Tuesday, October 29, 2013

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


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

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

Monterey, California, U.S.A.



  1. I would love your input, you seem very knowledgeable and I thank you in advance.
    Dr. Ramirez,

    About me: 32 year old, natural pregnancy and live birth in 2011, AMH .16, AFC ~4, FSH 7.5, Estradiol range from 80-99, about 30 lbs overweight, non smoker.

    Hx of 2 recurrent miscarriages since daughter's birth, resulting in 4 D&C's, the pill to induce the miscarriage after heart stopped (methotrexate???spelling), blood transfusion, etc.

    Started to see a reproductive endocrinologist in June and FINALLY we are starting my cycle after some road blocks from my wacky female organs.

    After I ovulated, he started me on 20 units of lupron and a week later I am growing follicles and a cyst!!! Interestingly, I started spotting old blood a day before I started the lupron and it lasted 5 days. But, if we're looking at a calendar, I should've started my period on 11/04, but have not.

    The tentative plan is to drop me down to 5 units of lupron and add menupur 225 and follistim 225....if I would suppress.

    Any suggestions as to why I'm not suppressing?

    Thanks so much.

    1. Hello. I thank you for your confidence but I'm afraid I don't have an answer for you.

  2. Hi Dr Ramirez,

    I am 8 days past 5 day frozen transfer. I do not know the quality of the embryo, but we had two frozen and they thawed one the night before and it failed in the morning. They thawed the second an hour prior to the transfer and I don't think it had fully expanded but they still transferred it. On the third day after transfer I began spotting and have continued on and off since. It has been only light but it has been both red and brown at times. I am on 400mg progesterone pessaries in morning and 600 at night, both rectally not vaginally. I am also taking 6mg progynova daily. I took a home urine test yesterday at 7 days past and it was negative.
    My questions are:
    Did we waste the embryo by not waiting to see if it was ok and expanding more? If not, why don't they just do that with all embryos? Did we waste the first one?
    Is my spotting because of too low progesterone? My clinic don't seem worried and haven't re tested my level, it was 80 on transfer day.
    Is it too early for the home test? Could my beta still be positive? I have given up hope :(

    Thank you in advance, your post on bleeding is reassuring however a lot of the explanations are from pessaries vaginally.

    Kind regards,

    1. I often feel that the uterus is a better culture environment than the lab incubator so I would have transferred as well and not waited. Whether or not the first or second was wasted is an unknown. No one, not me or any other Physician, can predict what the outcome is going to be. Sometimes we get success from embryos that we never would have expected to turn into a baby. Ultimately it is always in God's hands, so no, I don't think anything was wasted.

      I cannot explain the cause of your spotting exactly but most likely it is due to the endometrial lining starting to break down as a result of no pregnancy but even that surprises me sometimes. No never know until you know. Only a blood pregnancy test can answer that question. By day 8 post transfer, a blood pregnancy test should give you a valid result.

  3. Hello Dr. Ramirez,
    I am writing from New Zealand. I have seen your blog and encouraged to write down regarding my fertility complications to you. I am 35 yr now and my Husband 34 yr. I had my first pregnancy in 2008 and got tarminated the pregnancy which i should not have. I got an ectopic pregnancy in 2013 on my right side tube. The treatment was methotrexed or something like this to protect the tube. Again, I had a second ectopic in 2014 on my left side tube. so doctor removed my left tube. now ive got only Right tube left. After all these trauma we underwent an IVF treatment last month and it failed and it was our first attempt to IVF. It seems I am loosing my hopes to get pregnant easily now. In my mind, I am intending to try naturally again, though my doctor recommended me not to try naturally. However, I dont know what should i do now. They said i dont have any blockage in my tube. I dont understand why it happend then!!!

    Could you please give me your constructive feedback on my situation and I would respect your positive recommendations, Ramirez.
    I look forward to your reply.
    M from New Zealand

    1. Hello,

      Since you also sent your question to my website, I've already answered you via email. I hope that gave you the information that you were looking for.

      Good Luck



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