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Topic: good eggs but slow embryos? (Read 11251 times) |
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Fifka
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Hi,
On my 3 IVFs, I generate plenty of mature healthy-looking eggs. My husband's sperm analysis is good. Most of eggs will fertilize, but most if not all resulting embryos are slow. Our 3rd IVF was the best - 2 out of 8 embryos were at 7 cells on day 3, the rest of embryos were 5 cells of less.
It's not lab's issue, as we tried it on 2 different clinics. It should not be age issue, as I am 32 and healthy. So what is it? Is it defect cytoplasm in my eggs? Do I have just very few of good eggs and the rest is bad? I had 2 early m/c's from IUIs. Should we test my husband's sperm DNA fragmentation?
Thank you very much for your opinion.
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Dr Smith
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Re:good eggs but slow embryos?
« Reply #1 on: 06/20/05, 10:08 » |
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Slow division cycles in the first 2 days of embryonic development is most likely due to problems with the egg cytoplasm, resulting in excessive fragmentation and arrested development. If the embryo makes it to between the 4 and 8-cell stage of development and then arrests, it is likely due to genetic abnormalities, e.g. aneuploidy. An early miscarriage demonstrates that the embryo developed to the blastocyst stage, implanted and began to grow within the endometrium. Your miscarriages may have be due to genetic abnormailities of the developing embryo (which caused it to stop growing) or uterine factors (immunological or clotting disorder). Was there any genetic testing done on the M/C or any mention of an "empty sac"?
From the information you have posted, it would appear primarily to be an egg problem. Women have egg problems at all ages (we see egg problems even in young donors), so being 32 and healthy does not rule out anything. You could go through extensive additional testing (e.g. immunological, clotting disorders, sperm DNA fragmentation testing), but I'm not sure you'd be that much farther ahead. From the information you've provided, using donated eggs is probably the most efficient way for your to become pregnant. Sorry, I'm sure that's not what you wanted to hear, but I think that's your best chance.
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holly-co
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Re:good eggs but slow embryos?
« Reply #2 on: 06/20/05, 11:38 » |
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Sorry for the barge but I too struggle with this problem at a young age (32, healthy, nl fsh, good response to stims etc.). In my case though they do see some things with my eggs that aren't normal while doing ICSI for mf (dark, grainy cytoplasm, inclusion bodies in cytoplasm, areas of smooth endoplasmic reticulum etc.). What if you have slow cell division by day 3 but good quality embies grade wise (no/minimal fragmentation and even cell sizes). Would you still blame the cytoplasm or does the absence of fragmentation give you clues to another prob with the egg? I guess I would still think there was some deficiency in the mitochondria and ATP to power cell division. I just would assume in that setting you would also see fragmentation. I have had lots of fragmentation (along with the poor developing embies) at one clinic but when I switched to a "top tier" clinic, fragmentation was no longer an issue (just the slow cell division) so I do think a good lab helps. Is it possible for the eggs/embryos to actually be genetically/chromosomally normal (esp. when you are dealing with a younger pt) and just that there isn't the energy available in the cytoplasm to support continued cell division in the embryo?
Also, for someone who probably does have some sort of cytoplasmic defect, do you think a more slow and steady stim process could be better (so that the cytoplasm has the ability to develop and mature to the best of it's ability). I was successful on one of my ivf attempts despite this egg issue being present and I just wonder if the fact that that stimulation compared to my other 2 which did not result in +'s (which even though I stimmed for an appropriate number of days 9/10, I stimmed fast having very large follicles early on--22 follies on day 5 that were around 1.5 in size) was slow and the follicle grow more even and steady. We are going to try and replicate that for this next attempt.
There is a lot of chatter going on lately on IVF support websites (not great scientific data obviously but here is the link http://www.centerforhumanreprod.com/premature_ovaries.html ) that DHEA supplementation may help improve egg/embryo quality in women whos ovaries may act older than they should (young women with poor egg quality?). Have you heard about this and do you think DHEA has any promise at all or is at least worth looking into further?
Thanks for your time.
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Dr Smith
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Re:good eggs but slow embryos?
« Reply #3 on: 06/21/05, 10:07 » |
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Arrested development/slow division is not always accompanied by excessive fragmentation. When non-fragmented embryos are slow to divide during the first two division cycles (1 to 2-cell, 2 to 4-cell), this is indicative of problems in the cytoplasm. Prior to ovulation (or retrieval), the egg must make all the cytoplasmic components it will need to take it through the first two division cycles. In embryo cells, as in all cells, the cell division process is a sequence of events that must occur in a scheduled and orderly fashion for the process to complete and repeat again. If any one or more of the components of the sequence are in short supply or absent, the division process slows or grinds to a halt. As you pointed out, there must be sufficient energy available in the form of ATP for the division process to proceed. However, becasue of the sequential nature of the cell division process, any missing component can cause the failure of the process. Because the cell division process is so complex and involves thousands of steps, it is impossible to determine what goes wrong in each individual embryo.
Arrested development between the 4 and 8-ceel stage of development is another kettle of fish. That's usually caused by genetic problems (i.e. nuclear), not cytoplasmic problems.
Yes, slower, more controlled, stimulations can overcome some cytoplasmic defects. If the egg's cytoplasmic
"production phase" in the maturing follicle is cut short by a fast stimulation (i.e. the follicle gets too big too fast), the egg has not had an adequate time to manufacture and accumulate all the cytoplasmic components required to get through the first two division cycles. Accordingly, these eggs will fertilize, but exhibit slow division cycles and arrest development during the first few division cycles.
There might be something to the DHEA story, but the scientific evidence, at this point, is not very strong. I believe the DHEA hype is being used primarily as a marketing tool for CHR to attract patients with poor prognosis. Because the treatment is "experimental", cycles with DHEA (i.e. research cycles) will not appear on CHR's anual success rate statistics as published by the CDC. So, they have nothing to loose by attracting poor prognosis patients and everything to gain from a financial point of view. When the DHEA story is independently confirmed in a prospective, randomized, case-controlled study and published in reputable scientific journal, then I will be convinced. Until then, I have adopted a wait 'n' see position.
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jeanice
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Re:good eggs but slow embryos?
« Reply #4 on: 10/19/05, 23:26 » |
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I got pregnant with my own eggs (age 33, 37, & 38, 2 tubals, 1 ivf success(age 39), but lost the baby with a placenta problem @ 6 months(did CVS). I always had grade A eggs but my doctor did not freeze on day 3 so I lost 23(2 ivf cycles) grade A embroys on day 5(age 39). Now I am 41(just turned) and
the last IVF I did, my eggs did not divide too well so we moved to donar eggs. I went to Dr. Schoolcraft once and he said he bet it was the sperm even though it looked good because
I had been pregnant without tubals before too. Only with my husband did I start to
have problems. I have NO scaring in my tubes. When we have intercourse, it
feels like something is crawling in me. I can not stand it. It burns. Now IVF
has been unsuccessful--period.
We used donor eggs with a donor who had been used 8 months before on another
couple. They had success, got pregnant, plus had 5 blastocysts left to freeze.
Our embroys did not multipy well at all. 1 7 celled, 2 6 celled, rest 4 cells. It is hard for me to believe it is not the sperm. The donar has done it 3 times and
everyone has been successful with blastocysts to freeze.
You can not tell me a 23 year old just happened to produce bad eggs on our
IVF cycle? After the transfers, I always feel something weird happening about
day 3 after the transfer, almost like a rejection is going on. I feel that I am never going to get pregnant as long as my husbands sperm is involved and now
I am getting older--just turned 41.(Husband 47)
Does anyone have any knowledge in this area? I do not know what do do
from here. We have had 3 unsucessful IVFs now in a row and I am sooo
sick of it.
Any ideas--besides adoption? Please help. Did all the anti-sperm tests.
Please reply quicklly. Help.
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Dr Smith
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Re:good eggs but slow embryos?
« Reply #5 on: 10/20/05, 09:03 » |
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It is possible that you husband's sperm DNA is highly fragmented and this is causing the embryos to arrest development prior to reaching the 8-cell stage. Although DNA fragmentation is correlated with abnormal sperm morphology, morphologically normal sperm can also have fragmented DNA. If you are going to attempt another cycle, I would recommend that you husband have the Sperm Chromatin Structure Assay. For more information on this test, see www.scsadiagnostics.com.
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liz c
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Re:good eggs but slow embryos?
« Reply #6 on: 11/06/05, 17:15 » |
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I"m sorry to swerve off subject a bit, but I have question about quality of embryos. Which is better, more cells or better quality? The data from my clinic indicates that better quality has better implantation rates, but I guess that's not the same as preg rates. In a grading scale of 5 (5 being the best), I had 3 grade 3 8- cell embryos at day 3 and 1 grade 2 7 cell. I'm 36. However, I also had a lot of embryos that arrested. Thank you.
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Dr Smith
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Re:good eggs but slow embryos?
« Reply #7 on: 11/07/05, 09:06 » |
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Both the number of cells (cleavage rate) and the degree of fragmentation (grade) are important and are considered simultaneously when determining the developmental potential of the embryo.
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Trish
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Re:good eggs but slow embryos?
« Reply #8 on: 12/01/05, 18:41 » |
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This is a very interesting thread. I am not as sophisticated as the others who posted questions for me, but I will do my best!
I just completed my first IVF cycle and it was negative. I had 10 eggs retrieved, 5 fertilized successfully (the other 5 were fertilized with more than one sperm). My eggs divided, but they were slow. (On day three, I had one 5-cell, 2 4-cells and 2- 3cells). Nevertheless, two of my embies made it to blast and one to "almost" blast on day 6. All three were transferred but apparently none implanted because I did not achieve a positive beta. Based on what I read here, these three did not experience arrested development but were one day slow.
Do you think this means I also have an egg cytoplasm issue, even though some of my embryos made it to blast? I don't know about fragmentation since my clinic did not describe this to me. I do know at least one of my blasts was considered excellent quality.
Thank you.
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Dr Smith
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Re:good eggs but slow embryos?
« Reply #9 on: 12/02/05, 11:24 » |
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A significant number of embryos that make it to the blastocyst stage do so on Day 6. Although these embryos are "slow" they retain good developmental potential. I don't think there were any cytoplasmic maturity problems with those eggs. However, a polyspermy (more than one sperm inside the egg) rate of 50% is unusual and suggests that the 5 eggs that were polyspermic may have been of borderline cytoplasmic maturity at the time of retrieval. The expected polyspermy rate is about 3-5%. I suggest you speak with your doctor about the high polyspermy rate.
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Scott
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Re:good eggs but slow embryos?
« Reply #10 on: 12/15/05, 20:23 » |
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I apologize for latching on to this thread, but our situation has some similarities.
We are baffled and our RE is as well, though he has not yet had time to review everything. I'm hoping you have some thoughts or ideas. Here is the summary:
First pregnancy: conceived first month of trying, healthy boy.
Second pregnancy: conceived second month of trying, 20 week ultrsound shows borderline thickened nuchal fold, amnio shows no genetic abnormalities, stillbirth at 32 weeks (unexplained cause)
Decide on IVF due to severe hyperemesis. Use egg donor due to wife's medical history.
First IVF: Proven egg donor, proven surrogate, eight embryos progress to blastocyst. Fresh transfer 2 (failed). Thaw remaining six (do not look good following thaw). Transfer all (failed)
Start new cycle with new egg donor and new proven surrogate. Eleven embryos retrieved, all fertilized. On day 5, no expanded blastocysts. Two early blasts plus one morula transferred (failed). Only two moderately expanded blasts were viable on day six for freezing.
In both cycles, the embryos developed slowly and we did not have any expanded blastocysts on day 5 to transfer. The same donor from the second cycle did another cycle with someone else shortly after and had numerous fully expanded blasts on day 5.
The common factor is my sperm, although I have had chromosome analysis including karyotyping and everything is normal. In addition, we have not had any trouble getting pregnant naturally.
Help!! We are baffled. Is there something else about my sperm that would cause embryos to develop slowly in culture, but would not show up in chromosomal testing?
Any thoughts or ideas at all??!!
We appreciate your help.
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Dr Smith
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Re:good eggs but slow embryos?
« Reply #11 on: 12/19/05, 09:00 » |
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I need a bit more information. Could you please post the most recent semen analysis results (including morphology) and tell me whether or nor ICSI was performed in either or both IVF cycles.
DNA fragmentation in the sperm can cause fewer embryos to reach the blastocyst stage and also cause the embryos that do reach the blastocyst stage to be of poorer quality. Even though your karyotype was normal, there may be a sperm DNA fragmentation issue. There is a test for sperm DNA fragmentation. To read up on this, see www.scsadiagnostics.com.
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Hopeful in VA
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Re:good eggs but slow embryos?
« Reply #12 on: 12/28/05, 09:49 » |
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First of all, a big thank you to all of you who took the time to post on this subject. I am encountering the same issue right now with mature eggs and slow growing embryos. I would like to hear if in my case it would be worthwhile to pursue genetic testing (karyotyping) on both my husband and myself or if we are possibly having a cytoplasm issue.
History: 34 years of age, one ectopic (age 21) and left tube removed, one miscarriage (age 30). We have been "trying" for approximately 4 years.
First IVF (August 2005), approximately 13 day stim cycle on Follistim, Menopur, Lupron and baby aspirin. Retrieved 21 eggs, 19 mature, 16 fertilized normally. By day 3, arrested development was seen. RE chose to do a day 6 transfer of 2 embryos, neither of which was yet at the blast stage. No embryos developed to the blast stage, none were frozen. Negative HCG.
Second IVF (October 2005), approximately 13 day stim cycle on Metformin, Follistim (lower dose), Menopur, Lupron, and baby aspirin. Retrieved 12 eggs, 9 mature and 9 fertilized. By day 2, embryos were around 4 cells, some were 2 cells. Day 3 (day of transfer), there was one 4 cell and two 5 cell embryos to transfer. After day 3, development arrested, no embryos made it to blast, no embryos to freeze.
Met with the RE yesterday for our follow-up appointment and he discussed a number of tests to do, but he thinks that overall the cycle was fine. He recommended switching the Lupron for Antagon and perhaps drawing blood work for karyotyping.
We are not sure as to how to proceed. The RE thought that the length of stims was fine and that ideally a patient should have a stim cycle of between 8 and 15 days. Are we having a cytoplasm issue or could genetics be playing a role?
Thank you in advance for your help.
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Dr Smith
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Re:good eggs but slow embryos?
« Reply #13 on: 01/02/06, 16:55 » |
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I'd say the problem is genetic, but karyotyping may not reveal the source of the problem. Based on the information you provided, the problem appears to be with the genetics of the embryos, not necessarily the parents (i.e. you and your husband). Genetically abnormal embryos most often arrest on the 3rd day of development (just what you observed). If the karyotype of you and your husband is normal, another approach would be to perform pre-implantation genetic diagnosis (PGD) on the embryos of a subsequent IVF cycle. This will directly address the question. However, PGD may only serve to confirm what I already suspect - the embryos are abnormal. If that turns out to be the case, and the karyotypes of you and you husband are normal, it would leave you in a postion of using donor sperm and donor eggs as your most likely way to conceive.
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sheree
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Re:good eggs but slow embryos?
« Reply #14 on: 01/21/06, 03:06 » |
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Hi
Very interesting info! Thanks
My question is..we just did a day 4 transfer, because on day three, our one embryo was only at 4 cell..no fragmentation, but my doc likes to transfer 7-9 cells only..I insisted that my chances were zero, if we did nothing..so they transferred an embryo that looks like a morula today. It was still growing..had not arrested, but I was unclear as to whether I was seeing a morula, or a ton of frag. The shape was like the "rasberry" I have seen associated with day 4 embryo's, but there was some dark matter...If it was still growing at day four, is this a good sign?
Thanks
Sheree
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