IVF Disasters: No FertilizationJune 30, 2010Carole 43 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.
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.