Prevalence of <scp>HHV</scp>‐6 in endometrium from women with recurrent implantation failure

Coulam, Carolyn B.; Bilal, Mahmood Y.; Garcia, M.D. Salazar; Katukurundage, Dimantha; Elazzamy, Haidy; Fernández, E.; Kwak‐Kim, Joanne; Beaman, Kenneth D.; Dambaeva, Svetlana

doi:10.1111/aji.12862

Cited by 20 publications

(10 citation statements)

References 23 publications

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“…Varied explanations for this local change may be considered; it could be that the uNKs may not be limited in their toxicity as is the normal scenario [36] or the expansion of the uNK population is in response to an as yet unknown stimulus. Recent work indicates that human herpes virus 6a (HHV6a) may accentuate uNK cell percentages and has been demonstrated to have a strong association with implantation failure in particular [37,38]. While recognised as being more immature and less cytotoxic, the CD56 bright uNKs are important immune regulators and have use of varied cytokines, including IFNg and TNFa.…”

Section: Discussionmentioning

confidence: 99%

Detailed endometrial immune assessment of both normal and adverse reproductive outcome populations

Marron¹,

Walsh²,

Harrity

2018

J Assist Reprod Genet

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Flow cytometric endometrial evaluation has the ability to provide a rapid and objective analysis of lymphocyte subpopulations. The findings show significant variations in cellular proportions of immune cells across the patient categories relative to control tissue. The cell types involved suggest that a potential differential pro-inflammatory bias may exist in patients with a history of adverse reproductive outcomes. Immunological assessment in appropriate populations may provide insight into the underlying aetiology of some cases of reproductive failure.

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Section: Discussionmentioning

confidence: 99%

Detailed endometrial immune assessment of both normal and adverse reproductive outcome populations

Marron¹,

Walsh²,

Harrity

2018

J Assist Reprod Genet

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“…Intriguingly, HHV-6 is also able to integrate into germ cells and can be transmitted vertically, resulting in ~1% of the world population harboring the virus in every nucleated cell [ 4 , 7 , 8 , 9 , 10 , 11 ]. Reactivation of HHV-6 from both the inherited and exogenously acquired forms has been associated with various severe diseases such as heart disease, graft versus host disease (GVHD), neuronal disorders and unexplained infertility [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Viral Proteins U41 and U70 of Human Herpesvirus 6A Are Dispensable for Telomere Integration

Wight

Wallaschek

Sanyal

et al. 2018

Viruses

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Human herpesvirus-6A and -6B (HHV-6A and -6B) are two closely related betaherpesviruses that infect humans. Upon primary infection they establish a life-long infection termed latency, where the virus genome is integrated into the telomeres of latently infected cells. Intriguingly, HHV-6A/B can integrate into germ cells, leading to individuals with inherited chromosomally-integrated HHV-6 (iciHHV-6), who have the HHV-6 genome in every cell. It is known that telomeric repeats flanking the virus genome are essential for integration; however, the protein factors mediating integration remain enigmatic. We have previously shown that the putative viral integrase U94 is not essential for telomere integration; thus, we set out to assess the contribution of potential viral recombination proteins U41 and U70 towards integration. We could show that U70 enhances dsDNA break repair via a homology-directed mechanism using a reporter cell line. We then engineered cells to produce shRNAs targeting both U41 and U70 to inhibit their expression during infection. Using these cells in our HHV-6A in vitro integration assay, we could show that U41/U70 were dispensable for telomere integration. Furthermore, additional inhibition of the cellular recombinase Rad51 suggested that it was also not essential, indicating that other cellular and/or viral factors must mediate telomere integration.

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“…We first reported HHV-6A DNA presence in 43% of endometrial cells from women with idiopathic infertility, whereas no fertile control women harbored the virus 1 . Growing evidence confirms this implication [1][2][3][4][5][6] . We investigated the effect of HHV-6A infection on the immunological status of the endometrium.…”

Section: Objectivementioning

confidence: 95%

Endometrium infection by human herpesvirus-6A: implication in female idiopathic infertility

Rizzo

Luca

2018

Fertility and Sterility

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OBJECTIVE: A possible association between allergy and infertility has not been investigated. Our aim was to determine whether female allergy correlates with infertility treatment outcomes. DESIGN: Retrospective cohort study in an academic medical center. MATERIALS AND METHODS: Patient data from July 2010 through January 2017 was compiled from medical records. Mixed effects models were used to evaluate the relationship between presence of female allergy and type (fresh or FET) and cycle outcomes, controlling for type of procedure, number of embryos transferred, female patient age, BMI, smoking status, gravidity, parity, and Caucasian race. RESULTS: After exclusions for missing data, the cohort contained 493 patients with a total of 935 cycles. Of these, 90.7% identified as Caucasian with a mean age of 34.8 (SD¼4.6) at the time of each cycle initiation. Over half of the female patients had allergy (54.0%). Nonexclusively, among all female patients, allergy to antibiotics was most common (29.2%), followed by allergy to non-antibiotic prescription medications (22.3%). Allergies to pollen and dust (5.7%), foods (6.5%), latex (4.4%) and other substances (9.7%) including cat and dog allergens were less common. Among cycles with fresh embryo transfer (581 cycles from 408 patients), having an allergy to pollen and/or dust was significantly associated with having a negative beta-hCG test (p¼0.02). Pollen/dust allergy was not associated with SAB, biochemical pregnancy, or ectopic pregnancy alone; however, it was associated with whether an infant was born at the end of the cycle (p¼0.04), with only 15.4% of those with a pollen/dust allergy having a cycle which resulted in a live-born infant compared with 34.7% of those without such allergy. Overall, the presence of any allergy was not associated with negative beta-hCG or pregnancy outcomes, nor was other sub-classes of allergies. CONCLUSIONS: The high rates of allergy among patients seeking infertility treatment, as compared to the general population, are surprising. Female allergy to pollen and/or dust is associated with a greater chance of failed fertility treatment and a lower chance of a successful pregnancy resulting in a live-born infant. The reproductive performance of allergic patients needs further investigation using a larger dataset.

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Prevalence of HHV‐6 in endometrium from women with recurrent implantation failure

Abstract: HHV-6 infection is an important factor in RIF.

Cited by 20 publications

References 23 publications

Detailed endometrial immune assessment of both normal and adverse reproductive outcome populations

Detailed endometrial immune assessment of both normal and adverse reproductive outcome populations

Viral Proteins U41 and U70 of Human Herpesvirus 6A Are Dispensable for Telomere Integration

Endometrium infection by human herpesvirus-6A: implication in female idiopathic infertility

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