Clinical trial NCT00975546: HIV-discordant Couple Intrauterine Insemination
Official title: Intrauterine Insemination for HIV-discordant Couples
Study type: EXPANDED_ACCESS
Overall status: NO_LONGER_AVAILABLE
Conditions: Infertility
HIV Infections
Keywords: fertility
HIV discordant
HIV
Infertility in HIV-discordant couples
HIV seronegativity
Lead sponsor: University of Missouri-Columbia
Sponsor class: OTHER
First posted: 2009-09-11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 38
Standard ages: ADULT

Brief summary: 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.

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 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Columbia
country: United States
facility: Missouri Center for Reproductive Medicine & Fertility
state: Missouri
Study officials:
affiliation: University of Missouri-Columbia
name: Danny J Schust, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Missouri-Columbia
name: Erma Z Drobnis, PhD
role: PRINCIPAL_INVESTIGATOR
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