Herpesvirus variant possibly responsible for primary unexplained infertility
A specific strain of the human herpesvirus (HHV) may contribute to primary unexplained infertility in women, suggests a prospective randomized study from Italy.
“We found that the little-known member of the [HHV] family called HHV-6A infects the lining of the uterus in 43 percent of women with unexplained infertility but cannot be found in that of fertile women,” said study author Dr. Roberta Rizzo of the Department of Medical Sciences, Section of Microbiology, University of Ferrara, Ferrara, Italy.
HHV-6A DNA was not present in the peripheral blood mononuclear cells (PBMCs) of any of the subjects while HHV-6B DNA was found in the PBMCs of 25 and 28 percent of infertile and control group women, respectively. HHV-6B DNA was not present in endometrial biopsies of either group. [PLoS One 2016;doi:10.1371/journal.pone.0158304]
Estradiol levels were higher in infertile women with HHV-6A infection compared with those without infection (p=0.045).
“Our results indicate that the uterus of infertile women may constitute a site of active HHV-6A infection or replication,” said the authors. “Considering that these women have no HHV-6A in their PBMC, unidentified microenvironmental factors are probably required to allow HHV-6A infection of the uterine epithelial cells. Possibly, the estradiol high levels found in infertile women could act as a cofactor allowing HHV-6 infection of the endometrium,” they said.
Participants were women with primary unexplained infertility (n=30) who were compared with a control group of women who had at least one successful pregnancy (n=36). The women were age 21-38 years with regular menstrual cycles (24-35 days) and body mass index (BMI) of 18-26 kg/m2. Women with endometritis, endometriosis, tubal factor, ovulatory dysfunction, anatomical uterine pathologies, and recurrent miscarriage were excluded from the study.
According to Rizzo, it is suspected that a change in the endometrial environment is the potential mechanism behind the HHV-6A-infertility link.
“We hypothesize that the presence of HHV-6A infection in endometrial cells could modify endometrial environment, modifying immune cell behaviour and soluble molecule secretion that could interfere with endometrial receptivity and embryo implantation,” said Rizzo.
“This work opens up a new frontier in the struggle against fertility problems. Women with fertility problems could take advantage of antiviral therapy to recreate a receptive endometrial environment,” she said.
“The next step will be to determine further whether the infertile condition is due to the virus, or to changes in the endometrial immune system caused by the virus,” said Rizzo, who hopes to confirm the study findings using a larger population.