This post describes the effect of HIV on the male reproductive system and on the management of male infertility. HIV was not fully recognized by clinicians and scientists until 1981. In the year 2005, it has been estimated that there were 40.3 million people living with HIV. Currently the largest site of the epidemic is in sub-Saharan Africa. It is possible that the virulence of the virus may change or mutations may render current testing strategies ineffective; however, new and increasingly effective treatments are being developed. After infection with HIV, there is a latent period of a number of years when the person remains well but the virus can be detected in the blood. At this early stage, treatment with antiviral agents such as zidovudine (AZT) has been shown to delay the progression of the disease. For these reasons, it is important to have a cautious and flexible approach so as to minimize risk to infertile couples and to future children.

Transmission Of HIV Between Partners

Male-to-Female Sexual Transmission

The overall chance of transmission of HIV from an infected man to his female partner from a single act of unprotected receptive vaginal intercourse is 0.0005 to 0.0015. This risk may increase as the disease advances and white cell counts fall. The managing clinician is responsible for ensuring that both partners have full information about risks and strategies to prevent transmission.

Prevention of Sexual Transmission

Currently there is no effective vaccine against HIV, and prospects for a vaccine have been disappointing. At present the AIDS epidemic is out of control and whenever possible spread should be prevented. The only effective strategies are education (particularly of young men), enhancement of the status of women, and the use of barrier methods of contraception. The most effective barrier method is the male condom. The female condom is a slightly less effective barrier. It is common to advocate the use of spermicide with condoms but it is not known whether this reduces the risk of HIV transmission. There is evidence that treatment with AZT in men reduces the cellularity of the ejaculate and presumably reduces the chance of male-to-female transmission.

Table High-Risk Behavior

  • Men who have had sex with another man in the preceding 5 yrs
  • Persons who report nonmedical intravenous, intramuscular, or subcutaneous injection of drugs in the preceding 5 yrs
  • Persons who have engaged in sex in exchange for money or drugs in the preceding 5 yrs
  • Persons with hemophilia or related clotting disorders who have received human-derived clotting factor concentrates
  • Persons who have had sex in the preceding 12 mo with any person described in the above four categories or with a person known or suspected to have HIV infection Persons who have been exposed in the preceding 12 mo to known or suspected HIV-infected blood through percutaneous inoculation or through contact with an open wound, nonintact skin or mucous membrane
  • Inmates of correctional systems. (This exclusion is to address issues such as difficulties with informed consent as well as increased prevalence of HIV in this population)

Risk Factors for Sexual Transmission

High-Risk Sexual Behavior

Multiple partners and male homosexuality have both been identified as high-risk behavior with respect to the chance of HIV transmission. Table High-Risk Behavior provides the Center for Disease Control Guidelines for high-risk behavior associated with risk of HIV transmission.

Concurrent Sexually Transmitted Disease

Concurrent sexually transmitted diseases can increase the chance of HIV spread either because open genital sores or ulcers provide an entry port for HIV or because an increase in the number of immune cells in the ejaculate associated with urethritis increases the viral load in the ejaculate. In the context of infertility treatment for the couple where the male partner is HIV positive, sexually transmitted diseases should be treated in both the man and his parrner(s), and fertility management should be deferred until the conclusion of sexually transmitted disease treatment.

Circumcision

Three prospective randomized trials have shown that male circumcision reduces the risk of the man acquiring HIV by approximately 50%. The three studies involved a total of 10,912 men and three studies had to be stopped at interim analysis because it was judged unethical to continue because of the evidence of a significant reduction in risk of the circumcised man acquiring HIV. Nevertheless, the role of male circumcision in the context of HIV prevention strategy remains controversial because of concerns that circumcised men may cease to use proven methods of HIV prevention such as using condoms. There is a need for continued research to define the effect of male circumcision on the risk of transmission to the partner (female or male) and on the sexual behavior, condom usage etc. of men who have been circumcised.

Vertical Transmission

HIV transmission to a child may occur at the time of insemination if sperm from the HIV-positive father are used. It may also occur from the mother to the child through the placenta, at birth, or by breastfeeding. Many of these risks are not amenable to prevention but common sense indicates that good antenatal and obstetric care should be given and that situations such as undiagnosed placenta previa or obstructed labor should be avoided. Several studies indicate that breastfed infants are at greater risk of acquiring HIV from their infected mothers than bottle-fed infants. Thus, breastfeeding is best avoided in this situation unless there is potential for increased infant morbidity and mortality due to unsanitary water conditions.

Prevention of Vertical Transmission with AZT

The European Collaborative study reported transmission rates observed in 600 children born to HIV-positive mothers as of June 1990. The vertical transmission rate based on results in 372 children with at least 18 months follow-up was 12.9% (c.i. 9.5-16.3). At the time of this study, treatment with AZT was not widely used for HIV-positive pregnant women. There is good evidence that the chance of vertical transmission from the HIV-positive mother to the child may be reduced by treating the woman with AZT during the peripartum period and six weeks of AZT for the infants. This is an expensive treatment approach and is not available in all countries. Furthermore, it may be that shorter courses of AZT will be equally or nearly as effective, which is currently under investigation in clinical trials.

The Effect Of HIV On Male Reproductive Behavior

There is concern that in traditional societies, particularly in Africa where fertility is a mark of manhood, knowledge of HIV status may promote more promiscuous behavior because the man knows that he will not live a normal lifespan. In this situation, the problem is made more difficult by the unequal status of women. It is recommended that focused programs of testing and counseling need to target men, particularly those without access to modern media.

The Effect Of HIV On The Male Reproductive System

The Effect of HIV on Spermatogenesis

It is rare for HIV to cause infertility per se, although ill health associated with advanced disease may reduce fertility. In general, men who are seroposirive but without AIDS show little or no difference in semen characteristics, whereas those who have AIDS may have pyospermia and abnormal sperm.

Within the last five years, the infertility clinic at the Western General Hospital in Edinburgh, Scotland has seen no case where the primary presentation has been a male partner with infertility in association with HIV infection. HIV entered the Edinburgh population in the mid-1980s; the current prevalence is approximately 1 in 100 men under the age of 30. In the same period, we have seen more than 1000 couples in the infertility clinic. Our experience indicates that HIV is an uncommon cause of male infertility.

Reduced fertility in men with sexually transmitted disease may be the result of damage to spermatogenesis following orchiris or abnormal ejaculation in association with urethral stricture. Although both these conditions may occur in patients with HIV, they are not part of the primary disease process. It is worth mentioning that we have seen several young men present with HIV and urethral stricture and three young men who had difficult-to-treat orchitis.

The Effect of HIV on Male Sex Hormones

A relatively common autopsy finding in patients who have died of AIDS is adrenal necrosis, and several studies have identified adrenal defects in AIDS patients. Hypogonadorropic hypogonadism was identified in 24 of 63 patients with AIDS and a correlation was noted between this finding and lymphocyte depletion and weight loss. It has been postulated that the weight loss may be related to a defect in dihy-drotestosterone generation but clinical data does not support this hypothesis; however, rather surprisingly, there are also reports of an increase in total and free testosterone in some cases. With more effective treatment of HIV, emphasis will shift from cure to quality-of-life issues. Further work will be needed to define androgen status depending on the stage of the illness and the treatment given. In advanced cases, there may be a benefit from androgens to promote weight gain, but any benefit would be from the general anabolic effect of the androgen rather than correction of a specific defect.

Fertility Treatment For Couples In Whom One Or Both Partners Have HIV

If the decision is made that it is reasonable to proceed with treatment, the couple should cooperate to reduce the chance of infection of the uninfected partner, and, most importantly, to reduce the chance of the child becoming infected. In a survey in the United Kingdom in 1995, 9 of 58 in vitro fertilization (in vitro fertilization (IVF) centers were providing treatment for couples in whom the male partner was HIV positive. The ethical question of offering fertility treatment is discussed below.

Preventing / Reducing Male-to-Female Transmission in the HIV-Discordant Couple

HIV-discordant couples in this situation have used various approaches to avoid male-to-female transmission. The most common approach is artificial insemination with the sperm after laboratory processing to remove HIV. For those couples who do not have access to laboratory processing, an alternative is to use barrier methods at all times except the woman’s fertile period. Use of this strategy has resulted in the birth of 24 live born children and only one new HIV infection.

Couples should receive advice about sexual practices to minimize transmission to the unaffected partner. Advice given should include the use of condoms, proper treatment of any concurrent sexually transmitted diseases, and avoidance of sexual intercourse during menstruation and / or until any open genital sores have been treated and healed.

Insemination of HIV-Negative Women with Processed Sperm from an HIV-Positive Partner

Results from Milan indicate that the use of gradient centrifugation followed by swim-up effectively removed HIV-1 infected cells from the ejaculate of HIV-positive men. In 29 serodiscordant couples, 17 pregnancies were achieved in 15 women. There were no cases of seroconversion and 10 babies born to these mothers remain seronegative; however, centrifugation and swim-up, while reducing HIV-1 infected cells, may not altogether eliminate risk. In another study from Italy, HIV-1 particles have been found incorporated within human spermatozoa and can be introduced into the human oocyte.

In Vitro Fertilization and the HIV-Positive Couple

There is little information in the literature about the use of in vitro fertilization in the presence of HIV, but in principle, the same considerations that apply in other infertility treatments apply here. Special consideration must be given to the staff regarding proper disinfection of all nondis-posable equipment.

HIV And Surgery Of The Male Genital Tract

With the increasing prevalence of HIV, surgical staff have adopted universal precautions for every patient, with no special precautions for the HIV-positive surgical patient. Good practice includes regular review of universal precautions, and whenever possible, adoption of safer surgical practices.

Donor Insemination

HIV and Gamete Donor Recruitment

The clinician responsible for a donor gamete program has a duty to obtain healthy gametes that pose no risk to the couple or the future child; however, there is also a duty to the gamete donor. In many countries, donation of gametes is voluntary and without payment; hence, it is important to have a clinical practice that is kind to donors. If problems are encountered, there must be adequate facilities to offer donors appropriate advice and treatment. The consequences of discovering HIV must be discussed with a prospective donor before he or she agrees to participate. Sometimes this may result in a potential donor deciding not to go ahead with screening tests. If unexpected HIV infection or any other infection is discovered, the results have to be communicated to the potential donor and appropriate counseling and treatment must be made available. Lastly, potential gamete donors should sign a consent statement indicating that they have reviewed and understood the information regarding the spread of HIV, and that they will not donate should they be HIV positive or at risk of acquiring HIV.

All donors should be subject to a screening program to reduce the risk of transmitting HIV and other infections. Many of the of these precautions will also apply to donation of other tissues; for example, blood donation and organ donation. The screening program should include:

1. History taking and exclusion of prospective donors based on acknowledged risk behavior (see Table. Interviewers should ask direct questions about high-risk behavior.

2. Physical examination and exclusion of those with signs or symptoms of HIV or any other sexually transmitted disease, or needle tracks indicating drug abuse.

3. Tests to exclude those who are positive for HIV or any other sexually transmitted disease. Samples should be tested for antibody to both HIV1 and HIV2. Current tests rely on the detection of antibodies to HIV, but there is a period between inoculation and the detection of antibodies or antigen in blood samples and, in order to avoid missing infected donors, sperm are stored in liquid nitrogen and quarantined.

Storage Of Gametes In Liquid Nitrogen Banks And Quarantine

Quarantine Time for Stored Gametes in Relation to the Seroconversion Period of HIV

The quarantine period for stored gametes needs to exceed the seroconversion period for HIV; that is, the period from inoculation with the virus to the appearance of antibodies or antigens in the serum. It is difficult to obtain precise information about the seroconversion period because there is often doubt about the date of inoculation, except in those situations where there has been a transfusion with infected blood, implantation of an infected organ, or accidental needle stick. An analysis of published data led to an estimated median of 2.1 months from exposure to antibody detection. These investigators concluded that 95% of cases would be expected to seroconvert within 5.8 months and that HIV infection for longer than six months without detectable antibody was uncommon. It is also worth noting that with new testing technology, it is possible to detect virus antigen using the p24 enzyme immunoassay test, which can shorten the time from inoculation to virus detection compared with the usual seroconversion periods calculated from data obtained using antibody tests. Another important consideration is that HIV is a new disease that is now infecting large numbers of humans; in these circumstances, it is possible that there may be adaptation by the virus to the human host and virulence and incubation periods could change.

The main arguments against the quarantine of sperm have focused on the cost and reported lower success rates when frozen sperm are used compared with fresh sperm. There is variation in practice between countries; in 1987 it was estimated that 80% of donor inseminations in the United States were using fresh semen. Since then, with the advent of intracytoplasmic sperm injection ( intracytoplasmic sperm injection (ICSI), the need for donor insemination has diminished and the use of frozen semen has increased. In the United Kingdom, all donor insemination is performed using frozen quarantined sperm according to guidelines issued by the UK Human Fertilisation and Embryology Authority. The recommended quarantine period is six months; however, in our clinic in Edinburgh, for the last six years, we have quarantined all samples for one year because of occasional reports of longer seroconversion periods and to guard against the possibility of virus adaptation with longer seroconversion periods.

Quarantine as Protection Against Problems with Virus Detection

Another reason to quarantine sperm is to guard against virus mutation resulting from difficulties with virus detection. Problems with the detection of HIV are more than theoretical as seen in a study of British Public Health laboratories. A new HIV assay was put into use with the advantage of increased sensitivity for outlier HIV variants. However, following the reporting of false negative results, use of the assay was restricted. Out of 20,973 samples tested, there were four false-negative results giving a sensitivity of 99.2%. In this case, our one-year quarantine period in Edinburgh would have protected our patients against detection problems.

Prevention of Contamination of Stored Gametes within the Store

There have been no direct examples of HIV cross-contamination of sperm samples stored in a liquid nitrogen sperm bank; however, this must not be a matter for complacency. There has been evidence of cross-contamination of hepatitis B virus from a contaminated cryopreservation tank. Thus, there is a potential hazard when untested samples are stored alongside those in quarantine. It is not practical to sterilize the outside of the storage ampoule or straw. If there is contamination of the outside of the straw, then there is the possibility of contamination of the liquid nitrogen and the coating of all other ampoules in the store with virus particles. While not routinely practiced, consideration needs to be given to the use of storage straws or ampoules that are double wrapped. There is also a risk of lost straws or ampoules or small particles of contaminated material falling to the bottom of a large container. These may remain undiscovered for some time. It is recommended that the storage container be periodically emptied and cleaned, and this cleaning should be recorded in a log. Consideration needs to be given to designing storage straws or ampoules with a second outer wrapping to eliminate the risk of contamination of the outside of the straw by the liquid nitrogen.

HIV Transmission Using Infected Sperm that Have Been Banked in Liquid Nitrogen

In previous years the main form of help for couples with male factor infertility has been insemination with donor sperm. More recently this is used less frquently because of in vitro fertilization, and, in particular, intracytoplasmic sperm injection has enabled fertilization with a single sperm in situations formerly considered untreatable. As originally practiced, donor insemination involved the use of fresh sperm but with the advent of HIV infection, most clinics in the world have switched to the use of frozen and quarantined sperm.

There is a report of HIV transmission from fresh sperm used for donor insemination. Although there is a report of transmission of HIV from cryopre-served semen, no details are given about the quarantine period or retesring of the donor.

 Ethical Considerations When Treating Couples in Whom One Partner Has HIV

The main ethical problems center on risks to the future child and risks of transmission of HIV to the partner.

HIV Transmission to the Child

Most cultures put the interests of the future child ahead of the interests of the infertile couple. Some clinicians would regard any risk of HIV transmission to the child as a contraindication for any fertility treatment that would facilitate conception; however, if the actual risk of HIV positivity in the child is remote, other clinicians would regard help for the couple as acceptable; thus whether to proceed or not is judged according to risk.

HIV Transmission to the Partner

The transmission of HIV to the uninfected partner should be prevented, and clearly both partners need to be informed about HIV. When one partner is not willing to inform the other regarding HIV positivity, the clinician is in a difficult situation and must do everything possible to persuade the patient to change his or her mind. If the patient refuses, it would be very difficult to justify helping with any fertility treatment. Also, a decision has to be made about whether to inform the other partner. If the other partner is also a patient of the clinician, there is a conflict between the duty of confidentiality to patient one and the duty of care to patient two. In these circumstances, the duty of care would seem to override the duty of confidentiality. There can be little doubt about this if the uninfected partner is the woman who wishes to become pregnant.

Is It Right to Deny Fertility Treatment?

If a decision to help a couple with HIV toward fertility is made, it must be remembered that the child has a need for a healthy parent. Thus, it is in the interest of the future child to try to prevent cross-infection to the uninfected partner. For couples who are unable or unwilling to try to minimize transmission of HIV to the uninfected partner or to the child, the attending clinician must consider whether the interests of a future child are best served by helping with fertility treatments.

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