New Testing Method for Most Severe Male Infertility

Identification of two proteins could help develop a non-invasive testing method informing men with the most severe form of infertility about their chances of becoming a parent through in vitro fertilization.

About 15% of couples experience infertility, and the male factor accounts for roughly half of the cases. Some males have no or low sperm count in their semen because of an obstruction. About 2% of men don't produce enough viable spermatozoa for traditional insemination, a condition known as non-obstructive azoospermia, the most severe form of male infertility.

A new study published in Molecular & Cellular Proteomics identified two proteins, AKAP4 and ASPX, that are unique to viable sperm. The findings may help to develop a new diagnostic test to predict whether that surgery for non-obstructive is likely to be successful. Additionally, it would help surgeons identify viable sperm during the surgery.

"The routine semen tests typically show zero sperm in non-obstructive azoospermia, but is it really zero? With our approach, we are able to record a million images and, in some patients, find only 10 spermatozoa. But even a few would be enough for in vitro fertilization," says lead author Andrei Drabovich, a biochemist and assistant professor of laboratory medicine and pathology at the University of Alberta.

Treatment for non-obstructive azoospermia involves a surgery called microdissection testicular sperm extraction (mTESE), which dissects the testes in search of intact sperm. Extracted sperm is then frozen for later use with in vitro fertilization when live sperm is injected into a woman's eggs in a laboratory. This procedure is called intracytoplasmic sperm injection (ICSI).

In their previous studies, researchers at the University of Alberta identified proteins to diagnose whether azoospermia is obstructive or non-obstructive. Using an advanced mass spectrometry technique, they uncovered thousands of specialized proteins unique to the male reproductive system. Specialized techniques and equipment helped to identify semen cells that have the telltale elongated shape of sperm and the target proteins on both the head and the tail.

The researchers note that certain spermatozoa selected by imaging flow sorting approaches may not be suitable for ICSI procedures due to the use of ethanol permeabilization. Moreover, residual anti-AKAP4 and anti-ASPX antibodies are bound to spermatozoa after imaging flow cytometry analysis.

Infertility is defined as not being able to achieve pregnancy after onw year of having unprotected sex.

In about half of male infertility cases, causes cannot be determined. While problems that affect how the testicles work are the most common known causes of infertility, issues like hormone imbalances or blockages in the male reproductive organ can also lead to fertility problems.

Between 10% to 15% of infertile men experience a complete lack of sperm, most commonly caused by varicocele, an enlarged vein in the testicle.

The identification of AKAP4 and ASPX proteins may help develop a non-invasive test offering better diagnostics and treatment of the severe forms of male infertility.

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