Asma Sassi1, Fabienne Devreker1 and Yvon Englert1
(1)
Laboratory for Research in Human Reproduction, Medicine Faculty, Department of Obstetrics and Gynecology, Hôpital Erasme, Université Libre de Bruxelles (ULB), Route de Lennik, 808, Brussels, 1070, Belgium
Fabienne Devreker
Email: Fabienne.Devreker@erasme.ulb.ac.be
Yvon Englert (Corresponding author)
Email: yvon.englert@erasme.ulb.ac.be
Keywords
HIVHCVHBVMedically assisted reproductionCross contaminationSafetyQuality control
Risk of Cross-Contamination and Nosocomial Transmission
Worldwide, hepatitis B virus (HBV) accounts for an estimated 370 million chronic infections, hepatitis C virus (HCV) for an estimated 130 million, and HIV for an estimated 40 million. HBV, HCV and HIV share common routes of transmission, even if non-sexual transmission is more common in HCV transmission. The prevalence of potentially infectious individuals varies depending on the virus involved, the geographic region and the population subgroups. In developed countries, the general population prevalence of HBV is <0.5 %, HCV 1 % and HIV 0.15 % [1]. Sub-Saharan Africa accounts for most (65 %) HIV infections worldwide and has a high prevalence of chronic HBV infection. The population prevalence of HIV is 20 % in Southern Africa and at least 8 % of the population in these areas are chronically infected, with 70–90 % having serological evidence of previous HBV infection [2]. The highest prevalence of HCV infection has been reported from Northern Africa (particularly Egypt), and has been found in 25–30 % of HIV-positive persons and 72–95 % of injection drug users [2–5]. Some Asian countries have a high incidence of BBV carriers. Heterosexual intercourse represents the major vector of HIV transmission worldwide. The risk of seroconversion after an initial negative screen in co-habiting couples participating in an ART programme is negligible. The incidence in this population of hepatitis B surface antigen was 0.28 %, hepatitis C antibody 0.33 %, and HIV 0.007 % [6].
Viral transmission risk via ART is possible and has been reported. Cross-contamination between infected and uninfected patients and samples can potentially occur during clinical procedures and during subsequent laboratory procedures such as insemination, injection, incubation and cryopreservation [7, 8]. HBV is known to be present in many body compartments including blood, semen and vaginal secretions depending on the viral concentration [7, 9]. In addition, HBV (and HCV) can remain viable in dried blood on environmental surfaces at room temperature [3]. A case has been reported of an acute viral hepatitis B in a woman following artificial insemination with a sperm donor, which was subsequently found to be positive for hepatitis B surface antigen [10]. The infection of women whose embryos were exposed to HBV in contaminated human serum present in the culture medium during in vitro fertilisation (IVF) has also been reported [11]. In vitro and in vivo data suggest that the risk of HBV integration, and subsequent replication and expression, remains during IVF and intracytoplasmic sperm injection (ICSI) procedures as germ cells may be vectors for the vertical transmission of HBV [9, 12, 13]. HBV DNA, HBV RNA and HBsAg were found in oocytes and embryos of couples with at least one HBsAg-seropositive partner [12, 13]. HBV can integrate into human sperm and oocytes. Human sperm-mediated HBV genes are able to replicate and express themselves, as suggested by the detection and expression of the HBV X gene in one- and two-cell embryos from golden hamster oocytes fertilised in vitro with human spermatozoa carrying HBV DNA [14]. The entire HBV genome, introduced via pronuclear DNA microinjection, was integrated into mouse F1 hybrid embryos and stably transmitted to progeny until the F10 generation [15]. HBV DNA sequences are able to pass through the zona pellucida and oolemma to enter mouse oocytes and are also able to integrate into their chromosomes [16].
Performing ART in a patient with HCV infection may also lead to a possible risk of nosocomial contamination. In fact, HCV RNA was detected in unfertilised oocytes and in follicular fluid and culture media from HCV-positive women irrespective of the degree of blood contamination [17, 18]. HCV was also present in the seminal plasma of chronically HCV-infected males at varying prevalence [19] with no correlation with HCV virus load [20]. Two cases of nosocomial transmission of HCV in patients attending the ART centre for ICSI/FIV have been reported. In both cases the contaminated patient had had follicular puncture immediately after the HCV infected patient puncture one [21]. It should be remembered that HCV is an RNA virus and has no reverse transcriptase activity; therefore, it cannot succeed in DNA integration within infected cells, sperm or embryos [22]. One case of an HCV-infected newborn out of 30 born to HCV- and polymerase chain reaction (PCR)-positive women undergoing ICSI cycles has been reported and none of those born to PCR-negative females was infected [23]. HIV virus is present in semen as a free virus in the seminal plasma and as a cell-associated virus in the non-sperm cells. HIV may be able to attach to or infect spermatozoa, although this issue is controversial [7, 24]. HIV infection in artificial insemination with a sperm donor has been reported [25–27]. Transmission of HIV by artificial insemination by donor semen was first described in Australia by Stewart et al. [28], then by Chiasson et al. [25] in the USA. These accidents demonstrated early in the epidemic that sperm alone, independently of any sexual contact, can transmit the virus with very similar frequencies to situations of occasional sexual intercourse.
The blood plasma viral load of HIV is known to be related to the risk of HIV transmission [29, 30]; however, viral loads in semen and in blood plasma may be discordant [31]. The virus can persist in semen even during antiretroviral therapy and with an undetectable blood viral load [29, 32–34]. HIV RNA may be amplified in semen, when undetectable in plasma, in 2–8 % of patients under highly active antiretroviral therapy (HAART) [35, 36]. The female genital tract also represents a distinct compartment for HIV-1 replication/evolution. Genital shedding of the virus was demonstrated in 25 % of women with an undetectable plasma viral load [37]. The presence of HIV-1 in follicular fluids, flushes and cumulus oophorus cells of HIV-1-seropositive women during ART has been reported, which represents a cross-contamination risk within the laboratory setting [24, 38].
BBV Infection Risk Related to Cryopreservation
Although not yet reported, the cryopreservation of gametes and embryos in liquid nitrogen presents a risk of cross-contamination of HIV, HBV and HCV to other samples. In fact, these viruses are well known to have the ability to survive, and retain their virulence, in liquid nitrogen [39]. There have already been reports of the HBV contamination of negative bone marrow samples cryopreserved in the same liquid nitrogen tank as those harvested from an HBV-infected patient. The leakage of the cryopreservation bags used to store the infected bone marrow leads to contamination of the tank and its contents with HBV and with subsequent transmission to patients after transplantation [40, 41]. Cross-contamination may occur during semen processing before freezing in laboratories that use containers of polyvinyl alcohol (PVA) sealing powder for multiple patients or donors. In fact, PVA powder may accumulate microorganisms. Tamping straws from different patients into the same powder could result in cross-contamination [42]. The storage of semen in cryovials placed in direct contact with liquid nitrogen may not be safe, as cryovials are able to absorb up to 1 ml of potentially contaminated liquid nitrogen if their caps cannot maintain their seal [40]. Straws may leak or shatter during freezing or blow open during thawing and those that are inadequately sealed could absorb contaminated nitrogen [14, 42]. The type of straws and the sealing system and instruments used are also important. Letur-Könirsch et al. [39] have evaluated the safety of three types of straws under cryopreservation conditions: polyvinyl chloride (PVC), polyethylene terephthalate glycol (PETG) and high-security ionomeric resin (IR) straws. Only the heat-sealed ionomeric resin straws were found to be safe against leakage of HIV-1 into the surrounding medium [39]. Sealing PVC and PETG straws ultrasonically could incur the risk of not ensuring their impermeability [39, 43].
Safety Measurements
Patient admittance to ART treatment cycles must be regulated by physicians and the laboratory staff must be informed about the risks of handling potentially infected biological material. Certain strategies should be established to ensure the safety of ART and significantly reduce the risk of BBV infection and cross-contamination.
The first step consists of routinely screening patients for human HIV, HBC, HCV and other sexually transmissible diseases before processing or cryopreservation gametes and embryos [7, 44]. Screening is mandatory only for gamete donors, which is not the case for the donation of reproductive cells between partners who have an intimate physical relationship ([45], Annex III). However, systematic screening of couples attending assisted reproduction centres is strongly recommended, as it confers many benefits from the ethical and medico-legal standpoints [7, 8].
Where HIV-1 and -2, hepatitis B or hepatitis C test results are positive or unavailable, or if screening is refused by one or both partners, samples should be processed in a separate laboratory or designed space within the same laboratory, utilising a separate storage tank to minimise the risk of cross-contamination [7, 8, 46]. There is good evidence for recommending the use of antiviral drugs in an HIV-infected partner, to reduce HIV viraemia [47] and to use sperm-washing methods if the male is HIV+ or HCV+. In fact, reduction of HIV and/or HCV shedding in semen by density gradient centrifugation followed by swim-up is an efficient method [31, 32, 48–52] and should be performed to decrease the viral load before using and freezing the semen samples.
The sperm-washing procedure consists of density gradient centrifugation followed by a sperm swim-up step to separate motile sperm from free HIV and HIV-infected somatic cells [53, 54]. Virological testing of the sperm fraction using a PCR technique for the presence of residual detectable HIV before its use for insemination can provide an added measure of safety, as up to 8 % of samples may contain residual virus after the procedure [52]. Very sensitive RT-nested PCR assay for the detection of HIV-1 RNA in different parts of semen for which the sensitivity for HIV-1 RNA detection is 20–50 HIV-1 RNA copies per millilitre have been developed [32]. HIV-1 RNA could be detected even after swim-up and the inhibition of HIV-1 RNA amplification is relatively common; thus, when using PCR techniques for semen validation, inhibition of the reaction must be controlled by using an internal control that is well targeted at exploring the detection limit of the method. Extraction techniques using silica or resine breads seemed to increase the assay performance because of better washing [55]. The sperm-washing procedure could also be used in cases of sperm retrieval where sperm volume and density are low, allowing the treatment with testicular spermatozoa in azoospermic HIV-positive men [56–59]. HCV RNA was detected in 20 % of seminal plasma samples from HCV viraemic patients, but not in any seminal cells or motile spermatozoa fractions [31]. After density gradient centrifugation was either followed or not followed by a swim-up step, no HCV RNA was found in the purified 90 % fraction of the sperm, which is the one used for insemination [31, 60]. Even if no effective vaccine against HCV is available, ribavirin and peginterferon could be used to decrease the viral load before fertility treatment in a PCR-positive, HCV-infected partner (48 weeks). Pregnancy should be deferred for an additional 6 months after the conclusion of therapy, regardless of which partner is undergoing the treatment [46]. In male HBV patients, sperm-washing is not necessary for preventing the risk of sexual transmission unless the female partner has not been effectively vaccinated against HBV and in this case ART should be delayed until vaccination has taken place [7, 9, 46].
If the woman is infected by the HBV, the couple must be warned about the necessity of the specific vaccination of their newborn [44]. A systematic review of the literature has shown that lamivudine use in HBV carrier-mothers with a high degree of infectiousness in late pregnancy effectively prevented HBV intrauterine infection and mother-to-child transmission [61].
Universal precautions and adherence to strict safety guidelines should be applied in all ART laboratories, but those dedicated to chronic carriers of viruses should be equipped with the whole range of adapted facilities for handling of gametes, embryos or ovarian or testicular cells for ART [7, 8]. Preimplantation diagnosis may even be performed if needed [62]. To further minimise the risks of cross-contamination, infected patients should be separately treated in a dedicated facilities or at different time from non infected patients [7, 8, 63–65]. Infected patients can be seen at the end of the programme for vaginal echography, oocyte retrieval, transfer and insemination [7]. Vaginal ultrasound probes should be covered with a protective sheath and wiped with a germicide-impregnated tissue before and after each patient is scanned [66]. A separate adapted laboratory devoted to infected patients, with an airtight chamber and safety access procedures could be set apart for treating the biological material of patients (semen, oocytes and embryos) when HIV, HCV or HBV carriers are involved. A vertical laminar flow cabinet for viral culture with 100 % recirculation of filtered air was adapted with a microscope and video vision to provide the laboratory workers with a safe workplace [7, 8]. The laboratory designs include facilities for cleaning and disinfection; working surfaces and equipment used should be cleaned with additional non-embryotoxic disinfecting agents [7, 8].
Some other general protective measures should be applied, such as the use of laboratory clothing, non-toxic gloves and masks, eye and face protection where appropriate, and the use of cryogloves when handling cryogenic materials. A fume-hood should be used when using fixatives. Mechanical pipetting devices should be used for one procedure only and never for more than one patient at a time. Mouth pipetting should be prohibited. Needles and other sharps should be handled with caution and discarded in special containers. Any non-disposable equipment should be sterilised using non-embryotoxic products. Access to the laboratory should be limited to authorised personnel only [7, 8, 44, 46, 67].
During storage, proper measures should be taken to safeguard against the risk of cross-contamination. A system of separate storage should be considered [7, 8, 17]. Containers used for cryopreservation must be guaranteed by manufacturers to withstand freezing temperatures. Any straws found to be defective after thawing should not be used in ART. Adequate sealing is essential and should be checked carefully before freezing. A procedure whereby straws are heat-sealed at both ends should be implemented. The safety of heat-sealed shatterproof CBSTM ionomeric resin straws for the cryopreservation of semen-containing HCV [68] and HIV-1 RNA [39] have been demonstrated, with no reported cases of cross-contamination. The use of “double bagging” to store cryovials inside a second skin, such as those called Cryoflex, to prevent the direct contact of the cryocontainer with the liquid nitrogen, is recommended [40, 46]. The use of vapour storage for both oocytes and sperm may be a viable alternative to the storage of gametes and/or embryos in liquid nitrogen alone, which has the potential to become contaminated [40, 46, 69–71]. PVA powder sealing should be used for one patient only. Straws should be decontaminated after sealing [43, 68]. Incubators should be frequently cleaned and sterilised. Nitrogen tanks are recommended to be cleaned and sanitised at least every year [67]. The exterior surface of straws should be sterilised before cutting with the use of sterile scissors to open the straws. Only one patient biological sample should be processed for cryopreservation at a time, at a workstation separated from other biological samples. In addition, to diminish the risks further, ART using cryopreserved sperm should involve a semen preparation protocol employing density gradients and sperm-washing techniques [31, 60].
Concern About Natural Conception in HIV-Serodiscordant Couples
For serodiscordant couples with no infertility factors, natural conception could be an alternative to assisted reproduction under certain conditions. If the woman is the infected partner, conception is possible by auto-insemination with no risk to the partner. Some authors are in favour of conception by unprotected sexual intercourse limited to the fertile days for HIV-serodiscordant couples treated by HAART where there is an undetectable viral load [72, 73].
The Swiss HIV Commission stated in its guidelines that: “The risk of sexual transmission of HIV is negligibly low if three conditions are met: (1) the HIV-infected patient is receiving antiretroviral therapy with excellent adherence; (2) blood viral load has consistently been undetectable (<40 copies per ml) for more than 6 months; and (3) no sexually transmitted diseases (STDs) are present in either of the partners” [36].
Gray et al. [74] showed a lack of sexual HIV transmission through unprotected intercourse in couples in which males had viral load values <1500 HIV RNA copies/ml and estimated the average risk of heterosexual HIV transmission to be 0.001–0.0001 per sexual contact [74]. However, it is worth noting that the average number of acts of sexual intercourse necessary to achieve pregnancy at 26–35 years of age for a couple with normal fertility is hence 3–10 and thus for a risk of HIV transmission of 0.0001 per unprotected act of sexual intercourse, the risk of seroconversion would then be 0.001 per pregnancy [75]. This risk could be higher, as fertility could be altered in HIV-positive persons because of the infection itself or the potential impact of the HAART on ovarian function and the sperm quality and so the required numbers of cycles necessary to conceive are higher, especially if the woman is older [75]. Furthermore, to obtain an estimated risk of transmission of 0.001–0.0001 per sexual contact, a series of 3000–30,000 natural pregnancies would be needed to truly establish the safety of such an approach [72]. The couple should be informed that there is much better controlled experience with “sperm-washing” procedures, as natural conception is still registered in small series [72].
Antiretroviral pre-exposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. A randomised trial of oral antiretroviral therapy for use as pre-exposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda, enrolling 1584 couples randomly assigned to TDF, 1579 to TDF-FTC and 1584 to placebo, and followed monthly for up to 36 months, showed that the once daily intake of tenofovir (TDF) or a combination tenofovir–emtricitabine (TDF–FTC) are respectively associated with a relative reduction of 67 and 75 % in the incidence of HIV-1. The HIV-1-seropositive partners were not receiving antiretroviral therapy and did not meet Kenyan or Ugandan guidelines for initiation of antiretroviral therapy. TDF was given at a dose of 300 mg, and FTC 200 mg [76].
Whetham et al. [77] reported the first UK use of pre-exposure prophylaxis for conception (PrEP-C) in 32 male-positive/female-negative couples. The PrEP-C consists on TDF–FTC intake by the female at protocol-designated times before ± after timed ovulatory intercourse. Eleven pregnancies in ten couples have been obtained with no HIV transmission. Mugo NR et al. [78] showed the safety of PrEP with TDF alone or combination FTC+TDF taken at conception, as differences in pregnancy incidence, birth outcomes, and infant growth were not statistically different when compared with placebo [78].
Guidelines were proposed to further reduce the risk of sexual transmission:
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After six unsuccessful attempts a fertility evaluation is suggested [79].
Attitude Regarding Gamete Donors
According to Commission Directive 2006/17/EC [45] Annex III, of 8 February 2006 implementing Directive 2004/23/EC of the European Parliament and of the Council regarding certain technical requirements for the donation, procurement and testing of human tissues and cells, gamete donors other than partners must be screened for sexually transmitted infections and must be negative for HIV-1 and -2, HCV, HBV and syphilis on a serum or plasma sample, tested in accordance with Annex II, point 1.1, and sperm donors must additionally be negative for chlamydia on a urine sample tested by the nucleic acid amplification technique (NAT). Blood samples must be obtained at the time of donation. Sperm donations other than from partners are quarantined for a minimum of 180 days, after which repeat testing is required. No quarantine is needed when blood NAT testing have been performed on the day of donation. Human T-cell lymphotropic virus type I (HTLV-I) antibody testing must be performed for donors living in or originating from high-incidence areas or with sexual partners. Under certain circumstances, additional testing may be required, depending on the donor’s travel and exposure history and the characteristics of the tissue or cells donated (e.g. RhD, malaria, cytomegalovirus, Trypanosoma cruzi).
According to the guidelines for Gamete and Embryo Donation published by the Practice Committee of the American Society for Reproductive Medicine [80], the quarantining of oocytes is not practical. All potential recipient couples should be offered the option of cryopreserving and quarantining embryos derived from donor oocytes for 180 days, with release of the embryos only after the donor has been retested, with confirmed negative results. However, couples also should be informed that embryo cryopreservation may significantly reduce implantation rates. The recipient couple should be appropriately counselled in the event of seroconversion of the oocyte donor after cryopreservation of the embryos. Attitudes regarding oocyte cryopreservation for donation should be changed regarding the efficicency of NAT testing and the contemporary vitrification methods [81]. Cobo et al. [82] showed that the delivery rate (DR) per warming cycle using vitrified embryos developed from vitrified oocytes or vitrified embryos derived from fresh oocytes are comparable (33.8 % vs 30.9 %) and concluded that vitrification at the early cleavage or blastocyst stage of embryos obtained from previously vitrified oocytes has no effect on the DR/warming cycle. Dominguez et al. [83] also reported that oocyte vitrification does not disturb embryonic metabolomic profiles and that the outcome of cryotransfer of embryos developed from vitrified oocytes (double vitrification) has no impact on delivery rates.
BBV Infection Risk and Attitude Regarding Health Care Workers
The main risk to health care workers (HCWs) is through needlestick and other percutaneous and mucocutaneous exposures, which are frequent, and under-reported [84]. Laboratory technicians and hospital nurses are the most frequently exposed groups [1, 84, 85]. The average risk of HIV transmission after a percutaneous exposure to HIV-infected blood has been estimated to be approximately 0.3 % (95 % confidence interval [CI], 0.2–0.5 %) and that after mucous membrane exposure it is approximately 0.09 % (95 % CI, 0.006–0.5 %) [4]. Exposure to contaminated needlesticks among healthcare workers has demonstrated that HBV is 100 times more infectious than HIV and HCV is ten times more infectious than HIV [2]. This risk is related to the frequency of contaminated exposures, the prevalence of disease in the source populations, the risk of transmission given exposure to an infected source and the effectiveness of post-exposure management [1].
Post-exposure prophylaxis should be offered to all persons who have sustained a mucosal or parenteral exposure to HIV from a known infected source as urgently as possible and, at most, within 72 h after exposure [86, 87]. Antiretroviral agents from six classes of drugs are currently available to treat HIV infection. These include the nucleoside and nucleotide reverse-transcriptase inhibitors (NRTIs), non-nucleoside reverse-transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), a fusion inhibitor (FI), an integrase strand transfer inhibitor (INSTI) and a chemokine (C-C motif) receptor 5 (CCR5) antagonist [4]. In low-risk exposure, the treatment regimen consists of TDF (300 mg once daily) with FTC (Emtriva; 200 mg once daily); a combination drug available as Truvada (300/200-mg tablet once daily) or zidovudine (Retrovir; 300 mg twice daily) with lamivudine (Epivir; 150 mg twice daily); a combination drug available as Combivir (300/150-mg tablet twice daily) should be started. In high-risk exposure, the treatment regimen consists of TDF (300 mg once daily) with FTC (200 mg once daily) or zidovudine (300 mg twice daily) with lamivudine (150 mg twice daily), plus lopinavir/ritonavir (Kaletra; 400/100 mg, two tablets twice daily) or atazanavir (Reyataz; 400 mg once daily). All these regimens should be started within 72 h after exposure for 4 weeks [86].
In non-vaccinated HCWs or HCWs with an unknown antibody response to vaccination exposed to an HbsAg-positive or an untested source patient, post-exposure prophylaxis consists of a single dose of hepatitis B immune globulin, 0.06 ml per kg intramuscularly within 24 h of exposure, followed by hepatitis B vaccine series [86]. No effective post-exposure prophylaxis is available for HCV, and neither interferon nor immune globulin is recommended; however, it is crucial to identify HCV exposure and infection in health care [1, 85, 86].
The psychological impact of needlesticks or exposure to blood or body fluid should not be underestimated for HCWs [4, 7]. HCWs frequently experience intrusive thoughts, problems concentrating, sleeping difficulties, anger and a decrease in sexual desire. Some can even react aggressively as an expression of fear for their own safety [1, 7, 85]. Although the hepatitis viruses are more easily transmissible, the fear of HIV infection is the major cause of stress and anxiety experienced by many HCWs. Special attention should be given to motivation and training of the fertility clinic staff who are not accustomed to handling infected patients [7]. Vaccination of the medical staff against hepatitis is recommended [44].
Legitimacy of BBV Screening Before Infertility Treatment
Testing patients and gamete donors for HIV and other sexually transmitted diseases is recommended to be routinely adopted before treatment and gamete cryopreservation by the American Society for Reproductive Medicine practice guidelines, ESHRE guidelines for good practice in IVF laboratories 2000, the Commission Directive of the European Parliament and of the Council as regards certain technical requirements for the donation, procurement and testing of human tissues and cells (2004/23/EC and 2006/17/EC, Annex III). According to the latter, this screening must be performed for the donor other than the partner or the partner donor in the non-direct use of gametes, when reproductive cells are to be processed and/or stored and will result in the cryopreservation of embryos. However, from the ethical and medico-legal standpoints, all couples planning to have a child should be strongly encouraged to be screened for potentially transmittable infections before treatment, as recommended by the American Society for Reproductive Medicine practice guidelines, and many authors [7, 8, 68, 88]. The screening for BBV before ART is mandatory in belgium, however. This practice should be considered good medical practice, as the means of significantly reducing the risk of HIV transmission to an uninfected partner and to offspring are available: vaccination of the uninfected partner and neonates for HBV, decreasing the viral load of HCV in the pregnant female, which is associated with a minor risk of vertical transmission of HCV [23], or simply informing and counselling patients. Measures can be taken to inform these patients of their condition, prognosis and treatment, refer them to an appropriate physician and counsel them about their reproductive options and the safer reproductive choices [7, 89]. This requires the presence of a multidisciplinary team [7, 64, 89].
Multidisciplinary teams are essential in giving a comprehensive approach to patients planning a child while chronically ill with a transmissible and potentially lethal disease. The team in Brussels includes an assisted reproduction clinician, a biologist, a specialist in internal medicine, an obstetrician and a paediatrician all specialised in HIV patients, in addition to a psychologist and the head of the Virology Laboratory and the AIDS Reference Laboratory at the Université Libre de Bruxelles. These professionals are all working within the same academic hospital. All requests and patients’ files are reviewed collectively [7, 89]. Healthcare professionals should provide reproductive counselling, taking into consideration the following aspects: the need to minimise the risk of transmission to the uninfected partner and/or offspring; enabling informed reproductive choices; informing couples about the risks of HIV transmission and the chances of pregnancy, with both natural and medically assisted conception; preparing couples for the psychological impact of assisted conception (availability, duration of treatment, failure and logistics); discussing the possibility of fostering or adoptive parenting and informing and advising couples about the risks of sexual and vertical transmission of other frequently associated agents, such as hepatitis B or C [72].
Few people refuse these tests if offered in a non-repressive environment (no refusal has been observed in Brussels in 15 years). In the literature, rates of individuals refusing to undergo screening range from 0.5 to 6 %, probably according to the political and social context [1, 46]. Couples should consider BBV testing as part of responsible parenting and non-discriminatory if they know they will be hosted with respect and be correctly counselled and supported to optimise the control of their disease and the security of their uninfected partner and offspring. Moreover, screening enables patients presenting a risk to HCWs and other patients to be identified pre-treatment, thereby minimising the risk of transmission and cross-contamination when blood sampling, operating, laboratory processing and storing gametes and embryos.
Conclusion
Even if universal precautions are practised, a zero risk does not exist [7, 8, 68]. Patients are free to refuse the screening, but in these cases the centre should handle their gametes and embryos as those of patients who are chronic viral carriers [7, 90, 91]. The screening should not result in discrimination; fertility services should not be withheld from these individuals. The individual should always be referred to a centre that has the capacity to provide the necessary resources.
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