Tuesday, July 26, 2011

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


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.


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


  1. Hello!
    It's wonderful that you provide a second opinion for women who sometimes find it difficult or unavailable to see another RE. Thank you!

    I'm a 41y/o healthy female, never pregnant with 43 y/o male partner never fathered a child. We were TTC 2 years before starting IVF at 40y/o in Feb and 41y/o in November with 2 different clinics.

    My day 3 FSH was 7 both times, estradiol 179 both times. The first time prolactin was 31 and treated with bromocriptine but level not rechecked.
    Macroprolactin 19% and head MRI normal.
    Hysterosalpingogram was negative but a small external fibroma was seen on US.

    First protocol was Suprefact 50mg and Puregon/Repronex. Unfortunately I developed a 14mm leading follicle but we soldiered on and had 9 follicles irrigated with 7 eggs retrieved and 5 fertilized. No ICSI required. 3 made it to day 3 and were transferred. Grade: excellent. On estrace 2mg, Prometrium 100mg TID and ASA 81mg. Cramping in first 24hr of transfer, went to clinic where he could see cramping on US. He told me progesterone blood levels were not accurate and did not draw blood test but switched to 50mg PIO IM daily. Cramping stopped but blood HCG was <1 after 11 days. Stopped the meds and had bleeding.
    He wanted to try me on DHEA but I got a second opinion and they were not impressed with the large follicle and recommended a different protocol.

    Second attempt used cabergoline for hyperprolactinemia and blood test month before showed prolactin at 19. Protocol of Gonal F 300, Menopur 150 and cetrotide 0.25. Grew 9 follicles, estradiol rose well and triggered after >10000. Only 7 eggs retrieved, 5 mature and 3 fertilized. First sperm sample showed very little sperm so second sample done within 30 minutes and showed good motility and morphology. No ICSI required. Day 3 transfer of "average" embryos. Crinone 8% daily only for support. Started spotting 8 days after transfer. Told to remain on daily Crinone. Full period started 10 days post transfer. BHGC <1 on day 11.
    I had acupuncture for this protocol.

    In our debriefing, RE told me PIO would not help the spotting. My periods are 28-29 days and very regular although they have gone from 5 to 3 days in last 2 years. RE tells me that my eggs are poor quality and we could try a flare protocol (just to try something different) but my chances of pregnancy are 10% and he would not try again if we fail a 3rd try.
    I am disappointed and not interested in donor eggs.

    I am wondering about your opinion re: options. I think I have implantation issues and should be on PIO next time(as I did not have preHCG bleeding on PIO with first protocol). I have read about your estrace, ASA and medrol cocktail. I was also looking into assisted hatching (at yet another clinic) for the 3rd try. I am also taking 400mg Co Q enzyme.

    I do not want to become a fertility obsessed woman, if it won't happen it won't happen and I am going to be 42 this year. We are fortunate to be able to afford treatment but are in Canada where options are somewhat limited and air travel is required to see an RE. Thank you for any information, guidance and support you can offer.

  2. Hello,

    I am sorry to hear about your two failures thus far. As you continue your pursuit of a child, I need you to realize what it is you are up against what you have in your favor.

    First, with an FSH level of 7.0, that shows that you still have good ovarian function. That in combination with a decent stimulation in both cycles means that there is still sufficient ovarian "reserve" or capacity to continue tryin with your own eggs. I would have that checked, however, because with a CD#2 or 3 FSH level, the estradiol should be less than 100. Because the level was higher, the FSH level may not be accurate. In addition, based on a mid level protocol (450IU FSH combination protocol), you still had a decent response.

    On the other hand, you have to clearly understand what the hurdle is that you are trying to overcome. It is the age factor. What that means is that the eggs within your ovaries have and continue to deteriorate in quality. A woman is born with all the eggs she will have for her entire life. Those eggs age and deteriorate such that by 42 or 43, almost all the eggs are sufficiently poor quality that pregnancy does not occur. In the ones that do occur, there is a higher risk for miscarriage. This is the main factor you are trying to overcome. With this understanding, you can then see what your options are.

    If you will only consider a genetic child, then your only option is to coninue trying until you are ultimately successful or you change your strategy or you no longer respond to stimulation. The assumption is that there may still be some good eggs left within and you have to find them. It may take you several tries before you find the perfect egg. If you have the financial means to do so, then this is your best choice.

    In addition, to continue trying, I would recommend that you use a high protocols (600IU combined protocol) with antagonist (Cetrotide or Ganerelix) and NOT use a long protocol with Lupron or Buserelin. I also DON'T recommend a flare protocol. It has not been shown to be of any benefit. I would also recommend that you find a clinic that has a decent pregnancy rate at 41 years old. Not all clinics are alike. You will want a clinic that will give you the highest chances that you can have. Many factors go into getting pregnant and stimulation and embryo quality are just a couple of the factors. There are other factors as well, such as tranfer technique, lab quality, etc. Finally, as a matter of personal preference, I do add adjuncts such as low dose aspirin, medrol,heparin, in addition to my preference for using both POI and vaginal progesterone. I believe that there is no harm to too much progesterone and hate to not get a pregnancy because of inadequate levels. Spotting is very common with vaginal progesterone. It doen't mean anything.

    I would encourage you NOT to give up, however, and to keep an open mind about donor eggs. The resultant child may not be yours genetically, but it will be your husban'd genetic child and it will be your biologic child. You will be the one that is pregnant, nurture the pregnancy and deliver the child. When it is born, the genetics won't be important. For example, have you had your genetics checked to verify that you are from your mother and father? Know if anyone who has? The parents of a child are determined by who births them. There will be no question that this is your child. AND, you will have ALL the joys of motherhood depite the child not having your genes.

    If you are willing to travel to California, I think I could give you a significantly increased chance to get pregnant, although I can't guarantee success. Not that much travel is required. Costs might be higher than Canada, however. Hope this helps.

    Good Luck.

  3. Just another side note. I had a patient that tried IVF several times in her 40's at a different clinid, then gave up. At 55, she decided that she still wanted to have a child so she came to my center and underwent a donor-IVF cycle with success in her first attempt. She is now the mother of a beautiful baby girl, and enjoying every part of it. The only sad part is that she could have had this joy 10+ years ago, but like you, she decided it had to be hers genetically or she would be childless. I hope you won't make the same mistake. There is no joy like the joy you get from having a child. Don't shortchange your self.

  4. wow. this has made my day. your side note and detailed reasons why there is not thing wrong with donor eggs. i am 42 and going for that option afer a failed cycle 1 last year.
    I am on low dose aspirin and HRT (dont still understand why!) but i am looking forward to success with twins at delivery.

    In my failed attempt, I want to believe combining own egg and donor egg was not a good idea and I also had implantation problem cos I remember I saw a faint pink discharge but at test day, it was negative and my world caved in. I have since recovered and on my way to round 2.

    What do you advise for me to have successful implantation?

    1. I wish I could answer your question, but I would need to review your medical records and protocol to see how you are being treated. The key to donor IVF is the recipient (you) need to have an adequate endometrial lining of at least 9 mms thick and trilaminar on ultrasound. This is done with Estrogen used as either patches, suppositories or injections (I prefer the patches). The timing of the transfer is done based on the timing of the egg retrieval. When the donor triggers for the retrieval with HCG, that is the same day that you start your progesterone. The progesterone is essential to change the micro-architecture of the endometrial lining to make implantation occur (assuming all the other parameters are correct). If you are going to a fairly good IVF center, your chances of pregnancy should be identical to the chances based on the donor's age. For under 35 year olds, that is 73% in my center (cumulative rate). There are other things that I do but protocols are highly variable between clinics and docs so I won't detail them here. As long as your doctor's method works, that is all that counts.

      Good Luck



Related Posts with Thumbnails