Sperm Retrieval Rates in Non-obstructive Azoospermic Men Subjected to Gonadotropin Therapy
Condition: Non-obstructive Azoospermia; Hormone Deficiency; Hypogonadism, Male; Male Infertility
MeSH terms: Infertility; Infertility, Male; Azoospermia; Hypogonadism; Eunuchism
Study type: Observational

Summary: 
      Azoospermia is defined as the complete absence of spermatozoa in the ejaculate. Two-thirds of
      azoospermic patients have non-obstructive azoospermia (NOA); the latter comprises up to 10%
      of infertile men overall. NOA is an untreatable testicular disorder associated with
      spermatogenic failure and is the most severe male infertility phenotype. Among the available
      surgical sperm retrieval techniques, microdissection testicular sperm extraction (micro-TESE)
      is the procedure of choice due to its high sperm retrieval success rates (SRR), minimal
      tissue extraction, and low complication rates. Even with the use of micro-TESE, the
      likelihood of retrieving sperm in patients with NOA remain suboptimal (40% to 60%).
      Hypogonadism is detected in approximately half of the patients with NOA. Given the role of
      intratesticular testosterone (ITT) levels for spermatogenesis, some studies have explored the
      clinical utility of testosterone optimization by medical therapy before sperm retrieval.

      Moreover, some investigators have hypothesized that the follicle-stimulating hormone (FSH)
      reset might increase the expression of FSH receptors and improve Sertoli cell function.
      Hormonal therapy with human chorionic gonadotropin (hCG) has been shown to improve ITT
      production and decrease FSH levels in patients with NOA. The investigators, therefore,
      designed an observational cohort study aiming to evaluate whether hormone stimulation with
      gonadotropins (e.g., hCG alone or combined with FSH) previous to micro-TESE increases sperm
      retrieval rates in hypogonadal infertile men with NOA, candidates for sperm retrieval. The
      investigators hypothesize that optimizing ITT production and resetting FSH levels may improve
      spermatogenesis and successful sperm recovery.
    

Detailed description: 
      A single-center cohort study was conducted based on prospectively collected data inputted in
      an electronic medical record database, subsequently extracted and analyzed.

      The diagnosis of NOA was based on medical history, physical examination, semen analysis,
      reproductive hormone measurements, genetic and imaging studies, and confirmed by
      histopathology.

      Hypogonadism was defined based on total testosterone levels equal to or below 350 ng/dL,
      measured on a peripheric blood specimen taken in the morning (8:00 to 10:00 am).

      Sample size calculation:

      Based on existing evidence concerning SRR in patients subjected to micro-TESE with and
      without medical treatment to boost testosterone production, the investigators estimated a
      sample size of 464 participants (232 per group) to have an 80% chance of detecting, as
      significant at the 5% level, an increase in the primary outcome measure from 41% in the
      control group to 55% in the experimental group.

      Statistical Analysis:

      Demographic data will include patient age, BMI, infertility cause, testicular volume,
      reproductive hormone levels, histopathology findings, infertility duration, presence of
      clinical varicocele, and history of varicocele repair. Treatment variables will include type,
      dose, and duration of gonadotropin administration, change in reproductive hormone levels pre-
      vs. post-treatment, and sperm retrieval outcomes.

      Continuous data will be presented as median and 25-75% interquartile range. Categorical data
      will be described by the number of cases and percentages. As appropriate, categorical and
      continuous data will be analyzed using the Pearson Chi-square and Kruskal-Wallis or Wilcoxon
      test. Logistic regression analyses will be conducted to examine the association between
      demographic and treatment covariates and the binary response 'sperm retrieval success'
      (yes/no). Computations will be carried out using JMP® PRO 13 and SAS 9.3 (SAS Institute,
      Cary, North Carolina, USA).
    

Intervention name(s): Hormonal Therapy Agent
Intervention type(s): Drug
Intervention description(s): Consecutive patients with NOA and hypogonadism (defined by baseline total testosterone levels equal or below 350 ng/dL) subjected to microdissection testicular sperm extraction who received or not pre-sperm retrieval gonadotropin therapy.
Other intervention name(s): recombinant human chorionic gonadotropin; recombinant FSH
Intervention MeSH terms: Chorionic Gonadotropin
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        Hypogonadal patients with non-obstructive azoospermia seeking fertility.
      
Biospecimen description: 
      spermatozoa
    
Keywords: microdissection testicular sperm extraction; human chorionic gonadotropin; sperm retrieval rates; follicle-stimulating hormone; azoospermia; spermatogenic failure