Repeated fertilisation failure

It is difficult to predict whether fertilisation will be absent or poor. However, there are conditions with an increased risk of poor fertilisation:

• Extremely poor sperm quality: absence of any motile sperm and/or only severely abnormal sperm morphology.
• Poor oocyte quality.
• Absence of fertilisation in a previous treatment cycle.

While poor or absent fertilisation is difficult to predict, there are several possible causes of this condition. The cause may be related to the sperm, or to the oocyte, or to the interaction between both.
Severe morphological abnormalities of oocytes and sperm can be detected by microscopic assessment. However, in a large number of cases the real cause of the problem cannot be determined, as functional aspects of sperm and oocytes cannot always be assessed.

The following causes are possible.

• Oocyte factors:
  • (Too) low number of oocytes. when only one or a few mature oocytes can be collected, the theoretical risk of fertilisation failure increases.
  • Oocyte maturity. Oocytes which morphologically look mature, may be intrinsically too immature to be fertilised.
  • Oocyte quality. If oocytes are severely granulated, contain many vacuoles or other abnormalities chances of fertilisation are smaller.
  • Functional problems, such as oocyte activation abnormalities, may lead to abnormal fertilisation or fertilisation failure. Also, the oocyte may lack the different elements required for fertilisation.
• Sperm factors:
  • Extremely low numbers
    In an IVF|ICSI treatment of prospective parents with strongly reduced fertility of the man, sperm can sometimes be collected via a biopsy of the testicle. This is performed (among others) if no sperm is found in the sperm sample (azoospermia) and this condition was not caused by an obstruction, i.e. non-obstructive azoospermia (NOA). For more information about the procedure, see TESE on the CRG website.
    Accurate sperm selection in this situation is often impossible, which increases the risk of fertilisation failure.
  • Absence of motility. The motility of sperm is an indicator for vitality. When motility is absent the risk of fertilisation failure increases. This condition occurs more frequently in case of NOA.
  • Abnormal morphology of the sperm. When only very abnormal sperm can be used for injection, the risk of fertilisation failure increases.
  • Sperm functionality. If we detect incomplete acrosome reaction (necessary for the sperm to penetrate the egg) with ‘conventional’ IVF , sperm DNA fragmentation or abnormalities, failure of sperm to activate the oocyte, or other functional abnormalities, fertilisation failure is likely.
• Sperm-oocyte interaction:
  • Poor interaction between the sperm and the egg shell (zona pellucida). Sperm may not be able to bind to the zona pellucida and/or to undergo acrosome reaction with conventional IVF.
  • Defective oocyte activation: sperm may not be able to provide the factor which activates the oocyte, a process which precedes fertilisation.

After conventional IVF, fertilisation failure is observed in 10-15% of the treatment cycles. The introduction of ICSI (now more than two decades ago) solved many sperm problems as well as sperm-oocyte interaction problems. The overall rate of cycles with fertilisation failure dropped to less than 5%.
About the situations when things do go wrong, we can say the following.

• Our laboratory staff is highly trained to select the best sperm in case of low sperm numbers and/or severely abnormal sperm. Specific laboratory techniques such as laser-assisted selection, are used.
• In case of persistent complete sperm immotility, we can treat sperm to stimulate motility. Sperm that show slight motility after stimulation are vital and have a higher chance of fertilising the oocyte after ICSI.
• If immotility is the result of necrozoospermia (all sperm are dead), surgical retrieval of testicular sperm may be necessary. See the TESE procedure on the CRG website.
• A possible cause of non-fertilisation can be sperm failure to activate the oocyte. This occurs in patients with globozoospermia: the heads of most sperm are round without acrosomes — the hood on the head of the sperm necessary to penetrate the egg. Sometimes this can also occur with normal-looking sperm. In cases with globozoospermia or in cases with a history of unexpected fertilisation failure, we can offer artificial oocyte activation which may increase the chance of fertilisation.

If, however, fertilisation failure occurs repeatedly and remains unexplained, even after using artificial oocyte activation, your fertility doctor may suggest a treatment cycle with half of the oocytes injected with the partner’s sperm, and the other half with donor sperm. This allows us to find out whether a functional sperm factor is the underlying cause of the problem.
If so, you could consider an IVF-cycle with donor sperm to get pregnant.
If fertilisation also fails with donor sperm, an IVF cycle with oocyte donation may be an option to get pregnant.