Globozoospermia After Failed ICSI: What Assisted Oocyte Activation Found

A study of 33 couples affected by globozoospermia and previous total fertilization failure reported normal fertilization in 402 of 560 mature eggs after ICSI with assisted oocyte activation. Nineteen couples had at least one live birth, giving a cumulative live-birth rate of 57.6% per couple.

In their previous IVF treatment, no eggs had fertilized even though sperm had been injected directly into them. In subsequent treatment, adding a procedure intended to help the eggs start the fertilization process was followed by a fertilization rate of 71.8%. The findings concern a rare form of male infertility in which sperm have abnormally round heads.

The study, published online in Reproductive BioMedicine Online, examined 33 couples with globozoospermia whose earlier intracytoplasmic sperm injection (ICSI) treatment had resulted in no normally fertilized eggs. ICSI uses a fine needle to inject a single selected sperm into an egg and is widely used in severe male infertility when sperm have difficulty entering the egg themselves.

Why, then, can fertilization still fail after a sperm has been placed inside the egg?

Sperm entry does not complete the fertilization process

In globozoospermia, sperm heads are round rather than having the usual oval shape. The problem is not simply their appearance. The acrosome, a structure at the front of the sperm head, is often absent or abnormal.

Another important problem can involve the signal that activates the egg. Fertilization is not automatically completed when a sperm enters. Repeated changes in calcium concentration inside the egg must initiate the processes that follow sperm entry.

A sperm protein called phospholipase C zeta (PLCζ) plays an important role in generating this activation signal. After the sperm enters the egg, PLCζ helps trigger the calcium signaling that starts the fertilization process.

In globozoospermia, this signaling function may be impaired. ICSI can successfully place a sperm inside an egg without overcoming the failure to activate it. The sperm has entered, but the signal to begin the next steps may not have been delivered.

Assisted activation after previous total fertilization failure

The couples in this study had experienced precisely this severe problem. They had confirmed globozoospermia and total fertilization failure (TFF), meaning that no eggs had shown normal fertilization after their previous ICSI treatment.

When ICSI was performed again, the researchers added assisted oocyte activation (AOA). This procedure applies an artificial stimulus after sperm injection to help the egg begin the fertilization process.

The researchers used the calcium ionophore A23187 to help generate calcium signaling within the egg. In the study's laboratory protocol, eggs were exposed for eight minutes after ICSI, followed by an eight-minute interval and a second eight-minute exposure. This was described as dual activation.

The additional step was intended to help the egg respond to sperm entry, rather than ending the procedure with injection alone.

Fertilization reached 71.8%, with development to blastocysts

Of 560 mature eggs, 402 fertilized normally, giving a fertilization rate of 71.8%.

Among the normally fertilized eggs, 317 developed to day-three embryos and 195 reached the blastocyst stage. A blastocyst is an embryo that has undergone several days of cell division, usually reaching this stage around five to six days after fertilization as it prepares for implantation. The blastocyst formation rate was 48.5% of normally fertilized eggs.

Fertilization rates and embryo counts are not the final outcomes that matter to patients, however. The study also followed pregnancies and births.

There were 58 embryo transfers and 34 clinical pregnancies. Twenty-six deliveries resulted in 35 children.

Of the 33 participating couples, 19 had at least one live birth. The cumulative live-birth rate of 57.6% was calculated per couple; it was not a success rate for a single embryo transfer.

These outcomes are noteworthy because all of the couples had previously experienced an ICSI treatment in which no eggs fertilized normally.

Failed ICSI does not automatically mean AOA is appropriate

The findings should not be applied directly to the general IVF population or to every patient who has had one or two treatments with a low fertilization rate.

The study involved only 33 couples with a rare, specific male infertility condition and previous total fertilization failure. It was a small, retrospective analysis of records from one treatment center, covering 55 treatment cycles. These features limit how widely the results can be generalized.

AOA is not a routine addition for every ICSI patient. It artificially induces calcium signaling involved in normal fertilization, and more research is needed to establish which patients should receive it and which activation methods and exposure conditions are most appropriate.

Long-term safety information on children born after the procedure must also continue to accumulate. The authors emphasized the need for prospective studies to identify optimal activation protocols and evaluate long-term offspring safety.

The study illustrates that ICSI solves the problem of getting a sperm into an egg, but sperm entry alone does not resolve every cause of fertilization failure. The signals that activate the egg must also function.

In selected conditions such as globozoospermia, where an egg-activation problem is suspected, the investigation may need to consider both which sperm is injected and whether the egg receives the activation signal afterward.

A previous fertilization rate of zero does not necessarily mean that every later treatment will also have a zero rate. Understanding why fertilization failed is central to considering the next steps.

This article is based on the 2026 online publication “Dual Calcium Ionophore Oocyte Activation After ICSI in Globozoospermia: Fertilization and Cumulative Live Birth Outcomes.” It retrospectively examined 55 treatment cycles in 33 couples with globozoospermia and previous total fertilization failure. Its small, single-center population should be kept in mind when interpreting the findings.

Research references

Dual Calcium Ionophore Oocyte Activation After ICSI in Globozoospermia: Fertilization and Cumulative Live Birth Outcomes. Reproductive BioMedicine Online, 2026. DOI: 10.1016/j.rbmo.2026.105938.