British HIV Association, BASHH and FSRH Guidelines for the Management of the Sexual and Reproductive Health of People Living With HIV Infection 2008

A. Fakoya; H. Lamba; N. Mackie; R. Nandwani; A. Brown; E.J. Bernard; C. Gilling-Smith; C. Lacey; L. Sherr; P. Claydon; S. Wallage; B. Gazzard

Disclosures

HIV Medicine. 2008;9(9):681-720. 

In This Article

3.0 Sexual and Reproductive Health Issues Affecting Both Men and Women Living with HIV

3.1 Management of Sexually Transmitted Infections in HIV-positive Men and Women

3.1.1 STIs in HIV-positive Women. Of the 7450 HIV infections acquired through heterosexual contact that were diagnosed in the UK in 2005, 63% were in women.[2] Heterosexual women living with HIV infection are on average younger than heterosexual men, which may partly reflect an earlier age of infection and an earlier age at diagnosis. The increase of HIV infections in women has been greater than that in heterosexual men. Sixty-four per cent of diagnosed women were aged 25-39. Many of these women living with HIV remain sexually active and have SRH needs. HIV care providers are now being urged to include regular STI risk assessments and investigations in the ongoing care of their patients.[11] Women living with HIV should be supported and have access to services that enable them to benefit from optimal sexual health and prevent onward transmission of HIV or other sexual infections.

3.1.2 STIs in HIV-positive Men. Homosexual and heterosexual men accounted for over 60% of the 53 000 people living with HIV in 2004.[1] Although the best way to provide access to STI services for HIV-positive individuals is still not entirely clear, there are clear reasons why attention to service provision is important. Sexual transmission is the main route of transmission of HIV in the UK and globally; it is well documented that both ulcerative[14,15,16] and non-ulcerative STIs[17] increase the risk of HIV transmission and acquisition. There is also an increased possibility of complications from hepatitis B and C, syphilis and herpes simplex virus (HSV) in those who have HIV infection. Ensuring that HIV-positive individuals have access to effective sexual health services should improve their sexual health and reduce the risks of onward transmission and superinfection. Recent outbreaks of STIs in HIV-positive MSM groups have highlighted the need to ensure that the ongoing sexual health issues of PLHA are addressed.

3.1.3 STI Service Provision and Delivery. Recommendations from the BASHH on the development and arrangement of STI services for PLHA[11] suggest that services should develop either facilities for STI treatment or pathways of referral to sexual health/genito-urinary (GU) services. Having HIV services provided within GU settings is not a guarantee that STI screens will occur, so it is important that all clinics providing HIV care make provision for addressing the service requirements of patients to ensure prompt diagnosis and treatment of STIs and other sexual health-related issues.

Service delivery for women and men should include:[18]

  • sexual health assessment, including a sexual history, documented at first presentation and thereafter at 6-monthly intervals;

  • provision of key prevention activities including screening for hepatitis A, B and C and immunization for the former two;

  • access to investigation, diagnosis and treatment of STIs (including hepatitides) and partner notification;

  • syphilis serology included in the routine HIV blood tests at first diagnosis and at 3-monthly intervals thereafter;

  • annual cervical cytology performed in all HIV-positive women with access to colposcopy services if required;

  • counselling to serodiscordant couples with availability of post-sexual exposure prophylaxis;

  • information and advice regarding re-infection and superinfection;

  • access to contraceptive services including provision of condoms;

  • support around disclosure;

  • clear pathways for advice and services for conception, pregnancy and fertility issues.

The management of the following infections does not differ significantly in patients who are HIV-positive: gonorrhoea, non-specific urethritis, uncomplicated chlamydia and lymphogranuloma venereum. The presentation and management of syphilis differ compared to HIV infection. Guidance on the specific management of STIs in HIV-positive adults, including hepatitis B and C, is available.[11,12,19,20] One important aspect of the overall management of STIs in HIV-positive individuals is ensuring regular routine screening for asymptomatic infections, which can be performed in GU and non-GU settings.

3.1.4 HIV and the Sexual Transmission Risks of Hepatitis C. It is important to highlight the sexual transmission risk of hepatitis C (HCV)[21] and to ensure that this is not forgotten by clinicians. Although the transmission risk has been identified as being relatively low, with 1-3% of partners of HCV-infected patients found to be infected in cross-sectional studies,[22] literature reports highlight that the transmission risk may be increased in MSM.[23] Co-infection with HIV, the duration of the relationship or chronic liver disease may be independent co-factors increasing the risk of transmission. Ensuring that people living with HIV are aware of the risk of HCV transmission and undergo appropriate screening is an important part of a sexual health strategy for all HIV clinical services.

3.2 Key Points and Recommendations

3.2.1 Sexual Health Support. All HIV-positive individuals under regular follow-up should have:

  • a sexual health assessment including a sexual history documented at first presentation and at 6-monthly intervals thereafter (II);

  • access to staff trained in taking a sexual history and who can make an appropriate sexual health assessment (III);

  • access to ongoing high-quality counselling and support to ensure good sexual health and to maintain protective behaviours (IV);

  • an annual offer of a full sexual health screen (regardless of reported history) with the outcome documented in the HIV case notes (II);

  • documented local care pathways for diagnosis, treatment and partner work for STIs in people with HIV that can be actively communicated to all members of clinic staff and to HIV-positive people (II).

3.2.2 Management of STIs in HIV-positive Men and Women.

  • The majority of STIs in people with HIV, including gonorrhoea and chlamydial infection, can be managed the same as in people without HIV (II).

  • STIs should be considered in the differential diagnosis of presentations such as skin rash or proctitis in HIV-positive people (I).

  • Syphilis serology documented at baseline and at 3-monthly intervals should be taken as part of the routine HIV blood set (unless indicated otherwise) to detect asymptomatic syphilis (II).

  • There are BASHH UK guidelines for the management of syphilis, genital herpes and warts in people with HIV. These should be referred to if managing individuals with these conditions (I).

3.2.3 Management of Hepatitis and Blood-borne Viruses. All HIV-positive individuals under regular follow-up should have:

  • hepatitis A, B and C screening at baseline and, if not already immune to HBV, should be vaccinated against it regardless of sexual orientation (III);

  • screening for hepatitis B and C offered annually in those who have exposure risks (IV).

3.3 Post-exposure Prophylaxis Following Sexual Exposure

Detailed guidelines concerning the use of ARV drugs as PEP following sexual exposure (PEPSE) to HIV have recently been published by BASHH. The present writing committee endorses these guidelines, which should be read in detail.[13] Some general comments about PEP in this situation follow.

  1. Randomized controlled studies are difficult to organize and have not been performed. However, animal experiments indicate that infection of monkeys with simian immunodeficiency virus (SIV) virus can be prevented by ART up to 24 h after the exposure of rectal or cervical mucosa to SIV. Two cohort studies where some sexually active patients, but not others, have been given ART have indicated a reduced rate of transmission of HIV. It is widely accepted (in the absence of randomized controlled studies) that PEP following parenteral exposure to HIV in healthcare workers is associated with a reduced risk of transmission of HIV. There is no a priori reason to suppose that responses to PEPSE would be different. Thus the present state of evidence indicates but does not prove that PEPSE is likely to have a favourable risk-benefit ratio.

  2. The time following sexual intercourse at which PEP might be effective is unknown. Data obtained in monkeys indicate that following SIV exposure of the cervix, there is a latent period of 24 h when no HIV can be detected and is presumably present and replicating in the antigen presenting cells. Rapidly thereafter, HIV infection can be found in surrounding activated CD4 cells and local lymph nodes. Because ART given during this initial latent period has the greatest likelihood of preventing infection, most guidelines continue to suggest that PEPSE should be offered for up to 72 h after exposure but recognize that such prophylaxis is likely to be more effective the more quickly it is given. The guideline stops short of recommending PEPSE only up to 48 h but there is little basis to provide it after this time.

  3. One of the major problems with PEP is the ability of the patients to adhere to the regimen. Such individuals are often psychologically vulnerable and relatively intolerant of side effects. Therefore, the choice of drugs is crucial to prevent both short-term toxicity and the risk of serious toxicity in individuals who have little chance of developing HIV infection. Most guidelines recommend a PI-containing regimen. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are not usually recommended. Nevirapine is contraindicated in people with a normal immunological system and the side effects of efavirenz are likely to be a bar to short-term adherence. Lopinavir in the new tablet formulation, tenofovir and emtricitabine (Truvada) are recommended as drugs for PEPSE.

    The optimum length of PEP remains a matter of conjecture but again most guidelines recommend a month's course of treatment.

  4. It is recognized that the risks of HIV transmission following sexual exposure are low, with passive anal intercourse having a higher risk than active anal intercourse in MSM. Insertive vaginal intercourse is of lesser risk, and less so for the male partner compared to the female partner; passive oral sex has a very small but definite risk of HIV acquisition. (The precise risk remains unknown because of the difficulties of establishing a denominator in individuals practising exclusively oral genital sex only). Following sexual intercourse with a partner of unknown HIV serostatus, the risk will depend upon the prevalence of HIV in that particular population, but overall the risks are likely to be much lower than those following sexual intercourse with a person who is known to be HIV-seropositive.

  5. If PEP following sexual intercourse is going to become a public health priority,[24] this will require either the setting up of specialized clinics or the education of accident and emergency departments and general practitioners in the treatment and care of such individuals. A number of models have been used to look at the likely cost-effectiveness of such an approach. These models may not be directly applicable to the situation in the UK, having mainly been derived from American data. Nevertheless, it is likely that offering prophylaxis is cost-saving despite the cost of administration of drugs for a month to a relatively large number of individuals who would not develop HIV infection. In general, offering PEP to men having unprotected sex with other men is likely to be more cost-effective than offering PEP to heterosexuals, particularly when the serostatus of the partner is unknown. The risk of sexual transmission of an individual who is known to be HIV-positive but whose viral load is less than 50 HIV-1 RNA copies/mL using a sensitive polymerase chain reaction (PCR) assay is unknown for certain; however, data suggest that the risks in such individuals are extremely low.

In summary, with the incomplete data available to us, any recommendations have to be tentative but it is likely that the risk-benefit analysis is favourable for prescribing PEPSE for up to 72 h following an episode of sexual intercourse where there has been a risk of HIV transmission. This is highly likely to be cost-effective when the partner is known to be HIV-positive and is not on ART. Cost-effectiveness is also likely in homosexual relationships with a partner of unknown serostatus and in heterosexual relationships where the partner is known to be HIV-positive. We believe that these data are clearly strong enough to offer PEPSE on an adventitious basis and to encourage non-government organizations to explore innovative ways in which such prophylaxis can be offered within a short time of sexual intercourse, but recognizing the need for informed consent and an explanation of the possible risks of taking such prescription drugs. While there are theoretical worries that this more proactive approach might increase risk-taking behaviour, there is no evidence that this is the case.

The issue of providing widespread pre-exposure prophylaxis, i.e. taking ART (potentially just one drug) prior to risk-taking sexual activity, is controversial. Animal data suggest that such an approach may reduce but not obviate the risks of transmission of retroviruses. Trials mounted primarily in resource-limited settings to test pre-exposure prophylaxis have run into ethical difficulties surrounding the need for HIV testing prior to randomization in the trial, the provision of ART to those who develop HIV during the course of the study and the provision of adequate counselling advice to reduce high-risk behaviour. Nevertheless, there is anecdotal evidence that such an approach is already quite widespread and there is an urgent need to explore whether such treatment encourages risk-taking behaviour and is associated with protection or with the development of ARV resistance if monotherapy approaches are used.

3.4 Key Points and Recommendations

  • All units should have explicit policies and procedures on PEPSE.

  • All HIV-positive individuals should be made aware of the units' procedures to access PEP.

3.5 Conception Issues

3.5.1 Pre-conceptual Counselling, Natural Conception and Assisted Reproduction. The change in the natural history of HIV infection and reduction in mother-to-child transmission as a result of ART has led to a re-evaluation of the ethical and moral arguments previously used to deny assisted reproduction to HIV-infected patients.[25,26,27,28] Increasingly, parenting is regarded as a realistic option for couples where one or both partners is infected and the demand for reproductive care is rising.[29] Although few centres in the UK are equipped to offer assisted reproduction to HIV-positive patients, the needs of these patients are now recognized and increasingly supported by state funding.

The main objectives in offering reproductive care are to ensure that couples fully understand their reproductive options and the risks and benefits associated with each method so that they can make an informed choice. They should be advised on the risks of natural conception methods pertinent to their circumstances and on assisted conception techniques that can enhance protection of the uninfected partner and future child from viral infection and increase the chances of successful pregnancy when fertility factors are identified. Centres offering assisted conception to infected patients should address the safety of healthcare workers and other patients attending the fertility centre through formal risk assessment and consequent adaptations of all procedures and laboratory and clinical facilities used.

3.5.2 Natural Conception - Unprotected Intercourse. Conceiving through timed unprotected intercourse and abandoning condom use has previously been contraindicated in couples where one or both partners is infected with HIV. Current evidence supports a more open discussion of this option with the couple to quantify, as far as is reasonably possible, the risks in individual cases to enable them to make an informed decision on whether the level of risk is one that is acceptable to them as a couple and in particular to the HIV-negative partner in serodiscordant cases.

Viral transmission during vaginal intercourse in serodiscordant couples depends on numerous factors but those that are most relevant to couples in stable monogamous relationships who are attempting to conceive are plasma viral load of the infected partner, presence of STIs and frequency of intercourse. If an infected man is in a stable relationship but not taking ART, the risk of HIV transmission to his uninfected female partner is quoted as 0.1-0.3% per act of intercourse, provided the couple are not participating in any other form of high-risk activity.[30,31,32] The risk for female-to-male transmission is reported to be lower at 0.03-0.09%.[33] Because viral load in plasma is generally correlated well to that in genital secretions,[34,35] the risk is considerably lower in a man or woman with long-term undetectable viral load through use of ART. A review of 19 empirical studies (n = 1226) of the association between serum viral load and semen viral load found a mean correlation of 0.45.[36] Although semen viral load was in general lower than in blood plasma, the review concluded that the factors that had a major influence on the relationship between plasma viral load and semen viral load were co-existing STIs, use of and adherence to ART that had optimal penetration of the genital tract, and the absence of drug resistance.

When the infected man or woman is fully suppressed through long-term ART, biological data support the view that an undetectable viral load can also be achieved in genital secretions.[35,37,38]

The presence of STIs (e.g. syphilis, urethritis) increases viral load substantially in genital secretions but not in plasma, even when the patient is asymptomatic;[39,40] this effect is reduced by prompt treatment of the STI.[41] On the basis of this evidence, it is not unreasonable for serodiscordant couples where the infected partner has an undetectable serum viral load for more than 6 months through use of ART to consider the option of conceiving through carefully timed unprotected intercourse, provided they have also been counselled on the alternative options.[42,43]

One of the difficulties in counselling serodiscordant couples on natural conception methods involving unprotected intercourse is that the risk to the uninfected partner is difficult to quantify but can certainly not be quoted as zero. Mathematical models cite a risk of 1 in 100 000 per act of intercourse. In practice, viral shedding in semen has been reported to occur even in men fully suppressed on ART because of different compartmentalization of HIV in plasma and semen.[44,45,46] A recent retrospective study of 551 semen samples analysed in HIV-1 infected men undergoing sperm washing identified 15 cases of detectable HIV-1 in ejaculated semen in men with long-term undetectable plasma viral load through use of ART, highlighting a need for caution when couples consider a natural conception approach.[47] In the case of serodiscordant couples where the woman is HIV-positive, the evidence is equally concerning: detectable HIV has been identified in follicular fluid and endometrial samples from a series of HIV-positive women undergoing in vitro fertilization (IVF), even when plasma viral load was suppressed fully through the use of ART.[48]

A review of the retrospective and prospective epidemiological literature on sexual transmission risk in serodiscordant couples attempting to conceive through unprotected intercourse indicates that data are limited and sample sizes small. A prospective cohort study of 453 HIV serodiscordant couples in Rakai, Uganda, reported a dose effect for infected patients with no transmission in cases where the infected partner had plasma viral loads of <1000 copies/mL.[49] A prospective study of 393 heterosexual couples having unprotected intercourse over a 14-year period reported no HIV transmission when the infected partner was on ART compared to an 8.6% risk when not on ART.[50] A prospective study of 92 serodiscordant couples having unprotected intercourse reported no seroconversions in the partners of the 41 patients on ART compared to six seroconversions where the partner was not on treatment.[51] Three studies have analysed infection risk in serodiscordant couples attempting to conceive naturally. The first was a prospective study conducted prior to the widespread use of ART and examined the risk of unprotected intercourse timed to the fertile window in 96 discordant couples where the male was infected. Four seroconversions were noted in the female partners, two during pregnancy and two post-partum.[27] The seroconversions were identified in couples in whom condom use post-conception and outside the fertile window was inconsistent. A more recent, retrospective study attempted to quantify the risks of unprotected intercourse in discordant couples where the man had an undetectable viral load through use of ART for at least 6 months. There were no seroconversions in 62 discordant couples who conceived.[52] Apart from the small sample size, the study is further weakened by the fact that seroconversions were not analysed in couples who failed to conceive, where the risk might be enhanced by repeated exposures. The only study to prospectively assess viral transmission risk in serodiscordant couples attempting to conceive naturally where the man was fully suppressed on ART and additional pre-exposure prophylaxis (PrEP) was used in the female partner involved only 22 couples[53] (see section 4.6).

The number of reported cases is still far too small to provide couples with a precise risk index if they wish to conceive naturally, but does reflect an increasing tendency by serodiscordant couples to pursue natural conception methods if they cannot access, fund or do not wish to go down the sperm washing/assisted conception route. This review of the literature also emphasizes the need for much larger multi-centre prospective monitoring of both pregnancy outcome and viral transmission risk in these couples if we are to improve the advice we can give to them. The physician does need to ensure that the uninfected partner has a full understanding of the small possibility of becoming infected through unprotected intercourse. More importantly, the need for ART adherence and regular attendance for STI screening in the couple and viral load checks in the infected partner should be stressed. In order to reduce the risk of unnecessary exposure in couples experiencing fertility issues, the couple should be advised of the benefits of having a fertility screen prior to attempting to conceive naturally. This should include a semen analysis for the male partner and an endocrine profile and baseline pelvic scan in the early follicular phase of the cycle (day 2-5) for the female partner together with a mid-luteal progesterone to confirm whether ovulation is occurring and non-invasive test of tubal patency (e.g. hysterosalpingogram), unless there is a history of pelvic pain or infection (in which case, laparoscopy and dye should be used to assess tubal patency).[54]

Clinics should consider asking couples to sign a form confirming that they have received comprehensive pre-conceptual counselling covering all their options for conceiving, including natural conception, and that they fully understand the risks associated with each method.

For seroconcordant couples attempting to conceive through unprotected intercourse, there are no conclusive data on the overall risk of superinfection (see section 4.6.4). The only scenario where concordant couples should be discouraged from attempting to conceive naturally is when drug resistance has been identified in one or other partner.

3.5.3 Reproductive Options for HIV-positive Men and HIV-negative Women Involving Assisted Conception Techniques. HIV discordant couples where the male is infected who desire to eliminate or significantly reduce HIV transmission risk to their uninfected partner are limited to the following options:

  1. Insemination using donor sperm: this effectively removes the risk of viral transmission because sperm donors are screened for HIV and other blood-borne viruses. However, it also removes the option of genetic parenting from the infected male. In the UK, there is a current shortage of donor sperm because all donors are to be identifiable by the future child.

  2. Sperm washing: the female partner is inseminated with the infected partner's sperm, centrifuged first to separate spermatozoa from seminal fluid and associated non-sperm cells.

  3. Adoption: this is a more difficult option for couples because current adoption practice regards HIV in one or both partners as a significant undesirable factor when assessing the suitability of parents requesting to adopt. Nevertheless, this is an approach that has been successful for some serodiscordant couples.

3.5.4 Sperm Washing. Sperm washing is a well-established, effective and safe risk-reduction fertility option for both discordant couples where the man is HIV-positive and the woman HIV-negative and concordant couples where viral resistance has been identified. Semen is centrifuged to separate live sperm (which does not carry HIV) from seminal plasma and non-germinal cells (which may carry HIV) and then inseminated into the female partner at the time of ovulation. If a couple have additional fertility issues, sperm washing can be combined with ovulation induction, IVF or intracytoplasmic sperm injection (ICSI). The technique is based on the observation that HIV is present in seminal fluid and as cell-associated virus in leucocytes and non-spermatozoa cells (NSC) but is not capable of attaching to, or infecting, spermatozoa. This is well supported by the literature on the subject, which is extensive.[55,56,57,58,59]

In technical terms, sperm-washing involves centrifuging ejaculated semen in a 40-80% colloidal, silica density gradient to separate progressively motile HIV-free sperm from NSC and seminal plasma, which remain in the supernatant. The sperm pellet at the bottom is resuspended in fresh medium and centrifuged twice before the preparation of a final swim-up. As a quality control for the procedure, and to protect the service from medico-legal action, an aliquot of washed sperm (approximately 100 µL) should be tested for detectable HIV RNA prior to the sample being used for treatment.[54,60] A nucleic acid-based sequence amplification (NASBA; Biomerieux, Basingstoke, UK) or similar commercial assay can be used. The risk of the sample having detectable HIV is 3-6%.[61,62,63] This is because centrifugation fails to remove all the seminal plasma and leucocytes in a small proportion of cases. The number of washes is limited because repeated centrifuging leads to loss of sperm quality and quantity. A double tube technique has been proposed to increase yield and reduce the need for post-wash HIV testing but has not been adopted by the majority of centres offering this treatment because it is not currently available commercially.[64] There have been no reported cases of infection of the female partner when sperm washing is carried out following published protocols in over 3000 cycles of sperm washing combined with intrauterine insemination (IUI), IVF or ICSI published to date.[65] A multi-centre retrospective analysis of 1036 serodiscordant couples from eight centres in Europe offering sperm washing reported the results of 2840 IUI cycles, 107 IVF cycles, 394 ICSI cycles and 49 frozen embryo transfers with careful HIV follow-up of the negative female at least 6 months post-treatment. All tests recorded on the female were negative (7.1% lost to follow-up), giving a calculated probability of contamination equal to zero [95% confidence interval (CI) 0-0.09%]. Clinical pregnancy rates recorded with all forms of treatment were comparable to those found in cycles carried out in HIV-negative couples.[66]

3.5.5 Clinical Management of Couples Undergoing Sperm-washing Treatment. Clinical work-up prior to sperm washing should include a sexual health screen and fertility screen in both partners. The sexual health screen is performed to ensure that the viral status of both partners is known at the time of treatment and that any genital lesions or infections can be treated - these increase the risk of viral transmission[67] and reduce pregnancy rates. The purpose of the fertility screen is to define the optimum mode of treatment. The screen includes a semen analysis in the male partner and endocrine profile and baseline pelvic scan in the early follicular phase of the cycle (day 2-5) for the female partner together with a mid-luteal progesterone and non-invasive test of tubal patency (e.g. hysterosalpingogram), unless there is a history of pelvic pain or infection (in which case laparoscopy and dye should be used to assess tubal patency).

The couple should be advised to continue with protected intercourse prior to and during treatment. A case of female seroconversion has been reported following condom breakage in a couple awaiting IVF treatment with washed sperm. Failure to take adequate precautions could lead to the incorrect reporting of treatment failure because of poor sperm preparation technique.[68]

Most couples electing to have sperm washing are voluntarily infertile and do not have significant fertility issues. For these couples, IUI is the preferred first-line treatment and should be carried out in a natural cycle, unless the woman is anovulatory (in which case clomifene or injectable gonadotrophins are recommended). Ultrasound follicular tracking is used to time insemination accurately and, where possible, human chorionic gonadotrophin is administered to ensure that the timing of ovulation is known precisely. Between three and six cycles of IUI are recommended before a couple are offered assisted conception with either superovulation and IUI or IVF. If there is evidence of tubal blockage, the couple are advised to have IVF with washed sperm. If the semen analysis is poor then ICSI is advised. IVF and ICSI outcome are not affected by the use of washed sperm compared to the use of ejaculated sperm. The protocol described is similar to that used in the majority of European centres offering sperm washing and aims to minimize the high costs and risks of multiple pregnancy and ovarian hyperstimulation associated with IVF and ICSI treatment.

3.5.6 Effect of HIV on Semen Parameters and the Outcome of Sperm Washing and Intrauterine Insemination. The majority of HIV-positive men have semen parameters within the defined World Health Organization (WHO) normal range. In the largest analysis of semen parameters in HIV-positive men to date,[69] Nicopoullos and colleagues found all parameters to be significantly impaired compared to HIV-negative controls and a positive correlation between total count and total and progressive motility and CD4 cell count. There was no correlation between viral load, years since diagnosis, use of or duration of ART with any semen parameter. These findings are consistent with previous reports in the literature. Analysis of 140 cycles of IUI with sperm washing found that semen parameters did not have a significant impact on IUI outcome following sperm washing. However, markers of HIV infection affected IUI outcome significantly. Clinical pregnancy rate was significantly higher in cycles where the man had a low viral load (<1000 copies/mL) and where the man was on ART. CD4 cell count had no impact on IUI outcome. There are insufficient data at present to recommend starting ART purely to improve IUI success rates, and the decision to start medication should be based primarily on the health of the individual.

3.5.7 Management of HIV-positive Women. HIV-positive women planning to have children should receive pre-conceptual counselling on mother-to-child transmission risks, their long-term health and the possible effects of ARV medication on the foetus. Women not taking ART should be advised to avoid unprotected intercourse and be instructed on how to carry out self-insemination of her partner's sperm at the time of ovulation in order to minimize viral transmission risk through unprotected intercourse. Women with effective viral suppression through long term use of ART should also be instructed on self-insemination but also be counselled on the current evidence regarding the low, but possible, risk of viral transmission to their uninfected partner if they attempt to conceive naturally. Should they elect to attempt natural conception, the couple should have regular screening for STIs and be advised to limit intercourse to the time of ovulation; the woman should also be advised on the importance of adherence to medication and regular checking of plasma viral load.

There is increasing evidence to suggest that HIV-positive women have reduced fertility as a result of reduced ovarian reserve and tubal damage.[70] HIV-positive women undergoing IVF have been noted to have lower IVF success rates than HIV-negative controls because of a reduced response to superovulation.[71] In this study, there was no difference in IVF outcome in HIV-positive women undergoing ovum donation compared to HIV-negative controls - pointing towards an effect of HIV on ovarian response and ovarian reserve rather than implantation. Retrospective data from sub-Saharan Africa[72,73] and prospective data from the UK indicate an increased incidence of tubal infertility in HIV-positive women.[69] For these reasons, there is a good argument for carrying out a fertility screen from the outset on HIV-positive women electing to conceive naturally to avoid unnecessary exposure if they have a fertility issue that can only be overcome with assisted conception methods such as insemination or IVF. Women trying to conceive through timed self-insemination should be referred for fertility evaluation if they have not conceived within 6-12 months of self-insemination. Referral should be earlier if there is a history of pelvic inflammatory disease or they are over 35 years of age.

3.5.8 Reducing Risks Associated with Pregnancy. Minimizing risk in HIV-positive women lies primarily in reducing mother-to-child transmission. There are no specific measures that can be taken during fertility treatment to further reduce this risk. There is concern that invasive procedures such as IVF could increase the chances of the embryo becoming infected. The number of women treated so far is small and prospective data limited. A study of 10 women undergoing IVF or ICSI demonstrated that HIV was detectable in follicular fluid removed during vaginal egg collection in all patients with a detectable serum viral load and 60% of those with an undetectable serum viral load.[48] This raises the theoretical possibility of the embryo becoming infected at the laboratory stage, even before the embryo is transferred back to the woman. Centres electing to treat HIV-positive women need to monitor all IVF or ICSI cycles in positive women and audit short- and long-term outcome.

Management of HIV-positive women should involve a multidisciplinary team comprising HIV physician, fertility specialist and obstetrician with a special interest in HIV. The couple should have a sexual health screen for the same reasons as couples undergoing sperm washing. Likewise, they should have a fertility screen in a similar way to HIV-negative couples (early follicular phase endocrine profile and pelvic scan, mid-luteal progesterone and test of tubal function) and the male partner should have a semen analysis.

3.5.9 Pre-conceptual Counselling. The most important aspect in the management of serodiscordant and concordant couples wishing to conceive is reproductive counselling prior to starting treatment to enable them to make an informed choice about their reproductive options, the inherent risks and costs of each treatment and the likely chances of success. Pre-conceptual counselling of HIV discordant couples must include a summary of the available data on safety for each method together with advice on additional methods of reducing risk such as limiting intercourse to the fertile window, regular screening for STIs, the need to identify at an early stage the presence of reduced fertility or sterility in either or both partners and the use of PrEP. The discussion should balance the risk of natural conception with that of more established risk-reduction methods such as sperm washing or risk-free options such as donor insemination. Although it is well recognized that timed unprotected intercourse may be a preferable option for discordant couples unable to access (or finance) options such as sperm washing or donor insemination, the limited number of cases reported in the literature assessing the risk and safety of this approach should be emphasized. Consideration should be given to the duration of counselling and the specialist inputs required. Although there is currently little literature to inform units, establishing a multidisciplinary approach with fertility specialist and HIV counsellor could be considered (C. Gilling-Smith, personal communication).

Pre-conceptual counselling should also address the possibility of treatment failure and how the couple would cope if they successfully had a child but the infected parent became more seriously ill or died. Those electing to have assisted conception with sperm washing have to understand that this is a risk-reduction method and not a risk-free method; technically, virus could still be present in the washed sample at a titre below the detection limit of the HIV assay. When the female partner is HIV-positive they need to understand the risks of mother-to-child transmission and the methods used that will reduce this risk to < 2%. They should plan and agree to attend a specialist obstetric unit once pregnant to ensure that they receive the best possible advice to minimize mother-to-child transmission risk. Fertility clinics treating HIV-positive patients have a moral, ethical and medico-legal responsibility to ensure that specialist counselling is available at all stages of treatment and that the welfare of the future child has been taken into account.[74] Reproductive counselling is particularly pertinent in concordant couples where prognosis and life expectancy in each should be discussed carefully with the HIV physician.[75]

3.5.10 Safety of Healthcare Workers and Non-infected Patients. The Human Fertilization and Embryology Authority (HFEA), which regulates all UK assisted conception clinics, currently requires all patients undergoing assisted conception to be screened for HIV, hepatitis B and C before undergoing treatment. Under the HFEA regulations, gametes and embryos from patients with known viral infections must be cryopreserved in separate tanks for each infection and infection combination. Unfortunately, this requires large areas of the clinic to be dedicated to cryostorage and numerous storage tanks to be purchased, which in practice has led to only a few laboratories in the UK offering treatment to infected patients. Both the HFEA and European Tissue Cells Directive require assisted conception units to have quality management systems that ensure detailed risk assessments are performed regularly and audits carried out on all aspects of care. Handling and freezing gametes and embryos from patients who are HIV-positive carries a small risk of cross-contamination to samples from HIV-negative patients and health workers involved in assisted reproduction; viral cross-infection has been reported in other areas of laboratory practice.[76] Unfortunately, conventional methods of cleaning and sterilization cannot be applied in areas handling human gametes and embryos. For this reason, in addition to the deployment of universal precautions, it is recommended that samples from patients with known or suspected blood-borne viruses are handled in a separate laboratory or laboratory area with equipment (e.g. incubators, flow hoods, cryostorage tanks) dedicated to handling infected samples.[76] An alternative to this, if space and cost are issues, is to schedule viral-positive cases to be treated at a different time to viral-negative ones.

3.5.11 Demand for Fertility Care. It is difficult to estimate the demand for reproductive care among HIV-positive patients. A UK audit of demand for assisted reproduction techniques in HIV-infected patients found that 16% of men and 4% of women attending HIV specialist clinics had enquired about fertility treatment. Following the HFEA recommendation of compulsory HIV, HBV and HCV screening prior to offering assisted reproduction techniques, 30% of fertility centres stated that they planned to start treating HIV-positive males and 26% planned to treat positive females. In practice, very few centres in the UK have elected to treat HIV-positive patients and equipped themselves with the necessary laboratory facilities. Many patients arrange to have their reproductive counselling, investigation and monitoring in their local centres and have only the IVF or sperm-washing treatment in the specialist centre to minimize cost and travelling.

3.5.12 Key Points and Recommendations.

  • HIV-positive men and women and their partners planning to have children should receive pre-conceptual counselling on all their conception options including HIV transmission risks associated with each option so that they can make an informed choice (IV).

  • Detailed comprehensive pre-conceptual counselling should be available for couples considering conceiving. This should document the available options and the possible risks of each method. All discussions should be documented clearly in clinical notes (IV).

  • Clinics advising serodiscordant couples on risk-reduction strategies for natural conception should obtain signed consent that both parties understand and accept the small risks of HIV transmission (IV).

3.5.12.1 Management of Couples Where the Male is HIV-positive.

  • If the man is not taking ART, protected intercourse should be encouraged at all times and pre-conceptual counselling should explore the options of sperm washing, donor insemination and adoption.

  • If the man has long-term undetectable viral load (>6 months) through the use of ART, pre-conceptual counselling should also cover the risks of natural conception with intercourse timed to the fertile window, with and without the use of PrEP in the female, and the need for ART compliance, regular screening for STIs in the couple and regular checks on plasma viral load in the man.

  • If either natural conception or sperm washing is contemplated, both partners should undergo a sexual health screen and fertility screen.

  • Couples electing to have timed unprotected intercourse should be advised of any fertility factors identified and assisted conception options discussed if these are deemed to improve their chances of successful outcome. Any STIs should be treated and advice on the correct timing of intercourse to the fertile window given.

  • Couples electing to have sperm washing should initially be offered natural cycle insemination with washed sperm unless the fertility screen identifies abnormalities in the female or seminology.

  • Superovulation with insemination, IVF or ICSI using washed sperm should be considered if conception has not occurred after between three and six cycles of treatment or fertility factors are identified.

  • Sperm should be centrifuged in a density gradient according to published protocols and samples tested for the presence of HIV RNA before being used for insemination to protect the clinic from litigation.

  • To avoid cycle cancellation because of the sample testing positive post-washing, a previous sample of washed and tested sperm can be frozen as a back-up.

  • Couples should sign a consent form before sperm-washing treatment confirming they understand sperm washing to be a risk-reduction procedure.

  • An audit system should be in place to monitor the HIV status of the female partner post-treatment (HIV test 3 months after last treatment) and paediatric outcome.

3.5.12.2 Management of couples where the female is HIV-positive. In women not on ART, protected intercourse should be encouraged at all times and couples advised on the method of timed insemination into the vagina of sperm ejaculated into a condom free of spermicidals.

In women on ART with long-term HIV suppression (>6 months), pre-conceptual counselling should also discuss the risks of unprotected intercourse timed to ovulation in the female cycle and the need for regular viral load and STI monitoring along with adherence to therapy stressed if the couple elect to conceive in this way. Fertility screening of both partners should be offered from the outset to minimize unnecessary exposure of the uninfected male if fertility factors are identified.

Fertility investigations should be arranged when pregnancy is not achieved within 6-12 months of self-insemination or natural conception. In women with a history suggestive of tubal disease or anovulation, fertility investigations should be offered from the outset.

Assisted reproductive techniques (IUI, IVF or ICSI) should only be offered within centres equipped to carry out procedures on patients with HIV and trained to audit outcome: little is known of the impact of invasive procedures such as IUI, oocyte retrieval and embryo transfer on vertical transmission risk.

Treatment should be planned to minimize any risk of multiple pregnancy (i.e. controlled superovulation, maximum of two embryos transferred).

When the male partner is also infected with HIV and viral resistance has been identified, the sperm should be washed to reduce the risk of transmitting mutated resistant HIV strains to the female partner and offspring.

  • ARV medication should be discussed with the treating HIV physician and adjusted pre-conceptually according to BHIVA recommendations.[10] If the patient is not on ART, a plan should be made to initiate this by the third trimester, at the latest.

  • Known teratogenic agents such as efavirenz should be stopped pre-conceptually.

  • Once pregnancy is confirmed, referral should be made to a specialist obstetric centre if expertise in the antenatal management of HIV-positive females is not available locally.

  • The decision to provide licensed treatment in HIV-infected individuals, particularly when both are infected, should be based on a 'welfare of the child' assessment, as in any other couple.[74] The treating HIV physician should be asked to provide the assisted conception centre with a summary of the patient's care and prognosis; he/she is likely to be best informed of ongoing high risk activity and medical issues that might affect long-term health.

  • The couple should be advised to continue with protected intercourse during treatment and pregnancy, and not expose themselves to high-risk activity such as intravenous drug use.

  • Units electing to treat female patients infected with HIV on ART should monitor short- and long-term paediatric outcome to identify any potential adverse effects of ART at the time of conception on the child.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

processing....