Chat Transcipt: Carolyn Coulam, M.D. Unlocking the Mystery to Pregnancy Loss and Implantation Failure

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Chat Transcript
 Carolyn Coulam, MD 
Wed Jan 26, 9:00 PM Eastern Time

Jessie : How much of a factor does using frozen sperm with ICSI have on implantation rates.
Carolyn Coulam MD : Implantation rates depend on patient age and indication for IVF. In general the rate of implantation is the same for at least the first 3 cycles then decreases after that.
Markie : With a miscarriage at 10wks on the 1st IVF and no implantation on the 2nd IVF, are there any specific tests that you would recommend before doing a 3rd IVF cycle?
Jerri: How much of a factor does using frozen sperm with ICSI have on implantation rates.

Carolyn Coulam MD : Frozen sperm, if from a normal semen analysis, should not affect implantation rates. 
MaryKaye : With a miscarriage at 10wks on my 1st round of IVF and no implantation on the 2nd IVF, are there any specific tests that you would recommend before doing a 3rd IVF cy?
Carolyn Coulam, MD :If  we know the karyotype of the first miscarriage is normal we should look for both immunologic and thrombophilic risk factors

Mary Anne : Dr. Coulam, I recently miscarried at 8 weeks. The results of the chromosome testing showed Trisomy 7 and Turners Syndrome. I had a miscarriage 2 years ago but no studies done. I'm curious to know more about Trisomy 7.

Carolyn Coulam, MD : Trisomy 7 is lethal and should not be repetitive In other words "bad luck"
Frances : Can implantation failure be considered even if you had a pregnancy with heartbeat by detected by ultrasound, but then miscarried sometime afterward (especially in 1st trimester)?

Carolyn Coulam, MD : That is usually referred to as pregnancy loss rather than implantation failure.
Sara : Dr. Coulam, thank you for being here with us tonight.  How many IVF's are recommended for someone to have, for example I am 32 year old woman with mild to moderate endometriosis and have not had my initial IVF as of yet? This was a concern for us.
Carolyn Coulam, MD : How many would depends on why previous IVF cycles failed. If embryos are normal, then usually it takes 8 embryos transferred to get a 80% probability of pregnancy. 

Jennifer : A  friend of mine has had great difficulty stimulating and getting a pregnancy to go past 10 weeks. She is almost 40 at this point, with no specific issues determined. My friend has had all the standard testing is there anything you could recommend? Could the drug protocol she is on be affecting her egg quality?

Carolyn Coulam, MD : Egg quality is more likely related to age than stimulation protocol. She may want to consider PGD. http://www.inciid.org/article.php?cat=inciidinsights_issue11&id=22

Carrie : What can be done for a patient who has experienced several IVF cycles with implantation but then experiences a spontaneous drop in HCG level after a few days and the pregnancy ends very early?
Carolyn Coulam, MD : These are referred to as chemical pregnancy losses. Chemical pregnancy losses can be the result of a problem within the embryo or within the uterus. To read more about the different kinds of reasons for loss look at this article: Immunology may be key to pregnancy loss  http://www.inciid.org/article.php?cat=miscarriage&id=43 
Shelley : When should one consider immunologic testing and do failed IVF cycles with apparently good embryos count as pregnancy loss or implantation failure?

Carolyn Coulam, MD : Anything over 4 embryos transfered without success can be evaluated for risk factors for implantation failure.

Patti : Have there been any studies concerning the quality of embryos and use of ICSI? Are embryos created without ICSI of the same quality as embryos that left to be fertilized naturally?
Carolyn Coulam, MD : The results of the studies are conflicting, but the majority show no effect on implantation. There have been studies showing no effect with ICSI itself. There may be an effect if there is a male factor as the indication for the ICSI however.

Mary : do you recommend the use of low dose aspirin in helping to prevent miscarriage?
Carolyn Coulam, MD : Not routinely. Treatment depends on the risk factors present.
Linda : If one takes baby aspirin as part of the protocol, is heparin really necessary?
Carolyn Coulam, MD : Again it depends on the risk factor that we are treating. Read more about treatment options in this article: Immunology may be key to pregnancy loss

http://www.inciid.org/article.php?cat=miscarriage&id=43  
Sharon : My Re has told us that those who get pg once are more likely to get pg again. Do you find this to be true?
Carolyn Coulam, MD : In general, yes this is true. 
Nell : Thank you, I was wondering what is typically a "safe" number of IVF cycles. I have never had an IVF as of yet, my endocrinologist stated I am a candidate for it.
Carolyn Coulam, MD : IVF is a widely used and safe procedure. You theoretically could have as many as it takes to get pregnant. 
Kaye : Does an abnormal post-coital test (all sperm dead) have any predictive value as to the possibility of an immune problem in the woman?
Carolyn Coulam, MD : It can be either anti-sperm antibodies in cervical mucous or a problem with the sperm. 
Pauline : Thank you so much for being here to answer questions tonight. When you use the term “chemical pregnancy losses”  and discuss them as a possible problem within the uterus, would this include having a large fibroid? Could a large fibroid cause a chemical pregnancy?

Carolyn Coulam, MD : Yes it could if it protrudes into the cavity but usually these sub-mucous fibroids are associated with implantation failure rather than chemical pregnancy loss.
Helen: I have immune issues that were treated with IVIg during my 3rd cycle of IVF and subsequently, I  miscarried at 8 weeks (with Trisomy 7 and Turners syndrome). Also had another pregnancy 2 years ago where I miscarried at 8 weeks (no studies done). My last IVF cycle went very well I have 4 frozen blasts (2 with the HLA embryo marker and all either grade 1 or 2). I would like to do a FET, but am of course concerned about another miscarriage. I'm 35 and had  unexplained infertility up until Dr. Sher diagnosed me 6 months ago with immune issues.
Carolyn Coulam, MD : It sounds as if FET is your next step. 

Perry : How strongly do you consider the presence of moderate to severe endometriosis as evidence alone to do immune testing (particulary NK cells)?
Carolyn Coulam, MD : Individuals with endometriosis have autoimmune risk factors 65% percent of the time.
Julia : If I had a Endometrial function test and it came back saying everything was fine, could ther be other things affecting implantation? I'm 38 have done 7 IVF/ICSI , have i child from the 3rd cycle done at 34, put back many embryos that looked good, no other implantation except a small sac that reabsorbed when I did get pregnant. We have severe male factor, I have 7.5 FSH but need a lot of FSH meds. Trying to determine if it makes sense to keep trying and what the main factor for it not working is.
Cindy: Usually how many miscarriages does a woman need to have before testing will be done to try to resolve the reason?

Carolyn Coulam, MD : We believe testing should be done after 2 consecutive miscarriages. 
Lillie:  Good evening Dr. Coulam. I have had two unsuccessful IVF cycles and two unsuccessful IUI’s. I am 34 and my diagnosis is "unexplained" with mild endometriosis. In both IVF cycles I had 4 embryos transferred. Both times on day 3 my embryos looked to be between "good and fair" quality. What tests are available for "implantation failure" and do you feel my success rate is reduced? 
Carolyn Coulam, MD 
: I would suggest you may want to be evaluated for both immunologic and thrombophilic risk factors contributing to the failure. For more information about the tests included for implantation failure and Thrombophilia Panels you may visit the material on Implantation Failure on the INCIID Website. You might also look at http://www.millenova.com 
Nancy : Can a pregnancy loss trigger immune problems that might have not been there before? Carolyn Coulam, MD : Yes, it can.

Diane : I am  41 yrs old and have experienced  5 miscarriages with the longest lasting until 9 weeks gestation. I have been pregnant three times naturally and two others with IVF.  A D&C tissue test on one cycle showed a genetically normal male. We’ve done Kayotype and immune and blood disorders testing. However nothing comes back as abnormal. On my second IVF cycle, we transferred (cell 9,8,8,8,8,8) on day 3 used 40 grams of  IVIg; Prog. and 30 mg of Lovenox. We did not use PGD. I had a chemical pregnancy. Do you think it could have been an embryo issue or an implantation/environment issue? What would you suggest now?

Carolyn Coulam, MD : You should be evaluated for all of the risk factors contributing to failure  by both embryo and environment. For more information about all of the tests included in the evaluation, you may visit the material on Recurrent Pregnancy Loss on the INCIID website. 
http://www.inciid.org/article.php?cat=miscarriage&id=43
Barb: If an endometrial function test shows everything is fine and lining always looks good, could there be other implantation problems? 
Carolyn Coulam, MD 
: Yes, neither immunologic nor thrombophilic risk factors are measured by these tests. 
Karen:  Any tips on increasing the chances of implantation after IVF? 
Carolyn Coulam, MD 
: First we must identify the problem before we can recommend treatment. A thorough evaluation would be helpful.
Donna : Does stimulating the ovaries with gonadotropins again and again make you use your egg reserve faster? I know this may sound sill but I ask because my day 3 FSH went from 5.6 to 10.9 in 2 years after my first IVF cycle and I'm only 30 years old.
Carolyn Coulam, MD : No stimulation does not recruit more eggs to the cohort. It maintains growth of more eggs within the recruited cohort. 
Elizabeth :Are the autoimmune risk factors tested by through blood serum? 
Carolyn Coulam, MD 
: Yes, immune risk factors are tested in blood. Ready

Gwyndolyn: What tests are involved to confirm "autoimmune risk factor" for endometriosis? Carolyn Coulam, MD : Testing the following autoantibodies is recommended:

  • APA, (Antiphospholipids)                                  
  • ANA, (Antinuclear Antibodies)
  • ATA,  (Antithyroid Antibodies)
  • LA. (Lupus Anticoagulant)
  • Also NK (Natural Killer) cells and
  • Circulating Embryo Toxins 
     

Annie :  I am 41 years old and have experienced  5 miscarriages. The longest pregnancy lasted to 9 weeks. Three of them were naturally conceived and two were through IVF cycles.  I had a D&C tissue test with one. The finding with this pregnancy was of a genetically normal male. Karyotype Tests: Normal Female & Normal Male. Would PGD be useful? What is the PGD risk versus the reward? Do you recommend doing a two vs. one cell testing with PGD? 10 vs. 5 probe? 
Carolyn Coulam, MD 
: It depends on the number of embryos available. If sufficient number of embryos are available for selection, then PGD can be helpful. Usually 2 blastomeres are more accurate than one but not always available.

Betty : I tested positive for MTHFR (methylenetetrahydrofolate reductase) after I found out I was pregnant. I was put on Heparin twice a day. I have since miscarried due to chromosome abnormality. Going forward would it be important to start Heparin before getting pregnant? Also, I read about taking higher levels of Folic Acid (Folgard). What are your thoughts? 
Carolyn Coulam, MD : If MTHFR is your only risk factor then treatment with folic acid and vitamin B should be sufficient.
Harriet: Can you explain the triggered immune problems following a m/c?
Carolyn Coulam, MD : Sometimes, but certainly not always, the antigen that triggers the immune response if present in the pregnancy.
Tammy: How is the best way to go about finding a reproductive immunologist if my RE doesn't do much immune testing? I want to make sure based on my history, that the right tests are being ordered.
Carolyn Coulam, MD : It depends on where you live. If a reproductive immunologist is not available to you we can arrange a telephone consultation for you. (Editor’s note: If you are having problems finding a reproductive immunologist, please email us and we will try to help you find someone either in your area or through consultation. Email INCIIDinfo@inciid.org )

Zoe: I’ve put back 40 embryos over 7 IVF cycles, and only one became a baby. Are there other things to look at regarding implantation if the EFT was normal? Or is it more likely that the problem lies with our severe male factor or possibly ovarian reserve? I usually get 5-9 eggs and they almost all make it to blastocysts and look good.
Carolyn Coulam, MD : It could be either a sperm or egg contribution, but if you are transferring blastocysts and they are not implanting, we should really look at the environment (of the uterus). 

Joy:  I’ve been fully evaluated for immunologic and Thrombophic as well as Karyotype genetics. All have come back normal. We’ve experienced 5 miscarriages (two IVF cycles, one with IVIg abd three natural conceptions.) What would you suggest now?
Carolyn Coulam, MD : There are some new genetic tests for genes related to miscarriage such as HLA G mutation and  MYC/RPL from the sperm. Please visit the Millenova Immunology Laboratories website for more information about these tests:http://www.millenova.com .

Roberta: How likely is a person with multiple living children to have anything of significance found on a recurrent pregnancy loss work-up.
Carolyn Coulam, MD : It depends on the history of the pregnancy losses, but in general not as likely as individuals with few children. 

Mary:  Thank you Dr. Coulam. I had problems with "unexplained brusing" a few years back and had much blood work done. Do you think this could have anything at all to do with my implantation problem? for your time. 
Carolyn Coulam, MD 
: Not really. Implantation failure is manifest by either negative pregnancy test of chemical pregnancy loss. Ready
Barri:  Hello Dr. Coulam.  I just turned 39 and have been trying to get pregnant for over a year and a half. We’ve done extensive testing in all areas and have had 4 pgs, (1 chemical) during this time. Right now  I am in the midst of an IUI cycle. I started with 6 follicles, looks like 3 may mature At what point do we do go to IVF with PGD? Or do we use a donor’s egg? I am concerned about waiting until my chances are worse and of course insurance doesn't cover IVF or Donor’s Eggs.

Carolyn Coulam, MD : How you proceed depends on the individual need and indication for IVF. You should really discuss this with your doctor who knows you condition. 

Sherry : We've tranfered many good looking blastocysts and all our immune testing and EFT came back fine. We do have severe male factor, and takes a lot of stimulation to get the eggs. I do not have endometriosis or anything noticeable from the lap, except "old looking" ovaries (sort of looks like a brain) I'm 38. Do you have any suggestions for me?
Carolyn Coulam, MD :  Regarding male factor, there are 10 gene mutations that we now check for. You may get this list from the website of Millenova Immunology Laboratories at millenova.com.

Melody:  What are the risks of IViG to mother as well as fetus?
Carolyn Coulam, MD : Side effects usually occur during the infusion and can be uncomfortable. Also one can experience migraine headaches for 1-4 days after infusion. There is a theorectical risk of transmittable disease but there has never been a report of HIV transmission. There appears to be no effect on the baby. 
Erin: What symptoms or history would suggest I may have immunological problems?

Carolyn Coulam, MD : A history of recurrent pregnancy loss or implantation failure after IVF. Or a history of blood clots.

Susan:  Is a Leukocyte Antibody supposed to be positve when you are pregnant? How does this work? 
Carolyn Coulam, MD 
: Mothers can develop antibodies to fathers leukocytes as a result of exposure from pregnancy. But these antibodies have no detrimental effects. 

Lisa: At what point does one go to IVF with PGD or donor egg? 
Carolyn Coulam, MD 
: Donor egg would be indicated if you could not generate normal embryos with your own eggs. 

Liz : Are you familiar with studies that show IVF with PGD in women over 36 is less reliable or successful for recurrent pregnancy loss? 
Carolyn Coulam, MD 
: No, When PGD is done for patients with a history of recurrent pregnancy loss more abnormalities have been found and hence less embryos transferred. 

Vera: What is the difference between antibodies and natural killer cells?

Carolyn Coulam, MD : APA, ANA, ATA and LA are all autoantibodies. NK cells are white blood cells that are involved in the first line of immunity. For more information about each of these tests, Read the INCIID fact sheet on immunological problems causing miscarriage and implantation failure:

Bobbie:  Besides eating a healthy diet are there any foods, vitamins, or minerals that have either a positive effect on implantation or a negative effect causing implantation failure. I have heard certain things such as peanuts may hinder implantation but how much of an effect do these things have? 
Carolyn Coulam, MD 
: I’m not aware of any foods that hinder implantation.

 

Carolyn Coulam, M.D. is an INCIID Advisory Board member and answers questions for consumers regularly on the IMMUNE ISSUES and MISCARRIAGE Forums here at INCIID.

 

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