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

NCT05110391 | Completed FDA Drug

• 1 other identifier: ANDROFERT-03-20
• Study Type: observational
• Target: 616
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non-obstructive Azoospermia; Hormone Deficiency; Hypogonadism, Male; Male Infertility

Keywords

microdissection testicular sperm extraction; human chorionic gonadotropin; sperm retrieval rates; follicle-stimulating hormone; azoospermia; spermatogenic failure

Outcome Measures

Primary Outcomes (1)

• Sperm retrieval rates

  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 Outcomes (3)

• Sperm retrieval rates according to hypogonadism status

  At least 3 months

• Sperm retrieval rates according to histopathology findings

  At least 3 months

• Predictive factors for sperm retrieval success

  At least 3 months

Study Arms (2)

NOA_Treated

Hypogonadal patients with non-obstructive azoospermia who received gonadotropin therapy before sperm retrieval

Drug: Hormonal Therapy Agent

NOA_Untreated

Hypogonadal patients with non-obstructive azoospermia who did not receive gonadotropin therapy before sperm retrieval

Interventions

Hormonal Therapy Agent DRUG

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.

Also known as: recombinant human chorionic gonadotropin, recombinant FSH

NOA_Treated

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Hypogonadal patients with non-obstructive azoospermia seeking fertility.

You may qualify if:

• 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.

You may not qualify if:

• Patients subjected to sperm retrieval using percutaneous or non-microsurgical testicular biopsies and those with a history of a previous sperm retrieval attempt.
• Patients who had used any medication with known potential gonadotoxic effects six months before enrollment and patients under gonadotropin treatment who lost follow-up.
• Patients with NOA due to hypogonadotropic hypogonadism.
• 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.
• NOA patients with baseline total testosterone levels above 350 ng/dL.

Sponsors & Collaborators

• ANDROFERT - Clinica de Andrologia e Reproducao Humana: lead

Study Sites (1)

Androfert

Campinas, São Paulo, 13075-460, Brazil

Location

Related Publications (12)

• Andrade DL, Viana MC, Esteves SC. Differential Diagnosis of Azoospermia in Men with Infertility. J Clin Med. 2021 Jul 16;10(14):3144. doi: 10.3390/jcm10143144.

  PMID: 34300309 BACKGROUND

• Esteves SC, Prudencio C, Seol B, Verza S, Knoedler C, Agarwal A. Comparison of sperm retrieval and reproductive outcome in azoospermic men with testicular failure and obstructive azoospermia treated for infertility. Asian J Androl. 2014 Jul-Aug;16(4):602-6. doi: 10.4103/1008-682X.126015.

  PMID: 24759580 BACKGROUND

• Hussein A, Ozgok Y, Ross L, Rao P, Niederberger C. Optimization of spermatogenesis-regulating hormones in patients with non-obstructive azoospermia and its impact on sperm retrieval: a multicentre study. BJU Int. 2013 Mar;111(3 Pt B):E110-4. doi: 10.1111/j.1464-410X.2012.11485.x. Epub 2012 Sep 7.

  PMID: 22958644 BACKGROUND

• Reifsnyder JE, Ramasamy R, Husseini J, Schlegel PN. Role of optimizing testosterone before microdissection testicular sperm extraction in men with nonobstructive azoospermia. J Urol. 2012 Aug;188(2):532-6. doi: 10.1016/j.juro.2012.04.002. Epub 2012 Jun 15.

  PMID: 22704105 BACKGROUND

• Achermann APP, Pereira TA, Esteves SC. Microdissection testicular sperm extraction (micro-TESE) in men with infertility due to nonobstructive azoospermia: summary of current literature. Int Urol Nephrol. 2021 Nov;53(11):2193-2210. doi: 10.1007/s11255-021-02979-4. Epub 2021 Aug 19.

  PMID: 34410586 BACKGROUND

• Arshad MA, Majzoub A, Esteves SC. Predictors of surgical sperm retrieval in non-obstructive azoospermia: summary of current literature. Int Urol Nephrol. 2020 Nov;52(11):2015-2038. doi: 10.1007/s11255-020-02529-4. Epub 2020 Jun 9.

  PMID: 32519242 BACKGROUND

• Laursen RJ, Elbaek HO, Povlsen BB, Lykkegaard J, Jensen KBS, Esteves SC, Humaidan P. Hormonal stimulation of spermatogenesis: a new way to treat the infertile male with non-obstructive azoospermia? Int Urol Nephrol. 2019 Mar;51(3):453-456. doi: 10.1007/s11255-019-02091-8. Epub 2019 Feb 11. No abstract available.

  PMID: 30756283 BACKGROUND

• Esteves SC. Clinical management of infertile men with nonobstructive azoospermia. Asian J Androl. 2015 May-Jun;17(3):459-70. doi: 10.4103/1008-682X.148719.

  PMID: 25677138 BACKGROUND

• Esteves SC. Microdissection testicular sperm extraction (micro-TESE) as a sperm acquisition method for men with nonobstructive azoospermia seeking fertility: operative and laboratory aspects. Int Braz J Urol. 2013 May-Jun;39(3):440; discussion 441. doi: 10.1590/S1677-5538.IBJU.2013.03.21.

  PMID: 23849579 BACKGROUND

• Esteves SC, Agarwal A. Reproductive outcomes, including neonatal data, following sperm injection in men with obstructive and nonobstructive azoospermia: case series and systematic review. Clinics (Sao Paulo). 2013;68 Suppl 1(Suppl 1):141-50. doi: 10.6061/clinics/2013(sup01)16.

  PMID: 23503964 BACKGROUND

• Tharakan T, Corona G, Foran D, Salonia A, Sofikitis N, Giwercman A, Krausz C, Yap T, Jayasena CN, Minhas S. Does hormonal therapy improve sperm retrieval rates in men with non-obstructive azoospermia: a systematic review and meta-analysis. Hum Reprod Update. 2022 Aug 25;28(5):609-628. doi: 10.1093/humupd/dmac016.

  PMID: 35526153 BACKGROUND

• Esteves SC, Achermann APP, Miyaoka R, Verza S Jr, Fregonesi A, Riccetto CLZ. Clinical factors impacting microdissection testicular sperm extraction success in hypogonadal men with nonobstructive azoospermia. Fertil Steril. 2024 Oct;122(4):636-647. doi: 10.1016/j.fertnstert.2024.06.013. Epub 2024 Jun 22.

  PMID: 38909671 DERIVED

Biospecimen

Retention: NONE RETAINED

spermatozoa

MeSH Terms

Conditions

Eunuchism; Infertility, Male; Azoospermia

Interventions

Chorionic Gonadotropin

Condition Hierarchy (Ancestors)

Hypogonadism; Gonadal Disorders; Endocrine System Diseases; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Infertility; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pregnancy Proteins; Proteins

Study Officials

• Sandro Esteves, MD., PhD.

  ANDROFERT - Andrology and Human Reproduction Cente

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director

Study Record Dates

• First Submitted: September 27, 2021
• First Posted: November 8, 2021
• Study Start: February 1, 2014
• Primary Completion: September 15, 2021
• Study Completion: September 15, 2021
• Last Updated: November 3, 2022

Record last verified: 2022-11

Locations

BR (1)