Intrauterine Insemination In HIV-Discordant Couples

Infertility Clinical Trial

— ARTEMIS  

Official title:

Intrauterine Insemination In HIV-Discordant Couples

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01173276
• Other study ID #: ARTEMIS
• Status: Terminated
• Phase: N/A
• First received: July 28, 2010
• Last updated: February 19, 2016
• Start date: September 2009
• Est. completion date: October 2013

Study information

• Verified date: January 2012
• Source: Boston Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: October 2013
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fertility
• HIV-1
• Infertility

Intervention

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.

Locations

Country	Name	City	State
United States	Boston Medical Center	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Boston Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (16)

Anderson DJ, Politch JA. Providing fertility care to HIV-1 serodiscordant couples: a biologist's point of view. Am J Bioeth. 2003 Winter;3(1):47-9. — View Citation

Bujan L, Hollander L, Coudert M, Gilling-Smith C, Vucetich A, Guibert J, Vernazza P, Ohl J, Weigel M, Englert Y, Semprini AE; CREAThE network. Safety and efficacy of sperm washing in HIV-1-serodiscordant couples where the male is infected: results from the European CREAThE network. AIDS. 2007 Sep 12;21(14):1909-14. — View Citation

Bujan L, Pasquier C, Labeyrie E, Lanusse-Crousse P, Morucci M, Daudin M. Insemination with isolated and virologically tested spermatozoa is a safe way for human immunodeficiency type 1 virus-serodiscordant couples with an infected male partner to have a child. Fertil Steril. 2004 Oct;82(4):857-62. — View Citation

Centers for Disease Control (CDC). HIV-1 infection and artificial insemination with processed semen. MMWR Morb Mortal Wkly Rep. 1990 Apr 20;39(15):249, 255-6. — View Citation

Centers for Disease Control (CDC). Semen banking, organ and tissue transplantation, and HIV antibody testing. MMWR Morb Mortal Wkly Rep. 1988 Feb 5;37(4):57-8, 63. — View Citation

Centers for Disease Control and Prevention. Revised guidelines for HIV counseling, testing, and referral. MMWR Recomm Rep. 2001 Nov 9;50(RR-19):1-57; quiz CE1-19a1-CE6-19a1. — View Citation

Englert Y, Van Vooren JP, Place I, Liesnard C, Laruelle C, Delbaere A. ART in HIV-infected couples: has the time come for a change of attitude? Hum Reprod. 2001 Jul;16(7):1309-15. Review. — View Citation

Ethics Committee of the American Society for Reproductive Medicine. Human immunodeficiency virus and infertility treatment. Fertil Steril. 2002 Feb;77(2):218-22. — View Citation

Gilling-Smith C, Nicopoullos JD, Semprini AE, Frodsham LC. HIV and reproductive care--a review of current practice. BJOG. 2006 Aug;113(8):869-78. Epub 2006 Jun 2. Review. — View Citation

Gilling-Smith C, Smith JR, Semprini AE. HIV and infertility: time to treat. There's no justification for denying treatment to parents who are HIV positive. BMJ. 2001 Mar 10;322(7286):566-7. — View Citation

Marina S, Marina F, Alcolea R, Expósito R, Huguet J, Nadal J, Vergés A. Human immunodeficiency virus type 1--serodiscordant couples can bear healthy children after undergoing intrauterine insemination. Fertil Steril. 1998 Jul;70(1):35-9. — View Citation

Pasquier C, Anderson D, Andreutti-Zaugg C, Baume-Berkenbosch R, Damond F, Devaux A, Englert Y, Galimand J, Gilling-Smith C, Guist'hau O, Hollander L, Leruez-Ville M, Lesage B, Maillard A, Marcelin AG, Schmitt MP, Semprini A, Vourliotis M, Xu C, Bujan L; CREAThE Network. Multicenter quality control of the detection of HIV-1 genome in semen before medically assisted procreation. J Med Virol. 2006 Jul;78(7):877-82. — View Citation

Politch JA, Xu C, Tucker L, Anderson DJ. Separation of human immunodeficiency virus type 1 from motile sperm by the double tube gradient method versus other methods. Fertil Steril. 2004 Feb;81(2):440-7. — View Citation

Sauer MV, Wang JG, Douglas NC, Nakhuda GS, Vardhana P, Jovanovic V, Guarnaccia MM. Providing fertility care to men seropositive for human immunodeficiency virus: reviewing 10 years of experience and 420 consecutive cycles of in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril. 2009 Jun;91(6):2455-60. doi: 10.1016/j.fertnstert.2008.04.013. Epub 2008 Jun 13. — View Citation

Sauer MV. Sperm washing techniques address the fertility needs of HIV-seropositive men: a clinical review. Reprod Biomed Online. 2005 Jan;10(1):135-40. Review. — View Citation

Semprini AE, Bujan L, Englert Y, Smith CG, Guibert J, Hollander L, Ohl J, Vernazza P. Establishing the safety profile of sperm washing followed by ART for the treatment of HIV discordant couples wishing to conceive. Hum Reprod. 2007 Oct;22(10):2793-4; author reply 2794-5. Epub 2007 Jul 3. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pregnancy	A serum pregnancy test will be performed 16 days after IUI if menses is missed.	Sixteen days after IUI	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes