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.

 

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.

 

Protect Your Fertility!

Dear Readers,
The American Society of Reproductive Medicine has launched a campaign with the aim of educating women on how to protect their fertility by avoiding certain risk factors. The Society has made available a number of fact sheets, graphics and brochures that are all downloadable on their "Protect Your Fertility" page. At our center we also offer the ability to extend the fertility of a woman by either freezing her eggs or her embryos. See "Fertility Preservation" for more information.

Check out the selection of fact sheets, infographics and a brochure on the ASRM page, including:

• "Advancing Age Decreases Your Ability To Have Children"
• "Smoking and Infertility"
• "Protect Your Fertility Brochure"
• "Impact of Age on Female Fertility"
• "Practicing Safe Sex Now Protects Your Ability To Have Children Later"

To quote ASRM: "At the risk of sounding like your high school health teacher, the decisions you make today really can impact your fertility and ability to have kids later. That's why it's so important to learn how to take care of your body. After all, there's a huge difference between choosing not to have kids and physically being unable to conceive if and when you want to."

Be proactive about your fertility health!

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.

Follicles Too Big In Clomid Ovulation Induction Cycle

Hello,
I am writing from San Diego, CA.  I was on 100mg Clomid on Cycle Day 3-7, then 2mg estradiol on cd 8-12. I went in for an ultrasound to check follicles on cycle day 13.  My RE said that this was most likely a lost cycle because I had 2 dominant follicles at 26 and 31 mm.  He gave me an HCG trigger because he did not want the follicles to get bigger and become cysts.  My uterine lining was 14 mm, and my RE was happy with that.  My husband and I had intercourse the day of the trigger and the day after, then skipped a day and had intercourse one more time.  

Were the follicles too big?  Do we have any chance of conceiving this cycle?  I have also been feeling cramps since yesterday at 7 days after the trigger.  Is this normal?  

Thanks for your input. L. from San Diego

Answer:

Hello L. from the U.S. (San Diego),

I don't have the ability to foresee the future, and certainly exceptions can occur, however, the follicle sizes were too big.  Usually once the follicle is greater than 24 mms, the egg within is overmature and therefore no longer viable.  Ovulation may occur but that is the main problem.  Also, it is highly likely that these follicles will turn cystic (persist) and have to be suppressed with birth control pills. You need to make sure a baseline ultrasound is done to evaluate for this at the start of your next cycle.

So, statistically and physiologically speaking, this cycle is probably a bust.  Unfortunately, your doctor missed the appropriate point by not doing the ultrasound early enough.  Next cycle he should begin looking at cycle day #9 or 10, which is what I do.  If I'm too early that's okay because nothing is lost and gives me a better idea of follicular development.  If you're too late, as in your cycle, then then cycle is lost; a big price to pay.

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.

Similar IVF Protocol But Different Results: Why?

Question:

Hi Dr. Ramirez,

I'm back again with a question about my recent IVF (second one). This IVF (in vitro fertilization) cycle we did the same protocol as last time (antagonist) but started off at a higher dose of Gonal-f based on my response last cycle. This cycle we started off at 300iu gonal-f and 75iu menopur whereas last cycle we started with 225iu gonal f and 75 IU menopur but had to increase to 300 IU gonal f after day 4 showed an E2 of only 90. Both cycles I started out with similar AFCs of 10 and 12 at suppression check. My usual AFC is between 16-20. Last cycle it seemed that I recruited more follies along the way and ended up with an E2 of 3030 and 23 eggs retrieved (17 of which were mature based on icsi and conventional fert rates as we did 50/50 split fertilization). This cycle my E2 was 2100 at trigger and they retrieved 12 eggs (still waiting on fert report today but we are doing all conventional fertilization).

My question is why did I have such a different response this cycle given that we started off at a higher dose this cycle compared to last? Last cycle we went up from 225iu gonal to 300 IU gonal at day 4 and stayed there until trigger. this cycle we started at 300iu gonal and stayed there until we added ganirelex on day 7. At that point my E2 stalled and do they increased my gonal f to 375iu gonal f and kept me there until trigger.

As always thanks for your advice/insight. S. from the U.S.A.

Answer:

Hello S. from the U.S. (Virginia).

The human body is not a consistent nor predictable structure so I can't explain why your response is different.  I have always explained to patients that have low response to stims that the ovaries can react differently each cycle and your experience is a case in point.  That being said, I would not have increased your dosage since your stimulation was so good the previous time and you bordered on entering OHSS territory.  In any case, IVF is not a contest where the person with the highest number of follicles or eggs wins the prize.  The goal is to find 1 or 2 perfect eggs that will lead to perfect embryos and a successful pregnancy.  So despite the fact that you stimulated less, that might be a better thing.  Bottom line is you only need one good one.  Also, there have been some studies showing that when a patient stimulates hard with lots of follicles, sometimes the egg quality suffers and the pregnancy rate drops.  This is especially true in PCO patients.  In those patients, our preference is to stimulate less and get fewer follicles.

So, in any case, as the saying goes: "I don't think you should sweat the nitty gritty" i.e the fine details.  Hope for the one perfect one.  That is the goal.

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.

Is A Tubal Reversal A Good Option For Me?

QUESTION:

I am a 33 year old mother of two. My children are 11 and nearly 10 years old.  After the birth of my second child in 2003 I had surgery to prevent further pregnancies. (I was in an unhappy marriage and only 23, and couldn't see myself ever getting out with 2 children.) The doctor was reluctant, because I was so young, but he decided to go ahead and perform the sterilization surgery. My tubes are not cut or clipped or burnt, they just have little clips on them to prevent the egg from passing through.  But just as many people predicted, now I regret the decision.  

I am divorced, my children are growing up, and I am in a wonderful relationship with a man who has no children of his own but would very much like to have one.  Barring infertility issues on his part, is there much hope of us being able to reverse my tubal and conceive a child of our own?  I don't have any other medical issues. I am healthy and active, average healthy weight, non-smoking, non-drinking...same for him. He is 39 and I'll be 34 this year, so we feel like the clock is ticking on any opportunity for another child.  Can this surgery be done, what are the odds of conception afterwards, what factors do I need to consider, how long do you need to wait after the surgery before trying to conceive.  And what is the average cost??  I appreciate any answers you can give me on the matter.

Thank-you! K. from Kentucky

ANSWER:

Hello K. from the U.S. (Kentucky),

The type of tubal ligation that you have is the best to reverse because the majority of the tube is kept intact and there is minimal damage to adjacent tubes.  Also, considering you are young still, a tubal reversal would be a good option in your case. A good and experienced gynecologist or reproductive specialist can do the reversal either by laparoscopy (using a scope and little incisions) or by a mini-laparotomy (a small incision above the pubic bone. You would want to find a surgeon who is well experienced in this and does them a lot to get the best chances for success.  

I have had a patient who went to North Carolina to have hers done by a doc who only does reversals. The risks for this procedure are the same risks as for any surgery (infection, bleeding, general anesthesia, injury to adjacent structures, failure) but this is not considered a major surgery, but rather should be an outpatient (same day) surgery.  In terms of success, those rates can vary widely so I can't give you an exact number.  A good surgeon will have an 80% success rate in patients under 35 years old after 1 year of trying.  If a pregnancy does not occur within 1 year, then the procedure probably has failed.  

Basically, with a tubal reversal, all you are doing is attempting to restore your natural fertility rate. This rate is very age dependent.  Your chances of natural pregnancy at 25 years old was 85% per year whereas at 35 it will be 30% per year because your eggs have aged.  So, keep these statistics in mind. The alternative to a tubal reversal, and with a higher likelihood of success is In Vitro Fertilization, but the down side is you would have to do this every time you wanted a child from this point on.  With a reversal, you could continue to have children by natural means if you wanted more than one.  Cost wise, tubal reversal will vary depending on the doctor, the clinic and whether or not it is done in an outpatient surgery center or hospital.  The cheapest I have seen is about $6000 and is done in an outpatient surgery center.  Hospital performed reversals will be $15,000-18,000.  I hope that gives you the information you needed.

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.

Comment: Thank you so much, once again. Armed with the information you provided, we can now move forward! I feel like I got lucky having my question go to such a knowledgeable and open volunteer!

Secondary Amenorrhea: A Description, Not A Diagnosis

Question:

Hello Dr. Ramirez,

I'm 20 and 293 pounds. I have had  Secondary Amenorrhea for close to 4 years now. It is apparently being caused by my weight. I'm not planning to TTC for at least another 12 or 13 years. I don't hate babies but it's not just a good time on the emotional or financial level to have them. If I'm able to get down to a decent weight and get rid of this disease,  What are my chances of getting pregnant when it's time for me to TTC???

There's a history of Diabetes in my family and I haven't had a asthma attack since I was 8.My mom had thyroid disease before I was born but I don't think that's genetic. But I don't have any other diseases than the SA at the current moment and my hormone levels were just fine at my last doctor appt which was last October. I've been on progesterone more than I count and it gets me a period but I want to have it without the help of drugs. Is there some kind of natural cure to SA??

I know that it seems a bit silly to ask about this NOW but I'm not getting any real answers about this disease from my OB. Everytime I asked my OB about this, she would tell me not to worry about it or brings a therapist in the room to basically tell me that I'm crazy.

She's since moved her practice out of state and I have a new OB that I'll start seeing very soon. But how in the hell am I crazy for wanting to be proactive about my own health?? I'm sorry for the language but I'm just so fed up about this and at my wits end.

I know that I'm not producing eggs right now but what else could this be doing to my body?? Do I have a reason to be concerned about it besides the obvious infertility scare?? If I do get rid of this disease,  Is there some kind of leftover side effect that could cause me to get Ovarian Cancer in the future??

I don't have these answers and I need to know what's going on. Please help me clear at least some of this up.

Thank You. D. R. from Michigan.

Answer:

Hello D. R. from the U.S. (Michigan),

Good riddance to your previous Ob doctor!  "Secondary Amenorrhea" is a description of a problem and NOT a diagnosis.  It just means that you used to have periods and now you don't.  It doesn't explain the cause.  The most common reason for old women to have secondary amenorrhea is menopause.  The most common reason for young women to have secondary amenorrhea is pregnancy.  However, a close second is an ovarian disorder called "Polycystic ovarian disease."  This diagnosis is manifested by irregular or rare natural menstrual cycles and at least one of the following findings: ovaries that look like PCO ovaries on ultrasound, inverted FSH/LH ratio, obesity, hirsuitism (increased facial hair), elevated testosterone levels, diabetes, elevate insulin levels signifying insulin resistance.  I think that you have PCOD but without a thorough endocrine evaluation, I cannot say for sure. 

With this disorder, you have a hormonal imbalance and that needs to be corrected.  The most simple way to do that is to use a low androgen birth control pill such as Yaz.  Once you are ready for pregnancy, then you will have to use fertility medications, which actually do not increase your fertility but induce your ovaries to ovulate, so that you can give off an egg to get pregnant.  You need to see a COMPETENT gynecologist or a reproductive endocrinologist to be evaluated and treated correctly!

You may want to see a more detailed explanation of Polycystic Ovarian Disease on my website.

Glad you wrote! Good Luck,

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

www.montereybayivf.com

Monterey, California, U.S.A.