Published 04 October 2021
New guideline presents evidence on assisted reproduction in cases of six prevalent viruses - Hepatitis B (HBV), Hepatitis C (HCV), HIV, Human T-cell lymphotropic virus (HTLV I/II), Zika and HPV – with recommendations on virus transmission and prevention, and on factors affecting reproductive outcomes in couples with or without fertility problems.
SARS-CoV-2 gets only a passing mention in a new ESHRE guideline on medically assisted reproduction (MAR) in patients with a viral infection or disease.(1) By way of explanation, the guideline development group says they considered including a chapter on the virus that has dominated healthcare (and lives) for the past 18 months, but decided against it because ‘evidence is emerging and changing constantly’. Instead, they refer clinicians to ESHRE’s ongoing statements on COVID and its impact on ART.(2)
Aside from this explained omission, the guidance and accompanying patient guide provide long-awaited evidence-based information on safety and efficacy outcomes for six prevalent viruses: Hepatitis B (HBV), Hepatitis C (HCV), HIV, Human T-cell lymphotropic virus (HTLV I/II), Zika and HPV. Aimed at improving care for couples with or without fertility problems where at least one partner is infected, the guideline places particular emphasis on cutting the risk of horizontal transmission to partner/family and healthcare providers, reducing vertical transmission to MAR-conceived children and boosting efficacy (eg, in implantation and pregnancy rates).
For patients with chronic or transient viral disease, quality of life has improved thanks to effective treatment. Parenthood or adding to their family is now a possibility for these individuals, including through assisted reproduction. The guideline summarises the available data relating to questions on virus transmission and prevention, as well as factors affecting MAR outcomes for couples with or without fertility problems. In addition, it provides up-to-date and comprehensive details on prevalence, testing and risk of passing on the viruses through sexual intercourse.
Detailed in the 174-page document are nearly 100 recommendations for clinical management before, during and after MAR; and for laboratory safety. In the case of perinatal HBV transmission, the advice given is to vaccinate MAR services staff as well as partners of infected patients and their infants; and in HIV care, the guidance emphasises the need for fertility specialists, infectious disease experts and patients all to be involved in the decision to commence MAR or not.
C-sections are not advised in cases of virus infection to mitigate the risk of mother-to-infant transmission, with the exception of HIV where this surgical procedure is recommended to reduce the risk of passing the disease on to the baby. MAR techniques defined as preferential are IUI, IVF or ICSI (depending on the infertility work-up), although the guideline authors say infertility treatment should be postponed in cases of Zika disease if detected before MAR, and cancelled altogether if discovered during treatment. Even if semen is free from Zika virus, MAR is not advised on the basis that all patients with the disease may still be infectious through semen, ‘regardless of viral load’ (clearance of Zika is slower from semen than from blood).
As for laboratory safety, the guidance here relates to strict adherence to good practice, such as ‘careful management of cryobanks’ - with storage of infected reproductive cells separately from those that are viral negative, hermetical sealing of cryovials with additional covers to reduce cross-contamination risk, and disinfecting/changing personal protective equipment (PPE) between cases (again to reduce cross-contamination risk) are among the possible courses of action outlined.
The authors of the ESHRE guideline are former members of the SIGs Safety & Quality in ART and Ethics & Law, the task force on viral diseases and experts in the field. Edgar Mocanu was development group chair. Based on analysis of literature searches up to 3 November 2020, the guidance draft was open for review (after publication on the ESHRE website) for six weeks between 18 February and 1 April 2021, attracting responses from nine countries including the UK, USA and China.
Gaps in evidence clearly exist, such as a lack of data on whether the HPV, Zika and HTLV I/II viruses are present in oocytes. In some cases, the information is contradictory, unclear or unavailable, which has posed a challenge for the development group in determining the impact of infection/disease on the success of MAR. With the next review expected in 2025, the authors recommend that future research (ideally in well-designed randomised trials) focuses on areas including the association of HPV with infertility, and semen processing for HBV, HCV and HTLV I/II. And they say studies are needed on SARS-CoV-2, namely into its links with infertility and laboratory safety procedures.
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