Education, Infertility, Miscarriage

The Survival Guide to Recurrent Pregnancy Loss and Testing

March 29, 2011

What to do after you’ve had more than one miscarriage, especially if you’re also having trouble conceiving

I’m writing this post for all of you out there who have now had more than one miscarriage and want to know what to do and which tests to get.  You’re sad and overwhelmed and tired of hearing about how you just had bad luck.  I am writing what I wish I had read two miscarriages ago. I have since done tons of research, compared notes with many others going through this, have consulted with several doctors and I am still learning.

You are now a habitual aborter in clinical terms.  I tell you this so you are not surprised when it shows up on your paperwork.  Your situation is now called “repeat pregnancy loss” or “recurrent pregnancy loss,” or RPL for short.

My situation

I had a natural pregnancy and miscarriage and after 1.5 years trying.  Then, I was diagnosed with a uterine septum and had surgery to have it removed.  Then in my pre-IVF workup, I was diagnosed with luteal phase defect, which is treated by normal IVF protocols.  Then I had another miscarriage.   At that point, my doctor did genetic testing (karyotyping) for my husband and I and did other RPL tests for me.  This is where I wish I had known more and demanded even more tests. However, the tests revealed that I had Factor V Leiden, which is a clotting disorder.  At the time, when I got the clotting disorder diagnosis, I thought that we had finally found the problem.  I’m not sure why I thought that since it was the third problem we had found.  Why wouldn’t there be more? I was subsequently treated for my next three IVF cycles by taking Lovenox, but two of those cycles resulted in two more miscarriages.  So we have to assume that something else is going on.  I consulted by phone with another doctor who ordered a full immune work-up for me.  It showed some strange results indicating that I do have autoimmune issues, but it’s not really something they know how to treat. If I had activated natural killer cells, there is a treatment for that.  But, my results were on the fringe, as always.  First, he told me it could be treated with intralipids and later retracted that said it couldn’t.  See more here.  We ended up using gestational surrogacy to build our family as I was done with my body.

When to get testing?

Many doctors will suggest RPL testing after two miscarriages.  For some doctors and states, the protocol seems to be after two and for some, it could be three. If you’ve had one miscarriage, then testing usually isn’t advised because many normal, healthy women have a miscarriage, but go on to conceive just fine.  However, if you’re not concerned about insurance coverage or costs, then go for it.

How much testing to get?

Here is why I wish I had known more earlier.  I would suggest testing for everything that you possibly can NOW.  Even if it’s overkill, I think that’s better than the alternative, which in my case is four pregnancies and four miscarriages.  They seem to want to do a little testing, you have a miscarriage, then they do a little more testing, you have another miscarriage and so on. If you are worried about this, save yourself lots of heartache and test for everything now.  One potential issue is money.  See below for that.  Another issue is that your doctor may not “recommend” testing for all of this.  Too bad!  Tell him you want it done.  Or, if he doesn’t know enough about it or won’t do it, see a new doctor immediately.

RPL workup

If your doctor doesn’t suggest testing, then advocate for yourself and demand it.  Each doctor has their own set of tests they like to do for a RPL workup.  Some are more thorough than others.  So, ask which ones you will be tested for.  Do your research.  If some things aren’t there that you think should be, ask about them.  Many times, your doctor might just be doing genetic testing, which is called karyotyping.  This would be done for both partners.

Financial Aspects

I have no fertility coverage through my insurance, except for diagnostic purposes.  So, luckily most of my tests have been covered.  Even if you think you are not covered, like I did, pursue it and find out.  The process for me to get pre-approved took 3-4 weeks and was a pain in butt, but worth it.  Even if they are not, why would you spend thousands on IVF after having several miscarriages, only to skip paying a couple hundred or thousand dollars to potentially guide your treatment instead of risking yet another miscarriage?

Something else to consider if you need to save money is to skip the karyotyping (the genetic testing) which costs a lot and get all of the other blood tests at least. I’m not saying you shouldn’t get it, but if you can’t afford it, at least get some of the other basic blood tests that are cheaper. Also, it depends on your situation.  If you’ve had fetal tissue tested from a previous miscarriage that indicates a genetic problem, you would really want to do it.

Problems that could be causing miscarriage

  • None - you could truly have bad luck. Especially at the 2 miscarriage stage.
  • Hormonal - Hopefully you’ve already been tested for this stuff. If you’re doing IVF, then they usually test for all this before treatment. (FSH, TSH, progesterone, prolactin, estradiol)
  • Physical/Uterine -Again, you’ve probably already been tested and had saline sonograms or hysterosalpinograms.  If you’re doing IVF, then they usually test for all this before treatment.
  • Infections – Once again, if you are doing IVF, then you’ve probably already been pre-screened for many things that could be a problem here.  (i.e. HIV, chlamydia, etc.)
  • Thrombophilias - These are a group of disorders that promote blood clotting.
  • Immune – Thisis a tricky one.  I was initially tested  for antiphospholipid antibodies, but nothing else.  This would involve things like autoimmune and alloimmune issues, activated Natural Killer (NK) cells, among others.  Many doctors do not believe in immune issues in regards to implantation dysfunction.  Read my post about that.  However, lots of doctors do believe in it.  From everything I’ve read and heard, this is an extremely complicated area of medicine and most REs simply do not understand it.  Another reason for controversy is lack of studies.  However, it’s hard to prove almost anything related to this field because there are so many factors.
  • Genetic – 
    • You and your partner can be tested to see if you have predisposed problems. The typical test is for this is called karyotyping. This is essentially a picture of your chromosomes and tests all 23 pairs.  It should be done for the female and male partner. It takes a little while to get the results, because the chromosomes have to be isolated, stained and examined under the microscope. Also, besides the standard karyotyping, there is micro-array testing that is more detailed. I think that it’s uncommon as it’s newer technology and probably more expensive. More info here and here.  
    • During treatment, you can do Comprehensive Chromosome Screening (CCS) testing on your embryos.  See info on CCS vs. PGD testing.
  • Egg Quality - Even if you get the karyotyping and you and your partner get good results, that doesn’t mean that your embryos will be genetically healthy.  By yourselves, you’re fine, but when the egg and sperm get together, there can be problems and it’s usually because of the egg.  This is sort of one of those normal abnormalities.  Your doctor may be able to tell you whether he thinks your egg quality is good or bad.  You can keep trying and wait for that one good egg or you can move on to donor eggs or embryos.  Or, you can perform PGD or CSS testing on your embryos to determine if they are normal before transfer. 
  • Male Factor – Make sure your partner has a full semen analysis.  Usually this is done prior to treatment anyway.

Products of Conception Testing

If you ever miscarry again, please try to get the “products of conception” tested.  In other words, what you pass (the embryo/fetus).  If it’s at home, try to save it and keep refrigerated.  I know this sounds morbid and I’m sorry, but you really should know this. Then, get it to your doctor or hospital as soon as possible.  If you are miscarrying at the hospital or if you’re going to have a D&C, ASK FOR THEM DO TESTING, which would be karyotyping.  This could give you valuable insight as to what’s going on with your embryos or you.

Typical RPL tests

For me, this was the “RPL workup.”  I think this is pretty standard.  I have divided them into groups.

Thrombophilias

  • anti-thrombin III
  • beta 2 glycoprotein 1 ab, g, a, m
  • Factor II
  • Factor V Leiden
  • Protein
  • Protein S (total)
  • Protein S (free)
  • Protime
  • Partial Thomboplastin Time

Hormonal

  • Thyroid Stimulating Hormone

Immune

  • Antiphospholipid Antibodies: anti-phosphatidylserine (IGG/M/A)
  • Antiphospholipid Antibodies: anti-cardiolipin (IGG)
  • Antiphospholipid Antibodies: anti-cardiolipin (IGM)
  • Antiphospholipid Antibodies: Lupus anticoagulant
  • Rh blood type –  you need to  know whether you are Rh positive or Rh negative

Genetic

  • Karyotyping (both partners) – this is the typical testing that they will do

Other tests

  • Natural Killer cells – Some women I know were tested for this as part of their initial testing, which is an immune problem. However, as I understand it, the test that most doctors order is useless because they don’t check activation. The standard for this test is the K-562.  So, don’t bother getting it unless you get it done right.
  • MTHFR
  • Homocysteine levels
  • Vitamin D – It is thought that a deficiency of Vitamin D may lead among other things to ovulation disorders. Go here and here for more information.
  • Celiac Disease – Because of some GI problems I was having, someone suggested to test for celiac.  Initial bloodwork showed that I had it, but later an endoscopy showed that I did not.  If you have no reason to believe you have celiac and don’t have severe GI problems, then don’t get yourself tested for this.   More info here.
  • Carrier Screening – This is like karyotyping, but more in depth.  I had a friend that went through many IVF cycles and many losses and had all of the testing referenced here done including karyotyping.  However, her doctor decided to delve deeper into testing her for genetic problems.  They did carrier screening on her through Good Start Genetics and discovered two problems.  After many years, she finally had a reason.

Here is the full immune workup that I got

Keep in mind that many doctors do not believe in immunological problems related to infertility, including my RE.  Camp #1 says there’s not enough research.  Camp #2 says it’s very complicated and many doctors do not understand it.  Also, it’s been hard to prove with so many variables, but now with embryo chromosomal testing, conclusive research will be possible.

To have this done, we consulted via phone with another doctor, which turned out to be a mess, but I’m still glad I had the testing.   See more information on that here.

  • Antiphospholipid Antibodies: ACA (Anti-Cardiolipin Abs)
  • Antiphospholipid Antibodies: APA (IgG, IgM, IgA, αPS, αPC, αPl, αPE)
  • Antiphospholipid Antibodies: Anti-β2 Glycoprotein I Ab’s
  • NK (Natural Killer) Activation with IVIg (K-562)
  • HLA panel – 1. HLA, A, B, C, DR, DQβ 2. DQα RIA (DQ Alpha Matching)
  • RIP (Reproductive Immunophenotyping)
  • TPO (Thyroperoxidase Ab)
  • THAB (Thyroglobulin Ab)

Click here to see prices for immune testing from ReproSource in Woburn, MA.  (Keep in mind that this is several years old and likely has changed.)

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33 Comments

  • Reply Jessica March 29, 2011 at 10:15 am

    Hi Whitney,

    What a great post! I think its important that you put together that whole list of tests. Before I had RPL I had no idea about all the testing that could be done. Luckily, my RE did the “full” workup after a chemical pregnancy just to be proactive. Like you said, us IVFers spend tons of money and we don’t want to risk another miscarriage. Well, the workup did not prevent my blighted ovum, but it did help me get preggo after that. I give credit to the prednisone that I took this round. The RE said he “threw the book at me” but maybe I was having an immune reaction so the prednisone would do something for that. Anyways, I look forward to reading more from you and I am praying the future holds a beautiful baby for you. =)

  • Reply Kelly March 29, 2011 at 10:46 am

    Thank you so much for posting this. I wish I had a guide like this when I was starting to try to get to the bottom of things.

    She.r confuses me with their testing. After my elevated NK Cells diagnosis, I spent hours doing research. It was about split on both sides, which made things even worse to deal with and comprehend. I just wish someone, anyone, would take the lead on things in the medical community.

    Thanks so much for taking the time to do this. Please let us know what She.r finds.

  • Reply Alex March 29, 2011 at 11:31 am

    Thanks so much for this post – I wish I had this earlier. Very well written, and comprehensive!

  • Reply Lex March 29, 2011 at 4:32 pm

    This is a great post! I wish I had had it back in May after mc #2. Before I ever conceived even once I got a hormonal checkup and some ultrasounds, after mc #2 I got tested for clotting and immune factors as well as karyotyping (but I had time to get pregnant and miscarry again before I got the results because the lab slowed down for the Summer – gotta love France)
    It wouldn’t have changed anything because I’ve since had the full workup and everything wrong with me was found after mc #2 but I would at least have had more peace of mind.

  • Reply On Standby April 4, 2011 at 1:28 pm

    Here from LFCA. Thank you for this helpful post. I recently experienced my third miscarriage – the worst one so far physically and emotionally. Last week I asked to be provided with a complete copy of my file for review before we have our follow-up appointment with the RE at the end of the month. I know that my husband and I have had a bunch of different tests done, but I really don’t know exactly what has been done other than karotyping and some other genetic screens. I had just started reading about potentially immunology issues and I intend to review my records once I receive them and compare them to this amazing list you have provided. IVF is probably our next step, but I want to be completely informed before we spend mucho bucks out of our pocket only to have it end in another loss that might be preventable. Thank you!!!

  • Reply flmgodog April 4, 2011 at 4:52 pm

    Whitney,
    Thank you for putting this up. I have had most all of these tests but for sure it is something I will check out. I have another RE appointment very soon for a WTF appointment. 8 pregnancies, 7 losses (most recent one @ 20weeks in Feb 2011).

  • Reply Bea April 4, 2011 at 9:04 pm

    This is a great post.

    One thing I would say is that egg quality problems are not necessarily genetic. There’s more to the egg – and the sperm as well – than genes. There’s also (as it was explained to me) the energy content, etc.

    We also had SCSA testing (sperm) which has fallen out of favour a bit as it’s not as predictive as first thought (or perhaps not much predictive at all, depending on who you talk to). Some doctors have recommended switching to a sperm donor on the basis of results, even if normal SA is ok, but make up your own mind.

    The immune stuff is an interesting area and I look forwards to seeing how opinion resolves. I certainly don’t trust those either firmly in favour or firmly against, as the truth seems more subtle than that. (If it weren’t, there wouldn’t be any controversy.)

    If encountering doctors who “don’t usually” test or “wouldn’t recommend” testing etc, my best advice would be to respect that they have come to this opinion from a position of knowledge, and then ask them to share that knowledge with you. Why don’t they do the testing? What are the pros and cons? How likely is the test to lead to a change of plan – either a change of protocol or perhaps a complete walk away from infertility treatment?

    You will often be able to see your doctor’s point, but can explain to him that your priorities are different from those he has assigned to you. He may be trying to save you money, or be reluctant to put you through tests that won’t change a treatment protocol no matter what the results. You can tell him/her that money is not the issue/that you’d like answers even if the treatment wouldn’t change/that you are considering the value of further treatment at all/that you have weighed the medical risks and potential medical/psychological benefits and would like to go ahead anyway/etc.

    Bea

  • Reply Not Knocked Up – And Happy About It « mommyodyssey April 5, 2011 at 7:14 am

    […] last night, I ran across this post via LFCA. This woman has been through multiple miscarriages, and she basically wrote up a […]

  • Reply missohkay April 5, 2011 at 9:34 pm

    Landed here from mommyodyssey’s latest post – thank you for this write up! I had some tests recommended by my doctor after my second miscarriage and I insisted on some other tests that I’d learned about online. Despite my efforts, I wasn’t my best advocate because I let the doctor tell me “oh we’ll do some immune testing” etc and I didn’t insist that she tell me exactly what tests had been run until after I lost my third pregnancy too. This is a great resource!

  • Reply Misfit April 7, 2011 at 12:54 am

    This is a fabulous post. I wish I could dig up my post on tests to compare, but I found that reading others results helped shape questions for my doctor tremendously. I, too, wish I’d had the workup sooner rather than later. It wasn’t until my fourth miscarriage that I finally went to someone who did the whole enchilada.

    Andie at The Conceivable Future tipped me off to DFI testing and Adele at Delinquent Eggs are both armed with long lists of tests as well. I find new things with every person who shares their story.

  • Reply Ed April 7, 2011 at 3:10 pm

    This is really helpful. Thanks very much!

  • Reply SLINK April 15, 2011 at 1:59 am

    I am amazed to have found this only after timidly searching for what tests to have! I just had my second miscarriage within a year just a few weeks ago. This after having a completely healthy pregnancy in 2008. I don’t want to rely on my OB for all the answers because her belief is that I probably just won’t have a third miscarriage. I don’t want to rely on her “feeling” I want all the evidence that my body can give me now not later.I don’t want to have to go through this again if it is preventable now.There are a few tests I talked her into that I will be taking in a few weeks and I will definitely be taking this list with me and be pushing hard for what I need done! Thank you for sharing and posting this!

  • Reply Kim April 19, 2011 at 3:16 pm

    The other thing I’d strongly urge is to have the products of conception tested at the time of the miscarriage. I know you mention it in your related post, but it’s worth urging again here, or really any time people are talking about RPL. Another really common cause of miscarriage, especially early miscarriages, is chromosomal abnormalities. And this, sadly, can the the cause of RPL through just plain bad luck, as I personally know. I’m always amazed at how many people don’t have the PoC tested, and it would provide an explanation in SO many cases.

  • Reply Aprill April 22, 2011 at 4:07 pm

    Thanks Whitney! Dr. P is going to love you!

  • Reply Kim July 18, 2011 at 7:43 pm

    Thank you! This is so concise and informative. I really needed to see all of this stuff listed in one place so I can ask for specifics. I’ve just had my 4th loss and I want to know they have tested for EVERYTHING possible. We’ve had most of this done, but I’m sure there are holes somewhere in the process as we’ve been told we have “bad luck”. Thank you again!!

  • Reply Katy November 6, 2011 at 1:11 pm

    Thankyou!!
    I will be going to my fertility specialist armed with this list of needed tests. I have just suffered from my 3rd miscarriage ( 9 wks, 5 wks and 4 wks consecutive).
    Hubby nad I want all the necessary tests completed before we suffer another heartbreak. You have helped us tremendously- huge hugs and lots of baby dust

    • Reply Whitney Anderson December 16, 2011 at 7:32 pm

      Thanks, Katy. Best wishes to you.

  • Reply LH Smith December 16, 2011 at 5:48 am

    This was quite informative, but what i wonder is what sorts of tests you can eliminate because you’ve had successful pregnancies. I am struggling with later pregnancies after miscarriages and with some successful experiences, I don’t know which things would be unlikely or not the case so that I can just seek out the tests that I might need for my own situation.

    • Reply Whitney Anderson December 16, 2011 at 7:31 pm

      I am confused about your question b/c I have not had successful pregnancies.

  • Reply Sherry February 11, 2012 at 7:16 pm

    Thank you so much for this, Whitney. 2 miscarriages in and I’m ready to pay whatever I have to to go forward with the next attempt armed with more information. Really appreciate the post.

  • Reply Amy June 4, 2012 at 10:22 am

    Thankyou for your post. We have tried 4 times and I have got pregnant each time and lost at 6 weeks. I am 28 and keep being told it is probably bad luck but I am not so sure. I have had a diagnostic hysteroscopy and everything was fine. My dr told me that was all he could do and I should try again and take asprin to see if that helps. I’m so glad I have read your post because now I have the information for myself and can insist on some more testing. Thank-you

  • Reply Ani October 13, 2012 at 5:58 pm

    Thank you for sharing your experience. Here is mine i had my first pregnancy when i was 28 Miscarried on Day40 Naturally. Three months later magic of Clomid helped me to conceive my son who is a 5 year old naughty angel. Started trying for 2nd baby when by son turned 2and half year old. 3months later 8 weeks ultrasound revealed blighted ovum ended with a DNC. 5 months later pregnant again after series of blood tests and ultrasounds later on 8 weeks found out ectopic pregnancy in L F tube. had a laproscopic DNC. Now after 18 months later with Low GI diet, baby aspirin Lovenox, progesterone suppositories. ultrasound on 7w6d reveals perfect growth with 144 heart beat. 2 weeks later no heartbeat. Scheduled for another DNC. This time my Dr recommended chromosome testing on the fetal tissue.

    Have no Idea what future holds for me.

    • Reply WhitneyErick October 17, 2012 at 12:20 pm

      Ani, I’m so sorry for your losses. Yes, I would recommend any and all testing. Ask your doctor also about a complete RPL panel. Best wishes.

  • Reply Felynn December 12, 2012 at 9:41 pm

    I am glad I found this page. I am trying to demand as many test as I can. I changed doctors because my 1st doctor refused to do any test whatsoever. I am wondering because I have kids is there some test I do not need to bother with? I think its better to get any and all of them done, But b/c I have kids some may not pertain to me.

    Here is my situation in short detail. I have 3 kids 1st in 2004 2nd in 2006 and 3rd in 2008. With my 3rd it got complicated after I gave birth, I almost died and needed a blood transfusion, almost had my uterus removed but lucky for me an emergency d&c fixed the problem.

    Fast forward had my 1st loss in Sept 2011 resulted in d&e, I was suppose to be 11 weeks but gestational sac was only 5.5 weeks with yolk sac but no fetal pole. I then had a natural miscarriage in Jan 2012, didn’t know I was pregnant because I never got a period from my 1st loss. Had my 3rd loss in June 2012, baby’s heart stopped at 13.2 weeks, specialist said baby just recently died, my baby measured correctly he also recommended the d&e and testing on the baby. I had a d&e at 14 weeks. Test from my baby showed nothing wrong and my baby was a girl.

    My dr refused to do any test, The day I found out about my baby I went straight to my dr to talk about my options and I requested he do testing he said no there is no point. I thought if something wasn’t right with my blood we would know since my baby had just died. I then found a new dr that listened to me and didn’t rush me and she agreed to do some testing. She won’t do certain ones and I have asked her to do them. I am now debating and trying to find another dr. I want any and all test done even if they think I don’t need them.

  • Reply march16 March 20, 2013 at 12:27 pm

    Thank you for sharing, at least it makes me feel better, not so sad right know knowing that my 2nd miscarriage at least is something explainable, i was keep asking why and why this happens to me.. thank you..will try to get some test done and see if God allows, please dont take away my hope and faith, i really TTC and for the 3rd and the last time, if it happends again, i really dont know where to find the courage to be pregnant again…

  • Reply Dilcia October 29, 2013 at 7:54 am

    Hi there, I wanted to add something here to the testing list. After my second miscarriage, my doctor did a fairly good work up and explained to me that in addition to testing MTHFR genetic mutation, the homocysteine level needs to be sent. Apparently in the newest studies, the genetic mutation only affects fertility if the homocysteine level is affected. I tested positive for the mutation, but my homocysteine levels are normal and all other tests were fine, so we still have no answers– we will see. Good luck to everyone who reads this.

  • Reply Amelia's mommy January 10, 2014 at 6:41 am

    Someone referenced this blog on baby center- in looking at what to be tested for with RPL. Like you, there was a lot of things that I wish I would have discovered after the 2nd or 3rd mc, but it wasn’t until I had 5 that I started researching on my own. I have 2 clotting disorders – I didn’t see them on your list. Mthfr and PAI-1 , and these are frequently overlooked and brushed off by doctors, but in my case, it was the ONLY thing that showed up in all the bloodwork and genetic testing. Lots of people have mthfr, and have to suffer through RPL because doctors ignore it. Even after they found it, I had to find another doctor who was willing to treat me with lovenox. It worked, my miracle is here!

  • Reply Resolve to know more about recurrent pregnancy loss | Whitney & Erick April 21, 2014 at 3:17 pm

    […] For more information about possible reasons for RPL and available testing, check out the extensive post I wrote on recurrent miscarriage testing . […]

  • Reply Carla Alvarado April 23, 2014 at 10:40 pm

    I am now currently going through my 5th miscarriage. I have had a successful pregnacy at 18 delivered at 19 and I’m trying now that I’ve been with my husband for 8 years and nothing seems to stick. I am sick and tired of not getting the answers I need. Someone needs to tell me what’s going on… I am going to demand all the tests they give and get some answers enough is enough!!!

    • Reply Whitney Anderson April 24, 2014 at 8:36 am

      Carla, I’m so sorry. :( Yes, advocate for yourself. Don’t ask for tests. Tell them which tests you want. Best of luck.

  • Reply Shannon Freeman October 23, 2014 at 9:25 am

    Thank you so much for writing this. It’s one of the best things that I’ve seen out there on this topic. That’s why it’s so important to share our stories. Thank you for sharing yours and all this great information!

  • Reply MrsH November 14, 2014 at 1:25 am

    This is a fabulous post, and much needed info on the page. I have noticed a typo that I wanted to point out: under thrombophilias, it should say “protein C” instead of just “protein”. Thanks again.

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