Slow Developing and Arrested Embryos
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christi - June 13

Dear Dr. Smith,

I just had a negative test after our third cycle of IVF, but it was our first cycle that we were able to make it to egg collection and embryo transfer. I am 41 years old and my husband is 27 years old, we have been trying to conceive for over 3 years. I have one son from a previous relationship, and the pregnancy and birth was normal. We were told we had a male factor motility issue with some abnormal morphology. I've had extensive tests done to me and nothing was ever found. I was always told before how "young my ovaries act" because of my low FSH 5.7 and because of how well I responded to the IVF drugs. I develop many small follicles during IVF. My current doctor has told me she doesn't consider me PCOS because I have regular periods and none of the other symptoms. First, I will give you a brief summary of how our 3 IVF cycles have gone.

IVF #1 at Vincent IVF Unit, Massachusetts General Hospital, Boston Massachusetts USA

I don't have those records with me now, but they tried me on the long protocol. I was very happy with the treatment I received there, but since it was my first IVF they didn't know I would respond so well to the drugs. The doctors observed 15 to 20 follicles in each ovary. I was started out with an amount that was too high and I ended up over stimulated, so the cycle was canceled.

IVF #2 LUMC Netherlands (we moved overseas which is why we're having treatment in Holland now) - Short Protocol

Starting Day 1 of AF we began injecting Decapeptyl for 3 days before starting with Gonal f. We continued with the Decapeptyl daily until the cycle was canceled.
Day 1 of stimulation started on 150 Gonal f
Day 2 - 150 Gonal f
Day 3 - 150 Gonal f
Day 4 - 150 Gonal f (first scan and blood)
Day 5 - 150 Gonal f
Day 6 - 75 Gonal f (scan and blood - estrogen at 4,000 and the doctor sees 15 to 20 follicles in each ovary)
Day 7 - 37.5 Gonal f (scan and blood - estrogen at 7,500)
Day 8 - No Gonal f (scan and blood - estrogen at 12,000)
Day 9 - No Gonal f
Day 10 - 75 Gonal f (scan and blood - estrogen at 3,000)
Day 11 75 Gonal f (scan and blood - largest follicles at 14mm and 15mm but most are small)
Day 12 - cycle canceled estrogen at 700

IVF/ICSI #3 at LUMC Netherlands - Short Protocol - May 2010

Starting Day 1 of AF we began injecting Decapeptyl for 3 days before starting with Gonal f. We continued with the Decapeptyl daily until before egg collection. The last Decapeptyl injection was the day we administered the trigger shot.
Day 1 of stimulation started on 112.5 Gonal f
Day 2 - 112.5 Gonal f
Day 3 - 112.5 Gonal f
Day 4 - 112.5 Gonal f (first scan and blood, estrogen at 1,400)
Day 5 - 112.5 Gonal f
Day 6 - 112.5 Gonal f
Day 7 - 37.5 Gonal f (scan and blood, estrogen at 6,000 and largest follicles at 10mm and 11mm - doctor sees 15 to 20 follicles in each ovary)
Day 8 - 37.5 Gonal f (scan and blood, estrogen at 9,000 and largest follicles at 11mm and 12mm)
Day 9 - No Gonal f (scan and blood, estrogen at 11,000 and largest follicles at 16mm but most still very small - Instructed to give myself the Pregnyl injection 10,000 units at 11:30 in the evening)
Day 10 - Drug free day and no scan or blood test
Day 11 - Drop off sperm at 9:00am - 11:00am at hospital for sedation before egg collection - 11:30am egg collection and after we were told they collected 15 eggs - no blood test taken, but told to begin progesterone vaginally 3x daily
Day 12 - We were told 10/15 eggs fertilized - some done IVF and some ICSI - taking progesterone
Day 13 - Stayed home waiting - taking progesterone
Day 14 - 9:30am at hospital for embryo transfer - told 8/10 arrested and 2/10 at "4cells" - had two 4 cell embryos transferred - I was told the two surviving embryos were both from ICSI

There are a couple of things that didn't go well on our 3rd cycle and I wanted to ask about:

1) Because I have a history of over-responding to the drugs, my clinic tells me that this makes me a very difficult patient to treat. They end up having me come in every day for scans and blood tests to check my estrogen levels, which makes me happy they're monitoring me carefully. On my 2nd IVF they took me off gonal f for 2 days because my estrogen was at 12,000. Then they resumed the gonal f at 75 units for 2 days and my estrogen crashed to 700. They said my eggs could not survive that type of estrogen drop and my cycle was canceled.

So during my 3rd IVF, my estrogen levels were getting high again. They were afraid to take me off the gonal f because of what happened on cycle 2. So they lowered the dose of gonal f to 37.5, but my estrogen kept rising. On the 9th day of stimulation a couple of follicles were at 16mm, but all the others were still very small and my estrogen was at 11,000. When they called me later that day, they told me not to take any more gonal f and to give myself the Pregnyl 10,000 units at 11:30 that night. I asked if my follicles would be big enough at egg collection since all of them were very small except for the 2 or 3 at 16mm. She answered me "that they are hoping the follicles will be matured by then". I explained below what happened to our embryos. So I am wondering if what happened to them had anything to do with how difficult I am to treat and if they were forced to give me the pregnyl injection before my eggs were ready? Is it possible that had anything to do with how the embryos turned out or is it more likely due to my age?

2) On our 3rd cycle 10/15 eggs fertilized and we were amazed and so happy. They did a combination of IVF and ICSI on our eggs. They did 6 eggs with ICSI and 4 of them fertilized. The remaining 9 eggs were done IVF and 6 fertilized, making a total of 10 embryos on day 1. Then went in for ET on Day 3 and found out that eight of the embryos had stopped developing. We got two slow developing embryos transferred. The two embryos transferred were both at "4 cells" on day 3 when they should have been around 8 cells. Our clinic grades embryos as 1 being the best and 4 or 5 the lowest quality. They graded one of our embryos a 2 and the other embryo a 3. I asked the embryologist at the time why the others had just stopped, and she said sometimes they see this happen with older women. That was the first time I heard any indication that there could be something wrong with me. We always thought we were only dealing with a male factor issue. That day after leaving embryo transfer I felt crushed, almost like I was told the BFN news that day. I had little hope after learning 8/10 embryos arrested and the last 2 were developing very slowly. The two "4 cell" embryos that were transferred were both from ICSI.

- I am hoping you can tell me why this happened to all of our embryos and how can they just stop developing like this? Do you think it's a coincidence that the two surviving embryos were from ICSI? Would you recommend that I only have ICSI on my next cycle? Are there are any tests we should have now? Are there any supplements or drugs we can take to change things for next time? Was this due to the eggs or the sperm or both? Could it have happened because the Pregnyl injection had to be given when most of the eggs were still small with only a few at 16mm? Is the problem my age? 2/10 embryos is very close to 0/10 and I'm so worried that this could happen again next time. If it happened because of my age then I am scared nothing can be done to help us. I'm sorry for the long post, I just wanted to explain our situation so you have all the facts. Thank you, and I will be very grateful to hear your opinion.




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