Globozoospermia


Globozoospermia is a rare and severe form of monomorphic teratozoospermia. This means that the spermatozoa show the same abnormality, and over 85% of spermatozoa in sperm have this abnormality. Globozoospermia is responsible for less than 0.1% of male infertility. It is characterised by round-headed spermatozoa without acrosomes, an abnormal nuclear membrane and midpiece defects. Affected males therefore suffer from either reduced fertility or infertility. Studies suggest that globozoospermia can be either total or partial however it is unclear whether these two forms are variations on the same syndrome, or actually different syndromes.
Studies have suggested mutations or deletions in three genes are responsible for this condition: SPATA16, PICK1 and DPY19L2. ICSI has previously been used to assist reproduction in globozoospermic patients, however it has not been particularly effective in all patients, due to low fertilisation rates.

Types of Globozoospermia

There are two types of globozoospermia:
Aside from the effect on fertility globozoospermia is symptomless. People with globozoospermia have normal physical and mental development, normal clinical features and normal hormonal profile.

Genetics

Table 1: Gene mutations that have been identified in globozoospermia and the impact these mutations have on sperm function and successful fertilization.

Diagnosis

The presence of round headed sperm in a semen analysis sample confirms the diagnosis of globozoospermia. The lack of acrosome can be ascertained by a technique known as immunofluorescence.

Treatment

Until 1995, the only options for people with globozoospermia who wished to conceive were adoption or sperm donation. With the advancement of assisted reproductive techniques it is now possible for those with globozoospermia to conceive using their own sperm. The main technique used is intracytoplasmic sperm injection where fertilisation is achieved by a single sperm being injected into the egg. Some studies have shown it is possible for a viable embryo to be created with this technique alone, however others have found it necessary to also use calcium ionophore treatment for fertilisation to be successful. Calcium ionophore treatment is used to artificially activate the oocyte. This treatment may be necessary as globozoospermic sperm can be less likely to activate the oocyte, an important stage in fertilisation.
The treatment options currently available focus on overcoming the prognosis of infertility which is associated with globozoospermia. So far there are no treatment options to prevent or cure globozoospermia.

Research

Research into globozoospermia is aimed at improving understanding of its cause and developing treatment options.

Genetics

The observation has been made many times that globozoospermia arises in siblings which points towards an underlying genetic cause. Recent progress has been made into determining what genes could be implicated in this pathology, with the previously mentioned genes being found to play a role. There are more genes which have been shown to be mutated in globozoospermia in mice, but these are yet to be connected to the human disease process. Examples of these include Gopc, Hrb and Csnka2. There are thousands of genes which guide the process of spermatogenesis, and knowing how they’re involved in globozoospermia is an important current area of research.

ICSI

The development of intracytoplasmic sperm injection made conception a possibility for patients with a variety of male infertility conditions, including globozoospermia. However, fertility rates with this approach are still low, and research is ongoing into how this can be improved.
It has been found that treating globozoospermia with ICSI along with oocyte activation by calcium ionophore and postacrosomal sheath WW domain binding protein.