Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06154954 |
| Other study ID # |
MD-2024 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2022 |
| Est. completion date |
March 30, 2024 |
Study information
| Verified date |
November 2023 |
| Source |
Cairo University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Generally, azoospermia is characterized as obstructive (OA) or nonobstructive (NOA). Surgical
spermatozoa retrieval results vary in success rates. Proposing Intracytoplasmic Sperm
Injection (ICSI) to infertile couples with NOA depends on spermatogenesis, testicular
histology, and the ability to extract live spermatozoa from testis biopsy pieces.
Unfortunately, only 50% of testicular sperm extraction (TESE) results are positive (Zarezadeh
et al., 2021). Repeating sperm retrieval can cause TESE-induced hypoganadism, including
reduced testicular volume, erectile dysfunction, and testosterone deficiency (Eliveld et al.,
2018; Okada et al., 2002; Ozturk et al., 2011; Altinkilic et al., 2017; Akbal et al., 2017;
Binsaleh et al., 2017). The prognostic efficacy of hormonal, molecular, cytological, and
biochemical indicators for effective sperm recovery is limited (Corona et al., 2019).
Molecular, biochemical, clinical, and histopathological characteristics that identify NOA
males with advanced spermatogenesis foci up to the spermatozoon stage are crucial for
therapeutic purposes.
Recent research suggests that seminal protein expression patterns change dramatically between
azoospermic and fertile males (Zhang et al., 2021). TEX101 is a membrane protein only
produced by testicular germ cells and shed into seminal plasma (SP). Research suggests that
Tex101 malfunctions may impact male fertility (Jarvi et al., 2021). TEX101 is a germ cell
mono-specific marker present on sperm, round spermatids, and spermatocytes. At a threshold of
>5 ng/mL, TEX101 can distinguish NOA with Sertoli-cell only syndrome from other testis
histologies, such as hypospermatogenesis (67% specificity, 100% sensitivity) or maturation
arrest (54% sensitivity, 100% specificity) (Drabovich et al., 2013). ECM1, an epididymal
mono-specific marker, was below detection limits in males with OA semen but present in
detectable levels.
Research Template 3: Final Version: April 2019 NOA amounts in males. Clinical immunoassays of
ECM1 and TEX101 can predict sperm retrieval outcomes for assisted reproduction and lower the
cost of diagnosing azoospermia.
ELISA confirms that the lectin galactoside-binding, soluble 3 binding protein (LGALS3BP) is
expressed throughout the male genital tract. Its physiological role in cell-to-cell
interaction through extracellular matrix suggests a possible role in spermatogenesis,
particularly in the late stage, despite not being a germ-cell specific marker (Cannarella et
al., 2020). Patients with a good result of TESE had significantly greater levels of LGALS3BP
in the SP. A cut-off of 153 ng/mL was observed with 100% sensitivity and 45% specificity.
Freour et al. (2013) identified a key issue in their analysis due to the small number of
instances (n=40) with lower AUC values. Araujo and Bertolla (2021) propose that LGALS3BP may
predict TESE success in NOA patients before ICSI.
Description:
Azoospermia is mainly classified as obstructive azoospermia (OA) or nonobstructive
azoospermia (NOA). Surgical retrieval of spermatozoa yields various success rates. The chance
for proposing Intracytoplasmic Sperm Injection (ICSI) to infertile couple in case of NOA
depends on spermatogenesis, testicular histology and on the possibility to retrieve live
spermatozoa from testis biopsy fragments.
Unfortunately, this favorable outcome is obtained in only 50% of testicular sperm extraction
(TESE) (Zarezadeh et al., 2021). Repeating the sperm retrieval procedure may lead to TESE
induced hypoganadism (Eliveld et al., 2018) including the chance of reduced testicular volume
(Okada et al., 2002, Ozturk et al., 2011, Altinkilic et al., 2017), the probability of
erectile dysfunction (Akbal et al., 2017) and testosterone deficiency (Altinkilic et al.,
2017, Binsaleh et al., 2017). Various hormonal, molecular, cytological, biochemical
predictive parameters for successful sperm recovery offer limited predictive power (Corona et
al., 2019). It is obvious that the establishment of molecular, biochemical, clinical or
histopathological parameters that have a role in identifying subpopulations of NOA men
positive for foci of advanced spermatogenesis, up to the spermatozoon stage, has great
clinical importance. Recent studies demonstrated that the seminal protein expression pattern
could differ significantly between azoospermic patients and fertile men (Zhang et al., 2021).
Testis-expressed gene 101 (TEX101) is a cell membrane protein exclusively expressed by
testicular germ cells and shed into seminal plasma (SP). There have been indications that the
malfunction of Tex101 may affect male fertility (Jarvi et al., 2021). TEX101 is a germ cell
mono-specific marker found on sperm, round spermatids, and spermatocytes. TEX101, at a
threshold >5 ng/mL, could differentiate NOA underlined by Sertoli-cell only syndrome from NOA
due to other testis histology (e.g., hypospermatogenesis, with a 67% specificity and a 100%
sensitivity, or maturation arrest, with a 54% sensitivity and a 100% specificity) (Drabovich
et al., 2013). ECM1 is an epididymal mono-specific marker which was below detection limits
for men with OA, but present in the semen in detectable Research Template 3 Final Version: Ap
ril 2019 amounts in men with NOA. Clinical immunoassays of extracellular matrix protein1
(ECM1) and TEX101 have the potential to facilitate prediction of the outcome of sperm
retrieval procedures used for assisted reproduction, and reduce the total cost of azoospermia
diagnosis. The lectin galactoside-binding, soluble 3 binding protein (LGALS3BP) is expressed
in the whole male genital tract, with an expression level compatible with ELISA confirmation
method, and because its physiological role in cell to cell interaction through extracellular
matrix supports a possible role in spermatogenesis especially the late stage of spermatogenic
activity, even if it is not a germ-cell specific marker (Cannarella et al., 2020).
Significantly higher levels of lectingalactoside-binding, soluble 3 binding protein
(LGALS3BP) in the SP were found in patients with a positive outcome of TESE. The cut-off of
153 ng/mL was reported with a sensitivity of 100% and a specificity of 45%. However, the
limited number of cases (n=40) with a consequent lower AUC value represent a major flaw in
that study (Freour et al., 2013). Araujo and Bertolla suggest that LGALS3BP could potentially
be used as a predictive marker of success of TESE in NOA patients before ICSI (Araujo and
Bertolla 2021).
