must have “fallen out” because they did not rest sufficiently; or that the cycle failed because they are too stressed out or have too much “body heat”. This is why many women who undergo repeated implantation failure opt for surrogacy. This article has been written to help you understand what causes repeated implantation failure (is the cause really known ? and which is the culprit – the seed (embryo) or the soil (uterus) ?

What is implantation failure?

When an egg and sperm unite together an embryo is formed (this event takes place in the fallopian tube in your body and in the IVF lab it takes place in a “ test tube” ( actually a petri dish ) which contains nourishing culture medium). The embryo thus formed divides rapidly and reaches the uterus in the blastocyst stage (or is transferred to the uterus on day 3 or day 5 during an IVF cycle). When in the uterus, the blastocyst starts to communicate (initiates a molecular conversation) with the endometrium ( the uterine lining) by secreting protein molecules which results in implantation, if the embryo is competent enough and if the endometrium is receptive. Implantation is the attachment of the blastocyst stage embryo to the endometrial lining of the uterus , so that it further develops into a baby (imagine planting a seed in the soil).

When a woman undergoes three or more failed IVF attempts (with good quality embryos) or if implantation doesn’t happen even after transferring more than 10 ‘good-looking’ embryos over many cycle, then the woman is said to have “ implantation failure” . When an embryo fails to implant , there can only be two logical reasons: the embryo is not good enough (genetically abnormal), the endometrium is not “receptive” (doesn’t allow the embryo to implant) enough.  So, what really causes implantation failure? Please keep reading!

Which is the culprit – the seed or the soil?

Imagine a farmer who owns a piece of land and wants to cultivate rice. He ploughs and tills the land , making it ready for sowing, finds the right season (a season which provides good water, air and temperature so that the environment is conducive enough for the sprouting and growth of saplings) and he carefully selects the seeds. This is analogous to how an IVF doctor prepares a woman for undergoing an IVF cycle. He gives hormone injections so that the eggs are collected and fertilized with her partner’s sperms to form embryos (seeds), hormones (estrogen and progesterone) are also used make the uterus ready for accepting the embryo (just like ploughing the land, adding fertilizers and so on) . The woman needs to be in good health (analogous to waiting for the right season to sow the seeds).

When a farmer takes care of all these things and sows the seeds, he expects the seeds to germinate and grow. But what happens when the seeds fail to sprout? There are three plausible reasons for this happening:

  • Poor seed quality (embryo)
  • Soil which is not fertile (uterus)
  • The environment is not conducive enough (physical health of the mother-to-be)

There are also other minor factors which can prevent seed germination like, improper seeding (improper embryo transfer), the seed getting eaten by insects and so on!

In the same way, there can be three logical reasons for implantation failure:

·         Poor quality embryo (genetically abnormal embryos)
·         Non-receptive endometrium (due to defects in the uterus)
·         The body is unhealthy

Other minor factors which play a role in failed implantation are: difficult or traumatic embryo transfers, infections present in the uterus and so on!

How does embryo quality impact successful implantation?

It is a well-known fact that young women fall pregnant quickly when compared to their older counterparts. This is because eggs from older women are more prone to genetic defects , such as aneuploidies (presence of the wrong number of chromosomes ), and contain incorrect or insufficient genetic information necessary to build a healthy baby).When such eggs are fertilized by a sperm , it leads to the generation of embryos which are genetically incompetent (either such embryos do not implant and even if they do , the pregnancy ends in early miscarriage . In rare instances , they can also lead to a full-term birth , where the new born has genetic defects). With the advent of comprehensive chromosome screening, it is now possible to screen all “24-chromosomes” (22 autosomes and 2 sex chromosomes) for the presence of aneuploidy (even though the effectiveness of such a technique to increase live birth via ART in clinical practise is still not provem ). One such study using CGH showed that 96% of aneuploid embryos failed to implant ( This clearly shows that embryo competency plays a major role in implantation. This is why older women find it difficult to find success with IVF , or require more attempts than their younger counterparts.  When an older woman uses donor eggs her chance of achieving IVF success goes up dramatically! This is irrefutable proof that it is embryo quality which plays a major role in implantation and IVF success.

Role of endometrium in embryo implantation

The old scripture, Manu Smriti says “Subeejam Sukshetre Jayate Sampadyathe” i.e., Good seed in good soil yields abundantly. The importance of soil quality in agriculture is well-known.  Does endometrium play such a crucial role in embryo implantation? What happens when a fertile seed (genetically competent embryo) is seeded on defective soil (non-receptive endometrium)?

The period during which the uterus is able to receive the embryo (blastocyst) is called the “window of implantation.” Human uterus is receptive only during a short period of time and this period is also called as the period of “uterine receptivity”. In humans, the receptivity period is between day 20 to day 24 of regular menstrual cycle i.e, 7-11 days after the LH surge that triggers ovulation. During IVF, embryos are transferred to the uterus either day 3 (embryo transfer) or day 5 (blastocyst transfer) after egg collection (the day of ovulation) which coincides with the “window of implantation” of natural menstrual cycle. During FET transfer, the day of starting progesterone is taken as the first day of ovulation and embryo transfer is done accordingly.

Human embryo implantation is an enigmatic biological phenomenon – after all, in-vivo experiments are impractical and unethical to conduct; and studies with animal models do not translate well to humans. But it is well-known fact that embryo and endometrium exhibit cross-talk with each other (talk to each other) using molecular signals and such cross-talk is necessary for successful implantation. However, no reliable molecular markers for endometrial receptivity have been identified. This makes it difficult to find out whether an endometrium is receptive or not during an IVF cycle.

During IVF, endometrial receptivity is assessed crudely with the help of ultrasound images. Endometrial thickness is measured using ultrasound images and an endometrium of greater than 8mm which is trilaminar is said to be optimum for embryo transfer.

It is a well-known fact that the endometrium becomes receptive only after progesterone exposure. Progesterone brings about necessary changes in endometrium (converts the endometrium from proliferative to secretory phase) so that it becomes ready to accept the embryo. Recently, frozen embryo transfers are becoming much more successful than fresh embryo transfers in the field of IVF. It is hypothesized that high estrogen concentration in the body during the fresh IVF cycle compromises endometrial receptivity.

What are the possible reasons for “non-receptive” uterus during an IVF cycle?

  • If the uterus contain adhesions, polyps or fibroids in the cavity, then its receptivity will be impaired
  • If there is premature increase in progesterone levels (that is, rise in progesterone levels before egg collection due to premature luteinisation of follicles) during an IVF cycle, then the receptivity of the uterus doesn’t synchronize well with the time of embryo transfer and this can lead to failed implantation. This problem can be solved by careful monitoring of the IVF cycle.
  • It is believed that thin endometrial lining (a lining which is less than 8mm) is not receptive enough.
  • An infection of the uterus has also been hypothesized to prevent implantation, by making the uterine environment less optimal.

There are also so many unproved reasons cited for lack of uterine receptivity, which include: immunological theories like the presence of high number of uterine NK cells, excessive HLA matching between partners ; and blood clotting issues.

What factors other than the embryo and uterus might contribute to implantation failure?

The ease with which the uterus can be negotiated for the embryo transfer also plays a pivotal role in achieving successful implantation. If the uterus is hard to access via the cervix ( for example, in patients with cervical stenosis) , then other embryo transfer methods like ZIFT should be used in order to enhance implantation.

Can implantation failure be successfully treated? What kinds of evidence based therapies are available?

Yes, it can be treated , but only if the reason is known. The one and only well-known, scientifically proven reason for implantation failure is genetically incompetent embryos. If you are a women of advanced maternal age or if you have premature ovarian aging, even if you get some embryos to transfer during an IVF cycle, many a time they can be genetically abnormal and will not implant successfully. The irony is many women do not want to accept this fact ( after all, it is very difficult to accept the fact that they can’t have their genetic baby) and try to blame their uterus for the failed implantation. As a result they believe that surrogacy can help them conceive, which is not true! Doctors make use of their ignorance and “treat” them with many different therapies which are not evidence based. I have seen so many women of advanced maternal age subjecting themselves to many useless therapies and ultimately finding success when they finally use donor eggs. So if advanced maternal age or poor ovarian reserve is the cause of failed implantation, the only reasonable solution is to use donor eggs.

If your uterine cavity contains adhesions, fibroids or polyps which interfere with implantation, removing them will help in achieving embryo implantation.

The role of endometrial thickness in successful implantation is still a question. Many women with thin endometrium do have successful implantation, but the scientific literature shows that an endometrium thickness of more than 8mm is optimum for achieving implantation.

What kinds of “non-evidence” based therapies are available to treat implantation failure?

The following therapies do not have solid proof for their efficacy and are very speculative:

  • Use of blood thinners like aspirin and heparin.
  • Causing local injury to endometrium before embryo transfer, to improve local uterine blood flow
  • Therapies like use of steroids, IVIG, intralipids etc which claim to reduce NK cell levels in the uterus.
  • Paternal lymphocyte immunotherapy to “ treat “ HLA matching between partners.
  • Use of G-CSF (Granulocyte-Colony Stimulating Factor) which is commercially known as neupogen.
  • Use of embryo glue (a substance which is claimed to enhance the attachment of embryo to the uterus).
  • Routinely making a hole in the zona pellucida of the embryo (outer coat of the embryo) with the aim of helping the embryo to hatch out of the shell successfully. This is known as laser assisted embryo hatching.
  • Co-culturing embryos with endometrial epithelial cells.
  • Intrauterine administration of PBMCs ( Peripheral Blood Mononuclear Cell)

Doctors must actually resist offering such treatments that are not evidence based or at least they must share information honestly with their patients. They must make sure that the patient understands that the above mentioned therapies are not a panacea for their problem.

What can I do if I have repeated implantation failure?

  • Test your AMH ; day 3 FSH and E2 value ; and your antral follicle count – are they normal? Do you have good ovarian reserve? If you have poor ovarian reserve or are older than 40 years of age and have suffered repeated implantation failure, you should consider using donor eggs.
  • If you are young and have good ovarian reserve, ask the embryologist how your embryos look – are they of good quality? If they are of good quality (dividing well according to their age) , then the chances are that the embryos which were transferred may have been genetically normal ( sadly, we still do not have the technology to test for all possible genetic defects before the transfer)
  • Do you have PCOD? Did they retrieve lots of eggs (more than 25 eggs) from your ovaries? PCOD could be a reason for the lack of embryo implantation. Taking insulin sensitizers like metformin and myoinositol might solve your problem.
  • If your doctor has used the same ovarian stimulation protocol for retrieving eggs from your ovaries, you can try other ovarian stimulation protocols too. Mild ovarian stimulation protocols are found to be superior in producing better quality eggs and embryos in a selected subset of IVF patients (mostly patients with poor ovarian reserve).
  • If you have failed IVF several times by using a day 3 embryo transfer, try having a day 5 embryo transfer. The fact that embryos are developing to blastocyst stage is a good indication (not an ultimate proof though) that your embryos are good enough.
  • You can try doing a frozen embryo transfer instead of a fresh transfer. High levels of estrogen in the body during a fresh cycle can damage uterine receptivity.
  • If you have cervical stenosis and embryo transfer through cervical route becomes difficult you can try other modes of embryo transfer (like ZIFT )
  • You can try changing the clinic – sometimes this works!
  • Another option available is to use donor embryos!
  • If your uterine cavity contains adhesions, polyps or fibroids, you need to remove these. If there are lots of adhesions or if you suffer from a thin endometrial lining because of Asherman’s syndrome (and if it is untreatable!) you can opt for surrogacy.

So following are the options in front of you:

  • Change the ovarian stimulation protocol
  • Use frozen embryo transfer instead of fresh transfer
  • Change the mode of embryo transfer ( do a ZIFT ) if cervical embryo transfer is difficult
  • Change the clinic
  • Change the egg
  • Change the sperm
  • Use donor embryos
  • Consider surrogacy

What is the take home message?

When an embryo enters the uterus in the blastocyst stage, it initiates a molecular cross-talk with the endometrium. Perhaps it says, “Hey I am here and I want to establish connection with you, attach and grow, are you ready to accept me ? ” The endometrium senses the signal sent by the embryo and responds accordingly. All this cross-talk happens by releasing appropriate protein molecules. It is believed that if there is some problem with this cross-talk, embryo implantation fails.  

It is hypothesized that the endometrium acts as a biosensor of embryo quality. This means, if a genetically abnormal blastocyst enters the uterine cavity, the endometrium senses this by the signals sent by the embryo and prevents the implantation of the embryo. So if this biosensor mechanism is defective in some women, they paradoxically become “ superfertile” . That is, such women fall pregnant very easily because even genetically abnormal embryos are allowed to attach to the endometrium and establish a pregnancy. On the other hand, they suffer from recurrent biochemical pregnancies or miscarriages because even if the genetically abnormal embryo implants , it can’t develop into a healthy baby and gets aborted eventually.

There are also studies which show that even if the endometrium is not optimally receptive,  a genetically competent embryo can modify the endometrial environment to make it favourable,  so that successful implantation is achieved.

When you talk to a well-experienced IVF specialist, he will say from his practical experience that when women suffer from recurrent implantation failure, most of the time changing the egg can bring about successful implantation and pregnancy!

The endometrium seems to act as a passive recipient. After all a seed , can sprout even in the absence of soil ( for example, in women who have ectopic pregnancies, where the embryo implants in the fallopian tube, where there is no endometrium at all ! ) If you are suffering from recurrent implantation failure, please do not blame your uterus , if it doesn’t have any obvious defects.


  1. Thanks a ton as always for such a detailed note Manju. I hope you are doing well and I am eagerly waiting to read your next post on your journey. You are in my prayers!

    One question - I am in the middle of my FET cycle and my doc mentioned that I have some waves like structure in my endo lining which makes it a little harder to measue but its around 7.2-7.8 mm isoech on day 14 of Progynova..she inititally seemed a little concerned but on further prodding in the scan she seemed comfortable with it for the transfer which is due next Wed. I am a little confused and scared if everything is perfect for the transfer. Any thoughts here? Anything from your experience?

    Thanks a ton

    1. I do not think her comment has any significance. Your endometrium is in the proliferative phase (growth phase) when you are on estrogen. Proliferative phase endometrium is wavy in appearance. So do not panic what wavy means :) I am sure everything is perfect, take progesterone as instructed and lots of good luck !

  2. Thanks a ton Manu for your kind words, it has certainly helped put my mind to some ease. Based on your experience is there anything else I can do to increase chances of success in FET? Read on some forums that eating pineapple and some fertility supplements before transfer helps in implantation? Do you suggest anything few days before the transfer day and post the procedure? Getting a little jittery and scared... : (

    1. The truth is there is nothing we can do, but I can tell you few things

      Keep your cool. Getting jittery will not help. After transfer try to be very happy. Embryos like happy woman's uterus :) Try it, you will understand the truth.

      Pray to God but do not get obsessive. Some women pray obsessively all the time, it can create lots of pain.

      Do not lie down all the time, please ! Taking few hours of bed rest is OK to make you feel good. Carry on with your normal like.

      Take your folic acid and other medicines regularly. Eating pineapple is good - tasty, healthy. But don't overdo anything.

      All I would say is stay calm and believe in your body's ability to handle things well. Do not take any supplements, you will never know what they do to your body.

      Prepare yourself for the failure too. It might appear absurd but remember 50% of time there is chance of failure too.

      I pray that all goes well, lots of good luck ! Make sure you see your embryos and get photos of them.

      I hope this helps !

  3. Thank you so much Manju! I am really trying to follow what you mentioned and leaving everything else on god! I just got my TSH results and to my surprise the level has come at 4.2 while for last one year or so it has stayed around 2.7 levels..have been on thyrox 25 mg for almost 1.5 years now. In mid June it was 2.72. Could this be a problem? I changed my lab just wondering if it's an error or Ivf meds have any role to play here....really hoping for the best this time...!

    Looking foward to your next post. As always you are in my prayers!

    1. Do not panic. When is your ET ? Do you have anti-thyroid antibodies ? Is your BMI normal ? Do you have signs of hypothyroidism ? Feeling sleepy, lazy, feeling cold unusually, cold hands, excess hair fall ? I don't think it could be lab error !

  4. Nopes none of these signs as BMI is also normal..My ET is on Wed, day after tomorrow! I shared the results with my doc and she increased my dose of Thyrox but did not seem very concerned wrt the ET. I really hope it does not cause any issue with implantation Manju!

    1. I am not a medical doctor but let me give my two cents on this. Since you are taking estrogen, this increase in TSH is nothing to be concerned of. If I were you, I wouldn't increase my thyroxine dosage. Especially, without any hypothyroid symptoms, I wouldn't change your dosage just before ET.

      How much did she increases ?

  5. i was taking 25 mcg..she has not made it to is this rise due to estrogen given to prepare body for FET? I never knew its the direct outcome of IVF meds. Does it not affect implantation in any way then? Just read on net that docs at times cancel ET due to high TSH in women..very confusing!

    1. Yes, high estrogen can increase TSH value. 12.5 mcg is OK. I don't think it will drastically bring down your TSH. Yes, hyperthyroidism can be detrimental. That is why it is important not to change thyroxine dosage at the last minute. But, I believe an increase in the dosage by 12.5 mcg will not harm anything. Just watch for hyperthyroid symptoms like rapid heart beat, feeling warm unusually and so on.

      How are you taking your thyroxine ? Are you taking it on empty stomach, first thing in the morning and are you waiting an hour before you take your breakfast ?

  6. I take it first thing in the morning before eating anything...but after taking it, have my tea and few biscuits in that okay or should I wait longer? I hope all goes well on Wed! this is such a long journey and hats off to you Manju - you are truly an inspiration to all of us. I really look upto you whenever I feel drained with babymaking. Please pray for me !

    1. Please wait atleast half-an-hour before you take anything !

      My prayers are with you. Lots of good luck ! Will be thinking of you on Wednesday.

  7. Thank you Manju! You have been a great help for me throughout this journey! Cant appreciate your help enough! May God bless you too!

  8. For not being a doctor you seem very knowledgeable about this all. I'd love your input. I have had multiple miscarriages (this will be my 7th) and failed IVF's even with embryos that were genetically tested. We recently did a FET with 2 genetically tested embryos that looked perfect. 10 days post transfer my HCG was 111. 12 days it fell to 80, so we know that at least 1 tried to implant. At this point after many pregnancies that have failed prior to getting a heart beat, my heart tells me the NK cells could possibly be my issue. MY IVF doctor would not put me on Heparin. He did run labs months ago to check for autoimmune diseases and everything looked normal. He saw no reason for Heparin when I asked him multiple times if we could simply add it to my FET plan. I have always taken baby aspirin and extra folic acid however. My next step is to get a 2nd opinion. We have 1 more frozen embryo left that has been genetically tested that we would like to use, but not without something changing in the protocol. We have thought all along that I had chromosome issues with my embryos. At this point, I don't believe that is truly the case when even the perfectly tested ones aren't progressing. Any opinions or suggestions?

    1. Can you please let me know your age, day 3 FSH and e2 and AMH value ? Are all the m/c in first trimester ? Can you please specify on which weeks it happened ?

  9. All of my embryos stop progressing prior to getting a heartbeat. We have never even gotten a fetal pole during our ultrasounds with any. My day 3 FSH has always been normal per all my IVF doctors. I'm not sure on the exact numbers, but I am searching my notes. I want to say around 7. I will post it when I find that for sure. What is AMH value? Do you want the E2 level for day 3 also? I am 30 years old. My miscarriages all happen typically around week 6. The last one was the only one I had to go on to get a D&C with. However this one this week is being called a chemical pregnancy after my FET.

    1. Please read about AMH in my blog! Yes, would like to have e2 value too!

      I agree it is very hard to go through this without knowing what is wrong. I have some questions, please answer it.

      Do you have PCOD or any other problem?
      Are you overweight? What is your BMI?
      Does diabetes run in your family? Is your blood glucose normal?
      Did you and your husband go through genetic testing? Did they do karyotyping with both your chromosomes?
      How was the quality of your embryos? Do you have pictures of them?
      How many eggs and how many embryos you had?
      Did your doctor put you on any special medicines?
      Are you taking folic acid?
      Is your thyroid normal?

      Sorry for the delay in replying! Please answer these questions so that I could help you better.

  10. I've had my E2 tested soooooooooooo many times during this. My FSH and E2 are always normal on day 3 labs prior to IVF or FET. My FSH is always around 7. The highest it has ever been was a little above 9. I have had I think 18 or so eggs retrieved at once. However, only a handful if that have ever fertilized. At one time I had around 16 retrieved and NONE went on to make it to day 5. I have never been diagnosed with PCOD and I am pretty confident I have not gotten that. My doctor screens my E2 level VERY often during treatment. I do not have any other known problems. I am not overweight. I'm only 145 if that. However, I retain water horribly during these treatments. Especially once I start taking Progesterone. When I'm 4 weeks I always look to be 5 months along. Diabetes does not run in our family. I have been tested for all of that prior to IVF and it was all normal. Yes, I went through the genetic testing and karyotyping which was normal. My husband has 3 previous children so the doctors did not feel it was necessary for him to be tested. They tested him for some stuff but not the genetic testing. I also just did the NxGen screening to check for 20 of the most common genetic diseases and those came back perfect. The quality of my embryos are never good. Out of 18 maybe 6 fertilize then by Day 5 (when my transfer should take place) they are just then ready to be biopsied for the genetic testing so they must freeze them. My last round of IVF we switched Menopur with Luveris which I saw a much better result with that and had 3 that tested normal. 2 of those ended with the chemical pregnancy. I have only had 1 that was transferred fresh after an IVF cycle. I do have a picture of that one I will share. The rest have been frozen and transferred my next round of IVF or this last time was FET. My embryos take longer to develop for sure. I do not have pictures of the 3 that have been frozen and later transferred. I mostly focus on the reports from the scientist after the genetic testing which states they are "normal". As normal as they could be at that point and good to go. I take baby aspirin, folic acid and a prenatal vitamin only. Once I'm around 4-5 weeks and I find out I am pregnant then I start taking DHA on my own. I just recently had my thyroid checked and all 3 of my doctors said it's normal. I asked for 3 opinions because I felt that was an issue possibly as well. This is why I have been on a roll about the NK cells. Something is missing. Whether I get pregnant on my own, FET, or IUI I always fail right after implantation.

  11. Manju,

    There is lot of good information with clean explanation here that it takes months for people like me to gather online and comprehend.

    Hats off to you..
    Happy Holidays!!


    1. That's very kind of you Ravi! It feels very good to know that my work helps people who are in need. Happy holidays and good luck!

  12. Hi Manju.

    Don't know if you are still active at this blog. I have a question for you that have had me wondering a lot:
    What is the reason behind the lifting restrictions following egg transfer??
    Logically, I think that it could be something like - increased abdominal pressure causing some kind of negative influence on the uteris. However, if the egg can't fall out - what harm can be caused?

    Best regards

    Pernille (Denmark)

  13. Hi MANJU ,

    Your blog is really helpful . I have had two cycles ..frist one with pregnancy which resulted in pregnancy but miscarriage. Second one no pregnancy ... For my frist cycle endo was 12mm n for second it was 7.5 mm triple layer I am planning for third ..when ever I am going for tvs on 20th day my endo is coming between 5 to 6.5 mm .. is it like after ivf attempts it gets detoriated .. earlier I never had endo problem ... do I need to wait more to flush out ivf side effects ... its been 5 months since last cycle ..Please suggest

    1. Is the first one a fresh IVF , and the remaining two FETs ?

  14. Both are fresh cycles . Frist one was my own cycle . My amh is 5.5 . Second I used donor cycle as I have genetic disease history .... second one failed .third one I am planning for donor cycle .... but naturally without medicines my lining is 6.5 mm ... but earlier it use to be 12 mm. So why this sudden change.

  15. OK , this means for the last two cycles you took estrogen from outside to stimulate the growth of uterine lining. Unfortunately , for some women including me , how hard we try to stimulate uterine lining growth with externally supplied estrogen , the lining doesn't grow well. What you can do is , use femara and gonal f to mimic a stimulated cycle. Once ovulation happens and the lining thickens you can transfer donor embryo. Your uterus doesn't have any problem , do not believe if anyone says so. Once your body produces estrogen , the lining will grow automatically. The reason for this happening is unknown. My guess is , some women's body doesn't process synthetic estrogen well , or it is quickly removed from our body before it could act. The second reason might be , other than estrogen , our endometrium needs something else which is secreted by growing follicles for its growth. I conceived twins with a lining of 6.5 mm in a FET cycle , so a thin lining doesn't mean implantation won't happen.

  16. OK , this means for the last two cycles you took estrogen from outside to stimulate the growth of uterine lining. Unfortunately , for some women including me , how hard we try to stimulate uterine lining growth with externally supplied estrogen , the lining doesn't grow well. What you can do is , use femara and gonal f to mimic a stimulated cycle. Once ovulation happens and the lining thickens you can transfer donor embryo. Your uterus doesn't have any problem , do not believe if anyone says so. Once your body produces estrogen , the lining will grow automatically. The reason for this happening is unknown. My guess is , some women's body doesn't process synthetic estrogen well , or it is quickly removed from our body before it could act. The second reason might be , other than estrogen , our endometrium needs something else which is secreted by growing follicles for its growth. I conceived twins with a lining of 6.5 mm in a FET cycle , so a thin lining doesn't mean implantation won't happen.

  17. Hi Manju, Thank you so much for your blog. I had a first IVF cycle failure. I am 31 years old and have good AMH values, , I also have hypothyroidism and take a 50 mg Thyronorm tablet daily. The doctor told us that there were 3 grade 1 embryos transferred and we save the pics. I trust my doctor. After the failure to implant, he did an endometrium receptivity test (ERA). This was done on the 18 Day of the cycle and my period started the next day of the test. My reports for the ERA test cam back as negative suggesting that the integrin protein required for implantation is missing in my lining. I am very depressed due to this. Due you have any idea what treatment can be done for this? When I searched online it said that this test should be done 8 to 10 days after ovulation. Hence the timing of this test could be wrong. The doctor has asked us to do a repeat of this test with more monitoring this time and he said that if this is the issue I will take time to conceive with IVF. Please let me know your thoughts on this.

    1. May I know the reason for doing IVF ? As per science , 60% women get pregnant within 3 fresh IVF cycles. The rest might need more attempts. The science of IVF is not fool proof. Most IVFs fail because of poor genetic quality of the embryos. There are many other things which could go wrong , like , embryo transfer. Doing unnecessary tests after a failure will only create more confusion. Not only your doctor , no one knows when ERA must be conducted. There are no proper scientific evidence for the validity of such tests. The only good thing you can do after a failed cycle is , make sure you are with a good clinic , whether they handled your cycle well , if you believe they did so , just repeat the cycle - that's the only sane way to find success soon. Good luck !

    2. May I know the reason for doing IVF ? As per science , 60% women get pregnant within 3 fresh IVF cycles. The rest might need more attempts. The science of IVF is not fool proof. Most IVFs fail because of poor genetic quality of the embryos. There are many other things which could go wrong , like , embryo transfer. Doing unnecessary tests after a failure will only create more confusion. Not only your doctor , no one knows when ERA must be conducted. There are no proper scientific evidence for the validity of such tests. The only good thing you can do after a failed cycle is , make sure you are with a good clinic , whether they handled your cycle well , if you believe they did so , just repeat the cycle - that's the only sane way to find success soon. Good luck !

  18. Hi Manju, thank you so much for responding! The reason for doing IVF is that my husband's sperm motility is very low. We also did the DNA test recommended by our doctor and my results were normal where as for my husband the Y chromosome arm length was shorter. he has asked my husband to do another test and has said that based on the results of these tests ERA included, he will time the transfer of the embryos accordingly during IVF and will put on more progestrone. I have for the past year started to spot 3-4 days before my period starts. Have you ever heard of ERA test and its usefulness? Any other thoughts on this since we have been trying to conceive since 4 years.

  19. Hi Manju, thank you for this helpful article. I am 43 and my husband is 47. I take 50 mg of synthroid to keep my thyroid low (I have sub clinical hypothyroidism - my highest TSH before meds was 3.34). I am in excellent health and have had numerous tests including for autoimmune issues and Drs found nothing wrong. My husband is in good health but, unlike me, he doesn't eat that healthy - a lot of fast food although he never smoked and rarely drinks. We used a 29 year old proven donor and two high quality embryos have failed to implant. I am considering genetic testing or possible using donor sperm if we have to do this again. We have two remaining frozen embryos from this donor both good quality. (1) what are the chances that all of this donor's embryos our poor given the first two didn't implant? (2) would using donor sperm possibly help? My husbands sperm is pretty good but the motility is a little low but eggs fertilize after ICSI and produced 4 good quality blasts on day 5. (3) would genetic testing help? Thank you.

  20. Hi Manju, DO let me know your thoughts...

    1. I am really sorry for the delay in replying !

      First , women who go through IVF ( woman of young maternal age , who have good ovarian reserve ) 60 % of the time will find success within 3 full IVF cycles , others need more attempts. This is what scientific data show. Could you see how limited IVF success rates are ? IVF success depends on a lot of variables , and the most well - known and scientifically proven reason is egg quality. The lab conditions and placement of embryo in the proper place also play a pivotal role. Sperms are very rarely responsible for implantation failure. If the embryos become blastocysts and if your husband sperms don't have major genetic defects , sperm cannot be the reason for failure. If I were you , I will just repeat the cycles with donor eggs and with the sperms from my husband until I find success. Hope this helps ! Please have patience , do not do any unnecessary testing , it will work out.

  21. Hi Manju, I'm a 41 yr old woman. 4 donor egg IVFs, out of which 2 resulted in chemical pregnancies and 2 failed. My question is, does the age of the uterus have any major role in implantation success. By using the egg of young women, do I have the same rate of success as a woman of that age?

    1. No , age of the uterus has no impact on IVF success.

      Yes , using donor eggs will give you the same success rate as that of younger women , provided , the donor is young :)

    2. Manju, I am the same 41 yr person who asked the role of the age of the uterus in implantation success. I have PCOD and had 2 miscarriages with IVF's using my own eggs at age 37 and 38. But I have had 2 chemical pregnancies and 2 failed IVF's with donor eggs recently. Could this be because I have PCOD? I'm on metformin. Does PCOD affect implantation success or cause miscarriages even when I'm using donor eggs.

    3. I don't think PCOD can prevent implantation. But it can cause m/cs. How much metformin you are on ?

    4. Bigomet SR 500 - twice a day.

    5. I don't think PCOD is the reason. Why can't you try changing clinic ? Sorry I couldn't be of much help. But I am sure PCOD doesn't prevent implantation.

    6. I'm really fed up of all this Manju. Nothing seems to work for me. I'm such a failure, not only in matters of baby making but also in other aspects of life also.

    7. I understand you. Please be kind to yourself , please ! If you need to talk to me , please write to
      Send me your medical history , please !

  22. Hi Manju, Thank you for your interesting blog, I am a 31 year old woman and have just failed my second IVF. My husband has severe oligoteratozoospermia (1M/ml) with very low motility and few normal spermatozoids. On my side after a lot of testing no issues have been found. We have transferred so far (by counting IVF and frozen cycles) a total of 6x Blastocysts grade 1, the last 2 had already hatched when transferred. As you mention the sperm is unlikely to be responsible for the failures do you think further testing should be done on me? My AMH and ovarian reserve are very good. My hormone levels are also all good and my lining was good for all transfers. I am hoping to understand the reason for these implantation failures. Many thanks

    1. The research says , 60% women who are of young maternal age and with good ovarian reserve will get pregnant within 3 full IVF cycles , others need more attempts. Can you see how limited IVF success rates are ? I don't think you need any further testing. How many IVF cycles have you gone through ? It's very promising because you get good quality blasts. If I were you , I would just repeat until I find success. If there is a possibility to do CCS , it might throw light in the genetic quality of the embryo. Are your hubby's siblings fertile ? Have you both undergone genetic testing ?

    2. Thank you for your reply, my husband does not have brothers but all the specialists we met agreed on the fact that his infertility was due to a lack of development of his reproductive system at puberty. His karyotype was normal with no microdeletion of the chromosome y. My karyotype was normal too. We did 2 IVF cycles so far and I've lost all hope :(

    3. I did 7 IVF cycles ! Have hope , it will work out. You don't have implantation failure.

    4. Thanks Manju, this actually gives me some hope which was much needed :)


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