European Alternative to Sperm Washing
Feb 3, 2008
Hi Dr. Frascino:
There have been so many sperm washing questions recently and since the fertility rates go down so much and it costs so much per try, I was wondering what you thought of the study below by Vernazza: and also this study: Safety and efficacy of sperm washing in HIV-1-serodiscordant couples where the male is infected: results from the European CREAThE network. Louis Bujan, Lital Hollander, Mathieu Coudert, Carole Gilling-Smith, Alexandra Vucetich, Juliette Guibert, Pietro Vernazza, Jeanine Ohl, Michael Weigel, Yvon Englert, Augusto E. Semprini, for the CREAThE network. AIDS. September 2007;21(14):1909-1914
Pietro Vernazza, a physician at the Cantonal Hospital in St. Gallen, Switzerland, is going to talk a little bit about his poster, which is very interesting. Dr. Vernazza, could you tell me a little bit about why you decided to do this poster?
Yes. We have been involved in the past 10 years in insemination with processed semen from [serodiscordant] couples who wanted to conceive a child. Now, we also have studied, together with colleagues in the United States, the risk of transmission as a function of HIV viral load and semen. What I realized from 2000 onwards: All these couples that came in for treatment were very select couples, where the male [HIV-positive] partner was on a fully suppressive treatment. When we measured HIV in their semen, it was not existent at all. We couldn't find it. So I knew the risk of a transmission is very, very low.
Now, when we sent them, then, to the infertility clinic, this is a procedure that is quite time consuming. It's also costly. I started to ask myself whether this process is actually ethically correct. Then, in addition, I talked to Enrico Semprini, who was the first who started with the insemination [click here to view some of Semprini's publications].
Is this in Italy?
This is in Milan. And he followed ... About one third of the women who came for the first consultation would never show up for an insemination. And within Europe, all the centers have about one third no-shows, [these are people] who just don't follow up. Semprini followed up with them. And among the 500 couples, 250 are parents now.
So we realized we are giving a treatment for two thirds of the couples. About one third, or 40%, will get a baby. But the rest will do it [have unprotected sexual intercourse in order to conceive] by themselves.
We were sort of accepting that a major group of these clients, and all those outside of the program, were taking the risk and having unprotected sex. So we thought: It's okay. The risk is very, very low. It's probably in the range of one in 100,000, or one in one million. That's about the risk that you take when you mount an airplane.
We thought: Could we help these couples to reduce this, even very, very little risk? It's like wearing a seatbelt. We give them an additional safety. The additional safety is that we teach them just to have sex at the right time, when ovulation is happening (with a urine test).
Second thing: We make sure they don't have some asymptomatic chlamydia or other sexually transmitted diseases, because that increases the risk of transmission.
Then we make sure they are really stable, under a suppressive HAART. And the fourth point, which is probably the most important: We give a pre-exposure prophylaxis to the woman prior to the sexual contact -- the unprotected sexual act to conceive the baby.
We give them two doses of tenofovir [brand name: Viread; also known as TDF] at the time. When the urine test is positive [for ovulation], the next day, then the same evening, they have sex. Interestingly, the pregnancy rate in these couples is exceedingly high. After three unprotected acts, it's more than 50%. And it goes to a maximum, to a plateau, at around 70 to 75%.
I felt that is very interesting. It's certainly better than with the insemination practice, where we reach 40%. So I felt we should let people know about this experience.
Why did you choose tenofovir when the latest studies with chimpanzees showed FTC [generic name: emtricitabine; brand name: Emtriva] and tenofovir was better, or seemed to be a better prevention? My second question is: Why two doses, and not more, for a week? I know there are two days of ovulation, but it gives them more freedom.
Tenofovir has the advantage of a very, very long intracellular half-life that is about a week. So it is taken up over one or two days, and then it remains there at the place of action within the cells for a week. So that covers the risk period completely.
The question I have been asked at the poster discussion is: Why do you give it at all, since the risk is so low? I think that is probably the more relevant question. I think we give it to give a sort of psychological, additional argument, but I agree it's really a theoretically miniscule risk. And it's probably psychological. That would be the reason why I wouldn't go directly to a combination with FTC. But if you want to be more safe, safer than safe, that's fine.
I see. Because in actuality, we don't know whether the tenofovir did help at all in these couples. There's no way of teasing that out.
Of course. Right. We'll never find out.
How many couples did you do this with?
The ones that I recorded here [in this poster] are 22 couples. I also have, now, a collaboration with other clinics in Austria and Munich and in London. They are reporting that we're trying to get together a group of 35 or 40 couples. But it will never prove that there is no risk, because to prove that there is no risk is almost impossible, since we don't see any transmission from individuals with fully suppressed virus to the steady partner. There has been not a single case report worldwide.
But there haven't been any studies, so you can't ...
That's right. We know in the Swiss HIV cohort that approximately 150 to 200 [serodiscordant] couples always have unprotected sex, with fully suppressed virus, and they don't transmit.
In the Swiss cohort.
Yes. I'm sure it's the case with many, many other people. They just have sex. We see many new cases of HIV infection, but none of these new cases are associated with a sexual exposure to a partner on HAART with fully suppressed HIV.
Can you describe some of the illustrations in your poster?
Sperm washing. Reprinted with permission from Pietro Vernazza, M.D., et al. The first illustration shows a little bit of the technique that was developed by Semprini, where there is a two-step technique with a density gradient, where the larger cells, where the lymphocytes are, remain in the upper gradient of the centrifugation and then you collect the motile sperm in the pellet and do a second procedure, where you have a swim-up, where the sperm swim against gravity. And then you remove the upper layer, and that is used for the procedure.
Now, through this procedure you get about 1% of the motile sperm, which also explains a little bit why this method doesn't work as well as natural conception. There are also other reasons.
Pregnancy rates with natural conception. Reprinted with permission from Pietro Vernazza, M.D., et al. Right. Is this what we call sperm washing?
That is sperm washing. In the other graph, I show the number of cycles, and the number of couples. All of the couples started with the first cycle, and 20% of the women got pregnant after one exposure or sexual contact. Then after three [cycles] it's 50%, and it mounts to the plateau of about 70 to 75%. Then even after repeated exposures, you see that these couples very rarely get pregnant. It would mean, probably, that these [couples] have other fertility issues. That also needs to be addressed. I think it's important. All the fertility clinics in Europe that have now gained experience with HIV-positive individuals, they actually can also help them [these infertile couples]. I think there is still a role for fertility clinics to teach HIV-discordant couples. But for the majority of couples who just want to conceive a child, the natural way is much simpler.
A question related to this concerns stigma in Europe. I know in the United States a lot of fertility clinics do not want to publicly acknowledge that they help discordant couples. Is this similar in Europe, or is it more open?
I think it's more open, but there is still this stigma around, and there are still some people who think HIV-positive people, or discordant couples, should not have a child. It's sort of a belief ... or, I don't know ... it may also have to do with punishment. They are responsible for their disease, and they should get punished. It's not the way we think about people who smoke. It's very special for HIV. I think we should try to work against this stigmatization.
I think you're definitely helping with this study, and with explaining how couples do not, necessarily, need the help of fertility clinics to have a baby.
One interesting experience I had during the interviews with the couples: When I asked the couples, "What do you think is the risk of transmission when you have sex tonight?" Their estimate was in the range between 5 and 100%, a little bit higher for the women than for the men. So we haven't really properly informed these couples about the very, very low risk.
Of unprotected sex when one partner who is HIV positive is undetectable.
Exactly. Exactly. They still keep this high risk in their brain, and we haven't really openly talked about the changes in the risk of transmission, which we obviously observe. I think it wasn't a favor to them, because we sent them to the infertility clinics. They had to go through all this trouble. But on the other hand, we know it's not necessary, but we don't tell them. So that, during these interviews, causes a lot of questions, like, "Why I haven't I been told?" It also helps when I can reassure the couple that the question of sexual transmission risk is something that I have been involved with for the past 15 years. I have studied that and done research on that. Otherwise it would probably be a little bit difficult.
But within a few years, I'm sure that knowledge will disseminate, and it will change the habit of everybody.
So what's the reluctance, do you think? In the United States HIV specialists feel reluctant to say that. I have heard them say, "Well, I know the risk is minimal, but I ..." Because I guess they fear being responsible if a transmission occurs. Also, I guess, the second issue is: What if the positive partner becomes detectable? If I'm negative and my partner is positive, and even though he was undetectable the last time he went to the doctor, there is a possibility that he was not adherent and there was some viral breakthrough, so that he becomes detectable. But I believe he's still undetectable. And he doesn't have to go to the doctor for another month.
I think that's a very good point, and that's why I think this discussion about risk and behavior -- how do we make decisions about our sexual life -- is something that belongs in a steady partnership. The program that I'm talking about here is for steady partnerships. It's not about just in general. If I'm living with a partner and she takes drugs for HIV, I know exactly her adherence. I know exactly her virus. I have been talking with her doctor and herself.
So that is a little bit different situation than having sex with a partner who just tells me, "I'm suppressed." So I think it would be smart to restrict unprotected intercourse to couples where the partners know each other very well. I think that's important.
Click here to view Dr. Vernazza's study abstract.
Click here to view the slides from Dr. Vernazza's presentation.
Response from Dr. Frascino
I believe this is very encouraging data, but that the conclusions are premature. I certainly hope the follow-up studies confirm the preliminary results. That would truly be a wonderful advance for magnetic couples wishing to conceive. This report is generating considerable discussion. Stay tuned to The Body as the story evolves.
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