4 failed IVF's - what now
6 Replies
hope2be - November 8

Dr. Smith,

I am 31yo and DH is 32. WE have been ttc for 3 years. DH has male factor due to varicocele but we have always used ICSI. We have had 4 failed IVF's and we have never had any embryos to freeze. I have been told that I am a poor responder and that egg quality is the issue and that we need DE. First IVF 4 eggs, 2 embryos. Second 7 eggs, 4 embryos. Third(on 600 Follistim a day) 15 eggs and 10 embryos. Fourth 6 eggs and 6 embryos. This cycle resulted in a possible ectopic that was treated with methotrexate. Nothing was found in utero on 6w1d ultrasound and betas did not rise adequately. My lining is never above 8 and my top E2 level was 2300. Our fertilization has always been good but our embryos are very slow to develop. Our last cycle we did PGD and 5 out of 6 were normal. It seems that after 3 days they stop dividing. DH has had an SCSA which was normal. What could our problem be? Before using DE would like to exhaust all options. Is is possible that we both have some genetic problem? Would cycling again with donor sperm be wise or should we go straight to DE. Is there a definitive test for egg quality? I would hate to go to DE and have all embryos perish to find out that it is DH sperm. Thank you. I find these forum to be very helpful and educational.



Dr Smith - November 9

The varicocele can cause heat stress to the sperm which, in turn, can reslt in DNA fragmentation. But, you've covered that base with the SCSA. The PGD ruled out the most common aneuploidies, so that's unlikely the cause of the slow development (you or your husband). The endometrium was adequate, if it was 8mm or more.

I think the cytoplasm of your eggs is deficient in one or more essential developmental components (i.e. molecule or molecules). Embryo development is like a cascade. If one or more components are missing, the cascade stops at that point. For example, at the 2- to 4-cell stage.

I know you are very young to be considering DE, but I think its the right choice. We have had patients in their early 30s that needed DE, so it does happen. I'm happy to report that the vast majority of these patients are pregnant.


hope2be - November 9

Dr. Smith,

"I think the cytoplasm of your eggs is deficient in one or more essential developmental components (i.e. molecule or molecules). "

Thank you for your reply and your honesty. Could the cytoplasm be changed or improved with different protocals? I have always used Follistim and on the last 2 cycles dilute HCG and Lupron as well. One concern that I have had is that I was never stimmed on anything else. Would this make a difference? Also would stimming a 5th time be harmful to me? Before going to donor eggs would donor sperm and my eggs make sense? Could embryo demise be from something genetic that can't be tested for and that it is just not possible for DH and I to have biological child together. We know that our next move is donor one way or the other.

Thanks again.



Dr Smith - November 15

Sorry for the delay - I've been sick.

The definitive test for egg quality is IVF. So repeated IVF cycles with slowly developing embryos is strongly suggestive of an egg "problem". My hunch is that it is a problem with the egg cytoplasm.

Changing medication per se will not change much. All products are basically the same - FSH under different labels. The companies claim that their products are different for one reason or another, but that's all marketing and has little basis in biology. HOWEVER, when different medications are used (usually by different physicians since they all seem to have a favorite), they may be used in a different way resulting in a different rate of follicular growth and/or egg maturation. This may alter the developmental potential of eggs (i.e. cytoplasmic maturation). In your case, I think it is unlikely that changing medications will make a huge difference. I'm sure each of your cycles was a little different (i.e. number of days of stimulation, peak E2, etc) and the development of the embryos was pretty consistent.

Based on existing knowledge, there is no detrimental effect to repeated stimulated cycles. After all, the medications are the same hormones present in your body every month and the medications only act to "salvage" follicles that were recruited in a growing pool but would have died off anyway. You are not depleting you eggs at a faster rate that you would normally. There is no tie between the use of gonadotropins (FSH,LH) and any disease.

It is possible that you and your husband have a genetic problem that resultsin slow embryonic growth, but I think that's a long shot. Although I can't rule out a genetic problem with the sperm, embryonic arrest before Day 4 is almost always caused by cytoplasmic or gentic problems with the egg. Donor sperm and donor egg is always a possibility. It puts you and your husband on equal genetic footing. That is, neither of you is genetically reated to the child. In a sense, its adoption but you are in control of the prenatal care. From a purely biological point of view, I don't think donor sperm is necessary.

PGD tests only the tip of the genetic iceberg. It is a very crude tool. Although embryos can be considered "normal" by PGD, they may still be developmentally compromised.

As a precaution, you could go through immunological testing to determine if there is a problem on the uterine side which may be preventing implantation. Immune testing does not address the slowly developing embryo problem, but if you do decide to go to DE or DE/DS, it would be reassuring to know that implantation will not be an issue.


hope2be - November 15

Dr. Smith,

I'm sorry to hear that you have been ill and I hope you are doing better. Thank you for your honesty in your replies. I just want to feel as if I have exhausted all options before using DE. If I was your patient would you recommed DE with DH sperm as the next step?

Thank you,


Dr Smith - November 16

Yes, I would recommend DE/DH. I can't find enough wrong with the sperm to justify the use of DS.


hope2be - November 16

Dr. Smith,

Thank you for taking the time to respond to my questions. Your honesty is very much appreciated even though it is hard to accept.




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