Premenopausal women with hepatitis C virus (HCV) showed increased ovarian senescence, which was associated with a lower chance of live birth. Such women also had a greater risk of infertility, as reported in the Journal of Hepatology.

Researchers examined three cohort studies, which comprised an age-matched prospectively enrolled cohort study of 100 women who were HCV positive and had chronic liver disease, 50 women who were HBV positive and had CLD, and 100 healthy women; 1,998 HCV-infected women enrolled in the Platform for the Study of Viral Hepatitis Therapies (PITER) trial from Italy; and 6,085 women infected with HCV plus 20,415 uninfected women from a United States database, according to Aimilia Karampatou, MD, of the University of Bologna, Modena, Italy, and colleagues.

Age, reproductive status, and serum levels of anti-Müllerian hormone (AMH) – a marker of ovarian reserve – were collected from the women in the first study’s groups. There was a significant correlation between AMH levels and hepatic grade (P = .041) and stage (P = .038) in women who were HCV positive but not in those who were HBV positive. In addition, the incidence of miscarriages in women who were HCV positive was correlated with median AMH (1.0 ng/mL). No relationship was found between AMH levels in HCV-uninfected controls and risk of miscarriage.

In the second group examined, the women from the PITER trial, miscarriages occurred in 42% of the HCV-infected women with 44.6% of these women experiencing multiple miscarriages. The total fertility rate, defined as the average number of children that would be born in a lifetime, was 0.7 for the HCV-infected women, compared with 1.37 in the general Italian population.

Infertility data from the large U.S. study was assessed from a total of 27,525 women (20,415 HCV negative and HIV negative; 6,805 HCV positive; and 305 HCV positive/HIV positive). Women with HCV showed a significantly higher probability of infertility compared with uninfected controls (odds ratio, 2.44), and those women dually infected with HCV and HIV were affected even more (OR, 3.64).

Primarily based on the observations of AMH, which in many of the HCV-positive women fell into the menopausal range, the researchers suggested that “the reduced reproductive capacity of women who are HCV positive is related to failing ovarian function and subsequent follicular depletion in the context of a more generalized dysfunction of other fertility-related factors.”

With regard to the effect of antiviral therapy, AMH levels remained stable in women who attained a sustained virologic response but continued to fall in those for whom the therapy was a failure.

“HCV infection significantly and negatively affects many aspects of fertility. It remains to be assessed whether antiviral therapy at a very early age can positively influence the occurrence of miscarriages and can prevent ovarian senescence because the latter has broader health implications than simply preserving fertility,” the researchers concluded.

The authors reported that they had no conflicts of interest.

SOURCE: Karampatou A et al. J Hepatology. 2018;68:33-41 .


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