HIV-discordant Couple Intrauterine Insemination - Full Text View

Purpose

The investigators propose to treat couples who wish to have a child in which the man is HIV-positive and the woman is HIV-negative. The investigators call these couples HIV-discordant. On the average, an HIV-positive man, who does not participate in high-risk activities, will transmit HIV to a female partner one in every one thousand acts of intercourse without a condom. To reduce transmission of HIV, HIV-discordant couples are counseled to avoid intercourse altogether, or to use condoms during every act of intercourse. In order to have a child, these patients can use donor insemination. If they wish to have a natural child of the infected man, they can use a combination of medication of the man to reduce the amount of virus in his semen, and condom use except at the time of ovulation when the woman produces an egg. This reduces the chance of infecting the woman, but studies have shown that about 4% of women will be infected with HIV using this approach. Alternatively, they can use vitro fertilization (IVF) with intra cytoplasmic sperm injection (ICSI) in which eggs are collected from the woman after hormone-stimulation and are fertilized in the laboratory by injecting a single washed sperm from her husband into each egg. The resulting embryos can be transferred to the wife's uterus and/or frozen for later use. These procedures are believed to minimize the risk of HIV transmission (although the number of cases is low), but IVF-ICSI is very expensive and are not an option for everyone. A simpler method used for over 15 years in Europe is to collect the man's semen, wash the sperm in the laboratory, and test the sperm sample for HIV before placing it in the woman's uterus (intrauterine insemination; IUI). Although the risk of HIV transmission to the woman is presumably not zero with this method, over 4000 inseminations reported have not resulted in infection of any female patients or resulting children.

Condition	Intervention
Infertility HIV Infections	Other: Sperm washing and testing for HIV contamination Procedure: Intrauterine Insemination


Study Type:	Expanded Access What is Expanded Access?
Official Title:	Intrauterine Insemination for HIV-discordant Couples

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS Infertility

U.S. FDA Resources

Further study details as provided by University of Missouri-Columbia:

Intervention Details:

Semen will undergo specialized washing to reduce viral contamination of sperm. The sperm are first separated from leukocytes and other seminal constituents by centrifugation over a stepwise gradient. Motile sperm will be separated from the resulting pellet by a swim-up step in which washed sperm are overlaid with fresh medium into which sperm migrate. The final sperm suspension will be stored while testing for HIV is performed by reverse transcription polymerase chain reaction (RT-PCR)

Intrauterine Insemination (IUI) will be performed on the HIV-negative wife, following standard clinical practice, using washed sperm from her HIV-positive husband after testing the IUI sample for HIV.

Detailed Description:

This study will enroll couples who wish to have a child in which the man is HIV-seropositive and the woman is HIV-seronegative. The couple will be counseled about their reproductive options, including in vitro fertilization (IVF) donor insemination and adoption. The male patient will be using appropriate therapy to reduce the virus in his semen. Semen will undergo specialized washing to reduce viral contamination of sperm. The sperm are first separated from leukocytes and other seminal constituents by centrifugation over a stepwise gradient. Motile sperm will be separated from the resulting pellet by a swim-up step in which washed sperm are overlaid with fresh medium into which sperm migrate. The final sperm suspension will be stored while testing for HIV is performed by reverse transcription polymerase chain reaction (RT-PCR). Specimens found negative for HIV will then be used for IUI (review: Gilling-Smith et al, 2006; Bujan et al 2007). There is presumably some risk of HIV transmission to the woman and resulting child with this approach; however, over 4000 inseminations reported in Europe over the last 15 years have not resulted in infection of any female patient or resulting child. The woman will be followed for a year after the final IUI to assess seroconversion. If a child is born, he or she will be tested for HIV at 3 months of age.

Eligibility


Ages Eligible for Study:	18 Years to 38 Years
Genders Eligible for Study:	Both

Criteria

Inclusion Criteria:

Couple must:

attest to safe sex practices
know the HIV-status of their partner
be informed of risks of this procedure and alternatives, including donor insemination
have the ability to provide informed consent
been referred or self-refer to Dr. Schust for infertility treatment

Female must:

be 18-38 years of age
have a normal menstrual cycle before the IUI cycle
be negative for HIV, gonorrhea, chlamydia, syphilis, hepatitis B and hepatitis C
have a standard infertility evaluation and be a candidate for intrauterine insemination

Male must:

be at least 18 years of age
be HIV-seropositive
be under the care of an infectious disease specialist
disease must be under control without evidence of acquired immunodeficiency syndrome (AIDS), with viral load <50,000 copies/mL and CD4 count > 250 cells/mL for the preceding 6 month period
have semen quality adequate for intrauterine insemination

If the couple does not achieve pregnancy after IUI, they may continue in the study for 5 additional treatment subsequent cycles. The man must continue to receive care for his HIV and the disease must continue to be under control. Before each cycle of insemination, the couple must each sign an attestation statement that he/she is following safe sex practices, and have repeat testing for sexually-transmitted infections.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00975546

Contacts


Contact: Jacqueline D Leasure, RN	573-817-3105	leasurej@health.missouri.edu
Contact: Erma Z Drobnis, PhD	573-817-3124	drobnise@health.missouri.edu

Locations


United States, Missouri
Missouri Center for Reproductive Medicine & Fertility
Columbia, Missouri, United States, 65201
Contact: Erma Z Drobnis, PhD 573-817-3124 drobnise@health.missouri.edu

Sponsors and Collaborators

University of Missouri-Columbia

Investigators


Principal Investigator:	Danny J Schust, MD	University of Missouri-Columbia
Principal Investigator:	Erma Z Drobnis, PhD	University of Missouri-Columbia

More Information

Publications:

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.

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.

Chen JL, Philips KA, Kanouse DE, Collins RL, Miu A. Fertility desires and intentions of HIV-positive men and women. Fam Plann Perspect. 2001 Jul-Aug;33(4):144-52, 165.

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.

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.

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.

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

Kim LU, Johnson MR, Barton S, Nelson MR, Sontag G, Smith JR, Gotch FM, Gilmour JW. Evaluation of sperm washing as a potential method of reducing HIV transmission in HIV-discordant couples wishing to have children. AIDS. 1999 Apr 16;13(6):645-51.

Leruez-Ville M, de Almeida M, Tachet A, Dulioust E, Guibert J, Mandelbrot L, Salmon D, Jouannet P, Rouzioux C. Assisted reproduction in HIV-1-serodifferent couples: the need for viral validation of processed semen. AIDS. 2002 Nov 22;16(17):2267-73.

Lesage B, Vannin AS, Emiliani S, Debaisieux L, Englert Y, Liesnard C. Development and evaluation of a qualitative reverse-transcriptase nested polymerase chain reaction protocol for same-day viral validation of human immunodeficiency virus type 1 ribonucleic acid in processed semen. Fertil Steril. 2006 Jul;86(1):121-8. Epub 2006 Jun 6.

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.

Mandelbrot L, Heard I, Henrion-Géant E, Henrion R. Natural conception in HIV-negative women with HIV-infected partners. Lancet. 1997 Mar 22;349(9055):850-1.

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.

Politch JA, Mayer KH, Anderson DJ. Depletion of CD4+ T cells in semen during HIV infection and their restoration following antiretroviral therapy. J Acquir Immune Defic Syndr. 2009 Mar 1;50(3):283-9. doi: 10.1097/QAI.0b013e3181989870.

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.

Quayle AJ, Xu C, Tucker L, Anderson DJ. The case against an association between HIV-1 and sperm: molecular evidence. J Reprod Immunol. 1998 Dec;41(1-2):127-36. Review.

Quayle AJ, Xu C, Mayer KH, Anderson DJ. T lymphocytes and macrophages, but not motile spermatozoa, are a significant source of human immunodeficiency virus in semen. J Infect Dis. 1997 Oct;176(4):960-8.

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.

Semprini AE, Levi-Setti P, Bozzo M, Ravizza M, Taglioretti A, Sulpizio P, Albani E, Oneta M, Pardi G. Insemination of HIV-negative women with processed semen of HIV-positive partners. Lancet. 1992 Nov 28;340(8831):1317-9.

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.

Smith JR, Forster GE, Kitchen VS, Hooi YS, Munday PE, Paintin DB. Infertility management in HIV positive couples: a dilemma. BMJ. 1991 Jun 15;302(6790):1447-50.

Sunderam S, Hollander L, Macaluso M, Vucetich A, Jamieson DJ, Osimo F, Duerr A, Semprini AE. Safe conception for HIV discordant couples through sperm-washing: experience and perceptions of patients in Milan, Italy. Reprod Health Matters. 2008 May;16(31):211-9. doi: 10.1016/S0968-8080(08)31342-1.

Vernazza PL, Gilliam BL, Dyer J, Fiscus SA, Eron JJ, Frank AC, Cohen MS. Quantification of HIV in semen: correlation with antiviral treatment and immune status. AIDS. 1997 Jul;11(8):987-93.

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.

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.

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.


Responsible Party:	Erma Drobnis, Clinical Asssistant Professor, University of Missouri-Columbia
ClinicalTrials.gov Identifier:	NCT00975546 History of Changes
Other Study ID Numbers:	HIV-IUI
Study First Received:	September 10, 2009
Last Updated:	December 2, 2014
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Missouri-Columbia:


fertility HIV discordant HIV Infertility in HIV-discordant couples HIV seronegativity

ClinicalTrials.gov processed this record on March 03, 2015