1st IVF produced all embryos with chomosomal abnormalities

Dr. Wisot
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Re: 1st IVF produced all embryos with chomosomal abnormaliti

Post by Dr. Wisot »

First to JKPH:

I hate to say it, but I think the "quality" of those blastocysts is a factor in the chance of implantation even if they are chromsomally normal.

Before doing anything else I would suggest a formal second opinion.

Now to SAM:

You cannot determine whether an egg looks abnormal due to chromosomes without doing a polar body biopsy.

For you too I suggest before proceeding to another cycle have someone else take a look at your records and give you a second opinion.

Arthur L. Wisot, M. D.
Reproductive Partners Medical Group
Redondo Beach, California
Kristina

Re: 1st IVF produced all embryos with chomosomal abnormaliti

Post by Kristina »

Hello, Dr. Wisot

I'm happy to see that you're so close to me- I'm in Sherman Oaks. I am interested in switching to your office if my current IVF cycle doesn't work out.

I conceived my son naturally at age 37. My marriage didn't work out, and now I'm 40. I want a second child, and I don't have the time to find another man for that, so I'm doing IVF with donor sperm.

I went through an IVF cycle back in June, with agonist protocol and a combo of 225 GonalF and 75 menopur each day. 26 eggs were retrieved, 20 were mature, 15 fertilized, 7 made it to day 5 where PGD testing showed them all to be abnormal. I was devastated. Two of them had a monosomy, and only one of them was a complex abnormal. What did you mean when you wrote, "Were there some that showed a monosomy as the only abnormality which might suggest a problem with the process?" What do you mean by "a problem with the process?" A problem with the testing process? Or a problem with the IVF protocol itself?

My depression lead me to do a lot of research, and I read that for a woman my age, a stimulation drug that contains LH (like Menopur) could wreak havoc on my eggs. Also, I read that a high FSH dose in general could be detrimental to egg quality. I found out about the Afolia study, and I enrolled.

Afolia is supposedly identical to GonalF. The study is an agonist protocol with birth control pill prepping and 225 units of Afolia each day. The doctor retrieved 14 eggs (the lower number didn't surprise me, since my FSH stimulation dose was lower than that of the previous cycle), 10 were mature, 5 fertilized, and all 5 were still alive on day 3. PGD testing is not permitted in the study, so on day 3, we transferred the two best-looking embryos to my uterus.

That was three days ago, so I still have a while to wait before taking the pregnancy test. The lab does not yet have an update for me as far as the three remaining embryos, which I hope to be able to freeze. I am worried all of my eggs in this cycle are bad quality as well. Can you please tell me what you meant by "a problem with the process?" And also, what is the protocol that would be best for me, in your opinion? Please let me know, and thank you for your time.
Dr. Wisot
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Re: 1st IVF produced all embryos with chomosomal abnormaliti

Post by Dr. Wisot »

This is difficult to answer without the details of exactly what did not look normal and the stimulation protocol.

One cannot determine the chromosome makeup of an egg by merely looking at it and it would be unusual at your age and with a normal FSH level (if yours is normal) to have most of the eggs look abnormal.

Meet with your doctor to get the details and if he/she does not come up with a reasonable answer, take your records and hopefully pictures of the eggs for a second opinon before starting another cycle.

Arthur L. Wisot, M. D.
Reproductive Partners Medical Group
Redondo Beach, California
Kristina

Re: 1st IVF produced all embryos with chomosomal abnormaliti

Post by Kristina »

Thank you for your reply, Doctor. As far as what exactly did not look normal, here is the information:

embryo # 1- abnormal +9
embryo #2 - abnormal -15
embryo #3 - abnormal +9, +22
embryo #4 - abnormal -2p
embryo #5 - abnormal +1, +9, +12
embryo #6 - abnormal +11
embryo #7 - complex abnormal

As far as the stimulation protocol, it was was agonist with 300 units GonalF for 4 days, followed by a combo of 225 units GonalF and and 75 units menopur each day for the remaining days (5 or 6 days, I forgot exactly). Lupron was 20 units/day in the beginning, and was then decreased to 10 units/day when the stimulation drugs were begun. I was given a 10,000IU HCG shot to induce ovulation. Is there anything else that you need to know about the protocol? Please let me know.

My FSH level was measured at 7.63 mIU/ml
My AMH was measured at 3.08

As I already mentioned, today is day 6 for the embryos that are part of the IVF cycle that I'm currently going through - my second cycle. I mentioned previously that out of the 5 fertilized embryos, two of them were transferred into me, and we were keeping an eye on the remaining 3 until blastocyst stage. Well, I spoke to the lab today, and none of the 3 made it. They all just died off.

Given that information, my hope is very bleak that the two embryos still inside me will result in a pregnancy.

Please let me know if you need any additional information. Thank you again.
Dr. Wisot
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Posts: 1208
Joined: Fri Oct 14, 2005 11:16 am

Re: 1st IVF produced all embryos with chomosomal abnormaliti

Post by Dr. Wisot »

I thought you meant that the eggs looked abnormal, not that the PGS results on the embryo were abnormal.

What I meant in a previous post that a monsomy might be a problem with the process, you do not know if it is a real deletion of one of the pair of a particular chromosome or if it was just a loss of signal from the process.

Using some LH activity is not thought by most to be detrimental the egg development. You current study cycle was FSH only and you did not do as well as in the prior cycle when you used some Menopur.

Hopefully this cycle has a good outcome, but if not, listen to your doctor's recommendations, then take your records for a second opinion before signing on the dotted line for another cycle.

Arthur L. Wisot, M. D.
Reproductive Partners Medical Group, Inc.
Redondo Beach, California
Kristina

Re: 1st IVF produced all embryos with chomosomal abnormaliti

Post by Kristina »

Thank you, Dr, Wisot

Yes, I agree with everything you've said as far as my current cycle being FSH only and I did worse than the previous cycle, which contained LH. The funny thing is that with my previous cycle, I was also still a smoker, and I also wasn't taking any of the vitamins that are supposed to help with egg quality. But for cycle #2, I quit smoking, took a ton of vitamins, and lived an extremely healthy lifestyle. By that rationale, I guess I should start smoking again and eating junk food if those things are going to improve the outcome of my third cycle? LOL!

Getting a second opinion - yes, YOU are the doctor from whom I am trying to get a second opinion. I am local to your area. So please, tell me the protocol with which you would treat me if I were your patient.

And one thing that I still don't understand about the monosomies - you said that it might just have been a loss of signal from the process? I don't understand what you mean by that. What process? The process of the development of the embryo? The process of culturing the embryo in vitro instead of in utero? You're saying maybe the chromosome wasn't actually deleted; but rather, the chromosome perhaps didn't receive the signal to develop properly? Am I understanding you correctly? If I'm understanding you correctly, then what is the relevance of those two (evidently) opposing theories? Would one of them be more desirable than the other? If so, why?

Thank you!
Dr. Wisot
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Posts: 1208
Joined: Fri Oct 14, 2005 11:16 am

Re: 1st IVF produced all embryos with chomosomal abnormaliti

Post by Dr. Wisot »

Without really looking at all your details I do not know what protocol I would recommend.

The problem with monosomies is in the genetic process, performing the CHG array a technical issue causing it to look like a monosomy can be a loss of signal from a particular chromosome. It is thought not to happen too often so it is assumed that when a monosomy is discovered the embryo is not considered suitable for transfer especially if the monosomy is one of the sex chromosomes. Also they often are testing more than one cell so the chromsome would have to not show up in more than one cell so the situation is unlikely.

Arthur L. Wisot, M. D.
Reproductive Partners Medical Group, Inc.
Redondo Beach, California
DNA

Re: 1st IVF produced all embryos with chomosomal abnormaliti

Post by DNA »

Dear Dr. Wisot,

I am an MD and have just had an IVF cycle in which PGS (Genesis-24 chromosome PGS) of blastomeres (Day 3 embryos) showed abnormal results. I am over 40 so I suppose it can be explained by my age.

I produced a lot of eggs (29 eggs retrieved, 22 fertilized, 16 Day-3 embryos biopsied = all abnormal). While 14 embryos had multiple abnormalities, 1 embryo had single monosomy 4 and one single monosomy 20.

I have had multiple IFV cycles, all with aCGH, 3 pregnancies (2 late losses at 7 months for non-chromosomal reasons). Some cycles had "all abnormal embryos", while most cycles had 1-2 normal embryos.

So, while this is not the first "all abnormal" cycle, I am a bit surprised to see that 2 embryos had a single monosomy. Further, embryologist suggested to re-test the embryo with monosomy 4 at a blastocyst stage (tomorrow) - to confirm the result. I am not inclined to re-test the embryo, as evidence suggests high concordance between Day 3 and Day 5 results (notwithstanding the lower implantation potential for Day 3 biopsy), with error rate for Day 3 embryos of 1.8% (Munne, 2012).

However, I was intrigued by your comment about a potential for technical issue with monosomies during aCGH process. How often do you see a loss of signal from a single chromosome? I mean, is it generally considered to be a "red flag" (in the absence of other abnormalities) or not? Unfortunately, given that this was a Day 3 biopsy, the results reflect a single cell. I have little possibility to talk to the genetic lab (I live in Europe and generally don't get in-deapth answers to questions). This is the first time that I see that there is a technical problem with monosomies and I would really appreciate your thoughts on that.

Many thanks in advance and best regards
Dr. Wisot
Site Admin
Posts: 1208
Joined: Fri Oct 14, 2005 11:16 am

Re: 1st IVF produced all embryos with chomosomal abnormaliti

Post by Dr. Wisot »

Unfortunately I do not know the technical details of how they do things in Europe. With our newer more sophisticated techniques a signal loss appearing to be a monosomy is less of a risk.

More importantly at Day 3 there is more mosaicism, once cell being abnormal in a mostly normal embryo and vice versa. So I would suggest you do a rebiopsy on Day 5 and retesting.

We no longer do PGS on Day 3 embryos because of the limited information and risk of mosaicism.

Arthur L. Wisot, M. D.
Reproductive Partners Medical Group
Redondo Beach, California
DNA

Re: 1st IVF produced all embryos with chomosomal abnormaliti

Post by DNA »

Dear Dr. Wisot,

Thank you very much for your prompt response and advice.

I also think PGS on Day 3 is suboptimal and will have to re-think the whole testing strategy.

Thank you again for your time and expert opinion. Greatly appreciated!

Best regards
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