What Do Reference and Result Values Mean in the Context of Y Chromosome Microdeletions?

The fertility of males is a crucial aspect of their physical health, and it can be influenced by numerous factors, potentially leading to infertility. If a couple experiences normal sexual activity but fails to conceive, it is advisable to seek medical examination. In some male cases, the diagnosis may reveal microdeletions in the Y chromosome, a specialized concept that can be challenging to understand. Therefore, what do the reference and result values of Y chromosome microdeletions mean?

The Y chromosome harbors azoospermia factor (AZF) regions that affect sperm production. Due to the minuteness of these genetic loci, conventional methods cannot detect them, hence the term "Y chromosome microdeletions." Extensive research has been conducted on the relationship between the genetic type and phenotypic manifestations of Y chromosome microdeletions, providing valuable guidance for clinical practice.

Patients with complete deletions in all three AZF regions (AZFa, AZFb, and AZFc) will invariably present with azoospermia, meaning it is impossible to retrieve sperm from the testes through any means. Complete deletions in the AZFa region typically lead to Sertoli cell-only syndrome (SCO syndrome), clinically manifesting as azoospermia. If diagnosed with a complete deletion in the AZFa region, it is highly unlikely to retrieve sperm from the testes for intracytoplasmic sperm injection (ICSI).

The typical testicular histological features associated with complete deletions in AZFb and AZFb+c regions are SCO syndrome or spermatogenic arrest. Similar to the case of complete AZFa region deletions, these patients are unlikely to find sperm during testicular biopsy. Therefore, ICSI is not recommended for this patient population.

The clinical and testicular histological phenotypes associated with AZFc deletions are diverse. Generally speaking, patients with AZFc deletions retain residual sperm production capacity. AZFc deletions can be found in patients with azoospermia or severe oligozoospermia. In rare cases, they can also be naturally transmitted to male offspring. Among azoospermia patients, those with AZFc deletions have a much higher chance of retrieving sperm through testicular sperm extraction (TESE) and can undergo ICSI for conception. However, the male offspring of these patients will be carriers of AZFc deletions.

Additionally, studies have found that patients with oligozoospermia and AZFc region deletions have a progressive decline in sperm count, eventually developing azoospermia. Therefore, early treatment or cryopreservation of semen is recommended for these patients.

1. Microdeletions in the short arm of the Y chromosome are clinically manifested as azoospermia and small testes. Due to poor testicular development and abnormal spermatogenesis, these patients experience infertility.

2. Microdeletions in the long arm of the Y chromosome are clinically manifested as azoospermia or oligozoospermia. Some patients have basically normal sexual function, sometimes accompanied by premature ejaculation.

3. Mosaic Y chromosome microdeletions are clinically manifested as oligozoospermia with varying degrees of sexual dysfunction. These patients' wives may not conceive, or their embryos may stop developing and result in spontaneous miscarriages during early pregnancy.

4. Combined microdeletions in both the X and Y chromosomes, specifically in the long arms of both chromosomes, are clinically manifested as primary infertility, small testes, azoospermia, and hypoplasia of secondary sexual characteristics. It is possible that the combined effect of these two microdeletions has a cumulative genetic or synergistic gene effect that affects testicular development and sperm production.

5. Translocation involving Y chromosome microdeletions is clinically manifested as sperm production disorders and oligozoospermia.

6. Interstitial inversions in the Y chromosome arm can also be considered as microdeletions due to the significant reduction in the size of the long arm. These patients are carriers of interstitial inversions in the Y chromosome arm and have normal phenotypes. Clinically, they present with oligozoospermia. In one case, their wives experienced a miscarriage due to embryonic arrest during pregnancy, and they have not conceived since.