Canadian IVF Cycle Fails: Husband Asks, Try Again?

Question:

Hello Dr. Ramirez and thank you so much for answering these questions.

My wife and I just completed our first IVF (although there was no transfer). A previous attempt was cancelled due to only a couple follicles (150 Gonal F/150 Menopur). We had done 2 previous IUIs with Clomid (3 follicles).

My wife is 37 and has very low AMH (0.40), FSH that ranges from 7 to 14 and an AFC of 6 to 14. My analysis has been normal but we were recommended ICSI as it was unlikely we would get many follicles. The clinic said they generally like to aim for 2 good ones.

To bring down FSH, my wife used an estrogen patch before her period and had 3 Ganirelix injections. She then started 300 Gonal F & 150 Menopur on Cycle Day 2. From Day 9 to 15 she also used Ganirelix. She was told to change the patch every other day and on cycle day 4 stop changing the patch (but it would last 7 days so would still have medication until cycle day 10).

She was slow to respond, not developing any measurable follicles (greater than 1.0) until after 7 nights of stims, but in the end, used the same Gonal/Menopur dosages for 15 nights. Her AFC had been 14 and when she triggered (with 10,000IU HCG) on night 15 she had 7 follicles (2.2, 3 at 2.0, 1.6, 1.4, 1.0). On trigger night her e2 was just over 2,500 (I have converted this to the U.S. value - pg/nl).

35 1/2 hours later was retrieval. They got 4 eggs and had to skip a few on one ovary due to blood vessels. The next day the embryologist called and said they had been able to ICSI 3 of the 4 and as of that morning (day after retrieval) only 1 of the 3 remained. The next morning (2 days after retrieval) they called to say that embryo failed to divide. It was the same the next day so there was no transfer. They didn't have a definite answer as to why but said one of the eggs was soft and they weren't all smooth so it is probably egg quality issues.

Also - up until day 11 of stims her lining had been building well daily (to 1.2 cm). Over the next 3 consecutive days it got thinner each day (even though e2 was rising) and was 0.9 the day of trigger. Her lining has never been a problem in any other cycle (natural or medicated - even on Clomid).

We are trying to decide if it is worth it to do another cycle. Could this be a fluke? Could the long stim period have compromised egg quality (in addition to her age/FSH/AMH?) Could ICSI have damaged the eggs at all if they were soft? Will the blood vessels mean some follicles have to be left in one ovary at every retrieval?

Did the thinning lining indicate anything - coincidentally - when the lining started thinning her own e2 was raising daily quite a bit, but this was the same time the medication from her final estrogen patch would have worn off. She had a bit of bleeding a few hours before the trigger shot on night 15 and was put on 8 mg/day of estrace the day of retrieval in addition to progesterone because of that.

I would appreciate your advice. We would like to try again but I don't want my wife to have to go through another cycle of injections/monitoring/retrieval, etc. if our results would be the same. She had 12 days of blood tests & ultrasounds between day 2 & 15 and the 12 blood tests made it really hard to find a vein for IV at retrieval which took a couple tries.

We would like to at least make it to transfer before considering other options, but if we can't develop embryos in a lab, we're not sure if we should try again.

Thank you,

T. from Ontario, Canada

Answer:

Hello T. from Canada,

A lot of the answers you seek are due to technical quality issues and I cannot address that. Without a thorough review and evaluation of your wife's medical records, I cannot evaluate if I would have done things the same or differently, and whether or not that will make a difference. Suffice it to say that I am saddened by your results, but at the same time, I am a little leery about some of the embryology outcomes.

Let me just give some information that might help you in your review.

The dosage of 350/150 is NOT the highest stimulation protocol. Your wife could go up to the max dosage of 450/150 which might make a difference in the number of follicles recruited.
Based on the number of follicles formed, she actually stimulated well so the AFC, AMH and FSH may not be valid in predicting her decreased ovarian reserve (which does not predict fertility).
I have not heard of the failure to retrieve due to "veins" or "blood vessels". There are techniques that can be used to move and manipulate the ovaries to avoid those problems. I have, however, had patients where I could not retrieve completely because the ovaries moved too much and deep into the pelvis.
I think that ICSI in a 37 year old woman is appropriate and would concur with doing that procedure. Keep in mind that ICSI is a procedure and "technique and skill" are critical to preventing damage/injury to the embryo. It has been shown that ICSI done by an embryologist without adequate experience and skill can reduce embryo survival. That could possibly have been a problem, but certainly inherent egg quality can influence that as well.
Embryo quality (based on external features) are certainly based on inherent egg quality and that decreases with age. However, that does not mean that all the eggs are bad. Studies have shown that at 37 years old, 2 of 10 embryos formed will be normal. The trick is to find the two good ones. That may take several attempts or you would have the option of moving to donor eggs. Since you have never completed an IVF cycle, you certainly have not tested whether or not it will work.
Finally, I don't think I have ever had a patient that needed 12 blood tests during an IVF cycle. The maximum I've had was 7. Keep in mind that IVF success rates are highly variable between clinics and doctors. Even in the U.S., rates are highly variable as compiled by the CDC. I'm sure they vary greatly in Canada as well. Based on what you have told me in your review, I can't help but be a little skeptical of the level of care you are receiving, but again, I can't draw any conclusions without a careful review of your records.

Good Luck,

Dr. 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

Comment: Thank you very much for your quick and helpful response.