35 Year Old Responds Well To Low Dose Clomid IUI Cycle: NOT A Low Responder!

Question:

Dr. Ramirez,

My husband and I have been infertile for more than 2 years now. We have gone through a wide variety of tests. I have had a polyp removed through operative hysteroscopy and we were asked to try on our own for 3 months afterwards (unsuccessfully). I am 35 years with borderline bad FSH (around 10 on day 3). I have a low antral follicle count (usually around 7 if they can see both ovaries during the ultrasound). We have tried 1 IUI (negative for pregnancy) and I was prescribed 50 mg Clomid on days 3 - 7 for the IUI. I ovulated 3 eggs with this dose and was triggered with an HCG shot when the 3 follicles were between 1.7 - 2.0 and IUI took place approximately 24 and 48 hours after this injection.

I have 2 questions:

1. Is the fact that I developed 3 eggs on Clomid a good or bad sign? My doctor says I will likely be what he calls a poor responder to medications because of my low antral follicle count and IVF may not be more worthwhile than IUI because of this. Does the fact that I got 3 with Clomid mean I might do better with injections then he thinks or are the 2 medications so different that my response to Clomid doesn't indicate anything?

2. What is the purpose of a blood test the day of my second IUI? I have a lot of problems with all the blood work that is required for monitoring due to bad veins (day 3 plus 4 more days of blood tests/ultrasounds before my IUI). I thought when I was triggered that would be my last blood test, but I was told I needed another blood test/ultrasound the day of my second IUI (48 hours post trigger). I asked the nurse if the blood test was essential and she said yes and it is part of the cycle monitoring that all fertility clinics require it so I forced another blood test through my already bruised veins. I understand the ultrasound was to show if the follicles released, but what would the purpose of this blood test be and is it really as essential as they say it is? (I was also on progesterone suppositories 200 mg twice a day following the IUI so I don't think it was to measure progesterone since those were prescribed regardless of the blood results).

I really appreciate you providing this service and if we do decide to travel for treatment, California will be our choice. Thanks again, A. from British Columbia

Answer:

Hello A. from Canada (British Columbia),

The fact that you responded well to low dose Clomid is very, very reassuring and I completely disagree with your doctor's opinion. FSH levels and Antral counts are indirect measures of ovarian response but not absolute. In other words, studies have shown that these numbers can vary from cycle to cycle and so the response can vary from cycle to cycle. Besides, an FSH level of 10 is not necessarily that bad. Sure, we prefer the level to be 7 or less, but it is much better than a level of 12 or greater, which I often see. Even these patients do respond to stimulation albeit only a few follicles.

So, considering that you responded well to Clomid, low dose Clomid no less, is more of an indication that you are NOT a low responder. A low responder would have only one follicle despite high dose (250mg) of Clomid. One thing these two levels do tell you, however, is that you may not have as much time to work with as you would have thought. You will need to use your time wisely and strongly consider a more aggressive approach (such as IVF). I would not recommend more than 4 IUI attempts. If that does no work (which is the number where most patients will be pregnant), then you have to go to IVF.

In terms of your second question regarding the blood test, I have absolutely no idea why it is being done. It must be something specific to your doctor. You will have to ask him. Now, I do an ultrasound after each IUI so that I can see if ovulation has occurred. That way I know that the timing was good. Since I don't know what test they did or what it could be, I can't try to explain why they would do it. It can't or shouldn't be a progesterone level, which is what we often use to determine if ovulation occurred, but that test is not valid if progesterone supplementation is given.

Thank you for your question and consideration...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.

33 Yr. Old Low Responder Trying For A 5th IVF Cycle, One Stillbirth But Not Ready For Donor Eggs Yet

Question:

Dear Dr. Ramirez:

I've just recently gone through my 5th IVF Cycle. Yesterday at retrieval they got 11 eggs but said that 6 of them were empty. The embryologist called today to say that none of the eggs fertilized and they are not sure what is going on. To give you a brief synopsis of my history:I'm 33, my husband is 46. We have been together for 6+ years. I was first diagnosed with blocked tubes back in 2005. I had bilateral tubal repair which successfully opened both tubes. Since I did not get pregnant we moved to IUI, which most of those got cancelled due to relationship difficulties. In 2008 I had a chemical pregnancy using donor sperm. My RE didn't count it because my AF started the next day after the beta. We then found out that my husband had a low sperm count. He was not tested prior to this because he has a child from a previous relationship years ago.

We did our first IVF in May 2008 with the transfer of 3 day 3 embryos. I conceived on this first attempt. However, my son was stillborn when I was 25 weeks along. We don't know the reason why because an autopsy was not performed. All I know is that I had an amnio at about 19 weeks and things were never quite the same after that. After meeting with my RE a month later he said we could try again soon because I have a high FSH which normally measures around 10 or so. The last two cycles my FSH was 9.9 and 8.8. We have done 4 IVF cycles in 2009 and all have failed.

1/09--bcp for 1 week, lupron, follistim 450, and menopur 150. 5 Eggs retrieved, 3 fertilized only one made it to day 3 transfer. Result=BFN3/09--same protocal as above, retrieved around the same amount of eggs but none fertilized.

4/09--bcp, follistim 450, menopur 150, and ganirelix towards the end of stimulation. 7 eggs retrieved, 5 were mature, 4 fertilized, and 2 made it to day 5 transfer. My RE said the day 5 transfer was of morulas (by day 5 they should be blastocyst so they were lagging behind in thier development). Result=BFN. My RE did a hysterosonogram and indicated that my uterus looks fine.

6/09--At this point we've decided to go for a 5th try, although it is now out of pocket as I've maxed out on insurance benefits for IVF. This time around my RE starts me on stimulation day 2 of my cycle with 450 follistim, and 150 menopur. No suppression. I produced more follicles than in my previous cycles. What puzzles me is that as of last Friday I had 16 follicles measuring between 14mm - 18mm and a few that were below 12mm and a few that were less than 10mm. When they did the retrieval yesterday I was a bit surprised that they only got 11 and then more than half of those were empty. The trigger shot I take is two shots of Ovidrel, one on each side. The first cycle when I got pregnant the trigger I took was Novidrel in the butt.

During all of this, after I lost my son with the stillbirth last year, the only person that did any thorough testing on me was my hematologist to find a clue as to what happened. In May 2009 he did an entire work up and discovered I had a Protein S deficiency and something else that may cause my blood to clot along with a positive PPA which he indicated could cause congestive heart failure in a fetus. His recommendation to my RE was that I should be on 81mg of baby aspirin daily and once I conceive I should be placed on Lovenox. Of course this didn't seem like a big deal of concern to my RE. His take is lets get you pregnant first.

My question is, given what I've described above, is there any change in protocol that would be recommended? I'm 33 and not ready for donor eggs but can't afford the cost of more failed cycles. Are there questions I should be asking my RE that I'm not focusing on?

Answer:

Hello,

Boy, you have gone through quite an ordeal, and I'm sorry to hear it. At least you know that you can get pregnant. Despite the fact that you are a poor responder (high FSH), your chances should still be good at your age. I am very surprised that it has failed so many times.

The stimulation protocol that you used recently (Follistim 450/Menopur 150) is my highest protocol as well. I use ganerelix (GnRH antagonist) for 1-3 days prior to retrieval to prevent spontaneous ovulation. I also use Ovidrel to trigger (only 1 shot however). Your stimulation was very good. I am very shocked that there were "empty" eggs. I presumed that meant empty cumulus, not eggs. That is something that we usually only see in Older patients (over 40). That is highly suspicious.

My protocol for patients that fail two IVF cycle is to add the following:

1. Aspirin 81 mg daily beginning at the start of the cycle continue through the pregnancy.

2. Low Dose heparin 2000 units twice per day or Lovenox 30 mg per day starting at the beginning of the cycle. Continue until 10 weeks pregnancy.

3. Medrol 16 mg per day until embryo transfer then decrease to 8 mg per day until the pregnancy test then stop.

4. Both injectable progesterone 50 mg per day beginning after the retrieval and vaginal Endometrin 100 mg vaginally twice per day beginning after the transfer.

I NEVER take low responder patients to blastocyst. I do not believe the blastocyst culturing is perfected and there is still a high embryo loss rate. I only take high responder young patients to blastocyst to decrease the number of embryos to choose from. In most cases, I transfer at day 3.

I don't know if your RE will accept some of these things because they are not well established in studies. But when my patients fail, I pull out all the plugs. The medications are not harmful or dangerous and can only help. The aspirin, heparin and medrol help to decrease the immune response AND decrease the micro clot formation in the early blood vessels going to the implantation site.

Despite all the IVF cycles you have done, at your age I would still want you to continue to try, but certainly donor eggs would be the next option. If you have implantation failure, however, and don't use the above protocol, then even donor eggs might fail. One other option would be to consider trying a different clinic because success rates are highly variable among clinics and doctors within a clinic.

I hope this helps,

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