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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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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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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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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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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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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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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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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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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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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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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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hi, I am so confused about the cell division speed.

I have just had 1st attempt of IVf; 5 follicles, 4 eggs, 4 fertilised. Now day 2, 1 is not so good (6 celled with about 35% fragmentation), but 3 are grade A 1 or A 2 (ie very minor (about 5%) fragmentation).

My question is:- at 48 hours were still 2 cell. is this about average?

We have opted for a day 3 transfer, possibly with assisted hatching because of my age (41) rather than jepordise them by waiting until blastocyst stage.


I am hoping for a success (like everyone else), and have previous children. My endometrium was 14mm before retrieval, and E2 was 4530 p mol.
Is my embryo division too slow; the embryologist said it was right for day 2...



thanks

jacqueline

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At 48 hours post insemination, the embryos should be between 2 and 4 cells. Your embryos are on schedule.

The IVF process is a series of hurdles. I think sometimes patients are in a big hurry to get over the "transfer" hurdle and perfer to have the transfer on Day 3, just to make sure they get a transfer. This doesn't make a lot of sense to me. Your age affects the chances of embryos making it to the blastocyst stage, but leaving them in the lab until Day 5 does not "jepardize" their growth. If they are developmentally competent, they will continue to develop whether they are in the uterus or the lab.

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I did my first IVF this month and everything seemed great, 12/13 eggs fertilized and on day 2 I had 6 2-cell, 2 3-cell and 1 4-cell. Then on day 3, when I came in for the transfer I had only 1 6-cell, 3 5-cell and 1-4 cell with fragments and the others weren't developing or developing too slowly. My RE decided to transfer all 5. He said they were "good" quality, except for the fragmentmented one, but wanted to transfer all 5. Do you think I have a chance of pregnancy or am I another possible case of PGD. I have had one m/c at 9 weeks from IUI and I am 34 years old. Dh has above average sperm and is 33.

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Whenever embryos are transferred there is a chance of pregnancy. However, as you are aware, the embryos were diving slowly and had not developed to the 8-cell stage that is appropriate for Day 3. The usual cause for this kind of slow or arrested development is aneuploidy (the embryo has an abnormal number of chomosomes).

Yes, in theory, you are a candidate for PGD. However, it is prefered to perform the PGD biopsy on 6-8 cell Day 3 embryos to avoid removing too much of the embryo's cellular volume. Although a 3- or 4-cell Day 3 embryo can be biopsied, it may compromise their later development. I would suggest an alternative. If the current cycle is unsuccessful, try culturing the embryos to the blastocyst stage. Although there is no guarantee that the embryos that reach the blastocyst stage are genetically normal, the vast majority of genetically abnormal embryos fail to reach the blastocyst stage. If no embryos reach the blastocyst stage, you have the same answer you would have got with PGD - all the embryos were abnormal. If, however, some of the embryos reach the blastocyst stage, you can be confident that at least they have the capability to attach and implant (which you don't know at this point about the embryos from your recent transfer).

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Thank you so much for your informative reply, Dr. Smith. I guess only time will tell. I won't get my hopes up too much at this point. I'll let you know the outcome in a couple of weeks.

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Dr. Smith,
You replied to a question I posted earlier, and I really appreciated your response.
Yesterday I had the retrieval of my 4th IVF. My RE, it seems, finally found the right protocol for me, and I stimmed very well on Menopure and Cetrotide. From our experience, my eggs need time to mature and are found to be best in the larger follicles. So I stimmed for 14 days with the largest follicles reaching 28-30mm. Of a total of 24 follicles, 14 eggs were retrieved - my best yield yet. 7 were mature and looked very good. They were all ICSId (there's no sperm problem, but after 3 previous failed attempts our RE decided to take all measures).
Today (day 1) our RE called and said none of the eggs fertilized. He was in shock. They're still following them to see if maybe there was late fertilization, but I know the chances for that are close to zero. Our clinic and RE are very reputable. It seems like everything went so well this cycle. Do you have any thoughts on what could be the problem and whether it can be dealt with?
(I'm 34, day 3 FSH 4.7, LH 2.2, E2<30)

thanks, allison

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Fragmentation usually shows up early, in the first couple of days. The fact that the embryo reached the 4-cell stage without exhibiting framentation indicates that what you saw on Day 4 were true cells, not fragments. The cells get pretty smal by the time the embryo reaches the morula stage and can be confused with fragments if you don't know how much fragmentation was present at the earlier developmental stages (confusing even for embryologists). I would be more confident if the embryo had initiated the compaction process prior to transfer, but as such, a morula on Day 4 is considered developmentally "on time".

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Allison:

Every once in a while we get thrown a curve ball. I do not have a good explanation for what specifically went wrong. When ICSI fails to activate the eggs (assuming the ICSI was performed properly by an experienced embryologist), the problem lies with the cytoplasm of the eggs. This can usually be explained by inadequate cytoplasmic maturation caused by not waiting until the follicles are large enough or cutting the stimulation too short. Neither of these conditions apply to your cycle. So, I'm sorry to say, I'm left scratching my head too. Curve ball.

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Thanks for the answer. We consulted another RE who seems confidant that the stimulation was way too long and that the eggs must have been post-mature. He doesn't think that it is right that my follicles need to be so big for the eggs to maure. Do you think this could be the case? Would this type of result -- no fertilization at all (7 eggs) with ICSI be consistent with eggs that are post-mature?

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Yes to both questions, but hindsight is 20/20. Failed fertilization due to post-maturity usually occurs with conventional IVF insemination, not with ICSI. That's why I didn't menion it in my previous post, but it is possible.

Also, be aware that whenever you go for a second opinion, the new doc will find fault with the old doc. These guys are highly competitive amongst themselves and sometimes patients get caught in the crossfire. You mentioned that you did better on previous cycles when the follicles were left to grow a little bigger. O.K., so maybe this time the doc went a little too far to try to maximize the number of good, mature eggs, but a shorter stimulation is worse than a longer one. Beware of docs that promote themselves by criticizing others. There's no absolute right or absolute wrong way to do this. Ovarian stimulation is not an exact sceince.

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I have just finished my 5th round of IVF however this time they also included PGS (Pre Genetic Screening). I am 34 years of age however due to operations have blocked tubes. My issue has always been the growth rate of the embryos they only ever seem to become 4 cell on day 3. This time round they carried out a biopsy on 4 embryos on day 3 however they were only 4 cells. So by removing one cell from each embryo they could check the chromosomes (genetic make up). On day 4 they result came back as normal however they had only gone on to the 6 cell stage 2 have been put back & I now have the dreaded 2 week wait....Can anybody offer any advice or even maybe some encouragement I don't know If i can go through it again.

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Dr. Doom-n-Gloom here. I know you are looking for encouragement, but I play the part of a realist on this board. If you're emotionally up to it, let me know. I'll give you the objective, scientific point of view. If you're not emotionally up to it, that's O.K. too. Waiting for the pregnancy test can be the worst part of the whole process. I understand. I don't want to contribute to your woes by giving you cold facts when you need warm feelings. Best of luck.

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Dr. Smith,
I posted previously and wanted to let you know that as expected my first IVF was unsuccessful (I had plently of fertilized eggs, but none that made it to 8 cells by day 3). I met with my RE and he wants my husband to do a thorough sperm analysis (FISH) w/genetic testing (personally I think it's a waste) and for me to try another IVF with PCG and a 3dt. I suggested your recommendation to do a 5dt and he thought since I've had a previous miscarriage, a PGD with a 3dt (if applicable) would be a better route to take. I've heard PGD can be expensive and am wondering if I should strongly request a 5dt and take my chances that they will make it to 5 days. What do you think? Do you have any idea as to why my eggs would stop developing after everything else went so well? I know they were genetically abnormal, but do you think another IVF with my own eggs is a waste of time and $? Or is there a chance that I just had a bad batch and next time the result could be better?

I am just at a loss here and would greatly appreciate your honest opinion. Thanks, Sam

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A paternal DNA problem doesn't really explain what you observed, since abnormal paternal DNA usually causes arrested embryo development later on (i.e. Day 4-5, or later during the first trimester of pregnancy). So I agree with you that a comprehensive genetic analysis of the sperm may not be worthwhile. Of course, it can't hurt either (except your wallet).

If PGD is performed on Day 3 (as it usually is), then the embryos would not be transferred until Day 4 at the earliest because it takes 24 hours to get the PGD results back from the genetics lab. What would be the harm in waiting one more day to be sure they reach the blastocyst stage? Hmmm, your doctor's recommendation doesn't quite make sense. The miscarriage has nothing to do with the choice to go to Day 5 or not. Obviously the embryo that resulted in the miscarriage made it past Day 5. And a single miscarriage is not a justification for PGD. Recurrent miscarriage is a justification, but that means 3 or more successive miscarriages. That's not your situation. PGD is expensive and will add approximately $3K to the final price. I think your doc is grasping at straws trying to explain the failure (which may very well fall within the "sh** happens" category) and trying to give you something different to look forward to on the next cycle. Personally, I'm not so gung-ho about the PGD at this point.

I think you should try again. Every batch of eggs is genetically different and there may be a good one in the next batch. Did your doc suggest a change in your stimulation protocol? That could have been a problem too and could explain (to some degree) the high embryonic arrest you observed. If the cytoplasm of the eggs had not had an adequate amount of time to mature (short stimulation, small follicles), it can cause arrested development (although your situation is a bit extreme for that explanation).

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Dr. Smith, thank you so much for your thorough reply. I honestly don’t think there is a problem with the sperm, but his reasoning was that since they can’t genetically test the eggs (other than from the PGD), it would show where the genetic abnormality came from by ommission or confirmation and it’s a pretty easy test to do, so why not, but my feeling is why if it’s not necessary.

I don’t know what the harm in waiting one more day for the 5 day transfer would be either, but he seemed to think if we waited until day 5, we wouldn’t have anything to transfer (not very encouraging). I think he mentioned the miscarriage because he was proving his point that although the embryo made it past the blastcyst stage, obviously there was something genetically wrong with it and if he did the PGD he’d know what was worth and not worth transfering. I guess.

My RE doesn’t want to change the protocol because he said he was pleased by how I responded to the meds, but obviously it didn’t work, so I was hoping to try something different. I had my retrieval on CD14, which seemed a little early. I really like your recommendations and am now wondering if I should see someone else or at least see if he’s open to longer stimulation and 5 day transfer. Is my situation common, where you get a lot of fertilized eggs that don’t make it to 8 cells on day 3? Do you think it would be a good idea to meet with another RE? I am Newport Beach, CA so I am lucky to have a lot to choose from nearby. I apologize for so many questions, but greatly appreciate your feedback.

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PGD is a very superficial genetic analysis. Of the 23 pairs of chromosomes, PGD can evalauate a maximum of 9 to determine if there's one extra or one short. That leaves 14 other chromosome pairs that could make trouble. In addition, the number of chromosomes in a embryo is only the tip of the iceberg from a genetic point of view. Subtle genetic defects (like single gene mutations) can lead to miscarriage and these cannot be identified with PGD at present. I think that PGD is being over-pitched by the ART community. It has become the "next big thing" in assisted reproductive technology, but in actuality, it is a very crude tool to determine the genetic normalicy of an embryo. Although PGD can reduce the chance of miscarriage in women with recurrent miscarriage, PGD does not prevent miscarriages altogether (not by a long shot). Beware the PGD sales pitch.

I think a second opinion is a good idea. Have another RE review your records and see what they have to say about the stimulation protocol, the necessity of the sperm testing, the PGD option, Day 5 transfer, etc.

Lucky you in Newport Beach. We're getting 6-8 inches of snow in NYC tomorrow. Catch some rays for me California Girl.

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Thanks again Dr. Smith, I think I will get a second opinion. It definitely can't hurt. WOW -- 6-8 inches of snow! I won't even say what the weather is like here, but I'd actually rather be in NYC, I love it there! Take care.

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Perhaps you could evaluate this situation for me...

I had a 5 day transfer of one blastocyst the other day. On day 3 it was a perfect 16 cell morula that my RE classified as "best quality", which I assume means, even cell division. and little fragmentation. By day 5 the blastocyst was only 40 cells... Is the fact that the growth slowed down a bad sign?

Thanks for any comments...

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Dr Smith,

I had 3 failed IVF cycles. Unexplained Infertility. Never had a BFP. Husband's sperm is ok. Both DH and I had genetic testing.
1st Cycle @ reputable University - Gonal-F, Lupron, 17 retreived but the ones that fertilised stopped dividing at 2-4 cells, poor quality. They transfer 4 anyway on day 3. After I got the bad news, I made some lifestyle changes in terms of diet, exercies, herbs, and reducnig stress.
2nd Cycle - Gonal-F, Lupron, 21 retreived, ICSI 10 and Inseminated 10. Only 2 fertised with ICSI and 8 fertilised naturally. They said they picked the best eggs for ICSI. Embryo quality was more than 5 times better than the 1st, 6-8 cells. The embryologist was afraid to transfer more than 3 in case of multiple pregnancy. None good enough to freeze. Day 3 transfer. After negative result, I made real strict lifestyle changes. Also my hormal levels mimmicked that of a PCOS patient ONCE. So they wanted me to take Metformin. I decided to try it (one month) and when I went to a new clinic, the dr. told me to stop. I have no evidence of PCOS, just once my levels looked off.
3rd Cycle @ a new clinic - Follistim, Antagon, 24 retreived, 18 mature, 14 fertilised. By day 3, 9 fertilised correctly and were doing well, grades 1 and 2. Day 5 transfer they starting slowing down, none were blastocysts. 4 were compacted moruelas and one 8 cells by day 5. No pregnancy. February 06. .
I paid for 4 cycles up front and will get my money back if I dont acheive pregnancy/delivery. This was my first cycle at this clinic. He's one of the top doctors in the city. He doesnt thinlk I have a genetic issue. I dont know if he did Assisted Hatching. My question is, what do you make of my situation? Do you think AH would be beneficial for a day 5 transfer? Do you think diet, exercise, herbs, stress can have help make this kind of improvement? Is it weird that less eggs fertised with ICSI than without, especially since they picked the best quality eggs for ICSI?

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The major difference between cycles 1-2 and the third one is the absence of Lupron. Apparently, you respond better without Lupron. Some folks do and it looks like you're one of them. You new doctor gavit a try without Lupron and you had a better (more physiological) stimulation that resulted in better embryo development. Embryos at the compacted morula stage on Day 5 are within the expected range. When we observe this in our program, we wait until the morning of Day 6 to be sure they have reached the blastocyst stage before transferring them. They usually do, so no harm was done by transferring them on Day 5 at the compacted morula stage. However, the 8-cell had arrested, so there was no point to transferring that embryo.

It has been my experience (and that of others) that assisted hatching of blastocyst stage embryos immediately prior to transfer improves implantation rate.

The developmental potential of eggs cannot be assessed by just looking at the them. Hence, chosing the "best" eggs by their appearance is misleading. Your ICSI results make my point. The developmental potential of eggs lies in their genetic normalicy which cannot be determine by looking at them at the time of ICSI or insemination.

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