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.

36 Yr. Old Has Repeated Implantation Failure With Great Embryos...What's Wrong?

Question:

Dear Dr,

We have just had our 4th failed IVF (in vitro fertilization).

Our history.  I am 36, my husband is 39. 1st pregnancy was in 2009 after 3 IuI's (intra uterine insemination) and clomid, but had to terminate at 15 weeks due to large enphaloceale (was a random genetic mutation)and my 2nd pregnancy with IUI was a success with a full term healthy baby boy.

Started with IuI's for 2nd child in 2011! We had 10 IuI's and now 4 IVF's.  Each IVF has been with icsi (intracytoplasmic sperm injection) and this time we had Embryo hatching. Last 3 transfers were 3 top grade 8 cell embryos each time on day 3.  I am not a great responder and only ever have 5-7 eggs, of which usually 4 fertilise.

I have had all the immunity checks done, my husbands sperm dna damage is within normal, fertilisation rate is good.  My ovarian reserve was also checked and the level was 1.0- My specialist said that he wasn't overly worried about the reserve for my age.  I have had a hysteroscopy and all normal.  I have been on various drug protocols and this last one was the long Lupron cycle with menapur.

We are just not sure what to do next?  Do we keep going, as my doctors are very positive and we have the finances. Are my doctors missing something?  Is there anything else we can do to improve our chances.  I am on DHEA and Royal Jelly, and my hubby is also on supplements.

I am writing from CapeTown, South Africa.

Thank you for your consideration, R.

Answer:

Hello R. from South Africa,

The exact cause of your failure cannot be known as there are still four steps your embryo has to go through in order to produce a pregnancy: embryo has to develop to blastocyst, the blastocyst has to hatch our of its shell, it then has to attach to the uterine lining and the lining has to grow around it.  As of now, there is no technology that can make this happen.  "Assisted hatching" is just making a defect in the shell so that the embryo can exit (hatch) more easily.

Something I always worry about when I have patients tell me they have failed multiple cycles despite good embryos, is the quality of the final step of the IVF process, which is the transfer.  You can have the absolute best and perfect embryos but if the transfer technique is not done well, then it will fail.  This has been shown by numerous studies.  Since you have been going to the same clinic, I wonder if that is not the problem, in which case, I would recommend that you seek out a different clinic.

One thing that I do with my patients that is not universally accepted but done by many of us, is to use a recurrent miscarriage protocol to reduce the immune system, thinking that a heightened immune system might be at fault.  For this regimen I add low dose heparin or lovenox, medrol, low dose aspirin, extra estrogen and extra progesterone (both injectable and vaginal).  I don't think that DHEA does anything so I don't use it.

At 36 years old, I have a 66% pregnancy rate in my clinic.  By two to three attempts with good 8 cell embryos, you should already be pregnant.  Your rate should especially be increased over other 36 year olds since you have been pregnant before.  For these reasons, I think the fault may lie in your clinic and not in you or your husband. 

Good luck in your journey to have a second child,

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

 

Monterey, California, U.S.A.

Use Of Prednisone And Lovenox For IVF Cycle With Donor Eggs: How Long?

Question:

Dr. Ramirez:

I am a 44-yr old with a history of numerous IVF attempts. Miraculously, cycle 1 (2007) with my own egg (yes, only one egg was retrieved) resulted in a healthy baby. 1 additional IVF attempt (2009) with my own egg - unsuccessful. Subsequently, 4 IVF attempts with two different donors (some fresh, some frozen cycles) were also unsuccessful. With each attempt, the blastocysts were high-grade, and other recipients of same donor's eggs resulted in pregnancies.

For my current cycle, which begins this week, we will be using a cryopreserved embryo, and physician is adding two medications: Prednisolone 25 mg daily, starting 10 days before transfer, and Lovenox 40mg daily, starting 2 days prior to transfer. If successful, plan is to continue both meds (along with Estrogen and Progesterone injections) for the first trimester. This seems like an extremely large dose of prednisolone and lengthy duration. I am concerned about the potential side effects on me, as well as the developing fetus, assuming a positive outcome. Do you have any experience and/or information regarding the prednisolone and Lovenox? Thank you, C. from the U.S.

Answer:

Hello C. from the U.S.,

In my patients that fail 2 IVF cycles, I automatically add prednisone, Heparin (lovenox can be used as well). All my IVF patients get the prednisone (I use medrol), low dose aspirin, progesterone and estrogen, so in reality the only thing that is new is the heparin/lovenox. Because of the potential effects on the developing fetus, I do not use the prednisone longer that the first pregnancy test. The heparin, aspirin, progesterone and estrogen are continued until the patient reaches 10 weeks gestational age. In patients that have a history of recurrent miscarriages, I will sometimes continue the medications until 12 weeks gestational age.

I start the heparin (lovenox) with the start of the IVF cycle, just like I do with the prednisone and aspirin.

Incidentally, your experience with a pregnancy in the first IVF cycle with only one embryo transferred, at the age of 40, is the reason why I DON'T ever cancel a cycle if there is only 1-3 follicles. My belief is that this one egg may lead to the one perfect embryo left and I would hate to lose the opportunity to get a pregnancy from it. It may be a lower chance, but it is still the best chance that you've got. So I am glad to hear that your docs continued the cycle and did not cancel it like so many do!

Good luck with your upcoming donor cycle.

Dr. 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.

Comment: Thank you very much for your expert opinion and extremely timely response! I greatly appreciate your time and expertise.

Overweight Woman Trying To Conceive Has Irregular Periods And Multiple Miscarriages

Question:

Hi Dr. Ramirez,

I read your blog and I love it! I learned a lot reading all your archives, so I wanted to come to you for advice about my situation.

I am 24 years old and my husband is 26. When I was 21, I was told that I have problems ovulating because my cycles were just a week of spotting after 2-6 months of nothing. My OB/GYN says that I don't ovulate due to my obesity, so I have never had any tests to check for PCOS or anything else. I am working on losing weight, but it has been a slow process. I do menstruate when given progesterone supplements, typically within hours of finishing my 10th day of 200 mg Prometrium. I also have hypothyroidism (and a strong family history of the same), but it is under control with 50 mcg levothyroxine; my most recent TSH, in January, was 1.7. I also have a family history of lupus, but do not have lupus myself.

In July 2008, I got pregnant while on Sprintec and miscarried at 5w2d, then went back on Sprintec. In October 2009, I got pregnant in my first month off Sprintec and miscarried at 5w4d, then went back on Sprintec. In February 2010, I got pregnant again in my first month off Sprintec but had a chemical pregnancy (bleeding started at 4w2d). Additionally, just from knowing my typical pregnancy symptoms in retrospect, I suspect that I might also have had a chemical while on Sprintec in April 2009, but I did not test because I was taking active pills three months at a time so I did not have a period to miss.

I have been taking OPKs twice daily (12 hours apart) since the chemical but have not ovulated; in fact, I rarely if ever see a second line at all on the tests. My OB/GYN said I can start Clomid at any time, but he is unwilling to do any testing regarding the losses until I have another miscarriage. My husband and I do not want to try to conceive again until we have tried to get an explanation for our losses.

I actually have a few questions. One, is there a reason I seem to ovulate only when I have recently been on hormonal birth control? Is it a down-regulation thing like women have before their IVF cycles? Two, is it possible that just taking Clomid might allow us to make it out of the first trimester? Three, in your opinion, is it time to move to an RE even though we have not yet been trying for a year (the only one in South Dakota is more than 200 miles away from our home)? And four, what sort of tests would an RE want us to do regarding my pregnancy losses?Thank you so very much for your time and consideration.

You provide a wonderful service, and if I'm ever in California I'd love to become a patient!

Answer:

Hello B. from South Dakota,

Thank you for reading my blog and your kind comments. I hope the information was useful.

It certainly sounds like you have an ovulation problem, and Clomid would be an appropriate treatment. However, because you have had three miscarriages, you also have the problem of recurrent miscarriage. Both of these problems would fall into the infertility category and an infertility specialist would be the best person for you to see. That way, both problems can be managed, rather than just the ovulation problem as your current doctor suggests. Regarding your weight, I have had infertility patients who are overweight and still achieve a pregnancy. There are other issues that need to be addressed that take precedence over your weight.

Let me answer your questions specifically in order:

1. I find it interesting that you were able to ovulate on the birth control pill. I'm not sure that I can explain this. Most likely, the birth control pill caused an FSH/LH burst that led to ovulation. It usually suppresses FSH/LH discharge, which is how it works.

2. Clomid will certainly help you to ovulate, at the appropriate dosage, and may correct any hormonal problems if that is the cause of your miscarriages. I would not bet on it, however. Rather, I treat ALL my infertility patients will supplemental progesterone in order to help prevent any miscarriages caused by hormonal problems. In addition, with a patient with recurrent miscarriages like yourself, I would add low dose aspirin 81 mg per day beginning at the start of the menstrual cycle, medrol 16 mg per day beginning at the start of the cycle and tapering to 8 mg per day after ovulation, then stop with the pregnancy test and heparin 2000U injections twice per day beginning at the start of the cycle. Lovenox could be substituted for this as well. An RE is the most knowledgeable with this problem and protocol.

3. I answered the question regarding the RE above, but I would recommend that you see one because of the ovulatory dysfunction and recurrent miscarriages.

4. Recurrent miscarriage evaluation includes: Hysteroscopy, pelvic ultrasound, blood tests for antiphospholipid antibody (full screen), ANA, Lupus anticoagulant, Leidin factor V, RPR, Toxoplasmosis, Chromosomal analysis in you and your husband, hormone panel.

Good Luck,

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.

Comment: Thank you so much! I plan to see if my current clinic can run the panels, then follow up with a specialist.

40 Year Old With Multiple Miscarriages Needs Correct Specialist

Question:

I have been trying to conceive for 3 years, have had 3 miscarriages, all between 6-9 weeks (one was trisomy 22, the other two are unknown. Two pregnancies required progesterone suppository supplementation). I am 40 years old, hypothyroid, insulin resistant, have a bicornuate uterus, my DRVVT came back Borderline (lupus anticoagulant, recommended re-test in 12 weeks), positive for ANA's, 1:320 titer, speckled), and compound heterozygous MTHFR gene mutation (variants C677T and A1298C). I am getting ready to try again. I was already taking synthroid 88, and 850 mg metformin twice a day.

My doctor has put me on folgard in addition to my Prenate DHA prenatal vitamin, baby aspirin, 10 mg prednisone twice a day, and I am taking 1 tbs Maca Magic, as well as 1 tsp royal jelly. Should I be taking low dose heparin as well? Lovenox? Start the progesterone suppositories immediately after ovulation?

My high risk pregnancy doctor recommended I not do IVF, because he said that at 40, my eggs are much too fragile to undergo retrieval, fertilization, analysis and reimplantation. He also indicated I would have a harder time getting pregnant after this (likely) failed. Please let me know your thoughts on this. Also, do you have any research you can direct me to, indicating that only 1 in 40 or 50 of my eggs are normal at 40 years old?

Would love to know your thoughts. I can't bear to go through another miscarriage. Thank you.

Answer:

You seem to have lots of reasons for having miscarriages, but probably the most common and predominant reason is your age. This "age factor" leads to spontaneous chromosomal aberrations that lead to abnormal embryos and subsequent miscarriage.In terms of your immune factors, just to cover those bases I would recommend either low dose heparin or lovenox. The progesterone should be started right after ovulation and continued until the pregnancy test is negative or 10 weeks gestational age.

Although you are able to get pregnant naturally, the only method that would increase your chances of a successful pregnancy is IVF. The reason is that multiple eggs can be extracted thereby increasing the chances of having a good egg (normal). It is not for sure, but will statistically increase your chances. At your current age, you probably have 1 out of 40 to 50 eggs that are normal. (When this post was published in 2009 no one really knew how many "good" eggs exist in the 35+ woman...and although it is still not 100% certain, a recent 2013 study has come out with some answers. The study found that 2 out of 20 eggs retrieved from 40 yr old women were chromosomally sound and had the potential of fertilizing and implanting successfully.) When you go through a natural cycle, you are only ovulating one egg at a time, so you can see that your chances that it will be normal is low and the chances of being abnormal is high. That is where IVF can help. With IVF you could get anywhere from 10-20 eggs at a time, depending on your ovarian function. Because time is against you, that is what I would recommend. The aforementioned medications should be used in conjunction with the IVF cycle.

As far as what your high-risk (I assume perinatologist) ob/gyn has recommended, I think you need to decide who knows fertility better. A fertility specialist or a high risk pregnancy perinatologist. As a fertility specialist, I have to disagree with your perinatologist as to your chances of pregnancy. As mentioned previously, IVF is the treatment of choice at your age. He is correct in that the chances of pregnancy are reduced because of the age related egg factor, which means that the majority of your eggs are no longer viable and prone to genetic abnormalities (spontaneous breakages), but is incorrect in saying that IVF will worsen your chances because the "eggs are too fragile for retrieval, fertilization or implantation."

In order to educate yourself regarding age related infertility and egg quality, your best source is ASRM's new website, reproductivefacts.org, sart.org or the CDC website. Each of these have the information you are asking for regarding the age-related reduction in infertility.

Good luck in your journey and don't hesitate to look for the right approach by seeking a second opinion.

Sincerely,

Edward J. Ramirez, MD, FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF

http://www.montereybayivf.com/

Recurrent Miscarriage and Factor V Leiden

Question:
Hello Dr Ramirez,
I hope you can help me.
I live in London England. And am a patient at Kings College Hospital London.I have recently miscarried for the fourth time.I had 3 previous miscarriages and following tests discovered i am heterozygous for factor v leiden.Following this I had a successful pregnancy using one low dose clexane and baby aspirin daily.I now have a beautiful baby daughter who is 8 months.I got pregnant quickly afterwards but miscarried recently at 10.5 wks again using clexane and aspirin.Can you shed any light on why I miscarried again.I thought I would be ok using the clexane etc,I thought this was the answer,but it didn't seem to work this time round.Is it likely this may happen again if I get pregnant?Is there anything else I should be trying?I hope you can advise.
Kind Regards

Answer:
Hello Nicola from the U.K.

Factor V caused recurrent miscarriage through an increased risk of blood clots at the tiny vessels feeding the pregnancy. Therefore, the key to treatment is to use medications that decrease this clotting. Obviously the low dose aspiring was sufficient for your previous pregnancy. I don't think the Dexane (dexamethasone# contributed much. It is a steroid and used mainly to decrease the inflammatory response, however I also use it for my IVf patients to reduce the chances of rejection of the embryo. The recommended treatment is to use low dose heparin #2000 units twice per day) or Lovenox beginning at the start of the menstrual cycle or treatment cycle, in addition to the aspirin. I use both. I think that your overall chances for another successful pregnancy are good. You still might have additional miscarriages but that could be due to other reasons as well. There is an overall risk of miscarriage in 40% of pregnancies just due to random abnormalities. But don't worry about it too much. Keep trying, and I am confident that you will be successful.

Sincerely,

Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
http://www.blogger.com/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