Diminished Ovarian Reserve, First Time IVF: Low Estradiol (E2) Levels During IVF Stim Cycle

Question:

K. from NYC:

So, I took your advice and immediately wasted no time, and moved directly to IVF (in vitro fertilization). Dx: DOR (diminished ovarian reserve) @ age 35, one previous live birth 2 years ago, natural conception, (baby came from left ovary) after 12 months of trying @ 32 years old.

My recent HSG showed tubes open, but right tube slightly dilated. RE said not to worry about it at this time, as it was only slightly dictated and still spilling. Always have right ovary pain w/ ovulation, never left. I had b/w done on day 3 of my cycle before my ivf. FSH 10.4, e2 45, AFC 10, AMH 0.87. I started bcp's (birth control pills) for 21 days prior to stims. My AFC (antral follicle count) dropped to 6! ugg. For the last year i monitored my cycles very closely. 26 day cycles when i had ovulation pain on my right ovary, and 30 days when I had no pain from my left ovary. In my humble opinion I don't think my right ovary functions like it should.

Last month was my left ovary's turn, the month I had an AFC of 10 (6 antrals in left and 4 in right). This month it is my right ovary's turn and I only have 3 AFC in each #small too!~bcp's?. I also ovulate on cd 18 with my right ovary and cd 16 with my left, not sure if that is relevant.

My stims are NOT going well. I am on 300 follistim and 150 Menopur, I took no meds between ending BCP's and starting Follistim/Menopur 3 days later. On my the morning after my day 3 stims my e2 was a whopping 32.5! My clinic said to continue on my meds, no changes. Come back in 3 days for b/w and u/s. Per the nurse, "some people take a little time to get going". My questions are: why didn't they increase my meds? Did they expect a low e2 because I am DOR? Could this be over suppression with bcp's? Since I normally ovulate later in my cycle and not earlier like most DOR, could this just be my norm~my body taking it's time to develop the eggs? My cd3 e2 have always been between 30-45, I thought that was good for stimming? Could this be due to decrease blood flow to ovaries? I was told to stop my fish oil/baby asa/vitamin e before stims b/c they are blood thinners, but i thought these could help during stims?

This is my first IVF. Do you think they are just riding this out to see how I stimulate for next time? I am waiting for RE to call me back, but I want all the opinions I can get.

ANSWER:

Hello K. from New York.,

If I am understanding you correctly, your CD#3 E2 with this cycle was 32.5. That would be your baseline E2 for this cycle and does not necessarily indicate that you are not stimulating. The first estradiol level to check for stimulate would be four to five days after starting the stimulation (Follistim/Menopur) and you would be monitored approximately every three days after that to determine your progress. It is at the second E2 that you doctor might adjust your protocol and increase it if their protocol is not already at the highest. Some clinics use 450IU of medication (300IU Follistim/150IU Menopur) as their highest protocol. I go a little higher with 450IU of Follistim and 150IU Menopur. Because of your decreased ovarian reserve, it is expected that your ovaries will probably not stimulate strongly, but you will have to wait and see how things go. The goal is to have a peak E2 of around 2000 (when the follicles are ready to trigger).

I use low dose aspirin in all my IVF cycles, but not the Vit E or Fish oil. There is no problem with that.

It is certainly difficult to know how a person is going to respond in the first IVF cycle. There is a little guess work in determining how much medication to use with each patient. Your doctor has probably chosen this protocol as a good place to start and may make adjustments henceforth. You'll have to be patient and wait and see how things turn out. You may want to ask your doctor if you are on their highest protocol.

Follow-Up Question:

I never asked what my baseline e2 was, but the 32.5 was after 3 nights of stimulation. I had an u/s today (after 6 nights of meds) and NO CHANGE to baseline u/s, 6 unmeasurable follies. Waiting on new e2, but suspect it is going to be the same. I feel like I was completely suppressed. My cycle prior to this my CD3 u/s showed 10 juicy follicles, 6 in left and 4 in right. I know that this is a low count but I can't help to think that if i started my stims on that cycle I would have produced some eggs.

I am sure I will be cancelled on Monday. I hope my ovarian function returns. When they call w/ my e2's from this AM and if they don't increase my dose, I will ask why. I was told not to take any blood thinners (and listed: ASA, VitE, Foil due to risk of bleeding w/ ER.) When I suggested not using BCP's next time if needed they said ok, switch to Lupron, but wouldn't that suppress me too? Why can't we just start meds on CD3?? Thank you so much for your time!

Follow-Up Answer:

Hello Again,

Thanks for the clarification. The E2 on the third day of stimulation is called the CD#5 E2 level. It is the first check to see how you are stimulating, and you are correct, it shows that you are not stimulating at all. I don't do an ultrasound on that day because it is too early and the follicle sizes will still be small. The next check is usually done on CD#9 and an ultrasound is done with that visit. If you were in my clinic and the E2 were only 32 on CD#5, I would have increased your Follistim to 450IU. That is my maximum protocol (450IU Follistim/150IU Menopur). Then we would see how it goes from there. However, you have to understand that every clinic and every doctor is trained differently and uses different protocols. No protocol is better than any other. Your doctor's max protocol may only be 300/150. So you'll have to ask.

In terms of your decreased response, I don't think that it is due to the birth control pill, but there are some studies that show a decreased response if not enough days are given after the last pill and the start of stimulation. Basically, not enough time is given for it to leave your system.

In DOR (diminished ovarian reserve) patients I will usually want 6-7 days off the pill before starting stimulation. Again, you are correct that Lupron would also suppress the ovaries (this is known as the long protocol), and in fact, it will suppress the ovaries stronger than the birth control pill. I don't think that is any better.

The non-pill cycle that you are referring to is following the IVF cycle after a natural cycle. There are some clinics that do that but scheduling and making sure everything is suppressed appropriately, stimulated appropriately and timed appropriately is harder after a natural cycle. Some older studies also showed a better response if the ovary has been suppressed with the birth control pill for at least three weeks in the preceeding cycle. I always precede a cycle with birth control pills. That allows me to control the ovarian response. Decreased ovarian reserve or DOR basically means that your ovaries will not respond well to stimulation. That is to be expected. But, you should have had at least one follicle developing and that may mean that you are not being stimulated hard enough.

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.