Male Infertility, Azoospermia
Conditions
Keywords
Infertility
Brief summary
Men with infertility and normal hormone levels have few options for fertility treatment. Previous research suggests that men with infertility may have low levels of the active form of Vitamin A, called retinoic acid, in their testes. In a pilot study of 20 men with low numbers of sperm (\<10 million motile sperm), roughly half the men showed improvement in sperm production. Thus, we want to see if retinoic acid administration to men with azoospermia (no sperm present) can initiate sperm production.
Detailed description
Twenty men with infertility, aged 21 - 60, due to azoospermia (no apparent sperm in the ejaculate on two separate occasions) will be enrolled in a single-arm pilot trial of daily oral therapy of 20 mg twice daily of 13-cis retinoic acid for 32 weeks. The impact of treatment on the appearance of sperm in the ejaculate will be determined by monthly semen analyses. Note: The outcome measure of serum and seminal plasma 13-cis-retinoic acid concentrations was entered in error and not intended to be reported for this study. Information on these levels is available in our earlier study of 13-cis-retinoic acid in men with sub-fertility. Amory et al. Andrology 2017 5:1115-1123.
Interventions
Accutane is used for the treatment of severe acne
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
20 mg 13-cis retinoic acid twice daily (BID) with meals for 32 weeks
Eligibility
Sex/Gender
MALE
Age
21 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Infertile men with azoospermia on at least two semen analyses separated by at least one week, and no pregnancy with partner with normal cycles and normal hysterosalpingogram despite \>1 year of unprotected intercourse. \-
Exclusion criteria
hypogonadotropic hypogonadism (that might respond to gonadotropin injections); use of anabolic steroids,illicit drugs, or consumption of more than 4 alcoholic beverages daily; current therapy with retinoic acid (eg Accutane) or vitamin A- of use of isotretinoin within eight weeks of start of dosing;phenytoin, or medication containing tetracycline; personal history of serious psychiatric disorders, score of greater than 15 on the PHQ9 (mood) questionnaire; elevated serum serum triglycerides or other abnormal serum chemistry values; history of inflammatory bowel disease or bone disease; not living within catchment area; participation in another clinical trial \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Motile Sperm | up to 32 weeks | Number of participants with undetectable or detectable sperm in their ejaculates. |
| Total Sperm and Percentage of These Sperm That Were Motile | 32 weeks | Number of total sperm in ejaculate and percentage of these sperm that were motile |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious and Non-Serious Adverse Effects | 32 weeks | Number of participants with Serious and Non-Serious Adverse effects associated with treatment with 13-cis retinoic acid |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 13-cis Retinoic Acid 20 mg 13-cis retinoic acid twice daily (BID) with means for 32 weeks
13-cis retinoic acid: Accutane is used for the treatment of severe acne | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | 13-cis Retinoic Acid |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 36 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 1 / 10 |
| serious Total, serious adverse events | 1 / 10 |
Outcome results
Primary
Total Motile Sperm
Number of participants with undetectable or detectable sperm in their ejaculates.
Time frame: up to 32 weeks
Population: Men had idiopathic azoospermia, without evidence of obstruction or know genetic causes of azoospermia, although one man had known AZFc deletion
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Accutane-13-cis Retinoic Acid | Total Motile Sperm | undetectable | 8 Participants |
| Accutane-13-cis Retinoic Acid | Total Motile Sperm | detectable motile sperm | 1 Participants |
Primary
Total Sperm and Percentage of These Sperm That Were Motile
Number of total sperm in ejaculate and percentage of these sperm that were motile
Time frame: 32 weeks
Population: Only man who developed sperm in ejaculate on treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Accutane-13-cis Retinoic Acid | Total Sperm and Percentage of These Sperm That Were Motile | 20 Percent of sperm that were motile |
Secondary
Serious and Non-Serious Adverse Effects
Number of participants with Serious and Non-Serious Adverse effects associated with treatment with 13-cis retinoic acid
Time frame: 32 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Accutane-13-cis Retinoic Acid | Serious and Non-Serious Adverse Effects | 1 Participants |