Zika virus and reproduction: facts, questions and current management

Human Reproduction Update, Vol.23, No.6 pp. 629–645, 2017 Advanced Access publication on August 9, 2017 doi:10.1093/humupd/dmx024 Zika virus and reproduction: facts, questions and current management Sylvie Epelboin1,2, Emmanuel Dulioust3,4, Loïc Epelboin5,6, Alexandra Benachi7,8, Françoise Merlet9, and Catherine Patrat 2,10,* *Correspondence address. Hôpital Bichat, Service de Biologie de la Reproduction, 46 rue Henri Huchard, 75018 Paris, France. Tel: +33-1-40-25-88-84; Fax: +33-1-40-25-87-97; E-mail: orcid.org/0000-0003-4885-8885 Submitted on April 27, 2017; resubmitted on July 11, 2017; editorial decision on July 18, 2017; accepted on August 2, 2017 TABLE OF CONTENTS ........................................................................................................................... • • • • • • Introduction Epidemiology Diagnosis Methods ZIKV in reproductive organs: genital shedding, sexual transmission and impact on fertility ZIKV in the male genital tract: presence and sexual transmission ZIKV and male fertility (animal models) ZIKV in the female genital tract: presence and sexual transmission ZIKV and female fertility (animal models) Impact of ZIKV infection on pregnancy and offspring (vertical transmission, including hypothesis for the mechanisms of mother-to-child transmission) Maternal infection Pregnancy outcome and offspring malformations Hypotheses for the mechanisms of embryo/foetopathogenic impact of ZIKV Current management in pregnancy planning and ART in the context of ZIKV epidemics Authorities’ plans and strategies at the European and international levels Diagnostic means Pregnancy planning recommendations Guidelines for pregnant women during ZIKV outbreaks ART recommendations Conclusion BACKGROUND: Zika virus (ZIKV) is an arthropod-borne virus of the family Flaviviridae, genus Flavivirus. ZIKV is currently the focus of an ongoing pandemic and worldwide public health emergency. Although originally isolated in 1947, its pathogenesis was poorly known and very few documented infections were published until recently. Its route of transmission and its impact on reproduction and pregnancy have only recently begun to be disclosed. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: 1 Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Service de Gynécologie, Obstétrique et Reproduction, 46 rue Henri Huchard, 75018 Paris, France 2Université Paris Diderot, Sorbonne Paris Cité, France 3Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Centre d’Etudes et de Conservation des Ovocytes et du Sperme, 27 rue du Faubourg Saint Jacques, 75014 Paris, France 4Université Paris Descartes, Sorbonne Paris Cité, France 5Hôpital Andrée Rosemon, Avenue des Flamboyants, Cayenne 97300, France 6Université de Guyane, Equipe EA 3593, Ecosystèmes Amazoniens et Pathologie Tropicale, Cayenne, Guyane Française 7Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Antoine Béclère, Service de Gynécologie-Obstétrique, 147 rue de la Porte de Trivaux, 92140 Clamart, France 8 Université Paris Sud, Clamart, France 9Agence de la Biomédecine, 1 Avenue du Stade de France, 93212 La Plaine Saint Denis, France 10 Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Service de Biologie de la Reproduction, 46 rue Henri Huchard, 75018 Paris, France 630 Epelboin et al. OBJECTIVE AND RATIONALE: This review summarizes the most recent knowledge about ZIKV infection and pathogenesis and focuses on its impacts on male and female genital tracts, including the risks of sexual transmission and to pregnancy. The consequences of ZIKV infection for pregnancy planning and ART are also discussed. SEARCH METHODS: The PubMed and EMBASE databases were inter-rogated using specific terms, such as ‘ZIKV’, ‘transmission’, ‘male’, ‘female’, fertility’, ‘pregnancy, ‘semen’, ‘testis’, ‘ovary’ and ‘genital tract’, up to 17 March 2017. OUTCOMES: ZIKV has long been considered a harmless virus, but increasing evidence suggests that it has adverse effects on the neuro- WIDER IMPLICATIONS: These new and relevant findings have led many countries and institutions to release updated and regular guidance for preconception counselling and ART to prevent the sexual transmission of ZIKV. Progress in understanding the sexual transmission of ZIKV and its dissemination to genital systems would also help to better anticipate and control outbreaks of potentially sexually transmissible infectious agents. Key words: Zika virus / fertility / reproduction / human / assisted reproduction / pregnancy outcome Introduction Zika virus (ZIKV) infection is an emerging disease caused by ZIKV, an arthropod-borne virus, or arbovirus, transmitted by Aedes spp. mosquitoes. ZIKV belongs to the family Flaviviridae, as do dengue, yellow fever, St. Louis encephalitis, Japanese encephalitis and West Nile viruses. ZIKV was first isolated in 1947 from a febrile sentinel Rhesus macaque in the Zika Forest of Uganda, followed by isolation in 1948 in Aedes africanus mosquitoes in the same forest, suggesting the mosquito-borne transmission of the virus (Dick et al., 1952). Between 1952, the date of the first human description, and the first epidemic in 2007 on a small island in Micronesia, fewer than 10 cases had been reported. In 2013, a large outbreak started in French Polynesia, spread through the Pacific Ocean region, and invaded most of the countries in the Americas. ZIKV infection is predominantly a vector-borne disease and has long been considered a benign illness, likely asymptomatic in 50–80% of cases or causing mild symptoms (Duffy et al., 2009; Ioos et al., 2014; Aubry et al., 2017). Actually, it is now clear that other, nonvector routes of ZIKV transmission may also occur, including congenital (Martines et al., 2016), perinatal (Besnard et al., 2014), sexual (McCarthy, 2016; d’Ortenzio et al., 2016), blood transfusion (Musso et al., 2014), animal bite (Leung et al., 2015) and laboratory exposure (Simpson, 1964). Moreover, severe clinical sequelae, such as GuillainBarré syndrome (GBS) (Heymann et al., 2016) and microcephaly (Rodriguez-Morales, 2016), have also increasingly been associated with ZIKV. The World Health Organization (WHO) declared that the ZIKV infection is a public health emergency in February 2016 and initiated a strategic response, including recommendations for willing pregnant women. In this review, after a brief introduction to epidemiology and clinical and biological diagnosis, we will review the impacts of ZIKV infection on reproduction, risk of sexual transmission (from both males and females) and pregnancy and offspring. Finally, the management of pregnancy planning and ART in the context of ZIKV epidemics will also be discussed. Epidemiology Over the past 60 years, ZIKV has been observed circulating among African and Asian populations (Hayes, 2009), but has received litt (...truncated)