Gonadotropin Therapy in Idiopathic Hypogonadal Non-Obstructive
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: No intervention, hCG + FSH therapy.
- Who it may be relevant to
- Registry conditions: APHRODITE Group. Basic parameters: No limits · Male.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- India
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
"Gonadotropin Therapy in Idiopathic Hypogonadal Non-Obstructive Azoospermia (APHRODITE Groups 3-4): A Multicenter Randomized Controlled Trial"
Overview
The goal of this clinical trial is to determine whether short-term gonadotropin therapy (hCG + FSH) can increase sperm availability for ICSI in men with idiopathic non-obstructive azoospermia (NOA) and hypogonadism. The main questions it aims to answer are: Does hormonal optimization improve the likelihood of obtaining usable sperm (via ejaculate or micro-TESE) by Week 16? Does hormonal therapy reduce the need for micro-TESE or improve downstream embryological and clinical outcomes? Because there is a comparison group, researchers will compare hCG + FSH hormonal therapy with standard-of-care (no gonadotropins) to see if hormonal optimization increases sperm retrieval success and decreases surgical reliance. Participants will: Undergo baseline hormonal and semen testing Be randomized to either hormonal therapy or standard-of-care If in the hormonal arm: receive hCG and FSH with monthly dose titration and aromatase inhibitors if indicated Provide semen samples at Weeks 12 and 16 Undergo micro-TESE if no ejaculated sperm are found (timing per protocol) Complete safety assessments and follow-up through Week 16
Interventions
- Other No intervention
Standard of Care - Other hCG + FSH therapy
hCG + FSH therapy with monthly hormone-driven titration (hCG initial \~83 µg SC twice weekly; no preset min/max; target TT \>350-900 ng/dL) + FSH 150 IU SC twice weekly (increase to 150 IU SC three times weekly if 'FSH reset' \<1.5 IU/L); allow anastrozole 1 mg PO daily /letrozole 2.5 mg half tablet alternate day if T/E \<10
Primary outcome measures
- Success or Sperm Availability [Time frame: from randomization through Week 16 via ejaculate or micro-TESE]
Secondary outcome measures (10)
- Micro-TESE Sperm Retrieval Rate (SSR) [Time frame: The Micro-TESE Sperm Retrieval Rate (SSR) was assessed during the period from randomization through Week 16. The outcome was determined based on the availability of at least one viable sperm retrieved via microsurgical testicular sperm extraction (micro-]
- Need for Micro-TESE Surgery [Time frame: Up to Week 16]
- Safety / Harms [Time frame: Week 16]
- ICSI Fertilization Rate [Time frame: Within the ICSI cycle ≈ Day 1-3 after ICSI]
- Blastulation Rate [Time frame: Day 5-7 after fertilization]
- Blastocyst Quality [Time frame: Day 5-7 after fertilization]
- Top-Quality Blastocyst Rate [Time frame: Day 5-7 after fertilization]
- Clinical Pregnancy Rate [Time frame: ≈ 6-8 weeks after embryo transfer]
- Miscarriage Rate [Time frame: From pregnancy confirmation to 20 weeks gestation]
- Live Birth [Time frame: Up to delivery (~9 months after embryo transfer)]
Eligibility criteria
Inclusion criteria
\- Idiopathic NOA; hypogonadal (TT <350 ng/dL on two fasting morning tests); FSH ≥7.6 IU/L (APHRODITE Group 3: 7.6-12.0 IU/L; Group 4: >12.0 IU/L).
Exclusion criteria
cryptorchidism, chemo/radiation, genetic NOA (e.g., AZFa/complete AZFb), testicular trauma/torsion, post-orchitis. prior micro-TESE within 12 months; recent gonadotropin therapy (<6 months); uncontrolled endocrine disease; active malignancy; severe liver disease; polycythemia (Hct>50%); inability to comply. Varicocele>= Grade 3
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
India · 8 centers
- Recruitment — Patna
- Recruitment — Bangalore
- Recruitment — Bhāndup
- Recruitment — Pune
- Recruitment — Delhi
- Recruitment — Jaipur
- Recruitment — Allahābād
- Recruitment — Lucknow
Publications
- Esteves SC, Yarali H, Vuong LN, Carvalho JF, Ozbek IY, Polat M, Le HL, Pham TD, Ho TM. Low Prognosis by the POSEIDON Criteria in Women Undergoing Assisted Reproductive Technology: A Multicenter and Multinational Prevalence Study of Over 13,000 Patients. Front Endocrinol (Lausanne). 2021 Mar 12;12:630550. doi: 10.3389/fendo.2021.630550. eCollection 2021. PMID 33790862
- Esteves SC, Humaidan P, Ubaldi FM, Alviggi C, Antonio L, Barratt CLR, Behre HM, Jorgensen N, Pacey AA, Simoni M, Santi D. APHRODITE criteria: addressing male patients with hypogonadism and/or infertility owing to altered idiopathic testicular function. Reprod Biomed Online. 2024 Apr;48(4):103647. doi: 10.1016/j.rbmo.2023.103647. Epub 2023 Oct 29. PMID 38367592
- Chandra V, Esteves SC, Sanagoudar S. Gonadotropin therapy in idiopathic hypogonadal non-obstructive azoospermia (APHRODITE Groups 3-4): a multicenter randomized controlled trial. Front Reprod Health. 2026 Jul 9;8:1867412. doi: 10.3389/frph.2026.1867412. eCollection 2026. PMID 42495163
Identifiers
NCT: NCT07540611 · IIHL-UDR-P-002-2025 · IIHL-UDR-P-002-2025