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Introduction

Fertilization problems do arise for some patients being treated with conventional IVF or IVF with ICSI, and this is a devastating result for everyone involved. In spite of all the preliminary testing and recommendations provided, fertilization failure or low fertilization can still occur in spite of everyone's best efforts. Low or failed fertilization can be caused by sperm factors, egg factors or a combination of both. Fertilization is a very complex biological process, and while many of the steps and requirements involved are known, many others are still poorly understood.

Conventional IVF

Poor or failed fertilization may be due to a failure at any number of steps in the fertilization process.

  1. The sperm might have difficulty getting through the mass of cells surrounding the egg.
  2. This may be due to the lack of proper components in the head of the sperm which “digest” this complex.
  3.  The sperm might not be able to pass through the zona pellucida (ZP) which surrounds the egg. This could be a problem with the sperm or with the egg: the sperm might not be able to pass through a normal ZP, or the egg may have produced an abnormal ZP.
  4.  The sperm and the egg membranes might not be able to fuse so as to allow the contents of the sperm to enter the egg. Again this could be a problem with one or more components of either the sperm or the egg.
  5.  The sperm might not be able to undergo the process of “decondensation” (break down) once inside the egg. This is where the genetic material carried in the sperm head is “unpacked”, and both the egg and sperm participate in this process and either one could be lacking vital components.
  6.  Either the egg or the sperm (or both) might not form a “pronucleus” inside the egg. This is where the two sets of genetic material arrange themselves into separate “pronuclei” before they fuse and form the combined genetic material of the embryo. Most of the processes described above cannot be tested for in advance, it is only the process of IVF itself that reveals the problems. Should poor or failed IVF fertilization occur, the eggs and sperm will be assessed immediately for the following:
  7. Overnight survival of the sperm in the insemination dishes.
  8. “Binding” of sperm to the zona pellucida of the egg.
  9. Extra morphology assessment of the sperm sample produced for the insemination.
  10. The appearance of an additional polar body on the egg but two “pronuclei” are not present (two polar bodies are present if the egg has been “activated” by the sperm).
  11. The number of eggs where more than one sperm entering the egg. These assessments will provide valuable information that can help plan any future treatment. In some cases of failed fertilization, the laboratory might perform a “Rescue ICSI” procedure. This involves obtaining a fresh semen sample from the male partner and your consent to go ahead with performing ICSI on the eggs. The success of Rescue ICSI is low, but is the only immediate solution available to try and rescue the current treatment cycle. The suitability of the eggs to undergo Rescue ICSI is based upon the embryologist’s assessment of the eggs and sperm after the fertilization failure is noted. 

ICSI

Complete fertilization failure with ICSI occurs far less often than with IVF – but it does occur. More often is the occurrence of low fertilization. ICSI bypasses the initial steps of fertilization which involve the entry of the sperm into the egg. Any fertilization failure that occurs after ICSI is probably limited to problems affecting processes that occur once the sperm is inside the egg (i.e. the last two listed in the section on IVF, above). Lower fertilization results might be anticipated if the sperm being used is surgically retrieved or if the couple have severe male factor. Here, the results are dependent on the number of morphologically normal and viable (alive) sperm that can be found. Further treatment options are more limited when fertilization failure occurs in an ICSI cycle because there are no options for "rescuing" the cycle –more sperm cannot be injected into the eggs.

Fertilized and non-fertilized

Human eggs

  1. Figure 1: Human egg as retrieved from the ovary for IVF/ICSI. Surrounding the egg is the mass if cells (outer “cumulus mass” and inner “corona cells”) through which the sperm must pass in order to reach the egg.
  2. Figure 2: Human egg with normal fertilization. One of the circles (nucleus) in the center of the egg is from the sperm and the other is from the egg. Two polar bodies (PB) are also present between the egg and the zona pellucida (ZP).
  3. Figure 3: Human egg with no fertilization. No pronuclei are present and only one PB can be seen i.e. the egg was not activated by a sperm entering it). A single sperm can be seen bound to the ZP.
  4. Figure 4: Human egg with no fertilization. Two PBs are evident which indicates that a sperm went into the egg, but either the sperm or the egg did not form the second – essential – pronucleus. Rescue ICSI would not be performed on this egg.
  5. Figure 5: Human egg with no fertilization. Two PBs can be seen which indicates that the egg was activated, but neither the sperm nor the egg formed pronuclei. Rescue ICSI would not be performed on this egg.