Tuesday, October 29, 2013

Poor Responder Needs To Know IVF Is Not All About Numbers: It 's About One Good Embryo

Question:

Hi Dr. Ramirez,
My name is A. and I am writing from Michigan. I am 33 years old and have DOR with an AMH of <.16, Hashimoto’s and positive ANA’s. I am on day 10 of stims for IVF #2 and responding poorly compared to our first attempt. I am hoping you could answer a few questions regarding the cause of the diminished response (compared to the first) and also give your opinion regarding canceling the cycle.

IVF #1 (March 2013):
BCP suppression 5 weeks
225 iu Bravelle, 150 iu Menopur, Ganirelix days 8-10. Stimmed for 10 days.
Day 5 of stims: 6 follies: 9-10 mm, E2 301
Day 10 of stims: 7 follies: 19-21 mm, E2 724
Retrieved 8 eggs, 6 mature, 4 fertilized with ICSI, 2 transferred (grade B’s, no frag), none to freeze.

IVF #2 (in progress):
BCP suppression 4 weeks
225 iu Bravelle, 225 iu Menopur, Ganirelix added day 8 of stims.
Day 7 of stims: 6 follies: 12, 12, 9, 9, 9, 9 mm, E2 243
Day 10 of stims: 4 follies: 15, 14, 11, 10 mm, E2 495
There are five factors that have changed since the first cycle. 1) Menopur was increased by 75 iu. 2) Ganirelix was introduced when follies were smaller at just 12 mm. 3) Slightly less time on BCP suppression; less one week 4) Added Methylprednisolone 16 mg. 5) Discontinued DHEA 50 mg and Myo-Inositol 2 g.
What could be causing the poorer response, loss of follicles and slow growth? Is there anything that can be done to speed up growth and/or catch up the 10 and 11? Does the slow growth speak to poor egg quality?
I am okay with going to retrieval with so few follicles as I realize I have DOR and cannot expect a normal response. However, with having had a better response previously, would you recommend canceling at this point? Why?
This is such a stressful time for us, so I greatly appreciate your attention and feedback.
A. from Michigan
Answer:

Hello A. from the U.S. (Michigan),
First, you should know that ovaries can and will respond differently with each cycle regardless of the protocol used.  That is to say that even poor responders will respond better or worst from one cycle to the next.

In your case, I can make several observations which may be helpful to you:

1.  Despite a low AMH, you have responded pretty well with each cycle.  You had 14 follicles and 10 in the second.  This is not a sign of a poor responder.  Poor responders tend to have less than 10 total follicles.  In addition, your stimulation was not that high, so I would say you are a pretty average (normal) responder.

2.  As mentioned, your stimulation protocol was in the mid-range (375 IU and 450 IU).  The max protocol that most clinics use is up to 600 IU (450 FSH + 150 FSH/LH (menopur).  So in terms of stimulation, you have lots of room to improve.

3.  You mentioned starting Ganerelix when the follicles were 12 mms.  That is way too soon in my opinion.  Based on European studies and over 10 years of use by myself, I do not start Ganerelix until the lead follicles are at least 16 mms and preferably when the 30% or more are between 16-18 mms.  The purpose of Ganerelix is to prevent premature ovulation so I hold it until the very latest that I can to allow the follicles to develop without suppression.  Starting too early will lead the smaller follicles to stop growing.

None of this implies low egg quality or poor outcome.  It is part of the "art" of assisted reproduction and what distinguishes one doctor or clinic from another.  Bottom line is that IVF is not all about numbers.  It is about getting at last one good embryo to attach and lead to a pregnancy.  For that reason, even if there are fewer follicles I recommend that you keep going just in case the perfect embryo is in this group.

Good Luck,
Edward J. Ramirez, M.D., F.A.C.O.G.
Executive Medical Director
The Fertility and Gynecology Center
Monterey Bay IVF Program
www.montereybayivf.com

Monterey, California, U.S.A.

 

Tuesday, October 15, 2013

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.

 

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