Recurrent Miscarriages and Empiric Use of Enoxaparin - A Reader's Queries
The reader below related her obstetrical history which included three miscarriages surrounding the birth (one before and two after) of a healthy child. Her doctor chose a course of empiric therapy despite a completely ‘negative’ work-up (which did not include parental chromosomal studies by the patient’s request because of the “expense”). This is a very common practice (and I readily admit to it myself) when dealing with the supercharged issue of recurrent miscarriages where there is a sense of “need” on the part of both patient and provider to “do something.” However, this reader has some excellent questions and concerns regarding her obstetrical history, the choice of therapy, and the prognosis for her current pregnancy now that she has gotten to the end of first trimester. I have paraphrased and condensed her comments…
Seema left a new comment on your post "Recurrent Early Pregnancy Loss - 5 - Introduction ... at Fruit of the Womb on Tue Sep 04, 08:35:00 PM 2007...
I am 31 years old. I have a son who is 4 years old and I have had a total of 3 miscarriages. With my first pregnancy, I had bleeding at 4 weeks for 3 hours and it stopped. At 8-9 weeks an ultrasound showed a twin pregnancy with fetal poles but no heartbeats. The doctors said it was a missed abortion and I had a D&C. The biopsy results came back as hydropic abortion. My second pregnancy was uncomplicated and I delivered a boy. The third pregnancy, I had severe cramping at 7 weeks and subsequently miscarried completely. The fourth pregnancy there was very good heart beat at 6 weeks 4 days, but when I went at 10 weeks for a scan, they said the fetus stopped growing at 7 weeks 4 days and they evacuated it. All of these pregnancies are with the same partner.
I had many blood tests done including antiphospholipid antibodies, anticardiolipin antibodies, lupus anticoagulant, thyroid function tests, antithyroglobulin antibody, serologic screens for toxoplasmosis, cytomegalovirus virus (CMV), and herpes simplex virus (HSV) and everything came back negative.
With my current pregnancy at 4 3/7 weeks, the doctor started me on folic acid, low-dose aspirin (81mg), and subcutaneous low molecular weight heparin (enoxaparin) 20mg subcutaneously per day. Now I am pregnant 10 weeks and 3 days. I had a scan which showed the baby growing very nicely corresponding to 11+ weeks. I haven't had the genetic testing done. My doctor said I may have some immune problems which causes these abortions and enoxaparin helps prevent this. But I still have many doubts and concerns. Can you answer some of these questions? Kindly answer my concerns. I will be extremely grateful to you. Thanks a lot in advance...
Is it possible that such an immune problem caused my first pregnancy to miscarry and then remained inactive during my normal pregnancy and then started acting up again with my 3rd and 4th pregnancies?
Anything is possible, but I think this is unlikely in your case. At this point, I don’t think your laboratory data support the diagnosis of “an immune problem” as the cause of your pregnancy losses. You could potentially have a ‘genetic thrombophilia’ associated with polymorphisms of certain clotting factors, such as Factor V Leiden, methylene tetrahydrofolatereductase (MTHFR), or prothrombin (G20210A), deficiencies in the activity of Protein C or S, antithrombin III deficiency, or an overproduction of Factor VIII. These can lead to an increased tendency to form blood clots and/or a decreased ability to break them down and they are thought to be associated with recurrent pregnancy loss and poor pregnancy outcomes (fetal growth restriction, fetal death in utero, preeclampsia, etc.) related to abnormal placental development. However, even one of these abnormalities is unlikely because of your history of the uncomplicated term pregnancy in between the early pregnancy losses.
If I am having such immune problems, how could I have delivered my son?
It is possible to develop “immune problems” at any time in your life, but, again, the laboratory data you have presented would not support that diagnosis at this point. Of course, there could be other ‘immune factors’ we have not learned about yet that have caused your losses.
My doctor said such problems could develop at any time and in my case I may have developed it after my son was born. If this is true, then what happened to my first pregnancy, before my son was born?
There seems to be a high risk for spontaneous losses of true first pregnancies. This may be a ‘self-limited’ immunologic problem in a woman’s initial response to a baby that is only half her. Many women overcome that immunologic ‘barrier’ during the process of losing a pregnancy or two (ie., they become properly ‘immunized’ to their partner) and then go on to carry normal pregnancies successfully as you did. Some women do develop ‘immune problems' to pregnancy only after they have had uncomplicated pregnancies. These women have sometimes been termed “secondary aborters” and they can be among the most difficult of patients to treat successfully.
There is also the possibility that one or more of your babies was chromosomally abnormal. This can happen by repeated 'chance' but it can also occur quite frequently if one of the parents carries a ‘balanced translocation.’ Since neither you nor your partner had chromosomal studies done on yourselves, this could still be the case. Approximately 1-2 per 1000 individuals carry balanced translocations and because they appear perfectly normal (and they are ‘normal’ because they have the correct total amount of genetic material; it’s just rearranged in a way that decreases the likelihood of normal gamete, egg or sperm, production) they do not encounter problems until they try to have babies. Incidentally, estimates as high as 2-3 per 100 individuals with recurrent miscarriages have one of the couple (more often the woman) as a balanced translocation carrier!
My doctor says enoxaparin helps increase the blood flow to the baby. If this is so, then how will it increase the blood flow before 8 weeks, when there is no umbilicoplacental circulation?
Exoxaparin does NOT directly increase the blood flow to the baby. In fact, its actual mechanism for reducing the risk of early miscarriages and of poor pregnancy outcome is not entirely clear. Enoxaparin is known to bind to and to accelerate the activity of antithrombin III. By doing so, it helps to potentiate the inhibition of coagulation factors Xa and IIa. Factor Xa catalyzes the conversion of prothrombin to thrombin so enoxaparin’s action ultimately reduces fibrin clot formation. It is thought that activation of thrombin (and clot formation) is one of the events that limits the invasion of the placental trophoblasts into the endometrium, however, if the thrombin system is overactive, it may also prevent normal placentation. Thus, in early pregnancy exoxaparin may help to achieve a better ‘balance’ in women who have increased activation of the clotting system for any reason (immune-mediated or genetic thrombophilia).
In certain animal studies, enoxaparin has been found to have some immunomodulating properties as well, decreasing inflammatory responses and complement activation that may also interfere with normal early placental development. In the end, enoxaparin can improve the placental development and vascularization that is so important to a normal pregnancy outcome, but by itself, it has no effect on fetal blood flow.
The enoxaparin is really expensive and I would like to know if there is any use in continuing it, in my case?
Enoxaparin is REALLY expensive; that’s why when I offer ‘empiric therapy’ to women in your situation, I usually suggest unfractionated heparin as an option. It is still administered by subcutaneous injection. You are on a very LOW dose of enoxaparin, below what is commonly used even for prophylaxis, and well below that used in therapeutic regimens. Since you have no identifiable laboratory risk factors, you probably do not need to continue it throughout the pregnancy.
There is no ‘standard of care’ in this regard, and to some extent, the duration of therapy depends on the individual patient’s level of anxiety. In circumstances like yours, I will frequently discontinue the drug at 20 weeks and simply continue the baby aspirin. At higher levels of concern, I will assess fetal growth and perform Doppler flow studies on the umbilical cord, middle cerebral artery and uterine arteries at 26-28 weeks to get a better feel for placental vascularization from both the fetal and maternal sides. If all is ‘normal’ at that point, it is usually ‘safe’ to discontinue therapy. If you and your doctor choose to continue it longer than this, it is recommended to stpo it at least 72 hour prior to delivery so that the anesthesiologist feels comfortable using a regional anesthetic (spinal or epidural). Patients who do have documented clotting problems should be switched to heparin in anticipation of delivery because its effects can be readily reversed unlike those of enoxaparin.
If I lose my pregnancies due to chromosomal abnormalities, what will be the chance with my current pregnancy as now it is 10 weeks?
At least 90% of aneuploid fetuses are lost in the first trimester, so every day that goes by improves your prospects for carrying the baby.
Up to which week can I miscarry if the baby has a chromosomal abnormality?
Some babies with chromosomal abnormalities aren’t lost until the second or even the third trimester. Obviously, some even survive through and after delivery. Most babies that are going to die from a chromosomal abnormality in utero grow poorly and/or have physical abnormalities that can be detected by ultrasound.
Anyway, Seema, thanks for reading and for a bunch of great questions! I hope I have helped and I also wish you the best for this current pregnancy...
Dr T
Labels: enoxaparin, miscarriage, recurrent pregnancy loss
38 Comments:
At Tue Sep 25, 08:05:00 PM 2007,
Seema said…
Dear Dr. Trofatter:
Sorry for the delay in responding. I could not get connected thru the internet. First of all, let me express my sincere gratitude to you for answering all my concerns in such a beautiful way. The way you explained everything in detail helped me a lot in understanding things more clearly. Thanks a lot for all the help and reassurance you provide to the many pregnany women like us.
I have stopped the enoxaparin on my own once i completed 10 weeks. And I had gone for a 12-week ultrasound and everything was normal. Now i am 13-4/7 weeks. Next week I am going to see my doctor again. I stopped the enoxaparin for two reasons, one it is so expensive that we find it difficult to afford it, two, I had a gut feeling that I lost my previous pregnancies due to chromosomal abnormalities rather than any immune problem. Trusting in God, I took the decision to stop it, hoping that this time nothing will go wrong. Anyway I will keep in touch with you and let you know how things turn out.
I have one more concern, doctor. I had developed viral fever when I was 5 weeks and 4 days. My doctor advised me to take acetaminophen 650 mg every 6 hours. My temperature would come down 1 hour after I took the tablet, but it would rise again after 3-4 hours and I could take the next tablet only after 6 hours. I had above 101 temperature for 2-3 hours. Now I have read in the internet that high fever during early pregnancy at the time of neural tube closure will affect the baby's central nervous system and I am worried after reading it. Is it possible to have any serious anomalies resulting from the fever that I had? I have one more concern, doctor. Is there any harm in having frequent ultrasounds during pregnancy? I have had around 6 scans now, i.e., before 12 weeks. Is there any relationship between too many scans and lefthandedness. My son is lefthanded and while I was pregnant with him, I had too many scans. Kindly answer my concerns. Thanks in advance. Seema
At Wed Oct 03, 05:56:00 PM 2007,
Anonymous said…
I am 19 years old, and i know that im to young to have children in my eyes and in my families eyes but when i met my ex. boyfriend we thought that we would be together and so we desided that we would try and have kids! so a month later after desiding this we started noticing that i had some of the symptoms of Pregnancy and he was happier then i was! BUT then a couple weeks later i started to feel sick and that was when i had my 1st miscarriage then evey month after that till we broke up i still had them! its so devistating cause that was 4 babies that would have or could have been great people!and after that 1st one we never were the same! but its making me want to cry and im at work so im getting off now!
At Thu Oct 04, 05:37:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Anonymous Oct 3: If your boyfriend left you over that, then he probably would have left you with a child as well. Sometimes things work out for the best in the end. Sorry, but sometimes I am not known for my tact. I am also a little confused. How did you know you were pregnant. Did you just "feel like it" or did you have a pregnancy confirmed by a pregnancy test? Had you been on any form of birth control before you decoded to try to get pregnant. What I am getting at is that it is highly UNLIKELY that you got pregnant and miscarried 4 months in a row. If you had been on birth control pills, you might have developed some symptoms of 'feeling pregnant' due to the hormones your body produced. And, if you were not on pills, but started having unusually heavy or uncomfortable bleeding (periods?) afte having sex with your boyfriend, there is a possibility that those symptoms came from a sexuallt transmitted infection such as chlamydia or gonorrhea rather than a pregnancy. I think if you feel you are "too young" to get pregnant, you should go with your gut feeling and not let someone talk you into something you are not ready for. Raising a child is a BIG committment and will change your life FOREVER. Why don't you find a good doctor, have her/him check you out, including screening for sexually transmitted infections, then get on a reliable form of contraception until you really are ready - maybe with a guy who plans to stay around longer than a few months! Thanks for reading and best of luck to you. Dr T
At Thu Oct 11, 04:59:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Seema Sept 25: Hi Seema. Pardon my delay in responding to your excellent questions. Thinsg have been very busy at work lately and I am far behind in my blogging! Anyway, I tried to answer your questions related to lefthandedness and ultrasounds in my last two posts (October 8 and October 11) and I will try to get to the question related to maternal fever in another post soon since that is also a very good question. The bottomline is that yes, fever is associated with an inceased risk for multiple fetal anomalies, especially neural tube defects, but the risk depends on the time in embryogenesis, the height of the fever, and the length of the temperature elevation. It is possible that folic acid (which I believe you were taking) decreases the risk of fever in early pregnancy. Anyway, thanks again for writing and for all of your good questions. Hope the pregnancy is still going well and please let me know how things turn out. Dr T
At Mon Oct 15, 06:48:00 PM 2007,
Anonymous said…
Im 22yrs old and recently found out i was pregant,This will be my 4th pregnancy,my other 3 ended in miscarriages and they were 2 my ex at the time,now with this pregnancy im worried i will miscarry again,i havnt had tests as 2 why i have misscarried and i fear i will not be able too carry to term,theres no problem getting pregnant its carrying.My doctor says u cant predict wots going to happen,but its just a relly big fear i have of not being able to have my own children.
At Fri Oct 19, 07:32:00 PM 2007,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Anonymous Oct 15: It is not easy going through recurrent miscarriages, but you are still young and you certainly have no trouble getting pregnant. If you lose this baby, see if your doctor can do chromosomal studies on the tissue from the pregnancy. Then you should take a bit of a break from getting pregnant and ask your doctor to either evaluate you for recurrent pregnancy loss or send you to someone who will. Best wishes and I hope things turn out okay this time! Dr T
At Wed Dec 26, 08:25:00 PM 2007,
ALLI said…
Dear Dr.,
I am 26 years old and have recently suffered from third miscarriage. After my second miscarriage my husband and I decided to go see an RE. We had a karyotype done as well as several blood tests on me. Everything came back negative except for my blood sugar (GTT level was 103) and I have a heterozygous MTHFRI mutation. My RE gave me extra folic acid and prescribed prenatal vitamins. My husband and I don't have any difficulty getting pregnant,but, the three pregnancies have ended in miscarriage. In this last pregnancy since we were being monitored we saw a fetal heart beat of 110 bpm on 12.12.07. I was 7 weeks 2 days pregnant at this point. Three days later I started bleeding and had a miscarriage (passed tissue) that Monday (12.17.07). I honestly don't understand what could have happened within that short time. I passed the tissue and we are going to get tests done on it, but, I can't understand what is wrong. THe karyotype that my husband and I had done was fine. My only thought is that there is some autoimmune problem that they didn't catch since I was tested and it came back negative. I feel lost. My RE was very unsupportive and horrible. I am currently in the search to find another one. I do have a question regarding UVEITIS , however. I know that it is autoimmune with respect to the eye, but, could there be any correlation between my miscarriages and uveitis.. or no? What do you think it could be? I know my husband needs to get further testing, but, from a medical perspective what other tests should we get done to rule out any other potential problems?
I have been reading as well that some tests need to be run more than once (especially antiphos etc) since sometimes there can be a false negative. Is this true? ANye insight would be much appreciated.
Thanks in advance for your cooperation,
ALLI
At Thu Jan 03, 11:16:00 PM 2008,
Seema said…
Dear Dr. Troffatter:
I am the reader who asked you so many questions regarding enoxparin usage, fever in early pregnancy, and frequent ultrasounds causing left-handedness and I am really grateful to you for explaining everything in detail.
I am now 28 weeks pregnant and everything has been going on well until now. I have had 20-weeks anomaly scan and everything was okay.
Now I have some more concerns, doctor. I started experiencing fetal movement at about 18-19 weeks. After I completed 24 weeks, I feel that the baby is not moving sometimes. Some days it will move as normal, and some days I do not feel any movement for a full day or two and then the third day, again I start experiencing the movement. I had a scan at 26 weeks and my doctor said everything is okay except that the baby weighs a little less than what is expected for this age. during the times when i feel no movement, i used to try lying on the left side and drinking something cold and sweet etc. but still i could not experience any movement. Kindly explain if this means something significant.
My other concern is that I do not eat fish at all. Will it affect my baby in some way or other? i have read a lot that fish contains omega-3 fatty acids which helps a lot in the baby's brain development. If I don't eat fish at all, is it going to affect my baby? will supplementing with Vitamin E or omega-3 capsules be of any use? Is it safe to take flaxseed oil capsules durng pregnancy?
When i was pregnant with my son, I had less amniotic fluid after 32 weeks and i had to take complete bed rest for 2 weeks before i delivered my son at 38 weeks. Will drinking more fluid help in maintaining the amniotic fluid level? everybody says that you should drink lots of fluid and I donot feel thirsty at all and it is very much difficult to drink when you don't feel thirsty. will it really help drinking 1-2 liters of fluid per day in maintaining teh amniotic fluid level? Is there any relationship between maternal stress and amniotic fluid level?
Hope you will answer my concerns and thanks a lot in advance.
At Fri Jan 04, 12:08:00 PM 2008,
mm1981 said…
Hi Dr. T,
I am 26 years old and have had 2 miscarriages in one year. With the first one, my HCG was increasing but not at the appropriate rate, and I was spotting lightly. I had several ultrasounds over 8 weeks, all showing perfectly healthy baby appropriate for gestational age. At 14 weeks I had another ultrasound and there was no heartbeat, proceeded to have a natural miscarriage one week later. Seven months later I became pregnant and had a miscarriage at 6 weeks (no ultrasound). Following this miscarriage, I underwent extensive lab testing, and everything was normal with the exception of heterozygous MTHFR. My doctor placed me on a B6, B12, and Folate supplement, and seems to think this will fix the problem. I have found quite a bit of research indicating heterozygous MTHFR does not contribute to miscarriage. What are your thoughts?
At Thu Jan 17, 09:29:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To mm1981 Jan 4: Sorry for the delay in my response, but I have been quite overwhelmed (pleasantly) by the number of readers' comments lately. Anyway, I would have to agree with you. It is very unlikely that a single MTHFR polymorphism is the primary contributor to your losses. HOWEVER, that's not to say that the empiric therapy suggested, or tincture of time alone, might not result in a successful pregnancy for reasons we haven't yet figured out in your case. So go for it! And, if that doesn't work, perhaps, I can give you some other suggestions. Best wishes, thanks for reading and for your patience! Dr T
At Thu Jan 17, 09:40:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To ALLI Dec 26: Somehow your comment got lost in my mailbox, so I apologize for the delay in responding. As I understand from your letter, no reason for your early losses has been identified to date. The one thing you haven't told me is what has been done to date to help you carry a pregnancy, even if no cause for the losses has been identified. If you have regular periods, ovulate regularly, and have no trouble conceiving, you can still try the empiric approach to therapy that is widely used under these circumstances, e.g., aspirin, folic acid, progesterone support, heparin or lovenox, and even metformin, with or without ovulation induction. My suggestion is that you talk with your new REI doctor about these things after he/she determines if there are some additional studies that should be done first. Good luck to you! Dr T
At Thu Jan 17, 09:48:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Seema Jan 3: Girl, you WORRY so much that sooner or later I am worried that you will have a 'self-fulfilling' prophecy and things really won't be alright! If your baby is growing well, or even if it is a little small, if it has normal fluid, normal fetal heart tracings, and normal Doppler flow studies, things are probably okay. Don't worry about the fish if your diet is well-balanced otherwise. Some folks worry more about the heavy metals that can be concentrated in fish than the loss in nutritional value from not eating any! Go slow on extra vitamin E (above what is in the prenatal vitamins) because that is a fat-soluble vitamin that babies have a little more trouble handling than children or adults. A little ectra omega-3 and/or flaxseed oil should be just fine. Always drink plenty of fluids with a pregnancy - 8 glasses per day, but stay away from fluids that contain a lot of caffiene and free sugars. RELAX, and let me know how things turn out. You are ALMOST there, Girl! Best wishes. Dr T
At Tue May 27, 03:30:00 PM 2008,
Allison said…
Dear Doctor,
I have suffered three miscarriages within a years time. The first two were unexplained and the last pregnancy ended in a spontaneous abortion due to triploidy (69xxx) I also recently saw a hematologist who tested me three months after the miscarriage. I had a weakly positive LAC, that after careful review went undetected due to Medical negligence by my former RE. What I mean to say is that both times I was tested (three months after the second miscarriage and again after the third miscarriage the LAC was weakly positive. My hematologist ordered a third set of tests 4 months after the miscarriage (third miscarriage) and the results were still weakly positive (2 of the three tests can back slightly elevated). My hematologist said this was so weakly positive that he can't say with certainty that it was the cause of the first two miscarriages. He did say however, since I also have uveitis that I should take Lovenox when I am pregnant. My brother also has discoid lupus. I want to know what you think the course of action should be? Do you think that this could be the reason for the other two unexplained miscarriages? My husband and I have been checked and our karyotypes are normal. What do you think? Any insight would be greatly appreciated.
Thanks in advance,
A
At Wed May 28, 04:52:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Allison. It is possible that the lupus anticoagulant is your problem but I am curious to know what other studies you had done? You have a couple of choices: 1) If there is a family history of autoimmune disorders, then low dose aspirin and heparin (or low-molecular weight heparin) would be a reasonable form of empiric therapy; 2) You could have your doctors look for other causes that might be contributing and what those are depends upon what has not been done to date; 3) You can just try again and see what happens. I wrote about (in march or April of 2007) one of the first patients I ever had with recurrent pregnancy loss who also had a lupus anticoagulant that eventually resolved with time and was accompanied by successful pregnancies afterwards. Good luck to you and thanks for reading!
Dr T
At Thu Jul 03, 09:16:00 PM 2008,
Shelley said…
Dr. Trofatter:
I came across this post while researching what could be interfering with me conceiving a 2nd child after the loss of my first after giving birth at 32 weeks last May 7, 2007 (death was supposedly unrelated to my autoimmune/blood clotting disorders, as she died from fetal hydrops and severe anemia). I clicked on your name and lo & behold, found that you are the MFM Director with the very school my MFM, Dr. Anthony Gregg, is!!
I'd like some more information about using lovenox earlier in a pregnancy than I've been told by Dr. Gregg. He said to start it as soon as I have a positive pg test. But, I've known others who actually begin enoxaparin injections 3 days after ovulation. Could that possibly help me if I have a blood clotting and/or autoimmune disorder in the APS/Lupus family?? I don't have a firm diagnosis at this time, but have high antibodies (ANA, anticardiolipin, lupus anticoagulant, etc.). My husband and I wonder if we have several babies in heaven from previous missed miscarriages that we never even knew about. I'm in my early 40's and want so badly to have at least one biological child before it's too late. I've seen a local RE, been through 3 rounds of IUI, to no avail. Now, I want to look into my medical condition, to see if it could be interfering with implantation. If the Lovenox I have sitting in my closet (from my pregnancy) can help a baby implant, I want to begin injections this coming week, once I ovulate! Can you help me???
Thank you very much...
At Tue Jul 08, 07:03:00 PM 2008,
Shelley said…
I posted a comment one day last week (week of July 1st), but it seems to have gotten lost in cyberspace, so I'm posting it again. Forgive me if I'm duplicating it, but I really wanted an answer before I ovulate this week (which is any day, possibly YESTERDAY). Today is Tues, July 8, 2008. Here's the post I did last week:
Dr. Trofatter:
I came across this post while researching what could be interfering with me conceiving a 2nd child after the loss of my first after giving birth at 32 weeks last May 7, 2007 (death was supposedly unrelated to my autoimmune/blood clotting disorders, as she died from fetal hydrops and severe anemia). I clicked on your name and lo & behold, found that you are the MFM Director with the very school my MFM, Dr. Anthony Gregg, is!!
I'd like some more information about using lovenox earlier in a pregnancy than I've been told by Dr. Gregg. He said to start it as soon as I have a positive pg test. But, I've known others who actually begin enoxaparin injections 3 days after ovulation. Could that possibly help me if I have a blood clotting and/or autoimmune disorder in the APS/Lupus family?? I don't have a firm diagnosis at this time, but have high antibodies (ANA, anticardiolipin, lupus anticoagulant, etc.). My husband and I wonder if we have several babies in heaven from previous missed miscarriages that we never even knew about. I'm in my early 40's and want so badly to have at least one biological child before it's too late. I've seen a local RE, been through 3 rounds of IUI, to no avail. Now, I want to look into my medical condition, to see if it could be interfering with implantation. If the Lovenox I have sitting in my closet (from my pregnancy) can help a baby implant, I want to begin injections this coming week, once I ovulate! Can you help me???
Thank you very much!
Mama Shelley (baby at roman4 dot com)
At Sat Jul 12, 04:17:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Shelley: First of all, evemn though my academic appointment is at the University of South carolina, I am actually at the Greenville Hospital campus. However, I do know Dr Gregg well and he is a VERY good doctor. There is no standard of care for treament under these circumstances. If you have high levels of anticardiolipin antibodies and a lupus anticoagulant, I am very aggressive about therapy with heparin or lovenox, usually treating with THERAPEUTIC rather than prophylactic dosages. Usually I start midway through the luteal phase (within a week after ovulation), but no one has shown that is any better than starting as soon as a pregnancy is confirmed chemically. I do have several questions though: 1) Are you on any other medications? 2) Any other medical problems 3) Why did they think your last baby was severely anemic and what was the cause? Good luck and I am sorry I could not get to this sooner. Dr T
At Sat Jul 12, 04:17:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Shelley: First of all, evemn though my academic appointment is at the University of South carolina, I am actually at the Greenville Hospital campus. However, I do know Dr Gregg well and he is a VERY good doctor. There is no standard of care for treament under these circumstances. If you have high levels of anticardiolipin antibodies and a lupus anticoagulant, I am very aggressive about therapy with heparin or lovenox, usually treating with THERAPEUTIC rather than prophylactic dosages. Usually I start midway through the luteal phase (within a week after ovulation), but no one has shown that is any better than starting as soon as a pregnancy is confirmed chemically. I do have several questions though: 1) Are you on any other medications? 2) Any other medical problems 3) Why did they think your last baby was severely anemic and what was the cause? Good luck and I am sorry I could not get to this sooner. Dr T
At Sun Jul 13, 04:59:00 PM 2008,
Anonymous said…
Dear Dr. Trofatter:
I appreciate all your articles regarding recurrent miscarriages. It's so hard to find places that speak to balanced translocations. I started TTC in 04/06 when I was 36. Pregnant the on the first try, but ended in m/c. Pregnant again a year later and another m/c. Decided to get testing and found DH has a low sperm count 3-5 million and I have a balanced translocation of 2,19. Most recently was pregnant in 02/08 and lost it again, but had a D&C for testing. It came back that the baby had my balanced translocation, but also Trisomy 22. I'm 38 now and can't afford IVF, and believe it wouldn't be worth going through with my translocation anyway. So, my question...
Are there ANY success stories of women with recurrent miscarriages, going on to have normal pregnancies? I know I'm getting up there in age and I may be at a higher risk for chromosomal abnormalities in general. Just looking for a 'glimmer' of hope out there.
At Mon Jul 14, 05:25:00 AM 2008,
Shelley said…
Dr. T:
Thank you for your response. Yes, Dr. Gregg is a wonderful MFM doc! He very well could have saved my life by detecting my need for lovenox simply due to his notice of my false positive RPR & the risks that put me at for blood clots, stroke & early miscarriage or late term fetal demise (which my previous 2 ob's in the same pregnancy IGNORED!).
To answer your questions, my pregnancy unraveled some medical conditions I did not know I had prior to pregnancy. I was an overall healthy 40 year old, although about 50-60 pounds overweight. Gestational diabetes was detected at 15 weeks, with an A1C of 6.2%. Insulin therapy and diet controlled it very well during my pg.
1) Currently, I take 81 mg aspirin daily, 500 mg metformin twice a day for blood sugar control (my A1C has stayed around 5.2-5.3%, within normal limits)& about 1200 mcg of folic acid (to prepare for my next pg). I also take a liquid superfood, containing vitamins, minerals, enzymes, amino acids, etc...which I believe has kept my iron levels right where they need to be.
2) I was dx'd with Type 2 Diabetes about 5 months after my pg ended. Although I struggle with high fasting #'s (100-120's), I usually stay within somewhat normal range, up to the 140's after meals (metformin helps!). I thought I had beta thalassemia minor (dx'd by a doc back in 1988, and my dad and sis both have it) up until I began seeing a hematologist after Hannah's death. She r/o'd ALPHA thal, as that can be a cause of fetal hydrops. Now the question is do I really have thalassemia or merely iron-deficient anemia? Aside from those 2 conditions, I have very mild mitral valve prolapse. The blood clotting disorder and autoimmune disease both go UNdiagnosed, as I merely have elevated levels and no firm diagnosis. The rheumatologist I saw after Hannah's death originally thought I had full-blown lupus when he saw my titres (1:640). But, when he saw ME, he said that's not the case. He too left me with no firm diagnosis.
3) Hannah was severely anemic because she had full blown fetal hydrops upon delivery. They tried to do several blood transfusions and platelet transfusions in the 23.5 short hours she lived, to no avail. My hemoglobin was down to 9 during delivery, and I had to have 2 units of blood myself. None of this was detected prior to Hannah's birth. Dr. Gregg's residents cared for me in L&D, and they all thought Hannah was fine and needed to come OUT of my womb, because my womb was suddenly an "unfriendly" environment. They were all shocked to see her fully hydropic and not breathing upon birth. She did have a nice, strong heartbeat up until the ventilator was turned off just moments before she died.
You may consult with Dr. Gregg if you'd like about my case. He knows it well, as it is one of the "unsolved" mystery cases!!!
I have my thoughts about what happened, but there are no known causes of Hannah's death.
My thoughts are:
a) Hannah contracted anemia and subsequently fetal hydrops from my exposure to Parvo/B19 during my 16-20th week (although my titres, which were only run once after my exposure (prior to Dr Gregg becoming my OB), showed I had been exposed but had the antibody. The nurses all reassured me that there is NO way my baby would get it since I'd had a previous exposure.
b) I had a horrible virus (probably pneumonia) my last several weeks of pregnancy. They never drew blood to test me, but merely sent me home from the hospital one day telling me to drink lots of water and rest. No sonogram was done to check on Hannah's status during the 3 weeks of me being so incredibly sick, nor were any CBC's drawn to detect my anemia, which apparently I had become very anemic during that time (which could have led to Hannah's anemia as well, in my mind).
c) Finally, one of the OB's that worked with Dr. Gregg prescribed Zithromax once my husband called and told them how very sick I still was, and was only getting worse. I did NOT want to take anything, but was assured that it was used safely in pregnancy. While on Zithromax, Hannah's movements slowed down (during my 30th-31st weeks). I went in to L&D twice for lack of fetal movement. The 1st time, the resident doctor did a sonogram and said the baby was perfectly fine (got 8 of 8 on bio profile sonogram). The 2nd time is when they said we needed to get her out as soon as possible (failed bio profile with 2 of 10). So, I had to wait out my lovenox injection and aspirin and have an emergency c-section about 12 hours later. The rest is history.
Thank you for your concern, Dr. Trofatter! Unfortunately I have no answers for my baby's death (and never will).
Knowing about my blood clotting disorder and my AGE, I don't want to lose the opportunity for a new conception to implant, so I've been given the go-ahead by my current GYN to take 40 mg of lovenox along with progesterone suppositories. I am beginning them 3-5 days after ovulation, which is today. Once pg, I will be going back to see Dr. Gregg IMMEDIATELY. He's promised to follow me closely, knowing that I will be scared to death during my next pg...
I use fertilityfriend.com to track my cycles, and noticed that my temperature is not staying raised after ovulation this past week. I don't know if that means I'm not producing enough progesterone (which is needed for implantation). So, that's another issue I'm concerned about.
Again, I appreciate you taking time out of your incredibly busy schedule, to answer questions and help troubleshoot situations such as mine.
God bless you, Doctor!!!!
Mama Shelley
p.s. Although Hannah was my first and only pregnancy, I am blessed to be the adoptive momma of 2 precious daughters and the current foster mom to a precious 7 month old we call Sweet Pea, whom I hope to adopt! We still want the opportunity to have at LEAST one birth child, and will continue our fostering/adopting endeavors to help those less fortunate in our society...those precious abused/neglected children!
At Tue Jul 15, 10:37:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous July 13: Most women with balanced translocations will eventually have a normal baby or a baby that carries the same balanced translocation (and is therefore "normal"). But sometimes it can take a lot of tries and a lot of miscarriages. Unfortunately, you do have your age working against you...hang in there. If you can stand the losses (and understand that this is nothing you can do anything about), then push on and keep trying. You do have a few more good years left! Dr T
At Tue Jul 15, 11:03:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Shelley: That sounds like a reasonable approach! Best of luck to you and let us know how tings turn out! Dr T
At Fri Jul 18, 09:07:00 AM 2008,
Anonymous said…
Dear Dr. Trofatter,
I came across this website searching for answers & found your answers extremely informative. I feel lost right now. I am a 30 year healthy woman & my problem is recurrent miscarriages. I conceived last year within the first month of trying. I had a miscarriage in April 07 at 7 weeks & I aborted naturally. I got pregnant again in the first month of trying but again miscarried at 7 weeks in Dec 07. Again I aborted naturally though after waiting 3 weeks. My doc. Did testing on the tissue & found it to be chromosomally abnormal at 46 XXY.
I wanted answers before we tried again so we went to Dr. Scher in NYC who specializes in recurrent miscarriages. They did some testing (including a saline sonogram which was perfectly normal) & found:
1. High normal homocysteine
2. An elevated plasimongen Activator Inhibitor
3. One copy of C677T MTHFR mutation
4. Borderline (suspicious) IgM Phosphoethanolamine
5. Raised CD19 B cells, which is a marker for auto-antobody secretion such resuly (4) above.
6. Slight abnormality in my husband’s seminal fluid.
Dr. Scher put me on the following treatment:
1. Once Daily Primacare prenatal vitamin & thrice daily Folic Acid (Folgard OS).
2. On day 14 of cycle start baby Aspirin & on Day 18 40mg of Lovenox daily.
3. When pregnant use 200mg of vaginal progesterone in morning & 400mg at night.
In the meantime on strong suggestion of a friend I also went to see Dr. Miklos Toth with Cornell in NYC who found some bacterial infection in my husband’s sperm & found that I had some sub clinical infection symptoms already pushed deep in my tract. He found that my pelvic muscle adhering uterus to pelvis to be inflamed (almost double ), some fluid in my left fallopian tube, which was also not as free moving as usual but straight & tight & lastly my felt ovary which was starting to adhere to the other organs. His treatment for me was an antibiotic wash similar to a Sonohysterogram during which I was given slight anesthetic. It was extremely painful & I have vague memories of crying & asking the Dr. to stop. I was alone at the procedure. He also put my husband on 10 days of antibiotics.
Since then my monthly cycle which used to be very regular have become irregular spanning 28-34 days. I have also started spotting 2-3 days before my period & my PMS symptoms have increased. Most importantly we have been trying for 2 months now & I have not become pregnant unlike before. Could the antibiotic wash be responsible for this? I will appreciate if you can tell me why I am having trouble getting pregnant this time & if earlier miscarriages could be a cause for this. Secondly, if you feel that the baby aspirin, lovenox & progesterone cream will help in preventing further miscarriages. Thirdly, Dr. Scher has told me that he will put me on Clomid from next month which I feel is not necessary since I do ovulate. What do you think ?
I appreciate all your help.
At Sun Sep 07, 06:25:00 PM 2008,
Anonymous said…
Dr. Troffatter,
I am 27 years old. I had a daughter in 2001, and a son in 2005 I got my tubes tied in 2005 and my son died at 3months old (he didnt have any problems just SIDS) I got my tubes untied 10 months after having them tied (November 2005) since then I got pregnant Dec 2006 and had a miscarriage Jan 2007 about 5 weeks along, I got pregnant again and had another miscarriage March 2008 i was about 6 weeks along and then in May 2008 had another miscarriage I was around 6 weeks along again. I believe I was pregnant last month before my menstrual cycle came on because I started feeling nauseous and took an HPT (4 HPT just to make sure)and they came out positive a day before my cycle was due but then my cycle came on a day late but it was never confirmed by the doctor. I was seen by a RE last year and was on fertility drugs and did an IUI but I didnt concieve. I was wondering what would be my next step to figure out why I cant seem to have a baby.
At Tue Sep 23, 07:55:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous Sept 7: It appears you are having 'implantation' problems. The most likely causes for this are hormonal abnormalities (sometimes subtle such as thyroid disease), fetal chromosomal abnormalities, and abnormalities of the uterus. What sorts of studies have you had done to look for any of these? Have you had any of the pregnancies tested for chromosomal abnormalities? Have you had a sonohysterogram or hysteroscopy performed? One of the REI experts with whom I work feels very strongly that subclnical endometriosis contributes very commonly to recurrent early pregnancy loss. He recommends a 3-4 month course of Lupron followed by ovulation induction and/or another form of assisted reproductive technology. Talk with your doctors about these options. Best wishes! Dr T
At Sun Sep 28, 06:57:00 PM 2008,
Shelley said…
Dr. T: Hi, it's Shelley again...I'm writing to tell you that I ended up pregnant this month, but unfortunately just miscarried at 5w1d. I could beat myself up for not taking Lovenox and doing Progesterone after ovulation. I did it 2 months ago, then just decided to give up, after emotionally losing it, thinking I'll just NEVER get pregnant. Now that I got pregnant, I KNOW I can still conceive...but I believe keeping pregnant is going to be my issue.
This miscarriage was the only "event" needed for me to get an official diagnosis of APS. With that in mind, how often do you know that therapy using Lovenox starting 3-4 days after ovulation in patients with APS works to help implantation?
I probably would have started my lovenox, along with the 81mg aspirin I already take daily, plus Progesterone, which I was taking, last Tuesday after my initial prenatal workup had I not begun miscarrying the night before.
Is there any reason NOT to take Lovenox prior to a viable pregnancy? I think Dr. Gregg was concerned that I might have an ectopic pg and the lovenox may have caused me to hemorrhage. Barring an unusual situation like that, is there any other reason why it would NOT be beneficial to start the lovenox, along with progesterone supps, within 4 days of ovulation?
At Mon Oct 06, 05:33:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Shelley: In the toughest cases, I have frequently tried starting the lovenox and progesterone during the week after ovulation. You also may be someone who would benefit from low dose prednisone even before conception, but before you go there, try the midluteal phase therapy. Best wishes. Dr T
At Wed Nov 12, 09:26:00 PM 2008,
Rithika said…
Dear Dr.T,
I have been researching about recurrent miscarriages online and found your site. Thanks for posting all these details and taking the time to answer all our questions. I am 28 and was diagnosed with PCOS (with borderline insulin resistance) and high prolactin level. I had 2 chemical pregnancies and 1 miscarrige. After my first chemical pregnancy, I had IVF which resulted in OHSS and was a chemical pregnancy. After 5 months, I had FET done. I had miscarriage at 8 weeks after seeing the heartbeat. Fetal chromosome testing was done and was normal. I had HSG, sonohysterogram and hysteroscopy done prior to IVF. After that, I had thyroid and immune testing done which showed that I have Homozygous MTHFR A1298C. Homocysteine levels were normal. All tests were normal except the MTHFR. For FET, I was put on Baby aspirin, lovenox 40 mg (both of the above started 1 week after transfer), progesterone and folgard protocol. But, I still lost my baby after weekly appointments that showed healthy baby growth and heart beat. My husband and I also got karyotype blood work done. I had D&C last month and am currently on Metformin, Bromocryptine and Folgard. The transferred embryos were of good quality after the thaw. My RE said that may be the miscarriage was bcos the embryos were not my best ones and suggested that I could be on Heparin instead of lovenox next time I am pregnant. What do you think? I am not sure what is causing these losses. Sometimes, I wonder if I did not need lovenox at all. I am really clueless and want to make sure all tests are done and that I can give birth to a healthy baby. This will be our first child. Can you please share your thoughts and recommendations.
At Thu Nov 13, 09:51:00 PM 2008,
Seema said…
Dear Dr. Trofatter,
It is Seema, the reader who used to ask you so many doubts regarding enoxaparin, role of ultrasounds in lefthandedness, maternal hyperthermia etc. etc.
I don't have anymore questions... God has blessed us with a baby boy on March 19, 2008 by a normal spontaneous vaginal delivery. We were very much delighted because March 19th is my birthday too...
We named him Johann George.
Ever since he was born, I had wanted to inform you the good news, but I was too busy with so many things... I apologize for the delay...
And I remain grateful to you for helping me with your answers during those difficult times when I was tensed and worried about so many things. Thanks once again dear doctor and may the good God bless you in all your future endeavors...
Seema George
At Sat Nov 22, 01:56:00 PM 2008,
Anonymous said…
Dr. Trofatter, I googled for complications of a missed miscarraige and infection associated with it and having MVP. The reason I was looking for info on this is because I was diagnosed as having a missed miscarraige last tuesday through an ultrasound that showed an 8wk2day fetus with no heartbeat. This is my second miscarraige, and I found out about both only after going in for a routine ultrasound. I chose to wait a week this time and do another US before having a D&C. I don't want to go through another failed pregnancy but everthing I read says that tests are not done unless you have three or more. Is this true? Also today, I started having symptoms simular to what I had right before I was diagnosed with MVP. Symptoms include faintess, shortness of breath, and heavy limbs. I am starting to think that with my MVP, it might be too risky to wait a week for the next US. The doctor did say they wouldn't let me wait more than two weeks because of infection, but since I am not sure of my last menstruel Cycle, it may allready been two weeks since the fetus died. I took a positive pregnancy test on 10-23-08(just 2 days after a neg. test) Then the US was on 11-18-08. Today is 11-22-08, and I'm not sure if I should wait till my next US appt on 11-26-08 or call in to get the pill that induces miscarraige. Please give me your insight on all of my uncertanties. Also, if it is possible, do you think I can request to see a specialist at before the tissue is gone? Thank you, Lindsay
At Thu Nov 27, 05:52:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Rithika: I believe you are in very good hands with the doctors taking care of you. I would not change the regimen you have been given unless there is another reason to do so. If you are unsuccessful the next time, it might be worth placing you on Lupron for 3-6 months before another cycle of ovulation induction and IVF/embryo transfer. Best wishes and thank for reading. Dr T
At Thu Nov 27, 05:56:00 PM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Lindsay: At this point I see little benefit to waiting. If at all possible, see if your doctors can have chromosomal studies done on the pregnancy tissues. You do not have to wait until you have had 3 or more miscarriages for at least a modest evaluation for pregnancy loss, but I would not recommend the mega workup until you have because of the high cost and the high likelihood that you will be successful without it. Best wishes. Dr T
At Fri Nov 28, 08:59:00 AM 2008,
Kenneth F. Trofatter, Jr., MD, PhD said…
To Seema: Congratulations! Thanks for letting us know how things turned out. Have fun with your baby and please stay in touch with us as he grows up! Kind regards, Dr T
At Thu Dec 04, 08:21:00 AM 2008,
Anonymous said…
Hi Dr T
The article was just fascinating! I've had 4 early miscarriages and all the tests done including genetic and nothing comes up. My Doctor has put me on clexane and says I have to use it right to the end. What do you think? I also don't like this as she says it will probably mean I'll have to have a c-section with general anaesthetic.
Thank you
Shelley K.
At Sat Jan 10, 06:14:00 PM 2009,
Anonymous said…
Hi I am 34 years old and a mom of 4yrs old girl. I had a miscarriage at 6 weeks in Feb'2008. and had another miscarriage at 9 weeks in Jan'2009. both the times i got to know only when i went for my regular doctor visit.Though i spotted a little both of the time. and i did see the heartbeat at 8 weeks the second time.
i don't know why this is happening to me even after a healthy pregnancy. i am so depressed these days. and i really don't know what should i do furhter...plz suggest..
At Sat Jan 10, 06:18:00 PM 2009,
Anonymous said…
Hi I am 34 years old and a mom of 4yrs old girl. I had a miscarriage at 6 weeks in Feb'2008. and had another miscarriage at 9 weeks in Jan'2009. both the times i got to know only when i went for my regular doctor visit.Though i spotted a little both of the time. and i did see the heartbeat at 8 weeks the second time.
i don't know why this is happening to me even after a healthy pregnancy. i am so depressed these days. and i really don't know what should i do furhter...plz suggest..
At Mon Aug 31, 11:32:00 AM 2009,
Anonymous said…
Dear Dr. Trofatter,
I have just had my fourth miscarriage. I have been diagnosed with MTHFR (homozygous) and low protein S deficiency. During both my third and fourth pregnancy I took clexane(heparin), aspirin and duphaston(progesterone). I was also taking folic acid and prenatal supplements. My third and fourth miscarriage occurred 5 week plus. Both early pregnancies. I have carried out all tests and even chromosomal tests and no translocation was identified. I honestly do not what else I can do. Would highly appreciate your opinion about the matter...
At Tue Sep 01, 04:41:00 PM 2009,
Kenneth F. Trofatter, Jr., MD, PhD said…
To anonymous Aug 31: First my questions: How old are you? Do you have any other medical problems? Do you have regular 28 day cycles? Have you had thyroid studies done? Were chromosomal studies ever done on any of the pregnancies you lost? Have you had a sonohysterogram and/or hysteroscopy done?
Dr T
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