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  1. #1
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    Default Recurring chemical pregnancies - any advice?

    Hey all,

    I had my 3rd chem pregnancy this month, with a HCG of 36 at 10dp5dt. Can anyone recommend things I should discuss with my fertility specialist in terms of treatment? I'm at a bit of a loss at to which of the many factors that cause chemical pregancies are at play here, and I'm curious about how others have approached it.

    Complicating factors:
    1. PCOS diagnosis.
    2. Older sister (who has a DS via IVF) has endometriosis and high NK cells, neither of which I've been tested for but might be an issue given both are hereditary.
    3. This last cycle the embryo was fantastic quality, lining was great, progesterone was a bit on the low side but still within the range they'd be happy with (and I had plenty of progesterone support during the cycle - PIO shots every second day, pessaries every night).

    Should I push for more progesterone support, or has anyone had any luck with preemptive treatment of NK issues? What other tests can I request?

    Thanks in advance. Our appointment with our specialist is this Thursday and I want to go into it prepared and ready to fight for our last remaining embryo in August!

  2. #2
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    Sorry hon. Chemicals are frustrating xx

    1) I would suggest getting thoroughly tested for immune/implantation/clotting issues. This is my list of blood tests (mostly bulk billed, some clinics or labs may charge ~$250 max total).

    MTHFR c665C>T and c1286A>C
    Factor V Leiden
    ACL Anticardiolipin antibodies
    ACA
    ANA Anti nuclear antibodies
    Anti sperm antibodies
    ATA anti thyroid antibodies
    Prothrombin gene mutation
    Activated Protein C resistance
    Protein C thrombosis screen
    Protein S thrombosis screen
    Homocysteine levels
    TFT Thyroid function test
    Glucose tolerance test
    Vitamin B1, B6, B12, serum folate
    Lupus anticoagulant

    NK cells:
    CD3-56+
    CD69+(CD55) ‘Dim’NK cells
    CD57

    Not all FS believe in immune issues so try your FS and see if they’ll run the tests. If not you could see Dr M (Gamal Matthias)- he’s a reproductive immunologist and obgyn based in Sydney but does Skype consults nationwide. He’ll do extensive testing and tailor a plan to add on to your FS protocol to treat any immune issues. You can find out more about him on the series of “Natural killer cells” threads here on bubhub. If you are in Perth there’s a specialist there (Dr Saba) or in Melbourne (Nick Lolatgis) who are also pretty into immune stuff.

    I am a huge fan of Dr M! I have high NK cells and MTHFR diagnosed by FS. Dr M then picked up high ANAs and autoimmune markers, plus spotted that my NK cells weren’t responding to the basic meds so he switched up my protocol.

    2) Consider having a laparoscopy to check and remove endometriosis. There’s a good chance you could have endo. Again mixed views, some FS say just go on steroids to manage any inflammation it may be causing (which impacts implantation) and don’t worry about the endo. I figured I had a few issues the steroids were trying to combat so decided it was best to have the endo removed. If you have a lap, ask them to do a hysteroscopy and NK cells biopsy at the same time (some women have high NKs in uterus but not in blood or vice versa).

    3) If you are clear of immune issues then the other option is PGS testing to check embryos are ok.

    Best of luck!

    R

  3. The Following User Says Thank You to Risa78 For This Useful Post:

    Toebeans (22-07-2019)

  4. #3
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    Oh and yes ask for higher progesterone!

    Dr M increased mine to 1200mg of pessaries for my own egg IVF cycles. I’m now doing donor egg and i take a 100mg PIO shot daily + a 400mg pessary.

    R

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    Default Recurring chemical pregnancies - any advice?

    Following as potentially having my second chemical in a row..
    Last edited by amiracle4me; 22-07-2019 at 18:58.

  6. #5
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    Really sorry you find yourself here, it’s pretty awful. I had 3 in a row, 1 fresh then 2 frozen perfect hatching day 5 blasties. I did all the tests as mentioned above, and my NK cells came back as slightly elevated after an endo scratch.

    I think what got me over the line was steroid/clexane protocol. I took prednisone and that frozen cycle I fell pregnant with my second son.

    I was 31 at the time so age didn’t seem to be a factor.

    It’s usually either a lining/implantation issue or you might need PGD embies in case there is an issue there?

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    Toebeans (24-07-2019)

  8. #6
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    Quote Originally Posted by Risa78 View Post
    Sorry hon. Chemicals are frustrating xx

    1) I would suggest getting thoroughly tested for immune/implantation/clotting issues. This is my list of blood tests (mostly bulk billed, some clinics or labs may charge ~$250 max total).

    MTHFR c665C>T and c1286A>C
    Factor V Leiden
    ACL Anticardiolipin antibodies
    ACA
    ANA Anti nuclear antibodies
    Anti sperm antibodies
    ATA anti thyroid antibodies
    Prothrombin gene mutation
    Activated Protein C resistance
    Protein C thrombosis screen
    Protein S thrombosis screen
    Homocysteine levels
    TFT Thyroid function test
    Glucose tolerance test
    Vitamin B1, B6, B12, serum folate
    Lupus anticoagulant

    NK cells:
    CD3-56+
    CD69+(CD55) ‘Dim’NK cells
    CD57

    Not all FS believe in immune issues so try your FS and see if they’ll run the tests. If not you could see Dr M (Gamal Matthias)- he’s a reproductive immunologist and obgyn based in Sydney but does Skype consults nationwide. He’ll do extensive testing and tailor a plan to add on to your FS protocol to treat any immune issues. You can find out more about him on the series of “Natural killer cells” threads here on bubhub. If you are in Perth there’s a specialist there (Dr Saba) or in Melbourne (Nick Lolatgis) who are also pretty into immune stuff.

    I am a huge fan of Dr M! I have high NK cells and MTHFR diagnosed by FS. Dr M then picked up high ANAs and autoimmune markers, plus spotted that my NK cells weren’t responding to the basic meds so he switched up my protocol.

    2) Consider having a laparoscopy to check and remove endometriosis. There’s a good chance you could have endo. Again mixed views, some FS say just go on steroids to manage any inflammation it may be causing (which impacts implantation) and don’t worry about the endo. I figured I had a few issues the steroids were trying to combat so decided it was best to have the endo removed. If you have a lap, ask them to do a hysteroscopy and NK cells biopsy at the same time (some women have high NKs in uterus but not in blood or vice versa).

    3) If you are clear of immune issues then the other option is PGS testing to check embryos are ok.

    Best of luck!

    R
    Thank you for such a thorough answer, this gives me a lot of conversation points for my appointment with my specialist tomorrow. Forgot to mention in the original post that I had blood tests that showed I had the MTHFR gene. Wasn't entirely sure what that meant for falling pregnant, all my specialist said was I'd need to double up on my folate as my body struggles to absorb it. I don't think those blood tests included NK cells, so I'll raise the issue with her. If she isn't super keen on immune issues I'm not stressed, I'm with Melbourne IVF and there are a ton of other specialists I can speak with for a second opinion. I can only try, right?

    Is the laparoscopy very invasive, or is it quite a quick surgery? I ask because I'm recovering from a nasty bout of flu/bronchitis and I'm not sure my body is up for a big procedure. The laparoscopy would answer a lot of questions, it's just a matter of whether I proceed with a cycle with our final embryo and then do the lap, or squeeze one in before the next cycle.

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    Quote Originally Posted by Clementine Grace View Post
    Really sorry you find yourself here, it’s pretty awful. I had 3 in a row, 1 fresh then 2 frozen perfect hatching day 5 blasties. I did all the tests as mentioned above, and my NK cells came back as slightly elevated after an endo scratch.

    I think what got me over the line was steroid/clexane protocol. I took prednisone and that frozen cycle I fell pregnant with my second son.

    I was 31 at the time so age didn’t seem to be a factor.

    It’s usually either a lining/implantation issue or you might need PGD embies in case there is an issue there?
    Thank you for your response, it is pretty awful! I've got a personality type where I like to know the answers to every problem, so the ambiguity of all this drives me batty.

    I'll be asking my specialist about prednisone for the next cycle, even without a definitive NK cell diagnosis. She had me on Clexane this last cycle (as well as PIO, pessaries, aspirin, and Metformin) and in a sense the protocol worked. I did FALL pregnant, bub just didn't hang around.

    Any idea what stage they can do PGD testing? I've got one embryo left in storage, is it too late to do testing?

  10. #8
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    Ok so to try to answer some of your questions:

    MTHFR is a bit complicated and unfortunately quite misunderstood by many FS’s.

    Do you know what your MTHFR results are? There’s 2 genes and for each you can be either
    - ‘homozygous’ (2 mutated copies of that gene)
    - ‘heterozygous’ (1 mutated copy, 1 normal copy of that gene).
    - There’s also ‘compound heterozygous’ which means you have one mutated copy on both of the MTHFR genes. I have this one.

    If you are homozygous or compound heterozygous that’s when MTHFR can have an impact. Heterozygous for one isn’t such a concern.

    Basically the body has to convert folic acid (the artificial form in most vitamins, added to milk, cereal, bread etc) into folinic acid and finally into methylfolate (which is the natural form the body can then use). This process is caused methylation. With MTHFR your body has a reduced ability to convert the folic acid into usable folate, which could lead to folate deficiency. It is also associated with increased clotting which can increase risk of implantation/miscarriage.

    Treatment
    - Traditionally most FS’s prescribe higher dose folic acid. However this can be counterproductive and taking active folate may be better
    - Clexane to reduce clotting risk

    Why is higher dose folic counterproductive?The logic used by most FS’s is if you can’t convert folic acid well, you need to take more to end up with sufficient levels. So they prescribe 5mg folic acid. However when you look at how methylation works the body basically has a set number of ‘receptors’ floating around in your blood. The folic acid hitches a ride on these receptors to gets to where it needs to go. If your body can’t convert it, then it keeps floating around blocking those receptors - which means when you say eat spinach and get real folate your body can’t absorb that either if all the receptors are blocked by the folic acid. All the while you’ll likely show great folate numbers in blood tests because of all that extra unconverted folic acid floating around in the blood. So it can actually be counterproductive and hide a deficiency. In recent years, you can now buy vitamins and supplements with the active forms of folate - either methylfolate (fully converted) or folinic acid (partially converted).

    B vitamins
    The body also needs high dose of B vitamins to help absorb and use the folate. Again it’s best to take the active form of Bs as MTHFR means you can’t use the artificial Bs very well either.

    The tricky bit!
    - There is no definitive answer to what the equivalent dose is of how much active folate to take. I’ve been told 1mg by my reproductive immunologist (Dr M) and “I don’t care what type of folate as long as you take 5mg” from my FS. I personally ended up hedging my bets in the middle and take around 2-2.5mg a day of active folate
    - Start on max 1mg of methylfolate and if you want any extra dose take that as folinic acid. Over time you can slowly switch this over to methylfolate - but if you go into a high dose straight up you can get side effects (I got shaky and agro!). Give your body time to get used to it and build it up slowly.

    Here’s some forms of active folate available:

    Prenatal
    - avoid all the big brands like Elevit etc with folic acid and artificial Bs
    - Eagle Tresos Natal (a prenatal with 500mcg of active folate as a mix of methylfolate and folinic acid). Also has some active Bs. I use this one because it’s 1 a day. Some of the below are 6 a day!
    - Bioceuticals - I believe they now have one with active folate and it might also be 1 a day
    - Optimal Seeking Health - Mail order from their website in US
    - Thorne Basic Prenatal - available on iherb

    Methylfolate
    - Thorne Methylguard Plus (1 a day - this has 1mg methylfolate and gives the extra dose of active Bs). Available on iherb.
    - Solgar Methylfolate (various doses and great price). Available on iherb
    - Bioceuticals MTHF (500mcg?)

    Folinic acid
    - Bioceuticals Folinic Acid (500mcg)
    - Megafolinic (800mcg) on iherb.

    Bioceuticals and Eagle available at health stores/some pharmacies.

    Sorry for the essay but MTHF is a complex one to explain! More info available on the Natural Killer Cells threads on here or at MTHFR Australia website.

    R

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    Quote Originally Posted by Toebeans View Post

    Is the laparoscopy very invasive, or is it quite a quick surgery? I ask because I'm recovering from a nasty bout of flu/bronchitis and I'm not sure my body is up for a big procedure. The laparoscopy would answer a lot of questions, it's just a matter of whether I proceed with a cycle with our final embryo and then do the lap, or squeeze one in before the next cycle.
    It’s a day surgery with usually 3-5 small keyhole incisions (belly button, plus a couple more dotted around lower abdomen). But it depends what they find and where. If they don’t find anything it might take <1hour. Mine they found severe endo (stage IV-V) and some of this was near the bowel and ureter (more complex to remove). So it ended up taking a few hours and I had to stay in hospital overnight. I came home from the hospital with a cold and gastro (bad luck it was going around at the time!) but that meant a bit of a slower recovery. I took 3 days off work 1 for surgery 2 for recovery. I worked from home day 4 but was useless because of the virus.

    I’d be inclined to get over your flu before doing a lap based on my experience. Also need to ensure it’s timed in the right phase of your cycle. Best time is around CD21 and they can do a hysteroscopy to check out your uterus too at the same time (check for polyps, fibroids and do an NK cells biopsy to see if NK cells present around implantation window).

    R

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    PGD is best done at day 5 before the embryo is frozen.

    If an embryo is already frozen they can thaw it, test it and refreeze. But that’s a lot for an embryo to go through and you could risk an otherwise ok embryo running out of puff. Since you only have one, I’d say just transfer it as is and if it doesn’t take and you have to do a new cycle do PGD before freeze.

    R


 

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