Tuesday, December 7, 2010

Placental pathology results

(pic brought to you by whywouldyouknitthat.blogspot.com)

Not sure if I mentioned it, but after our most recent miscarriage, my RE here in NYC recommended we send slides from the chorionic villi to a placental pathologist at Yale for review (the same guy who performed my endometrial function test).

So we did.

Once I looked into it, I found out that this placental pathology analysis would be covered by insurance, and so I decided to send slides from not only this miscarriage but also from the other four we've had tested.

Results just came back. All of the reports are similar in saying that there were various findings that provided evidence of chromosomal abnormality (including this latest one with the CCS normal blastocyst, which demonstrated trophoblast hyperplasia - it will be so interesting to see what the genetics come back as). All of the losses also demonstrated that maternal uteroplacental blood flow was normal.

All of the miscarriage reports also report what was NOT found:
  • no evidence of immunologic rejection
  • no evidence of bacterial ascending infection
  • no evidence of thrombotic pathology
Not sure if I want this latest loss to be a chromosomal abnormality that somehow slipped through the cracks or rather have it unexplained. Pretty much would rather not be in this situation at all! I guess the best I can come up with is that it will be good to get the information back and then try to make sense of it.

On the placental pathology report from the latest loss, there was one section that has me a bit confused.

Any medical types are most welcome to weigh in...

On this last report only, the pathologist said "this patient and/or her spouse may also have an occult genetic abnormality. A genetic consultation, including high resolution karyotyping and array analysis of the parents, may therefore be beneficial."

Now what in the world is an occult genetic abnormality? I'm assuming here that word occult means "hidden," rather than "supernatural." Aren't one's genetics always hidden?

Is this different from a "regular" genetic abnormality?

And what is high resolution karyotyping and array analysis? is this different somehow from the type of karyotyping we've had done already? We both came up as genetically normal...

Anybody have any thoughts or knowledge?

Feel like I'm starting to emerge from my cave of sorrows, pick myself up again, and try to figure out next directions. Geesh, this loss and all else going on have been hard.


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  1. If the testing is available for you...go for the higher resolution karyotype testing. Something is not right...especially since this embie was CCS'd. It will be interesting to hear what CCRM's Dr. Mandy Katz-Jaffe would have to say...that's who we spoke with regard to my abnormal karyotype. This woman is a genius.

  2. Hmmmmph. I know nothin' 'bout occult genetic abnormalities, but I'll be interested in hearing what it turns out to be. When do the genetic tests come back, anyway?

    You around this week? Give me a call when you get a chance. We'll go xmas shopping or sit around and chat while we knit placentas, (great website, btw), or go out to eat or something.

    Thinking of you.

  3. Have you already had your own genetics analyzed? Forgive me, I don't recall ... it may have been before I started following ....

    You all would know more about this than I, but would something like a "balanced translocation" ... the kind that this blogger's partner has ... http://booferd.blogspot.com/ ... a genetic abnormality that does not affect her husband himself, but which affects his gametes and has a high probability of becoming unbalanced in his offspring ... would that be considered an occult genetic abnormality? Have you ruled something like this out? forgive me if I'm way off here.

    My best thoughts and wishes are with you.

  4. I'm wondering..when we had our karotypes done the analysis indicates that not all translocations will be readily apparent. When we talked with the geneticist (I have a BT) I believe he indicated that some BTs are very small and may not be picked up through the regular karotyping process. Perhaps this is what it refers to---those genetic abnormalities which are too tiny to be picked up without the high resolution process? Could be completely wrong, but it seems like a good guess.

  5. I am not a medical type but two things come to mind reading your post.

    1. I had a friend who had repeated pregnancy loss which was discovered to be due to a genetic problem that (I think) her husband was passing on - it was not evident in the karyotyping they had each had during rec miscarriage testing and only showed up in the embryo at a particular stage. My memories of this are vague and I'm not in touch with this friend anymore, so I can't check it out. But I do remember her saying that their own genetic testing and genetic testing of embryos would not identify the abnormality - it was a matter of trying to get pregnant and waiting to see if it hung in there.

    2. I have had 6 losses and a few failed treatments myself, including one with a normally testing egg. When I spoke to the Prof in charge of my new clinic (where we successfully did a cycle with DE), he told me that the genetics of an egg can test normal, result in an initially normal embryo, but the cytoplasm (?) of the egg can be poor quality (he described it as the fuel and glue to the genetic division process) and lead eventually to a fault in the replication of the genetic info of the embryo. Basically the blueprint and initial materials (the genetic information in the egg) is sound, but the cement is faulty! It certainly seems that this was our issue.

    I really hope you get some answers!

  6. Mo, I'm a pediatrician with expertise in genetics.

    Have you and Will had a microarray done?

    Microarray is different from chromosomal karyotype. It will pick up deletions, rearrangments, etc... The chromsomal karyotype should be a high resolution G-band analysis of chromosomes at the 650 band level. Look at your chromosomal report-- it should say "650 band".

  7. Genetics are the great unknown. My first daughter was the result of genetic abnormalities. That is as far as I ever took it. I was in a different place at that time. I wish I had more answers now.

    I followed the advice of my doctors who told me I would very likely not get any additional information from performing an autopsy on her. I couldn't bear the thought of the intrusion. I would make the same choice again, but the lure of potentially getting information is great. I only hope they can actually produce something.

    I am glad to see you surface.

  8. It just means, I think, that whatever it is, its at below the detection sensitivity of the tests you have done so far. Our tests are pretty crude and can only pick up so much :(

    Following the suggestion of a pediatrician who works with geneticists (her blog is the 'Baby Chase project') I sent my baby's DNA for SNP microarray analysis- is that what they are referring to?

    You do need to consult with a geneticist. I'm going to do the same when I get back, as well.

    Genetics are pretty much the final frontier, and the tools we have are too crude:(

  9. My understanding of an occult genetic abnormality, is that there is not the usual type of genetic abnormalities (like extra chromosome or a part of one chromosome moved to another), but that there might be some errors in gene expression or something like that.

  10. Mo,

    How completely frustrating to have a potential genetic issue slip though the cracks. Yes, from the very meager sources that mention this phrase, it seems that "occult genetic problems" are those that standard tests don't (yet) pick up on. So, something "unusual" so to speak. (Wonder if many single gene tests would fall into this category?)

    http://en.wikipedia.org/wiki/Occult has a short part on how occult is defined medically.

    Dr. K is great at emailing patients back...please just send him a note and I am sure he can explain the results more clearly for you himself. Or, call directly - his assistant can hunt him down and ask.

  11. Second attempt to post a comment - last one seems to have gone astray.

    I am not a medical type but two thoughts occur as a result of your post.

    1) I had a friend I met through a rec miscarriage support group who had repeated losses that were a result of some kind of hidden genetic problem that she or her husband were passing on to the foetus. It did not show up on their individual karyotyping they had done as part of their miscarriage testing, nor could PGD help as the abnormality only showed up at a certain point in the development of the foetus. Their only solutions were to take pot luck and keep trying or go for donor eggs, sperm or embryos. By good luck, their next try worked.

    2. I've had 6 losses myself and a few failed treatments, including one with an egg that tested normally on CGH array. When I spoke to the consultant at my latest clinic (where I ended up doing a successful IVF with donor eggs), he told me that eggs and embryos can initially test normal, but if the cytoplasm (?) in the egg is not good, then the embryo can eventually become genetically abnormal through faults occurring in replication. Apparently, this stuff (the "egg white", I think he analogised it as) is what fuels the division of the embryo and "glues" the genetic information together. It can be faulty, especially as women get older, even in eggs whose chromosomes test normal. This certainly seems to explain what happened to us.

    I do hope you get some answers!

  12. Sorry that you're having to muddle your way through all of this... hopefully once all the testing is in, you'll have a better picture of where to go from here. I will be very interested to hear what CCRM thinks.

  13. Hi, i am sharing this information as i have been in your position and faced with the same report. I have had my losses analyzed by the same Dr. He put the same comments in each of my reports- the occult genetic and the high resolution karotyping. I have two other friendship who have had losses analyzed as well and he put the same comments in their reports. I asked a genetic counselor about the high resolution karotyping and was told that is what karotyping is, and how it is done. I asked my MFM Dr. and RE about the occult genetic issue and the" coin flip" or 50/50 chance of the occult genetic issue reoccurring, all of them were dismissive of his conclusions on this point, noting that this was rare and unlikely. In addition, one pointed out that they like his reports for ruling out certain issues, but his basis for his conclusions such as the occult genetic issue are based on studies that were conducted by him. This seems to be boiler plate language that is in each of his reports. I am sharing this with you just you have some information. I hope it helped. I am sending from my telephone so sorry foe typos. Lynne

  14. I have no idea about any of this, I just hope you get some concrete answers soon.

  15. Mo, I forgot to tell you. If you have genetics questions or would like curbside consult with genetics stuff, feel free to contact me. I would be happy to help you in any way I can.. Hugs.

  16. Wow. Frustration reigns.

    As a previous commenter mentioned, I also thought of a balanced translocation.

    But the point of the microarray is to test the level of expression of different genes. If the array finds twice as much of a gene product, that would indicate a duplication of genetic material. If the array found no gene product, that would indicate a deletion. Depending on the size of the duplication/deletion, the karyotype could still test normal (because the resolution may not be high enough).

    I think the difference (between karyotype and microarray) is that the karyotype is like looking at the volumes of an encyclopedia- are A through Z present? Do they look to be the right size? etc.

    The microarray actually checks the contents of each volume to see how they are organized, how much of the various contents are present, etc.

    A karyotype may not pick up on small changes- but those small changes could be crucial to an embryo.


    Praying for some clarity.

  17. I just wanted to say Ive been thinking about you!

  18. I am a new reader but I would just like to say, you impress me with how strong of a woman and couple you are. My husband and I had miscarriage number 4 in February, and after just two years I am wondering how we will stay strong if the next two are the same. But Mo and Will, you give me hope that we will prevail in this awful journey. Thank You for writing.


  19. I have no idea what that means, but I wanted to offer thoughts, prayers, and hugs.

  20. I'd ask the doctor, or have your primary doctor ask, just to make sure. To me it sounds like an undiscovered genetic issue -- whether that is because current tests cannot pick it up, because it's an unknown mutation or because you simply haven't been tested for it, I don't know.
    I hope you get some more, and helpful, answers soon. Thinking of you.

  21. wow....'occult' is NOT a word you want to hear from your Dr!

  22. 'Lawsie, Ms. Mo, I don't know nothin' about occult genetic abnormalities', however, I do want to wish you the best and say that I hope that you get clarity on this soon (and if it is a balanced translocation, is that something they can test the remaining embryos for?) Also, you are continually in my prayers both as you grieve the loss of your baby and your other personal upheaval. On the bright side, it's good information to know that there's no evidence of rejection, infection or thrombotic pathology... Hugs from here.

  23. "Occult genetic abnormalities" refers to chromosomal abnormalities that are not detectable by current standards. Common karyotyping methods like G-banding only show prominent structural changes and thus smaller structural changes can go undetected. Potentially it only takes one base pair of a gene to be incorrect for a problem to happen - that is a tiny change.

    It's not different from a regular abnormality, per se. It's just referring to undetectable abnormalities.

    Definitely head towards high resolution karyotyping if you can afford to - higher resolution means better detection of structural changes to the chromosomes.

    I hope you get lucky soon Mo.


  24. PS when I said 'methods like G-banding' I meant the lower resolution G-banding techniques. (I wasn't disputing anything BabyChase said.)

  25. Thinking of you two everyday. I don't know what most of the post means, I'm sorry. I do know that you two are very special people and you will get through this. Hugs


  26. hang in there. you two are incredibly strong. i can't imagine how hard all of this has been.

    wishing you all the best

  27. I've been through the gamut with 4 miscarriages myself...I'm wondering if one of you could have a genetic translocation?

    Have the doctors talked anythinga bout that?

  28. Hey, Mo. Thinking of you and awaiting your return. I hope you're finding small moments of peace, in the chaos and grief.

    I'd like to start that colorado cocktail of claritin/pepcid (I'll push Dr. G on the steroids when it comes to DE). Would you mind letting me know your doses? Also curious about your experience with the endometrial function test; would you recommend doing it? I appreciate whatever thoughts you have. Feel free to email me at gwinne (at) yahoo (dot) com. Thanks!


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