History of Miscarriages, Now 9 Weeks Pregnant: Continue Progesterone Supplement (Crinone) ?

Question:

I'm from the U.S. After a long struggle with secondary infertility and 2 miscarriages, I am pregnant again, 9 weeks along. I'm on supplemental progesterone, Crinone 8% once a day. When can I feel okay about stopping the Crinone? I was supposed to see my doctor in 2 days, but he experienced a family tragedy, and I'm not sure when he'll be back. I think he had talked about stopping the Crinone at 9 or 10 weeks, but I was going to confirm that with him at my appointment, and I have no way of asking now.

Thank you for your time. M. from the U.S.

Answer:

Hello M. from the U.S.,

With your history of two miscarriages, I will usually be very conservative and continue the progesterone until 12 weeks gestational age.  However, medically, it would be okay to stop at 10 weeks.  By then, the placenta should be fully functional and providing all the hormone necessary to maintain the 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 

Monterey, California, U.S.A.

 

**For my readers who are unfamiliar with the use of progesterone to support a pregnancy, here are some additional facts: "Progesterone is essential for the normal functioning of the reproductive system. After ovulation, the corpus luteum (which is the empty follicle from which the egg was released) produces progesterone, which acts on the womb lining and causes it to thicken in preparation for a fertilized egg to implant. This is known as the luteal phase of the menstrual cycle. If an egg implants successfully into the womb, the corpus luteum continues to produce progesterone to maintain the pregnancy until the placenta develops fully. The placenta produces increasing amounts of progesterone until it is fully developed, when it then takes over the production of progesterone to continue to support the pregnancy.

In some women, insufficient progesterone is produced during the luteal phase and this causes problems with implantation of fertilized eggs into the womb lining and maintaining a pregnancy in the early stages. Crinone vaginal gel is used to treat this hormone deficiency. One applicatorful is inserted into the vagina every day, starting either one day after ovulation is known to have occurred, or on day 18 to 21 of the woman's cycle. (Day one is the first day of your period.) The gel is usually continued until the placenta is producing enough progesterone to support the pregnancy.
Crinone vaginal gel is also used to support pregnancy in women having in vitro fertilization (IVF). In this case the gel is used daily, starting after the embryo has been transferred into the womb, for the first 30 days of confirmed pregnancy." www.netdoctor.co.uk/pregnancy/medicines/crinone.html

 

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

 

Finally Pregnant After Multiple Miscarriages: "I Am A Nervous Wreck!"

Hello Dr. Ramirez,

I've written you in the past regarding my fertility challenges and your responses have been very encouraging. In my last, I discussed how I'd experienced an early loss in March after our first IVF attempt. You encouraged me to be strong and keep trying that my chances were good. You were right. I waited until my next cycle began and started a more simple IUI cycle again with just Follistim injections. My first miscarriage in April 2012 after IUI with Femara/GonalF was caused by trisomy 3. I found studies that said use of Femara in some women could increase the chances of aneuploidy. This time we tried without the Femara and I have become pregnant again.

I have gone through the complete RPL panel-DNA analysis, autoimmune, alloimmune, thyroid, hysteroscopy, etc. Everything has been normal. I believe the second miscarriage, because it began just 16 days after embryo transfer, was due to my body being weak (I was very sick during stimulation and had a lap/hysteroscopy/cystectomy 3 weeks before I started stimulants). I am 32, maybe borderline diminishing reserve (last AMH was .9), but otherwise nothing really bad with me.

So I am currently past 9 weeks. My betas doubled and were actually in the higher end of the ranges for weeks along. I did a viability ultrasound at 5 weeks and could see the heartbeat. Embryo measured exactly the right size. At 7 weeks we could hear the heartbeat at 174. RE saw me again at 8 weeks and said I looked good, released me to my OBGYN, said most women miscarry between 7-8 weeks. I've had no spotting or cramping. OBGYN is letting me do weekly scans until I'm through my first trimester. Heartbeat has stayed in the 170 range. Growth is continuing. Last ultrasound at 9 weeks showed the baby kicking its legs.

Here's the thing - I'm a nervous wreck. I'm terrified of something going wrong again. I am fighting to follow reason rather than fear but it is so hard. I have hardly any symptoms certainly none of the "noticeable" ones which means most of the time I don't feel like I'm pregnant. My last HCG was only at 102,900 when it was checked at 8.5 weeks, which I felt was low for where it had been but I know it slows down. My progesterone in the beginning was all the way up to 75 and is now holding at 30 (I had cysts leftover from after the IUI, made 3 follicles).
The statistics are all over the place. Some say less than 5% when heartbeat is detected but that can jump to 20% if you've had prior losses. I read it's even less once you enter the fetal stage past 8.5 weeks.

I feel stupid for asking but your answers are thoughtful. What do you think my chances are of carrying this baby to term? What would you say my change of miscarriage is? And why in the world do I hardly feel anything? I'm a little tired in the evenings and I pee in the middle of the night with crazy dreams, breasts are bigger but not sore, no nausea, etc.  But hardly anything to notice. Thank you so much for your time.  L. from Indiana

Answer:

Hello L. from the U.S. (Indiana),

CONGRATULATIONS :)  Like your RE, I release my patients at 8 1/2 weeks gestational age because the risk of miscarriage is minimal.  Statistics show that the risk of miscarriage is up to 50% prior to 8 weeks gestational age and then decreases to 5% up to 12 weeks gestation.  So you are now at 5% risk but the fact that all the signs have been good, is very encouraging and I would not worry about miscarrying.  At this point, the only risk of a miscarriage would be if there is a major genetic abnormality, and this would be a baby that you wouldn't want to go to term any way.  You should certainly consider genetic testing early to check on that.  There is now a blood screening test that can be done at an early stage.

In my experience, and as evidenced by the data, most patients will have a successful pregnancy and delivery at this point.  The fact that you "don't feel any different" with this pregnancy is irrelevant.  Every pregnancy is different and different people experience pregnancy differently.  Some have pregnancy symptoms and some have none.  You may be one of the lucky ones that doesn't have to suffer with the "morning sickness" or other such symptoms.  For now, pray that all continues to go well and thank God for the blessing.

Good Luck,

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

www.montereybayivf.com

Monterey, California, U.S.A.

 

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.

Recurrent Pregnancy Loss: 5 Miscarriages Since 2009

Question:

Hello Dr. Ramirez,

My husband and I have been trying to conceive since 2007. I have PCOS (polycystic ovarian syndrome) and I have had 5 miscarriages, first one in April 2009 at 10 weeks and the others at 6 weeks. I've also lost a baby due to an incompetent cervix at 6 months. My most recent miscarriage was last month after an IFV cycle at 6 weeks. I was on baby aspirin, progesterone shot, metformin and Estrace. My fertility specialist was not able to say why I am having these recurrent miscarriages. My doctor has done blood work and all standard testing.

After numerous IUI cycles we went ahead with IVF which also led to a miscarriage. I still have four embryos left and don't want to pursue with another IVF cycle until I can get some answers as to what might have gone wrong or what I can do to change the outcome. Do you have any suggestions for me? Any feedback is greatly appreciated. N. from Canada

Answer:

Hello N. from Canada,

I am sorry for all your losses! The incompetent cervix is something that can easily be handled with your next  pregnancy by doing a cerclage (either a TVC or a TAC by the 16th week of gestation--a TAC can also be done pre-pregnancy). But you need to achieve and hold that next pregnancy. First, let me say that you should also read my website page where I have written extensively regarding evaluation of Recurrent Pregnancy Loss (RPL) and a possible protocol for treating this problem. Anyone who has miscarried three times or more needs to have this type of comprehensive evaluation. Some of the possible reasons you may be miscarrying include:

• Genetic/Chromosomal Causes (you don't state your age, but that could be factor)
• Polyps, Fibroids & Uterine Disorders
• Hematologic Disorders
• Hormonal (you have PCOS, so your cycle day 9 & 10 LH needs to be checked )
• Infectious, Genetic & Immune Factors

With a diagnosis of "Recurrent pregnancy loss", there is a protocol that is usually followed to evaluate for the possible causes. As stated above, this includes genetic testing (both you and your husband), immunological testing, infectious disease testing, anatomical testing, hematologic testing and hormonal testing. It is quite an extensive array of tests and can take up to two months.This is what should be done BEFORE you proceed with any more IVF cycles. The treatment will then depend on what is found. In some cases, for those with genetic causes, IVF with PGD (preimplantation genetic diagnosis) can be done to test the embryos for viability and chromosomal abherrations.

What is good is that you are able to ovulate, that your eggs fertilize and that you have been able to get pregnant. It is very difficult to go through as many miscarriages as you have and I hope that with proper evaluation you will be able to deliver a beautiful, healthy child in the near future.

Good Luck,

Dr. 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.

Recurrent Pregnancy Loss (RPL) Workup Shows MTHFR: What Next?

Question:

Dear Dr. Ramirez,

I am 31 years old and have had 3 chemical pregnancies in the past 12 months. They have run a slew of genetic testing and a RPL (recurrent pregnancy loss) workup and all has come back normal with exception to the MTHFR test. I have tested positive for 1 copy of the MTHFR mutation. The nurse told me that because I was considered heterozygous that this was not a big deal. They prescribed me with a high dosage of Folic Acid. She said that it was likely not contributing to the repeat losses. I have been reading online and while the homozygous mutations seem to be more serious, there seem to be mixed reviews on whether this can contribute to early miscarriage.

Do you prescribe Lovenox or Heparin in this type of situation (only 1 copy?) Should I be concerned about this and demand that they treat it somehow? It doesn't seem like they are planning on doing anything besides the folic acid.

Also, given that this test has come back as it did, is there any other testing that you would reccommend that may be related to this? I am a little frustrated because this test was not originaly included in the work up and I had heard about it from online research and specifically requested it.

I just want to make sure that I am not missing anything.

Thank you,

D. from Boston

Answer:

Hello D. from the U.S. (Massachusetts),

The treatment for MTHFR (Methylenetetrahydrofolate reductase), is increased Folic acid (for more information MTHFR.net). But with your history of recurrent pregnancy loss or RPL, I usually will add the following to my patients, although there is not clear research backing it up if you are immunologically negative:

1. Low dose aspirin 81 mg starting with the start of the cycle

2. Low dose heparin 2000 units bid starting with the start of the cycle (you can substitute lovenox but it is more expensive).

3. Medrol 16 mg starting with the beginning of the cycle until ovulation then decrease to 8 mg

4. Increase progesterone supplementation of either Crinone 8% per day or Endometrin 100 mg three times per day starting after ovulation.

This cocktail has been shown to be effective in recurrent miscarriages (see Reproductive Immunology Associates for further information regarding immunological causes of miscarriage). My presumption is that you have had immunological testing, specifically antiphospholipid antibodies?

I hope this helps!

Good Luck,

Dr. 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

Will Removing Blocked Fallopian Tube Help This Patient Conceive?

Question:

Hi again Dr Ramirez, it's K. in NY.

I have written in the past about my multiple miscarriages/chemical pregnancies. I tested positive for the MTHFR mutation this past fall. I had a miscarriage at 9 weeks in August, which you believed was most likely due to a virus I contracted. I have followed up with a new specialist recently, and received some new information today.

First of all, my right tube is definitely blocked (although most of my miscarriages/chemical pregnancies resulted from ovulating on the right) We are led to believe that I most likely had a few early ectopic pregnancies. The specialist today suggested that I undergo surgery to remove the right tube completely. I am not sure how I feel about this, as surgery for any procedure is risky. Do you feel that having the tube removed would increase my odds of becoming pregnant? I am willing to do it if it makes sense, but hate to do it "just because". I am not sure if research supports this practice or if it doesn't really make a difference in the long run.

The second piece to this scenario is that my husband was diagnosed with a translocation between chromosomes 11 and 13 (46xy,t(11;13)(q21;14)). IVF (in vitro fertilization) was suggested to us, but we do not have the money for this and it is not an option unfortunately. Our Dr prefers to remove the tube and discuss fertility meds and other options after that point. While it explains many of our losses, I am curious if you have any other treatment suggestions. We have two healthy children that we had no difficulty conceiving. I have taken femara multiple times (pregnancy x1) and progesterone. We have not tried IUI, but were wondering if it would be of any benefit. I am just confused with all of this new information as to how to proceed conservatively. I am willing to take meds and try IUI, but I would rather not have surgery at this time unless there is a strong link between increased fertility and tube removal. Also, if we continue with meds and u/s, is there a point in being aggressive on months where I ovulate on the right?

We are just looking for the best path to take and I am hoping that you have some input to help us make an informed decision. Obviously this journey gets more difficult with every diagnosis. Thank you for your time.

Answer:
Hello K. from the U.S.(New York),

So sorry about your secondary infetility problems. To begin, there are no studies to either validate or invalidate the recommendation to remove a nonfunctioning tube unless it is blocked at the fimbriated end (called a hydrosalpinx). In that case, it has been shown to decrease pregnancies via IVF and is thought to impair implantation. It is recomnended to remove or separate the tube from the uterus. However, your doctor's recommendation is not unreasonable. Considering that it is not predictable as to which tube the egg will go into, each month you have a 50/50 chance that the egg will get picked up by the wrong/damage tube, and therefore will not get pregnant. In addition, you are risking ectopic pregnancy should the sperm get through on that side. I think that removing the tube might give you a better chance at getting pregnant because that only leaves one tube where the egg can go, and it does not matter which side the egg is ovulated from. They all go into the culdesac where the tubes lie.

In terms of your husband's translocation, that certainly can be a cause for miscarriages, just as your postive MTHFR can be a cause. There are no real good solutions for his problem other than doing PGS (preimplatation genetic screening) in conjuction with IVF. You'll just have to take your chances. I am not sure that IUI will offer you any more than trying as you have been, but statistically it does give a slightly increased chance of pregnancy if 2-3 eggs are ovulated at a time. That's the only advantage.

Good Luck,

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.

39 Yr Old TTC With Previous Miscarriage: Clomid Vs. Gonadotropins? Flare Vs. Antagonist Protocol?

Question:

Dear Doctor,

I am from India. I am 39. I had two missed abortions at 36 and 37 both in the eighth week and after the heart beat was felt.After leaving a gap of four months I have been trying to conceive naturally for 14 months without any result.

Subsequently I started Clomid 100 mg (day 3-7) at the advice of doctor.I did 3 cycles with Clomid out of which I got two follicles of ovulatory size (more than 18mm) in two of the cycles and one follicle (20mm) in one of the cycles.I did not conceive. My FSH and other hormones are normal.

I consulted a IVF specialist who examined me and said that my ovary volume is good and said that she will go for two cycles of IUI, if they are not successful she will go for IVF.

In my first cycle of IUI, the doctor did a trans-vaginal ultra sound on day 2 and gave the following medications from day 2 to day 5 (1) Suprefact 10 markings in the insulin syringe with 100 markings (BD 100 mark syringe) (between 1 to 2 pm daily)(2) GMH (human menopausal Gonadotropins (FSH+LH)) 225 IU (between 7-9 pm daily)

On day 6 she checked and told me that there is no response and the follicles have not grown.She changed the medication to GMH 375 IU per day on day 6 and day7 (between 7-9 pm daily) (She stopped Suprefact)

On day 8, she checked and told me that the follicles have not grown and advised cancellation of the cycle.Further she said that my follicles are not good enough for future trials of IVF or IUI and advised IVF with donor egg.

I asked her how I could get two ovulatory sized follicles (above 18mm) with Clomid in two of my three monitored cycles but nothing in this cycle and she is ruling out the possibility of the future trials. Her answer was that with Clomid or Letrozole even empty follicles grow and give a false impression that the follicles are growing and ovulating. But with Gonadotropins only follicles with good eggs will grow and that is the reason why my follicles did not grow with Gonadotropins. Is the above statement about Clomid and Gonadotropins correct. I will be grateful for your answer. R. from India

Answer:

Hello R. from India,

The simple answer is "NO. Her explanation is NOT correct." The gonadotropins are more effective than Clomid or Letrozole in recruiting and growing follicles because it IS the hormone the brain sends to the ovary for that purpose. Clomid and Letrozole work by an indirect method to cause the brain to increse its FSH output.

Also, she is NOT correct that gonadotropins only grow "good" follicles whereas Clomid grows "false" follicles. This explanation is made up and not scientific at all. In fact, no such thing exists. Sorry.I am not sure why your doctor cancelled your cycle. If the CD#8 ultrasound (which is early) or Estradiol level are showing a low response, the proper protocol is to continue going. Sometimes the follicle can grow slower. I have had patients get up to 21 days before ovulation occurs. In addition, the FSH should be increased if the stimulation is slow. I do not expect to have ovulatory sized follicles until at least CD#12.

I agree with you that since you stimulated with Clomid previously, you should readily stimulate with Gonadotropins as well. Maybe you should find a new IVF specialist. One thing to keep in mind, however, although your chances are still good at 39 years old, your previous miscarriage show what part of the problem is, which is that the eggs have aged and more and more of them are not of good quality. As a result, there is a higher chance of abnormal embryos which increases the miscarriage rate. IVF should help that because it increases the amount of eggs that are retrieved which in turn increases the possibility of finding an egg that is still good quality. You probably will need a high dose protocol using up to 600IU of FSH. IVF is definitely the way to go!

Follow-Up Question:

Dear Doctor,Thanks for your kind advice.The IVF specialist said the protocol given to me is the flare protocol meant for poor responders. Is that so? Then I do not understand why I did not respond to the protocol.

During my Clomid cycles my follicles reach ovulatory size by day 12. Do you think the poor response in the Gonadotropins cycle could be due the Suprefact Injection which was given from day 2 to day 5 along with Gonadotropins? Also kindly advise if it is necessary to add Suprefact or lupron early in the cycle or giving only FSH will help. Besides doctors here give Gonadotropins (FSH+LH) not Recombinant FSH. Is it better to give Recombinant FSH?

Kindly advise. R.

Follow-Up Answer:

Hello Again,

I do not like to comment on protocol specifics because there is no one way to do things. Please keep that in mind as I answer your questions. The "flare" protocol is one type of protocol used to stimulate the ovaries with IVF. It has no advantage over other protocols, but sometimes is used in patients that are designated as "poor responders". Studies have not shown it to be any better. I personally do not use the flare protocol. My preference is to use an antogonist protocol so that there is no suppression of the ovaries during the initial recruit phase, but I am in the minority in terms of centers that use this type of protocol.

In terms of your stimulation, I still think that a higher amount of medication may be warranted.

Both Suprefact and Lupron are medications called "gonadotropin agonists" and what they do is suppress the brain from producing FSH and LH.Gonadotropins are either pure FSH, pure LH or mixed FSH/LH. This is the name for that class of medications. Some IVF clinics only use FSH, some will use a mixed protocol of FSH and FSH/LH. Examples are Follistim (pure FSH) and Menopur (FSH/LH). My preference is the mixed protocol but many clinics will use FSH only protocols and some will use only the mixed FSH/LH medications. Studies have not show a necessary benefit of any of these protocols so they cannot be compared or criticized. Each doctor and/or clinic has their preferences. The most important aspect is how much FSH is being given because FSH (follicle stimulating hormone) is the hormone that stimulates follicle growth in the ovaries. Also, Natural vs Recombinant forms are equal. There is no difference.

Wishing you good luck with your TTC journey,

Dr. 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.

Patient On Metformin To Prevent Miscarriage: Is It Necessary?

Question:

HI Dr. Ramirez,

Sorry to keep this up about the Metformin, but you have been so helpful in the past...thought I would try your take on this.

I talked with my Doc about low dose heparin, and he told me that he does not prescribe this unless tested and confirmed thrombophilia is present, which he says I do not have. He would really like me to take the metformin. I have had one chemical pregnancy and one 9 week miscarriage and am currently 5 weeks pregnant. I took his advice and so far have taken 5 pills. I am extremely nauseated, which I know is from the Metformin as a few hours after it started. I REALLY DO NOT want to take this stuff after just recovering from OHSS. IS there any greater risk of miscarriage stopping now that I've started, and is there a greater risk of miscarriage if I don't take this med. I would love your thoughts on metformin and PCOS. Many sites are saying it really helps in the early stages of pregnancy for PCOS women to stay pregnant.

Thanks so much for your time....once again! C. from Canada

Answer:

Hello C. from Canada,

Metformin does nothing to help with a continuation of pregnancy and does not need to be continued once pregnant unless it was prescribed for diabetes. It is a pregnancy category B medication so is safe in pregnancy if your doctor insists that you continue it. If you were my patient, you would not be on it now. Metformin, given to help some PCO patients ovulate, is for that specific reason only. Once pregnant, the Metformin has done its job and is no longer required. If it is causing side effects, which it usually does, then I think I would recommend that you stop. There are absolutely NO recent studies that show that continuation of Metformin in PCO patients helps the pregnancy to survive or continue. Pregnancies continue or miscarry for many other reasons. Your doctor is mistaken but since he is the doctor you have chosen for your care, you have to decide if you are going to abide by his recommendations or not.

By the way, based on his comment about heparin, it is clear to me that he doesn't understand its use in recurrent miscarriage patients or infertility patients. It is obvious that he is not a specialist in that field. Please see my section on "Recurrent Pregnancy Loss".

P.S. Regardless of what many sites may be saying on the internet, you are wise to ask the advice of a medical professional.

Good luck,

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.

Secondary Infertility Patient With Seven Miscarriages: Cannot Afford IVF

Question:

Hello-I am 33 and have a healthy 3 1/2 year old daughter who was conceived naturally. I have had 7 miscarriages (1 before my daughter and 6 consecutive since her birth). I have had 4 chemicals, 2 confirmed blighted ovums and 1 xxx69..this one had a heartbeat and all hormones were great, heart stopped at 8 weeks and did a karyotype on fetal tissue.

I've been to an RE and have had the following tests: Karyotype, HSG, Day 3 Hormone Panel, Clotting Disorder Panel, ultrasound to measure lining of uterus and to check for any abnormalities...all results are "normal". I have also supplemented with progesterone after a positive pregnancy test as well, my LP is usually 11-12 days. My hubby has only had a karyotype and he is "normal" as well. The RE said that our XXX69 was more than likely due to a mutated sperm containing an entire extra set of chromosomes. He has recommended we do IVF (in vitro fertilization) with PGD (pre genetic determination).

Our insurance doesn't cover ANY fertility, so that is really not an option for us.The RE wanted to me to try a monitored clomid cycle as a plan "B". In doing some research, I just don't think clomid will help with unknown recurrent pregnancy loss...what is your opinion? I "O" just fine without any meds. What else would you recommend? I am in excellent shape, eat organic whole foods, don't consume any alcohol or caffeine..

I take prenatals and fish oil daily. Do you think that all my miscarriages could be a sperm issue? I'm really at a loss....what do you think our chances are of having another healthy child without doing IVF/PGD? Thanks, S. from Maryland.

Answer:

Hello S. from Maryland,

I am sorry for your losses. You certainly have recurrent abortion as a diagnosis, but the exact cause is unknown. Granted that the fetal tissue from the last miscarriage showed a genetic abnormality, but if your husband's genetic testing was normal, then I would not expect that all the miscarriages were for the same reason. I would think that it is more likely to be a spontaneous genetic abnormality occurring with division of the embryo. Hopefully that is the case because that means that there is still a good chance of having a normal pregnancy. If the problem is a sperm abnormality causing a genetic problem, then there is very little that can be done to change that other than using donor sperm.

One alternative would be to try IUI (intra uterine insemination), since the sperm will be washed and the best sperm will be made available for fertilization. There is no guarantee with this but it is an option. Your RE is correct in that the only way to make sure that a normal embryo is available for implantation is to do preimplantation genetic screening with IVF. Since you cannot do IVF, then the only option is to continue to try and hope/pray for the best. I do not think you need to do Clomid either. It doesn't help with this problem. The good thing is that you are still young and have time to keep trying. Hopefully with continued trying, you will be successful.

If you were my patient, I think I would add low dose aspirin 81mg per day, PNV with folic acid, Medrol 16 mg per day, progesterone supplementation in the luteal phase (Crinone or Endometrin) and low dose heparin 2000 unit injections twice per day with each cycle. These are more to cover the immunologic causes of miscarriage, but have been shown in numerous studies to help. Since we cannot be sure exactly why the previous miscarriages occurred and can't conclude that it is ONLY a genetic problem, I would favor covering those bases.

Good Luck,

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.

High Dosage Of Clomid For A "Good Egg": Why Double The Dose? Will It Affect Egg Quality?

Question:

Hi Dr. Ramirez,

I am writing from Philadelphia, PA and am 39 years old. I have had 9 pregnancies, 7 miscarriages and 2 live births. Since my last child I have had 4 miscarriages and two of the pregnancies I got pregnant with clomid (100mg a day, days 2-6).

I recently switched doctors and the new one recommended IVF with genetic testing because three of my misses were confirmed chromosonal abnormailites - but nothing else has ever been found wrong and I do have two perfectly healthy children. Well, I decided I don't want to do IVF and just take my chances of getting a "good egg" (although the last 4 weren't, I'm still hopeful that one will be). O.k, now for the question... this new doctor wants me to take 250mg of clomid days 4,5,6 and then 200mg days 7 and 8. Why more than double the dose when the lower dose got me pregnant before? Is this safe? necessary? When I call, the nurse says they want to increase my chances, but clomid doesn't effect egg quality does it? Thank you for any advice, thoughts, you can offer.

Answer:

Hello J. from the U.S.,

I am very sorry to hear about all your losses, but your age is the culprit. That is what I call the "age related egg factor". As the woman ages, the quality of her eggs decline and so there is an increased risk of abnormal embryos leading to pregnancy failure or miscarriages. IVF is recommended because we are able to get multiple eggs at the same time. With the increased number of eggs, there is a higher chance of getting a good egg that will lead to a healthy pregnancy.

PGD (pre implantation genetic diagnosis/screening) does not necessarily need to be done. In fact, I am not a big proponent of PGD if this were the only reason. I believe that the poor quality eggs will not work with IVF (i.e. not progress to viable embryos in the petri dish) and if a pregnancy ensues from the good embryos the chances are higher that it will be normal. If you absolutely want to make sure that only genetically normal embryos are transferred then PGS will be required. But then, you would have to do IVF, which you have opted not to.

The reason your doc is recommending high dose Clomid is to increase the number of eggs that you ovulate. Clomid is not the best drug for this but it is the least expensive. Using injectable medications is better but a lot more expensive. That is the only reason for using high dose Clomid in your case. By increasing the number of eggs ovulated, he is hoping that one of the eggs ovulated with be a good quality egg, just like we are trying to do with IVF. However, it may take several attempts, and you may still have miscarriages, whereas IVF would work faster and your chances of a successful pregnancy are higher.

To address your last question, Clomid will not affect the egg quality. That is already inherent in the egg. Perseverance is key in your case. I believe in letting my patients decide how they want to progress with their treatment path. You will need to keep trying, but it may take many cycles. If the miscarriages and heartbreak continue, and you truly wish to have another child, then you may have to consider in vitro fertilization.

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.

36 Year Old With 3 Miscarriages On Prometrim Using OPK : Continue With Calendar Method or Go For An Infertiity Consult?

Question:

Hi, My name is R. I am 36 years old living in Atlanta GA. My husband is 41 we do not have any kids and would like to have a baby.

In the past I have had 3 miscarriages. prior to my miscarriages, I had a hystersalpinogram(sp) when I was in my early 20's unblocking both of my tubes. Recently I had been diagnosed with Pcos and placed on Metformin 750mg 2x a day, although I have always had a regular period lasting only 3 days but it comes like clockwork every 28 days. So now let me bring you up to date. Today 08/15/2010 I had detected my LH surge via clearblue ovulation kit. But last month my doctor recommended the Clearblue ovulation test and prescribed me Prometrium.

I do not understand why I was prescribed the medication and 2 I am confused as to when to take it, the bottle says to take 3 days after ovulation, when is that? I just detected the LH surge so when should I begin taking it? In the meantime, shouldn't me and my husband be having intercourse to try and conceive? The Prometrium is a 30 count, so should I take the medication starting day 3 until its all gone? I am so confused and excited, I have never used the ovulation predictor and so I am surprised that I see this happy face, what should I do next? Beside sit and worry!

Thanks for your answer, I am anxiously awaiting to hear back from you.

Answer:

Dear R. from Georgia.,

I don't know why you have the diagnosis of PCO if you have very regular cycles, but there is a variant of PCO that you would fit into. You would not need to take Metformin, however. Did your doctor check an insulin level or how did he decide to put you on Metformin?

In terms of timing your ovulation, that is good but if you want to save yourself money, since you have such a regular cycle, the calendar method would work just as well. If using the OPK, when it turns positive, you begin intercourse (on that day#, once per day for four consecutive days #only one ejaculation per episode). With the calendar method, mark you calendar on the first day of your period then count each days in sequence. Stop having intercourse on cycle day #10 then on CD#13 begin having intercourse once per day for four consecutive days as explained above. In both cases, start the Prometrium on CD#16 and use it twice per day. Because this will suppress your menses, you will need to do a pregnancy test around CD#30.

You know, I need to emphasize that time is a critical factor in your case. I presume you have been trying for pregnancy for a while, so you & your husband really should see an infertility specialist. Your age, the miscarriages, previously blocked tubes and possible PCO diagnosis all indicate that it may be necessary. The specialist will lead you in the right direction, doing the tests that need to be done before starting an arbitrary treatment plan, and be the most efficient in helping you to get pregnant. Sometimes it may only take doing one Intra Uterine Insemination. With each year, your pregnancy rates are decreasing, even with the highest level of treatment, which is IVF, so don't waste time.

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.

32 Year Old Has Multiple Miscarriages With Secondary Infertility On Clomid With No Success: Should She See An RE?

Question:

I am 32 and writing from Texas. We are trying to have our 4th child. In Jan. 2010 I had a miscarriage at 7 weeks and subsequent D&C. It took 2 months for my cycles to even begin. Then I was put on Clomid 50mg days 5-9 for 4 cycles. I was monitored with progesterone blood checks, 14th day ultrasounds, hcg shots, and checking for over-stimulation. I ovulated every time (with a progesterone level of 27) and the doctor said my follicles and lining looked good. However, I am not pregnant and it has been 6 months since the miscarriage! My first child was conceived with clomid the 1st time.

Why is the clomid not working for me? Has it changed the cervical mucus and lining? Do other women struggle to become pregnant after a miscarriage too? The last two times that I conceived (3rd child and miscarriage) I became pregnant naturally the 1st effort made. Does miscarriage change your fertility? Should I not have clomid??

My doctor wants to take a break and then come back later and 'blow out' my tubes. Is this necessary? Do I need a different regime of medicine? I feel as though I am out of luck since the clomid did not help in conception. Should I see an RE (reproductive endocrinologist) soon?

Thank you for helping! I feel overwhelmed and just want to bring this baby into our lives. L. from Texas

Answer:

Hello L. from Texas,

I think the easiest way to answer your questions is to take them individually one at a time:

1. Since you are stimulating with the Clomid (and I presume you are ovulating more than one egg per cycle because that is the purpose of Clomid), you are responding to the Clomid. I don't know why your doc even put you on the Clomid since you were able to get pregnant on your own before. Any idea? All Clomid will do is increase the number of eggs you ovulate. It does nothing else. The body still has to go through the 9 step natural process for a pregnancy to occur. It is NOT a magic drug.

2. Clomid at high doses can change the endometrial lining causing it to thin because it is an estrogen receptor blocker and similarly change the cervical mucous. Often a Clomid cycle will have to be supplemented with estrogen if this is the case, or changed to a different medication such as Femara. The lining can easily be seen and measured by ultrasound.

3 Miscarriage is very common. It has been reported that the miscarriage rate is as high as 40% of pregnancies. This includes women who have late periods that don't even realize that they are pregnant. Statistically, 85% of women that have miscarriages will go on to have a successful pregnancy so you shouldn't worry. Your previous miscarriage does not worsen you chances of getting pregnant unless you had a major complication from it such as hemorrhage or uterine rupture.

4. The procedure to "blow out" your tubes is actually called an HSG (hysterosalpingogram). It is the test that we use to see if the tubes are open. Sometimes women will form a mucous plug in the tubes thereby inhibiting sperm passage. The HSG can push out this mucous plug and open it. It is worthwhile to make sure that the tubes are open but I would not count on it for anything else. It does hurt by the way.

5. I think that if you want the expertise of a specialist in infertility, and feel you are not getting it with your current doc, then an RE (reproductive endocrinologist) would certainly be more specialized and have more knowledge. You might want to consider that. It would be the same as going to see a Cardiologist for your heart instead of being treated by your Family practice doc. The basic knowledge of a specialist and the treatments they can offer are greater.

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.

Possible Uterine Abnormality Or Immunologic Disorder Causing Four Miscarriages In 32 Year Old: IVF With Surrogate Again?

Question:

Background: I am 32 as is my husband. We had an ectopic pregnancy 10/2005, 8.5 week miscarriage 3/2006, 10 week miscarriage 8/2006, 9 week miscarriage 2/2007 (genetic testing done - female/chromosomally normal), and 9 week miscarriage 8/2007 (male/chromosomally normal).

We had a healthy son via gestational surrogacy with my egg in 2008. During the IVF (in vitro fertilization) procedure for this surrogacy, I only produced 6 eggs and only 1 blastocyte made it to the 5 day transfer as an 8 cell blastocyte. I have Hashimoto's Disease (on medication since 2000), diagnosed with Endometriosis in 2005 (2nd lap in 1/2010 showed it is gone) and diagnosed with Adenomyosis in 1/2010, after which I took Depot Lupron for 4 months.

I have had every genetic test I've heard of and the only issue is one copy of the MTHFR gene. I took 81 ASA and Heperin with my last two pregnancies, and progesteronne with the last four. I even did IVIG with the 5th pregnancy. Two weeks ago I tested my FSH and it was normal. I also had an AMH test and it was 0.2, very low.

My RE has told me that I should try IVF (with me being the carrier) but I'm not sure. I know they are concerned about the number of eggs I have left and the quality of the eggs that are left. What I want to know is if my 2nd through 5th pregnancies could progress to 8-10 weeks with normal hearbeats and the last two we know were chromosomally normal, does this have anything to do with poor egg quality? How could these last two pregnancies test normal but be of poor quality? Is that possible?

Thanks! D. from the U.S.

Answer:

Hello D. from the U.S.,

To answer one of your last questions, since your pregnancies were know to be genetically normal, this is not an indication that you have poor egg quality. Poor egg quality leads to abnormal embryos (genetically) because the chromosomes within are fragile and break during division. It is most likely that you have either an immunologic disorder or a uterine abnormality. The latter might be the case because a surrogate was successful with your eggs.

I don't see any reason for you not to try with your own uterus if you can afford it financially. The only downside is if the uterus is a problem, you will end up miscarrying again and will have spent the money for that IVF cycle. I am not sure that I am convinced that it is a uterine problem, however, because the previous pregnancies progressed as far as they did. I would recommend that you go the gamut with the next in vitro fertilization cycle, using aspirin, heparin and IVIG if you decide to use your own uterus. That may be what it takes. If finances is an issue, then I would recommend that you use a surrogate again.

I know these are tough decisions but your young age, the positives that you have had, in addition to the child you have already had via surrogate two years ago, make your chances for another pregnancy very likely.

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.

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.

32 Year Old Canadian With Multiple Miscarriages: Do Not Despair! You Can Conceive!

Question:

Dear Dr.Ramirez,

I am a 32 years old and my husband is 34. We have been trying for a baby since July 2008. In early 2009 we conceived and were over the moon. An early dating u/s at 6 weeks showed a heartbeat but sadly I started bleeding 2 days later and naturally lost the pregnancy.

Two months later we conceived again and my doctor suggested progesterone supplements. At the 7 1/2 week u/s the baby had an extremely slow heart rate and passed one week later. I had another natural m/c.

After the second miscarriage we decided to go to a Fertility Clinic and do a full work up. Everything came back perfect. Good FSH (5.9 & 6.8), AFC count of 20, normal karyotypes, no autoimmune or blood clotting issues. All other hormones were great as well including husbands DNA sperm test.

We decided to try agian with the aid of a low dose fertility drug (puregon) and timed intercourse. I got pregnant that first cycle this January. All of early ultrasounds were perfect but sadly we found out the baby had a large cystic hygoma and T21 at 12 weeks. I just had my D&E and am totally devastated.

Could we really have such bad luck? Or is there something else going on like poor egg quality at my age? What would you recommend we try for next time?

Your response is much appreciated. D. from Canada

Answer:

Hello D. from Canada,

Despite the fact that you had three losses, I am not sure that you can bunch them together. For one thing, the last loss was due to a congenital anomaly. It was not technically a miscarriage. I presume that you doctor checked chromosomes in both you and your husband to make sure that you are not passing something along. If that is the case, and it was normal, then the congenital anomaly was just chance, as was the miscarriages.

The most common reason for miscarriage is spontaneous genetic defects. That means that when the egg was dividing, there was chromosomal breakage and so the embryo developed abnormally. In most cases, the body detects the abnormal embryo/fetus and stops the pregnancy leading to a miscarriage. It is known that most patients with multiple miscarriages will eventually be successful, so one piece of advice is to not give up. Certainly, getting pregnant is not an issue for you. Also, because you are still young, it is unlikely that you have "bad" eggs or poor egg quality. That is usually an age related phenomenon.

I know that it is emotionally draining and an absolute heartbreak to go through all these losses. But you will eventually be successful if you keep trying, so, not to belittle the losses, but it might help if you think of these as practice runs for the real thing. Also, in addition, to the progesterone supplements with each cycle, you might want to add low dose aspirin and folic acid to the regimen. Hopefully, the next pregnancy will be the good one.

Good Luck and God Bless,

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: Dear Dr.Ramirez, Thank-you so much for your prompt and informative response. My husband and I will certainly try again in the future after we take some time to heal emotionally. Your answer has given me much hope ! Also, yes we had our karyotypes checked and we do not have any genetic/inheritable issues. All of those tests were normal. I pray for a healthy baby soon.

German Woman Suffers Multiple Miscarriages Over Two Year Period - Proceed To Clomid Superovulation?

Question:

I´m 31 years old and writing from Germany. I have no children and have suffered four miscarriages. My husband and I have been TTC for 2.5 years now. After using the implanon hormone implant for birth control, I had it removed in 09/07 to begin TTC. In 11/07 I fell pregnant only to miscarry at about 5w3d. My hormone levels showed an hcg level of less than six. I was told to wait three months and try again, that I would have better luck. In March of 08 I fell pregnant a second time. At my first appt. at 8w5d it was discovered that there was a large sac with no fetal pole. I began to miscarry at 11 weeks and had an emergency D&C because I was losing so much blood. I asked that the tissue be analysed, but was told it was not done for a second loss and that this was in all likelyhood caused by a chromosomal problem. I was told to wait three months before trying to conceive again. Exactly 28 days after the D&C I got my period. I fell pregnant the next cycle, but did not realize it until I started miscarrying. My doctor did not do a blood test, only looked at an ultra sound, shrugged her shoulders and said I wasn't pregnant anymore, if I had ever been. She suggested that I could go for genetic counseling if it would make me feel better.

My husband and I went for genetic counseling, had kareotypes done, both of which came back normal, were tested for various thrombophilic conditions and immune disorders plus thyroid. My results came back as normal for everything but Leiden Factor V. I carry one copy of the gene. I was told by the geneticist that it would be good to start heparin at 8weeks in my next pregnancy and sent on my way.

In December of 08 I fell pregnant a fourth time, was given 100mg of aspirin to take starting at 4w5d. At 5w1d I began to bleed, but the ob/gyn felt that my lining still looked good, gave me progesterone supplements to take and told me to come back in five days for another ultrasound. On my return visit she could not find a sac in the uterus, and was unsure if she wasn´t seeing a sac in müllerin duct. I was told to stop the progesterone immediately and go to the hospital immediately should I have any sharp pains. Otherwise I was to report to the hospital in another five days for a beta draw. After stopping the progesterone I miscarried the next day. Three days later my hcg levels were drawn at the hospital and found to be 144, so I was required to come back every 48 hours for another draw to be sure that they were indeed falling. My levels fell nicely and I was sent home to wait three months before ttc again.We have been trying for a year now, and have not been able to get pregnant.

I have charted, used the clear blue fertility monitor and opk's to no avail. After six months I went to see an RE hoping that he would be able to give me some answers about my miscarriages, but he offered no ideas as to why, only said that my miscarriages were not a result of the Leiden Factor V. He did some bloodwork at CD13 to check my hormone levels, which he said looked very good, did a SA for my husband and a penetration test and said he saw no reason for us not to be pregnant. He suggested a doing a lap but made no further recommendations.

My regular ob/gyn was not in favor of the lap and suggested that I try a bit longer, and that if I wanted to we could try clomid and progesterone to get a stronger ovulation.I am unsure and very confused as what my next course of action should be testing and treatment wise, and if I really have a chance at having a biological child. I would appreciate any thoughts you might have on this subject. Thank you very much for your time.

Answer:

Hello L. from Germany,

Recurrent miscarriages are a difficult problem. The most common reason is because of a spontaneous chromosomal abnormality. That means it occurred when the egg was dividing, and not because you are carrying something. Hematologic disorders, such as Factor V, have been shown to increase the risk of miscarriage. Since you underwent evaluation and that was the only abnormality found, that is good because most patients with recurrent miscarriage due to spontaneous abnormalities will eventually be successful.

You mentioned that you were 31 years old, which is a good thing. Age plays a significant role in the risks of spontaneous anomalies and increases the risk of miscarriage with increasing age, especially after 35 years old. I call this the "Age related egg factor." Most patients that have recurrent miscarriages are because of age related spontaneous genetic defects. In your case, although there may still be "abnormal" or "weakened" eggs within your ovary, your chances of spontaneous defects are low. That means that your chances for success are high.

It sounds like your RE was addressing the issue of your infertility and not the recurrent miscarriage problem. Laparoscopy would be indicated to evaluate for infertility only. I don't think it is indicated at this point as well, but I wonder why you have not gotten pregnant after 1 year of trying. Something has changed and an evaluation is definitely warranted. I would go back to doing a full basic infertility evaluation and not make any assumptions, despite having gotten pregnant in the past. A hysteroscopy would be warranted to evaluate the uterine cavity because of your history of D&C. Therefore, you might also want to consider laparoscopy to complete an infertility evaluation, but not for evaluation of recurrent miscarriages.

If you don't want to do an evaluation but want to proceed with trying for pregnancy, then it is a little shot in the dark. Certainly doing Clomid "superovulation" is an option. This is where the fertility drug Clomid is used to increase the number of eggs that you ovulate per month. This can be paired with either timed intercourse or IUI. I might suggest the latter, IUI (Intra Uterine Insemination) for a higher pregnancy rate between these two. You might want to use low dose aspirin (81mg)per day and heparin (2000 units/twice per day) and medrol 16 mg per day starting from the beginning of the cycle, as well as, supplemental progesterone (vaginal or injectable) and estrogen.

The other option would be to proceed with IVF (in vitro fertilization). In this case, embryonic genetic testing, called PGS (preimplantation genetic screening) can be done to determine which are the normal embryos so that only these would be transferred. If you decided to pursue this option, I would recommend that you choose a clinic that has experience doing this and can do testing at the blastocyst stage (trophectoderm testing), rather than an earlier stage where they take one of the cells, and test with CGH (comparative genomic hybridization) .

I hope this gives you some information to consider.

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.