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If the embryos that were transferred on Day 5 were at the morula compacted morula stage ( the stage immediately preceeding the blastocyst stage), there is a chance, as these embryos will likely develop to the blastocyst stage by Day 6. If the transferred embryos were at an earlier stage than compacted morula, then the chances of a pregnancy are slim to none.

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So if the embryos did not get to the preblastocyst stage does this mean that there is an issue with the cytoplasm of the embryos? If so, what options are available to treat slow growing embryos?

Thanks

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There's two main reasons why embryos fail to develop to the pre-blastocyst stage (compacted morula). If there are problems with the cytoplasm of the egg (i.e. immature or defective), the resulting embryo will stop growing prior to reaching the 8-cell stage, usually accompanied by slow division cycles and excessive fragmentation. The second reason for embryo arrest prior to reaching the pre-blastocyst stage is the genetics of the developing embryo. If the embryo has an abnormal number of chromosomes (aneuploidy), the embryo usually arrests development prior to or at the 8-cell stage (with or without fragmentation). If the genetic abnormality is more subtle, the arrested development can occur at the 16 cell stage when the embryo fails to undergo compaction.

There is no treatment for defective cytoplasm or genetic abnormalities. Cytoplasmic immaturity can be addressed by modifying the ovarian stimulation protocol to allow for additional follicular growth.

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Thanks for the information Dr. Smith. My bestfriend and I are going through IVF together and she has had this issue in both of her IVF cycles. Her RE tells her that people have gotten pregnant with the same type of development as she has experienced. I don't think that he is being very honest about how he feels about her embryo growth and her chances for pregnancy given the quality of her eggs. Your information will definitely help us to figure things out.

-Hopeful dc

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I had an embryo transfer this week. My dr. transfered a 3 cell embryo on the third day, with little fragmentation and said it may have a chance if it was transfered. But he cautioned me to chromonal problems inwhich it would miscarriage. Is it a normal procedure to transfer this embryo or would most doctors not bother. Is there a potential for a normal live birth and if not why did he recommend this.

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I guess I am expecting the worst. I am 42 and 2 months. I had 6 follicles and 4 eggs. one egg fertilized and was the 3 cell embryo on day 3. Do I have a chance of using myown egg or is it too late for me. I did not know of any nutitional supplements or accupuncture during this cycle. Is there hope for me?

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At 42, its just a numbers game. There's probably a few "good" eggs in there, but it may take several attempts to get one. It boils down to how many disappointments are your willing to endure attempting to get the "good" egg.

I think some REs would not have transferred a 3-cell embryo on Day 3; some would. As an embryologist, I would not have recommended it. To be honest, I don't hold out much hope because the embryo was two division cycles behind where it should have been on Day 3 (8-cell). I think, in all likelihood, the embryo had stopped dividing before they transferred it. Sorry to be Dr. Doom and Gloom, but I guess you wanted a straight answer.

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Is there a difference between a morula and a compacted morula? I'm in this exact situation right now. I had a 5 day transfer of 3 morulas on Saturday. My Reproductive endocrinologist told me that I had a slim to no chance of them implanting. I have pictures of them, but can't count the cells in the pictures.

Also, have you heard the statistic that 5 day transfers are more likely to be boys because boy embryos develop more quickly from day 2 to 5? I read on another site that 71% of 5 day transfers are boys because since the fastest, furthest along embryos get picked for transfer, by elimination, the slower girl embryos don't get put back. Could it be that my 3 morulas are just slower girl embryos?

jw

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Compaction is a necessary process in embryo development. During compaction, the cells of the embryo adhere very tighly together and the surface of the embryo takes on a "smooth" appearance (as opposed to a "lumpy" appearance when individual cells are recognizable). If the embryos had reached the morula stage, but failed to undergo compaction by Day 5, I agree with your doc that the chances were slim to none. It would appear that the embryos arrested development on Day 3-4. I don't think they were just slowly developing girl embryos.

Most studies examining the possibility of an altered sex ratio following blastocyst transfer have a limited number of patients in the study and therefore, their conclusions are suspect. However, I did come across one study that combined their own data with that of others and came to the conclusion that the M/F ratio was altered slightly (not 71%) by blastocyst transfer. See below:

Comparison of the sex ratio with blastocyst transfer and cleavage stage transfer.

Milki AA, Jun SH, Hinckley MD, Westphal LW, Giudice LC, Behr B.

PURPOSE: To evaluate the sex ratio in births conceived with blastocyst transfer compared to day 3-ET. METHODS: A retrospective analysis of IVF patients who became pregnant after blastocyst or cleavage stage transfer at Stanford University Hospital and a literature review were performed. RESULT(S): In the day 3-ET group, the male-to-female (M/F) ratio was 157/139 (53%/47%) compared to 97/66 (59.5%/40.5%) in the blastocyst group (P = 0.18). Similar trends have been found in individual studies in the literature but reached statistical significance in only one out of six reports reviewed. The combined data from our study and the literature show a male-to-female ratio of 797/594 (57.3%/42.7%) in blastocyst transfer compared to 977/932 (51.2%/48.8%) in day 3-ET (P = 0.001). CONCLUSION(S): Although individual studies may lack power to show an altered sex ratio with blastocyst transfer, the combined data presented in this report do suggest that the M/F ratio is higher with blastocyst transfer compared to cleavage stage transfer.

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Thanks Dr. Smith. Your information is so helpful. I hope you know what a God send you are to those of us who are desperate for candid, accurate information on this process.

My IVF attempt, as suspected, was a failure. We got a negative beta yesterday. But after reading extensively online, I'm starting to question something my clinic did and its really bothering me. I would appreciate your objective insight.

My husband has very low/slow sperm. So, we did three IUI's with doner sperm last spring. They were unsuccessful, so we did a laperoscopy, which basically turned up nothing, other than a tube that was blocked, but they are not sure why (no endometriosis or other visible reasons)

So, we moved on to IVF. When we had our pre-cycle visit with the RE, he said that ICSI would "level the playing field" (his terms, not mine) for my husband, because they could hand select good sperm from him. My husband was concerned about using his sperm, and we specifically brought up that concern. The RE reassured us that ICSI would be a good alternative for us, and that we would have back-up doner sperm at egg retrieval, just in case. We made it clear that we are comfortable using a doner, as shown by our three IUI cycles.

At egg retrieval, the embryologist told us that he would be able to use my husband's sperm, and we were delighted, because based on his last test, we didn't expect to be able to. 5 of my 7 mature eggs fertilized. 3 progressed onto 7 & 8 cells by day three.

On day of transfer, (we did a day 5) our RE informed us that our embryos were alive, but had not grown past morula stage, and our chances were slim. He said it wasn't clear if it was an egg or sperm issue. My husband and I were surprised, as we thought that with ICSI, the sperm wasn't an issue.

Later that week after reading much of this site's posts and many other sites, I discovered that the sperm's job doesn't end with fertilization, but that it was key in development past three days. Further frustrating to me was finding out that ICSI done with severe male factor seems to have low success rates.

My question is, shouldn't the RE have told us we would have diminished chances using my husbands sperm, particulary when we expressed concerns about it pre-cycle and were completely happy to use doner sperm? We have spend $28,000 in fertility treatments at this clinic, which is supposed to be the best in Michigan. This was our only chance at IVF due to the cost. Had we known we TOTALLY would have used doner sperm. I feel a little cheated.

What do you think?

I'm wondering if another fresh IVF attempt with doner sperm would even work.

Also, does your clinic ever do Embryo adoption transfers? I would consider using your clinic for it because of your honesty and expertise.

Thanks so much.

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Well... You do have a point. ICSI does "level the field" in terms of fertilization, BUT (as you found in your reading), sperm genetics play an important role from Day 3 onward. When the percentage of sperm with normal morphology is low (i.e. <2% by strict criteria), I've seen embryos arrest prior to compaction. Since this also occurs when donated eggs are used, I attribute it to problems with the sperm genetics. Poor morpholgy often accompanies low concentration and motility. If your husband's sperm morphology was also low, your RE should have at least informed you that the chance of success would be lower with your husband's sperm and left the husband/donor choice up to you. I agree this is kind of a stinker because you specifically brought this up prior to initiating the cycle.

FYI: We published our findings that poor sperm morphology results in lower blastocyst development a number of years back (see below). This observation has been confirmed by subsequent studies by other programs.

Human Reprod. 2001 May;16(5):918-24.

The effect of intracytoplasmic sperm injection and semen parameters on blastocyst development in vitro.

Miller JE, Smith TT.

The present study compares the development and quality of blastocysts derived from conventional oocyte insemination with those derived from intracytoplasmic sperm injection (ICSI). Oocytes were collected from patients undergoing ovarian stimulation with human menopausal gonadotrophins for IVF. Patients with normal semen were assigned to conventional oocyte insemination while those with progressive motility <20% and/or normal sperm morphology < or =4% were assigned to ICSI. Resulting embryos were cultured for up to 6 days. The mean number and percentage of embryos reaching the blastocyst stage and the mean number and percentage of blastocysts of high quality on days 5-6 were assessed for both treatment groups and compared. The influence of paternal factors (sperm concentration, motility, progressive motility, morphology) on blastocyst development and quality were assessed by regression analyses. Significantly more ICSI-derived embryos arrested at the 5- to 8-cell stage (P = 0.024) concomitant with the activation of the paternal genome than those derived from conventional oocyte insemination. Significantly fewer ICSI-derived embryos reached the blastocyst stage on days 5-6 (P<0.001) and significantly fewer ICSI-derived embryos were of high quality (P = 0.002) compared with conventional oocyte insemination. When treatment groups were combined and evaluated by regression analysis, progressive motility and sperm morphology were significantly correlated with diminished blastocyst development and quality (P < 0.05). From these data, we conclude that paternal factors and/or performing ICSI in cases of severe male factor infertility may have a detrimental effect on blastocyst development and their quality.

If you can afford it, I would recommend a IVF subsequent cycle using donor sperm. I think your chances would be better with donor sperm.

Yes, we do have an embryo adoption program at North Hudson IVF (201-871-1999). Most people instruct us to destroy their embryos when they no longer wish to attempt pregnancy, but some people are generous enough to realize that donated embryos is the only option for people that have spent all their money on IVF attempts and come up with zip. Kudos to them. I'm not sure how many embryos we currently have available for adoption, but I can check. Why don't you email me and I'll get back to you.

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I just had a day 5 transfer today of 2 eggs: one pre-blastocystic and one compacted. From what we've read, we didn't think we should be disappointed, but the way our doctor described them to us, gave us reason to wonder. He automatically said (without us asking), "But there isn't any reason to be discouraged." We werent. Until he said that. This is my first IVF cycle, with my husband's fresh sperm. I am 36 and in relatively good shape. Is there something he isn't telling us?

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After reading this study I have questions regarding my most recent IVF. I emailed you on another post so I'll recap. I'm 36, 3rd IVF, (2nd IVF - BFP w/DD 5 yrs ago - transferred day 3 - 4 8 cell and stimmed 11 days), first IVF 6 months prior BFN - transferred 2 blasts, RE commented immature eggs (only stimmed 8 days) so stimmed longer on 2nd. This cycle, stimmed 9 days, 16 follies - 13 eggs initially mature all ISCI'd but only 3 fertilized and on day 3 only 1 cell each and 2 PN disappeared on all and arrested. Later that first day 2 more fertilized and grew to 8 and 10 cell Grade A- by day 3 and that's what we transferred, Beta in 2 days. According to your help with embroyology abbreviations, the rest was as follows: 6 had M2, (2 PB then 2 PN for only 2), 3 others had 2 PB but not PN and last one of the 6 had no more comments. 4 of the original 16 were labeled lyse, one had GV and the final one was "emergency ISCI'd" the next day when it matured but by day 3 had arrested also. My DH had 44% normal sperm 5 years ago using the WHO method so we didn't do ISCI and last cycle 7 of 7 fertilized. This time he only had .04 morph using strict method so ISCI'd all. With such a low fert rate on this cycle would you say it's could be attrible to low morph? What would be our next testing if this one didn't work? Would we have to do PGD to see if I have poor eggs? Thanks for responding.

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Poor sperm morphology can contribute to a decline in the fertilization rate following ICSI (if the embryologist can't find a normaly shaped sperm to inject). However, decreased fertilization following ICSI is usually caused by inadequate cytoplasmic maturation of the egg. Thats related to the stimulation and that's where I would start looking for answers with your doctor.

In your case, I don't think PGD will provide any definitive answers. Decreased fertilization and embryonic arrest is occuring before the genetics of the embryo kick in and start directing development (that happens on Day 3). So determining the chromosome number of the embryos won't shed any light on the problems with fertilization and early embryonic arrest.

Because your husband's sperm morphology score is really low, he may want to consider having the Sperm Chromatin Structure Assay perfomed. For more information on the SCSA, see www.scsadiagnostics.com.

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