A standardized approach for evaluating the penetration of human spermatozoa into cervical mucus in vitro

Pandya, Ila J.; Mortimer, David; Sawers, R. S.

doi:10.1016/s0015-0282(16)49217-4

Cited by 35 publications

(2 citation statements)

References 17 publications

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“…To detect ovulation and time cervical mucus assessments, participants returned approximately twice weekly after IVR initiation, to have serum estradiol (E2) and P4 measured. We performed a cervical mucus check for Insler score [ 28 ] and sperm penetration assay (modified slide test) [ 29 – 33 ] at the next regularly scheduled visit, usually within 48 hours, if the serum E2 was between 75–150 pg/mL. If the serum E2 was over 150 pg/mL, indicating imminent follicular development, we brought the participant in for a cervical mucus check within 24 hours.…”

Section: Methodsmentioning

confidence: 99%

Randomized, placebo controlled phase I trial of the safety, pharmacokinetics, pharmacodynamics and acceptability of a 90 day tenofovir plus levonorgestrel vaginal ring used continuously or cyclically in women: The CONRAD 138 study

Thurman

Brache²,

Cochón³

et al. 2022

PLoS ONE

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Multipurpose prevention technologies (MPTs), which prevent sexually transmitted infection(s) and unintended pregnancy, are highly desirable to women. In this randomized, placebo-controlled, phase I study, women used a placebo or tenofovir (TFV) and levonorgestrel (LNG) intravaginal ring (IVR), either continuously or cyclically (three, 28-day cycles with a 3 day interruption in between each cycle), for 90 days. Sixty-eight women were screened; 47 were randomized to 4 arms: TFV/LNG or placebo IVRs used continuously or cyclically (4:4:1:1). Safety was assessed by adverse events and changes from baseline in mucosal histology and immune mediators. TFV concentrations were evaluated in multiple compartments. LNG concentration was determined in serum. Modeled TFV pharmacodynamic antiviral activity was evaluated in vaginal and rectal fluids and cervicovaginal tissue ex vivo. LNG pharmacodynamics was assessed with cervical mucus quality and anovulation. All IVRs were safe with no serious adverse events nor significant changes in genital tract histology, immune cell density or secreted soluble proteins from baseline. Median vaginal fluid TFV concentrations were >500 ng/mg throughout 90d. TFV-diphosphate tissue concentrations exceeded 1,000 fmol/mg within 72hrs of IVR insertion. Mean serum LNG concentrations exceeded 200 pg/mL within 2h of TFV/LNG use, decreasing quickly after IVR removal. Vaginal fluid of women using TFV-containing IVRs had significantly greater inhibitory activity (87–98% versus 10% at baseline; p<0.01) against HIV replication in vitro. There was a >10-fold reduction in HIV p24 antigen production from ectocervical tissues after TFV/LNG exposure. TFV/LNG IVR users had significantly higher rates of anovulation, lower Insler scores and poorer/abnormal cervical mucus sperm penetration. Most TFV/LNG IVR users reported no change in menstrual cycles or fewer days of and/or lighter bleeding. All IVRs were safe. Active rings delivered high TFV concentrations locally. LNG caused changes in cervical mucus, sperm penetration, and ovulation compatible with contraceptive efficacy. Trial registration: ClinicalTrials.gov #NCT03279120.

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Section: Methodsmentioning

confidence: 99%

Randomized, placebo controlled phase I trial of the safety, pharmacokinetics, pharmacodynamics and acceptability of a 90 day tenofovir plus levonorgestrel vaginal ring used continuously or cyclically in women: The CONRAD 138 study

Thurman

Brache²,

Cochón³

et al. 2022

PLoS ONE

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“…The post‐coital test assesses the presence of erratic and progressively motile sperm in the cervical mucus collected 4–24 h post‐coitus. BCMPT and post‐coital test have a significant positive correlation with sperm concentration, progressive motility, and velocity 118 and are potential predictors of fertility, as cervical mucus selectively allows the penetration of motile and morphologically normal sperm. Importantly, the apparently normal, but infertile semen was found to have poor cervical mucus penetration ability 119 .…”

Section: Visco‐elasticity ‐ a Preliminary Gatekeeper Of Fertilitymentioning

confidence: 99%

Microenvironment of the male and female reproductive tracts regulate sperm fertility: Impact of viscosity, pH, and osmolality

et al. 2021

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Background: Terminally differentiated mammalian sperm are exposed to gradients of viscosity, pH, and osmolality both in the male and female reproductive tract during their perilous journey to quest the ovum. The complex physicochemical factors play an integral role in preparing sperm for the fertilization process.Objectives: To elucidate the influence of the reproductive tract microenvironment especially viscosity, pH, and osmolality in regulating sperm functional and fertilization competence. Materials and Methods:The data used in this review were collected from the research papers and online databases focusing on the influence of viscosity, pH, and osmolality on sperm function. Discussion:The gradients of viscosity, pH, and osmolality exist across various segments of the male and female reproductive tract. The changes in the viscosity create a physical barrier, pH aid in capacitation and hyperactivation, and the osmotic stress selects a progressive sperm subpopulation for accomplishing fertilization. The sperm function tests are developed based on the concept that the male genotype is the major contributor to the reproductive outcome. However, recent studies demonstrate the significance of sperm genotype-environment interactions that are essentially contributing to reproductive success. Hence, it is imperative to assess the impact of physicochemical stresses and the adaptive ability of the terminally differentiated sperm, which in turn would improve the outcome of the assisted reproductive technologies and male fertility assessment. Conclusion:Elucidating the influence of the reproductive tract microenvironment on sperm function provides newer insights into the procedures that need to be adopted for selecting fertile males for breeding, and ejaculates for the assisted reproductive technologies.

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Semen Analysis and Other Standard Laboratory Tests

Mortimer

1994

Male Infertility

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A standardized approach for evaluating the penetration of human spermatozoa into cervical mucus in vitro

Cited by 35 publications

References 17 publications

Randomized, placebo controlled phase I trial of the safety, pharmacokinetics, pharmacodynamics and acceptability of a 90 day tenofovir plus levonorgestrel vaginal ring used continuously or cyclically in women: The CONRAD 138 study

Randomized, placebo controlled phase I trial of the safety, pharmacokinetics, pharmacodynamics and acceptability of a 90 day tenofovir plus levonorgestrel vaginal ring used continuously or cyclically in women: The CONRAD 138 study

Microenvironment of the male and female reproductive tracts regulate sperm fertility: Impact of viscosity, pH, and osmolality

Semen Analysis and Other Standard Laboratory Tests

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