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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
860
Standard of Care
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
Recruitment
Patna, Bihar, India
Recruitment
Bangalore, Karnataka, India
Recruitment
Bhāndup, Maharashtra, India
Recruitment
Pune, Maharashtra, India
Recruitment
Delhi, National Capital Territory of Delhi, India
Recruitment
Jaipur, Rajasthan, India
Recruitment
Allahābād, Uttar Pradesh, India
Recruitment
Lucknow, Uttar Pradesh, India
Success or Sperm Availability
Sperm Availability for ICSI was defined as the presence of viable sperm suitable for intracytoplasmic sperm injection (ICSI) at any time from randomization through Week 16. Sperm could be obtained either through ejaculate or via microsurgical testicular sperm extraction (micro-TESE). Assessment of sperm availability was performed by a centralized adjudication committee, which was blinded to treatment allocation to ensure objective and unbiased evaluation.
Time frame: from randomization through Week 16 via ejaculate or micro-TESE
Micro-TESE Sperm Retrieval Rate (SSR)
Whether sperm are retrieved during micro-TESE
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
Whether the participant requires micro-TESE
Time frame: Up to Week 16
Safety / Harms
All adverse events (AE/SAE) related to treatment or procedure
Time frame: Week 16
ICSI Fertilization Rate
% of injected oocytes that form normal 2PN embryos
Time frame: Within the ICSI cycle ≈ Day 1-3 after ICSI
Blastulation Rate
% of embryos reaching blastocyst stage
Time frame: Day 5-7 after fertilization
Blastocyst Quality
Grading of blastocysts based on standard morphology criteria
Time frame: Day 5-7 after fertilization
Top-Quality Blastocyst Rate
% of "top-1 quality" blastocysts formed
Time frame: Day 5-7 after fertilization
Clinical Pregnancy Rate
Presence of gestational sac with cardiac activity on ultrasound
Time frame: ≈ 6-8 weeks after embryo transfer
Miscarriage Rate
Pregnancy loss before 20 weeks
Time frame: From pregnancy confirmation to 20 weeks gestation
Live Birth
Delivery of a live infant
Time frame: Up to delivery (~9 months after embryo transfer)
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