and involvement of a hepatologist to ensure that the female partner does not have any signs of chronic liver disease.
Hepatitis C
Previous HCV infection is not known to directly affect fertility [14]. Therefore, natural pregnancy may occur in HCV positive couples. When pregnancy is naturally conceived, HCV increases the risk of preterm birth, which is thought to be due to the effects of HCV on trophoblasts [15]. The risk of vertical transmission in pregnancy is estimated to be approximately <1% when there is positivity for HCV‐antibody but negative results for HCV RNA testing. If both HCV‐antibody and HCV RNA tests are positive, the vertical transmission rate is estimated at 11%. HIV co‐infection increases the risk of transmission further to 15% [16]. Pregnancy does not appear to impact the course of chronic liver disease secondary to HCV infection. Importantly, there is no immunoprophylaxis available for neonates born to HCV positive women; instead HCV status can be checked at 3 months of age using an HCV RNA PCR test or serum HCV antibody testing after 18 months of age.
Antiviral therapy for HCV infections can lead to cure of infection in 90% of HCV carriers. It is therefore important that known HCV carriers are reviewed by a hepatologist before commencing fertility treatment. Hepatic function can be ascertained, and the risks of vertical transmission can be reduced with HCV antiviral therapy.
In male HCV carriers, HCV RNA has been detected in sperm, but the risk of sexual transmission is very low. Similarly, the risk of transmission of HCV from spermatozoa to fetus has not been proven. There is some evidence to suggest that male HCV carriers have worse sperm results, fertilization rates and pregnancy outcomes when compared with males without HCV infection [17]. However, other studies have shown conflicting evidence with similar pregnancy rates achieved in couples with male HCV carriers compared to couples unaffected with HCV.
In female HCV carriers having ART treatment, it has been suggested that the response to gonadotropin stimulation is reduced. This effect is thought to be due to altered granulosa cell function in ovarian follicles recruited during stimulation [18]. Studies have also suggested that HCV positive women have reduced fertilization, implantation and clinical pregnancy rates when compared with unaffected women. However, the evidence is conflicting, and HCV infection is not thought to cause adverse pregnancy outcomes in those undergoing ART [18]
Overall, ART is considered to be safe in HCV‐positive couples (Case History 2). Treatment should be started after liaison with a hepatologist and consideration for HCV antiviral therapy. If antiviral therapy is not effective, ART should be commenced when HCV viral load is low. The HCV viral load can then be monitored during pregnancy.
Prevention
For HBV, staff and uninfected partners should receive vaccination to reduce the risk of infection. Approximately 90% of adults who are vaccinated produce a protective antibody response. HBV vaccination should be provided to neonates born to HBV‐positive women. Unfortunately, there is no effective HCV vaccine, although HCV antiviral therapy is now proven to be highly effective in eradicating HCV infection.
Importantly, precautionary measures should be implemented in ART laboratories to reduce the risk of transmission of HBV and HCV to technicians handling infective gametes and embryos. Similarly, protective measures should be taken to reduce the risk of cross‐contamination of HBV or HCV during cryopreservation of samples and embryos.
Key points
Challenge: Previous HBV and HCV infection in ART patients.
Background:
HBV and HCV are common viral infections, which may lead to chronic liver disease.
The risks in ART are transmission of infection to an uninfected partner and vertical transmission to the neonate. Additionally, there are risks of infection for staff in the ART laboratory.
All patients undergoing ART should have HBV and HCV screening.
Management:
ART in HBV‐or HCV‐infected couple is considered to be safe.
HBV and HCV infection do not have an adverse effect on ART pregnancy outcome.
In HBV, the uninfected partner should be vaccinated. No vaccination is available for HCV.
In an HCV‐positive patient, effective antiviral therapy is available
The risk of vertical transmission from an infected mother to the neonate is similar in natural pregnancies and those conceived by ART.
Babies born from HBV‐positive women should receive immunoprophylaxis in the first 24 hours of life.
Precautions should be taken to reduce the risk of laboratory transmission and cross‐contamination of gamete samples and embryos during cryostorage.
Answers to questions patients ask
1 Q1 I am a carrier of hepatitis B, but my husband is clear. Is it safe for me to have IVF treatment? A1. IVF treatment is considered to be safe in those who have had previous HBV infection. We will ask you first to see a liver doctor to ensure that there are no manifestations of chronic liver disease. If not already immune, your partner may need to be vaccinated to reduce the risk of transmission.
2 Q2 Will my previous HBV (or HCV) infection affect whether I can get pregnant with IVF? A2. Previous HBV (or HCV) infection is not known to reduce the chances of pregnancy with IVF treatment.
3 Q3 I have previously had hepatitis B; will my baby be infected if I get pregnant? A3. There is a small risk of transmission to the baby. If you have had HBV infection before, the risks can be reduced through vaccination of the baby soon after birth.
References
1 1 Trépo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet. 2014; 384(9959):2053–2063.
2 2 Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012; 380(9859):2095–2128.
3 3 Te HS, Jensen DM. Epidemiology of hepatitis B and C viruses: a global overview. Clin Liver Dis. 2010; 14(1):i–vii.
4 4 Beasley RP. Rocks along the road to the control of HBV and HCC. Ann Epidemiol. 2009; 19(4):231–234.
5 5 Ansaldi F, Orsi A, Sticchi L, Bruzzone B, Icardi G. Hepatitis C virus in the new era: perspectives in epidemiology, prevention, diagnostics and predictors of response to therapy. World J Gastroenterol. 2014; 20(29):9633–9652.
6 6 Wilkins T, Akhtar M, Gititu E, Jalluri C, Ramirez J. Diagnosis and management of hepatitis C. Am Fam Physician. 2015; 91(12):835–842.
7 7 Castillo E, Murphy K, van Schalkwyk J. No. 342‐Hepatitis B and pregnancy. J Obstet Gynaecol Can. 2017; 39(3):181–190.
8 8 Society for Maternal‐Fetal Medicine (SMFM), Dionne‐Odom J, Tita AT, Silverman NS. #38: Hepatitis B in pregnancy screening, treatment, and prevention of vertical transmission. Am J Obstet Gynecol. 2016; 214(1):6–14.
9 9 Mak JSM, Lao TT. Assisted reproduction in hepatitis carrier couples. Best Pract Res Clin Obstet Gynaecol. 2020;S1521–6934( 20)30041–9.
10 10 Pirwany IR, Phillips S, Kelly S, Buckett W, Tan SL. Reproductive performance of couples discordant for hepatitis B and C following IVF treatment. J Assist Reprod Genet. 2004; 21(5):157–161.
11 11 Lam PM, Suen SH, Lao TT, Cheung LP, Leung TY, Haines C. Hepatitis B infection and outcomes of in vitro fertilization and embryo transfer treatment. Fertil Steril. 2010; 93(2):480–485.
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