To elucidate the roles of human herpesvirus (HHV)-6 primary unexplained infertile women, a prospective randomized study was conducted on a cohort of primary unexplained infertile women and a cohort of control women, with at least one successful pregnancy. HHV-6 DNA was analyzed and the percentage and immune-phenotype of resident endometrial Natural Killer (NK) cells, as the first line of defense towards viral infections, was evaluated in endometrial biopsies. Cytokine levels in uterine flushing samples were analyzed. HHV-6A DNA was found in 43% of endometrial biopsies from primary unexplained infertile women, but not in control women. On the contrary, HHV-6B DNA was absent in endometrial biopsies, but present in PBMCs of both cohorts. Endometrial NK cells presented a different distribution in infertile women with HHV6-A infection compared with infertile women without HHV6-A infection. Notably, we observed a lower percentage of endometrial specific CD56brightCD16- NK cells. We observed an enhanced HHV-6A-specific endometrial NK cell response in HHV-6A positive infertile women, with a marked increase in the number of endometrial NK cells activating towards HHV-6A infected cells. The analysis of uterine flushing samples showed an increase in IL-10 levels and a decrease of IFN-gamma concentrations in infertile women with HHV6-A infection. Our study indicates, for the first time, that HHV-6A infection might be an important factor in female unexplained infertility development, with a possible role in modifying endometrial NK cells immune profile and ability to sustain a successful pregnancy.

BackgroundInfertility represents a major challenge to the emotional balance and sexual life of couples, with long-lasting and gender-specific effects. The objective of this study is to explore personality features of infertile patients and detect possible sexual disorders in couples undergoing infertility treatment.Materials and methodsIn this prospective study 60 infertile couples and 52 fertile control couples were asked to complete standardized and validated questionnaires: the Adjective Check List (ACL) to enquire about personality features and the Female Sexual Function Index (FSFI) or the International Index of Erectile Function (IIEF) to assess sexual functioning of female and male partners. The study population was divided into 3 groups: Group A (N = 30, recently diagnosed infertile couples) Group B (N = 30, infertile couples already undergoing Intrauterine Insemination) and Group C (N = 52, fertile control group).ResultsInfertile patients did not display any distinguishing personality features. Regarding sexual function, men of all the three groups scored higher in both questionnaires (sexual satisfaction, desire and orgasm) than their female partners. Comparing results between groups, Group A male partners obtained lower scores in all the subscales. Women belonging to Group A and Group B showed an impairment of sexual arousal, satisfaction, lubrification and orgasm when compared to fertile controls.ConclusionsEven if at the very first stages of infertility treatment no personality disturbances can be detected, the couples’ sexual life is already impaired with different sexual disorders according to gender.

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Appropriate measures should be designed to identify sexual disorders in infertile couples, and the medical team should be trained to deal systematically with the couple's sexuality and propose strategies to overcome sexual disturbances. This approach could preserve the quality of the couple's sexual relationship and maximise pregnancy chances in ART.

Significant evidence supports that many endocrine disrupting chemicals could affect female reproductive health. Aim of this study was to compare the internal exposure to bisphenol A (BPA), perfluorooctane sulphonate (PFOS), perfluorooctanoic acid (PFOA), monoethylhexyl phthalate (MEHP), and di(2-ethylhexyl) phthalate (DEHP) in serum samples of 111 infertile women and 44 fertile women. Levels of gene expression of nuclear receptors (ERα, ERβ, AR, AhR, PXR, and PPARγ) were also analyzed as biomarkers of effective dose. The percentage of women with BPA concentrations above the limit of detection was significantly higher in infertile women than in controls. No statistically significant difference was found with regard to PFOS, PFOA, MEHP and DEHP. Infertile patients showed gene expression levels of ERα, ERβ, AR, and PXR significantly higher than controls. In infertile women, a positive association was found between BPA and MEHP levels and ERα, ERβ, AR, AhR, and PXR expression. PFOS concentration positively correlated with AR and PXR expression. PFOA levels negatively correlated with AhR expression. No correlation was found between DEHP levels and all evaluated nuclear receptors. This study underlines the need to provide special attention to substances that are still widely present in the environment and to integrate exposure measurements with relevant indicators of biological effects.

This paper provides a comprehensive overview of the literature dealing with HyCoSy to support its use as a first-line technique in standard infertility work-up.

Background: We have recently reported the presence of Human herpesvirus-6A (HHV-6A) DNA in the 43% of endometrial epithelial cells from primary idiopathic infertile women, with no positivity in fertile women. To investigate the possible effect of HHV-6A infection in endometrial (e)NK cells functions, we examined activating/inhibitory receptors expressed by eNK cells and the corresponding ligands on endometrial cells during HHV-6A infection.Methods: Endometrial biopsies and uterine flushing samples during the secretory phase were obtained from 20 idiopathic infertile women and twenty fertile women. HHV-6A infection of endometrial epithelial cells was analyzed by Real-Time PCR, immunofluorescence and flow cytometry. eNKs receptors and endometrial ligands expression were evaluated by immunofluorescence and flow cytometry.Results: We observed the presence of HHV-6A infection (DNA, protein) of endometrial epithelial cells in the 40% of idiopathic infertile women. The eNK from all the subgroups expressed high levels of NKG2D and NKG2A receptors. Functional studies showed that NKG2D activating receptor and FasL are involved in the acquired cytotoxic function of eNK cells during HHV-6A infection of endometrial epithelial cells. In the presence of HHV-6A infection, eNK cells increased expression of CCR2, CXCR3 and CX3CR1 chemokine receptors (p = 0.01) and endometrial epithelial cells up-modulated the corresponding ligands: MCP1 (Monocyte chemotactic protein 1, CCL2), IP-10 (Interferon gamma-induced protein 10, CXCL10) and Eotaxin-3 (CCL26).Conclusion: Our results, for the first time, showed the implication of eNK cells in controlling HHV-6A endometrial infection and clarify the mechanisms that might be implicated in female idiopathic infertility.

BackgroundTubal and uterine cavity diseases commonly compromise female fertility. At the present time, hysteroscopy, laparoscopy with chromopertubation and RX-Hysterosalpingography (RX-HSG) are widely accepted screening procedures enabling the effective assessment of both tubal patency and uterine cavity. Nevertheless, consistent evidence supports the reliability of Hysterosalpingocontrast sonography (HyCoSy) in uterine cavity and tubal patency investigation, as a part of the standard infertility work-up. This prospective study was aimed at evaluating the tolerability of the technique as well as the incidence of related side effects and complications in a large series of infertile patients.MethodsPain perception of 632 infertile women was measured by means of an 11-point numeric rating scale. Side effects and late complications were also recorded.ResultsThe mean numeric rating scale was 2.15 ± 2.0 SD. Most of the patients (374/632, 59.17%) rated HyCoSy as a non-painful procedure, whereas 24.36% (154/632) women reported mild pelvic pain and 9.96% (63/632) classified the discomfort as “moderate”. Only 6.48% (41/632) of the patient population experienced severe pelvic pain. Fifteen (2.37%) patients required drug administration for pain relief. Twenty-six patients (4.11%) showed mild vaso-vagal reactions that resolved without atropine administration. No severe vaso-vagal reactions or late complications were observed.ConclusionsHyCoSy is a well-tolerated examination and the associated vagal effects are unusual and generally mild. Consequently, we support its introduction as a first-line procedure for tubal patency and uterine cavity investigation in infertile women.