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Why do eggs not fertilize in IVF?

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4 fertility expert(s) answered this question

Why do some eggs not fertilize in IVF?

Our experts have shared valuable insights about IVF, offering clarity on why some couples may not conceive naturally. Learn how undergoing IVF can provide important diagnostic information, such as when eggs fail to fertilize. Understanding these details can be key in addressing fertility challenges effectively.

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Answer from the fertility expert:
Michael Carroll, Reader (Associate Professor) in Reproductive Science at Manchester Metropolitan University

There can be many reasons why eggs don’t fertilize during the IVF process. It can be down to poor sperm quality (that is the sperm could not reach the egg or bind to the egg), it could be down to the egg quality itself, not being able to receive the components of the sperm in order for it to fertilize. Another aspect is the deficiency of the sperm (fracture). This is a little chemical found within the sperm that activates the eggs and knocks the eggs out of its arrest and allows for embryonic development. So there can be many reasons. To summarize, could be the sperm problem which is they can’t get the egg and bind to the egg or penetrate zone a pollution, they can’t bind to the membrane of the egg or activate the egg, fertilize the egg and or it could be egg quality as well – not been able to respond to those signals from the sperm.

Answer from the fertility expert:
Sokratis V. Grigoriadis, Reproductive Biologist-Clinical Embryologist, Postgraduate Researcher at Assisted Reproduction Unit of Aretaieio University Hospital

This is a very interesting and challenging question. Fertilization success is the first and foremost crucial step in achieving a live-birth for both natural conceptions and in vitro fertilization cycles. In the context of IVF treatment, the incidence of fertilization failure ranges between 5-16% regarding the conventional IVF cycles and 1-3% regarding intracytoplasmic sperm injection cycles (ICSI), respectively. Elaborating on the factors that could detrimentally affect fertilization rates, it should be noted that fertilization is a complex procedure with several steps rendering it challenging to identify the underlying factor leading to fertilization failure.

Generally speaking, it is widely accepted that in order for an oocyte to be normally fertilized via conventional IVF, a large number of motile morphologically normal spermatozoa is required. Thus, in cases of severe male factor infertility, where the number and/or the motility of spermatozoa is significantly compromised, the preferred method for fertilizing an oocyte is the intracytoplasmic sperm injection (ICSI), where a single spermatozoa is directly injected into the oocyte’s cytoplasm. However, even if semen parameters are normal, there is still a chance of fertilization failure. Commonly this is attributed to low oocyte quality and/or co-existing abnormalities in spermatozoa, which are difficult to be identified via standard semen analysis. For example, spermatozoa present with fragmented DNA are of compromised fertilization dynamics. Thus, in cases where an unexpected high fertilization failure rate is observed, we subject spermatozoa to more accurate tests and functional analysis in order to identify possible factors leading to compromised fertilization dynamics.

Focusing on the role of the oocyte, it should be mentioned that several abnormalities, especially related with the zona pellucida as well as with oocyte cellular membrane and cytoplasm functionality, could lead to impaired spermatozoa attachment and/or impaired oocyte activation. Moreover, oocytes obtained from women of advanced maternal age tend to be of compromised quality and subsequently of compromised fertilization dynamic. Finally, specific mutations in genes expressed in both oocytes and spermatozoa could lead to fertilization failure affecting several steps of the fertilization process, including spermatozoa activation, spermatozoa binding, fusion of spermatozoa with the membrane of the oocyte, as well as oocyte activation. In conclusion, the identification of the underlying factors leading to fertilization failure could at the same time be straightforward or extremely complicated. However, we now have advanced tools and protocols in order to significantly improve the efficiency of IVF treatment with regards to couples presenting with unexpected increased incidence of fertilization failure.

Answer from the fertility expert:
Lucy Lines, Business Owner at Two Lines Fertility

Look, I could talk about this for hours and hours but I won’t. I think that when we collect eggs for IVF, we’re collecting all of the eggs from one cohort of eggs that were previously growing up to just one ovulation. When we ovulate, we only ovulate one egg and all the other eggs in that cohort die out and that’s probably because most of them weren’t up to the task. When we do IVF, we collect all of the eggs from that cohort. We have to expect that there are going to be some in there that just aren’t up to the task. They’re not good enough and that’s only natural and to be expected.

 

Answer from the fertility expert:
Saghar Kasiri, Director of European Operations, Cryos International

The eggs may not fertilize in IVF if they’re not mature eggs. We can have eggs that are very very immature. We could have eggs that are just the stage before complete maturation or we can have very very poor quality eggs or even degenerate eggs which is that unfortunately they are not viable eggs. These can be some of the reasons why eggs don’t fertilize in IVF.
As mentioned also, because through the IVF process we don’t separate the eggs from the cushion of cells that is around them, it is very difficult for us to assess in IVF if the egg is mature or not. All the eggs that are collected are put in a dish with the right amount of sperm to fertilize it and it’s the sperm that does the hard work to make its way through the egg. The next day when we check in the lab, we check the fertilization. We can see whether we have got mature eggs, immature eggs, good quality, poor quality or even degenerated eggs. The other reason that the eggs may not fertilize is if the shell around the egg could be very hard, which is what we call the zona and it can be a hard zona: a situation where the sperm would find it very difficult to break that shell and enter in order to fertilize the egg. If we find that sometimes it is visible under the microscope that the shell or the zona is quite thick and therefore, we know that thick zona next time we would need to actually use a process called ICSI. The ICSI would hopefully help with the fertilization rate the next time around.
Sometimes there’s not enough binding the sperm and eggs just don’t attract each other and if there is no binding between the sperm and the egg and we can see that under the microscope from from the number of sperm that is attached to the zona trying to get inside because in a natural process of fertilization many sperm gather around the egg, they try to penetrate the zona and if the egg is good quality it would only allow one sperm to enter it and then the zone gets hardened and won’t allow the entry of any other sperm, so if we have low fertilization as a result of IVF we look at is there a good binding between the two, has the sperm survived well because that’s another factor: has the sperm survived well within those hours that they are the egg and the sperm are left together because sometimes if the sperm cannot swim well enough to get itself to the egg, it could be that there is a sperm issue that there has been low fertilization.

In general, it depends whether the quality of the egg is good, whether it is mature, whether there is a binding, whether there is a problem with the shell around the egg or whether there is an issue with a sperm penetrating more than one sperm penetrating into the egg which causes abnormal fertilization.

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