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

 

38 Year Old Has Five Failed Fresh IVF Cycles But Has Frozen Embies: Should She Try FET?

Question:

Hello - I have been reading you blogs for some time now and am so thankful that you take the time you do with such thoughtful answers.

I am 38 and husband is 41. My history is as follows: 2009 wasted time on clomid prescribed by my obstetrician, 2010 saw RE (reproductive endocrinologist) and began the real journey. Major issue is male factor morphology but I suspect with my age quality may be issue too.

In 2010 we had 2 Fresh IVF (in vitro fertilization) cycles, first was a failure 3 eggs collected, thankfully 3 fertilized and implanted 2 (1 frozen) but no pregnancy, cycle 2 doubled my stim meds to 300 gonal f and 150 repronex, collected 13 eggs but transferred 2 "decent" but beta was very low around 70 the pregnancy continued to around 11 weeks saw heartbeat but clearly there was issues as the size kept loosing ground until miscarriage and D&E. Cycle 3 same meds, 13 eggs, transferred 2 on day 5 and then arrived my beautiful baby girl delivered 12/29/2011.  Fast forward to 2013 where I have done two more fresh cycles same protocol, birth control, 10 lupron, to 5 lupron when stimming, retrievals after 9-10 days of stims. Cycle 4 resulted in collecting 20 eggs, 2 "decent" transferred on day 5 (blastocyst and morula) very low beta resulted in loss about a week later.  Cycle 5 same protocol except menopur instead of repronex, collected 18 eggs, 14 fertilized and transferred 2 blastocysts on day 5. This was a negative. BTW all cycles are ICSI and included medrol, baby aspirin, antibiotics, vivelle patches and  progesterone in oil injections. 

My question is what are your thoughts on FET (frozen embryo transfer).  I have 4 frozen embryos 1 from cycle 1, 1 from cycle 4 and 2 from cycle 5. RE and hubby think I should take a break and try for FET. I and concerned as I don't want to "waste" a cycle insurance will cover on the lower cost option but the meds did really affect me this time and see their point about giving my body a rest. I am at a very reputable clinic in Boston and doc said 4 frozen is a lot due to their strict freezing criteria so am optimistic although obviously embyro age has no advantage. Would FET also be something you would recommend at this point? Fresh cycles are a big logistical challenge as my husband travels 70% of the time.

Also if I go back to fresh cycle is there anything significantly different you would do (btw I am also doing acupuncture). Thank -you in advance for your time. I also want to say I am very grateful for my daughter and don't want to seem selfish but I would really like her to grow up with a sibling. 

J. from Boston

Answer:

Hello J. from the U.S. (Boston),

It sounds like you are in good hands.  Your clinic has accomplished several pregnancies, which is an IVF success.  Keep in mind that IVF can only give you the "opportunity" to become pregnant.  It can't make you pregnant because the last three steps (embryo hatching from its shell, attachment to the endometrial lining, and lining growing around the embryo are natural processes that are in God's hands.  That fact that you got a pregnancy (positive bHCG) shows that those steps occurred.  Continuation of the pregnancy is then based on pregnancy factors and not IVF factors.  Because of your age, your chances of a miscarriage are high due to abnormal embryos.  You've shown that you can get pregnant, and your ovaries stimulate very well.  Now it is just a matter of finding the perfect egg/embryo which will then lead to a successful pregnancy.  I wish all my 38 year olds responded as you do.  So hang in there!

I think I would advise proceeding with the FET cycle before another fresh cycle.  It is a much easier cycle on your body, and some newer studies are showing better pregnancy rates than fresh, probably because of the lack of overstimulation of the endometrial lining.  I don't completely agree that FET is "better" but it certainly gives a good chance.  If they fail, you can certainly try fresh cycles again.  I would advise two FET cycles consecutively.  In fact, I always advise my patients to do an FET cycle, if they have frozens, before trying a fresh cycle again.  You never know. . . the frozen might work.
In terms of additional protocol changes, you are doing everything that I have my patients do in terms of supplemental medications, but I also add low dose heparin (2000 U per day).  Not all RE's agree with this protocol, but it is an accepted protocol for recurrent pregnancy loss so you might want to ask your RE.

Thanks for following my Blog.

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.

Comment: Thank you much for the quick and thoughtful answer. I have several time contemplated seeking a more aggressive clinic despite my comfort level. Your response puts many of my worries at ease. You are truly a huge help to those of us in a constant state of limbo. Thanks again.

 

32 Yr. Old Losing Hope After One IUI Miscarriage and One IVF Chemical Pregnancy: I Say Don't Give Up!!!

Hello, I don't even know how to begin because my infertility process has been so exhausting. I suppose I have diminished ovarian reserve. My last FSH check was 8.5. My AMH is 1. My stimulation cycles response seem to change--one time will be a nice response and the subsequent ones won't be. I started my first IVF this year and I fear repeating the same pattern as last year. Last year, my first IUI on 75 follistim/femara produced 4 mature eggs. I conceived, hcg was high, but ultimately a miscarriage due to trisomy 3. Did a complete RPL work up (I had a chemical pregnancy unmedicated 6 mos earlier). Nothing was abnormal, even karotyping. I had two more IUIs after that, producing 2 eggs, then only 1 egg. No success. I battled recurrent simple follicular cysts for about six months (would bounce from one ovary to next, two cyst aspirations and they would still come back) and finally had a cystectomy and laparoscopy in early February 2013. He found very mild endometriosis and treated it. I had started birth control pills in early January, on for 5 weeks, and then carried on with an antagonist protocol later in February with 150 follistim/75menopur. My day 4 E2 was over 700, thought I had another cyst, but instead had several follicles, dropped follistim to 75, then E2 dropped to 500, then up to 100 follistim and eventually my growth balanced out. Ultimately, I had 14 follices, 12 mature, 9 eggs retrieved, 6 fertilized, 4 day 3 embryos, then 2 highest grade blastocysts, 1 morula. Transferred the two blasts. Positive beta, 175 14 days after transfer. But my 48 hour beta dropped to 77. So I'm having another chemical pregnancy/miscarriage. This is exactly a year from my last miscarriage. I am terrified that in continuing IVF I will repeat this same pattern--that the next IVFs will not work. I just don't know what to do. I don't want to be 32 and have bad eggs when I know I don't have a translocation. I feel like I do respond to lower doses of medications, which should be indicative of decent reserve, but I don't know why I would keep having such problems likely due to embryo abnormalities. I suppose my uterus may have not been ready after the surgery and it wasn't the embryo but I took the good stuff-PIO, vivelle, dexamethasone, prednisone. Anyway, can these protocols be causing me an increased risk for aneuploid embryos? What could be changed? Any comforting words that I won't face the same fate with more IVFs that I did with the repeat IUIs? With it happening the same way all over again, I am believing I'll never have a baby. Last year was so hard, this IVF was hard. I’ve had to miss so much work, surgeries, U/S, procedures, etc. And I love my husband so much. I hate that I put him through this. Thank you, L. from Oklahoma Answer: Hello L. from the U.S. (Oklahoma), First let me clarify and emphasize to you that the IVF cycle worked, and you certainly have a good chance that it will continue to work in the future.  Your doctor probably did not explain that IVF only gives you the "chance" to get pregnant.  It, in fact, cannot MAKE you pregnant because the last three steps of the reproductive process are still beyond our technology to make happen.  These steps have to happen naturally (that part is still in God's hands).  So the fact that you got pregnant on your first IVF cycle is significant because it shows that you can get pregnant!  It is unfortunate, however, that it ended as a miscarriage. In terms of going through all of your previous pregnancies and this one, that would involve a more comprehensive analysis and explanation, that is beyond this venue.  I can do that by private consultation only. Second, I think you need to get the terms "decreased ovarian reserve" and "never" out of your vocabulary.  You DON'T have decreased ovarian reserve.  Keep in mind that in IUI cycles, we only want up to three mature sized follicles so that you don't get triplets, quadruplets, etc.  So, your responses were appropriate.  With your IVF cycle you were on a very low dose protocol and the yield was appropriate. . . not too strong and not too light.  You certainly could have been stimulated a little stronger, but it looks like your ovaries are very sensitive to the fertility medications so some care needs to be taken, as your doctor did. Finally, there is no technology that can predict or evaluate for internal embryo quality.  We can evaluate chromosomes so one option you certainly could consider with IVF is to have preimplantation genetic screening (PGS).  If you decide to do PGS, I would recommend a D#5 biopsy to reduce harm to the embryo, but your embryos would need to be frozen and transferred at a different cycle.  But that would allow you to evaluate the genetics of the embryo prior to transfer.  Your doctor would also need to stimulate a little stronger to have more embryos to work with and test since surely some will return abnormal.  This will then allow you to transfer normal embryos. All clinics, doctors and the protocols they use differ and that is what influences the pregnancy rates which vary from clinic to clinic.  There are other treatment protocol options; for example, I use low dose aspirin and low dose heparin in my recurrent pregnancy loss patients.  It has been well documented to help.  You might want to discuss that with your doctor. I want you to not lose hope.  You are young, your ovaries are still responsive and you've been pregnant, so now the goal is just to get a perfect embryo so that you can have the perfect baby.  Statistically, your chances are very very high, so you will eventually be successful.  You just need to hang in there and get the best treatment that you can.  Then once you have your baby, let me know so that I can celebrate your success as well.  You are on the road to success.  The only way you will surely fail, is if you deviate from than road.  Like Law school, this is a hard road, and it may not be fair, but in the end, it will be the most wonderful experience you've ever had in your life!  Greater than falling in love.  It was for me, and I thank God for his blessing that gave me my beautiful soon to be 16 year old IVF daughter.  Keep the faith in your path and in yourself.  Sorry for the long answer...good luck! Dr. Edward J. Ramirez, M.D., FACOG Executive Medical Director The Fertility and Gynecology Center Monterey Bay IVF Program www.montereybayivf.com

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.

Second IVF Fails Despite Implantation: Thin Lining? Embryo Issue?

Question: Dear Dr. Ramirez,

I am here to seek your advice once again. I just found out my second IVF (in vitro fertilization) attempt finished with a chemical pregnancy. I tested HCG levels at 11dp2dt and it was 19,2 miu/ml (pretty low), and 48h later it was already 4,7 miu/ml.

I am nearly 37yo, have high FSH levels and my antral follicle count was 12 for this past cycle, 8 follicles grew, 6 were collected and 4 eggs retrieved. We got 100% fertilization and we transferred two 8-cell embryos with perfect morphology and no fragmentation.

I think my biggest problem is my endometrium. It is usually very thin. Although I still have 2 frozen embryos from my first IFV, two transfer cycles were cancelled due to thin lining that would never pass 6.9mm. I tried estradiol patches, vaginal estradiol (creme and pills) which resulted in poor endometrial growth (estradiol levels reached 3500pg/ml in one cycle) even after 3 weeks of use. I also tried vaginal viagra, vitamin E, baby aspirin, prednisone, and nothing worked... the endometrium would grow up to 5.5 to 6mm in the first 8-9 days of the cycle and then would take 14-21 days to reach 6.9mm. In one of the cycles it even decreased 1mm in one week.

Before my first IVF I did a hysteroscopy and everything looked fine. I have a couple small intramural fibroids, none projecting into the uterine cavity. I had a big fibroid removed 4 years ago, but it was intramural and the endometrium was not touched during surgery.

So, in my last IVF that turned out as a chemical pregnancy, my endometrium was 7.1mm at the 6th day of stimulation with FSH (Bravelle), which was really encouraging. However, 2.5 days later, it decreased to 6.4mm... Because at that time I already had bid leading follicles, my doctor wanted to triger that night. He then injected into the uterine cavity, using a catheter, 300 ug of filgrastim (G-CSF), since there are two papers from Dr. Gletcher that mention it as a possible treatment for thin lining. My RE explained to me it was experimental and I agreed to try it.

48h latter and on the time of egg retrieval, my endometrium was 7.6mm. Still not ideal, of course, but the best I got in a long time, so my RE advised us to carry on with the transfer (2 beautiful 8-cell embryos).

So my questions are:

1)What is more likely to be the cause of the chemical pregnancy: genetically abnormal embryo or my thin lining?? I know my age is a factor, but I have been taking Coq10 for nearly a year now. My embryos always look good and I have 100% fertilization rate.

2) Also, I wanted to know if it is normal to have a 8-cell embryo at the end of day 2 (I collected the eggs on Mon 9am and the embryos were transferred Wed 6pm).

3) Is it normal for the endometrium decrease during stimulation phase? What could have caused mine to go from 7.1 to 6.4mm in a little over 60h?

3) Do you think I should try filgrastim on my next transfer cycle? I don´t think my body likes synthetic estradiol though, it never responded well... so maybe a natural cycle (in which I usually reach 7mm) with filgrastim could work?

Taking my history into account, what would you recommend for my next FET in order to be suscessful in overcoming thin lining? Should I start to look into surrogacy?

As always, I really appreciate your time and expertise, and most of all the beautiful work you do here at your blog (for which I am a subscriber :)  C. From Brazil

Answer:
Hello C. from Brazil, Thank you for your kind words and for following my blog! Let me answer your questions in sequence to make it easier.

1. If endometrial thickness were the problem, implantation would not have occurred. Technically, the minimum endometrial thickness required is 6.5 mms so your lining was adequate for implantation to occur, which did happen. The miscarriage was most likely a genetic issue considering your age. Unfortunately, we do not have a technology to evaluate internal egg quality nor change the quality. Keep in mind that the CoQ 10 study was in mice and not humans so we don't know if that will work or not.

2. An 8-cell embryo on D#2 is not normal. That is a rapidly dividing embryo and may indicate that it is genetically abnormal, as has been found on preimplantation genetic studies in the past. Division rate is one of the criteria I use to evaluate embryos, in addition to the external quality.

3. The endometrium does not decrease. The difference in widths are variations in ultrasound measurements. Because we are dealing with mms, the difference between 7.1 and 6.4 (0.6) is within the margin of error and not significant.

4. I cannot comment regarding the "filgrastim" as I am not familiar with this medication or its usage. I would recommend that you consider the frozen embryo transfer in a natural, unmedicated cycle, but I would follow a natural cycle without transfer first to evaluate if your body growth the endometrium to adequate width. Then if it does, I would schedule to make do the transfer in the next cycle. I would still use supplemental hormones after the transfer, namely progesterone to help support implantation and the early pregnancy.

5. If the FET fails, despite everything that has been done, the only other recommendation I could make, if you are still going to try your own eggs, is to have preimplantation genetic screening done (trophectoderm biopsy) on a Day #5 embryo. Some studies have shown increased pregnancy rates in older patients when embryos are screened for normal genetics. That will at least give you an indication on the genetic health of the embryos you are making and whether or not you should consider donor eggs. I would only recommend surrogacy if you are absolutely sure that you cannot get implantation and in your case, you've had implantation. I think it might be more of an embryo issue.

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.

Smoking And Infertility

Question:

Dear Dr. Ramirez,

I'm 18 and I just started smoking, but I'm afraid it will effect my ability to have children. I know smoking can cause cancers, but in females, does smoking cause permanent infertility? A friend of mine told me it just causes temporary infertility, and since I'm 18 and no where near ready for a baby, I wasn't too worried. But I do want to have children when I'm older. Could you please help give me advice on this? A. from Georgia

Answer:

Hello A. from the U.S. (Georgia),

Smoking does not cause permanent infertility but has been shown to affect fertility i.e. reduce the chances. More importantly, it can cause other permanent diseases such as lung cancer, heart disease, throat cancer, stroke and deep venous thrombosis. Smoking at the time of pregnancy can lead to poor fetal development, poor fetal outcomes and other complications.

Because smoking reduces the blood vessel diameter (vascularity), it affects the chances of pregnancy by reducing blood flow to the implantation site, developing embryo and placental flow. There is also an increased risk of miscarriage.

I hope that gives you enough reason to stop while it is still easy to do so. Keep in mind that smoking is a ADDICTION and gets harder and harder to stop with time.

Good Luck,

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

Canadian Is Nine Weeks Pregnant, Has Enlarged Yolk Sac And No Fetal Pole: Is There A Problem?

Question:

Hi Dr Ramirez,

I was prescribed Clomid this cycle and am now pregnant. I am currently 9 weeks along. I went for an ultrasound at 8 weeks, 1 day pregnant and my measurements indicated that I was 8 weeks, 6 days pregnant. There was no fetal pole found. The yolk sac is measuring 8.6 mm. I am doing HCG/progesterone testing every other day -- so far all levels are within range. I am going for a follow up ultrasound at 10 weeks pregnant. Is the enlarged yolk sac a bad sign, even though my measurements and bloodwork are good?

Thanks, E. from Canada.

Answer:

Hello E. from Canada,

Assuming that your dates are correct, the yolk sac size is not a problem but the fact that there was no fetal pole or fetal heart motion at 8 weeks is bad. Usually by 6.5 weeks gestational age, a fetal pole and heart beat can be detected. This is seen for sure by 8 weeks. An empty gestational sac is called a "blighted ovum" and basically means that the sac developed but the fetus did not. You should not have to wait until 10 weeks gestational age to make the diagnosis. Your doctor should make that diagnosis already and recommend treatment.

If you wait too long, then a D&C (surgery) would be required to clear the uterus. At an earlier stage it can be done using medication alone. I should not be the one to be the bearer of bad news so I am sorry that this answer is not reassuring. You need to talk with your doctor right away and don't let them put you off or avoid the issue, like they seem to be doing.

Take care and good luck,

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

38 Year Old With One Fallopian Tube: Miscarriage With 2nd IVF

Question:

Hello Dr. Ramirez!

I am 38 and trying to conceive my 2nd child. I did 2 rounds of IVF at 35 and had a healthy daughter at age 36. We just went through another round of IVF and got pregnant, however it ended up in a miscarriage at 10 weeks. We can't afford another IVF so we're trying a few rounds of IUI with Clomid 100 mg. I'm now going for my second round.

My issues are stemmed from a ruptured appendix at 16 which left one of my fallopian tubes badly scarred. I did have a laparoscopy and had that one closed and my other one is totally open. In all the testing for my IVF, everything came back good..."for my age". My husband has a fantastic motility and count, so there's no issues there. My questions are:

1. My RE says that follicle growth is completely random and that they do not alternate sides every month. What are your thoughts on this? I hate to waste the time and money if the follicles grow on the bad side.

2. Have you seen much success with clomid/IUI at my age? Everything is totally normal with me and my husband. We eat good, (I was a smoker from 16-30 but haven't smoked in 8 years) and I rarely drink.

3. If this doesn't work, any suggestions on where to go from here?

BTW, I'm writing from Milwaukee! Thanks!

Answer:

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

First of all, it is wonderful that you were able to already have one child via IVF! This is encouraging.

1. Yes, your RE is correct that it does not alternate but is random. Also, your assumption that the side that it ovulates on is the side where it enters the tube is not correct. In fact, the ovary, being three dimensional, can have a follicle rupture at any part of its surface, even the side that is opposite where the tube is located. So how then does it get to the tube? Well, when the ovary ovulates the fluid surrounding the egg rushes out taking the egg with it and flow down-hill into a space called the culdesac. The culdesac is like a little bowl. The fluid collects here and then with simple fluid motion, it moves around. In normal anatomy, the end of the tube that picks up the egg, called the fimbria, is located in the culdesac, so it you are lucky, the egg contacts the fimbria of one tube and is brought into the tube (like an elevator) where it meets the sperm. This is why a woman who only has one tube on one side and one ovary on the opposite side can get pregnant.

2. Pregnancy rates at 38 years old are around 5% per cycle, which is not very good but it is not zero.The pregnancy rates are less with Clomid than IVF because you and your body still need to go through the 9 step process to achieve a pregnancy whereas with IVF, steps 1-7 are done by the IVF procedure and there is only two steps left to contend with.

3. Monterey, California :) I'm only kidding. You have already shown that IVF can work. The reason that you miscarried is because the embryo was probably abnormal, which is a risk that you have because of your egg. The goal is to eventually get a perfect egg that will give you a perfect and healthy baby. That is probably just a matter of time. The only alternative, which gives you a higher chance for pregnancy per cycle and less chance of a miscarriage, is using donor eggs. But you can do that at any age, so I would try again with IVF if you are not successful with your Clomid cycles, although I understand that finances are an issue. You don't have much time, though. If you do manage another IVF cycle and it fails, then you can always do donor eggs. I recently had a patient who tried IVF in her early 40's, miscarried then failed, and then gave up. At 55 she decided she wanted to try again and went with donor eggs. She now has a beautiful daughter. With donor eggs, your age is not a significant factor.

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

Implantation Problems & Causes Of Chemical Pregnancy

Question:

Hi again, it's K. in NY. I have written to you in the past about my difficulties staying pregnant. I have had 7 chemical pregnancies in the past 18 months and one miscarriage at 9 weeks after using femara (you felt it was probably due to a respiratory virus I contrated around 6 weeks). I tested positive for MTHFR mutation heterozygous but also this didn't appear to be the issue.

I guess I have a 2 part question for you. The first would be related to causes of chemical pregnancies. My progesterone levels have been on the low side of normal (even during the pregnancy that ended in miscarrige) and I really thought that was the cause. I was placed on 50 mg suppositories 2 months ago and I did get a positive result this month (8 DPO Hcg 12, progesterone 18.8, took femara and progesterone) but my HCG level was back to <5 on 10 DPO.

Are there other implantation issues that could be my problem besides chromosomal abnormalities and low progesterone that lead to a pregnancy not progressing? I know I shouldn't test early, but I was trying to establish if low progesterone levels were the cause of my losses.

Part 2: is it possible to just have an underlying HCG level that elevates above 5 regularly, and if so, what would that signify? As you may remember, my old RE wrote off the HCG values as me eating too much cereal and developing an antibody to HCG that triggers pregnancy tests. I will be visiting a new RE soon and want to be sure to ask the right questions and supply the best information.Thank you very much for all of your insight and for volunteering your services. Merry Christmas!

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

Let me take the second question first since it is the easier of the two to answer. The answer is NO, you can't have an underlying HCG level from cereal or any other source other than pregnancy. Serum pregnancy tests are very sensitive and testing for the beta subtype (bHCG), so there is no cross reaction even if the cows you were using the milk from were given hormones for some reason (I presume that is what your old RE was thinking as a source. A little far fetched if you ask me).

In terms of your chemical pregnancies, that is a difficult problem to answer. If you have already undergone a complete recurrent miscarriage evaluation (hormones, infectious diseases, anatomical, genetic, immunologic) then we may not have the technology to find the exact cause. However, the hormonal is easy to check through blood tests, and I automatically place my patients on progesterone supplementation just in case; anatomical testing would take an ultrasound and hysteroscopy, again an easy test; and infectious diseases and genetic are also easy to test. The only one that is difficult and not completely understood is the immunologic component. Many authorities have looked into many different immune factors.

If you look at a website by Reproductive Immunology Associates, who have made a practice of the immunologic causes of miscarriage, you will see lots of different test that they recommend. Because this component is so difficult to define, experts have conflicting opinions.

If you were my patient, I would put you on a protocol that I use and, for the most part, have been successful with. It involves taking aspirin 81 mg per day starting at the beginning of the cycle, medrol (prednisone) 16 mg per day taken from the beginning of the cycle then decreasing to 8 mg after ovulation, progesterone vaginal suppositories beginning after ovulation and, finally, heparin 2000 units twice per day subcutaneously beginning at the start of the cycle. The aspirin, medrol and heparin treat for subclinical immunologic problems and the aspirin and heparin also help to increase blood flow at the microvascular level at the implantation.

Good Luck & Merry Christmas to you too :) ,

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 SO much for your opinion. I will definitely have to look into these additional things. Glad to hear that I am doing all that I can do on my own and that I am advocating for the right things. It makes a HUGE difference when you have an idea what direction you should be headed so that you can work with a doctor to get there. Merry Christmas!

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.

Secondary Infertility With Miscarriage And Possible Luteal Phase Defect: Is Clomid OK?

QUESTION:

Hi Dr. Ramirez. Here I am writing again. I previously emailed you, I had a miscarriage in Feb 2010, at about 7 weeks. I have a 4 year old and a 3 year old, conceived the first month I tried with both. I also got pregnant the first time with the miscarried pregnancy. Since March I have been trying to get pregnant and nothing has happened. I have been getting my period every 25-27 days, and the last 2 months I have been doing BBT charting so I am pretty sure I am ovulating. I had hormonal blood work done in June and another estrodial draw in July and all were within normal range, Although the estrodial was a little low.

I had an HSG procedure last month; normal tubes and uterus. Now we have to have my husband's sperm checked. It has been 8 months now and for the last 6 weeks I have been having acupuncture/taking chinese herbs, to strengthen my uterus and help me relax. I have told you before that my periods are shorter and lighter since the loss, the tend to start and stop and the flow is very limited. My obgyn has now suggested that I start a low dose clomid to see if that will help me.

I have read your blog and I understand that you do not agree with clomid for people that already ovulate on their own. I am wondering if you think I should see a specialist. Also, since I have started charting I have noted that my cycle last month was just 25 days, and from the temp drop indicating ovulation to the start of my next period was only 9 days (luteal phase). This month the luteal phase was 11 days. My obgyn said that the way they would help that would also be through clomid. I thought, from reading your blog that progestorone is only suggested. If I start the clomid, do you think I should also ask for estrogen since my period is so short.

I am trying to relax doctor, but I am worried that I won't be able to get pregnant again. I am 31 years old. My husband is 38. Thanks in advance for your time and advice. J. from the U.S.

ANSWER: Hello Again,

Thank you for following my blog.

I think you misunderstood a little. I don't disagree with ovulating patients using Clomid, I just don't like docs who turn to that immediately in ovulating patients without having done a full infertility evaluation. There certainly is a place and time to use Clomid in ovulating patients, and we call that "super-ovulation". I use this especially is older patients to help them ovulate more than one egg at a time to increase there chances because as a woman ages, more and more of her eggs are debilitated and poor quality. By increasing the number ovulated, you increase the chances of getting a good egg.

In your case, even though you are ovulating, your luteal phase is too short. It is likely that you have a luteal phase defect. Your doctor is correct that Clomid can correct a luteal phase defect, although not always. What it does is correct the ovulatory-hormonal problem that is leading to the LPD. In addition, by getting you to ovulate more than one egg, it increases your chances for a pregnancy with each cycle. But, because it doesn't always correct the LPD, the treatment of choice would be supplemental progesterone such as Crinone, Procheive, Prometrium or Endometrin. You would start that after ovulation.

If you continue to fail to conceive, my recommendation would be to see a fertility specialist, instead of undergoing treatment that is more of a "shotgun" treatment. That way you don't waste too much time. But if you want to try some low dose Clomid with your current doc, that would be okay too. The advantage you have is that you are still young. If the low dose Clomid does not work, or your doc is not doing the cycles correctly, then definitely go see a fertility specialist.

I don't think you need supplemental estrogen.

Follow Up Question (Sometimes Great Things Happen When You Least Expect!):

Hi Dr. Ramirez,

I just wanted to repost and thank you so much for all your help and advice in taking the time to answer my questions over the last several months.Your answers to my questions and that of many others have always been honest, reassuring and optimistic. I never got to take the clomid, I was supposed to start January 2011, but with prescription in hand, I instead bought a HPT and I am now 10 weeks pregnant! So yes, a bit more patience and relaxation helped...9 months after my miscarriage I am pregnant. I saw the heartbeat at 6 weeks 7 days and again at 9 weeks 3 days, so I know we are not in the clear yet but we are headed to 12 weeks!

My OBGYN said that once you see the heartbeat, there's a low chance of loss. I am also taking prometrium (spelling) progesterone by mouth. My levels were good in the beginning, but my doc is just being safe with me. Is around 10 weeks gestation the time you have your patients stop taking them? Just wondering what your protocol was.

Thanks again! Keeping my fingers crossed that everything will go smoothly this time around!

J. from the U.S.

Follow Up Answer:

Hello Again,

Thank you for the kind words and CONGRATULATIONS! Once the pregnancy reaches 8 weeks and the size is appropriate for dates and the heart rate at 120 or higher, the chances of a miscarriage drop to 5% (from 40%). So, you are in a very good position for this pregnancy to keep going.

One thought: Studies have shown that progesterone (prometrium) orally does not help with luteal support. Too much of the chemical is lost in the liver. For that reason it is usually used vaginally. I usually will stop it at exactly 10 weeks gestational age, but some clinics will keep going until 12 weeks. By 10 weeks, the placenta has taken over so it doesn't do much. I think the extra time is for peace of mind.

Good luck with the pregnancy and congratulations again.

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: Excellent source of information from Dr. Ramirez. Highly value his thoughts and advice!

Alaskan Worried After First Miscarriage: Was The Cause Low Progesterone? No!

Question:

Hello, I am writing to you from a remote community in Alaska,

We have a clinic and Doctors here but, no hospital or specialists, so I am glad to have found your site and hope to receive an answer to my concern. I suffered a miscarriage on Jan 10th at 8 weeks. For the year leading up to my pregnancy I had mid cycle bleeding starting around 7 DPO. I now believe that I bled and lost my pregnancy due to low progesterone.

My MD here in town tested my levels on days 10-12-14 post ovulation and the results were 7.8 - 17.9 - 20. She says these are all normal and I can try again, but everything I see online says the numbers are in fact low and supplements should be started after I ovulate next. I also have been BBT charting and my temp drops to pre ov levels within 2 days of the ovulation spike and stays low. Do you see a low progesterone issue here and would you recommend suppositories? Please respond as I am so confused and somewhat upset that the info I am getting from my Doc. does not match the info on the web. Thank you so very much for taking the time to consider this.

I appreciate it more than you know. S. From Alaska, USA

Answer:

Hello S. from Alaska,

Thank you for writing me with your concerns. Progesterone levels measured at the mid-luteal phase do not make the diagnosis of luteal phase defect. They are mainly used to confirm ovulation. Any level above 10 confirms ovulation if the test is done in the mid-luteal phase (CD#20-22). In order to make a diagnosis of luteal phase defect, an endometrial biopsy would need to be taken at the end of the cycle to check for endometrial dating. This is usually done around CD#26-28 (before your period starts).

Progesterone is such a simple treatment with no side effects and much benefit that I do not see any harm from using it after ovulation. We certainly use it with every type of fertility treatment that we give. There are two that are made specifically for infertility treatment called Crinone and Endometrin. Another one that is used is called Prometrium but is not specifically for infertility use. You would start the supplementation on cycle day #16 and continue until a pregnancy test is done at the end of the month. Do not stop the medication until a pregnancy test is done and do not wait for a period because the progesterone will likely prevent that from occurring. If you are pregnant then you would continue it until you are 10 weeks gestational age.

Now with all that being said, a lack of progesterone is NOT the reason why you miscarried. The placenta takes over progesterone production at the 6th week so a luteal phase defect or lack of progesterone would not cause a miscarriage at that point. It is usually earlier. The most common reason for a miscarriage in the first trimester is a spontaneous chromosomal defect that occurred at the time of embryo division. This led to an abnormal embryo, which the body detected and stopped. It is most likely that you will have a successful pregnancy subsequently.

You have to take the information you find on the web with a very large grain of salt, and don't try to micro-interpret what may or may not have happened or is happening. Since you were able to get pregnant naturally before, you chances of a successful pregnancy are high. We don't worry about recurrent miscarriages until there have been at least three consecutive miscarriages. Keep trying!

Good Luck,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

www.montereybayivf.com

UK Patient Has PCOS, On Clomid For Ovulation: After First Miscarriage, Should She Continue With Clomid Or Start Injectables?

QUESTION:

I was put on 50mg Clomid due to pcos and long cycles (42-43 days). Right away, my cycles reduced to between 26-32 days. I got pregnant on my 3rd cycle of Clomid, then miscarried.

My RE recommends that I go back on Clomid, and would like me to increase my Clomid dose to 100mg so that we can recruit more than 1 egg (since I was only ovulating one egg on the 50mg dose). I will also be taking progesterone this time.

1) Do you recommend that I increase my dose of Clomid to 100mg to recruit more than one egg (even though I was ovulating normally on the 50mg dose)?

2) If the next 3 months of Clomid are unsuccessful, my doctor recommends that I try FSH injections (since I will have been on clomid for a total of 6 consecutive months, including the 3 months before my miscarriage). Do you recommend moving to FSH injections, or staying on the Clomid since it was successful previously?

3) If I cannot get pregnant again during the next 3 months on Clomid, my doctor recommended getting a laparoscopy. Just wondering if you would recommend I proceed with a laparoscopy if I fail to get pregnant again? I feel like I just got pregnant after 3 months of Clomid, so that the procedure seems unnecessary to me. (I have also had bloodwork, SA, and HSG all come back as normal).

Thank you for your advice. Sincerely,S. from the U.K.

ANSWER:

Hello S. from the U.K.,

I am sorry for your miscarriage. Considering your treatment plan, because you responded to 50mg of Clomid previously, you certainly don't need to increase the amount. However, your doctor's strategy is to get you to ovulate more than one egg at a time to increase your chances of pregnancy with each attempt. We call that super-ovulation. With increasing the number of eggs, you certainly will be increasing the chances of a multiple pregnancy. If that is not acceptable then stay with just 50mg.

I do not recommend moving to FSH injections yet. They certainly have a place but since you have gotten pregnant with Clomid before, I would just increase the Clomid dose. You can go up to 250 mg of Clomid. 3 months also seems like a short time frame for the trial unless you are over 35 years old. Then you might want to proceed more aggressively.

If you move up to the injections then I would also recommend that you add IUI in order to increase your chances even more. I don't recommend a laparoscopy at this time because I don't see a reason for it. I keep in mind that you were successful already with Clomid which shows that everything your body needs to do in order to achieve pregnancy can occur. The pregnancy re-sets the time frame. Now you just need to go back to the same plan and keep trying!

Follow Up Question:

Dr. Ramirez,

Thank you for your prompt reply. It is extremely helpful. I just have a few follow-up questions:

I mentioned previously that I was on Clomid for 3 months and got pregnant on the 3rd month (and miscarried). I have now been on Clomid for another 2 months since the miscarriage and not gotten pregnant yet. So I will be starting my 6th consecutive month of Clomid this month.

You recommended I continue with Clomid at a higher dose (rather than move straight to the FSH injections), since Clomid worked for me before.

1) Could please tell me what is the longest period that I can safely be on Clomid for? [I keep reading that one is only supposed to be on Clomid for a limit of 6 consecutive months. I am going to be starting my 6th consecutive month of Clomid this month]

2) I also keep reading about two negative effects that can occur with continuous use of Clomid. One is thinned lining (my lining has been fine so far). The second effect I have read about is hostile cervical mucus.

My RE said she is willing to do a post-coital test to check on cervical mucus if I want one, but that she does not consider it a reliable test. So my question is - how am I supposed to know if my cervical mucus is being affected by the Clomid? Also, since I am now entering my 6th month of Clomid use, should I consider taking an estrogen supplement which can possibly improve cervical mucus? Thank you very much for your advice. Regards,S.

Follow Up Answer:

Hello Again, When I answered your previous question, I was not implying that I agreed with continuous Clomid cycles. I do not. Because of the "antiestrogenic" effects of Clomid, I do not use Clomid on a continuous monthly basis. I alternate with Femara, but if that is not used, then Clomid should be used on an every-other month basis so as not to block the estrogen receptors, for exactly the reasons you indicated. Yet, as I stated above, your pregnancy reset the time frame.

In terms of the maximum number of months to use Clomid, there is no rule that says that Clomid needs to be stopped after a certain number of months. However, if pregnancy does not occur, then you should move on to the next level of treatment after six months. In your case, since you became pregnant, that reset the count. Because fertility treatments cannot control the pregnancy, and can only give you the opportunity to become pregnant, that is where treatment success ends. So you are now on your second cycle of Clomid, not your 5th.

Certainly if you want to move to the higher level of treatments such as Follistim, there is no reason that you should not. I only suggested the Clomid because it is less expensive, easier to use and worked for you before.

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.

Positive Beta But I Missed Dose Of Prometrium, Now Spotting: Am I Miscarrying?

Hello Dr. Ramirez,

I am on prometrium 200mg/1morning and 2evening. I forgot evening dose on my 12th dpo. Experienced spotting and pencil line blood in mucus next 3 days. Since I forgot to take the prometruim could I be miscarrying? Today it's 16dpo and my beta came back + but at 77. Thanks! M. from the U.S.A.

Answer:

Hello M. from the U.S.,

It is unlikely that this missed dose would cause you to miscarry. Remember, the progesterone you are taking (prometrium) is a supplement and not the only source of progesterone. Your ovary, or follicle that you ovulated from, becomes a corpus luteum cyst and is the natural source of progesterone to support implantation and an early pregnancy. Once the placental develops, it takes over the production of progesterone.

The number for your first bHCG is fine. It should double approximately every other day (48 hrs) and the trend gives a good indication of how the pregnancy is progressing until an ultrasound can be done at 6 weeks gestational age. The actual amount of rise of the bHCG is at least 80% so if it doesn't double completely, don't be worried as long as it is going up.

Good Luck and don't worry too much,

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 for the information! I appreciate the advice. I am actually moving to santa clara county and will see if it is feasible to use Dr. Ramirez as my physician!

American In The UK Taking Clomid & Has Thin Uterine Lining: Needs A Specialist

Question:

Hi Dr. Ramirez,

I will try to keep this as concise as possible. I am very healthy, slim and 29 years old, and have never had issues with my periods. My husband (29 years also) and I conceived on our first try last year, but unfortunately had a missed M/C at 12 wks (fetus stopped growing at 8 wks). Tests confirmed non-recurring genetic abnormality. After the D&C I had only spotting, until 5 days after when I had a very heavy bleed with large clots lasting only one day. Then I got my first period 6 weeks later. The 3 subsequent cycles were 42-45 days.

Pelvic ultrasound revealed PCOS, hormone levels were all normal, including thyroid. Lining on this ultrasound was only 5.5 on day 40, just before I started my period. I have just completed one round of 50 mg Clomid unmonitored due to travel, and BBT shows clear ovulation on day 18 with 12 day luteal phase. This cycle I have had my first follicle tracking on day 11 which showed dominant follicle at 15 mm, but lining of only 4 mm. My questions are:

1. Could the thin lining be due to problems from the D&C?

2. My gyn prescribed Progesterone pessaries for the second half of this cycle to help thicken the lining- is this the appropriate treatment?

3. When should I consider seeing a fertility specialist?

Thank you for your time- I am writing from London. M.

Answer:

Hello M. from the U.K.,

A thin lining could certainly be due to an over-vigorous D&C, leading to scarring in the uterus. This is called Asherman's syndrome. A procedure called hysteroscopy can be done to evaluate the uterus cavity for this. However, that being said, it is not very common to develop this with D&Cs. The more common possibility is a thin lining due to the use of Clomid.

Clomid is an estrogen receptor blocker and so blocks estrogen receptors at the endometrium (uterine lining). For that reason, many patients have to use extra estrogen given vaginally in order to overcome the blockage from the Clomid, or they use a different medication such as Femara or injectables.

Progesterone is NOT the hormone that thickens the uterine lining. Endometrial thickening and priming is dependent on ESTROGEN in the first half of the cycle. The fact that your doc told you the wrong info makes me skeptical that he/she clearly understands the physiology of this treatment. So, I think you should go see a fertility specialist instead. Without proper estrogen priming, the uterine lining will not be ready for implantation. The progesterone, which is given after ovulation, is to convert the endometrial lining to develop the "pinopodes" that are necessary for implantation. (See diagram up above, the "pinopodes" are small finger-like protrusions in the endometrium) Without the proper priming, the pinopodes will not develop.

Good Luck and keep trying, you should succeed with the right treatment path,

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 Dr. Ramirez! I am very grateful to have your opinion, which confirmed to me that I need to see a specialist. As an American living abroad, it can be daunting to find the same quality of health care that we take for granted in the US. Again, I really appreciate your help.

A Positive BHCG But Now Bleeding Two Weeks After Embryo Transfer: Am I Miscarrying?

Question:

Hello. I did an IVF transfer June 24th, was told it was a beautiful transfer of 3 beautiful embryos. This past Tuesday, July 6th, I got a positive result, however doc told me to be cautiously optimistic as it could be a chemical pregnancy because my level was 33. The next morning I woke up to cramps and started brown (old blood like) spotting, which is kind of weird for me to be honest. My cautious optimism diminishes to despair. Called doc, told me it was normal and had to wait. Retested 48 hrs later (yesterday) and it was 60, so it nearly doubled! Which was a big shocker...I was really expecting it to go down. But yeah, right?

This morning, July 10th, I woke up to heavier spotting and an actual clot like thing (which kind of looked like a massive amount of my Crinone gel). Mostly brown blood with a little red now, but mostly when I wipe after going to the bathroom (sorry TMI). They say it could be a number of things, irritation from the progesterone gel, passing of one of the embryos, or just normal pregnancy symptoms. I think they are miscarry symptoms. I go back for blood draw Monday and I am just beside myself. I am normally a pretty together person but this has turned me upside down as I feel like I'm on an emotional roller coaster. One day I think I am dealing with a m/c and then we get news that my hcg doubles. This bleeding after my embryo transfer worries me.

I guess what I'm asking is should I look at the doubling as good news or could it be my levels haven't caught up with what will happen? Could I be passing one or two embryos while one implants? Is a m/c imminent in your opinion? Any help would be most appreciated. Thank you in advance. D. from the U.S.

Answer:

Hello D. from the U.S.,

First, let me answer your last question. Based on your symptoms and bHCG levels, you CANNOT make a diagnosis of imminent miscarriage. It can go either way, but I tend to focus on the good side.

The bHCG levels doubled as they were supposed to. I generally follow them every 48 hrs for the first four levels, but your doctor has a different protocol. As long as they continue to rise and approximately double (they don't have to double exactly), then we wait and see how things go. There is only a limited amount of information that you can gather from this blood test. If they are going up, you are pregnant and things are looking good. If they plateau or drop then things are not good. One cannot necessarily predict the outcome based on the levels.

Second, I would totally disregard the spotting that you are having, and not worry unless it is bright red blood that flows like a period. Anything less than that can be "normal" at this point. Bleeding after embryo transfer is more common than you think. We see this very, very often. . . in almost 90% of our IVF patients using Crinone. In fact, there have been studies showing increased spotting with vaginal progesterones like Crinone. It is thought that the progesterone makes the cervix more prone to oozing from the surface. In any case, this type of spotting with Crinone is very common.

Not much can be known about the pregnancy at this very early point, except that you are pregnant! Now, despite the worry, you have to wait and see how things progress. Try to be optimistic and keep the stress level down. I would not assume that you are destined for a miscarriage or are miscarrying yet. It can still go either way. Whatever is destined to happen, will happen and we don't have the power to change that at this point. We can only hope and pray for the best. By the way, it is never "TMI" (too much information), rather, all the information you can provide is appreciated by a physician.

The very best of luck to you both, my thoughts are with you. Sincerely,

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

Husband & Wife With Different Blood Types: Did Rh Factor Lead To A Fetal Demise?

Question:

Hi,

I'm 33 years old my husband is 39. We are a healthy couple. Twice in one year we've gotten pregnant. First pregnancy, very early, I began to have spotting and eventually was diagnosed with an ectopic pregancy, I was given Methotrexate. This past May I was pregnant again, and during my first evaluation at 6 weeks everything was fine, except my progesterone level was low (12.17) and I began using shots and pills daily. After one week my levels reach 96.14.

At 8 weeks my evaluation showed no heartbeat, I was diagnosed with fetal demise. I'm concerned because my husband and I have different Rh and blood group (B- and O+) is this a problem? What should we do next? Infertility evaluation?

Thank you, M. writing from Puerto Rico

Answer:

Hello M. from Puerto Rico,

First of all, your difference in blood types does not lead to miscarriages. However, regarding your blood type differences, if you have a negative Rh factor (B-) and your husband is positive (O+) then you will need to receive an immunization called Rhogam (an Rh immune globulin injection), which should be given with this miscarriage, and should have been given already with the ectopic. This is because in a future pregnancy, the fetus can be affected by an immune response and develop a disorder called erythroblastosis fetalis. This is because your Rh antibodies may cross the placenta and attack the baby's red blood cells. The Rh positive baby then may develop Rh disease, a life-threatening condition that could cause anemia or other serious problems. For more on Rh factor, please visit the Mayo Clinic website: http://www.mayoclinic.com/health/rh-factor/MY01163

Secondly, you have to separate your two pregnancies because they are completely different. An ectopic is a pregnancy that implants in the tube. This is different from a miscarriage, which is in the uterus. They are not related. The only conclusion you could make is that because of a previous ectopic, you are at risk for another. However, you have already shown that you can get pregnant within the uterus despite this risk. Miscarriages are a natural occurrence. They occur in up to 40% of pregnancies, and the most common cause is a chromosomal abnormality in the developing fetus. The body (nature) realizes that the fetus is abnormal and stops the pregnancy or severe defects in the fetus causes it to die off. The good news is that most women that have miscarriages are eventually successful. You just need to keep trying and I don't think that you need to do anything different, necessarily.

Because of the progesterone issue, you might want to add supplemental progesterone after ovulation, just as a precaution. This can be given as injections or vaginal suppositories.

Despite the setbacks you have had, I am confident that you will be successful. Please follow up with your Ob/Gyn regarding your Rh factor!

Sincerely,

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.

Male Factor Infertility -- IVF Cycle FET Positive But Ended With Miscarriage: Should I Seek A Second Opinion?

Question:

Dr. Ramirez,

My husband and I are a 29yo healthy couple with male factor infertility. Motility is less than 1%, morphology is about 25-30%, and count is pretty low-normal. There are no female issues. We have done 2 IVF/ICSI cycles and one FET (frozen embryo transfer). The first IVF (in vitro fertilization) cycle, I was mildly hyperstimmed. The egg quality wasn't great, and we had about a 50% fertilization rate. We transferred 2 grade A embryos that did not result in pregnancy. No embryos made it to day 5. IVF #2 was much better and had an 80% fertilization rate. 2 day-3 grade A embryos were transferred, but there was no implantation. There were 2 day-6 blasts that were frozen. Both were starting to hatch upon thawing, and the FET resulted in a singleton pregnancy with a heartbeat at about 7 weeks. Unfortunately, I miscarried (no heartbeat) at 8 weeks.

My question to you is when should I seek a second opinion? We had planned on obtaining a 2nd opinion if the FET was unsuccessful, but we feel like technically it was successful. We like the place we go to right now and feel that they are familiar with us. We are planning to do IVF #3 in the near future and are torn as to whether we should stay here or move on. If we stay with the current practice, we will not be changing the protocol since it was successful last time. Although it has been suggested, we are not ready to use donor sperm since we were able to grow 2 blasts and achieve a pregnancy. We are located in Missouri.

Thanks in advance for your time.

Answer:

Hello L. from Missouri,

I agree with your statement that technically the FET was successful. In fact, the FET cycle WAS successful. Remember, IVF can only give you the opportunity to become pregnant. It cannot MAKE you pregnant because the last two steps in the natural process, embryo hatching and implantation, are NATURAL steps and we don't have the technology to make that happen. So, the fact that an embryo did those two steps and the pregnancy went to 7 weeks is a success. And, it is a very good sign because it now shows that what you are doing can work!

I would not give up on that clinic yet. In fact, pregnancy rates with FET are lower than fresh cycles, so a success with an FET is good. They deserve the credit. Now that they have stimulated you twice, know how you react, etc., they are hopefully in a good position to build on that the next cycle. You have to give them some credit for that.

Overall, I would hang in there. You've proven that it can work. Whether or not the pregnancy continues is solely and completely dependent on the embryo. It was probably an abnormal embryo. Now, you just need to get a good one there and you'll go all the way. Don't look back, just look forward. You should now be more encouraged than before because you know that it can work. It is just a matter of time!

On a personal note, I have a patient that I was able to get pregnant on her first try at the age of 36 and she had a beautiful child. She just came back to me for her second child at 39 (worse chances statistically) and became pregnant again, but it was an abnormal pregnancy and ended in a miscarriage. I found out today, that she is planning to transfer to another clinic because they have a "special" research program going on that gives patients a significant discount. You can't believe how heart broken and how I feel rejected by this. I put my heart and soul into my patients, and they get the best care that they can receive. I know that logically the cost is a significant issue, and this is what is driving the patient, but having gotten so close to a success, when we have been successful before, is difficult for me. That is what your clinic will think too. They'll ask themselves, "why is she leaving when we were successful under less odds?"

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.

Twitter with me at @montereybayivf, and follow me on Facebook at http://bit.ly/9Iw9oV

Comment: Dr. Ramirez clearly stated his opinion and seemed to have genuine answers. I appreciate his advice and his providing this service