40 Yr Old German Woman With Great Ovarian Stim Fails IVF: Likely Abnormal Embryos, Try Again!

Question:

Dear Dr. Ramirez,

My name is A. from Germany, 40 years old, never pregnant before. I had 2 failed IVF this year (1 in March, 1 in June). My FSH=10.6, AMH=0.8. progesterone level is normal.

The 1.IVF had 6 eggs (2 embryos were transferred: 1 grade 1 and 1 grade 2) and 2.IVF had 7 eggs (3 embryos with grade 1 were transferred in July).

The 2.IVF was done in North Cyprus. Do you think the failure was caused by taking airplane back home on the 2.day after transfer? It was just about 3.5 hours flight.I will try the 3.IVF this year.

How long should I take a break before trying the 3.IVF? Because I heard that the hormone level, uterus lining and ovary need time to get back to normal. Are these correct? I have also read an answer of yours regarding implantation failure.

You wrote in March this year:

"My approach to patients with implantation failure is to add the following medications:
1. Aspirin 81 mg per day beginning at the start of the cycle.
2. Heparin 2000 units twice per day beginning at the start of the cycle.
3. Medrol 16 mg daily until transfer then 8 mg from that point until positive pregnancy, then stop.
4. Increase progesterone to 50 mg injection plus Endometrin 100 mg twice per day vaginally. The injections starts on the day of the retrieval and the suppositories start the day after the transfer. "

My questions are:

1.what for an effect is the heparin in the case of repeated failure? I did not have this in the last 2 IVF. Do I need this, even I do not have thrombosis problem?

2. Do I need to increase my progesterone level even I have a normal level?

3. I will do an autoimmune test next month. Which tests should I do in addition?Thank you very much for your time. Best Wishes. A.

Answer:

Hello A. from Germany,

I was impressed to see that your ovary stimulated well and gave you an adequate number of embryos despite your age and elevated FSH levels. One thing to keep in mind is that despite having a good IVF cycle with reasonable embryos, IVF is not a perfect technology. The last two steps, embryo hatching and attaching to the endometrium and implantation, must occur naturally. This does not always happen. Also the embryos have to be completely genetically and otherwise normal. There is a higher chance of abnormal embryos with increasing age. That is what is called the "Age factor."

What that means for older women (35 years and older) is that it may take a lot more attempts to achieve a pregnancy, but as long as the ovaries still respond and put out eggs and embryos, then you have a good chance. Also keep in mind that pregnancy rates are highly variable among clinics so the clinic you go to is very important.

With multiple failed attempts, I add the protocol that you cited. There is a saying in the U.S. called "throwing in the kitchen sink" which basically means doing everything you can possibly do. That is the reason for this protocol. These medications are mainly used in patients that have recurrent miscarriages. But in IVF failure patients, it seems to work as well.

The Heparin and aspirin are at low doses so they are mainly targeting very small clots that occur in the micro-vessels that feed the implantation site. It is not enough to prevent a large clot in your vasculature. At that level they also have an anti-immune action to prevent failure due to an increased immune response from your body. That is also the reason for the Medrol or prednisone. It is an anti-immune drug. Some women are found to have an increased immune system when an antiphospholipid antibody screen in done (21 points). Finally, the increased progesterone is to insure that adequate progesterone is reaching the endometrium because this hormone is vital to implantation and survival of the pregnancy.

Travel is not an issue. I have many patients that come to me from far away places, yet they have been successful. Studies have shown that travel has no impact on pregnancy rates. What is more important is finding a good IVF center that uses state of the art techniques and has good pregnancy rates in your age group. I have many patients that come from Europe so that is always an option as well.

Good Luck,

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

Progesterone Injections & Travel After IVF

Question:

Dear Sir,

Our first IVF (during June 2008) failed and so, we are going for the second IVF which is FET (frozen embryo transfer). I have the following questions:

a) Progesterone-in-oil shots: During the last IVF it was very difficult and stressful to have the intra-muscular shots every day. After a week, the muscle became very rigid and at some point could not even poke the needle into the muscle. Will it be okay if I do a hot water massage after every shot? I am concerned because some nurses are saying it may raise the body temperature and could cause problems.

Are there any alternatives for intra muscular injections (for progesterone)? One of the nurses is suggesting to apply directly into the vaginal area. Since we haven't done that before we are not sure how tedious is that and the possibilities it could go wrong.

b) Will it be okay to travel long distance (approx. 3 hours) in a car - three days after the transfer?

Thanks so much in advance for your valuable suggestions.

Roger

Answer:

Dear Roger,

The progesterone injections are probably the worst of all the injections because it requires a bigger needle and the fluid is thick. I have changed from a prgesterone in sesame oil to a progesterone in canola oil that my pharmacy make us (MDR). Because it flows easier, we can use a smaller bore needle to reduce the pain and it doesn't harden up. You might want to check into that formulation. MDR Pharmacy is an infertility specialty pharmacy and you can get your meds via mail. It is also less expensive.

In terms of hot packs at the injection site, that would be fine. I don't expect that will change anything at all if it stays local.

Also, make sure you are rotating the sites i.e. one buttock then the other. You can also change the specific sites in the buttocks as long as you are in the upper outer quadrant. Make sure your nurse shows you all the areas that you can use.

As an alternative to IM progesterone, you can also use vaginal progesterone. There are several formulations: Crinon 8%, Prochieve 8%, Endometrin 100mg and pharmacy formulated versions. Several very good studies have shown equal efficacy to IM progesterone. However, most RE's are trained on IM Prog and so don't want to make any drastic changes. I happen to use both. Some programs, such as USC, have switched to vaginal completely. If your wife cannot tolerate the IM Prog or has an allergic reaction to it, then you can switch to the vaginal version. Crinone and Procheive are twice per day, and Endometrin is three times a day. They are messy but they don't hurt.

In terms of travel, yes it is okay to take a three hour trip after the transfer. As long as your wife is in a resting position, such as sitting, then you can travel. I only don't recommend strenuous activities such as exercise, karate, horse back riding, running and the like.

I hope this helps!

Edward J. Ramirez, MD

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

Monterey, California, U.S.A.

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