Intrauterine Insemination In HIV-Discordant Couples

Study Overview
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Brief Summary
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This study aims to assess the feasibility of a novel standard of care technique for intrauterine insemination (IUI) in HIV-discordant couples in the United States. This study will involve couples in which the male partner is HIV positive, but the female partner is negative. The investigators will institute a protocol similar to those used presently throughout Europe with good success. To date, no HIV seroconversions have occurred in over 4000 inseminations performed in HIV serodiscordant couples. All male subjects will be on stable HAART, and have undetectable serum viral loads prior to insemination. Semen samples will be subjected to a stringent sperm wash procedure and screened for HIV RNA. Female subjects will be followed post-insemination for seroconversion and pregnancy. Infants will be followed for seroconversion at birth through 4 months of age.

Detailed Description
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This study aims to assess the feasibility of a novel standard of care technique for intrauterine insemination (IUI) in HIV-discordant couples in the United States. This study will involve couples in which the male partner is HIV positive, but the female partner is negative. The investigators will institute a protocol similar to those used presently throughout Europe with good success. To date, no HIV seroconversions have occurred in over 4000 inseminations performed in HIV serodiscordant couples. All male subjects will be on stable HAART and have undetectable serum viral loads prior to insemination. For semen samples, seminal fluid will be separated from sperm using a density gradient/swim-up separation technique. The purified sperm sample will be washed, and screened for HIV RNA using sensitive real-time RT-PCR. Samples with detectable traces of HIV RNA will not be used for insemination. Samples with no detectable traces of HIV RNA will be used for a standard intrauterine insemination of the female partner. Female subjects will be followed post-insemination for seroconversion and pregnancy. Infants will be followed for seroconversion at birth through 3 months of age. The data being collected in this pilot feasibility study will be mostly descriptive, lacking sample size to achieve statistical power for testing. However, the investigators will use case-control analysis to compare couples who achieve pregnancy with those who do not across demographics and markers of HIV disease progression. Additionally, the investigators have developed a 14 item, 5-point Likert scale to assesses the psychosocial impact of reproductive health issues stemming from HIV-discordance in both the female and male participants. The expected duration for any unique subject couple is 3 to 12 months, depending on pregnancy. It is expected that the interventional portion of this study will continue for up to 2 years, depending on pregnancies.

Official Title
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Intrauterine Insemination In HIV-Discordant Couples

Conditions
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HIV-1, Fertility, Infertility

Intervention / Treatment
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* Other: Sperm Washing with Intrauterine Insemination (IUI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Couples with HIV discordance with an HIV seronegative female partner and HIV seropositive male partner Men must be HIV positive with an undetectable viral load (<75 copies/ml) Men must be clinical stable on antiretroviral therapy for 6 months Men must have a CD4 count > 250 at screening Men must be between 18-50 years of age Men must have a baseline test sperm preparation demonstrating at least 10 million motile sperm per sample Men must have a letter of medical clearance specific for this procedure from primary care physician stating that subject is in good health and psychologically stable Men must be willing to have constituent follow-up of HIV care throughout study participation Women must have an HIV-1/HIV-2 negative serology at screening Women must be between 18-40 years of age Women must have a body mass index (BMI) less than 30 Women must be a non-smoker Women must be ovulatory (as determined by LH tracking) Women must have normal uterine cavity with at least one documented patent fallopian tube (as determined by hysterosalpingogram) Women must have adequate day 3 ovarian reserves: FSH,12 mlU/ml and estradiol<80pg/ml Women must have no evidence of active urogenital infection at screening Women must have a normal PAP smear and GC/Chlamydia at screening Women must have a letter of medical clearance specific to this procedure from subject's primary care physician stating that subject is in good health and psychological stable. Exclusion Criteria: Subjects with untreated sexually transmitted diseases (syphilis, GC, CT) Men with detectable viral load (>75) at screening Subjects with any condition (including, but not limited to alcohol and drug use), which, in the opinion of the investigator, could compromise the subject's safety or adherence to the protocol Subjects with any uncontrollable medical or psychiatric condition that,in the opinion of the investigator, cannot be adequately stabilized and could be considered a contraindication to participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Sperm Washing with Intrauterine Insemination (IUI)|For semen samples, seminal fluid will be separated from sperm using a density gradient/swim-up separation technique. The purified sperm sample will be washed, and screened for HIV RNA using sensitive real-time RT-PCR. Samples with detectable traces of HIV RNA will not be used for insemination. Samples with no detectable traces of HIV RNA will be used for a standard intrauterine insemination of the female partner.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy | A serum pregnancy test will be performed 16 days after IUI if menses is missed. | Sixteen days after IUI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-IUI HIV Infection of Female Subject | The female subject will be tested for HIV by branch-DNA (b-DNA) test four weeks after each insemination. | Four weeks after IUI | 
| Female Subject HIV-1/HIV-2 Serology | If the female subject does not become pregnant, she will be tested for HIV-1/HIV-2 serology at 3 months, 6 months and 12 months after the insemination. If repeat inseminations are performed, the above-stated timeline will be followed based on the last insemination performed. If the female subject does become pregnant, she will be tested for HIV-1/HIV-2 serology at 3 months, 6 months and 9 months after the insemination, and again at 3 months postpartum. | Three, six, nine (pregnant only) and twelve months after insemination | 
| Infant HIV-1/HIV-2 Serology | For a successful birth, the infant will undergo an HIV-1/HIV-2 serology test at three months of age. | Three months of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acquired Immune Deficiency Syndrome, Assisted Reproductive Technology, Fertility, HIV, HIV Discordant, Infertility, Intrauterine Insemination, Sexually Transmitted Diseases, Sperm Washing