36 Yr. Old Has Repeated Implantation Failure With Great Embryos...What's Wrong?

Question:

Dear Dr,

We have just had our 4th failed IVF (in vitro fertilization).

Our history.  I am 36, my husband is 39. 1st pregnancy was in 2009 after 3 IuI's (intra uterine insemination) and clomid, but had to terminate at 15 weeks due to large enphaloceale (was a random genetic mutation)and my 2nd pregnancy with IUI was a success with a full term healthy baby boy.

Started with IuI's for 2nd child in 2011! We had 10 IuI's and now 4 IVF's.  Each IVF has been with icsi (intracytoplasmic sperm injection) and this time we had Embryo hatching. Last 3 transfers were 3 top grade 8 cell embryos each time on day 3.  I am not a great responder and only ever have 5-7 eggs, of which usually 4 fertilise.

I have had all the immunity checks done, my husbands sperm dna damage is within normal, fertilisation rate is good.  My ovarian reserve was also checked and the level was 1.0- My specialist said that he wasn't overly worried about the reserve for my age.  I have had a hysteroscopy and all normal.  I have been on various drug protocols and this last one was the long Lupron cycle with menapur.

We are just not sure what to do next?  Do we keep going, as my doctors are very positive and we have the finances. Are my doctors missing something?  Is there anything else we can do to improve our chances.  I am on DHEA and Royal Jelly, and my hubby is also on supplements.

I am writing from CapeTown, South Africa.

Thank you for your consideration, R.

Answer:

Hello R. from South Africa,

The exact cause of your failure cannot be known as there are still four steps your embryo has to go through in order to produce a pregnancy: embryo has to develop to blastocyst, the blastocyst has to hatch our of its shell, it then has to attach to the uterine lining and the lining has to grow around it.  As of now, there is no technology that can make this happen.  "Assisted hatching" is just making a defect in the shell so that the embryo can exit (hatch) more easily.

Something I always worry about when I have patients tell me they have failed multiple cycles despite good embryos, is the quality of the final step of the IVF process, which is the transfer.  You can have the absolute best and perfect embryos but if the transfer technique is not done well, then it will fail.  This has been shown by numerous studies.  Since you have been going to the same clinic, I wonder if that is not the problem, in which case, I would recommend that you seek out a different clinic.

One thing that I do with my patients that is not universally accepted but done by many of us, is to use a recurrent miscarriage protocol to reduce the immune system, thinking that a heightened immune system might be at fault.  For this regimen I add low dose heparin or lovenox, medrol, low dose aspirin, extra estrogen and extra progesterone (both injectable and vaginal).  I don't think that DHEA does anything so I don't use it.

At 36 years old, I have a 66% pregnancy rate in my clinic.  By two to three attempts with good 8 cell embryos, you should already be pregnant.  Your rate should especially be increased over other 36 year olds since you have been pregnant before.  For these reasons, I think the fault may lie in your clinic and not in you or your husband. 

Good luck in your journey to have a second child,

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

 

Monterey, California, U.S.A.

Recurrent Pregnancy Loss (RPL) Workup Shows MTHFR: What Next?

Question:

Dear Dr. Ramirez,

I am 31 years old and have had 3 chemical pregnancies in the past 12 months. They have run a slew of genetic testing and a RPL (recurrent pregnancy loss) workup and all has come back normal with exception to the MTHFR test. I have tested positive for 1 copy of the MTHFR mutation. The nurse told me that because I was considered heterozygous that this was not a big deal. They prescribed me with a high dosage of Folic Acid. She said that it was likely not contributing to the repeat losses. I have been reading online and while the homozygous mutations seem to be more serious, there seem to be mixed reviews on whether this can contribute to early miscarriage.

Do you prescribe Lovenox or Heparin in this type of situation (only 1 copy?) Should I be concerned about this and demand that they treat it somehow? It doesn't seem like they are planning on doing anything besides the folic acid.

Also, given that this test has come back as it did, is there any other testing that you would reccommend that may be related to this? I am a little frustrated because this test was not originaly included in the work up and I had heard about it from online research and specifically requested it.

I just want to make sure that I am not missing anything.

Thank you,

D. from Boston

Answer:

Hello D. from the U.S. (Massachusetts),

The treatment for MTHFR (Methylenetetrahydrofolate reductase), is increased Folic acid (for more information MTHFR.net). But with your history of recurrent pregnancy loss or RPL, I usually will add the following to my patients, although there is not clear research backing it up if you are immunologically negative:

1. Low dose aspirin 81 mg starting with the start of the cycle

2. Low dose heparin 2000 units bid starting with the start of the cycle (you can substitute lovenox but it is more expensive).

3. Medrol 16 mg starting with the beginning of the cycle until ovulation then decrease to 8 mg

4. Increase progesterone supplementation of either Crinone 8% per day or Endometrin 100 mg three times per day starting after ovulation.

This cocktail has been shown to be effective in recurrent miscarriages (see Reproductive Immunology Associates for further information regarding immunological causes of miscarriage). My presumption is that you have had immunological testing, specifically antiphospholipid antibodies?

I hope this helps!

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

Fourth IVF Cycle Ends In A Chemical Pregnancy: What Can Be Done?

Question:

Hi Dr. Ramirez,

I have been on a rollercoaster ride for the past week and I am hoping that you can offer me your opinion.


I received a positive beta after my 4th IVF on Monday (11dp3dt). It was 14.3 and my RE said that it was quite low. I held out hope as I am convinced that I tend to implant a little later than others. In a previous cycle I had a negative beta 12dp3dt and found out that I was pregnant a couple of weeks later. I tested 3 days later and my beta was up to 52.8. I was so excited and felt so much better about things. I am scheduled to go back on Sunday morning for another beta.

I am currently taking Crinone 2xday. For the past week, I have had dark brown Crinone gunk(sorry for TMI). Last night and this morning there was some red blood on the applicator tip. At 1st I thought it was just irritation but for the past couple of hours, when I wipe there has been more red blood. I am also getting some minor cramping.

I am freaking out and I am so worried that things are moving in the wrong direction. I called my clinic and they said that they cant know anything until Sundays beta. They said it could be start of a miscarriage given the low beta #'s or it could be irritation from the Crinone or even pregnancy spotting.

I was hoping that you could offer some advice as I remember in the past that you prescribe Crinone to your patients.

Is RED spotting normal? How much spotting is normal? Was I foolish to be hopeful after my #'s doubled? Do you think its likely that this will end in miscarriage?

Any insight would be greatly appreciated. I dont know if i can hold out until Sunday's beta.

Thank you,

D. from Boston, Mass.

Answer:

Hello D. from the U.S.(Massachusetts),

The advice that your doctor gave you is completely correct. It could be from the Crinone, and I have seen an increased incidence of spotting in my patients using Crinone), it could be implantation spotting or pregnancy spotting or it could be indicating an abnormal pregnancy. There is no way to know which of these is the correct diagnosis. In general, I reassure my patients not to worry about spotting. I only worry if the bleeding is bright red flow like a period with accompanying cramping. The only way to determine the fate of this pregnancy at this point is to continue to follow the bHCG's every other day. This trend will then give you a better idea of how the pregnancy is doing. AS long as the bHCG is rising, then you can be reassured. If it plateaus or drops, then that is not a good sign.

Follow-Up Question #1:

 Dr. Ramirez,


Thank you for getting back to me. Unfortunately, my beta level dropped on Saturday so it looks like I will be having another chemical pregnancy. I am devastated of course. I was hoping that you might be able to provide me with some insight as to an explanation as to why this keeps happening.

A little history:

Me: 31 years old- normal FSH but AMH is .8

Husband: Very low morphology (less than 1%)

This was our 4th IVF cycle and 3rd chemical pregnancy. I have had tons of testing... RPL work-up, HSG, genetic testing, uterine biopsy and all came back normal.

I am a low responder and in previous cycles have had poor egg quality. I just switched REs and had a better response with an Estrogen Priming Antagonist protocol. He used a low dose HCG with Gonal F. Quality and ICSI fertilization rate was much better so I was hopeful that this was it.

My RE said that it was likely a chromosomal issue with the embryo and probably because of poor egg quality and we just need to keep trying and hopefully will get that “one” good egg. I don’t know if I am comfortable with that answer. We only have 2 insurance tries left and I want to make sure we are exploring all options before proceeding again. What would you recommend for your patients at this point? Do you think that it is worth doing a Sperm DNA fragmentation test?

What could be the reason for all of these chemical pregnancies?

Any insight is greatly appreciated.

Follow-Up Answer #1 :

Hello Again,

The exact reason cannot be known, of course but the most common reason for chemical pregnancies are a genetic abnormality in the embryo. With poor morphology in the semen analysis and your young age, definitely the genetic weakness could be from the sperm. I don't recommend the sperm DNA fragmentation test because it only gives the indication for the batch of sperm that it tests and not the sperm as a whole. In addition, the treatment recommendation is to use ICSI, which I presume you are doing already. So you won't gain anything from that test. If we suspect the sperm, other than ICSI you have the choice of either using donor sperm the next time or maybe try using a supplement for three months before doing IVF again. The supplements that your husband can try, which might help with sperm quality, are either Proxeed or Fertility Blend (vitamins) and CoQ10 600 mg per day. He will have to wait three months because sperm are on a 90 day cycle #the sperm made today won't be expressed for 90 days.

The only other options I could give are what I would do with my patients who have recurrent miscarriages (which is what you have even if it is a chemical pregnancy). Studies have shown the benefit of these meds and it is standard of practice to use these with recurrent miscarriages.

I would add: aspirin 81 mg per day, Medrol 15 mg per day until transfer then decrease to 8 mg per day, Heparin 2000 units twice per day and CoQ10 600 mg per day, all starting with the start of the cycle (CD#2). The Aspirin and Heparin are withheld from the day of HCG trigger until the day after the retrieval. The only other option you might want to consider is genetic testing of the embryos prior to transfer, called preimplantation genetic screening (PGS). That way you will know if the embryos are normal genetically or not. The downside of using PGS is I have observed and some studies have shown a drop in pregnancy rates after this. Some of my colleagues say that if it is done by a very experienced embryologist who does lots of these procedures, the pregnancy rate does not drop.

You'll have to discuss these options with your doc. I'm afraid there are no exact answers to your dilemma. But, studies on patients with recurrent pregnancies have shown that eventually these patients are successful. So, hang in there, even if your insurance coverage expires.

Follow-Up Question #2:

Thank you so much for your thorough response. I really appreciate it.

I am only 31 years old but I do have a low AMH (only .8) so along with that and the fact that I am a low responder, my RE suspects that I may have a diminished ovarian reserve. So, unfortunately, both my husband and I seem to have issues.

Do you think that the low AMH and dimished ovarian reserve contribute to the repeat miscarriages? Or do you think it is likely a sperm issue?

Is there any way to tell who is main contributor to this issue? We are not ready to talk about donors at this point and will continue to try with our own eggs/sperm for now but in the event that we need to explore other options, it would be helpful to know if we would be more likely to succeed using donor egg or donor sperm.

My RE has given us the impression that it is more a egg issue but hasn't given us any explanation of why.

Any help with this would be hugely appreciated.

Follow Up Answer #2:

Hello Agian,

There is no way to know what the exact cause of the recurrent miscarriages is. It could be egg or sperm derived since the genetics of the embryo come from both. Considering that you are ONLY 31 years old, I would suspect that it is NOT an egg issue but there is no way to be sure.

It is definitely not related to AMH or low ovarian reserve. The AMH is a measure of follicle availability and low ovarian reserve is a description of ovarian response to stimulation.

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/

How Can I Overcome Implantation Failure After Failing Multiple Fresh & Frozen Cycles?

Dear Dr Ramirez,

I'm a 43 years old female (from Australia) and for the last 2 years have been unsuccessful with IVF (in vitro fertilization) after 3 stimulated cycles and 10 Embryo transfers. I produce a good number of eggs (approx 18) with a stimulated cycle of 300iU/day of Gonal F. This egg number usually decreases at each stage; eg of 19 eggs, 13 are mature to fertilise, 6 fertilise and finally 1 or 2 reach day 5 blastocysts which can be transferred or frozen. All frozen eggs have always thawed well and transferred.

The pattern each cycle is similar however I'm finding that in this latest cycle only one embryo was transferred and the 2 remaining did not reach an acceptable stage for freezing. Implantation has always failed, even with the use of progesterone pessaries after transfer. I've also tried implanting 2 embryos with no positive result.

My specialist has resigned to the fact that my eggs are not of good quality due to my age. No testing on this has been suggested.

In terms of health I have PCO's and have a BMI of 30 (90kgs). I find it difficult to lose the weight which has been gradually gained in the last 8 years, have mild anxiety on the odd morning upon waking and trouble getting quality sleep 2 -3 nights per week. At times I suffer from low mood but put it down to the drugs and loss of hope. But I pull though with the support from family but use no medication. I do take a prenatal multivitamin 150mg of CoenzQ10 and fish oil. In your experience are there other treatments that could be explored for recurring implantation failure? Thank you, S. from Australia

Answer:

Hello S. from Australia,

Based on your embryo development and transfer of at least one good blastocyst, the cause of your failures is not determinable. We classify this as implantation failure but in reality there are two steps that have to occur naturally after the embryo is transferred. These are embryo hatching and attaching to the uterine wall and the endometrium growing around the attached embryo (implantation). We have no way to confirm that these steps are occurring. For that reason, there are no specific therapies to overcome failure at this point, but there are many suggestions for things to try. I say "things to try" because these are not proven remedies either. Also keep in mind that IVF success is not only dependent on embryo quality/normality and endometrial processes, but also on the doctor's transfer technique.

I think that what I would do if you were my patient is:

(1) Abandon the blastocyst transfer. Blastocyst culturing does not guarantee a quality embryo or success. Laboratory techniques, media, etc are not perfect. I wholly believe that the uterus is a better culture media and environment than the lab. Also, some embryos that might be the normal and healthy ones may not develop to blastocyst, as has been shown by numerous studies looking at preimplantation genetic screening.

(2) You could consider PGS to determine which embryos are genetically normal, and therefore have the highest chances for success.

(3) I empirically add low dose aspiring 81 mg per day, Medrol (Prednisone) 16 mg per day and Heparin 2000 Units twice per day starting at the beginning of the IVF cycle in my patients that have had repetitive failures. This is a formula that has been proven to decrease recurrent miscarriages with the thought that adequate micro blood flow and immunological factors may be leading to failure. I also increase my progesterone supplementation by using both injectable and vaginal supplementation, and add estrogen supplementation after the transfer by patch. Acupuncture has also been found to increase success in some studies, possibly by increasing blood flow or by reducing stress. All of these latter treatments are, as I said earlier, unproven. We call it "throwing the kitchen sink in" which basically means trying everything under the sun.

Finally, if you really suspect that it is an embryo problem, then donor embryos would be the remaining option, or you could consider using a surrogate if you think your embryos are okay but the uterus is not hospitable (my presumption is that a diagnostic hysteroscopy was already done to make sure of this).

Keep trying and 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.

Secondary Infertility Patient With Seven Miscarriages: Cannot Afford IVF

Question:

Hello-I am 33 and have a healthy 3 1/2 year old daughter who was conceived naturally. I have had 7 miscarriages (1 before my daughter and 6 consecutive since her birth). I have had 4 chemicals, 2 confirmed blighted ovums and 1 xxx69..this one had a heartbeat and all hormones were great, heart stopped at 8 weeks and did a karyotype on fetal tissue.

I've been to an RE and have had the following tests: Karyotype, HSG, Day 3 Hormone Panel, Clotting Disorder Panel, ultrasound to measure lining of uterus and to check for any abnormalities...all results are "normal". I have also supplemented with progesterone after a positive pregnancy test as well, my LP is usually 11-12 days. My hubby has only had a karyotype and he is "normal" as well. The RE said that our XXX69 was more than likely due to a mutated sperm containing an entire extra set of chromosomes. He has recommended we do IVF (in vitro fertilization) with PGD (pre genetic determination).

Our insurance doesn't cover ANY fertility, so that is really not an option for us.The RE wanted to me to try a monitored clomid cycle as a plan "B". In doing some research, I just don't think clomid will help with unknown recurrent pregnancy loss...what is your opinion? I "O" just fine without any meds. What else would you recommend? I am in excellent shape, eat organic whole foods, don't consume any alcohol or caffeine..

I take prenatals and fish oil daily. Do you think that all my miscarriages could be a sperm issue? I'm really at a loss....what do you think our chances are of having another healthy child without doing IVF/PGD? Thanks, S. from Maryland.

Answer:

Hello S. from Maryland,

I am sorry for your losses. You certainly have recurrent abortion as a diagnosis, but the exact cause is unknown. Granted that the fetal tissue from the last miscarriage showed a genetic abnormality, but if your husband's genetic testing was normal, then I would not expect that all the miscarriages were for the same reason. I would think that it is more likely to be a spontaneous genetic abnormality occurring with division of the embryo. Hopefully that is the case because that means that there is still a good chance of having a normal pregnancy. If the problem is a sperm abnormality causing a genetic problem, then there is very little that can be done to change that other than using donor sperm.

One alternative would be to try IUI (intra uterine insemination), since the sperm will be washed and the best sperm will be made available for fertilization. There is no guarantee with this but it is an option. Your RE is correct in that the only way to make sure that a normal embryo is available for implantation is to do preimplantation genetic screening with IVF. Since you cannot do IVF, then the only option is to continue to try and hope/pray for the best. I do not think you need to do Clomid either. It doesn't help with this problem. The good thing is that you are still young and have time to keep trying. Hopefully with continued trying, you will be successful.

If you were my patient, I think I would add low dose aspirin 81mg per day, PNV with folic acid, Medrol 16 mg per day, progesterone supplementation in the luteal phase (Crinone or Endometrin) and low dose heparin 2000 unit injections twice per day with each cycle. These are more to cover the immunologic causes of miscarriage, but have been shown in numerous studies to help. Since we cannot be sure exactly why the previous miscarriages occurred and can't conclude that it is ONLY a genetic problem, I would favor covering those bases.

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.

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

37 Yr Old Failed Two IVF Cycles, Has Frozen Embies And Husband With Slow Swimmers: What Would You Suggest?

Question:

I just failed my second IVF (in vitro fertilization) procedure. I am 37 years old living in the Bay Area. My husband has slow swimmers and not great morphology either. We used ICSI (intra cytoplasmic sperm injection) with both IVF procedures.

The first cycle I had 8 eggs, 6 fertilized and only two made it for transfer. The second cycle I had nine retrieved, 8 fertilized and we transferred two embryos on day 3, one an 8 cell and one a nine cell. We were able to freeze 3 embryos, not of as high quality. I believe the frozen embryos are 5 and 6 cells. I am planning to use the frozen embryos, but it seems like a lost cause as the quality of the embryos are not as good as the fresh ones that were transferred. I am doing acupuncture treatments as well.

Any advice would be most helpful. L. from San Francisco, California

Answer:

Hello L. from the U.S.,

I am sorry to hear of your failures, but IVF is certainly the best treatment for you based on your husband's problem and your age.

Without reviewing your IVF records, I cannot give you any specific information regarding your cycles or chances. Keep in mind that each IVF center uses different protocols and methods and pregnancy rates vary. For example, my pregnancy rate in your age group with ICSI is 56% per attempt with 41% continuing pregnancies. Pregnancy rates are very dependent on the stimulation, how many mature eggs are retrieved, embryo development and transfer technique. In addition, in your age group, having failed one IVF cycle already, I would have placed back all four embryos, even though the lesser celled ones were not as good quality. There is no utility to freezing them, and the prognosis with those embryos is not good as you already know. The success rate of a frozen embryo transfer cycles with good embryos is approximately 30%. Your best chance, once you have tried with the frozens if you choose, is to keep trying with fresh embryos.

In my protocol, I would probably place you at the max stimulation protocol, add low dose aspirin, low dose heparin, medrol and increased progesterone with the next cycle. Acupuncture certainly does not hurt and I would recommend that you continue it. On a side note, when my wife & I went through IVF she was 37 like you. We also did ICSI. She had 14 eggs retrieved, eight fertilized, and we ended up with one nine cell, one eight cell and the other two 5 cell. After conferring with her RE, (she was under the care of my colleague at the time) we decided to transfer all four. She became pregnant with a singleton, our daughter, who is now a healthy young teenager (her baby picture is on the Doctor's Background page of my blog). Needless to say, we did not regret our decision :)

Good Luck on your journey, I will keep my fingers crossed for you both!

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

Monterey, California

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.

IVF Patient Asks: What Supplements Can I Take To Increase Implantation Success?

Question:

Good day Dr Ramirez,

I was wondering what supplements and vitamins can I take to increase my chances of implantation in an IVF cycle?

Thank you! V. from the U.S.

Answer:

Hello V.,

There are no natural supplements that I know of that can help with implantation. I do add aspirin 81mg per day, Heparin and Medrol to my patients that have had implantation failures or failed IVF cycles because these meds have been shown to increase endometrial oxygenation and decreased miscarriage rates. Before you use these, however, it should be done in consultation with your IVF doctor so that you are not going against any protocols that he/she may be using.

In addition to supplements, you may want to look into doing acupuncture. While I cannot endorse the procedure on a purely scientific basis, some research has been done to see if acupuncture does have a beneficial effect with IVF patients. My patients are always given this option and a referral to local acupuncturists who specialize in infertility.

One in particular here in Monterey, Rikke Blessing (http://www.blessingacu.com/), has referenced some studies you may want to look at. This one was published in 2002 in Fertility & Sterility, the medical journal of reproductive medicine. "Researchers in Germany have looked at acupuncture to determine its efficacy with the use of traditional TCM combined with assisted reproductive techniques with embryo transfer (IVF). The acupoints chosen were used to relax the uterus. The main purpose of the study was to evaluate whether acupuncture accompanying embryo transfer increases clinical pregnancy rates. The results showed that the pregnancy rate for the acupuncture group was considerably higher than the control (42.5% acupuncture group versus 26.3% control group)".Paulus, W., Zhang, M., Strehler, E. Influence of Acupuncture on the Pregnancy Rate in Patients who Undergo Assisted Reproduction Therapy. Fertil Steril 2002;77:4;721-24

Good Luck,

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.