A Phase 3 interventional study of Clomifene Citrate and Placebo in Azoospermia, Nonobstructive, sponsored by Hospices Civils de Lyon. Withdrawn at 1 site in France. Open to male participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2026-06-17.
Sponsored by Hospices Civils de Lyon · Phase 3, Interventional, and Treatment
In the absence of sperm in the semen (azoospermia), there is no chance of natural paternity. It is found in about 1% of men and is either due to an obstruction of the seminal tracks (obstructive azoospermia (OA)) in 1/3 of the cases, or a spermatogenic failure (non-obstructive azoospermia (NOA)) in 2/3 of the cases. To date, no medical treatment had proved its efficiency to induce spermatogenesis in case of NOA.
The development of Intracytoplasmic sperm injection (ICSI) in 1992 allowed to obtain pregnancies from a small number of spermatozoa. The next year, testicular sperms were extracted from testicular tissue obtained surgically in cases of OA , allowing paternity for azoospermic men. In case of NOA, TESE allowed to obtain few sperms in an unexpected number of cases. It was shown that spermatogenesis remains active in rare portions of seminiferous tubules, a phenomenon called focal spermatogenesis, which allows to extract testicular sperms with an average SRR of 50%, and to obtain pregnancy by ICSI. Thus, TESE-ICSI revolutionized the prognosis of NOA, however, half of the cases of NOA had no sperm extracted and remained sterile . Since sperm donation and adoption are unacceptable for several of these couples, there is a real demand for additional treatment.
Two ways to improve chances of paternity in case of NOA are currently discussed:
This prompted us to develop this clinical trial to investigate the effect of Clomiphene Citrate versus placebo on the results of a second TESE in NOA.
Results of hormonal therapy in case of NOA were heterogeneous and of poor methodological quality, none was randomized versus placebo: Anti-aromatases or Gonadotropins administered before the first TESE or the second TESE gave positive results. Hussein at al in 2013, suggested a positive effect of Clomiphene citrate (CC), administrated before the first TESE (57% of the CC treated group versus 33.6% in not treated group) but with drop out of patient positive to sperm analysis. However, in these positive studies, sample sizes were small or selected patients on hormonal status or histology criteria suggesting subgroup of favourable NOA. Thus, there is no strong evaluation of the interest of hormonal treatment in NOA, after a negative first TESE.
The investigators decided to evaluate the effect of the CC, the most convincing and convenient hormonal treatment, in patients with negative first TESE for NOA. It is of main interest to known if CC could enhance the SRR of a second TESE, that is the ultimate possibility to have their own child for these patients.
23 studies on the registry are indexed under Azoospermia, Nonobstructive; 7 are open to participants now.
Browse Azoospermia, Nonobstructive studies →Hospices Civils de Lyon is the lead sponsor of 1,866 studies on the registry; 448 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
a daily dose of 50mg of Clomifene Citrate per os during 9 months
Drug: Clomifene Citrate
a daily dose of 50mg per os of placebo (lactose monohydrate) during 9 months.
Other: Placebo
After randomization, the andrologist will give a prescription with the first three months of treatment (Clomifene Citrate or placebo) to be collected to the local hospital pharmacy. The andrologist will be blind of the treatment arm. Treatment unit and their shipment to local pharmacy will be provided and organized by the East group pharmacy of the Hospices Civils of Lyon which is the coordination pharmacy for this study. Prescription and delivery will be renewed for three months at the 3 month and 6 months visit. The experimental treatment consists in a daily dose of 50mg of Clomifene Citrate per os during 9 months followed by a second TESE if no spermatozoid has been obtained from semen. The dose level was set according to Chua et al 2013 (cf 1.2.2). One capsule containing 50 mg of CC will be orally administered in the morning every day.
The placebo treatment consists in a daily dose of 50mg of lactose monohydrate per os during 9 months followed by a second TESE if no spermatozoid has been obtained from semen. The capsule containing the placebo will have the exact same size, weight, color, taste and will be delivered in the exact same condition as the experimental treatment capsule.
presence of sperm cells point of view
Evaluate, versus placebo, the interest of 9 months treatment by 50 mg of Clomiphene citrate to increase the proportion of patient for which at least one sperm cell can be isolated either from the semen at 9 months of treatment or, in case of persistent azoospermia, from a second TESE attempt performed at 9 months of treatment
Time frame: 9 months
number of sperm cells point of view
Evaluate, versus placebo, the interest of 9 months treatment by 50 mg of Clomiphene citrate to increase the number of spermatozoa obtained, from the semen at 9 months of treatment or, in case of persistent azoospermia, from a second TESE attempt performed at 9 months of treatment
Time frame: 9 months
Follicle Stimulating Hormone (FSH) level evolution
Evaluate the evolution of FSH in both groups
Time frame: 9 months
testosterone level evolution
Evaluate the evolution of testosterone in both groups
Time frame: 9 months
Luteinizing hormone (LH) level evolution
Evaluate the evolution of LH in both groups
Time frame: 9 months
Sex Hormone-Binding Globulin (SHBG) level evolution
Evaluate the evolution of SHBG in both groups
Time frame: 9 months
Bioavailable testosterone Inhibin B level evolution
Evaluate the evolution of bioavailable testosterone Inhibin B in both groups
Time frame: 9 months
number spermatogonia
Evaluate Hypospermatogenesis status
Time frame: 9 months
number of spermatocytes,
Evaluate Hypospermatogenesis status
Time frame: 9 months
number of round elongated spermatids
Evaluate Hypospermatogenesis status
Time frame: 9 months
prevalence of Sertoli cell only syndrome
Evaluate Sertoli cell only syndrome status
Time frame: 9 months
prevalence of maturation arrest
Evaluate maturation arrest status
Time frame: 9 months
number of Clomiphene citrate capsules
Compliance will be measured by counting the number of Clomiphene citrate capsules remaining in the brought back at each visit
Time frame: 9 months
number of adverse events
Evolution of Clomiphene citrate proportion of side effects
Time frame: 9 months
proportion of complications at the second TESE
Time frame: 9 months
proportion of Pregnancies
proportion of pregnancies after Intracytoplasmic sperm injection
Time frame: 9 months
proportion of Miscarriages
proportion of Miscarriages after ICSI
Time frame: 9 months
number of Newborn
proportion of Newborn after ICSI
Time frame: 9 months
Plan to share: No
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This study is withdrawn, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Clomiphene