Surgical Sperm Retrieval in Non-obstructive Azoospermic Men: mTESE vs. TESA

NCT03550716 | Completed

• 1 other identifier: H-16033784
• Study Type: interventional
• Target: 110
• Locations: 2 countries
• Sites: 4

Brief Summary

Infertility is a significant social- and health problem in the Western World and at the moment in Denmark one in ten babies are born with the help of assisted reproduction. In 50% of infertile couples a male factor can be identified as a contributing cause (1). Azoospermia is defined as the absence of spermatozoa in the ejaculate and it is a condition affecting 10-15% of infertile men (2, 3). Azoospermia is divided into obstructive azoospermia (OA) and nonobstructive azoospermia (NOA) of which the latter constitutes 60% (2, 3). In NOA the production of spermatozoa in the testis is either absent or markedly decreased. Since 1999 microdissection testicular sperm extraction (mTESE) has become the preferred treatment option for NOA in many centers worldwide (4). The procedure is performed in general anesthesia using an operating microscope to carefully examine the entire testicular tissue for the presence of spermatozoa which can be used for assisted reproduction. An alternative to mTESE is a percutaneous testicular sperm aspiration (TESA) or needle biopsy. This procedure is simple to perform using a biopsy needle to aspirate testicular tissue. The aspirated tissue is examined for the presence of spermatozoa that can be used in assisted reproduction. Today there is no robust evidence on the optimal sperm retrieval protocol on men with NOA. This is in part due to the fact that no randomized trials have been performed to compare procedures. This study is the first to randomize procedures for surgical sperm retrieval. Hypothesis In men with NOA, the investigators hypothesize that TESA is a viable first line approach compared to mTESE in regards to success rates of finding spermatozoa, complication rates and pregnancy outcomes. A total of 110 men will be randomized to either mTESE or TESA and the rates of finding spermatozoa will be compared. However, for ethical reasons, because some believe mTESE have a greater chance of finding sperm cells, all men with a failed TESA will have a mTESE afterwards.

Conditions

Non-obstructive Azoospermia

Keywords

azoospermia; microdissection testicular sperm extraction; testicular sperm aspiration; male infertility; surgical sperm retrieval

Outcome Measures

Primary Outcomes (1)

• Sperm retrieval rate

  Rate of succesful sperm retrievals defined as at least one spermatozoa found suitable for intracytoplasmic sperm injection (ICSI)

  Assessed immediately after the procedure

Secondary Outcomes (25)

• Conversion rate to mTESE

  Recorded immediately after the procedure

• Sperm retrieval rate after salvage mTESE

  Recorded immediately after the procedure

• Complication rates

  Recorded in the first 6 months after surgery

• Pregnancy outcomes

  Recorded in the first 9-15 months after surgery

• Difference in perceived stress scale (PSS) score

  Three months before to three months after surgery

Study Arms (2)

mTESE

ACTIVE COMPARATOR

Patients randomized to mTESE

Procedure: mTESE

TESA

ACTIVE COMPARATOR

Patients randomized to TESA

Procedure: TESA

Interventions

mTESE PROCEDURE

mTESE is performed according to the initial description by Schlegel (4). General anesthesia is used. Midline incision of the scrotum is made and carried down to the level of the tunica vaginalis, which is opened to deliver the testis. Equatorial incision is made and the testis bivalved. The operating microscope is used to identify plump-appearing seminiferous tubules, and biopsies are taken from these areas. These samples are examined by an embryologist in the operating room after initial gross dispersion by passing the tissue through a 24G angiocatheter. The procedure is stopped if spermatozoa are found. If no plump tubules are found, random biopsies targeting every area of the testis are taken. If necessary the procedure is carried out on the contralateral testis. Hemostasis is obtained with careful bipolar cautery, and the tunica albuginea and the tunica vaginalis are closed with a running 4-0 Vicryl. Standard scrotal closure is performed and gentle pressure dressing is applied.

Also known as: Microdissection testicular sperm extraction

mTESE

TESA PROCEDURE

In general anesthesia an 18 gauge needle is introduced into each testis, and negative pressure applied with a 10 ml syringe. Multiple passes throughout the entire testis, numbering 50-100 passes, are made through a single percutaneous/tunical entry and continued until tissue is visible in the hub of the needle. This is removed by brisk extraction of the needle and pressure held to tamponade bleeding. The aspirated tissue is examined by an embryologist in the operating room after initial gross dispersion by passing the tissue through a 24 gauge angiocatheter.

Also known as: Percutaneous testicular sperm aspiration

TESA

Eligibility Criteria

• Age: 18 Years - 70 Years
• Gender Eligibility Details: 46XY
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Azoospermia verified in at least two semen samples within the past six months, including assessment of the centrifuged pellet as per the WHO 5th edition (13)
• Testis volume (Prader's orchidometer) ≤ 15ml on both sides
• No indication of obstructive causes of azoospermia in medical history or physical examination (ex. absent vas deferens, vasectomy, scrotal trauma/injury, hernia repair or other operations potentially damaging the vas deferens)
• Capable and legally competent individual

You may not qualify if:

• Previous attempts of surgical sperm retrieval
• Previous testicular biopsy
• Anejaculation
• Retrograde ejaculation
• Bleeding disorders rendering surgery too high a risk
• Klinefelters Syndrome
• XX male
• AZFa/b microdeletion
• CFTR mutation
• Inability to understand and/or stick to the written information
• Patients not deemed suitable for general anesthesia
• A patient can at any time during the study withdraw their consent of participation
• Normal histology on testis biopsy following TESA or mTESE

Sponsors & Collaborators

• Herlev and Gentofte Hospital: lead
• Rigshospitalet, Denmark: collaborator
• Holbaek Sygehus: collaborator
• Skane University Hospital: collaborator
• University of Michigan: collaborator

Study Sites (4)

Rigshospitalet

Copenhagen, DK-2100, Denmark

Location

Herlev and Gentofte Hospital

Herlev, DK-2730, Denmark

Location

Holbæk Sygehus

Holbæk, DK-4300, Denmark

Location

Malmö University Hospital

Malmo, 20502, Sweden

Location

Related Publications (15)

• Sharlip ID, Jarow JP, Belker AM, Lipshultz LI, Sigman M, Thomas AJ, Schlegel PN, Howards SS, Nehra A, Damewood MD, Overstreet JW, Sadovsky R. Best practice policies for male infertility. Fertil Steril. 2002 May;77(5):873-82. doi: 10.1016/s0015-0282(02)03105-9. No abstract available.

  PMID: 12009338 BACKGROUND

• Jarow JP, Espeland MA, Lipshultz LI. Evaluation of the azoospermic patient. J Urol. 1989 Jul;142(1):62-5. doi: 10.1016/s0022-5347(17)38662-7.

  PMID: 2499695 BACKGROUND

• Willott GM. Frequency of azoospermia. Forensic Sci Int. 1982 Jul-Aug;20(1):9-10. doi: 10.1016/0379-0738(82)90099-8. No abstract available.

  PMID: 7095683 BACKGROUND

• Schlegel PN. Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. Hum Reprod. 1999 Jan;14(1):131-5. doi: 10.1093/humrep/14.1.131.

  PMID: 10374109 BACKGROUND

• Dabaja AA, Schlegel PN. Microdissection testicular sperm extraction: an update. Asian J Androl. 2013 Jan;15(1):35-9. doi: 10.1038/aja.2012.141. Epub 2012 Dec 17.

  PMID: 23241638 BACKGROUND

• Deruyver Y, Vanderschueren D, Van der Aa F. Outcome of microdissection TESE compared with conventional TESE in non-obstructive azoospermia: a systematic review. Andrology. 2014 Jan;2(1):20-4. doi: 10.1111/j.2047-2927.2013.00148.x. Epub 2013 Nov 6.

  PMID: 24193894 BACKGROUND

• Donoso P, Tournaye H, Devroey P. Which is the best sperm retrieval technique for non-obstructive azoospermia? A systematic review. Hum Reprod Update. 2007 Nov-Dec;13(6):539-49. doi: 10.1093/humupd/dmm029. Epub 2007 Sep 24.

  PMID: 17895238 BACKGROUND

• Bernie AM, Mata DA, Ramasamy R, Schlegel PN. Comparison of microdissection testicular sperm extraction, conventional testicular sperm extraction, and testicular sperm aspiration for nonobstructive azoospermia: a systematic review and meta-analysis. Fertil Steril. 2015 Nov;104(5):1099-103.e1-3. doi: 10.1016/j.fertnstert.2015.07.1136. Epub 2015 Aug 8.

  PMID: 26263080 BACKGROUND

• Amer M, Ateyah A, Hany R, Zohdy W. Prospective comparative study between microsurgical and conventional testicular sperm extraction in non-obstructive azoospermia: follow-up by serial ultrasound examinations. Hum Reprod. 2000 Mar;15(3):653-6. doi: 10.1093/humrep/15.3.653.

  PMID: 10686214 BACKGROUND

• Okada H, Dobashi M, Yamazaki T, Hara I, Fujisawa M, Arakawa S, Kamidono S. Conventional versus microdissection testicular sperm extraction for nonobstructive azoospermia. J Urol. 2002 Sep;168(3):1063-7. doi: 10.1016/S0022-5347(05)64575-2.

  PMID: 12187223 BACKGROUND

• Ramasamy R, Yagan N, Schlegel PN. Structural and functional changes to the testis after conventional versus microdissection testicular sperm extraction. Urology. 2005 Jun;65(6):1190-4. doi: 10.1016/j.urology.2004.12.059.

  PMID: 15922422 BACKGROUND

• Jensen CF, Ohl DA, Hiner MR, Fode M, Shah T, Smith GD, Sonksen J. Multiple needle-pass percutaneous testicular sperm aspiration as first-line treatment in azoospermic men. Andrology. 2016 Mar;4(2):257-62. doi: 10.1111/andr.12143. Epub 2016 Jan 20.

  PMID: 26789006 BACKGROUND

• WHO laboratory manual for the examination and processing of human semen. World Health Organization. 2010;5th ed.

  BACKGROUND

• Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.

  PMID: 15273542 BACKGROUND

• Argyle CE, Harper JC, Davies MC. Oocyte cryopreservation: where are we now? Hum Reprod Update. 2016 Jun;22(4):440-9. doi: 10.1093/humupd/dmw007. Epub 2016 Mar 22.

  PMID: 27006004 BACKGROUND

MeSH Terms

Conditions

Azoospermia; Infertility, Male

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Infertility; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The randomization will be performed when the patient is asleep.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Trial type: Clinical randomized multi-center controlled trial Randomization: Block randomization is performed with the use of a computer generated block randomization list Participants: Patients with NOA undergoing fertility treatment

Study Record Dates

• First Submitted: May 14, 2018
• First Posted: June 8, 2018
• Study Start: April 1, 2017
• Primary Completion: October 30, 2020
• Study Completion: April 30, 2021
• Last Updated: September 10, 2021

Record last verified: 2021-09

Locations

SE (1); DK (3)