Medically Assisted Reproduction: Viral Infection or Disease

Medically Assisted Reproduction (MAR) in Patients with Viral Infections/Diseases: ESHRE Guidelines (2021)

Disclaimer

• ESHRE's clinical practice guidelines aim to aid healthcare professionals in clinical decisions, but adherence doesn't guarantee specific outcomes or establish a standard of care.

• Healthcare professionals should use their clinical judgment based on individual patient conditions and wishes.

• ESHRE provides no warranty regarding the guidelines and is not liable for damages related to their use.

Contents

• Covers Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV), Human Papilloma Virus (HPV), Human T-Lymphotropic Virus I/II (HTLV I/II), Zika Virus, and SARS-CoV-2.

• Includes sections on prevalence and testing, prevention of transmission, assisted reproduction techniques and impact, and reducing/avoiding vertical transmission.

Introduction

• Guideline based on well-documented methodology outlined in the Manual for ESHRE guideline development.

• The guideline aims to provide evidence-based information for professionals on medically assisted reproduction options for couples with viral infections/diseases.

• MAR Techniques include IUI, IVF and ICSI.

• Excludes natural conception and other viral infections besides the ones mentioned.

• Focus on managing MAR in couples affected by viral infections.

• Target users: reproductive medicine specialists, obstetricians, gynecologists, embryologists, andrologists, policy makers, and regulators.

Terminology

• MAR refers specifically to IUI, IVF, and ICSI, using the international glossary on Infertility and Fertility Care (Zegers-Hochschild, et al., 2017).

Outcomes

• Outcomes include safety (risk of horizontal and vertical transmission) and efficacy (implantation, pregnancy, live birth, and miscarriage rates).

List of Recommendations

Hepatitis B Virus

A2. Prevention of Transmission Before MAR

• Recommendation A2.1 (Strong, ⊕): Partners of HBV-positive individuals should be vaccinated; barrier contraception until completing HBV vaccination protocol (Strong, ⊕⊕).

• Recommendation A2.3 (GPP): MAR staff should be vaccinated against HBV.

• Recommendation A2.4 (Strong, ⊕): Patients with active/chronic HBV must be reviewed by a liver specialist before MAR.

• Recommendation A2.5 (Strong, ⊕): Joint decision required between patient, partner, fertility doctor & liver specialist before MAR.

• Recommendation A3.7 (Strong, ⊕): The cause of infertility dictates the specific MAR technique (IUI/IVF/ICSI) used.

A3 Assisted reproduction techniques and impact on outcomes

• Recommendation A3.8 (GPP): Women positive for HBV should be informed that MAR does not eliminate the risk of vertical transmission.

• Recommendation A4.9 (GPP): Men positive for HBV should be informed that no semen preparation can ensure HBV DNA-free spermatozoa.

• Recommendation A4.10 (GPP): Routine semen processing according to ESHRE guidelines should be employed.

• Recommendation A4.11 (Strong, ⊕): HBV DNA testing on seminal fluid/sperm is not recommended.

• Recommendation A5.12 (Strong, ⊕⊕): Caesarean delivery not recommended solely on maternal HBV-positivity.

• Recommendation A5.13 (Conditional, ⊕⊕): Breastfeeding is probably not contraindicated in HBV-positive women.

Reducing/avoiding vertical transmission

• Recommendation A5.14 (Strong, ⊕⊕⊕): Neonates born to HBV-positive couples should be vaccinated.

• Recommendation A5.15 (Strong, ⊕⊕): HBIG administration recommended, following local/national guidelines (GPP).

Hepatitis C Virus

B2 Prevention of transmission before MAR

• Recommendation B2.17 (Conditional, ⊕⊕): Barrier contraception not indicated in monogamous heterosexual relationships >12 months in HCV-serodiscordant couples.

• Recommendation B2.18 (GPP): All patients with active or chronic HCV infection must be reviewed by an infectious disease/liver specialist before any MAR Treatment.

• Recommendation B2.19 (Strong, ⊕): Commencing with MAR in HCV-positive patients should be a joint decision.

Assisted reproduction techniques and impact on outcomes

• Recommendation B3.21 (Strong, ⊕): Cause of infertility dictates the specific technique (IUI/IVF/ICSI).

• Recommendation B3.22 (GPP): Women positive for HCV should be informed that MAR does not eliminate the risk of vertical transmission.

• Recommendation B5.23 (Strong, ⊕): Discontinuous gradient centrifugation followed by swim-up and washing recommended for semen processing.

Semen processing

• Recommendation B5.24 (Strong, ⊕): After advanced semen processing, PCR testing for HCV is not necessary.

• Recommendation B5.25 (GPP): Good laboratory practice should be applied irrespective of whether one or both partners are HCV positive.

Reducing/avoiding vertical transmission

• Recommendation B6.26 (Strong, ⊕): Caesarean delivery is not recommended based on maternal HCV-positivity alone.

• Recommendation B6.27 (Strong, ⊕⊕): Breastfeeding is not contra-indicated.

Human Immunodeficiency Virus (HIV)

• Recommendation C2.28 (Strong, ⊕⊕): HIV-1-serodiscordant couples should use barrier contraception and ART to reduce viral load.

• Recommendation C2.29 (Strong, ⊕⊕): HIV-1-positive individuals can achieve minimal transmission with ART adherence and undetectable viral load.

Assisted reproduction techniques and impact on outcomes

• Recommendation C3.33 (Strong, ⊕): HIV infection status is not a reason to deny MAR treatment.

• Recommendation C3.34 (Strong, ⊕⊕): Assisted reproduction techniques and technique (IUI/IVF/ICSI) used for MAR in couples where one or both partners test positive for HIV

• Recommendation C3.35 (Strong, ⊕): Advanced semen processing should be used for male patients testing positive for HIV-1 to reduce the likelihood of viral presence.

• Recommendation C3.36 (Strong, ⊕): No special laboratory techniques are needed for processing of oocytes from female patients testing positive for HIV.

• Recommendation C3.37 (Strong, ⊕): HIV-1 serodiscordant male do not impact mar efficacy
  Recommendation C3.38 (Conditional, ⊕): MAR is conflicted by the HIV infection of the female partner.

Semen processing

• Recommendation C5.39 (Strong, ⊕⊕): Density gradient centrifugation followed by 2 semen washing steps, followed by swim-up for males testing positive for HIV

• Recommendation C5.40 (Strong, ⊕⊕): Semen samples from males should be PCR tested before use.

• Recommendation C5.41 (Strong, ⊕⊕): Only a HIV-negative sperm sample should be used for MAR from serodicsordant male couples testing positive for HIV.

• Recommendation C5.42 (GPP): Good laboratory practice regarding semen processing should be applied irrespective of whether only the male or both partners are testing positive for HIV.

• Recommendation C5.43 (Strong, +): Advanced semen processing is recommended for male patients testing positive for HIV, regardless of viral load in serum and therapy status.

Reducing/avoiding vertical transmission

• Recommendation C6.44 (Strong, +): Caesarean section is recommended in wormen with detectable HIV viral loads.

• Recommendation C6.45 (Strong, +): HIV Female testing positive should refraint froms Breastfeeding when safe alternatives can be used.

• Recommendation C6.46 (Strong, +): Combined neonatal prophylaxis is recommended for neonates born to mothers testing positive for HIV.

Human Papilloma Virus (HPV)

Prevention of transmission before MAR D2

• GPP, Human Papilloma Virus D2.47: Barrier contraception advised to lower the risk of HPV transmission.

• GPP, Human Papilloma Virus D2.48: All women starting MAR should undergo testing to detect HPV-related cervical lesions.

Assisted reproduction techniques and impact on outcomes D3

• Strong, + Human Papilloma Virus D3.49: Specific technique (IUI/IVF/ICSI) based on the cause of infertility.

• GPP, Human Papilloma Virus D3.50: Women infected with HPV should be informed that MAR does not eliminate the risk of vertical transmission.

Prevention/reduction of transmission during assisted reproduction D4

• GPP, Human Papilloma Virus D4.53: HPV-positive males should be informed that no current semen preparation can eliminate the virus from the infected semen sample.

Reducing/avoiding vertical transmission D5

• Strong, ++ Human Papilloma Virus D5.54: Caesarean delivery is not recommended on the basis of maternal HPV-positivity alone.

• Conditional, + Human Papilloma Virus D5.55: Breastfeeding is probably not contraindicated in HPV-positive women.

Human T-cell lymphotrophic virus I/II

Prevention of transmission before MAR E2

• Conditional, + Human T-cell lymphotrophic virus E2.56: Suggest informing HTLV I/II- serodiscordant couples on sexual transmission risk and advising barrier contraception + reproductive counselling.

Assisted reproduction techniques and impact on outcomes E3

• Strong, + Human T-cell lymphotrophic virus E3.57: Specific technique (IUI/IVF/ICSI) based on the cause of infertility.

• GPP, Human T-cell lymphotrophic virus E3.58: Women testing positive for HTLV I/II should be informed about MAR not eliminating the risk of vertical transmission.

Reducing/avoiding vertical transmission E5

• Strong, + Human T-cell lymphotrophic virus E5.59: Caesarean delivery is not recommended on the basis of maternal HTLV I/II-positivity alone.

• Strong, + Human T-cell lymphotrophic virus E5.60: HTLV I/II-positive women should refrain from breastfeeding when safe nutritional alternatives exist.

Zika virus

Prevention of transmission before MAR F2

• GPP, Zika virus F2.61: Male diagnosed with ZIKV should use barrier contraception for 3 months.

• GPP, Zika virus F2.62: Female diagnosed with ZIKV should use barrier contraception and avoid pregnancy for 2 months.

Assisted reproduction techniques and impact on outcomes F3

• GPP, Zika virus F3.63: If diagnosed, MAR should be postponed for 3 months.

• GPP, Zika virus F3.64: Approach should be tailored to the situation in case of fertility preservation

• GPP, Zika virus F3.66: Cycle should be stopped for diagnosed male or females and proceed to take barrier contraceptives for 3 months.

Prevention/reduction of transmission during assisted reproduction F4

• Strong, + , MAR is not advised even if serum is free of ZIKZ. Because of poor correlation between plasma and semen

Laboratory Safety

• GPP, LABORATORY SAFETY H.68: Separate cryo tank storage to prevent cross contamination.

• GPP, LABORATORY SAFETY H.69: Cryo tanks and shippers should be inspected regularly.

• GPP, LABORATORY SAFETY H.70: Dewars should be used to quarantine gametes from unknown infectious status.

• Conditional, + , Vapor phase is more safe than LN2

• GPP LAB SAFETY H.73: Wipe the cryo device and sealed semen straws with disinfectant

• Conditional, +, Cryovials should be hermatically sealed with additional covers.

• Strong, +,High security straws should be used and thermally sealed

• GPP H.76 Decontamination of the exterior of the straw is recommended by using sterile scissors

• GPP H.77 Given use of personal protection eqipment

• GPP H.78 The recommended procedures should be used for all virally positive samples