Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window.

During the implantation window, the endometrium becomes poised to transition to a pregnant state, a process driven by differentiation of stromal cells into decidual cells (DC). Perturbations in this process, termed decidualization, leads to breakdown of the feto-maternal interface and miscarriage, but the underlying mechanisms are poorly understood. Here, we reconstructed the decidual pathway at single-cell level in vitro and demonstrate that stromal cells first mount an acute stress response before emerging as DC or senescent DC (snDC). In the absence of immune cell-mediated clearance of snDC, secondary senescence transforms DC into progesterone-resistant cells that abundantly express extracellular matrix remodelling factors. Additional single-cell analysis of midluteal endometrium identified DIO2 and SCARA5 as marker genes of a diverging decidual response in vivo. Finally, we report a conspicuous link between a pro-senescent decidual response in peri-implantation endometrium and recurrent pregnancy loss, suggesting that pre-pregnancy screening and intervention may reduce the burden of miscarriage.

Effect of diaphragm and lubricant gel provision on human papillomavirus infection among women provided with condoms: a randomized controlled trial.

OBJECTIVE: To estimate the effect of providing women with a latex diaphragm, lubricant gel, and male condoms (intervention) compared with condoms alone (control) on human papillomavirus (HPV) incidence and clearance. METHODS: Participants were 2,040 human immunodeficiency virus (HIV)-negative Zimbabwean women enrolled in a randomized trial estimating the effect of the intervention on HIV acquisition. Clinicians collected cervical samples for HPV testing at baseline, 12 months, and exit. L1 consensus polymerase chain reaction primers were used to determine HPV presence and type. RESULTS: We found no differences in the following outcomes: HPV prevalence at the time of the first postenrollment HPV test (intention-to-treat analysis, relative risk [RR] 1.02, 95% confidence interval [CI] 0.90-1.16); HPV incidence at 12 months among women HPV-negative at baseline (RR 0.95, 95% CI 0.80-1.14); and HPV clearance at 12 months among women HPV-positive at baseline (RR 0.80, 95% CI 0.61-1.05). Clearance of HPV type 58 was lower in the intervention group at 12 months (RR 0.67, 95% CI 0.48-0.92), but not at exit (RR 0.93, 95% CI 0.75-1.16); clearance of HPV type 18 was lower in the intervention group at exit (RR 0.55, 95% CI 0.33-0.89), but not at 12 months (RR 0.55, 95% CI 0.29-1.05). Women reporting diaphragm/gel use at 100% of prior sex acts had a lower likelihood of having one or more new HPV types detected at 12 months (RR 0.75, 95% CI 0.58-0.96) and exit (RR 0.77, 95% CI 0.59-0.99). CONCLUSION: Among women receiving risk reduction counseling and condoms in an HIV prevention program, diaphragm plus lubricant gel provision did not affect HPV incidence or clearance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00121459 LEVEL OF EVIDENCE: I.

Effect of Replens gel used with a diaphragm on tests for human papillomavirus and other lower genital tract infections.

OBJECTIVE: Little is known about effects of vaginal lubricants with barrier contraceptives on detection of sexually transmissible infections. We hypothesized that Replens gel used with a diaphragm would neither inhibit human papillomavirus (HPV) detection in cervical samples and chlamydia (CT) and gonorrhea (GC) detection in urine samples, nor affect cervical cytology quality. MATERIALS AND METHODS: After a clinician-collected cervical sample and a self-collected vaginal sample for HPV detection ("pregel" specimens), women placed a diaphragm containing Replens gel into the vagina. Participants (n = 77) removed the diaphragm after 6 hours and performed vaginal HPV self-sampling at several time points thereafter. Clinicians performed cervical cytology sampling and HPV testing ("postgel" specimens) 24 hours after diaphragm removal. Pregel and postgel specimens were analyzed with and without added SiHa cells (source of defined numbers of HPV16 genomes). HPV was detected by polymerase chain reaction using MY09/11 primers. Urine samples were obtained for CT and GC testing. Proportions of samples testing positive were compared using relative risk (RR) regression models. RESULTS: Proportions with detectable HPV in the clinician-collected cervical pregel and postgel samples were not statistically different for samples with added SiHa cells (88.3% vs 93.2%, RR = 1.06, 95% confidence interval = 0.96-1.14) or for native HPV infection (32.9% vs 28.2%, RR = 0.87, 95% confidence interval = 0.71-1.06). In self-collected vaginal postgel samples, there was no trend for decreased HPV detection after gel exposure. Gel affected neither urine tests for CT and GC nor cytological quality. CONCLUSIONS: Recent Replens gel use with a diaphragm does not inhibit cervical HPV testing, urine testing for CT and GC, or cervical cytology quality.

Increased risk of high-grade anal neoplasia associated with a human papillomavirus type 16 E6 sequence variant.

Expression of the E6 and E7 genes of human papillomavirus (HPV) type 16 have been implicated in the etiology of anogenital premalignant and malignant lesions. To evaluate whether variations in the HPV-16 E6 sequence were related to the incidence of high-grade anal neoplasia, 628 HPV-16-positive anal specimens from 193 human immunodeficiency virus (HIV)-positive and 59 HIV-negative participants were typed for variations in 15 E6 nucleotide positions. Although most participants were infected with a prototype strain, 15 (6%) carried the G131 variant, and 12 (5%) were infected with the Af1a variant. Two new variants not previously reported were identified as well. An elevated risk for high-grade anal squamous intraepithelial lesions was associated with infection by G131 variants, compared with the prototype strain (odds ratio, 3.4; 95% confidence interval, 1.1-10), after controlling for HIV status. These data provide further evidence for HPV strain variation as a factor in determining the natural history of anogenital neoplasia.