Zika virus and reproduction: facts, questions and current management.

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. 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 neurological system and on pregnancy outcomes. In mice, ZIKV slows foetal growth and damages the foetal brain. In humans, the virus is able to cross the placental barrier and to induce foetal death and major anomalies, such as microcephaly, brain defects and long-term neurologic sequelae, i.e. the 'congenital Zika syndrome'. In addition to its transmission by mosquitoes, ZIKV may be transmitted sexually. Currently available data indicate that ZIKV RNA can remain detectable in semen for several months, whereas shedding in the female genital tract appears to be rare and of short duration. Current guidance on preventing the sexual transmission of ZIKV is based on the assumption that transmission occurs from a male partner to a receptive partner. Furthermore, in mouse models, the virus can actively replicate in male genital organs and induce severe orchitis, which raises concerns about its possible impact on human male fertility. 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.

Regulatory framework in assisted reproductive technologies, relevance and main issues.

Assisted reproductive technologies (ART) have changed life for the past 25 years and many ethical and social issues have emerged following this new method of conception. In order to protect individuals against scientific and ethical abuses without inhibiting scientific progress, a specific legal framework is necessary. The first French law on Bioethics was voted after an extensive debate in 1994 then reviewed in 2004. This review previously scheduled every five years is currently being discussed. Legal provisions applying to ART are part of a large framework including the protection of the patients' rights and biomedical research. The key principles consist of respect for human life and ban on commercial practices of human body parts, eugenic practices and any kind of cloning. These key principles apply to ART. Donation is anonymous and free. Created in 2004, the Agence de la biomédecine is a government agency and one of the main tools of the French regulations. The missions focus on improving the quality and the safety of the management of ART. Evaluation of activities is available to all from the annual report. The agency represents the French competent authority for medical and scientific aspects of ART. Substantial differences in European legislations exist from the open-up "laissez faire" to the most restrictive one. As a consequence a large reproductive tourism has developed particularly for egg donation or surrogacy. The medical and ethical conditions of management of patients and donors represent the main critical points. In order to avoid ethical abuses, homogenization regarding the key principles is necessary in Europe. It is an opportunity to reassert that human body parts should not be a source of financial gain.

Pregnancy outcome and live birth after IVF and ICSI according to embryo quality.

PURPOSE: The pregnancy outcome and the chances of birth were assessed according to embryo quality after IVF or ICSI. METHODS: The implantation rate (IR), the loss of gestational sacs rate (LGSR), and birth rate (BR) were determined according to the cleavage stage and the integrity of blastomeres after day-2 homogeneous embryo transfers (n = 1812). RESULTS: The LGSR was higher after transfers of 2-3-cell or 5-6-cell embryos and was significantly increased when more than 20% of the embryo volume was fragmented in 4-cell embryos. After transfers of 4-cell embryos without fragmentation, the BR was significantly higher than the BR after transfers of 4-cell embryos with 1-20% fragmentation (16.6% vs 13.1%). The difference was the consequence of a higher IR (20.4% vs 17.3%) but also of a lower LGSR (18.9% vs 24.2%). CONCLUSIONS: Not only implantation and the ability to give a pregnancy, but also the capacity to give a live birth are dependent on the embryo quality.

Low dose recombinant FSH treatment may reduce multiple gestations caused by controlled ovarian hyperstimulation and intrauterine insemination.

OBJECTIVE: To evaluate the rate of multiple pregnancies in intrauterine insemination cycles stimulated with a minimal dose of recombinant follicle stimulating hormone (rec-FSH). DESIGN: Retrospective study. SETTING: University Medical Center. POPULATION: A total of 1256 patients underwent 3219 consequent intrauterine insemination cycles with minimal ovarian stimulation. METHODS: Patients received 50 or 75 IU of rec-FSH from day four to day seven. The dose was adjusted according to oestradiol (E(2)) levels in order to achieve a maximum of two follicles on the day of hCG administration. MAIN OUTCOME MEASURES: Peak E(2) levels, the number of follicles >15 mm and pregnancy rates were calculated. The predictive value of E(2) levels for multiple gestations was also estimated. RESULTS: Of 3219 cycles, 334 resulted in pregnancies (10%). Of these, 238 (91%) were singletons, 28 (8%) twins and 1 (0.3%) was a triplet. The cumulative overall pregnancy rate was 43%. Patients over 40 years old had a significantly lower pregnancy rate per cycle and overall live birth rate (P < 0.05). Most pregnancies (83%) occurred during the first three cycles. Pregnancy rates per cycle varied from 8% for tubal factor to 14% for anovulation infertility. CONCLUSIONS: Minimal FSH stimulation in intrauterine insemination cycles may reduce the rates of twins and high order multiple pregnancies without affecting overall pregnancy rates.

A simplified method for the detection of Y chromosome microdeletions in infertile men using a multiplex sequence-tagged site-based amplification.

Sixteen sequence-tagged sites (STSs) were combined in five amplification reactions, to screen for deletions of DNA fragments located within the AZFa, AZFb, and AZFc regions of the Y chromosome. This multiplex strategy is fast and reliable, and most of the azoospermia-associated deletions reported so far are detected with this simplified method. Internal control STSs are included that allow discrimination between deletion and failure of amplification.