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

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ClinicalTrials.gov Identifier: NCT03550716
Recruitment Status : Recruiting
First Posted : June 8, 2018
Last Update Posted : June 8, 2018
Sponsor:
Collaborators:
Rigshospitalet, Denmark
Holbaek Sygehus
Skane University Hospital
University of Michigan
Information provided by (Responsible Party):
Christian Fuglesang S. Jensen, Herlev and Gentofte Hospital

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.


Condition or disease Intervention/treatment Phase
Non-obstructive Azoospermia Procedure: mTESE Procedure: TESA Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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

Masking: Single (Participant)
Masking Description: The randomization will be performed when the patient is asleep.
Primary Purpose: Treatment
Official Title: Surgical Sperm Retrieval in Non-obstructive Azoospermic Men: Microdissection Testicular Sperm Extraction vs. Multiple Needle-pass Percutaneous Testicular Sperm Aspiration
Actual Study Start Date : April 1, 2017
Estimated Primary Completion Date : April 1, 2020
Estimated Study Completion Date : December 31, 2020


Arm Intervention/treatment
Active Comparator: mTESE
Patients randomized to mTESE
Procedure: mTESE
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.
Other Name: Microdissection testicular sperm extraction

Active Comparator: TESA
Patients randomized to TESA
Procedure: TESA
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.
Other Name: Percutaneous testicular sperm aspiration




Primary Outcome Measures :
  1. Sperm retrieval rate [ Time Frame: Assessed immediately after the procedure ]
    Rate of succesful sperm retrievals defined as at least one spermatozoa found suitable for intracytoplasmic sperm injection (ICSI)


Secondary Outcome Measures :
  1. Conversion rate to mTESE [ Time Frame: Recorded immediately after the procedure ]
    Rate of conversion from TESA to mTESE in the TESA group

  2. Sperm retrieval rate after salvage mTESE [ Time Frame: Recorded immediately after the procedure ]
    Rate of succesful sperm retrievals following salvage mTESE

  3. Complication rates [ Time Frame: Recorded in the first 6 months after surgery ]
    Any complication after surgery

  4. Pregnancy outcomes [ Time Frame: Recorded in the first 9-15 months after surgery ]
    Fertilization rate (per injected oocyte), chemical pregnancy rate, clinical pregnancy rate and live birth rate (per IVF cycle)

  5. Difference in perceived stress scale (PSS) score [ Time Frame: Three months before to three months after surgery ]
    The validated questionnaire PSS measures the perception of stress. The scale range is 0-40 with a higher score indicating more perceived stress.

  6. Difference in PainDetect pain scale score [ Time Frame: Three months before to three months after surgery ]
    Based on the validated questionnaire PainDetect. The scale range is 0-38 with a higher score indicating a larger neuropathic pain component

  7. Difference in pain score - Visual Analog Scale [ Time Frame: Three months before to three months after surgery ]
    Pain reported on the visual analog scale with the range 0-10. A higher score indicates more pain.

  8. Difference in erectile function score [ Time Frame: Three months before to three months after surgery ]
    Based on the validated questionnaire the International Index of Erectile Function (IIEF-5). The scale range is 5-25 with a higher score indicating a better erectile function.

  9. Difference in Hospital Anxiety and Depression Scale (HADS) scores - subscale anxiety. [ Time Frame: Three months before to three months after surgery ]
    Anxiety measured with the validated questionnaire HADS. The subscale range is 0-21 with a higher score indicating more anxiety.

  10. Difference in Hospital Anxiety and Depression Scale (HADS) scores - subscale depression. [ Time Frame: Three months before to three months after surgery ]
    Depression measured with the validated questionnaire HADS. The subscale range is 0-21 with a higher score indicating more depresssion.

  11. Difference in Short-Form 12-item Survery (SF-12) mental health summary score [ Time Frame: Three months before to three months after surgery ]
    Mental Health Composite Scores (MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.

  12. Difference in Short-Form 12-item Survery (SF-12) physical health summary score [ Time Frame: Three months before to three months after surgery ]
    Physical Health Composite Scores (PCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of Health measured by the scales and 100 indicates the highest level of health.

  13. Age as a predictor of successful sperm retrieval [ Time Frame: Calculated 1-3 years after surgical intervention ]
    Age

  14. Body Mass Index (BMI) as a predictor of successful sperm retrieval [ Time Frame: Calculated 1-3 years after surgical intervention ]
    BMI

  15. Testis histology as a predictor of successful sperm retrieval [ Time Frame: Calculated 1-3 years after surgical intervention ]
    Testis Histology

  16. Testis size as a predictor of successful sperm retrieval [ Time Frame: Calculated 1-3 years after surgical intervention ]
    Testis size

  17. Biomarkers as a predictor of successful sperm retrieval [ Time Frame: Calculated 1-3 years after surgical intervention ]
    Relevant (not identified yet) biomarkers in blood, seminal fluid and/or testicular tissue,

  18. Intra-testicular testosterone level as a predictor of successful sperm retrieval [ Time Frame: Calculated 1-3 years after surgical intervention ]
    Intra-testicular testosterone level

  19. FSH as a predictor of successful sperm retrieval [ Time Frame: Calculated 1-3 years after surgical intervention ]
    Baseline Follicle-stimulating hormone level

  20. LH as a predictor of successful sperm retrieval [ Time Frame: Calculated 1-3 years after surgical intervention ]
    Baseline Luteinizing hormone level

  21. Testosterone as a predictor of successful sperm retrieval [ Time Frame: Calculated 1-3 years after surgical intervention ]
    Baseline Testosterone level

  22. Inhibin B as a predictor of successful sperm retrieval [ Time Frame: Calculated 1-3 years after surgical intervention ]
    Baseline Inhibin B level

  23. AMH as a predictor of successful sperm retrieval [ Time Frame: Calculated 1-3 years after surgical intervention ]
    Baseline Anti-Müllerian hormone level

  24. Estradiol as a predictor of successful sperm retrieval [ Time Frame: Calculated 1-3 years after surgical intervention ]
    Baseline Estradiol level

  25. Prolactin as a predictor of successful sperm retrieval [ Time Frame: Calculated 1-3 years after surgical intervention ]
    Baseline Prolactin level



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   46XY
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Exclusion during follow-up

  • A patient can at any time during the study withdraw their consent of participation
  • Normal histology on testis biopsy following TESA or mTESE

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03550716


Contacts
Contact: Christian Fuglesang S. Jensen, MD +4538686088 cjen0421@regionh.dk
Contact: Jens Sønksen, MD, PhD, DMSc +4521203162 jens@sonksen.dk

Locations
Denmark
Rigshospitalet Recruiting
Copenhagen, Denmark, DK-2100
Contact: Niels Jørgensen, MD,PhD         
Herlev and Gentofte Hospital Recruiting
Herlev, Denmark, DK-2730
Contact: Christian Fuglesang S. Jensen, MD    +4538686088    cjen0421@regionh.dk   
Holbæk Sygehus Recruiting
Holbæk, Denmark, DK-4300
Contact: Anne Lis Englund, MD         
Sweden
Malmö University Hospital Recruiting
Malmö, Sweden, 20502
Contact: Aleksander Giwercman, MD, PhD         
Sponsors and Collaborators
Herlev and Gentofte Hospital
Rigshospitalet, Denmark
Holbaek Sygehus
Skane University Hospital
University of Michigan

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

Responsible Party: Christian Fuglesang S. Jensen, Principal Investigator, Herlev and Gentofte Hospital
ClinicalTrials.gov Identifier: NCT03550716     History of Changes
Other Study ID Numbers: H-16033784
First Posted: June 8, 2018    Key Record Dates
Last Update Posted: June 8, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Christian Fuglesang S. Jensen, Herlev and Gentofte Hospital:
azoospermia
microdissection testicular sperm extraction
testicular sperm aspiration
male infertility
surgical sperm retrieval

Additional relevant MeSH terms:
Azoospermia
Infertility, Male
Infertility
Genital Diseases, Male