Recurrent Miscarriages: Is It A Hormonal Issue?

Question:

Dear Dr. Ramirez,

I am writing from Pennsylvania. In 2006, I had two or three miscarriages.  After that, I went to a fertility clinic and had TSH, prolactin, DRVV, and anti-cardiolipin antibodies tested.  All were normal.  I also had progesterone level checked at the very beginning of one of the pregnancies as well as a non-pregnant menstrual cycle after ovulation.  Both were normal.  I had irregular cycles that were anywhere from six to ten weeks apart.  I knew when I ovulated because I got pain in whichever ovary released the egg and always had a luteal phase of 14 days. I also conceived easily.  

 

The doctor felt the lining of my uterus was getting too old to sustain a pregnancy since so much time elapsed between cycles. In February 2007, I conceived on one round of Clomid and carried that child full-term.  I then had two more children in 2009 and 2011 with no help despite still having the same irregular cycles.  My cycles are a little better now and usually five to six weeks apart, but I have had three miscarriages again in September 2012, December 2013 and June 2014.  All the miscarriages I ever had were missed abortions with embryo development ending between week 5 and 6 with the exception of the most recent which ended at 11 weeks 5 days despite fetus having a strong heartbeat and normal looking development.  Since a drop in progesterone causes shedding of the lining of the uterus, is it safe to assume that since my miscarriages were not spontaneous that progesterone was not an issue?  Could other hormones be issues or was chromosomal defect the likely issue all these times? 

Thank you for your time. Sincerely, M. from Pennsylvania

Answer:

Hello M. from the U.S. (Pennsylvania),

There are basically five known causes of recurrent miscarriages from the following abnormalities: genetic, anatomic, immunologic, hormonal and infectious.  When a woman has had two or three miscarriages, she automatically has earned the diagnosis of "recurrent pregnancy loss" and as such, needs to undergo a thorough evaluation of these elements.  The most common cause of miscarriages is genetic abnormalities and is responsible for 85% of miscarriages in women over 35 years old.  A recent study showed this cause to be less in younger women.  Genetic abnormalities can be caused from an inherited disorder or a spontaneous disorder, whereby the egg makes a genetic error when it is dividing leading to an abnormal embryo.  Most of these pregnancies will end before 12 weeks gestational age.

The recommended testing is as follows:

Genetic: wife and husband chromosomal analysis, saliva DNA analysis

Anatomic: diagnostic hysteroscopy, pelvic ultrasound, end cycle endometrial biopsy for dating and b-Integrin

Immunologic: Complete antiphospholipid antibodies, natural killer cells, Factor V Leiden, MTHFR, Antinuclear antibodies, Lupus anticoagulant, anti-Thyroid antibodies

Hormonal: FSH, LH, TSH, Prolactin, Estradiol, Mid-luteal Progesterone

Infectious: GC, Chlamydia, Ureaplasma/Mycoplasma, Toxoplasmosis

Age is probably the most common major cause which leads to an increase in genetic abnormalities.  Since you don't mention your age, that could be part of the problem if you are over 35 years old.  The good news is that most women with recurrent miscarriage will eventually have a successful pregnancy.

Good Luck,

Dr. Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

www.montereybayivf.com

 

39 Year Old With Recurrent Chemical Pregnancies

Question:

Hello there! I’m writing to you from Florida. I have recently suffered two miscarriages. One in Oct of 2012 and one in March of this year. Both occurred at about two weeks so very early. I guess the term is chemical pregnancy when it is that early. I don't know how I know I am pregnant so early but I just know. My body is sensitive! I am 39 years old so my Dr. watches me closely and had me do the clomid challenge test to check the fsh which I think tests egg quality. Mine was 7.6. I also had a vaginal ultrasound and everything looks perfect. No fibroids or cysts. Then in March 2013 I got pregnant again and I was immediately sent for an hcg blood test. My hcg levels kept going up and down 241 to 119 over the course of three weeks and it would not leave my system completely so I ended up having to have another ultrasound that found nothing as they were worried about an ectopic pregnancy but did not find a sac or anything. I ended up taking a methotrexate shot.

Finally my levels went back to zero and 6 weeks later I did a complete recurrent miscarriage blood panel test and they found that I tested positive for two copies of the mthfr CT677 gene. I also was out of range for the PAI-1 test which was 51. Everything else was normal. My Dr. put me on foltx and a daily aspirin plus I take my prenatal vitamins and she told me that as soon as I find out I am pregnant again I need to start administering lovenox injections and progesterone suppositories. Right before delivery it would change to heparin. I enjoy reading your blog and appreciate all of your knowledgable answers. I would like to know what your thoughts are about the regimen she has planned for me and if there is anything else I should be doing. I am a bit nervous to try again. We really want to have a baby!  

Thank you, M. from Florida

Answer:

Hello M. from the U.S. (Florida),

The CCCT is to check for ovarian reserve (ability of the ovary to respond to stimulation) and not egg quality.  Thought you should know that.

It sounds like your Ob/Gyn doctor is well versed in the evaluation and treatment of recurrent pregnancy loss, which makes her a little better than the average Ob/Gyn doc.  One thing to keep in mind, however, is that you have the "age factor" which means that your eggs are old and debilitated and therefore have a propensity to forming abnormal embryos.  In most cases these embryos will not continue and lead to a miscarriage (especially before 8 weeks gestational age).  The age factor is the main factor that you are trying to overcome.  There is no treatment that can make eggs better.  The good news is that your ovaries are still functioning well, and you know that you can get pregnant.  Now it is just a matter of getting a perfect egg.

The increased folic acid, low dose aspirin, low dose heparin or lovenox and progesterone supplementation are all reasonable and acceptable treatments for recurrent pregnancy loss. What I would recommend is that the heparin/lovenox start immediately with the start of your period, NOT once you become pregnant.  It should already be in your system when implantation occurs to help with increased blood flow at the implantation site, and decrease the immune response to the embryo.  Starting after pregnancy would defeat the purpose.

Based on your age, I would agree with the above regimen, add CoQ10 600 mg per day (found to help with egg quality in mice.  No human studies yet but it can't hurt) and strongly recommend that you consider IVF rather than continuing to try naturally.  I know that you are able to get pregnant naturally, and it may eventually happen, but the only way to increase your chances of success (overcome the age factor) is to increase the number of eggs and embryos you have to choose from.  With IVF, you have a better chance of finding the perfect egg.  I explain it to my patients with the following analogy: imagine that you have a bucket of blue balls and a few red balls. There are mostly blue balls and only 4-5 red balls.  The red balls represent your good quality eggs and the blue balls the poor quality eggs.  These balls are all mixed up together and you lift the bucket above your head so that you can't see inside.  Now you have several options.  You can take one ball out at a time (like you would in a naturally ovulatory cycle) whereby you will eventually get a red ball, but you can see that it will take a long while; or you can take out a handful of balls out at a time (like using superovulation with fertility drugs); or you can dump out a bunch of balls at a time (like doing IVF).  You can see that the latter method is the fastest for getting to a red ball.  That is why IVF (in vitro fertilization) is the recommended treatment.  With a red ball (good quality egg) not only will you get pregnant, but you will have a successful pregnancy because a normal embryo will develop.

Sorry for the extremely long explanation, but I hope my answer has been clear.

Good Luck,

Edward J. Ramirez, M.D.
Executive Medical Director
The Fertility And Gynecology Center
Monterey Bay IVFwww.montereybayivf.com

Monterey, California, U.S.A.

40 Year Old TTC After Termination Of Trisomy Pregnancy

Hello, Doctor.


I am a 40 YO who has never had any trouble conceiving. I've been pregnant seven times. I had a child when I was 37; all went fine.

My husband and I are TTC (trying to conceive). GYN did an AMU (.86) a year ago. He said there was little hope. Nevertheless, I was pregnant in January, but the CVS @ 11 weeks revealed a double trisomy (13/21). We terminated the pregnancy.

Beginning with that particular pregnancy I have experienced pronounced pg symptoms within days of fertilization. They are symptoms I would expect to arise @ 6 weeks. I have had these symptoms each month when my husband and I try (with the exception of one month). My assumption is that I am experiencing hormone surges, but I have my period on time, and I have not had a positive urine test. I have tried a "control month" of abstiinence, and there were no symptoms. Also, no symptoms one other month (although we had tried).

I had a hormone panel on day 3 of my cycle, and another when I had begun to experience the nausea, tenderness, food aversion, fatigue, etc. GYN reported that the baseline was totally normal (FSH 3 and all other #s in range). The second test indicated that levels had changed, but still in normal range and not consistent with pregnancy. He has no explanation for these symptoms U/S's have been clear. No cysts or fibroids.

I did not experience these symptoms with my daughter or any other pregnancy.

I began taking lamictal in 09 150mg daily and .5 Klonopin daily. The addition of these meds and age are the only variables. My dx is Bipolar 1. I have found no research that supports either medication as interfering with implantation. The genetic counselor said the meds are a nonissue.

I have wondered if perhaps the procedure with the trisomy situation has harmed me somehow. My GYN said I never should have been able to implant an egg so defective.

So it seems, now, I will continue to experience these incredibly uncomfortable symptoms every time I fertilize an egg although my prospects for implantation seem dismal. I get all the bad stuff and hope for a good result that doesn't materialize.

Any words of wisdom would be appreciated.  Thanks, S. from California

Answer:

Hello S. from the U.S. (California),

Your symptoms are confusing and not easily explained. First, you cannot tell whether or not fertilization takes place. That occurs within the embryo and nothing within the body is changed at that point. You would not have symptoms. It is possible that the symptoms you are having are "hormonal shifts" or physiologically the result of the rise in progesterone in the luteal phase. Why would you be more sensitive to this now than before? I can't clearly explain that but you are also older now than you were before so maybe that had something to do with it. Normally, the pregnancy symptoms don't begin until weeks after implantation occurs, so it is unusual. But the progesterone is the culprit for PMS (premenstrual syndrome) which does have some of the symptoms that you describe. I don't think it was the D&E (dilation and evacuation).

Your doctor is right and wrong about the trisomy. It is well known that age is a significant factor and leads to increased numbers of embryos with chromosomal abnormalities. This leads to infertility and increased miscarriage rates. In most cases of complex or multiple abnormalities, the embryo never gets to the point of implantation. But if the defect is not significant enough, as in trisomies, implantation can occur but then most will end in miscarriage. Few will continue to the point where genetic testing finds the abnormality but they do occur.

As you continue to attempt pregnancy you have to remember these facts. Due to your age, it will be more difficult for you to get pregnant, you have an increased risk of miscarriages and an increased risk of abnormal embryos. Aside from your one successful pregnancy, you note that you have had six that miscarried which is troublesome. You have what we call "secondary infertility". Since there is no technology that can change the quality of your eggs, the only way to increase the chances of a successful pregnancy in older patients (over 35 years old), is to increase the number of eggs that have the opportunity to implant. This is done by increasing the number of eggs that ovulate (superovulation) or through IVF (even higher numbers of eggs). In addition, with IVF, genetic testing can be done on the eggs to eliminate the ones that are genetically abnormal so that only normal embryos are transferred. This is just food for thought.

I hope I was able to ease your concerns.

Good Luck,

Dr. Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
www.montereybayivf.com

37 Yr. Old Malaysian Woman Gets Chemical Pregnancy With First IVF: How Did Her First Cycle Look And What Are Her Chances With The Second?

Question:

Dear Doc, I would appreciate an opinion on this current IVF cycle I'm on and my previous failed cycle. I'm 37. My period is regular ie 28-32 day cycles. This is my second IVF. I started suprefact on day 21, 40 units for 13 days, 15 units from the 14th day onwards. 300 iu Gonal F on the 16th day for 4 consecutive days now. I will be seeing my RE tomorrow. My period came on the 10th day I was on Suprefact, 30 days after my previous period.

My first IVF also started on day 21, I was on suprefact for 14 days @ 40units. I started puregon 350iu on the 15th day-was on 350iu for 11 days, 250iu on the 12th day and 225 on the 13th day; suprefact was at 15 units. 13 eggs retrieved, 9 fertilised but only 4 left on the 3rd day when the transfer was done. 13dp 3dt my HCG was 375. At 18dp 3dt, my HCG was 2065. I was bleeding lightly post transfer and when the time came for the ultrasound, no sac was found and my hcg level had dropped to 117-end of my BFP. What do you think my chances are for this second cycle? I would appreciate any advise you might have. A. from K.L., Malaysia

Answer:

Hello A. from Malaysia,

Thank you for writing me all the way from Kuala Lumpur! Let me comment on the information that you have given me. The first IVF cycle looked pretty good except that the embryo development was poor. If 9 eggs fertilized, you should have had 9 embryos formed. Despite this, you were able to get pregnant, which proves that this treatment plan (IVF or in vitro fertilization) can work for you. The miscarriage has nothing to do with the IVF. Once the pregnancy occurred, it becomes an independent entity and will either progress or miscarry on its own. In your case, a chemical pregnancy occurred leading to a miscarriage. Most miscarriages occur because of spontaneous genetic/chromosomal abnormalities that occur at the time of cell division. Because the embryo was abnormal, a fetus did not develop, thus leading to the miscarriage. This was probably due to the "age factor."

As a woman ages, more and more of her eggs become weakened/debilitated leading to abnormal embryo formation. Therefore the miscarriage rate increases. Keep in mind that IVF can only give you the opportunity to get pregnant. Whether or not implantation and pregnancy occur are up to your body's and the embryo's natural processes. We do not have the technology to make that happen. It has to happen on its own. So the fact that those processes occurred is a very good sign :) and all you need now is to get a good and healthy embryo into position. Then you'll have a successful pregnancy.

I'm glad to see that you are now in another IVF cycle. Since you had a chemical pregnancy, I am confident that you can achieve pregnancy eventually. Because of your age, it will just require persistence on your part.

Good Luck on your second cycle,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

http://www.montereybayivf.com/

Monterey, California, U.S.A.

44 Year Old Woman Has Faith That She Will Conceive - Fact or Fiction?

Recently on the All Expert's site, I had an interesting comment from 44 year old woman who feels that RE's are unfairly pessimistic towards "older women" who come to them for infertility evaluations and treatment. I want to publish her point of view because it is a valid one and to point out that there is reason for optimism. It also brings to mind the recent publicity on 41 year old Celine Dion, the feature article in People magazine (Feb. 10, 2010) and her appearance on the Oprah Winfrey show. Celine has admitted publicly that she will not give up despite her age, four failed IVF cycles, and a recent miscarriage, championing the cause for those women like her who wish to conceive past the age of 40.

Comment:

I know what the stats say but I am a 44yr who went into an ivf specialist who did an iui and advised me even as he was doing it that it won't work nor will the ivf if I tried and advised me to just get a donor egg. Well, I did get pregnant on the first try even if I miscarried. I am now trying iui with injectables since I was advised by the new specialist it would work better than an ivf at this point. All my labs each time are consistent with that of a younger woman of childbearing years. Why are you guys so pessimistic for older women? Why do you suppose I got pregnant right away the first time?

I started my period at fourteen and I don't know if it has anything to do with it. I think that sometimes IVF clinics tend to cherry pick their cases to increase the level of "success" stories they can tell. I think it only fair that you fight just as hard for older patients before nudging us to donor eggs..after all the whole point of my husband and me trying to conceive is to see a by product of the two of us, otherwise we can as well adopt. I am just as confident that this cycle will work too, but when I read what you say, it's easy to loose hope but I am a faith filled woman. Pls let older folks out there know their situation is not as hopeless as stats make it sound, at least that has not been the case for me thus far.

Answer:

Thank you for your letter, although it is not a question for me to answer.

I am sorry that your RE was so pessimistic with you. However, there are two sides to this. First, we base our recommendations on statistical chances. Our purpose, as your consultant, is to give you the best and most accurate advice that we can. We cannot predict outcomes, only give you the "statistical" chances. Because IUI is a "natural" procedure, the chances of pregnancy are based on your natural pregnancy rates, which is less than 0.5% per month in your age group. That is NOT a 0% rate, so there are some 44 year olds that get pregnant naturally and with IUI and IVF. It is just a reflection of the possibilities. Part of that decreased pregnancy rate is a very high risk of miscarriage, as you experienced. That is due to old eggs leading to abnormal embryos. Nature (your body) realizes that it is an abnormal embryo and thus stops the pregnancy leading to a miscarriage. Despite the fact that you became pregnant, you need to be prepared to possibly undergo several miscarriages before being successful.

But you are correct. There are always exceptions to the rule. In fact, in November 2009, the New York Post reported a case of a woman who was 49 years old, the doctor using an egg that was retrieved & frozen from her at 48 and who successfully delivered the child conceived by IVF (Dr. Zhang of NYC see related link: http://bit.ly/5PX4k9). It took her two years of many, many IVF cycles, but her perseverance paid off. She is now the oldest woman to conceive with IVF using her own eggs, and I am sure that she was advised to use donor eggs all along the way.

Now the other side of why we advise, as we do, is because we want you to have success, NOT because we want higher statistics or make more money. I'm sure there are doctors who are unscrupulous, but most of us are not. Our mission is to help our patients get pregnant, and for you to have the highest chances of having a successful pregnancy. In addition, we also get criticized by patients, and the press, when we let patients do lower level treatments, such as IUI, for several tries and they are unsuccessful. We are then scolded for allowing the patient to attempt a procedure that would not have worked so that time was wasted. We should have "urged" or "made" the patient go directly to IVF, these patients say. Then they say that "they were not told" that the success rates were too low and that we let them try that procedure because we just wanted to take their money. I have read about MANY such cases in print and on the internet.

In general, we are NOT advising that the case is hopeless, and I know that patients don't want to hear that as well. We are advising what would give the patient the highest success rate, so that they don't get disappointed, which takes its emotional, as well as, financial toll. In my practice, I have let patients as old as 47 years old try both IUI and IVF, with very clear counseling regarding their chances for success. I do not tell them what to do. I let them choose, just as you have done. You became pregnant in your first IUI cycle, which is a triumph. That means that you still have good ovarian function, a key component to getting pregnant. The goal is to get a good egg so that you can have a successful pregnancy. IVF is more suited to this because we are able to get lots of eggs out at one time. That is why it is suited for the "age related egg factor." In an IUI cycle, you are not stimulated to the maximum point (for good reason), so the chances of getting a good egg are reduced (3-5 eggs). Whereas, with IVF, if you respond well, we can get 10-20 eggs out at a time, increasing the chances that we will find a "good" egg in that group.

If, despite all the information and knowledge you have acquired, you feel that IUI is the best route for you to take, then GO FOR IT and give it your best shot. Feel comfortable with this decision and don't doubt or regret it because you made the decision you thought was best for you. Each and every infertility patient has to do this as well.

I wish you the best of luck,

Sincerely,Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

www.montereybayivf.com

D and C or not for miscarriage.

Question:

I wrote to you several months back and took your advice on seeing a fertility specialist since I was approaching and now am 41 years of age (as of late July 2009). In mid-July I went through the pre-testing treatment, including the estrodiol day 3 levels and hsg to check for fallopian tube blockage. My estrodial was 9.6, which was ok, and my tubes were not blocked, per my doctor's review of the testing results. Well, found out that I did get pregnant just after the hsg test, and today at 8 weeks pregnant found out by ultrasound that there is no fetal heartbeat/viable pregnancy. Not sure what to do. It looks like the development stopped around week 6, and at 8 weeks my body has not registered the loss. Should I go for a DNC in a week or so or wait for a natural miscarriage. I would like to do what is best for trying to conceive as soon as possible again. Does a DNC cause extra recovery period than a natural miscarriage? I had a DNC about 3 years ago and it took me about 6 cycles to conceive at the age of 38 (which I had a beautiful girl). Now at 41 there seems to be less time, so any advice would be very appreciated. My ob/gyn told me to come to her office in a week to discuss my options - especially if I have not naturally started to miscarry in a week. Should I head back to the fertility specialist after this time and start treatment? Ultimately my question is whether a DNC has a longer recovery than a natural miscarriage? Thanks, Kim

Answer:

Hello Kim from the U.S.,
　
At this point you have three options:
　
1. Await natural miscarriage.
PROS: It is the most natural method.
CONS: It could take up to 4 weeks, it will be painful and lots of bleeding, it is unpredictable, and you may still need a D&C if all the tissue does not pass.
　
2. Medical induction of miscarriage (vaginal tablets)
PROS: Onset of miscarriage is within 24 hours, easy to use medication
CONS: Just like natural miscarriages except no waiting.
　
3. D&C (Dilation and Curettage)
PROS: Over quickly, scheduled procedure, done under anesthesia so you won't feel anything
CONS: Surgical procedure with surgical risks (infection, perforation, bleeding, anesthesia)
　
With all miscarriages, it will take time for the ovaries to reset so that you can get pregnant. This will take 6-8 weeks. Because of the inflammation caused by the D&C, you need to wait at least 6 weeks.
　
Because of your age, you are at increased risk of miscarriages due to spontaneous chromosomal abnormalities, and, yes, you time is running short. You might want to consider a more aggressive treatment method such as IVF, rather than the natural methods you are using now. IVf increases your chances of a successful pregnancy better than any other method. Otherwise, be prepared for more miscarriages before you are finally successful. Your infertility specialist should have explained exactly what your chances for pregnancy are with each method. If not, then ask.
　
I hope this helps,
　
Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
www.montereybayivf.com
　
Monterey, California, U.S.A.

for additional information check out my blog at http://womenshealthandfertility.blogspot.com check me out on facebook and twitter with me at @montereybayivf.