Comparison of intracytoplasmic sperm injection outcomes in azoospermic men who underwent testicular sperm extraction vs. microdissection testicular sperm extraction: A cross-sectional study

Abstract Background Outcomes of intracytoplasmic sperm injection (ICSI) may be different in azoospermic men who undergo testicular sperm extraction (TESE) vs. microdissection-TESE (micro-TESE). Objective This study was conducted to compare the ICSI outcomes in men who underwent TESE vs. micro-TESE due to obstructive azoospermia and nonobstructive azoospermia, respectively. Materials and Methods A total of310azoospermic men who underwent ICSI from September 2016 to September 2020 were enrolled in this cross-sectional study and divided into two groups (172 cases in the TESE and 138 cases in the micro-TESE group). The paternal and maternal age, and the fertilization, biochemical pregnancy, abortion and live birth rates were compared between the two groups. Results Maternal mean age was significantly higher in the TESE group (34.9 ± 4.2 yr vs. 32.3 ± 5.7 yr). The fertilization and biochemical pregnancy rates were significantly higher in the TESE group, but the abortion rate was similar in the two groups. The live birth rate was higher in the TESE group, but this difference was not significant (p = 0.06). Also, the maternal and paternal age did not affect ICSI outcomes. Conclusion Individuals who underwent TESE had higher fertilization and biochemical pregnancy rates than those who underwent micro-TESE, but the live birth rate was not significantly different.

Azoospermia is defined as the complete absence of sperm in the semen sample and is categorized into two groups: obstructive (OA) and nonobstructive (NOA) (4,5). With the advent of intracytoplasmic sperm injection (ICSI) in 1992, the azoospermic men who once were considered sterile, regained the chance to have their own biological children (6). OA is further categorized as primary (congenital) or secondary (acquired).
Assisted reproductive techniques are commonly advised in cases of the primary form and when the reconstruction of the complex secondary structure is impossible. Given that there is normal spermatogenesis in the testes in OA, sperms can be retrieved through different methods (5).
Conversely, azoospermia in NOA may be due to disrupted spermatogenesis. Given the aggressiveness and low success rate of sperm retrieval by testicular sperm extraction (TESE) in NOA, Schlegel introduced microdissection sperm retrieval (micro-TESE) to improve the sperm recovery rate and testis viability preservation. The sperm retrieval rate of micro-TESE is about 16%-63% (7,8).
Different studies have reported different fertilization, pregnancy, miscarriage and live birth rates between these two groups. For instance, one study found lower fertilization rates in men with NOA but similar clinical pregnancy rates between OA and NOA groups (5). Some studies have reported similar ICSI outcomes in men with OA vs. NOA, including a retrospective study in 2008 which found that the miscarriage rate did not significantly differ between the NOA and OA groups (9). Other studies have shown higher pregnancy rates in OA cases (10)(11)(12). Furthermore, some studies have revealed that factors like maternal age can influence the success rate of ICSI (13).
For successful in vitro fertilization, it is necessary for both the sperm and oocyte to be high quality (14,15). Some oocyte quality criteria that can be assessed non-invasively are the dispersion cumulus cell, and the existence of a first polar body which shows nuclear maturity and no sign of atresia. Other abnormalities which can affect oocyte quality and total fertilization failure (TFF) are the accumulation of smooth endoplasmic reticulum discs and asynchronous nuclear and cytoplasmic maturation (16).

Materials and Methods
A total of 310 azoospermic men who underwent ICSI for the first time from September 2016 to September 2020 in the Yazd Reproductive Sciences Institute, a tertiary referral center for infertility in Iran, were enrolled in this retrospective cross-sectional study. Cases were divided into two groups: one group underwent TESE for sperm extraction (n = 172) and the other group underwent micro-TESE (n = 138). The inclusion criteria for the TESE group were normal testes volume and acceptable hormonal assay (which was defined as blood luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels < two times higher than the normal range).
The inclusion criteria for the micro-TESE group were low testicular volume and high hormonal assay (blood LH and FSH levels ≥ two times higher than the normal range).
The inclusion criterion of the female partner was the best quality of oocyte (spherical, no cytoplasmic granules, no aggregation of the smooth endoplasmic reticulum discs, no vacuoles). The included women were aged < 40 yr and the men were < 50 yr.
Men with a history of bilateral vasectomy, varicocelectomy, a testicular tumor, chemoradiation, hypogonadotropic hypogonadism, epididymo-orchitis, or genetic abnormality were excluded from the study.

Results
Over  Table   I.
Logistic regression analysis was done to evaluate the impact of maternal and paternal age on ICSI outcomes, and it revealed that there was no relationship between these variables (Table II).  (26). However, in research conducted in 2015, no differences were observed in the fertility rate or clinical pregnancy rate between the OA and NOA groups (27). In 2005 a metaanalysis revealed that fertilization rate is lower in NOA cases (5).
A retrospective study showed lower pregnancy rates in men with NOA than in men with OA (9).
In another study, it was indicated that the clinical pregnancy rate in men with NOA was lower than in men with OA (28). In another comparison of NOA and OA outcomes, the implantation rate was found to be lower in the NOA group (29).
Factors that can affect the outcome of ICSI when using non-ejaculated sperm include the azoospermia etiology, the age of the female partner, and the sperm status (fresh or thawed) (30). A younger maternal age has been found to have a positive effect on the fertilization and clinical pregnancy rates of OA men (30). However, some studies have suggested that maternal age does not impact fertilization rates but only affects pregnancy rates (13,31

Conclusion
This study confirmed previous findings that men with OA had significantly higher fertilization and biochemical pregnancy rates than men with NOA.
The live birth rate was higher in men with OA, but this difference was not significant.