Premature ovarian senescence and high miscarriage rate impair fertility in women with hepatitis C virus infection

5 years ago

Premature ovarian senescence and high miscarriage rate impair fertility in women with hepatitis C virus infection

Premenopausal Hepatitis C Virus positive (HCV+) women have failing ovarian function.We thus investigated reproductive history,risk of infertility and pregnancy outcomes in HCV+ women of childbearing age.

Methods

Three different groups were studied:1) Clinical cohort:100 HCV+ women with chronic liver disease (CLD), age matched with 50 HBV+ women with CLD and with 100 healthy women consecutively observed in 3 Italian Gastroenterology Units;2) 1998 HCV+ women enrolled in the Italian Platform for the Study of Viral Hepatitis Therapies (PITER);3) 6.085 HCV mono-infected and 20.415 HCV-negative women from a large de-identified insurance database from United States. Measurements:Total fertility rate (TFR) defined as the average number of children that a woman would bear during her lifetime. For reproductive stage definition, anti-mullerian hormone (AMH) and 17β-Estradiol were measured.

Results

Clinical cohort: HCV+ and HBV+ women had similar CLD severity and age at first pregnancy. At multivariate analysis,HCV+ women had higher risk of miscarriage than HBV+ (OR: 6,905;95%CI:1.771-26.926).Among HCV+ women, miscarriage related with median Anti-Müllerian hormone levels (1.0 ng/ml).Achieving SVR after antiviral treatment reduced the risk of miscarriage (OR:0.255,95%CI:0.090–0.723). In PITER cohort, miscarriage occurred in 42.0% of women (44.6% had multiple miscarriages).TFR for HCV+ women between 15 and 49 years was 0.7 vs. 1.37 of Italian population of the same age range. US cohort: HCV+ vs.HCV- women were significantly more likely to have infertility (OR 2.439;95%CI:2.130-2.794), premature birth (OR:1.34;95%CI:1.06-1.69), gestational diabetes (OR:1.24; 95%CI:1.02-1.51), pre-eclampsia (OR 1.206;95%CI 0.935-1.556) and less likely to have a live birth (OR 0.754;95%CI:0.622-0.913).

Conclusions

Ovarian senescence in HCV+ women of child-bearing age is associated with a lower chance of live birth, greater risk of infertility, gestational diabetes, pre-eclampsia and miscarriage, which may be positively influenced by successful HCV cure.

Lay summary

The majority of new hepatitis C virus (HCV) infections are among people who inject drugs, many of whom are young women in their childbearing years. HCV-positive women of reproductive age display markers of ovarian senescence. This is associated with an increased burden in terms of infertility and adverse pregnancy outcomes, including still births, miscarriages, fewer live births and gestational diabetes. Early viral suppression with therapy is likely to mitigate these risks.

Publisher URL: www.sciencedirect.com/science

DOI: S0168827817322596