The Y chromosome microdeletions are one of the most common causes for male infertility (6). The Y chromosome AZF region contains many genes that are important for spermatogenesis. The region known as azoospermia factor (AZF) includs AZFa, AZFb, and AZFc (7). The AZFa region contains USP9Y, DBY, the AZFb region contains CDY2, EIF1AY, HSFY, PRY, RBMYL1, RPS4YS, SMCY, XKRY, and the AZFc region contains BPY2, CDY1, CSPG4LY, DAZ, and GOLGA2LY (8). Study by L. Tiepolo et al. shows Y chromosome microdeletions to be involved in testicle differentiation and testicle maturation (9). Y chromosome microdeletion plays an important role in predicting sperm extraction from testes. Some studies have shown that Y chromosome microdeletion is associated with testicular cancer and recurrent pregnancy loss (10–12).
Our groups Y chromosome microdeletion study is the first-ever study in Mongolia carried on infertile patients. The study data shows a frequency of Y chromosome microdeletion in the among 75 patients with azoospermia and severe oligozoospermia was 2.66%. The frequency of Y chromosome microdeletion for infertile male patients was 0.7–34.5%, with an average of 8.2% (13, 14). According to the 2008 report, the frequency of AZF microdeletion among infertile men in Sweden, Germany, and Austria had showed the lowest frequency at less than 2.5% whereas the highest showed more than 10% in Australia, China, and Brazil (4). A comparative study carried throughout Asia among patients with idiopathic azoospermia or severe oligozoospermia showed frequencies of 19.4% in China, 10.6–11.7% in Taiwan, 15.8% in Japan, 9.6–12.0% in India, 3.2% in Saudi Arabia, 3.3% in Turkey, and 2.6% in Kuwait (15–17). We used six different markers for AZFa regions sY84, sY86, AZFb regions sY127, sY134, AZFc regions sY254 and sY255 according to guidelines published by the European Academy of Andrology (EAA) and the European Molecular Genetics Quality Network (EMQN). In a 2012 study of Y chromosome microdeletion with 115 patients in Iran, 1.7% showed deletion in AZFc and AZFbc. They used six markers such as sY84, sY86 (AZFa), sY127, sY134 (AZFb), sY254, sY255 (AZFc) which are the same as what we used in our study (18). In 2011 study, Haluk Akin et al reported Y chromosome microdeletion in 7 patients (3.93%) among 178 infertile men. They were detected in the AZFc and AZFa region (19). From the study of 1738 infertile men by Yong-Sheng Zhang et al in China, the frequency of Y chromosome microdeletion was 8.57%. Of note, the frequency of the AZFa deletion was 2.2%. From the study of 3654 males by Totonchi et al., the frequency of Y chromosome deletion was 5.06%. The deletion in AZFa was 2.16%, which is similar to our results (20, 21). Most patients with AZFa deletion were diagnosed with Sertoli cell only syndrome (22). In the case of complete deletion of AZFa, no sperm was retrieved. However, in partial deletions, it is reported that sperm is retrieved by TESE (22, 23). In our study, the patient with Y chromosome AZFamicrodeletion was 31 years old, with azoospermia, no sperm retrieved from the testis, and histologic examination showed Sertoli cell only syndrome. These results were similar to the results from Kamp et al (22).
Both patients with Y chromosome microdeletion had azoospermia, and FSH and LH hormone levels were higher than normal. FSH was 40.93 ± 17.07 mIU/ml and LH hormone was 12.5 ± 0.71 mIU/ml, but there was a significant difference in FSH hormone level compared to non Y chromosome microdeletion group (P < 0.05). These results were similar to the results from Li-Quan Wang and Rajeev Kumar et al (24, 25).
The mean age of the sperm retrieval group was 38.3 ± 5.1 years old. The mean age of the sperm non-retrieval group was 31.5 ± 3.63 years old, showing a significant difference. Studies by Yi-Ru Tsai or Kuo-Chung Lan et al showes that IVF results, pregnancy rates, and miscarriage rates correlate with male age (26). According to the results of a micro TESE study by Noritoshi Enatsu and Hideaki Miyake, the average age of the sperm retrieval group from the testis was 35.0 ± 5.6, and the average age of the sperm not-retrieval group was 33.2 ± 4.9 (p < 0.05) (27).
The 14 patients with no sperm retrieved by TESE were diagnosed testicular histopathology. Histopathological examination showed Sertoli cell only in 12 patients (85.71%) and seminiferous tubule hyalinization in 2 patients (14.29%). Of the 25 patients who had sperm retrieved from TESE, 18 (72%) patients had In Vitro Fertilization (IVF) treatment. Of these, two (11.1%) patients were embryo banking and sixteen (88.9%) had embryo transfer. Six patients (37.5%) had successfully clinical pregnancy. Where one patient gave birth to a twin baby and others are successful in ongoing pregnancy.
In conclusion, current data shows that there is a low frequency of Y chromosome microdeletions, in azoospermic and severe oligozoospermic infertile men in the Mongolian population. In the case of non-obstructive azoospermia, AZFa, AZFb and AZFb/c microdeletion occurs in 1–2%, but sperm is not retrieved by TESE. So there is no need for unnecessary TESE procedure. In patients with AZFc microdeletion, sperm formation functions properly. IVF can be performed with sperm of a patient with microdeletion of AZFc, which can result in a successful pregnancy. However, the microdeletion of the AZFc part is inherited to his male child. However, we recommend a larger group of patients and controls to be screened for this microdeletion for confirmation.