In June 2011, the Southern African HIV Clinicians’ Society, together with an expert working group, developed the Guidelines on Safer Conception in Fertile HIV-Infected Individuals and Couples.¹ Since then, interventions to manage and prevent HIV have evolved and, similarly, options for safer conception have expanded. These updated guidelines provide healthcare providers with up-to-date information to support efforts to optimise safer conception care.

Key game changers between 2011 and 2018

Introduction

In southern and sub-Saharan Africa, the majority of HIV-positive individuals are adults of reproductive age,²³ many of whom desire children^{24,25,26,27,28} and between 30% and 50% of them have an HIV-negative partner,^29,30 although many may remain unaware of their own or their partner’s status.^31,32,33 Attempting natural conception, without using any HIV risk reduction strategies, places HIV-affected couples at increased risk of HIV transmission.²⁸ This likely contributes to regional estimates that up to 60% of new HIV infections occur in stable serodifferent couples.³⁴ Acknowledging the considerable overlaps between high HIV prevalence in reproductive-aged individuals, HIV transmission risks and active fertility desires, safer conception services need to be scaled up across the region.^35,36

Modern ART, which is highly effective, with lower toxicities and pill burden, ensures that HIV can be managed as a lifelong, chronic disease and that MTCT and infection of an HIV-negative partner can be almost entirely avoided if testing and treatment are effectively offered and utilised. With this in mind, the medical and ethical arguments previously used to deny the rights of HIV-positive women to become pregnant, or HIV-positive men to have biological children, are becoming increasingly irrelevant.³³ Healthcare providers need to actively engage with people living with HIV (PLHIV), and their partners, to respect and support the fulfilment of their reproductive rights and desires. Parenting should now be normalised for any individual or couple affected by HIV. These guidelines attempt to provide practical information about how this goal can be achieved safely, with optimal health and minimal HIV acquisition risks for any uninfected partner and the resulting child.

The routine provision of appropriate contraception and safe prepregnancy planning support holds the potential to impact adult HIV testing and ART uptake, VL outcomes, adult HIV prevention efforts and the achievement of elimination of mother-to-child transmission (EMTCT).³⁵ It is one of the few cross-cutting interventions that can positively impact across numerous HIV and sexual and reproductive health programmes to the benefit of women, men and children. This requires accessible and safe fertility planning services and includes both the prevention of unplanned pregnancy through the use of appropriate contraceptive methods and the achievement of a planned, healthy pregnancy.

Scope of the guidelines

The guidelines are designed to assist healthcare providers to, first, identify clients’ fertility desires and second, provide safe and effective pregnancy planning guidance to a presumed fertile couple who currently desire a child and where one or both partners are known to be living with HIV or are at possible risk of acquiring HIV because of having condomless sex with a partner(s) of unknown HIV status.

Both resource-limited settings, such as most public health sector facilities across the region, and resource-intensive clinical settings, including the private sector, where assisted reproductive technologies may be available, have been considered. However, even in resource-intensive settings, with effective ART and other risk reduction strategies, costlier assisted reproductive technology, for example, sperm washing, IUI and in vitro fertilisation (IVF), should no longer be considered necessary purely for the prevention of HIV transmission.^20,21,35

It is important to recognise infertility and refer individuals or couples who are unable to achieve pregnancy; however these guidelines do not cover the management of infertility.

It should be noted that much of what is covered in these guidelines is relevant to all couples desiring pregnancy.

Structure of the guidelines

The first section, ‘Discussing fertility and childbearing with HIV-affected women and men’, discusses how providers can raise the issue of fertility planning and help identify the desires of HIV-affected women and men in relation to preventing an unwanted pregnancy or planning a desired pregnancy.

The second section, ‘HIV-affected clients who express a desire to have a child’, focuses on the management of individuals and couples who desire pregnancy, with an emphasis on management of HIV and other comorbidities prior to attempting pregnancy. This section includes strategies for serodifferent and seroconcordant couples, as well as undisclosed individuals or individuals with an unknown status partner, to minimise risks of horizontal and vertical HIV transmission.

The third section, ‘Clients with no immediate plans for a child’, provides a very brief overview of contraceptive provision within the context of HIV for those who do not desire a child at present or in the future.

The fourth section, ‘Additional considerations for optimising prepregnancy health’, provides an overview of several additional service delivery issues, including prepregnancy counselling, basic assessment for underlying infertility, as well as management of comorbidities, pregnancy in older women and basic management if pregnancy is confirmed or a miscarriage occurs. Special considerations for the provision of counselling for HIV-affected single women, same sex and transgender individuals and couples desiring pregnancy are briefly covered.

A word on terminology used in the guidelines

Safer conception

Safer conception is the term used throughout these guidelines to refer to the overall process of choosing one or more risk reduction strategies to try and minimise HIV transmission and acquisition risks while attempting to achieve a healthy pregnancy. Although in the field of fertility medicine the word conception is no longer used because it is not a distinct biological event,³⁷ for the purposes of these guidelines it was felt important to maintain continuity with existing literature and guidelines, which speak to safer conception with particular reference to minimising HIV risks during the time when an HIV-affected couple is attempting pregnancy.

HIV-affected individuals and couples

The term HIV-affected individuals and couples includes a range of HIV relationship combinations, all of which require specifically tailored support to minimise HIV risk and to maximise the possibility of a safe pregnancy. Couples may be in a mutually disclosed seroconcordant or serodifferent relationship, relationships where one or both partners have unknown HIV status or partnerships in which one individual is living with HIV and feels unable to disclose their status to their partner. HIV-positive and -negative individuals without a stable partner may also desire a child. HIV-affected men who have sex with men, women who have sex with women, bisexual and transgender individuals and couples may also have reproductive desires requiring the support of healthcare providers. In high HIV prevalence settings all HIV-negative individuals who have a known positive or unknown status partner fall within this definition of ‘HIV-affected’ and should be offered safer conception services if they desire a child.

Safe pregnancy

Safe or healthy pregnancy in this case refers to a minimised risk of HIV transmission to an uninfected partner and/or a foetus.

Horizontal HIV transmission

The transmission of HIV from one sexual partner to another is called horizontal transmission. It can also occur between people who inject drugs if they share injecting equipment.

Vertical HIV transmission

Vertical transmission is the transmission of HIV from mother-to-child, either during pregnancy, labour and delivery or breastfeeding.

Condomless sex

These guidelines specifically use the term condomless sex as opposed to unprotected sex because, with the availability of ART and PrEP, when a couple undertake sexual intercourse without a condom they are not unprotected; they are simply using other measures to protect themselves and their partner from HIV transmission and acquisition. This distinction is important because the phrase unprotected or unsafe sex creates anxiety in couples and also implies unsafe and irresponsible behaviour when, in fact, many of these couples are very committed to doing everything possible to achieve pregnancy safely and reduce risk to the HIV-negative partner.

Timed condomless sex

Timed condomless sex is one safer conception strategy that individuals or couples may choose to use to reduce the total number of HIV risk exposures undertaken while trying to achieve pregnancy. With this strategy, condomless sex acts are limited to the peak fertile window, which occurs around the time that the female partner ovulates. This strategy has also been referred to as timed periovulatory unprotected intercourse.

Healthcare provider(s)

This term refers to all clinicians, including doctors and nurses, and other staff such as counsellors and community healthcare workers who provide contraception, fertility planning and prepregnancy services for people affected by HIV, as defined by their scope of practice.

Serodifferent (serodiscordant)

The guidelines use the term serodifferent instead of serodiscordant to describe relationships in which one partner is HIV-positive and the other is HIV-negative. Other terms with the same meaning are seromixed, mixed status or magnetic couples. The term serodifferent is used in these guidelines rather than serodiscordant in response to the expressed preferences of PLHIV and their partners.

Disclosure and partial disclosure

In the context of these guidelines, disclosure is the process of revealing one’s HIV status to another person. Disclosure may also involve telling another person about his or her HIV treatment, health status or VL.

Partial disclosure, for the purposes of this document, refers to a situation in which one partner has disclosed their HIV status but may not have told the other partner all of the details of their HIV history. This situation can commonly arise when an individual who already knows his or her status, and may be well established on ARVs, chooses to disclose by attending for couples testing and counselling with their partner as if testing for the first time.

Partial disclosure may also refer to other aspects of a person’s history including previous pregnancies, children, miscarriages, terminations of pregnancy or failure to conceive with other partners.

Undetectable = uninfectious (U=U)

U=U is an abbreviation for undetectable = uninfectious or untransmissible. Over time, evidence has shown that if an HIV-positive person is well established on ART, adherent to treatment and has a recently confirmed, undetectable plasma VL, this person is considered uninfectious and will not transmit HIV (untransmissible).^8,9,10 This is discussed further in Box 2.

Infertility

Infertility is defined as the failure to establish a clinical pregnancy after 12 months or more of regular, condomless sexual intercourse in a non-contracepting couple. Infertility may be a result of an impairment of a person’s capacity to reproduce either as an individual or with his or her partner and can be a result of female factors, male factors or a combination of both.³⁷

Discussing fertility and childbearing with HIV-affected women and men

Despite improved quality of life and normal life expectancy resulting from effective ART, many HIV-positive and HIV-affected clients remain reluctant to discuss sexual activity, fertility and childbearing with their healthcare providers.^25,26,33 It is important for providers to provide culturally sensitive prepregnancy counselling (see Appendix 1) and reproductive health services.^2,27 Providers should be able to confidently initiate the discussion, create a conducive environment for open discussion and be able to provide fertility planning services tailored to the individual’s or couple’s goals and choices (section ‘Important points to note when discussing fertility choices and desires’, Figure 1 and Table 1).

Important points to note when discussing fertility choices and desires

Concluding the discussion – Different outcomes require different approaches

Working with couples

Working with couples and disclosure

Engaging both partners together requires full HIV status disclosure. This can raise many issues about which a provider should be sensitive:

HIV-affected clients who express a desire to have a child

Between 30% and 50% of HIV-positive individuals desire a child.^24,25,26,27 Many may already be actively trying to achieve pregnancy at the time of clinical consultation. In supporting these individuals, there are a number of considerations that need to be taken into account.

These guidelines focus on low-cost, low-technology strategies. For those clients who can access more resource-intensive options, such as sperm-washing with IUI, IVF or intracytoplasmic sperm injection (ICSI), these may also be considered. However, where there are no concerns about infertility, these interventions may not add any additional benefit, add extra cost and unnecessarily medicalise what can now be a safe, natural process.^21,35 Where available, these assisted reproductive technologies may provide additional options for couples who have suspected or confirmed underlying infertility. Identifying such couples is discussed briefly in the fourth section, ‘Additional considerations for optimising prepregnancy health’.

UTT and improved access to ART provide an important option for HIV prevention in serodifferent couples – as explained in Box 2.

In the context of U=U, all other safer conception strategies and approaches discussed in the following represent additional safety measures that should be offered to all couples and may assist those couples who remain anxious and prefer to use additional strategies for their own peace of mind.

However, these strategies do remain critically important options for those couples where viral suppression cannot be confirmed, because it is unavailable as a result of local resource constraints or where maintained VL suppression cannot be assured. They also apply during the period where the HIV-positive partner has not yet started or only recently started ART and is not yet virally suppressed. It is essential that providers remain aware that many HIV-positive people may not be able to attain an undetectable VL because of barriers to treatment access or adherence; others may have ART primary acquired drug resistance or secondary resistance as a result of previous ART exposure, and some may choose not to access HIV testing or, once diagnosed, may not feel ready to start treatment.⁷ In these situations, these other strategies, including PrEP for the HIV-negative partner, provide important options.

Achieving pregnancy as safely as possible – Choosing appropriate options

Figure 2 gives an overview of a range of strategies available to HIV-affected individuals or couples seeking to achieve pregnancy. The choice of strategies depends on what is appropriate, based on the HIV status of each partner, clinical considerations, available resources and, most importantly, client preferences (see section ‘Integrated package of care’, Table 3). Table 4, at the end of this chapter following the section ‘Medical male circumcision’, presents the recommended strategies for serodifferent, seroconcordant and sero-unknown couples in more detail.

ART with viral suppression and regular STI screening and management form the foundation of safer conception support. In cases where the partner’s serostatus or VL is unknown, other modalities such as PrEP become critical.

Antiretroviral therapy, viral suppression and pregnancy planning

For couples who plan to achieve pregnancy through condomless sex, the most important determinant of HIV transmission risk is plasma HIV VL. Effective ART reduces the plasma and genital HIV VL in the infected individual to undetectable levels.⁴³ Plasma HIV levels generally correlate positively with the concentration of HIV in genital secretions, rectal mucosa and saliva, although inflammation can stimulate local replication,⁴⁴ which is why screening for STIs is such an important component of safer conception care.

Many HIV-affected couples still have much anxiety about trying to conceive in the context of HIV risk. It is important to share with them the robust evidence around U=U in order to provide evidence-based reassurance that they can, in fact, reduce the risk of HIV transmission between partners, and from mother-to-child, to zero if the positive partner or partners are established on ART and confirmed virally suppressed with maintained high levels of adherence over the long-term (see Box 2).⁷

Antiretroviral therapy initiation

Key information and recommendations regarding dolutegravir safety in the periconception period and early pregnancy

Recommended duration of antiretroviral therapy before attempting to achieve pregnancy

Antiretroviral drugs in pregnancy

We recommend standard first-line, second-line and third-line regimens be used in pregnancy.⁶ Based on the accumulated evidence, we endorse the WHO guidance that efavirenz can safely be used in pregnancy and in women who intend to become pregnant.¹⁴ Their guidance was based on a meta-analysis that found that the incidence of NTDs and all congenital abnormalities among women exposed to efavirenz in the first trimester was similar to that of the general population.¹⁵ The FDA category D classification of efavirenz, and accompanying package insert, should be discussed with women, explaining that this was based on animal studies; human cohort studies have not demonstrated an increased risk of congenital abnormalities, but there is a background low risk of congenital abnormalities in all pregnancies, unrelated to drugs.⁵³ Providers are also referred to the section ‘Key information and recommendations regarding dolutegravir safety in the periconception period and early pregnancy’ which presents recommendations pertaining to dolutegravir use in women of childbearing potential.

Providers are encouraged to maintain high levels of pharmacovigilance, reporting any adverse outcomes seen in women on any ART drug during pregnancy (for either treatment or prevention) to their local ART pregnancy registry.

HIV-positive women not yet on antiretroviral therapy and confirmed pregnant

Many countries, including South Africa, have implemented UTT ART guidelines so all people testing positive for HIV should be offered immediate ART, regardless of their CD4+ count or clinical staging. Prior to this, South Africa had implemented the Option B+ PMTCT strategy, which made provision for any women commencing ART during pregnancy to then continue ART lifelong.¹³ Any HIV-positive woman presenting pregnant before HIV diagnosis or ART initiation should be initiated as soon as possible, preferably on the day that pregnancy is confirmed, and then reviewed in one week to follow up on baseline bloods and continue with treatment literacy and adherence counselling. Refer for antenatal care (ANC)/PMTCT services as soon as pregnancy is confirmed or as early as possible in pregnancy.

Similar to horizontal transmission, viral suppression is critical to reduce the likelihood of vertical HIV transmission to the foetus in utero or to the infant during delivery. The longer a woman is on ART during pregnancy, the better the outcomes – for herself and for her infant – because of an increased likelihood of an undetectable VL at delivery, thus preventing peripartum MTCT.^54,55 Undetectable VL also reduces the risk of HIV transmission during breastfeeding as well as transmission to any serodifferent partner during this time.

Pre-exposure prophylaxis

Pre-exposure prophylaxis for serodifferent and sero-unknown couples

It is recognised that for many women, the involvement of their male partners in couples counselling and testing or in any part of the health system remains a challenge.^56,57,58 While health systems grapple with the challenge of developing male-attractive health services, it is important that HIV-seronegative women and their unborn offspring be protected even when there are demands for condomless sex.

There is now considerable evidence that PrEP, in the form of tenofovir and emtricitabine, effectively prevents HIV transmission in serodifferent couples.^59,60 Studies have also shown efficacy with tenofovir alone, but to date WHO recommendations are for the combination of tenofovir and emtricitabine.

PrEP may thus offer additional risk reduction for the HIV-negative partner in a serodifferent relationship or be the only protection option in some cases. However, evidence and careful modelling have shown that PrEP would be unlikely to provide additional risk reduction benefit where the HIV-positive partner has been on ART for at least six months with optimal adherence or has confirmed viral suppression < 200 copies/mL by formal laboratory or point of care monitoring. In this situation, the risk of HIV transmission is already considered to be so low that PrEP would not add a further benefit.⁶¹

Using pre-exposure prophylaxis for HIV prevention

Pre-exposure prophylaxis and pregnancy

Where pregnancy is confirmed in a woman taking PrEP, the risks and benefits of continuing PrEP should be carefully discussed. There is currently no clear evidence of harmful effects resulting from significant in utero foetal exposure to tenofovir or emtricitabine. A systematic review that included studies observing HIV-negative and hepatitis B-positive women who took tenofovir and emtricitabine treatment throughout their pregnancies provided reassuring evidence including the following:⁶⁵

However, increased neonatal mortality risk with tenofovir exposure has been noted in two studies in relation to significantly higher very preterm delivery (< 34 weeks) and associated neonatal mortality when women were taking a tenofovir-based ART regimen compared to non-tenofovir ART regimen.^65,66 There also remains a need to assess longer-term infant growth and bone effects.

A limited number of PrEP studies including HIV-negative women who became, or were already, pregnant when taking PrEP are starting to emerge with similarly reassuring data to that seen among women using tenofovir or tenofovir and emtricitabine (Truvada^) for HIV or hepatitis B treatment.^{18,67,68,69,70}

Based on the accumulating evidence, the risks for pregnant or breastfeeding HIV-negative women using PrEP for HIV prevention are thought to be minimal and are outweighed by the prevention benefit where the woman remains at substantial risk of acquiring HIV during this time.⁷¹ It is important to explain to women who are taking PrEP and are confirmed pregnant that most current evidence is based on women using tenofovir or tenofovir and emtricitabine (Truvada^) as a form of treatment for an existing infection (HIV or hepatitis B), not as a prevention strategy. The woman’s risk of HIV acquisition during pregnancy and breastfeeding should be carefully considered and, where a woman remains at substantial risk of HIV infection, SAHCS, in alignment with recent WHO recommendations, advises that the woman be maintained on PrEP throughout pregnancy and during breastfeeding. This is particularly important for women who cannot negotiate consistent condom use and where the partner is either of unknown HIV status in a high HIV prevalence setting or known to be HIV-positive but not accessing care, not virologically suppressed or not adhering optimally to treatment. The benefits of continuing PrEP throughout pregnancy and breastfeeding in order to avoid seroconversion in the pregnant or breastfeeding woman, with consequent significant risk of MTCT, are considered to far outweigh any potential risk of tenofovir or emtricitabine exposure to the foetus or breastfed infant.^59,60,65

Note for South African providers: Currently the National South African Department of Health (DoH) Guidelines do not recommend PrEP during pregnancy because of regulatory issues as the Medicines Control Council regulatory approval includes a paragraph stating that PrEP use is contraindicated in pregnancy. Studies are currently underway to increase the exposure of pregnant and breastfeeding women to tenofovir-based PrEP and it is hoped that the DoH guidelines will soon be updated to synchronise with WHO recommendations. In this context, the final decision should be made through full consultation between clinician and client with a balanced consideration of risks and benefits.

The importance of HIV retesting

Post-exposure prophylaxis

Post-exposure prophylaxis (PEP) is recommended for accidental exposure to HIV, either occupational or non-occupational.⁷⁸ It is, however, no longer recommended as a key strategy for persons trying to achieve pregnancy because of the repeated risk exposures usually required to achieve pregnancy, which then necessitates repeated rounds of PEP. Any individual trying to achieve pregnancy who presents for PEP after condomless sex within the last 72 hours should be provided with a single course of PEP as per existing guidelines. They should then be counselled and offered to transition to daily PrEP, if available, as a preferred prevention method because of the expectation of repeated HIV risk exposures as they continue to try and achieve pregnancy.

Other components of prepregnancy workup

Table 3 (see section ‘Integrated package of care’) shows recommended basic investigations that may be undertaken in primary care facilities as part of prepregnancy workup in both resource-limited and resource-intensive settings.

Integrated package of care

Integrated care should be strongly supported. Clients should be counselled prior to their prepregnancy workup about these investigations and why they are important for their health.

Sexually transmitted disease screening and treatment

All males and females should be screened, using a basic questionnaire⁸¹ for new STI symptoms at each visit. If either partner is confirmed, or suspected, to have an STI then both partners should be managed according to local guidelines. The treatment course must be completed before pregnancy attempts begin. In most settings, STI screening and management will be based on the syndromic approach.⁸¹ However, because of the high rate of asymptomatic STIs seen in many populations,⁸² if available, tests for Chlamydia trachomatis, gonorrhoea (Neisseria gonorrhoeae), Trichomonas vaginalis, syphilis and herpes simplex virus-2 should be performed and any positive results managed by treating the client and his or her partner according to current treatment algorithms.

Effective STI screening is not only important for HIV transmission risk reduction but also to avoid the negative consequences of STI infections during pregnancy. These include higher risks of miscarriage, intrauterine growth retardation, premature labour and delivery, and the possibility of neonatal, congenital STI infection.⁸³

Timed condomless sex

Self-insemination

Sperm washing

In resource-intensive settings, a serodifferent couple with an HIV-positive male partner may opt to use sperm washing as a risk reduction strategy.⁸⁸ Following sperm washing, the couple would need to undergo IUI, IVF or ICSI, which are costly and invasive procedures when compared to natural conception. Again, the pros and cons to this approach should be discussed with the couple. As the risk of timed condomless sex is now considered to be so low in the setting of viral suppression with ART, even couples in resource-intensive contexts may prefer to opt for natural conception and avoid the costs, hospital visits and stress that can be associated with utilising IUI or other assisted reproductive technologies.

Medical male circumcision

HIV-negative men should be counselled on the benefits of male circumcision as an additional HIV risk reduction strategy.⁸⁹ There is also possibly a smaller benefit for partners of HIV-positive men in serodifferent relationships as circumcision may slightly reduce male-to-female HIV transmission risk.⁹⁰ Medical male circumcision (MMC) also reduces the risks of some other STIs and cervical cancer in female partners.⁹⁰ If medical male circumcision is performed, the couple should wait before trying to achieve pregnancy for at least six to eight weeks or longer if there is still discomfort to ensure complete healing of the circumcision wound.

Clients with no immediate plans for a child

Couples and individuals who wish to prevent a pregnancy in the near future should be offered a reliable contraceptive method of their choice, within a rights-based framework, as per existing national^2,91 or global²² contraceptive guidelines.

Although fertility may be reduced, particularly in advanced HIV disease, the overall incidence of pregnancy is seen to increase following access to ART.⁹² Importantly, the rate of unintended pregnancy remains high among HIV-positive women, just as seen in the general population.⁹³

Access to contraception contributes to the goals of EMTCT by strengthening Pillar 2 of the PMTCT programme (prevention of unplanned pregnancies), which remains one of the weakest areas of PMTCT programme implementation in many countries.

Using contraception is also an option for couples who do wish to achieve pregnancy but where certain aspects of their health need to be optimised before pregnancy attempts are undertaken. Initiating short-term contraception in this situation may help to prevent pregnancy being achieved under suboptimal conditions and different contraception options should be discussed. Examples where this may be relevant include when the HIV-positive partner is taking treatment for an acute opportunistic infection such as tuberculosis or other infection such as bacterial STI; where the female’s CD4+ count is still low but expected to improve; where the positive partner is only just initiating on ART and is not yet virally suppressed or where a new non-communicable disease is diagnosed and treatment is being optimised. An important consideration is to use a method with immediate return to fertility, as summarised in Box 3 (‘Special considerations when providing contraception to HIV-positive women’ section). These couples should be encouraged to continue using male or female condoms as part of dual protection.

Important points to note when providing contraception services

Where an individual or couple communicates that they prefer not to use condoms, the following counselling messages should be covered:⁵⁹

Special considerations when providing contraception to HIV-positive women

A range of detailed resources are available that provide guidance on contraceptive provision, including for women living with HIV.^22,94 Key points are highlighted as follows:

It is also important to note that for HIV-negative women there are concerns that DMPA/NET-EN hormonal injectable contraceptives may be associated with an increased risk of HIV acquisition and transmission.⁹⁹ Any HIV-negative female who chooses this contraceptive option should be counselled about the importance of consistent condom use to prevent HIV-infection, the option of treatment as prevention where her partner is on ART and virally suppressed and the increasing availability of PrEP.

Additional considerations for optimising prepregnancy health

Identifying and managing comorbidities

Deferring pregnancy for HIV-positive individuals or couples – Is it ever appropriate?

Ultimately the decision whether or not to achieve pregnancy rests with the client and providers should avoid personal judgements, especially concerning socio-economic or relationship status. However, there are medical circumstances in which a clinician should encourage the couple to consider deferring pregnancy, including the following instances:

In these instances, clients should be encouraged to attempt pregnancy only once health has been optimised. Where absolute contraindications exist, making pregnancy permanently inadvisable, the couple needs to be counselled accordingly, including the availability of other options such as fostering and adoption.

Expected time to pregnancy and fertility assessment

Trying to achieve pregnancy through condomless sex should only be undertaken if the couple are presumed fertile and expected to have a reasonable chance of achieving pregnancy. In contexts where resources are limited, this can be difficult to accurately assess. Where fertility potential is untested, the couple should try for at least six months before investigations are considered.

HIV itself can negatively impact male and female fertility.¹⁰⁷ Fertility, although improved with ART, may not return to normal. In the female, HIV may be associated with anovulation, amenorrhoea and premature ovarian failure. In males, HIV may negatively impact testosterone levels, libido and may contribute to erectile dysfunction.¹⁰⁷

Expected time to pregnancy

It is recommended that a presumed fertile, HIV-affected couple attempt pregnancy for at least six months before considering possible infertility.¹⁰⁸ The best chance of pregnancy is seen in the first six months of attempting pregnancy.¹⁰⁹ Although infertility is defined as the failure to achieve pregnancy after one year of regular, condomless intercourse, HIV-affected couples should be referred sooner, where referral options exist, to avoid prolonged HIV risk exposure. Failure to achieve pregnancy can be a considerable source of relationship stress so the provider should explain to any presumed fertile couple that, depending on age, up to 50% of couples in the general population will achieve pregnancy in the first six months, a further 30% – 40% of couples who continue trying will achieve pregnancy by 12 months and a further 5% – 15% will achieve pregnancy if they continue trying up to 24 months. Up to 5% – 10% of couples will not achieve pregnancy, suggesting underlying infertility.^110,111

Pregnancy testing

It is recommended that female clients perform a pregnancy test, using a home testing kit or by consulting with their provider for testing, if they miss their next expected menstruation. Urine beta-human chorionic gonadotropin (BHCG) is a reliable test to confirm pregnancy.

Suspected infertility

Where infertility is suspected, it is important that couples understand that male and female causes of infertility are equally common and it should never be assumed that one partner is ‘responsible’ for difficulty in conceiving (see Table 5).¹¹² In 22% of couples the infertility is male cause only. In 31% it is female only, with secondary infertility being more common than primary. In 21% both partners have an underlying problem. In up to 14% of couples no cause is found and 12% of couples conceive while undergoing infertility investigations.

Fertility assessment in low-resource settings

A thorough history can detect warning signs of possible underlying fertility issues, including the following:

Where referral options for further investigation and management do not exist, couples should be counselled about the risks of trying, or continuing to try, to achieve pregnancy where infertility is suspected. Alternative parenting options or adjusting to the possibility of childlessness should be discussed.

Fertility assessment in high-resource settings

Where resources are available, clients with a history indicative of infertility, or who have already tried to conceive for more than six months, may be referred to specialist fertility services for further workup, including hormone profiles in women and semen analysis for male partners. Fallopian tube blockage is also a common cause of infertility, which can be readily investigated via a hysterosalpingogram and, if a uterine abnormality such as fibroids is suspected, then a pelvic sonar should be performed. Where a couple is confirmed to be infertile, they may be candidates for assisted reproductive technologies such as IVF, IUI or ICSI, although these are often either unavailable or unaffordable for the majority of people living in high HIV prevalence settings.

Managing safer pregnancy outcomes

When pregnancy is confirmed

Counselling for those experiencing miscarriage

If an individual or couple returns to report a miscarriage, appropriate counselling should be provided and the woman managed as per local guidelines. It is important to acknowledge the disappointment and grief associated with miscarriage and to emphasise to the couple that no one is to blame and that early pregnancy loss is usually a result of an abnormality that occurred during early development of the foetus. Miscarriage is common, occurring in up to 25% of pregnancies. A couple is not at any increased risk of a further miscarriage unless they have had three or more miscarriages, at which point they should be referred to a specialist for further investigations. After a miscarriage, couples may want to start trying to conceive again straight away. It is recommended that the couple can start trying within three months from their loss, if they feel ready to do so.¹¹⁶ The preconception workup should be repeated to ensure that the couple are still ‘safe’ to start trying again.

Special situations

What if an HIV-positive woman desires a child but does not have a partner?

Options include insemination from alternative sperm sources such as a sperm bank or known male sperm donor (HIV status should be known), surrogacy or adoption. It is worth knowing what resources exist in your area, what the stipulated eligibilities are and what financial resources would be required.

A man or woman may also present without a stable partner, communicating their desire for a child. Whether they have one or multiple current, but not necessarily long-term, partners, they should still be offered all the available risk reduction strategies without judgement. Counselling should include a discussion about the increased risks associated with attempting to conceive via, or impregnate, multiple partners, if that is their chosen approach to fulfil their fertility intentions.

Men who have sex with men, transgender and female same sex couples

Options also exist for couples who may not be able to conceive naturally because they are in a same-sex relationship or one or both partners are transgender. Where necessary, further advice should be sought from the appropriate specialist to support these couples to achieve their reproductive goals as they have the same reproductive rights as heterosexual couples. Options include surrogacy for same-sex male couples and sperm donation for same sex female couples. A transgender male who is in a relationship with a cis-male (Cis-male is a male whose gender identity corresponds to the biological identity assigned at birth) may still be able to conceive and carry the pregnancy to term and should remain engaged in care to appropriately manage hormone therapy throughout pregnancy.

Acknowledgements

Thanks to the Wits Reproductive Health and HIV Institute (Wits RHI), in particular Natasha Davies and Melanie Pleaner, for their support in writing and editing these guidelines. Thanks also to those working in the international safer conception community and the clients of safer conception services, who helped to inform these updated guidelines.

No funding or assistance was provided for this process. And no authors have any conflict of interest to declare.

N.E.C.G.D. was the committee chair and primary author of the guidelines. All other authors either reviewed and contributed to the manuscript electronically and/or attended a full-day committee meeting where the guidelines were discussed and developed. T.R., M.P. and M.M. edited the document to produce the final version.

References

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Department of Health Republic of South Africa. National contraception and fertility planning policy and service delivery guidelines. Pretoria: South African National Department of Health; 2012.
National AIDS & STI Control Program Ministry of Health Kenya. Guidelines on use of antiretroviral drugs for treating and preventing HIV infections in Kenya. Nairobi: Kenyan Ministry of Health; 2016.
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Appendix 1: Prepregnancy counselling – Checklist and key messages

Prepregnancy counselling should ensure an informed choice about reproductive options, including any risks and costs involved with each strategy, as well as the likely chances of success.

Prepregnancy counselling should include the following:

A summary of available data on the safety of different strategies, and the impact of combining strategies to optimise risk reduction.
All safer conception strategies are considered risk reduction strategies and no provider should guarantee a risk-free process.
The importance of viral suppression for the HIV-positive partner with continued full adherence to ART (undetectable equals uninfectious: U=U) should be clearly explained.
- Because VL cannot be monitored continuously, full adherence is key to this approach, particularly if it is to be used in isolation, without any other strategy.
- Should there be an interruption in ART drug supply, or suboptimal adherence, at any point the client must alert their provider and pregnancy attempts should be deferred until viral suppression can be reconfirmed or other prevention strategies introduced.
A discussion of PrEP as an option in certain situations, especially where viral suppression may not be guaranteed, for example, HIV-positive partner recently initiated ART or concerns about adherence, not yet engaged in care or of unknown HIV status.
The importance of regular STI screening.
The need to assess for reduced fertility at an early stage to avoid the possibility of prolonged risk exposure during ongoing pregnancy attempts in the context of infertility where a couple has not conceived after at least six months of correctly timed pregnancy attempts.
The risk of transmission to a non-infected partner and MTCT if the female partner is HIV-infected, or becomes HIV-infected, and is not established on ART with an undetectable VL.
The importance of reporting any pregnancy as soon as possible to ensure early access to antenatal care so that maternal healthcare and PMTCT interventions can be optimally provided throughout the pregnancy.
Information about available PMTCT strategies for use throughout the pregnancy and breastfeeding period.
The importance of lifelong adherence to ART for any HIV-positive partner, for their own health and the prevention of horizontal and, for women living with HIV, vertical HIV transmission.
All female partners, regardless of HIV status, should be started on folic acid supplementation, as per local guidelines, prior to undertaking pregnancy attempts.

Key counselling points about conception options

Prepregnancy counselling should include the presentation of all safer conception options so that the individual or couple can make an informed decision about which strategy, or combination of strategies, they would like to use:

Condomless intercourse, even without peak fertility timing, is now considered a very safe option in the setting of consistent ART use with confirmed viral suppression (< 200 copies/mL), ongoing full adherence and STI screening for both partners, where possible.
Where viral suppression cannot be confirmed, explore additional strategies including limiting condomless intercourse to the peak fertile window, PrEP and MMC.
In resource-intensive settings, explore pros and cons of undertaking more costly conception options, including sperm washing and IUI, IVF or ICSI.

Appendix 2: Determining a woman’s fertile window

The basics: Ensure that clients understand how a woman’s reproductive cycle works. This is often poorly understood and forms the basis for optimising the strategy of timed condomless sex or self-insemination for safer conception.

Remember: For those HIV-affected couples who are U=U, precise timing of condomless sex to the fertile window is not considered necessary. If they are comfortable to do so, the couple should be advised to have regular, condomless sex, two or three times per week spread out equally over each week when the woman is not menstruating. For those couples who are anxious about multiple condomless sex acts, the strategy of timing condomless sex to limit them to the days of highest fertility can be explained.

Explain the following:

When an HIV-affected couple is advised to, or chooses to, limit their condomless sex acts to peak fertility, determining a woman’s fertile period is necessary to establish the timing of periovulatory intercourse. There are various ways in which a woman’s fertile period can be determined. The methods described here presume normal fertility and require minimal resources.
In situations where a woman’s fertility may be impaired, more resource-intensive methods such as Day 21 progesterone measurements or serial ultrasound monitoring, with or without ovulation stimulation through clomiphene administration, may be used by a reproductive specialist. These more intensive methods may also be used in women living with HIV (who have presumed normal fertility) in order to increase their chance of fertility prediction.

Fertile dates

The average normal duration of a menstrual cycle is 28 days. The first day of a woman’s menstrual period is considered to be Day 1 of her menstrual cycle. Ovulation is anticipated to occur 14 days before the next period is due to start. Her fertile period would be from five days before predicted ovulation up until 1–2 days after ovulation. For example, in a woman whose cycle is 28 days long, ovulation would be assumed to occur on Day 14. The woman’s fertile period would therefore occur between Days 9 and 16 of her menstrual cycle. This creates a seven-day window. This may be narrowed down to a peak fertile window of four days if the couple would like to minimise risk exposure further. This would be calculated as two days before predicted ovulation, the day of ovulation and one day after predicted ovulation.

However, menstrual cycle length may differ considerably between women and may even differ from month to month for an individual woman. It is therefore essential that a woman keeps a record of her menstrual cycle (typically taking into account the first day of her menstrual period) in order to determine an average menstrual cycle length. It is important to explain to patients that regular menstrual cycles may not necessarily indicate that ovulation has occurred. Ovulation is less likely to be occurring in women whose cycle is 24 days or less or 35 days or longer. There are now several mobile phone applications that are available for free that can assist women to keep track of their cycles and to predict ovulation. This can be a very helpful resource. Examples include CycleBeads™ and Dot™. It may take up to four months to establish an average cycle length where cycles are irregular and the more months that are recorded the more accurate the timing can become when using this method.

Ovulation prediction kits (for urine and saliva)

A number of over-the-counter products are available that enable ovulation prediction. These methods may utilise sampling and analysis of either urine or saliva and detect the surge of luteinising hormone that occurs immediately before ovulation. These test kits are becoming more affordable and can limit risk exposure to just two days per cycle because of their high levels of accuracy. The use of ovulation prediction kits can be particularly useful for women with irregular cycles where the calendar method is often not as helpful. In women where there may be a concern about anovulatory cycles, ovulation test kits may also help to identify if the luteinising hormone surge is not happening and there is a need for further investigation and management to promote ovulation.

Cervical mucus monitoring

Monitoring the cervical mucus changes that occur around the time of ovulation is also a useful means to identify peak fertility. During non-fertile days, the cervical mucus is thick and acidic. In contrast, during fertile days, the mucus undergoes a change to become thin, profuse, transparent and ‘stretchy’ (spinnbarkeit), like raw egg white. A woman’s awareness of these changes in her cervical mucus may help her to predict her fertile period and guide her pregnancy attempts. However, this method may not be as easy to use for some women, particularly those who use certain hygiene practices including douching or vaginal drying, as the cervical mucus is disrupted or washed away so changes in vaginal secretions may not be as easily observed. If the provider gathers a history of vaginal hygiene practices, it is advisable to counsel the client against such practices as there may be an association between vaginal douching or drying and increased rates of bacterial vaginosis,¹¹⁷ which in turn may be associated with increased rates of HIV transmission and pregnancy loss.^118,119

Appendix 3: Low-technology sperm collection and self-insemination techniques

Artificial insemination is the process whereby semen is introduced into the female reproductive tract other than by sexual intercourse. It may be intrauterine or vaginal, the former being a specialist procedure. The latter is a low-risk procedure that can be carried out by a healthcare provider or at home by the patient herself or her male partner.

It is advisable that vaginal insemination be attempted at the most fertile time in the menstrual cycle, as described above.

Semen needs to be provided in a clean receptacle, either by male ejaculation into a condom during intercourse or by male ejaculation into a clean specimen jar provided for the purpose. The semen (most men ejaculate 1.5 mL) should be inseminated as soon as possible, and within an hour of ejaculation. If the ejaculate is collected from a condom the couple must ensure that the condom is one that does not include spermicide and the transfer to syringe or clean jar should be done immediately, as latex condoms can cause sperm immobility if exposure is prolonged.

Other equipment to carry out the vaginal insemination would include a ‘turkey baster’, 5 mL or 10 mL plastic needleless syringe or plastic disposable pipette. These items should be supplied to prospective couples or individuals along with the instructions in the diagram.

FIGURE 1-A3: Diagram of self-insemination.

Guidelines

Guidelines to support HIV-affected individuals and couples to achieve pregnancy safely: Update 2018

Foreword

Key game changers between 2011 and 2018

Introduction

Scope of the guidelines

Structure of the guidelines

A word on terminology used in the guidelines

Safer conception

HIV-affected individuals and couples

Safe pregnancy

Horizontal HIV transmission

Vertical HIV transmission

Condomless sex

Timed condomless sex

Healthcare provider(s)

Serodifferent (serodiscordant)

Disclosure and partial disclosure

Undetectable = uninfectious (U=U)

Infertility

Discussing fertility and childbearing with HIV-affected women and men

Important points to note when discussing fertility choices and desires

Concluding the discussion – Different outcomes require different approaches

Working with couples

Working with couples and disclosure

HIV-affected clients who express a desire to have a child

Achieving pregnancy as safely as possible – Choosing appropriate options

Antiretroviral therapy, viral suppression and pregnancy planning

Antiretroviral therapy initiation

Key information and recommendations regarding dolutegravir safety in the periconception period and early pregnancy

Recommended duration of antiretroviral therapy before attempting to achieve pregnancy

Antiretroviral drugs in pregnancy

HIV-positive women not yet on antiretroviral therapy and confirmed pregnant

Pre-exposure prophylaxis

Pre-exposure prophylaxis for serodifferent and sero-unknown couples

Using pre-exposure prophylaxis for HIV prevention

Pre-exposure prophylaxis and pregnancy

The importance of HIV retesting

Post-exposure prophylaxis

Other components of prepregnancy workup

Integrated package of care

Sexually transmitted disease screening and treatment

Timed condomless sex

Self-insemination

Sperm washing

Medical male circumcision

Clients with no immediate plans for a child

Important points to note when providing contraception services

Special considerations when providing contraception to HIV-positive women

Additional considerations for optimising prepregnancy health

Identifying and managing comorbidities

Deferring pregnancy for HIV-positive individuals or couples – Is it ever appropriate?

Expected time to pregnancy and fertility assessment

Expected time to pregnancy

Pregnancy testing

Suspected infertility

Fertility assessment in low-resource settings

Fertility assessment in high-resource settings

Managing safer pregnancy outcomes

When pregnancy is confirmed

Counselling for those experiencing miscarriage

Special situations

What if an HIV-positive woman desires a child but does not have a partner?

Men who have sex with men, transgender and female same sex couples

Acknowledgements

Competing interests

Authors’ contributions

References