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  1. #1
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    Default IVF and the million dollar question?

    I saw my FS about a month ago and I just can’t stop thinking about what she said. When I questioned her about why some embryo’s don’t implant her response was “Well, that’s the million dollar question”.

    Is she right or have any of you been given an explanation of what helps or hinders implantation? Why don't all high grade embryo's implant?

    I’ve only heard about eating pineapple core for the first 5 days after ET, not drinking 2 litres of pineapple juice like I did, unfortunately I found this out after my BFN (** singing If I Could Turn Back Time **).

    Would NK cells have something to do with implantation? FS wasn’t too keen on getting me tested though …

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    My FS told me (only today) that it is usually down to a chromosomal abnormality with the embryo. He said it's very very common, and happens to everyone. He also said that they can undergo a high grade screening process to select even better embryos than normal, but that requires them to take a biopsy from the embryo, and that can harm the developing cells and, in some cases, stop it from developing further - so at this stage they don't do it. In his words "it can make the embryo very raggedy".

    He also said that for the reason it can often take a completely 'normal' couple 6 months (or more) to get pregnant, is that often the sperm has fertilised an egg, but there are chromosomal problems with the embryo, and therefore your body usually gets rid of it rather than implanting/ keeping. If this happens at a later stage then it would be a miscarriage, but it's very common to happen extremely early on - prior to implantation.

    Hope that makes sense! It did to me, but not sure I'm putting it very well...

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    AceOfBase  (27-04-2012)

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    Hi Girl X,

    This is a question I have asked my FS many times, unfortunately it is the million dollar question and it's where most IVF research is now focussed. My FS explained it that due to the fact that the embys are created in a 'perfect' environment many more of them survive until day 3 or 5 blasty's than what naturally would. It is impossible to know how many 3 or 5 day embryos a person who has a natural conception has before they actually get lucky and one sticks.

    NK cells can play a part but they are very rare and the test for them does come with risks that could cause even more fertility problems. DH and I have had e everything done except for NK cells and I am supposedly perfect, I've had laparoscopies, hysteroscopys, salpinpographys, DNA and chromosome testing, and pretty much every test under the sun. I also started IVF when I was only 23, our embies are grade A, day 5 & 6 embryos and some have even begun the hatching process and yet I am currently in the 2WW for transfer #5.

    If there was an answer to that question then the researcher who discovered it would make a fortune, not to mention that they would be mobbed by a group of crazy IVFers.

    All you can do is hang in there and hope for the best.

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    AceOfBase  (27-04-2012)

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    Thanks Girl X and Grebbeci, very interesting to hear your thoughts, maybe others who have had BFPs through IVF have something to add as well (shameful hint at a bump).

    I just would love to know why some emby’s stick and some don’t and, yes, Grebbeci, I would be in the mob of crazy IVFers after that researcher who discovers it too!

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    It is indeed the million dollar question!

    I've had 6 transfers now using a total of 8 embryos. All of them high grade Day 5 blasties, several have been hatching blasts. Fed up with waiting for the right embryo to come along, DH & I decided to have our embryos biopsied and tested with array CGH (a screening test to check for chromosomal abnormalities).

    With today's techniques, biospy process rarely harms the embryo, and in our case the biospy was done at blastocyst stage with the sample removed from the trophectoderm (cells that forms the placenta). The Inner Cell Mass that becomes the baby is not touched. It is more risky to biopsy Day 3 embryos, which only have 6-8 cells at that point and are therefore more vulnerable when a cell is removed.

    We had 3 blastocysts biospied on our last cycle, the one that was graded the highest actually turned out to be abnormal. The other 2 were fine. Just goes to show that looks can be deceiving.

    NK cells are definitely relevant, although there is still some divide in the FS community about this. The test for it is a simple uterine biopsy. Getting the testing done does not hinder fertility at all, in fact there are numerous studies showing that the biopsy stimulates a healing response in the uterine lining which improves receptivity to implantation. It is also known as a 'scratch biopsy'.

    I have spent hours trawling through medical journals and reading articles on this subject (I have access to these through my work in the pharmaceutical industry). I have a list of tests that I'm happy to share with anyone who'd like it, just send me a PM with your email address & I'll forward it to you.

    If your FS is one of those that won't support you in running the tests, then switch to one who will! IVF is too expensive and the failures too heartbreaking to keep going when you have concerns that are not being addressed. My philosophy is leave no stones unturned and do not die wondering. Thankfully my FS is on the same page as me.

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    There'll be more than one answer, and they'll boil down to bad embryos, bad environment or bad luck.

    Bad embryos can be genetic, epigenetic, physical problems.
    Bad environment can be hormonal, physical, immunological.
    Bad luck can be a result of the stochastic nature of biological processes.
    (That's just off the top of my head, no doubt I've left out some broad reasons.)

    And then as you investigate each of those subcategories for specific reasons, e.g. trisomy 21 (not good example for implant failure), failure of paternal imprinting on chromosome 17 (also not good example), thick egg "shells", stress-related steroids, uterine scar tissue, NK cells, adhesion molecules didn't result in attachment for long enough, etc. you'll get a massive list of individual reasons.

    It's not a small question that's being asked. It can be made smaller by asking "Why didn't THIS embryo stick." But often there isn't sufficient evidence available to answer it, eg to answer for genetic abnormalities you'd need to retrieve the failed embryo and test it, and that's not feasible.

    Edit: Realised my specific genetic and epigenetic examples aren't actually implantation failure examples, although they do affect development (Down Syndrome and Prader-Willi Syndrome). Also, a better hormone example for an embryo that doesn't stay sticky would be low/no progesterone production by ovaries in response to hCG.
    Last edited by felicita; 27-04-2012 at 14:53.

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    Felicita, I hope you won't mind me chiming in with this bloody fabulous response you wrote a while ago on the LTIVFWW thread which I thought might be helpful here:

    Quote Originally Posted by felicita View Post

    OK, so we're discussing why the embryos which don't go to term but stop early don't all stop at the same point. We're all aware of the phenomenon since some embies are expected to stop growing in the lab before transfer day, and so stopping after transfer, or after implantation, or after a few weeks or a few months is an extension of this to varying degrees.

    First for the super-early stops. An egg contributes more to the embryo than just chromosomes. It has the proteins (microtubules) in place to effect the first cell division. It has the machinery for reading RNA and making proteins. It has pre-formed RNA made from the mother's DNA, and the proteins made from these RNA are more concentrated on one side of the egg or embryo and less concentrated on the opposite side and this difference in protein concentration is absolutely necessary for proper development. Different RNAs set up gradients of these early proteins in different orientations in the egg. The mother's genes and the way the egg has been set up internally have a huge influence on development up to 8 cell stage. The sperm is also important early on in a non-chromosome way - the first division usually produces one cell on the side of the egg that the sperm entered and a second cell of the far side of the egg. The cell closest to the site of sperm entry is more likely to go one to form the embryo, while the cell on the far side is more likely to form placenta. Any changes in these non-chromosome components can lead to changes (including stopping) in embryo development.

    Then after 8 cells the embryo starts relying entirely using its own chromosomes to direct protein production and growth, so obviously this is another potential stopping point. During growth the embryo needs to make different proteins depending on the stage it's at. So things might go fine up to a point, and then it needs to use a new protein and discovers that the DNA instructions for that protein are broken, so development will stop.

    Sometimes the damage isn't all or nothing, but instead results in a reduction in efficiency of embryo growth and development. If the emby happens to have a lot of little reductions to efficiency then the combined effect may halt all growth at some point, but the exact timing of that depends on which proteins are affected and also the importance of the affected proteins at that particular stage of development.

    Also, for some genes it depends on whether you inherit them from the mother or the father (genetic imprinting). If the proper imprinting pattern isn't applied to the eggs or sperm correctly then the embryo will try to use twice as much or none of some important genes and neither of those options end well. The effect on embryo growth will only be apparent when it is time to use those particular genes.

    The all-too-common miscarriage at the end of the first trimester corresponds with the timing of the ovaries handing control for maintaining the pregnancy over to the placenta.

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  13. #8
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    Thanks so much Lindy, Felicita & Starf1sh for sharing your info. I suppose it is a million dollar question after all as there are many variables that I hadn’t considered as to why embryo’s don’t implant.

    I don’t know why I have trouble believing my FS, she is lovely and is much more educated and has more experience with fertility issues than I do, but for some reason I still think I know more than her, go figure?????


 

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