45 Year Old Danish Couple On Sixth IVF Attempt: Should They Alter Meds & Blastocyst Transfer?

Question:

Dear Dr. Ramirez,

We are a 45 year old couple from Denmark on our sixth IVF attempt. The first three attempts produced 5/5/9 eggs with 225-275 units of Gonal-F and a fertility rate of 100%/60%/60% respectively. Eggs for transfer were three 8-cells on try one on day three, two 8-cells and one 10-cell on try two on day three and two morulas and a 10-cell on the third attempt on day five.

We then increased Gonal-F to 375 units and got 12 and 13 eggs in the next two attempts and a fertility level of 85%-100% and decided to go for Blastocysts and had two BC's and a Morula in the fourth attempt on day six and one BC and a Morula transferred the last time on day six. On the recent attempts we've been supplementing with Ovitrelle prior to aspiration (as well as folic acid, acupuncture and considerate food and no alcohol of course). After aspiration a dose of 16mg Medrol was administered for four days, then 8mg and then 4mg, as well as 81mg of Aspirin for the duration.

Our questions are: 1)should we continue to go for Blastocysts for transfer, and 2) do you have any suggestions as to an altered protocol perhaps in terms of increasing the dose or frequency of Medrol or any other meds that might help us?

Thanks in advance for your reply. T. From Denmark

Answer:

Hello T. from Denmark,

The good news is that your wife's ovarian response is still good and strong. She has done very well on her current stimulation protocols. The problem that you have is not so much the external quality of the embryos formed, they have been good, but the internal quality of the embryos. We know that with age, the quality of the eggs and thus the embryo quality deteriorates. That is probably what is leading to your failure. We rarely see pregnancies after the age of 43 in a woman using her own eggs. However, there was a case in New York of a woman who was successful at 49 years old, and is currently the oldest to become pregnant with her own eggs using IVF. It did take her two and 1/2 years of trying, however. Statistically, your chances of pregnancy with IVF are less than 1% per attempt based on age factors alone.

In terms of whether to do D#3 or D#5 transfers, I don't think it makes any difference. One is not better than the other. The embryos that would make it to blastocyst would still have done so in the uterus. In fact, I think the uterus is a better culture environment than the lab. I generally transfer at D#3 for this reason. In fact, in your case if you were my patient, I would transfer ALL embryos back on D#3 to maximize your chances.

In terms of what other protocols, I use Medrol starting at the beginning of the cycle (D#2) taken as 16 mg until the transfer then decreasing to 8 mg thereafter. I stop with the pregnancy test. I also use aspirin 81 mg per day starting at the beginning of the cycle and heparin 2000 units twice per day injections starting at the beginning of the cycle. I also use a "mixed" protocol of Gonal-f or Follistim + Menopur/Repronex for a total FSH dose of 600IU to start. In most cases, the patients stay at that level but some will decrease based on their response. In your case, your wife does not need more meds since she stimulated well, but a mixed protocol might be advised.

Your only option is to keep trying or move to donor. I am amazed that you have done so many cycles already. Most in the U.S. will not do that many cycles due to cost issues.

Good luck with this upcoming cycle & never lose sight of your goal...it can be achieved if you are open to options.

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.

Diminished Ovarian Reserve: I Have Failed 3 IVF Cycles, Blighted Ovum -- Where Should I Go Next?

Question:

Dr., I am 34 and have been diagnosed with diminished reserve.

I have done three IVF cycles. In the first, we got 5 eggs, after fertilizing all had testing and all found to have some anomoly, none transferred. Second, the clinic let me ovulate...didn't even get to extract eggs. Third got 2 eggs, only 1 fertilized, only a 4 cell with a lot of fragmentation, & I knew it was not going to work. Just found out I have a blighted ovum.

My question: Obviously my chances are not very good on my own and I realize donor eggs are my best option but I am finding it difficult to give up.

I am in health care and I guess my question if you can offer any advice is: For example in certain types of cancer there are certain centers that are more leading experts than others for certain types of cancers. Is that possibly the case with this disease? Is there a center that is the leading expert at diminished ovarian reserve that can help me? I had these 3 IVF at 2 different clinics and neither were very compassionate and treated me just like a number taking a shot in the dark at my protocol.

The last clinic the MD REALLY got my hopes up and now that it hasn't worked has dropped off the face of the planet. So my question is, are there leading experts in this arena that maybe know more specifics about what type of protocol might work best for me??

Answer:

Hello B. from the U.S.,

First of all, let me say that diminished ovarian reserve is NOT a disorder and is not a cause of infertility. It simply means that the patient's ovaries don't stimulate well and is often indicated by a high cycle day #2 or 3 FSH level. It is not an indication of egg quality in any way. Secondly, you are still young. You still have a good chance of pregnancy with your own eggs even if only a few are retrieved. I would still expect your pregnancy rate to exceed 50% per cycle (ours is 73%). I would not have wasted any of the cycles because there is no way to know if the good egg was in that batch. Even normal women do not ovulate good eggs all the time, and that is why it can take several months of trying to get pregnant. It is the same with IVF. Even if my patient has only one follicle I still try for this reason.

In terms of your question regarding the best center for your problem, I'm afraid there is no one center that is best for this problem. All IVF clinics have patients with decreased ovarian reserve, and each IVF center has different statistics and different ways of taking care of their patients. We all use different protocols as well. One question I would ask is what was your protocol? Were you given the max stimulation (600IU of FSH in either pure FSH (gonal-f, follistim, bravelle) or a combination (one of the previous with Menopur, Pergonal, Repronex). These latter medications have FSH in them as well so for instance if you took 450IU of Follistim + 150IU of Menopur, you would have a total dose of 600IU of FSH. I use this as my highest protocol.

In addition, timing is critically important. If the HCG trigger was given with the follicle size of 18 mms, it is possible that the egg did not have adequate time to mature, whereas 20 mms or 24 mms would have been better. As you can see, there are many variations in treatments. That is why there is no one center that is better than any other.

In my center, for example, I have extensive experience with low responders and use a high protocol for those patients. I also am a smaller, boutique-type center that prides itself and excels in providing one-on-one personalized care from beginning to the end. I am the only doctor, involved with my patients' progress from day one. That is what makes us different from some of our competitors in the big cities that operate more impersonally and do not give you access to the RE as much. All of these are facts and qualities that a patient should look for and seek out. They are paying a LOT of money for this treatment so they should demand their money's worth in all aspects.

With all that said, low responders are difficult because part of the success of IVF comes from having a large pool of eggs to work with. We know that in all cycles, there are going to be good eggs and bad eggs, so if we have an increased number, then there is a higher likelihood of getting a good egg. For low responders who don't stimulate well, and hence, don't give a lot of eggs to work with, that just means it may take more attempts before that good egg emerges. I would recommend that you NOT give up. After all, you have really only done two IVF cycles since the second one was cancelled. I am confident that you will be successful if you can continue to try. If you want a quicker solution, then donor eggs would be the option, only because a donor with normal ovarian function will yield more eggs to work with. Since you have had a blighted ovum, it means that the IVF cycle worked (remember, IVF only can produce embryos. The pregnancy, because of the last implantation step, still has to occur naturally). This confirms that you can get pregnant, and it is just a matter of getting a good egg/embryo into you. If you were 40, I would advise differently and lean more toward donor, but at your young age, you should keep trying.

Maybe you should consider coming to Monterey :) ! It is a beautiful place to visit as well.

Good Luck and don't give up hope!

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

Failed IUI In 38 yr old - Inadequate Protocol & Advice

Question:

I'm 38 and my menstrual cycles became erratic after an abdominoplasty removed approximately 1.2kg from my stomach area this past January. I am trying now to become pregnant and have undergone my first intra-uterine insemination (IUI), which failed.

I've had to use Provera twice to start my cycle after it went over forty days. Recently my OBGYN had me take Clomid on days 3-7 then Repronex on day 9. An U/S on day 12 revealed that I had a 20mm follicle so I was given a hCG trigger then had an IUI the next day. A later U/S revealed that the follicle was still there and that the hCG trigger apparently hadn't caused ovulation. Do you have any information on possible reasons why the trigger failed or whether it would be worth my time and money to try this same process again given this first failure?

Thank you very much for your time.

Answer:

Thank you for your question. It is not possible to know if ovulation actually occurred or not. We presume, based on the ultrasound that if the follicle disappears, then ovulation occurred. However, even an ovulatory follicle can reaccumulate with fluid, as we often see after IVF. So, it does depend on when the ultrasound was done. I always do two back-to-back IUI's on my patients. With each IUI, I look with the ultrasound again to see if ovulation occurred. It is generally good at seeing that ovulation occurred because it is within a very short time period that I am looking. In your case, because the ultrasound was done later, it is not accurate. In addition, some people will ovulate later than expected after the HCG injection. Remember, once the HCG is given, people will ovulate within 24-52 hours. I want my patients to succeed, and if that means doing the IUI on a Saturday & Sunday, in order to guarantee this success, then we come in on the weekend.

There is no reason to think that this treatment plan will not be effective, unless there is something else preventing you from becoming pregnant other than ovulation. From your history, the clomid is giving you the chance of getting pregnant with each cycle and you should continue. I would not recommend more than four cycles, however, because statistically, the chances for pregnancy decrease significantly after four cycles. I would also increase your Clomid dose and/or Repronex dose to try to get you to ovulate up to five eggs per cycle.

One thing that needs to be mentioned is the impact of age on your fertility. You certainly can get pregnant with IUI but it is not the best option. At 38 yo, the chances of pregnancy per IUI cycle is 5-10%. Because of this, we generally recommend proceeding with IVF after the age of 36yo. With IVF, in a good program, you can have a 52% chance of pregnancy per cycle. Because of your age, I would limit the number of IUI cycles to three or less. If your OB/GYN cannot get you to form at least 3-5 follicles, then IUI should be abandoned. It is not significantly increasing your chances. You should also have a cycle day # 2 or 3 FSH level done. If it is 7.0 or above, then I would go straight to IVF. You are looking at time passing, which is affecting your chances even with IVF.

Good luck and don't hesistate to query your Ob/Gyn regarding his success rates with IUI's.

Sincerely,

Edward J. Ramirez, M.D.

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF

www.montereybayivf.com

Empty Follicle Syndrome

Question:
Sorry for the long question but I wanted to make sure you had a good picture.....
I am 38 year old and have been trying to get pregnant for a while. I got pregnant using clomid and HCH shot but had a pregnancy lost in 2007 at approx 24 weeks. I did a thrombophilia work up and one of my clotting factors was borderline so the action that I was to go on blood thinners with a next pregnancy. High FSH has been a problem as it peaked at 20.23 during one cycle when I was doing the IUIs. I had to date 3 unsuccessful IUIs and two cancelled IVF due to empty follicles. The first IVF cycle I had two follicles after using Lupron in the beginning and then repronex and gonal F for several days and finished with Novarel HCG shot.
　　
The second attempt my RE did a different approach. I was placed on birth control for one cycle and the next cycle I start with clomid and then repronex and gonal followed by ganirelix and the last norvarel shot before retrieval. Note that my FSH was 8.8 but estradiol was high at about 90 so that made my FSH skewed. I had four follicles (the most I had have) and they were all empty. I was concerned that the shot was given properly but my RE said that does not have anything to do with them being empty. After the miscarriage I was always taking baby aspirin but no heparin.
　
Mentally I am not ready for donor eggs and my husband has flat out said no. I want to exhaust all options before I give up. As you would say, "pull out the full court press". I want to try one more cycle but I have doubts whether I should try again with this RE or try someone else. Can you shed some light on the empty follicle syndrome and if I have a chance? I am so desperate that I am trying acupuncture and herbs while I am on "ovary rest" break.
　
Answer:
Hello Patrice from the U.S.,
　
"Empty follicle" syndrome is a description/name of a condition that is found when no eggs are retrieved from obviously adequate sized follicles. It can occur at any age, but seems to be more prevalent the older one gets. So, a woman in her 40's could still have regular menstrual cycles and ovulation, but no egg will be ovulated so pregnancy does not occur. With IVF, we find this when we go to retrieve and get no eggs back. It is thought that this is the "normal natural condition" in the aging ovary. A woman essentially runs out of eggs. However, that does not seem to be the case in younger woman, since younger women stil have a full complement of eggs. So, "running out of eggs" does not seem to be the whole answer.
　
I have had several cases of empty follicles in both younger and older women. In the younger patients, I have concluded that they did not get adequate HCG stimulation. Previously I had used a generic HCG and worried that it was not produced properly or suffered some type of inactivation in shipping or storage. I therefore switched to Ovidrel. Since then, the incidence of empty follicles has been resolved except in a couple of exceptions. I had two moderately obese young woman have a very poor retrieval despite lots of follicles (both were PCOD patients). By poor retrieval, I mean that there were either no eggs or we only retrieved 1 or 2 eggs despite 25+ follicles. They had given the Ovidrel as instructed, into there belly. In the subsequent cycle, I had then give it in the back of the arm where there was some fatty tissue but much less than the abdomen. They then had good retrievals. This lead me to suspect that HCG stimulation was the problem, and that the increased fatty layer of the abdomen did not allow adequate absorption of the HCG, therefore the eggs did not release to be retrieved.
　
In your case, with an elevated FSH level, your age and poor ovarian stimulation, the problem may actually be a lack of eggs. However, you did not mention your weight so you might want to look at that possibility. In addition, you may not be stimulating well if you are not getting a large enough dosage of medication. For example, I use a total of 600IU of gonadotropins in the combination 450IU of Follistim and 150IU of Menopur. Are you using that much? If you are, then the poor stimulation is because of ovarian resistance as manifest by an elevated FSH level.
　
You certainly have the option of continuing to try with your own eggs if that is your only choice (per your husband) and you can afford continuing to try, AND you doctor agrees to allow you to keep trying. However, based on the cycles you have had, realistically Donor eggs is your best option, and the most cost effective since you would probably get pregnant quickly. Using your own eggs is a long shot.
　
If you don't think that your doctor is giving you an adequate chance, or being aggressive enough, then you certainly can consider changing doctors. The Doctor-Patient relationship is based on TRUST. If you don't have that trust, then you need to move on. If you trust your doctor's abilities then stick it out, albeit, every clinic and doctor have different protocols and treatments for difficult cases so that must be a consideration as well.
　
　
If you were my patient, as I mentioned, I would have you on 450IU follistim/150IU Menopur from the start, Aspirin 81mg per day from the start, Medrol 16mg per day from the start, Heparin 2000U twice per day from the start, Estrogen patches and progesterone from retrieval on and I use Ganerelix once the follicles reach 16 mms, NOT Lupron which will inhibit the ovaries from the start (called the long protocol).

I hope this gives you some information to think about.
　
Sincerely,
　
Edward J. Ramirez, M.D., FACOG
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
http://www.blogger.com/www.montereybayivf.com