IVF Disasters: No Fertilization

June 30, 2010Carole 170 Comments »

Hopefully, this never happens to you, but sometimes after adding sperm to egg or injecting sperm into egg, the next morning, we have nothing good to report. Sometimes, we see the sperm swimming around the egg, with no signs of attachment to the egg. Sometimes, sperm attach all over the egg, but the egg looks unchanged. See my earlier post “Happy Zygote Day!” for pictures of eggs before and after fertilization.

Rescue ICSI. If eggs and several thousand sperm are put together in a drop- the co-culture method- then we have the option of performing “Rescue” ICSI if it looks as though sperm did not enter the egg. It’s a tricky call to make because sometimes the sperm will be inside the egg but we can’t see it. If we inject yet another sperm into the egg, we have injected additional chromosomes and produced an abnormality.

Intracytoplasmic Sperm Injection or ICSI

Intracytoplasmic sperm injection or "ICSI"

Criteria for using rescue ICSI. Usually we would do rescue ICSI if zero eggs fertilized. If some were successfully fertilized, we can’t assume that sperm entry was the problem and so we may already have a sperm in those eggs that don’t “look” fertilized. Secondly, we like to see that the egg has only a single polar body, suggesting that it is mature but unfertilized. These two criteria give us some confidence that no sperm are already in the eggs we plan to inject.  Rescue ICSI does produce pregnancies but typically is  less successful compared to ICSI performed on a fresh egg. Research studies have demonstrated that the earlier the rescue ICSI is performed, the better the outcome, because the egg is “fresher”.

Fertilization Failure Post-ICSI. If none of the eggs fertilized after ICSI, there are few options. You can’t inject another sperm because sperm entry wasn’t the problem if you did the ICSI correctly. Assuming there are not technical issues, a number of problems can explain fertilization failure after ICSI.

  • The egg didn’t survive the injection process. Eggs may not survive if the eggs are relatively immature or post-mature due to membrane changes that happen with maturity. Stimulation was sub-optimal.
  • The sperm head did not decondense after entering the egg, so the DNA remained locked in the sperm head.
  • The egg was not activated and didn’t participate in the intracellular steps of fertilization. Failure of egg activation may the main reason according to a study that performed a microscopic evaluation of the sperm head and cellular structures after injection.
  • A small number of eggs were available for injection. For example, the stimulation was poor and only three eggs were retrieved or patients limit the number of eggs injected to three or less for religious reasons. Statistically speaking, you were simply unlucky that the three (or fewer) eggs that were injected did not fertilize.

Experiencing complete fertilization failure after ICSI, while emotionally devastating, does not mean that a future IVF cycle won’t succeed. In a study of 21 patients who had complete ICSI failure, half of them went on to try another cycle and had a 45 percent clinical pregnancy rate per transfer. The point is that often times a poor stimulation can be corrected in a subsequent cycle and make a difference. If sperm were barely motile or immotile at the time of injection, a better sample or donor sample may result in fertilization in a future cycle.

Split ICSI cases. If there are concerns in advance that ICSI may be necessary, but it’s a borderline case, it is possible to use ICSI on half the eggs and conventional co-culture on the other half, to ensure that sperm entry won’t be an issue in half the eggs.

Chemical Activation. It is possible to activate the egg artificially by introducing a calcium ionophore or other chemical agent into the egg with or after injecting the sperm into the egg. This is currently a research application and there are relatively few clinical case studies reported in the literature. This study described chemical activation for a couple with repeated total fertilization failures after ICSI. There is no safety data or longterm outcome data to show that chemical activation is safe. Chemical activation may be validated for clinical use in the future, but currently, it is not considered part of routine clinical care.

Restricting the number of eggs that are fertilized. We have honored patients requests to only inject or inseminate three eggs to avoid the problem of having excess embryos in the freezer. I understand that this is a valid ethical/religious concern for many patients, but it effectively hobbles the full power of the in vitro fertilization technique. We can try to guess which three eggs look most likely to fertilize but we are only guessing. By allowing us to inject only three eggs and throwing away the rest, you have effectively reduced your odds of success with this technique. In the not too distant future, egg freezing may be a highly successful technique in every IVF lab so it won’t be a big deal to only inject three because we can freeze the rest for later. In the future, your previously thawed eggs may be just as fertilizable as the fresh eggs. We are getting close to that dream and some labs report that they are already freezing eggs with great success. But we aren’t there yet in every lab. So technically speaking, it is best to let the lab attempt to fertilize every mature egg to optimize your chances of pregnancy in the fresh cycle. Of course, it is your choice but you should understand the technical risks of this choice.

© 2010, Carole. All rights reserved.

170 Responses to this entry

  • Carole Says:

    Hi Lara,
    It is possible to have an empty follicle and it is possible for either the physician or the embryologist to miss an egg during the retrieval. Obviously, I don’t know if any of these possibilities apply to your case. I think that you should be able to ask your physician these questions and get answers. If you feel you can’t ask questions or if you ask questions and get harsh or angry responses, you probably need to find another clinic/physician who feels that communicating with the patient so that they understand their diagnosis, treatment options and alternatives is an important part of healthcare delivery to their patients. Good Luck!!! Carole

  • Lara Says:

    Hi Madame Carole,
    Thanks infinitely for taking time to answer my question. I appreciate it a lot!! I have another question please: How much time should an embryologist keep a follicle after looking into it? Is there a specific procedure to follow?
    Thanks again!

  • Carole Says:

    HI Lara,
    The follicle actually stays in the ovary. The physician suctions out the fluid from the follicle-which is a structure on the surface of the ovary which supports and grows the egg. When the fluid is suctioned from a follicle by the physician, he/she will hand the tube of fluid –which hopefully has an egg- to the embryologist. The embryologists dumps the fluid contents into a shallow sterile plastic dish and searches the fluid for an egg, which they then pick up, rinse in culture media and transfer to another sterile dish containing culture media. The general procedure is similar in each lab, with some differences. But every lab should have a single written protocol that all embryologists are trained to follow. For instance, in my lab, we had a second person check each dish containing fluid to ensure that nothing was missed. To know exactly how it in a particular lab, you should ask your embryologist how he/she does it in their lab. They shouldn’t mind talking about their work. Good Luck!! Carole

  • Lara Says:

    Hi madame Carole,
    Thanks again for answering my question, yet I still have another question please. You wrote in your first message to me that it is possible for the physician to miss an egg during the retrieval. Would you please explain this to me?
    Thank you very much for your collaboration!

  • Carole Says:

    Hi Lara,
    The ultrasound image is useful to direct the tip of the suction needle to the follicle, and the doctor can see the image of the follicle collapse as the follicular fluid is sucked out. The image is not so good that the doctor can actually see the egg inside the follicle. Verification that the follicle contains an egg–and is was suctioned out successfully — is made by the technician who examines the follicular fluid under a high power magnification and can verify that an egg is in the fluid. IF there is no egg in the dish under the microscope – then either there was no egg in the follicle to begin with or it was not successfully pulled out with the suctioned fluid–or less likely, the technician failed to identify the egg in the dish under high mag. So the physician or the technician can miss retrieving or finding the egg in the fluid.

  • Lauren Says:

    My husband is 42 and had a vasectomy 11 years ago when married to his previous wife. I just turned 36. Last year my amh was 1.3 and my ob/gyn ran a few other tests and said everything looked good. 6 months later we decided to go forward with IVF. When they ran my amh again it was down to .3. My husband had a tese done and while in the or they were unable to find any motile sperm. When they took the samples back to the lab they were able to find ~10,000 that were testicular sperm that we could use and froze 6 tubes. I was on 300 follisitm and 225 of menapur for 10 days (150 follistim and 150 menacer for the last day) and trigger on day 11. They collected 11 eggs during retrieval with 9 that were mature. Only one fertilized and it was 2 cell high quality on day 2 and never progressed past day 2. Obviously we were not expecting this result. My Dr spoke with the embryologist today (high volume clinic) and they reiterated they thought my eggs looked very good. Dr is encouraging us to try again with a lupron flare protocol hoping if we can get more eggs that we will have a higher chance of having some fertilize and feels we can’t rule this totally sperm related unless the same thing happens again. We planned to do pgd. Is there anything else we can do to prevent this from happening again? (other tests? different protocol?) Thank you!

  • Carole Says:

    Hi Lauren,
    I am sorry you are having such a hard time. TESE sperm tend to give poorer fertilization results, even with ICSI. Regarding other stim protocols, I can’t advise you – that is a question for your RE. The low AMH result is an indicator of number of eggs, but is not usually considered a very good test for egg quality. The low fertilization is most likely sperm related. THis article may be helpful: http://www.advancedfertility.com/amh-fertility-test.htm
    Good Luck!! Carole

  • Lauren Says:

    Thank you- is there anything else we can do to get a better sample of sperm from my husband? Now that they know where they found sperm previously is TESA an option in a few months instead of full surgical TESE again? Thanks again.

  • Carole Says:

    Hi Lauren,
    It might be possible- that’s a better question for the urologist who did the procedure. However, if either some of the tissue or some of the sperm extracted from the tissue was cryopreserved, then this could be thawed and used in a future ICSI without another surgery. There are other methods for sperm retrieval which are explained in this article :http://theturekclinic.com/services/male-fertility-infertility-doctor-treatments-issues-zero-sperm-count-male-doctors/sperm-retrieval-ivf-success-rates/ Some of the methods remove sperm from the epididymis, the storage organ above the testis, others extract sperm from the testis. I would follow up with your doctor to see what the next steps might be. Good Luck!! Carole

  • Lili Says:

    Hello. I am 36 years old. My DH did have cancer. He got retrograde ejaculation. I have done two IVF+ICSI cycles with Testicular bipsy sperm. The first we did 14 egg 8 fertilized 6 did fine at 2 days, I did have 4 transfers, no pregnancy.

    2 cycle 18 eggs 13 mature just 6 fertilized 2 survived 3 days. 8 cells 10 cells. we did transfer, chemical pregnancy. I thought that ICSI will solve all the male infertility problems, specially when you read all these fertility websites saying that 90% of the issues are int he egg and that ICSI is like a mirracle for male infertility issues. But The clinic advise us to get a sperm donor, the possibilities of getting pregnant trying my husbands sperm are low, even using ICSI. WHY????

  • Carole Says:

    Hi Lili,
    I am sorry you are having such a difficult time. ICSI is an excellent solution if the only problem is few normal sperm– selection of a normal looking sperm and injection directly into the egg often has very good results. Your husband had cancer . Chemotherapy and radiation are both negative factors for normal DNA in the sperm, that is why men with cancer are encouraged to bank sperm ahead of time. If he was unable to bank sperm before and he had these exposures, he may have mostly or all damaged sperm now. This sort of damage is not visible to the naked eye because it is at the level of the DNA so the technician can’t avoid selecting these sperm. Also, testicular sperm is already a less mature sperm and even if there was no exposure to chem/radiation, ICSI results are poorest with testicular sperm compared to ejaculated sperm. This is a likely explanation for what you are experiencing. Donor sperm may be a good technical option if that is acceptable to you and your husband. There are many paths to parenthood. I wish you and your husband MUCH GOOD LUCK in whatever you decide going forward! Carole

  • Ana Says:

    We just had failed IVF cycle #1 and embryologist said out of 5 only 3 matured and with those non fertilized. He said it simply did not activate. Is this an egg quality issue or sperm issue and how can it be corrected?

  • Carole Says:

    Hi Ana,
    Egg activation requires active participation of both sperm and egg so either or both could be the cause of failure. I am sorry that you had such a disappointing result. I am not aware of any mechanism to fix this- although there seems to be a problem with egg maturation so there may be something to be optimized regarding egg maturation from the stimulation protocol. I would ask your doctor what he might suggest, if anything, for a another attempt. Good Luck!! Carole

  • Denise Says:

    Hi. I am 39 years old, DH is 46 and had a vasectomy with previous wife. A reversal was done 2015 and we have been advised he has antisperm antibodies. I have an amh of 2.9 but did not get a positive result from ovulation stimulation. I was put on modified ivf with icsi but after my one egg was retrieved, it had 3 pronuclei.
    I have one cycle left and wonder if it is too soon to go down donee egg route or if I am just wasting my chance going through the cycle myself again? My husband is worried about chromosomal abnormalities but I don’t feel as though we have exhausted our chances just yet after only two cycles, one egg retrieval.
    Is this lab result an indicator that my eggs are not of good enough quality to fertilise? Should I take my chance or go down DE route please?

  • Carole Says:

    Hi Denise,
    So there are really two distinct answers when you ask- Should we go down the donor route?
    Yes, if you want the greatest liklihood of conception soonest. There is some possibility that a much better stim could give you some more eggs, but at 39, you are already at increased risk of chromosomal abnormalities- donor egg from a younger- proven- donor could be very helpful here.
    No, if you will forever wonder “what if”, preventing you from bonding with said child arising from donor option. That’s probably the bigger question. Please consider the donor option carefully because it is much more complicated than the simple “technical fix” it can be in the lab.There are fertility counselors that can help you work through your feelings about this before you move down the donor road or decide to give another own-egg IVF cycle another try. Your doctor should be able to refer you- otherwise- Resolve.org should have some information. Good Luck with whatever you decide. There are many paths to parenthood! Carole

  • Jessica Says:

    I’m just 34, husband is almost 32. We’ve been trying to conceive without success for almost three years. Initial investigations of blood tests and sperm analysis showed no issues. A hsg showed a blocked Fallopian tube which I’ve had surgery to unblock. We have had to failed rounds of iui and our first ivf attempt was cancelled due to zero fertilisation. The embryologist said there was no binding and believe my eggs have tough shells. They’ve suggested icsi to overcome this but after so many setbacks I want to rule out any other potential issues. I don’t understand how they can be certain it’s the egg shell that is the problem. I can’t find much information on icsi and female issues as it is more frequently used to treat male issues.

  • Carole Says:

    Hi Jessica,
    They can’t be certain it is the egg shell (zona pellucida). It could also be a lack of receptors on the sperm. But ICSI was created to solve the problem of the sperm not either successfully binding to the egg and/or the sperm penetrating the egg. ICSI will guarantee that the sperm will enter the egg, but it does not always guarantee fertilization. There could be either egg or sperm problems even after the sperm and egg are together, that can prevent a zygote (fertilized egg) and /or embryo from forming. IVF generally is a poor diagnostic tool for this reason so you may never know why it doesn’t work. ICSI is a logical next step- assuming the eggs look healthy- no dark centers, for example, and the clinic ha a good track record with ICSI. (if you are interested, here is a quick pictorial of fertilization with pictures so you can see there are a lot of steps involved. If you decide to continue with IVF, trying ICSI next would be reasonable. Good Luck!! Carole

  • kandace92 Says:

    I disagree, look at http://tmp.gtk.uni-miskolc.hu/volumes/2011/01/TMP_2011_01_05.pdf Kandace

  • Marie Says:

    Hello, I’ve recently gone through my second ICSI cycle due to my husband having a vasectomy 13 years ago. All of my hormone levels, bloods and egg store results are normal. I am 33 and husband 39. The first cycle they got 14 eggs, 9 mature and my husband had a TESA on the same day to collect the sperm. We had zero fertilisation, though no eggs died from the ICSI procedure. The second time there were 14 eggs, 10 mature, and we used my husband’s frozen sperm that they’d collected via surgical procedure a few weeks earlier. The sperm looked fine, it defrosted ok, but again zero fertilisation and 4 eggs died from the ICSI procedure.The head scientist said it was a 70% chance it was an issue with my eggs and 30% chance it was a sperm issue. We had the sperm tested and all results came back ok.
    I can’t find much information about egg issues during ICSI. Can eggs ever not respond to ICSI but then respond to normal IVF? Could some eggs be too fragile for ICSI? Would it help if I took vitamins l, didn’t drink, did acupuncture etc for a few months before it is that just grasping at straws? Any info you have would be appreciated. Thanks!

  • Carole Says:

    Hi Marie,
    It is so hard to diagnose egg issues becasue eggs die from the ICSI procedure because either the egg is inherently fragile or the tech or their tools are not adequate to perform the procedure expertly. It’s hard to tell from the outside. First thing, I assume you have checked your clinics pregnancy and live birth rates on http://www.sart.org and compared to the national averages? I encourage everyone to go to the best clinic they can reasonably get to–and don’t go to clinics that are worse than average. So if you have been reassured about the clinic stats, then it becomes harder to troubleshoot. The quality of the ovarian stimulation can also affect egg quality. Having more eggs does not necessarily mean that you will have more good eggs. SO changes in the stim may be beneficial. Every RE has their favorite cocktail for stim. TESE sperm are always the most difficult to get good results with so I am not sure why they are so carefree about the sperm. Ejaculated sperm work best, surgically recovered epidydmal sperm are second best and TESE sperm are usually the least effective. Why? Because they get more mature and fertilization capable as they move from testis to epididymis to being ejaculated. Various culture methods and even chemical stimulants have been used to get them more egg -ready but it’s a heavier lift when they are in the testis, vs in the last part of the epididymis. Yes, eggs can respond to IVF but not ICSI but usually this is because there are technical issues. Yes, some eggs are inherently too fragile for ICSI but when this is rare. I don’t know of any self-care that would impact on egg fragility. I wish I could be more help. Good Luck!! Carole

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