Monday, December 26, 2011

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!

Saturday, December 17, 2011

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.

Monday, December 12, 2011

Can I Thicken Endometrium With Estrogen?


Question:

Dear Dr. Ramirez,

I´m 35 years old (will be 36 in Feb). I have been trying to get pregnant for 2 years (had a miscarriage a year ago). After going to a reproductive clinic, I´ve tried Clomid for 2 cycles with no success, an it really thinned up my endometrium, which usually wasn´t very thick (7-8mm). So my RE recommended to change to Menopur in the next cycle and do a IUI (My husband´s Kruger morphology is 5% - lab reference 4% all the rest is good). This current cycle (no meds) she did an sonogram on me on day 12 (my last period, which followed the Clomid treatment, was only 21 days longer and she wanted to check me for cysts). I had a 20mm follicle and several smaller ones, but my endometrium although trilaminar was only 7mm. For all I have been reading 7mm is not optimal thickness, although my doctor seems to think it´s ok and there´s no need to do anything.

So I was wondering how can I prime it before ovulation? Will taking estrogen help? Will it interfere with ovulation? What are the cycle days you normally recommend your patients to take it and what is the dosage?

Thanks for your time. I really appreciate it. C. from Brazil

Answer:

Hello C. from Brazil,

Yes, you can use estrogen in addition to the Menopur. I use it as an estrogen patch (Climara 0.2 mg per week up to 0.4 mg) or vaginal tablet (FemHRT, Estrace 1 mg up to 4 mg per day). As the follicles grow, they produce more and more estrogen so that should help as well. 7 mm is the minimum size needed, but ideally it should be 9 mms.

In terms of treatment, keep in mind that you have three problems going on. My opinion is that the more problems there are, the higher the treatment level you need to use. The problems identified are: (1) thin endometrial lining, (2) age factor (going on 36yo) and (3) severe male factor. Because of the age and SEVERE male factor, I would advise IVF with ICSI as the treatment of choice. The sperm may not have the ability to fertilize the egg naturally and so ICSI is required. This can only be done with IVF. IVF is also the only treatment that helps to increase pregnancy rates related to age, which is an egg problem, by increasing the number of eggs available to fertilize.

Follow-Up Question:

Thanks for answering my question, Dr. Ramirez.

When would I start taking the estradiol, cd1 and go up to ovulation? I´d like to know so I can talk to my doctor about it.

Also, now I am really concerned about the severe male factor. Is a 5% Kruger morphology that bad even if the sperm concentration is high (85 million/ml) and they show good motility (>70%)? For the IUI procedure, after swim up test and washes, can the doctor choose only the sperm that have good morphology? I´ve read that some doctors think that the Kruger method is really too strict and based on it, most males would be called fertile. What´s your opinion on that? Is there any treatment for sperm morphology (my husband is 37yo)?Thanks again for your valuable time and input! C. from Brazil

Follow-Up Answer:

Hello Again,

1. The estradiol patch or vaginal suppository would begin with CD#1 or 2.

2. If only 5% of the sperm are anatomically normal (morphology), even with an 85 Million count that means only 3.2 Million are available to actually fertilize the sperm (85 Million x 75% motility = 63.75 Million motile x 5% = 3.2 Million). This is inadequate for natural fertility. In addition, when there are sperm abnormalities, there is a high chance that there could be a defect in its ability to fertilize, and there is no test for that other than with IVF. For that reason ICSI is recommended. The embryologist will only take anatomically normal forward swimming sperm for the ICSI (if they are good embryologists).

3. I somewhat agree with the opinion regarding Kruger, but the decision has to be made based on the information that you have. Even 5% normal morphology is pretty low using Kruger.4. Unfortunately, other than ICSI there is no good treatment methods available to change morphology. There are two products that he can try, which are basically vitamins, called Proxeed and Fertility Blend. These can be purchased via the internet. He would need to use them for 3 months minimum. He can then repeat the semen analysis and see if this helps at all.

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.

Comment: Thank you again Dr. Ramirez. I wish I was still living in the US to go to your clinic :)

Tuesday, December 6, 2011

Did IVF Then Got Shingles: Could It Have Caused BFN?


Hello,

I was 5 days into my 2ww after a second IVF (in vitro fertilization). My first IVF unfortunately was a BFN (big fat negative), when I got my first ever shingles outbreak.

Then, my IVF ended up as BFN! Could shingle cause an IVF to fail. I had 4 gradeA embryos transferred. I am devastated! Thank you for your answer. A. From Georgia

Answer:

Hello A. from Georgia,

I am so sorry that your second cycle resulted in a negative and that you had to suffer shingles on top of that. I've had it myself and it is not a pleasant condition at all.

To answer your question: Yes, it is possible that a shingles outbreak could affect an implanting embryo. The immune response would be greatly heightened and could kill the embryo. That may not be the reason for the failure, but is a possible cause.

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.

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