Sperm Retrieval Rates in Non-obstructive Azoospermic Men Subjected to Gonadotropin Therapy

November 1, 2022 updated by: Sandro C. Esteves, ANDROFERT - Clinica de Andrologia e Reproducao Humana

Sperm Retrieval Rates by Microdissection Testicular Sperm Extraction in Non-obstructive Azoospermic Men Subjected to Gonadotropin Therapy

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Observational

Enrollment (Actual)

616

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • São Paulo
      • Campinas, São Paulo, Brazil, 13075-460
        • Androfert

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Sampling Method

Probability Sample

Study Population

Hypogonadal patients with non-obstructive azoospermia seeking fertility.

Description

Inclusion Criteria:

  • Consecutive NOA patients with a baseline total testosterone level equal to or below 350 ng/dL who had a sperm retrieval procedure by microdissection testicular sperm extraction (micro-TESE) during the study period. Only patients with histopathology-confirmed NOA, absence of Y-chromosome microdeletion in the azoospermia factor 'a' (AZFa) and/or azoospermia factor 'b' (AZFB) region, and with a complete data record for analysis of primary and secondary outcomes were included.

Exclusion Criteria:

  1. Patients subjected to sperm retrieval using percutaneous or non-microsurgical testicular biopsies and those with a history of a previous sperm retrieval attempt.
  2. Patients who had used any medication with known potential gonadotoxic effects six months before enrollment and patients under gonadotropin treatment who lost follow-up.
  3. Patients with NOA due to hypogonadotropic hypogonadism.
  4. Patients who had any number of sperm detected in the ejaculate by routine semen analysis with centrifugation before micro-TESE, including the analysis carried out on the surgery day. The latter relates to the fact that our study is designed to include only patients with NOA confirmed by histopathology, from a specimen obtained during micro-TESE.
  5. NOA patients with baseline total testosterone levels above 350 ng/dL.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
NOA_Treated
Hypogonadal patients with non-obstructive azoospermia who received gonadotropin therapy before sperm retrieval
Drug: Hormonal Therapy Agent
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 Names:
  • recombinant human chorionic gonadotropin
  • recombinant FSH
NOA_Untreated
Hypogonadal patients with non-obstructive azoospermia who did not receive gonadotropin therapy before sperm retrieval

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sperm retrieval rates
Time Frame: At least 3 months
Sperm retrieval success rates by micro-TESE in men with non-obstructive azoospermia subjected or not to pre-operative hormonal stimulation
At least 3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sperm retrieval rates according to hypogonadism status
Time Frame: At least 3 months
Sperm retrieval success rates by micro-TESE in men with non-obstructive azoospermia subjected or not to pre-operative hormonal stimulation, according to hypogonadism categories based on baseline total testosterone levels
At least 3 months
Sperm retrieval rates according to histopathology findings
Time Frame: At least 3 months
Sperm retrieval success rates by micro-TESE in men with non-obstructive azoospermia subjected or not to pre-operative hormonal stimulation, according to testis biopsy histopathology findings
At least 3 months
Predictive factors for sperm retrieval success
Time Frame: At least 3 months
Assessment of independent co-variables affecting the binary response sperm retrieval (yes/no)
At least 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ANDROFERT - Clinica de Andrologia e Reproducao Humana

Investigators

  • Principal Investigator: Sandro Esteves, MD., PhD., ANDROFERT - Andrology and Human Reproduction Cente

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2014

Primary Completion (Actual)

September 15, 2021

Study Completion (Actual)

September 15, 2021

Study Registration Dates

First Submitted

September 27, 2021

First Submitted That Met QC Criteria

November 2, 2021

First Posted (Actual)

November 8, 2021

Study Record Updates

Last Update Posted (Actual)

November 3, 2022

Last Update Submitted That Met QC Criteria

November 1, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANDROFERT-03-20

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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