2 failed IVF cycles
3 Replies
OLu - August 21

Dear Dr. Smith,

I am 23 years old and my DH is 32. 3 years ago I have been diagnosed with PCOS. Since that time we have been TTC naturally and then used Clomid for 3 cycles, all of which failed. In February 2006 we had our first IVF cycle. I was on a long protocol (Buserelin/Puregon). As a result 29 eggs were collected, 26 mature, 14 fertilized, 10 embryos (all of them been grade 2, as I was explained they grade embryos on a scale from 1 to 5, 1 – only embryos conceived naturally, 2 – the best possible in IVF cycle). 2 embryos were transferred on day 3 (8 and 6 cell), 8 embryos frozen. I had a mild case of OHSS, the pregnancy test on day 16 after collection was negative. My RE couldn’t give me an explanation for a failed, “It was a perfect cycle” (except for BFN). He also told us that the fertilization rate was low and suggested ICSI. We had a second cycle in July 2006. I was on the same long protocol (Buserelin/Puregon), but the dose of Puregon was decreased from 150 IUs in the 1st cycle to 150/100 IUs. I have produced 26 eggs, 18 mature, only 6 fertilized (my DH and myself decided not to do ICSI as we thought that it was needed only when there are problems with the semen, and the sperm quality on the day of collection was good; now we realize it was our mistake). The transfer was on day 2, 3 embryos (4, 3 and 2 cell, quality 2) transferred + AH. Again BFN on day 16.
Do you have any suggestions on why we have such low fertilization rate and no implantation? I haven’t had a chance to talk to my RE yet (I have an appointment scheduled for September 12). I wanted to know what questions to ask during my visit before we have our third IVF cycle. Should I do any additional tests (for example immunological)? I am thinking about ICSI + AH + blastocyst transfer next time (for some reason they have never told us about a possibility of Day 5 transfer). Also how many embryos would you suggest to transfer in my case?
I am sorry for a long post, I am just starting to get confused and desperate as I realize that my RE is not doing everything he can (and we have already paid for a 3 cycle package, so we cannot change a Clinic now).

Thank you


Dr Smith - August 22

When eggs are retieved from PCOS patients, they may not be fully mature. Maturity is define in two ways. Nuclear maturity (has the egg kicked out half the chromomsome to make room for the ones the sperm will bring in). The egg must of reached nuclear maturity to be ICSI'd. This is what they meant when they used the term"mature"to decribe 26 "mature" or 18 "mature". There's more to egg maturity than just nuclear maturity. The second aspect of maturity is cytoplasmic maturity. This process occurs while the egg is maturing in the follicle. Cytoplasmic maturation is required so that the egg has all the "goodies" in needs to make it through the first 2 days of life. If this process is incomplete, often the egg will not fertilize naturally, or fail to develop properly. Eggs retrieved from smaller follicles may not have completed cytoplasmic maturation. In PCOS, a significant number of the eggs are retrieved from smaller follicles. Low "natural" fertilization rates are expected in PCOS patients. ICSI may be used to force the fertilization issue, and sometimes you get a little farther ahead with increased fertilization rates, BUT you can't make a bad egg good by putting a sperm inside. ICSI can be justified in PCOS patients to improve fertilization rates and you may want to consider it in subsequent cycles. Assisted hatching may also improve implantation.

The hyperestrogenic state of PCOS patients can also interfer with implantation. We sometimes freeze all the embryos if the E2 get too high (i.e. >5000 pg/ml).

"Perfect" cycles that do not result in a pregnancy are not "perfect"cycles are they?. This kind of statement is just another way of shifting blame to you. What your RE was implying was that he did his job "perfectly", the lab did their job "perfectly", but you dropped the ball. Funny how that works. They take credit when it works and shift blame when it doesn't. Hmmm....

Your transfers were on Day 3 and Day 2. This is before the developmental competence of the embryo can be determined. I think the reason blastocyst transfer (Day 5) was never mentioned is because they don't do it, particularily for PCOS patients becuase, in PCOS patients, there is significant attrition of the embryos between Day 3 and Day 5. If a significant number of embryos stopped growing on the way to blastocyst (which is common in PCOS patients), who should be blamed? The RE? The lab? The truth is, its nobody's fault. PCOS patients are the trickiest patients to manage and their pregnancy rate, as a group, is significantly below patients of the same age with different diagnoses.

I agree that blastocyst transfer is your next step. Brace yourself for the high attrition rate common in PCOS patients. You can request it, but if they agree, make sure they have a consistent track record growing emryos to the blastocyst stage. If they only do it once in a while, seek out a program that performs blastocyst transfer routinely.

Best of luck


OLu - August 22

Dear Dr. Smith,

Thank you for your prompt and detailed answer.
I wanted to ask you one more question before discussing the options for my next IVF cycle with my RE. Do you think that the reason I am not getting pregnant is because the embryos that were transferred just stopped developing due to PCOS or should I also start thinking about the problem with implantation and have some additional test done (if yes what tests would you suggest)?

Thank you in advance


Dr Smith - August 23

It is impossible to tell in any specific case what went wrong after a Day 3 transfer. A Day 5 transfer would have at least answered the embryo question. Unfortunately, all we have to go on is generalities like PCOS embryos tend not to do well or high estrogen levels are associated with implantation failure. We do not know what causes these associations. Sorry I can't be more specific, but that's the extent of our knowledge base at the present time.



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