Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV

Aimilia Karampatou, Xue Han, Loreta A. Kondili, Gloria Taliani, Alessia Ciancio, Filomena Morisco, Rosina Maria Critelli, Enrica Baraldi, Veronica Bernabucci, Giulia Troshina, Maria Guarino, Simonetta Tagliavini, Federica D'Ambrosio, Laura Bristot, Laura Turco, Stefano Rosato, Stefano Vella, Tommaso Trenti, Isabella Neri, Antonio La MarcaShivaji Manthena, Andrea S. Goldstein, Savino Bruno, Yanjun Bao, Yuri Sanchez Gonzalez, Erica Villa, A. Craxì, S. Petta, V. Calvaruso, M. Brunetto, B. Coco, L. Chessa, M. C. Pasetto, E. Bigliotti, F. Tamburrini, G. Montalto, M. Monti, E. Finati, M. Milella, F. P. Russo, M. Gemma, A. Gori, R. Bruno, S. Cima, C. Coppola, G. Simonetti, G. Brancaccio, M. Mondelli, S. Ludovisi, M. Persico, PITER framework investigators

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background & Aims Premenopausal women who are HCV positive (HCV+) have failing ovarian function, which is likely to impact their fertility. Thus, we investigated the reproductive history, risk of infertility, and pregnancy outcomes in women of childbearing age who were HCV+. Methods Three different groups were studied: (1) Clinical cohort: 100 women who were HCV+ and also had chronic liver disease (CLD), age matched with 50 women who were HBV+ with CLD and with 100 healthy women; all women were consecutively observed in three gastroenterology units in hospitals in Italy; (2) 1,998 women who were HCV+ and enrolled in the Italian Platform for the Study of Viral Hepatitis Therapies (PITER); (3) 6,085 women, who were mono-infected with HCV, and 20,415 women, who were HCV−, from a large de-identified insurance database from the USA. Measurements: total fertility rate (TFR) defined as the average number of children that a woman would bear during her lifetime. To define the reproductive stage of each participant, levels of anti-Müllerian hormone (AMH) and 17β-estradiol were measured. Results Clinical cohort: women who were either HCV+ or HBV+ had similar CLD severity and age at first pregnancy. Based on a multivariate analysis, women who were HCV+ had a higher risk of miscarriage than those who were HBV+ (odds ratio [OR] 6,905; 95% CI 1.771–26.926). Among women who were HCV+, incidence of miscarriage was correlated with median AMH level (1.0 ng/ml). Achieving a sustained virologic response (SVR) after antiviral treatment reduced the risk of miscarriage (OR 0.255; 95% CI 0.090–0.723). In the PITER-HCV cohort, miscarriage occurred in 42.0% of women (44.6% had multiple miscarriages). TFR for women who were HCV+ and between 15 and 49 years of age was 0.7 vs. 1.37 of Italian population of the same age range. In the US cohort: compared with women who were HCV−, women who were HCV+ positive were significantly more likely to have infertility (OR 2.439; 95% CI 2.130–2.794), premature birth (OR 1.34; 95% CI 1.060–1.690), gestational diabetes (OR 1.24; 95% CI 1.020–1.510), and pre-eclampsia (OR 1.206; 95% CI 0.935–1.556), and were less likely to have a live birth (OR 0.754; 95% CI 0.622–0.913). Conclusions Ovarian senescence in women of childbearing age who are HCV+ is associated with a lower chance of live birth, greater risk of infertility, gestational diabetes, pre-eclampsia and miscarriage. Such risks could be positively influenced by successful HCV cure. Lay summary Most new cases of HCV infection are among people who inject drugs, many of whom are young women in their childbearing years. Women of reproductive age who are HCV+ display markers of ovarian senescence. This is associated with an increased burden in terms of infertility and adverse pregnancy outcomes, including stillbirth, miscarriage, fewer live births, and gestational diabetes. Early viral suppression with therapy is likely to mitigate these risks.

Original languageEnglish
Pages (from-to)33-41
Number of pages9
JournalJournal of Hepatology
Volume68
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

Birth Rate
Spontaneous Abortion
Odds Ratio
Infertility
Gestational Diabetes
Live Birth
Liver Diseases
Chronic Disease
Pregnancy Outcome
Pre-Eclampsia
Hormones
Reproductive History
Hospital Units
Stillbirth

Keywords

  • Anti-Müllerian hormone
  • Antiviral therapy
  • HBV
  • HCV
  • Sustained viral response

ASJC Scopus subject areas

  • Hepatology

Cite this

Karampatou, A., Han, X., Kondili, L. A., Taliani, G., Ciancio, A., Morisco, F., ... PITER framework investigators (2018). Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV. Journal of Hepatology, 68(1), 33-41. https://doi.org/10.1016/j.jhep.2017.08.019

Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV. / Karampatou, Aimilia; Han, Xue; Kondili, Loreta A.; Taliani, Gloria; Ciancio, Alessia; Morisco, Filomena; Critelli, Rosina Maria; Baraldi, Enrica; Bernabucci, Veronica; Troshina, Giulia; Guarino, Maria; Tagliavini, Simonetta; D'Ambrosio, Federica; Bristot, Laura; Turco, Laura; Rosato, Stefano; Vella, Stefano; Trenti, Tommaso; Neri, Isabella; La Marca, Antonio; Manthena, Shivaji; Goldstein, Andrea S.; Bruno, Savino; Bao, Yanjun; Gonzalez, Yuri Sanchez; Villa, Erica; Craxì, A.; Petta, S.; Calvaruso, V.; Brunetto, M.; Coco, B.; Chessa, L.; Pasetto, M. C.; Bigliotti, E.; Tamburrini, F.; Montalto, G.; Monti, M.; Finati, E.; Milella, M.; Russo, F. P.; Gemma, M.; Gori, A.; Bruno, R.; Cima, S.; Coppola, C.; Simonetti, G.; Brancaccio, G.; Mondelli, M.; Ludovisi, S.; Persico, M.; PITER framework investigators.

In: Journal of Hepatology, Vol. 68, No. 1, 01.01.2018, p. 33-41.

Research output: Contribution to journalArticle

Karampatou, A, Han, X, Kondili, LA, Taliani, G, Ciancio, A, Morisco, F, Critelli, RM, Baraldi, E, Bernabucci, V, Troshina, G, Guarino, M, Tagliavini, S, D'Ambrosio, F, Bristot, L, Turco, L, Rosato, S, Vella, S, Trenti, T, Neri, I, La Marca, A, Manthena, S, Goldstein, AS, Bruno, S, Bao, Y, Gonzalez, YS, Villa, E, Craxì, A, Petta, S, Calvaruso, V, Brunetto, M, Coco, B, Chessa, L, Pasetto, MC, Bigliotti, E, Tamburrini, F, Montalto, G, Monti, M, Finati, E, Milella, M, Russo, FP, Gemma, M, Gori, A, Bruno, R, Cima, S, Coppola, C, Simonetti, G, Brancaccio, G, Mondelli, M, Ludovisi, S, Persico, M & PITER framework investigators 2018, 'Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV', Journal of Hepatology, vol. 68, no. 1, pp. 33-41. https://doi.org/10.1016/j.jhep.2017.08.019
Karampatou, Aimilia ; Han, Xue ; Kondili, Loreta A. ; Taliani, Gloria ; Ciancio, Alessia ; Morisco, Filomena ; Critelli, Rosina Maria ; Baraldi, Enrica ; Bernabucci, Veronica ; Troshina, Giulia ; Guarino, Maria ; Tagliavini, Simonetta ; D'Ambrosio, Federica ; Bristot, Laura ; Turco, Laura ; Rosato, Stefano ; Vella, Stefano ; Trenti, Tommaso ; Neri, Isabella ; La Marca, Antonio ; Manthena, Shivaji ; Goldstein, Andrea S. ; Bruno, Savino ; Bao, Yanjun ; Gonzalez, Yuri Sanchez ; Villa, Erica ; Craxì, A. ; Petta, S. ; Calvaruso, V. ; Brunetto, M. ; Coco, B. ; Chessa, L. ; Pasetto, M. C. ; Bigliotti, E. ; Tamburrini, F. ; Montalto, G. ; Monti, M. ; Finati, E. ; Milella, M. ; Russo, F. P. ; Gemma, M. ; Gori, A. ; Bruno, R. ; Cima, S. ; Coppola, C. ; Simonetti, G. ; Brancaccio, G. ; Mondelli, M. ; Ludovisi, S. ; Persico, M. ; PITER framework investigators. / Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV. In: Journal of Hepatology. 2018 ; Vol. 68, No. 1. pp. 33-41.
@article{4027feffb7d942529c15af95b04e1e5b,
title = "Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV",
abstract = "Background & Aims Premenopausal women who are HCV positive (HCV+) have failing ovarian function, which is likely to impact their fertility. Thus, we investigated the reproductive history, risk of infertility, and pregnancy outcomes in women of childbearing age who were HCV+. Methods Three different groups were studied: (1) Clinical cohort: 100 women who were HCV+ and also had chronic liver disease (CLD), age matched with 50 women who were HBV+ with CLD and with 100 healthy women; all women were consecutively observed in three gastroenterology units in hospitals in Italy; (2) 1,998 women who were HCV+ and enrolled in the Italian Platform for the Study of Viral Hepatitis Therapies (PITER); (3) 6,085 women, who were mono-infected with HCV, and 20,415 women, who were HCV−, from a large de-identified insurance database from the USA. Measurements: total fertility rate (TFR) defined as the average number of children that a woman would bear during her lifetime. To define the reproductive stage of each participant, levels of anti-M{\"u}llerian hormone (AMH) and 17β-estradiol were measured. Results Clinical cohort: women who were either HCV+ or HBV+ had similar CLD severity and age at first pregnancy. Based on a multivariate analysis, women who were HCV+ had a higher risk of miscarriage than those who were HBV+ (odds ratio [OR] 6,905; 95{\%} CI 1.771–26.926). Among women who were HCV+, incidence of miscarriage was correlated with median AMH level (1.0 ng/ml). Achieving a sustained virologic response (SVR) after antiviral treatment reduced the risk of miscarriage (OR 0.255; 95{\%} CI 0.090–0.723). In the PITER-HCV cohort, miscarriage occurred in 42.0{\%} of women (44.6{\%} had multiple miscarriages). TFR for women who were HCV+ and between 15 and 49 years of age was 0.7 vs. 1.37 of Italian population of the same age range. In the US cohort: compared with women who were HCV−, women who were HCV+ positive were significantly more likely to have infertility (OR 2.439; 95{\%} CI 2.130–2.794), premature birth (OR 1.34; 95{\%} CI 1.060–1.690), gestational diabetes (OR 1.24; 95{\%} CI 1.020–1.510), and pre-eclampsia (OR 1.206; 95{\%} CI 0.935–1.556), and were less likely to have a live birth (OR 0.754; 95{\%} CI 0.622–0.913). Conclusions Ovarian senescence in women of childbearing age who are HCV+ is associated with a lower chance of live birth, greater risk of infertility, gestational diabetes, pre-eclampsia and miscarriage. Such risks could be positively influenced by successful HCV cure. Lay summary Most new cases of HCV infection are among people who inject drugs, many of whom are young women in their childbearing years. Women of reproductive age who are HCV+ display markers of ovarian senescence. This is associated with an increased burden in terms of infertility and adverse pregnancy outcomes, including stillbirth, miscarriage, fewer live births, and gestational diabetes. Early viral suppression with therapy is likely to mitigate these risks.",
keywords = "Anti-M{\"u}llerian hormone, Antiviral therapy, HBV, HCV, Sustained viral response",
author = "Aimilia Karampatou and Xue Han and Kondili, {Loreta A.} and Gloria Taliani and Alessia Ciancio and Filomena Morisco and Critelli, {Rosina Maria} and Enrica Baraldi and Veronica Bernabucci and Giulia Troshina and Maria Guarino and Simonetta Tagliavini and Federica D'Ambrosio and Laura Bristot and Laura Turco and Stefano Rosato and Stefano Vella and Tommaso Trenti and Isabella Neri and {La Marca}, Antonio and Shivaji Manthena and Goldstein, {Andrea S.} and Savino Bruno and Yanjun Bao and Gonzalez, {Yuri Sanchez} and Erica Villa and A. Crax{\`i} and S. Petta and V. Calvaruso and M. Brunetto and B. Coco and L. Chessa and Pasetto, {M. C.} and E. Bigliotti and F. Tamburrini and G. Montalto and M. Monti and E. Finati and M. Milella and Russo, {F. P.} and M. Gemma and A. Gori and R. Bruno and S. Cima and C. Coppola and G. Simonetti and G. Brancaccio and M. Mondelli and S. Ludovisi and M. Persico and {PITER framework investigators}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.jhep.2017.08.019",
language = "English",
volume = "68",
pages = "33--41",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier B.V.",
number = "1",

}

TY - JOUR

T1 - Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV

AU - Karampatou, Aimilia

AU - Han, Xue

AU - Kondili, Loreta A.

AU - Taliani, Gloria

AU - Ciancio, Alessia

AU - Morisco, Filomena

AU - Critelli, Rosina Maria

AU - Baraldi, Enrica

AU - Bernabucci, Veronica

AU - Troshina, Giulia

AU - Guarino, Maria

AU - Tagliavini, Simonetta

AU - D'Ambrosio, Federica

AU - Bristot, Laura

AU - Turco, Laura

AU - Rosato, Stefano

AU - Vella, Stefano

AU - Trenti, Tommaso

AU - Neri, Isabella

AU - La Marca, Antonio

AU - Manthena, Shivaji

AU - Goldstein, Andrea S.

AU - Bruno, Savino

AU - Bao, Yanjun

AU - Gonzalez, Yuri Sanchez

AU - Villa, Erica

AU - Craxì, A.

AU - Petta, S.

AU - Calvaruso, V.

AU - Brunetto, M.

AU - Coco, B.

AU - Chessa, L.

AU - Pasetto, M. C.

AU - Bigliotti, E.

AU - Tamburrini, F.

AU - Montalto, G.

AU - Monti, M.

AU - Finati, E.

AU - Milella, M.

AU - Russo, F. P.

AU - Gemma, M.

AU - Gori, A.

AU - Bruno, R.

AU - Cima, S.

AU - Coppola, C.

AU - Simonetti, G.

AU - Brancaccio, G.

AU - Mondelli, M.

AU - Ludovisi, S.

AU - Persico, M.

AU - PITER framework investigators

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background & Aims Premenopausal women who are HCV positive (HCV+) have failing ovarian function, which is likely to impact their fertility. Thus, we investigated the reproductive history, risk of infertility, and pregnancy outcomes in women of childbearing age who were HCV+. Methods Three different groups were studied: (1) Clinical cohort: 100 women who were HCV+ and also had chronic liver disease (CLD), age matched with 50 women who were HBV+ with CLD and with 100 healthy women; all women were consecutively observed in three gastroenterology units in hospitals in Italy; (2) 1,998 women who were HCV+ and enrolled in the Italian Platform for the Study of Viral Hepatitis Therapies (PITER); (3) 6,085 women, who were mono-infected with HCV, and 20,415 women, who were HCV−, from a large de-identified insurance database from the USA. Measurements: total fertility rate (TFR) defined as the average number of children that a woman would bear during her lifetime. To define the reproductive stage of each participant, levels of anti-Müllerian hormone (AMH) and 17β-estradiol were measured. Results Clinical cohort: women who were either HCV+ or HBV+ had similar CLD severity and age at first pregnancy. Based on a multivariate analysis, women who were HCV+ had a higher risk of miscarriage than those who were HBV+ (odds ratio [OR] 6,905; 95% CI 1.771–26.926). Among women who were HCV+, incidence of miscarriage was correlated with median AMH level (1.0 ng/ml). Achieving a sustained virologic response (SVR) after antiviral treatment reduced the risk of miscarriage (OR 0.255; 95% CI 0.090–0.723). In the PITER-HCV cohort, miscarriage occurred in 42.0% of women (44.6% had multiple miscarriages). TFR for women who were HCV+ and between 15 and 49 years of age was 0.7 vs. 1.37 of Italian population of the same age range. In the US cohort: compared with women who were HCV−, women who were HCV+ positive were significantly more likely to have infertility (OR 2.439; 95% CI 2.130–2.794), premature birth (OR 1.34; 95% CI 1.060–1.690), gestational diabetes (OR 1.24; 95% CI 1.020–1.510), and pre-eclampsia (OR 1.206; 95% CI 0.935–1.556), and were less likely to have a live birth (OR 0.754; 95% CI 0.622–0.913). Conclusions Ovarian senescence in women of childbearing age who are HCV+ is associated with a lower chance of live birth, greater risk of infertility, gestational diabetes, pre-eclampsia and miscarriage. Such risks could be positively influenced by successful HCV cure. Lay summary Most new cases of HCV infection are among people who inject drugs, many of whom are young women in their childbearing years. Women of reproductive age who are HCV+ display markers of ovarian senescence. This is associated with an increased burden in terms of infertility and adverse pregnancy outcomes, including stillbirth, miscarriage, fewer live births, and gestational diabetes. Early viral suppression with therapy is likely to mitigate these risks.

AB - Background & Aims Premenopausal women who are HCV positive (HCV+) have failing ovarian function, which is likely to impact their fertility. Thus, we investigated the reproductive history, risk of infertility, and pregnancy outcomes in women of childbearing age who were HCV+. Methods Three different groups were studied: (1) Clinical cohort: 100 women who were HCV+ and also had chronic liver disease (CLD), age matched with 50 women who were HBV+ with CLD and with 100 healthy women; all women were consecutively observed in three gastroenterology units in hospitals in Italy; (2) 1,998 women who were HCV+ and enrolled in the Italian Platform for the Study of Viral Hepatitis Therapies (PITER); (3) 6,085 women, who were mono-infected with HCV, and 20,415 women, who were HCV−, from a large de-identified insurance database from the USA. Measurements: total fertility rate (TFR) defined as the average number of children that a woman would bear during her lifetime. To define the reproductive stage of each participant, levels of anti-Müllerian hormone (AMH) and 17β-estradiol were measured. Results Clinical cohort: women who were either HCV+ or HBV+ had similar CLD severity and age at first pregnancy. Based on a multivariate analysis, women who were HCV+ had a higher risk of miscarriage than those who were HBV+ (odds ratio [OR] 6,905; 95% CI 1.771–26.926). Among women who were HCV+, incidence of miscarriage was correlated with median AMH level (1.0 ng/ml). Achieving a sustained virologic response (SVR) after antiviral treatment reduced the risk of miscarriage (OR 0.255; 95% CI 0.090–0.723). In the PITER-HCV cohort, miscarriage occurred in 42.0% of women (44.6% had multiple miscarriages). TFR for women who were HCV+ and between 15 and 49 years of age was 0.7 vs. 1.37 of Italian population of the same age range. In the US cohort: compared with women who were HCV−, women who were HCV+ positive were significantly more likely to have infertility (OR 2.439; 95% CI 2.130–2.794), premature birth (OR 1.34; 95% CI 1.060–1.690), gestational diabetes (OR 1.24; 95% CI 1.020–1.510), and pre-eclampsia (OR 1.206; 95% CI 0.935–1.556), and were less likely to have a live birth (OR 0.754; 95% CI 0.622–0.913). Conclusions Ovarian senescence in women of childbearing age who are HCV+ is associated with a lower chance of live birth, greater risk of infertility, gestational diabetes, pre-eclampsia and miscarriage. Such risks could be positively influenced by successful HCV cure. Lay summary Most new cases of HCV infection are among people who inject drugs, many of whom are young women in their childbearing years. Women of reproductive age who are HCV+ display markers of ovarian senescence. This is associated with an increased burden in terms of infertility and adverse pregnancy outcomes, including stillbirth, miscarriage, fewer live births, and gestational diabetes. Early viral suppression with therapy is likely to mitigate these risks.

KW - Anti-Müllerian hormone

KW - Antiviral therapy

KW - HBV

KW - HCV

KW - Sustained viral response

UR - http://www.scopus.com/inward/record.url?scp=85031788530&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85031788530&partnerID=8YFLogxK

U2 - 10.1016/j.jhep.2017.08.019

DO - 10.1016/j.jhep.2017.08.019

M3 - Article

AN - SCOPUS:85031788530

VL - 68

SP - 33

EP - 41

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 1

ER -