Advances offer some hope for safer reproduction
Discuss pros and cons with HIV clients
There are no perfectly safe ways for an HIV person to reproduce and prevent transmission to either a partner or a baby. But medicine has improved considerably in recent years, and physicians may offer HIV-infected couples some hope that they could give birth to healthy babies without placing the uninfected spouse at undue risk.
"Usually the bigger problem is when there’s an HIV discordancy," says Rani Lewis, MD, associate professor of obstetrics and gynecology in the Division of Maternal Fetal Medicine at Vanderbilt University in Nashville.
"When the female is HIV-positive and the male partner is not, then the issue is how she can become pregnant and minimize the risk to him and to the baby," Lewis says. "That issue actually is a little bit easier."
It’s when the man is HIV-positive and the woman is not infected that it becomes more difficult, Lewis says. "In that case, we have a tremendous number of problems, because just in the course of ejaculation to get the sperm to the woman so that she can get pregnant, he’s also going to be spreading HIV in his ejaculate," Lewis says.
While a reproductive specialist theoretically could fertilize the woman’s eggs by high-tech methods of inserting the sperm into the woman’s egg without the virus attached, this method has not been scientifically proven safe for use with HIV-infected patients, and it’s prohibitively expensive for most HIV-infected couples.
There is also a problem with even finding a specialist to do such a procedure for an HIV-infected person.
"Unfortunately, most of the reproductive endocrinologists and fertility subspecialists who assist people in getting pregnant are relatively uncomfortable with trying to inseminate someone with what they believe to be potentially HIV-positive sperm," Lewis says. "They want to maximize the chances of a woman becoming pregnant in that specific instance where she and a partner will be healthy and able to take care of a baby."
Here are some of the methods clinicians might recommend or that HIV-infected patients might try on their own:
• Sperm washing: Although sperm washing as an assisted reproductive technique is not new, it has rarely been used for the purpose of "cleaning" sperm of HIV. Where this technique is available, it has proven useful. However, it may not be an option in states where it’s illegal to knowingly expose someone to sperm from an HIV-infected man.
Also, the Centers for Disease Control and Prevention in Atlanta does not recommend this or any other technique purported to help serodiscordant couples achieve pregnancy.
"It’s possible that you could in some ways process semen to separate out sperm from the rest of the fluid and test for the virus, but we haven’t used this technique enough, and we don’t have data on it at this point as to advise people that it would be safe to use," says Ida Onorato, MD, associate director for science in the CDC’s Division of HIV/AIDS prevention.
French and Italian researchers presented information about successful sperm-washing studies at an October meeting of the American Society for Reproductive Medicine in San Diego. French researchers used 101 blood and semen samples from HIV-positive patients and found that 59 of the blood samples and 20 of the semen samples tested positive. After processing the sperm through a sperm-washing technique, only 12% of the semen plasma samples were positive, and none of the sperm cells themselves were positive for the virus.
An Italian team led by investigator Augusto Enrico Semprini of Milan conducted a similar analysis with more than 500 semen samples from HIV-positive men and found that sperm washing could reduce the HIV-positive samples to a very low rate. However, the study also found that determination of HIV-1 nucleic acids in whole semen can give erroneous results and that clinicians should test all final spermatozoa aliquots before using them for assisted reproductive technology.1
Semprini has announced more than 180 successful births after sperm washing for couples in which the men were HIV-positive and the women were HIV-negative. All of the women remained negative after they gave birth. Semprini mixes Percoll with sperm in a test tube and uses a centrifuge to force the infected semen through the fluid. The infected cells are eliminated, and the resulting sample is checked for HIV.
Japanese researchers have developed a variation on the sperm-washing technique by using Percoll gradient centrifugation followed by a "swim-up" method to separate virus from semen. This reduced proviral DNA to undetectable levels according to a polymerase chain reaction (PCR) test.2
There appears to be less enthusiasm for sperm-washing in the United States. While Harvard researchers have provided sperm-washing to some serodiscordant couples, there has been limited availability of the technique because of the high cost, which includes PCR testing, and other factors.
Moher Downing, MA, of the University of California at San Francisco, addressed the issue of sperm washing for HIV-positive men in a paper published on a UCSF Web site (http:// hivinsite.ucsf.edu/prevention/prev_contro/ 3098.0085.html). Downing describes the sperm-washing technique as one in which the semen is layered over a more dense solution. Then it’s placed in a centrifuge that separates the semen into three layers. Next, the sperm is washed twice in a chemical solution, and the washed sperm is divided in half, with one half frozen for later use and the other half used for PCR testing to detect HIV. If HIV is detected in any of the three parts, the sample is discarded. If it’s not discarded, the sperm is combined with an artificial semen solution and used for fertilization.3,4
• Intracytoplasmic sperm injection (ICSI): This is the most costly technique used to help serodiscordant couples, with a price tag of about $50,000. With ICSI, a reproductive specialist cleans the sperm and then takes one sperm and injects it into an egg cell that has been prepared, Lewis says.
"This is very high-tech in vitro fertilization," Lewis says. "And it somewhat decreases the likelihood of transmitting HIV."
Mark Sauer, MD, a professor of obstetrics and gynecology at Columbia University in New York City, has begun a clinical trial to evaluate the safety of in vitro fertilization using ICSI in cases where the men are HIV-positive and the women are not. Further information about the trial can be obtained by calling (212) 305-4665.
Again, until there is a body of research supporting this method, the CDC cannot recommend ICSI, Onorato says.
"It’s possible you can separate out the sperm, that is true, and you can test it and make sure there is no virus there," Onorato says. "It is theoretically possible that these things can be done, but at this point, without an adequate number of people on which this has been tried and without adequate follow-up, it’s hard to say whether or not it’s effective or safe."
• Artificial insemination: When the woman is HIV-positive and the man is HIV-negative, artificial insemination can eliminate risk of the man becoming HIV-infected. Because the easiest and least expensive method is what is commonly called the "turkey baster" method, couples often will opt for a home version of artificial insemination rather than using the services of a clinic or doctor’s office, Lewis says.
"But before we’d recommend somebody do this, we would recommend they optimize the health of the woman who is HIV-positive," Lewis says. "So we’d want to get her off of medications that are known to be bad for fetuses and preferably get her on an antiretroviral regimen that contains AZT or didanosine."
$30 device might do the trick
Bodner has helped HIV-infected women use an alternative form of insemination called an Algiospermia Cap, a device that enhances the likelihood that semen will inseminate or fertilize an egg.
"It gets a big quantity of semen to go into the uterus, and it’s used when a man’s sperm count is low," Bodner says. "It’s about like intrauterine insemination and puts the sperm at the beginning of the cervix."
One of Bodner’s patients used the $30 device and gave birth to two children. "If a woman is careful and knowledgeable and knows approximately when she ovulates, the chances of fertilization are excellent," Bodner adds.
• Alternative methods: Many clinicians might be uneasy mentioning any of the alternative methods that a serodiscordant couple might use to achieve pregnancy. But it’s likely that any guidance from a clinician will be preferable to the couple attempting to get pregnant without taking any precautions.
Lewis once worked with a couple in which the man was HIV-positive and the woman was negative. They wanted to have a child but had very limited financial resources, and so assisted reproductive technology methods were ruled out.
"We came up with a plan of management that they could both live with, and it wasn’t ridiculously expensive," Lewis recalls. "It involved maximizing her chances of becoming pregnant and treating him with antibiotics to decrease the number of white blood cells in his semen, because the white blood cells are the ones that carry HIV."
Then Lewis started the man on antiretroviral therapy for several months to decrease the number of potentially infected white cells in his semen. The couple was told that they had two days in which to attempt pregnancy. After they had intercourse, the woman took a short course of antiretroviral therapy as a prophylactic measure.
The expense was low because the man’s medications were covered by a third-party payer, the antibiotics were expensive, and the ovulation test sticks were inexpensive, Lewis notes. The short course of antiretroviral therapy also is relatively inexpensive.
"The idea is to not allow them to have indiscriminate intercourse at any time, but to maximize everyone’s potential," Lewis says.
If an HIV-serodiscordant couple wish to have a child and they don’t receive medical guidance, there’s a good chance they’ll figure out their own method of protection.
For instance, some couples in which the woman is HIV-positive have attempted using a condom with a hole in it during intercourse as a way to protect the man and still achieve pregnancy.
"There are a range of ways to protect the uninfected spouse," says Rebecca Denison, founding director of Women Organized to Respond to Life-Threatening Diseases in Oakland, CA. Denison, who is HIV-positive, is married to a man who is HIV-negative. They have twin daughters whom Denison conceived and delivered after she found out she was HIV-positive. The Denison’s daughters remain HIV-negative after 4½ years.
"I know someone who had sex with an uninfected partner, using a condom, and when he was about to ejaculate they whipped off the condom," Denison says. "People try to look at their most fertile periods and get the viral load as low as possible before trying."
In other cases, the HIV-negative wife has said that she doesn’t care about whether she becomes infected, and they’ve had unprotected intercourse, Denison adds. The drive to give birth is that strong, she notes.
"When I met my husband, the thing that made him not just a boyfriend but the person I wanted to spend the rest of my life with was the life I saw us building together with children," Denison explains. "I knew he’d be the most fabulous father in the world, and I knew I’d be a wonderful mother, and he is and I am."
References
1. Semprini AE, Persico T, Savasi V, et al. Semen washing in ART for uninfected women with HIV-positive partners. Program O-043. Abstract presented at American Society for Reproductive Medicine meeting. San Diego; Oct. 25, 2000.
2. Hanabusa H, Kuki N, Kato S, et al. An evaluation of semen processing methods for eliminating HIV-1. AIDS 2000; 14:1,611-1,616.
3. Downing M. Sperm washing: Reducing the risk of father to mother transmission. InSite. Available on Web site: hivinsite.ucsf.edu/prevention/prev_contro/9098.0085.html. Aug. 7, 2000.
4. Marks R. "Sperm Washing: How it Works." American Radio Works. 1999.
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