embryo development/transfer ???
12 Replies
teacher-ttc - November 13

Hello Drs.

Thank you in advance for taking time to respond to the questions that are posted on your website. It is such a valuable and priceless tool!

1) I often see that embryo development is discussed in hours past fertilization. (i.e. 48, 96, etc) We began our ER at 11:30, and my husband provided his sample after the ER. Therefore the earliest the eggs/sperm would have been fertilized is after 1:30. If the embryologists look at our embryos in the morning, like 7:30 am, wouldn't our embryos be slightly behind in their development? (about six hours????)

2) Our first IVF cycle we had 3 - 12 cell embryos transferred on day five. We did achieve a chemical pregnancy. This IVF we had 2 transferred on day five....one cavitating morula and one morula. I am trying to remain hopeful and optimistic that we could achieve a successful pregnancy with these embryos.....

3) We are both 30 years old and the only thing that has ever been mentioned is I sometimes present a bit PCOS like----yet ovulate on my own regularly, insulin/glucose levels very good, etc. My fsh and lh levels tend to be reversed, but within the "normal" range.

Thank you for your time
Teacher-ttc

 

Dr Smith - November 16

It is pretty standard for IVF labs to collect eggs in the morning and inseminate in early afternoon, so, compared to others, your embryos wre not behind per se. What levels the playing field and allows us to compare apples with apples is time post insemination (when the clock starts running for embryo development). Embryos are assessed for fertilization 17-19 hours post insemination (zygote stage on the morning of Day 1) and undergo a division about every 20-22 hours postinsemination that. For example, 2 cell afternoon of Day 1, 4-8 cell afternoon of Day 2. 6-8 cell morning of Day 3, 12 cell to morula (morula=16 cell) afternoon Day 4, cavitating morula to expanded blastocyst moring of Day 5.

12 cell on Day 5 is significantly behind schedule and the resulting "chemical" pregnancy was not altogether unexpected. This time around, your embryos are within the normal expected variation in development on Day 5. Cautious optimism is in order.

Best of luck.

 

teacher-ttc - November 21

Thank you for your reply. The doctor called this afternoon with our beta results, and it seems to be an exact repeat of our first IVF attempt. Our hcg level is 10---very low for 9dp5dt. Our two embryos were the morula/cavitating morula stage, but embryo quality was rated a 3 (on a scale of 1-3). We have mixed emotions...my body is obviously getting pregnant, we just aren't capable of producing quality embryos to put back. I know there is still a (small) chance this could result in a viable pregnancy, but I am also realistic.

What would you suggest if we decide to do another IVF?
Would you consider another clinic's opinion? Do you ever offer recommendations for other area's of the U.S. (Minnesota)???

Both times we've had good stimulation (using Follistim/Menopur), retrieval (15 eggs/17 eggs), and fertilization (13 eggs/12 eggs)...our problems occur in the growing stages.....and we just don't know what to do or what to ask for.

Thanks again for your time on these boards.

 

Dr Smith - November 22

Sorry for the typos in my previous post. Sometimes my brain works faster than my fingers. Actually, most of the time...

The slow/somewhat slow embryo development in last two cycles may have been a result of sperm DNA fragmentation. You didn't mention any problem with the sperm in your previous post, but there may be a more "cryptic" problem with the sperm. One which is not readily apparent by just looking them under a microscope. If you get a chance, review the embryology records. If embryo development is normal up to day 3 (i.e. the embryos are at the 6-8 cell stage on Day 3), but they slow down after that, this is indicative of a problem with the sperm DNA. There sperm DNA does not become active until Day 3, so that's when Sperm DNA problems show. If its true that the embryos slow down after Day 3, I would suggest a Sperm Chromatin Structure Assay to determine if there is a problem with sperm DNA. See http://www.scsadiagnostics.com/MoreInf
ormation/FAQ.cfm

Alternatively,
the explanation for the repeated "chemical" pregnancies my lay in the endometrium, or, more specifically, in an overzealous immune system. It may be that the embryos are prevented from continued development/implantation because they are recognized as "foreign" by the Natural Killer Cells (a subset of white blood cells). I would also recommend immune testing, just to rule that out as a contributing factor. For more information, see http://www.millenova.com/tests/nkassay.asp

 

BekyVice - November 27

Hello! I've very interested by the fact that the male genomes don't even come into play until day three, which possibly explains (or was a factor in) our 15 good eggs that all fertilized nicely and went to day 3 in good shape, but hit the wall on day 4 and we had only one grade A blast to transfer on day 5, along with 2 grade A embryos, and nothing to freeze.

My question is: is there a chance that any egg could have made it to a Grade A blast if the problem was indeed male DNA factor? Right now we have a sluggishly-growing (in my opinion) "thing" (don't know what you call them 21 days post 5d transfer), with beta levels crawling upward (day 11 post 5dt beta = 41, day 15 =150, day 21 = today, no answer yet.)

We are proceeding with "cautious optimism" but knowing this one could end in a miscarriage at any minute... and I want to gear up for DNA testing if something goes wrong... but it's going to take some DH-convincing, since he thinks that if this one made it this far, there is no DNA problem.

[Footnote: DH took steroids for 5 years (bodybuilder) 15 years ago, and had terribly low levels of morph, motility, and count at the last check, thus we went ICSI.]

Thanks again for any brilliance you can shed, as always.

 

Dr Smith - November 28

Yes, embryos can make it to the blastocyst stage and still be genetically abnormal. The first weeding out occurs on Day 3 (but observed on Day 4 when they do not continue development). However, some anueploidies and subtle genetic problems do slip through. This is one of the reasons for first trimester miscarriages, which are fairly common even among the "fertile" population. So, no, you are not out of the woods yet. The slow rise on hCG is definately not a good sign. Early miscarriage (including chemical pregnancies) can be caused by genetic abnormalities in the embryo or, less commonly, problems with the endometrium. So its not always a genetic problem. In your case, it sounds like it is. It may or may not be caused by the sperm. Depending on your age, it could have been caused by genetic abnormalities in the eggs too, so don't rule that out either.

To the best of my knowledge, anabolic steroids do not affect the genetics of the sperm directly. But, when there are very few sperm to choose from for ICSI, the embryologist may have to use abnormally shaped sperm (which have a higher chance of being genetically abnormal) for ICSI.

 

BekyVice - November 28

Okay. Good to know. Thank you!

Got our HcG results: on day 21 post 5-day transfer, my levels were 1,680. Thus, to recap:
Day 11 post 5dt = 41
Day 15 =150
Day 21 = 1680

Is this still a "slow rise" in your opinion, and "not a good sign"? (Nurses won't give any hints either way... so I have to assume the worst.)

From what all I can research, the HcG levels can be all over the place and can vary by the thousands! Why such a variance? Do the higher levels signifify a stronger/healthier/smarter/bigger baby should both low levels and high levels go to term?

 

Dr Smith - November 28

Well, it seems to be going up O.K. now. It has caught up to where it should be and appears to be doubling appropriately. Cautious optimism is still in order. At this point, the upcoming U/S will be more telling than the rise in hCG.

You are correct that hCGs are all over the place and I don't place much stock in the number itself. As long as it doubles (or so) every 2 days in the first couple of weeks, it looks O.K. The nurses are taking the high road - as so they should. It really is too early to tell what's going on.

hCG levels are not directly related to stronger/healthier/smarter/bigger baby. To some degree, in the early stages of pregnancy, they are predictive of whether of not the pregnancy will continue (i.e. the doubling rule of thumb). But there are lots of excceptions.

Best of luck.

 

HopeAndPray - November 28

I had a blastocyst transfer on Nov 6 with 2 transfered. My HCG levels are rising slowly. However, last HCG rose appropriately.
11/16 - HCG 166
11/20 - HCG 318
11/22 - HCG 339
11/24 - HCG 486
11/27 - HCG 1562

On 11/27, gestational sac at 5w2d in uterus and progesterone 40. Stopped progesterone shots on 11/22 since my doc told me I'd either have a mis or ectopic. But still good progesterone... Could this be a late starter? Since I'm 5w5d in my cycle. My 1st IVF cycle. Male factor infertility. I'm 29, husband 27.

 

Dr Smith - November 29

Your question is more of a clinical nature and I'm not really qualified to answer. I will forward your post to Dr. Jane Miller, the RE I work with. She will post a reply and hopefully give you some insight as to what may have happened.

 

Dr Jane - November 30

I'm sorry about the cycle outcome - I know how frustrating it can be living from blood test to blood test. I do, however, agree with your doctor . Stopping the meds was appropriate. It is not uncommon for a person's progesterone level to be "teasingly" sky-high when she is on progesterone shots - even if the pregnancy is not progressing normally.As far as the pregnancy being a "late starter" - be wary of this. Occasionally we see a first BHCG level lower than we'd like 2 wks post ET (ie - we are happy with a level around 120 or above). The subsequent level a few days later is much higher - even more than a doubling in 2 days - and then the pregnancy "takes off". We postulate that that may have been a result of a later i mplantation. However levels that lag or just barely make the requisite 66% increase every 2 days in the first 7 weeks and then leap are rarely normal. In these cases we often see a gestational sac with an abnormal yolk sac or a heartbeat that is too low. These pregnancies usually "take care of thamselves" and just stop growing. By 5wks 5 days one should see a gestational sac, a yolk sac and usually a heartbeat as well.I'm sorry for the failed cycle. Your doctor is right in saying that it could be an ectopic (which he/she would treat you medically for) or just nature's way of stopping the progress of a pregnancy that was not genetically normal.

 

HopeAndPray - November 30

Thanks for your response. I went in today for another ultrasound and HCG test. The gestational sac is size 5w3d. Has an yolk sac but no fetal pole. I am at 6w1d in my cycle. My HCG is 3800 today. My HCG is finally rising normally (double every 48-72 hrs is good, right?). I'm still hanging onto that little bit of hope. My DR said I have a 1% chance of having a viable pregnancy. This waiting is hard! I never thought I'd miscarry.

11/16 - HCG 166
11/20 - HCG 318
11/22 - HCG 339
11/24 - HCG 486
11/27 - HCG 1562
11/30 - HCG 3800

 

JoyYara - June 26

Dr. Smith, please I would appreciate your opinion for my case:

My husband is 35 years old and I’m 33. All of the ultrasounds, blood work hormones, basil ultrasound, FSH, seaman sperm analysis, sperm chromatin structure assay, DNA fragmentation, chromosome tests all were good and normal at the three different clinics. We’ve been trying to conceive one healthy baby since 2007.

Dec 2011 – first failed IVF/ICSI – at 1st clinic retrieved 8 eggs 6 got fertilized. Transfer back one on day five early morula, BFN. From day 1 to day 3 embryos were good. From Day 3 five embryos started to slow in development till all got arrest on Day 5. Doctor suggest its chromosome problem but wasn’t sure from which side sperm or the egg.

March 2013 – second failed IVF/ICSI – at 2nd clinic retrieved 6 eggs and 5 got fertilized. Transfer back two morula and early blastocyst on day five, BFN. Medication used Gonal F, Luveris, HCG shot. For unknown reason embryos are at excellent shape from day 1 to day 3. Beyond day 3 embryos are starting to slow down in their development and got arrest in day 5 day 6. Doctor suggested it’s an egg quality issue. Doctor also mentioned that we do better with IVF than with ICSI. He also said that we might want to try different ways of treatments; we may use different drugs, try IUI treatment or a natural IVF, but he isn’t guarantee of the results.

April 2013 – we tried on our own right after our second failed IVF. Got pregnant and miscarriage in about 6-8 weeks of the pregnancy May 31/2013. Doctor said it got to due with embryo abnormality chromosomes.

March 2013 – Third failed IVF – at 3rd clinic retrieved 21 eggs and 9 got fertilized. Transfer back two morula on day five, BFN. Medication used Gonal F. Repronex Lupron, HCG shot. For unknown reason embryos are at excellent shape from day 1 to day 3. Beyond day 3 embryos are starting to slow down in their development and got arrest in day 5, day 6. Doctor doesn’t really know the reason as it could be a sperm issue or an egg issue. As he noted that the sperm dna does something on day 3,4,5 of the embryo development. He suggested egg donor with my husband sperm and the same egg donor with sperm donor.

What do you Dr. Smith suggest?

 

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