After Failing 3 IVF, Reader Has Pregnancy Success After Writing To Me

Dear Readers, Sometimes I get great news from one of the many couples I help on AllExperts.com and this is one I would like to share with you. Over a year ago I began corresponding with this woman regarding her failed IVF cycles. Her original questions appear right after the good news I received from her a few days ago. Makes it all worthwhile :)

October 7, 2013

Comment:   Dr. Ramirez helped me conceive from across the country thanks to his blog. We've never met and my husband and I credit him with the birth of our healthy baby boy. When my RE rejected our suggestions, Dr. Ramirez provided facts that played a major role in our "self" treatment which was to try naturally with baby aspirin. More doctors should provide online guidance and provide proven medical facts and suggestions to help those of us who are skeptical of patient forums. 

July 2012

Question:

Hello Dr. Ramirez,

I am writing from the United States.  I have been TTC for 2 years.  I began RE treatment 6 months after trying to conceive naturally at 34 yrs old. I am 36 now. I have failed 6 Intra Uterine Inseminations and Three IVF (in vitro fertilization) cycles. Below are the details: (for privacy purposes I have omitted the precise details of each cycle…except for the transfer details)

First IVF: 7 mature eggs, All ICSI 1 fertilized, transferred 4 cell Grade AB on day 3

Second IVF: 17 mature eggs, 9 fertilized, transferred 2 Grade AA on Day 3, one made it to blast and freeze (poor quality)

Third IVF - 18 mature eggs, 14 fertilized, 9 made it to blast, transferred 2 Grade AA, froze 6 good quality blasts ranging from Grades AA - BB

I never had a positive beta or urine test.  I've done all the preliminary testing, water sono, bloodwork, HSG, etc. everything is normal.  My husband’s tests and sperm are also normal.

I asked about immunology testing and Doctor said there is nothing to support that treating it helps.

I don't believe the early bleeding is normal. My luteal phase naturally is about 11 days long.  Dr said the PIO is plenty for me and would not recommend increasing it.

I asked about baby aspirin and heparin. They said baby aspirin is ok, but heparin can be dangerous.  I've read in your posts that you recommend that if there is one IVF failure.

Is there harm in taking heparin? I don't know what else to do to make them implant.  What are your thoughts considering my history?  I do not want to transfer any frozens unless the protocol is changed. I feel like continuing the same PIO / medrol protocol is setting me up for failure again.  I appreciate your advice. Thank you!

Answer:

Hello,

Since you have had decent embryos to transfer in at least two of your three IVF cycles, this would be regarded as implantation failure.  Thanks for reading my posts.  I also discuss these issues in my blog.

Your doctor is right in that the correct general opinion, kind of like being politically correct, is that the studies do not show any benefit to treating for immunologic problems in IVF.  However, it remains to be seen and depends which studies you prefer to believe.  There are certainly studies that show that immunology plays a role in miscarriages and some studies that show immunological treatments help with IVF.  I don't think it can be discounted completely but at the same time, don't believe in every treatment that is offered.

I certainly advocate low dose aspirin, low dose medrol and low dose heparin in my patients that fail two cycles of IVF for no clear reason.  I have had many be successful thereafter with that protocol, which I have been using for the past 18 years.  There is NO danger in using low dose heparin.  Full dose heparin is another matter.

I think that the dilemma you now face is whether to continue with this doctor or not.  If you want more, such as using the protocol mentioned, then you'll probably have to find a doctor that will provide that to you.  I certainly think your doctor needs to reevaluate and consider what else he/she can do since what is being done so far has failed.

You certainly can always fly out to California. :)  For an FET cycle, you would only need to be here for one day.

Good Luck,

Dr. Edward J. Ramirez, M.D., FACOG

Follow-Up Question:

Hello again,

We consulted with our RE again regarding the transfer and he suggested doing nothing differently and chalked it up to bad embryo genetics.  Again he reiterated no baby aspirin so we pleaded for him to do immunologic testing, cytogenetics (on us) and blood clotting work ups to which he agreed.

Everything came back normal, including cytogenetics on my husband, with the exception of my protein s free antigen level. It was 151 and regarded as "high" by the lab that ran it.  He referred me to a hematologist who ran protein s activity testing which thankfully came back normal. He said a high level protein s is not concerning and that only a low level would be.

So here we are again with his recommendation of transferring with the same protocol.  I asked again how about baby aspirin and he remained firm on "no".  I told him 3 doctors, including one at his practice, the hematologist and an online doctor i have emailed have said there is no harm in using it along with my friends who have used it with no pre-existing blood clotting disorders and went on to have successful IVFs.

He said taking baby aspirin with no blood clotting problem can cause more complications than help.  He said it can interfere with the growth of the placenta.  Is this true?  So far he is the only doctor that has said no to baby aspirin including the doctors of everybody I know who has gone through ivf unexplained.

Are there any facts you know of with baby aspirin and placental defects?

Again, I truly appreciate your knowledge and advice and thank you for your responses.  There should be more doctors like you who help others online with honest, professional opinions!

Follow –Up Answer:

Hello Again,

There are no studies that show any adverse affects of low dose aspirin on embryo or placental development.  In fact, and either you or he can look this up in any Infertility textbook, low dose aspirin is an approved and advocated treatment for recurrent pregnancy loss (now why would they endorse it if it caused placental problems?).  We have extrapolated its use in failed IVF with the same idea that it increases blood flow to the implantation site and reduces the formation of micro-clots in the tiny vessels supplying the implantation site.  There is no way to test for these. 

Since this doctor is not willing to work with you on this very simple and innocuous treatment, which may or may not help, I think you should seriously re-consider using him.

Good Luck,

Edward J. Ramirez, M.D.

Follow-Up Question:

QUESTION: Hello again

Have you noticed this email is more than nine months after your last reply?

Our RE did not budge again on the baby aspirin so we decided to wait on the next transfer and try naturally with baby aspirin.

That month I became pregnant for the first time. I went to my RE and he confirmed it with blood though the levels were low and I was bleeding and he did not offer progesterone cream. He said he doubted the pregnancy was due to the baby aspirin. At 5 weeks I miscarried, and although it was sad, I was elated at the fact that I did get pregnant. So we tried again naturally the following cycle with baby aspirin (2 weeks after miscarriage) and what do you know?

I got pregnant again.  I went back to RE and he confirmed with a blood test. I started bleeding again so he suggested progesterone cream.  I told him we did the baby aspirin thing again and if I should continue taking it and he said YES! 

He followed my progress until 2 months and referred me to my obgyn to monitor the pregnancy. I continued the progesterone cream until the end of the 3 months and continued taking baby aspirin until 37 weeks. Yes, 37 weeks.

Our healthy baby boy was born at 41 weeks, weighing 9lbs, 4oz and measuring 20.5 inches.

If I did not read your blog, he would not exist. My husband and I attribute his existence to your blog and cannot thank you enough.  Please continue your public advisement as it made our dreams come true.

Thank you!!!!!!
 

Follow-up Answer:

Hello,

I am absolutely delighted for you.  Congratulations :)  I'm saddened to see that you had to prescribe a therapy for yourself, but glad that it might have done the trick.  No one will ever know for sure if it helped or not and what the mechanism is, but it seems to help many people with your type of history.  I now put all my infertility patients on low dose aspirin from the beginning, IVF or not. Another possible factor is that you tried soon after your miscarriage--studies show that there is a higher chance of pregnancy after a miscarriage.

I'm shocked and a little disappointed that your Ob doctor allowed you to go post-dates (41+ weeks) because that posed significant risk to the baby such as a fetal demise, fetal distress, etc.  I NEVER let my infertility or IVF patients go past 40 weeks.  The sooner the baby was out the safer it was at that point.

Thank you for reading my blog and using this service (AllExperts) as well.  I do it in tribute to the task and gifts that God has given me, which is a part of the love he has for us.  Your baby is also a gift from God for you to treasure and teach of his ways.  Devote your love to this son and shower him with Goodness so that when he grows up, he will shower others with goodness as well, and thereby contribute toward making this world a better place.  It is not often that I get feedback of successes attributed to my writings, but know that your feedback reinforces my dedication to this task.

Congratulations!

 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.

 

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.

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.

Possible Uterine Abnormality Or Immunologic Disorder Causing Four Miscarriages In 32 Year Old: IVF With Surrogate Again?

Question:

Background: I am 32 as is my husband. We had an ectopic pregnancy 10/2005, 8.5 week miscarriage 3/2006, 10 week miscarriage 8/2006, 9 week miscarriage 2/2007 (genetic testing done - female/chromosomally normal), and 9 week miscarriage 8/2007 (male/chromosomally normal).

We had a healthy son via gestational surrogacy with my egg in 2008. During the IVF (in vitro fertilization) procedure for this surrogacy, I only produced 6 eggs and only 1 blastocyte made it to the 5 day transfer as an 8 cell blastocyte. I have Hashimoto's Disease (on medication since 2000), diagnosed with Endometriosis in 2005 (2nd lap in 1/2010 showed it is gone) and diagnosed with Adenomyosis in 1/2010, after which I took Depot Lupron for 4 months.

I have had every genetic test I've heard of and the only issue is one copy of the MTHFR gene. I took 81 ASA and Heperin with my last two pregnancies, and progesteronne with the last four. I even did IVIG with the 5th pregnancy. Two weeks ago I tested my FSH and it was normal. I also had an AMH test and it was 0.2, very low.

My RE has told me that I should try IVF (with me being the carrier) but I'm not sure. I know they are concerned about the number of eggs I have left and the quality of the eggs that are left. What I want to know is if my 2nd through 5th pregnancies could progress to 8-10 weeks with normal hearbeats and the last two we know were chromosomally normal, does this have anything to do with poor egg quality? How could these last two pregnancies test normal but be of poor quality? Is that possible?

Thanks! D. from the U.S.

Answer:

Hello D. from the U.S.,

To answer one of your last questions, since your pregnancies were know to be genetically normal, this is not an indication that you have poor egg quality. Poor egg quality leads to abnormal embryos (genetically) because the chromosomes within are fragile and break during division. It is most likely that you have either an immunologic disorder or a uterine abnormality. The latter might be the case because a surrogate was successful with your eggs.

I don't see any reason for you not to try with your own uterus if you can afford it financially. The only downside is if the uterus is a problem, you will end up miscarrying again and will have spent the money for that IVF cycle. I am not sure that I am convinced that it is a uterine problem, however, because the previous pregnancies progressed as far as they did. I would recommend that you go the gamut with the next in vitro fertilization cycle, using aspirin, heparin and IVIG if you decide to use your own uterus. That may be what it takes. If finances is an issue, then I would recommend that you use a surrogate again.

I know these are tough decisions but your young age, the positives that you have had, in addition to the child you have already had via surrogate two years ago, make your chances for another pregnancy very likely.

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.

Overweight Woman Trying To Conceive Has Irregular Periods And Multiple Miscarriages

Question:

Hi Dr. Ramirez,

I read your blog and I love it! I learned a lot reading all your archives, so I wanted to come to you for advice about my situation.

I am 24 years old and my husband is 26. When I was 21, I was told that I have problems ovulating because my cycles were just a week of spotting after 2-6 months of nothing. My OB/GYN says that I don't ovulate due to my obesity, so I have never had any tests to check for PCOS or anything else. I am working on losing weight, but it has been a slow process. I do menstruate when given progesterone supplements, typically within hours of finishing my 10th day of 200 mg Prometrium. I also have hypothyroidism (and a strong family history of the same), but it is under control with 50 mcg levothyroxine; my most recent TSH, in January, was 1.7. I also have a family history of lupus, but do not have lupus myself.

In July 2008, I got pregnant while on Sprintec and miscarried at 5w2d, then went back on Sprintec. In October 2009, I got pregnant in my first month off Sprintec and miscarried at 5w4d, then went back on Sprintec. In February 2010, I got pregnant again in my first month off Sprintec but had a chemical pregnancy (bleeding started at 4w2d). Additionally, just from knowing my typical pregnancy symptoms in retrospect, I suspect that I might also have had a chemical while on Sprintec in April 2009, but I did not test because I was taking active pills three months at a time so I did not have a period to miss.

I have been taking OPKs twice daily (12 hours apart) since the chemical but have not ovulated; in fact, I rarely if ever see a second line at all on the tests. My OB/GYN said I can start Clomid at any time, but he is unwilling to do any testing regarding the losses until I have another miscarriage. My husband and I do not want to try to conceive again until we have tried to get an explanation for our losses.

I actually have a few questions. One, is there a reason I seem to ovulate only when I have recently been on hormonal birth control? Is it a down-regulation thing like women have before their IVF cycles? Two, is it possible that just taking Clomid might allow us to make it out of the first trimester? Three, in your opinion, is it time to move to an RE even though we have not yet been trying for a year (the only one in South Dakota is more than 200 miles away from our home)? And four, what sort of tests would an RE want us to do regarding my pregnancy losses?Thank you so very much for your time and consideration.

You provide a wonderful service, and if I'm ever in California I'd love to become a patient!

Answer:

Hello B. from South Dakota,

Thank you for reading my blog and your kind comments. I hope the information was useful.

It certainly sounds like you have an ovulation problem, and Clomid would be an appropriate treatment. However, because you have had three miscarriages, you also have the problem of recurrent miscarriage. Both of these problems would fall into the infertility category and an infertility specialist would be the best person for you to see. That way, both problems can be managed, rather than just the ovulation problem as your current doctor suggests. Regarding your weight, I have had infertility patients who are overweight and still achieve a pregnancy. There are other issues that need to be addressed that take precedence over your weight.

Let me answer your questions specifically in order:

1. I find it interesting that you were able to ovulate on the birth control pill. I'm not sure that I can explain this. Most likely, the birth control pill caused an FSH/LH burst that led to ovulation. It usually suppresses FSH/LH discharge, which is how it works.

2. Clomid will certainly help you to ovulate, at the appropriate dosage, and may correct any hormonal problems if that is the cause of your miscarriages. I would not bet on it, however. Rather, I treat ALL my infertility patients will supplemental progesterone in order to help prevent any miscarriages caused by hormonal problems. In addition, with a patient with recurrent miscarriages like yourself, I would add low dose aspirin 81 mg per day beginning at the start of the menstrual cycle, medrol 16 mg per day beginning at the start of the cycle and tapering to 8 mg per day after ovulation, then stop with the pregnancy test and heparin 2000U injections twice per day beginning at the start of the cycle. Lovenox could be substituted for this as well. An RE is the most knowledgeable with this problem and protocol.

3. I answered the question regarding the RE above, but I would recommend that you see one because of the ovulatory dysfunction and recurrent miscarriages.

4. Recurrent miscarriage evaluation includes: Hysteroscopy, pelvic ultrasound, blood tests for antiphospholipid antibody (full screen), ANA, Lupus anticoagulant, Leidin factor V, RPR, Toxoplasmosis, Chromosomal analysis in you and your husband, hormone panel.

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.

Comment: Thank you so much! I plan to see if my current clinic can run the panels, then follow up with a specialist.

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.

32 Year Old Canadian With Multiple Miscarriages: Do Not Despair! You Can Conceive!

Question:

Dear Dr.Ramirez,

I am a 32 years old and my husband is 34. We have been trying for a baby since July 2008. In early 2009 we conceived and were over the moon. An early dating u/s at 6 weeks showed a heartbeat but sadly I started bleeding 2 days later and naturally lost the pregnancy.

Two months later we conceived again and my doctor suggested progesterone supplements. At the 7 1/2 week u/s the baby had an extremely slow heart rate and passed one week later. I had another natural m/c.

After the second miscarriage we decided to go to a Fertility Clinic and do a full work up. Everything came back perfect. Good FSH (5.9 & 6.8), AFC count of 20, normal karyotypes, no autoimmune or blood clotting issues. All other hormones were great as well including husbands DNA sperm test.

We decided to try agian with the aid of a low dose fertility drug (puregon) and timed intercourse. I got pregnant that first cycle this January. All of early ultrasounds were perfect but sadly we found out the baby had a large cystic hygoma and T21 at 12 weeks. I just had my D&E and am totally devastated.

Could we really have such bad luck? Or is there something else going on like poor egg quality at my age? What would you recommend we try for next time?

Your response is much appreciated. D. from Canada

Answer:

Hello D. from Canada,

Despite the fact that you had three losses, I am not sure that you can bunch them together. For one thing, the last loss was due to a congenital anomaly. It was not technically a miscarriage. I presume that you doctor checked chromosomes in both you and your husband to make sure that you are not passing something along. If that is the case, and it was normal, then the congenital anomaly was just chance, as was the miscarriages.

The most common reason for miscarriage is spontaneous genetic defects. That means that when the egg was dividing, there was chromosomal breakage and so the embryo developed abnormally. In most cases, the body detects the abnormal embryo/fetus and stops the pregnancy leading to a miscarriage. It is known that most patients with multiple miscarriages will eventually be successful, so one piece of advice is to not give up. Certainly, getting pregnant is not an issue for you. Also, because you are still young, it is unlikely that you have "bad" eggs or poor egg quality. That is usually an age related phenomenon.

I know that it is emotionally draining and an absolute heartbreak to go through all these losses. But you will eventually be successful if you keep trying, so, not to belittle the losses, but it might help if you think of these as practice runs for the real thing. Also, in addition, to the progesterone supplements with each cycle, you might want to add low dose aspirin and folic acid to the regimen. Hopefully, the next pregnancy will be the good one.

Good Luck and God Bless,

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.

Comment: Dear Dr.Ramirez, Thank-you so much for your prompt and informative response. My husband and I will certainly try again in the future after we take some time to heal emotionally. Your answer has given me much hope ! Also, yes we had our karyotypes checked and we do not have any genetic/inheritable issues. All of those tests were normal. I pray for a healthy baby soon.

German Woman Suffers Multiple Miscarriages Over Two Year Period - Proceed To Clomid Superovulation?

Question:

I´m 31 years old and writing from Germany. I have no children and have suffered four miscarriages. My husband and I have been TTC for 2.5 years now. After using the implanon hormone implant for birth control, I had it removed in 09/07 to begin TTC. In 11/07 I fell pregnant only to miscarry at about 5w3d. My hormone levels showed an hcg level of less than six. I was told to wait three months and try again, that I would have better luck. In March of 08 I fell pregnant a second time. At my first appt. at 8w5d it was discovered that there was a large sac with no fetal pole. I began to miscarry at 11 weeks and had an emergency D&C because I was losing so much blood. I asked that the tissue be analysed, but was told it was not done for a second loss and that this was in all likelyhood caused by a chromosomal problem. I was told to wait three months before trying to conceive again. Exactly 28 days after the D&C I got my period. I fell pregnant the next cycle, but did not realize it until I started miscarrying. My doctor did not do a blood test, only looked at an ultra sound, shrugged her shoulders and said I wasn't pregnant anymore, if I had ever been. She suggested that I could go for genetic counseling if it would make me feel better.

My husband and I went for genetic counseling, had kareotypes done, both of which came back normal, were tested for various thrombophilic conditions and immune disorders plus thyroid. My results came back as normal for everything but Leiden Factor V. I carry one copy of the gene. I was told by the geneticist that it would be good to start heparin at 8weeks in my next pregnancy and sent on my way.

In December of 08 I fell pregnant a fourth time, was given 100mg of aspirin to take starting at 4w5d. At 5w1d I began to bleed, but the ob/gyn felt that my lining still looked good, gave me progesterone supplements to take and told me to come back in five days for another ultrasound. On my return visit she could not find a sac in the uterus, and was unsure if she wasn´t seeing a sac in müllerin duct. I was told to stop the progesterone immediately and go to the hospital immediately should I have any sharp pains. Otherwise I was to report to the hospital in another five days for a beta draw. After stopping the progesterone I miscarried the next day. Three days later my hcg levels were drawn at the hospital and found to be 144, so I was required to come back every 48 hours for another draw to be sure that they were indeed falling. My levels fell nicely and I was sent home to wait three months before ttc again.We have been trying for a year now, and have not been able to get pregnant.

I have charted, used the clear blue fertility monitor and opk's to no avail. After six months I went to see an RE hoping that he would be able to give me some answers about my miscarriages, but he offered no ideas as to why, only said that my miscarriages were not a result of the Leiden Factor V. He did some bloodwork at CD13 to check my hormone levels, which he said looked very good, did a SA for my husband and a penetration test and said he saw no reason for us not to be pregnant. He suggested a doing a lap but made no further recommendations.

My regular ob/gyn was not in favor of the lap and suggested that I try a bit longer, and that if I wanted to we could try clomid and progesterone to get a stronger ovulation.I am unsure and very confused as what my next course of action should be testing and treatment wise, and if I really have a chance at having a biological child. I would appreciate any thoughts you might have on this subject. Thank you very much for your time.

Answer:

Hello L. from Germany,

Recurrent miscarriages are a difficult problem. The most common reason is because of a spontaneous chromosomal abnormality. That means it occurred when the egg was dividing, and not because you are carrying something. Hematologic disorders, such as Factor V, have been shown to increase the risk of miscarriage. Since you underwent evaluation and that was the only abnormality found, that is good because most patients with recurrent miscarriage due to spontaneous abnormalities will eventually be successful.

You mentioned that you were 31 years old, which is a good thing. Age plays a significant role in the risks of spontaneous anomalies and increases the risk of miscarriage with increasing age, especially after 35 years old. I call this the "Age related egg factor." Most patients that have recurrent miscarriages are because of age related spontaneous genetic defects. In your case, although there may still be "abnormal" or "weakened" eggs within your ovary, your chances of spontaneous defects are low. That means that your chances for success are high.

It sounds like your RE was addressing the issue of your infertility and not the recurrent miscarriage problem. Laparoscopy would be indicated to evaluate for infertility only. I don't think it is indicated at this point as well, but I wonder why you have not gotten pregnant after 1 year of trying. Something has changed and an evaluation is definitely warranted. I would go back to doing a full basic infertility evaluation and not make any assumptions, despite having gotten pregnant in the past. A hysteroscopy would be warranted to evaluate the uterine cavity because of your history of D&C. Therefore, you might also want to consider laparoscopy to complete an infertility evaluation, but not for evaluation of recurrent miscarriages.

If you don't want to do an evaluation but want to proceed with trying for pregnancy, then it is a little shot in the dark. Certainly doing Clomid "superovulation" is an option. This is where the fertility drug Clomid is used to increase the number of eggs that you ovulate per month. This can be paired with either timed intercourse or IUI. I might suggest the latter, IUI (Intra Uterine Insemination) for a higher pregnancy rate between these two. You might want to use low dose aspirin (81mg)per day and heparin (2000 units/twice per day) and medrol 16 mg per day starting from the beginning of the cycle, as well as, supplemental progesterone (vaginal or injectable) and estrogen.

The other option would be to proceed with IVF (in vitro fertilization). In this case, embryonic genetic testing, called PGS (preimplantation genetic screening) can be done to determine which are the normal embryos so that only these would be transferred. If you decided to pursue this option, I would recommend that you choose a clinic that has experience doing this and can do testing at the blastocyst stage (trophectoderm testing), rather than an earlier stage where they take one of the cells, and test with CGH (comparative genomic hybridization) .

I hope this gives you some information to consider.

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

43 yr. old Trying To Conceive Needs High Stim Protocol

Question:

My Medical History: TTC 4.5 yrs. (3.5 with RE) Many IUI's & IVF's. 3 chemical pregnancies - 2 with IUI 1 with IVF. AMA - 43ys young.

Had a Coagulation Panel done - Mutation found -

heterozygous MTHFR C677T

Results negative for Factor V mutation

Factor II DNA Analysis

Results WNL for

ANA

APA

Lupus anticoagulant

Homocystein

Elevated levels for

Protein C Functional (187)

Factor II Activity (133)

Plasminogen (161)

B2 Glycoprotein (low positive)

Do I need to supplement my prenatal with extra folic acid and b vitamins? Baby aspirin? If so - can I just add extra supplements or do I need an Rx for something like Folgard?

Could this be the reason for all of my failed IUI's, IVF's and chemicals? Before finally agreeing to do this testing, my RE kept telling me that immune issues are too controversial and that the risks of their treatment outweighed their assumed potential benefits. I don't know what his thoughts are now as I couldn't get a Dr. callback for 3 weeks.

Many thanks, Dr. Ramirez, for so graciously donating your time in answering our questions! Your services are invaluable! Oh, yes - I am located on the east coast.

Answer:

I'm afraid I am in agreement with your RE, although for slightly different reasons. We do know that the immune system does contribute to miscarriages, although I am not sure that is the problem that you have. There are definitely some very controversial treatments, such as IVIG, which are very expensive and have not been shown to be of benefit in multiple studies. However, the alternative, which I try with all my patients is low dose aspirin (81 mg) per day, progesterone (injections and suppositories) and low dose heparin 2000 U twice per day. This regimen has been shown to help with recurrent miscarriages and is very low risk. That is why I use it. I have had some successful pregnancies in patients with recurrent miscarriages using this cocktail.

However, although you are still very young in my book, your fertility age may be the basic problem. You have shown that you can get pregnant. The problem is an egg problem. It is what I call "age related egg factor." We know that because a woman is born with all her eggs, and they age with her, and the lifetime of the eggs are about 43 years old, they deteriorate with time and age. This deterioration causes internal problems in the egg, including fragile chromosomes. This leads to bad embryos that either don't progress in their development, don't implant or end in miscarriage. There is a 40% chance of miscarriage with each pregnancy in your age group. Chromosomal abnormalities is probably the major reason for your losses.

There are only two ways to mitigate this increased risk: you can keep trying until you are successful (and hopefully you will be eventually) as long as your ovaries are still functioning well, or you can do preimplantation genetic testing (PGD) to identify the normal embryos prior to transfer (however, keep in mind that this is a new experimental technology, is very expensive, and does lower the implantation rate because of the "injury" to the embryo.).

I think that if you were to present to me, I would continue to recommend IVF with a high stimulation protocol and put you on my cocktail. I don't necessarily recommend PGD. I think nature will take care of that. The key would be to keep trying if you are determined to have a baby. There have been successes in your age group but time is running out for you.

I hope this helps,

Edward J. Ramirez, M.D.

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF program

http://www.montereybayivf.com/

Recurrent Miscarriage and Factor V Leiden

Question:
Hello Dr Ramirez,
I hope you can help me.
I live in London England. And am a patient at Kings College Hospital London.I have recently miscarried for the fourth time.I had 3 previous miscarriages and following tests discovered i am heterozygous for factor v leiden.Following this I had a successful pregnancy using one low dose clexane and baby aspirin daily.I now have a beautiful baby daughter who is 8 months.I got pregnant quickly afterwards but miscarried recently at 10.5 wks again using clexane and aspirin.Can you shed any light on why I miscarried again.I thought I would be ok using the clexane etc,I thought this was the answer,but it didn't seem to work this time round.Is it likely this may happen again if I get pregnant?Is there anything else I should be trying?I hope you can advise.
Kind Regards

Answer:
Hello Nicola from the U.K.

Factor V caused recurrent miscarriage through an increased risk of blood clots at the tiny vessels feeding the pregnancy. Therefore, the key to treatment is to use medications that decrease this clotting. Obviously the low dose aspiring was sufficient for your previous pregnancy. I don't think the Dexane (dexamethasone# contributed much. It is a steroid and used mainly to decrease the inflammatory response, however I also use it for my IVf patients to reduce the chances of rejection of the embryo. The recommended treatment is to use low dose heparin #2000 units twice per day) or Lovenox beginning at the start of the menstrual cycle or treatment cycle, in addition to the aspirin. I use both. I think that your overall chances for another successful pregnancy are good. You still might have additional miscarriages but that could be due to other reasons as well. There is an overall risk of miscarriage in 40% of pregnancies just due to random abnormalities. But don't worry about it too much. Keep trying, and I am confident that you will be successful.

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

Monterey, California, U.S.A.

for additional information check out my blog at http://womenshealthandfertility.blogspot.com/ check me out on facebook and twitter with me at @montereybayivf