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Womens Health

Women's Health - Poster Session E

Poster BB20 - Raman Spectroscopy as a Non-Invasive Method for Detecting Biomedical Changes in the Cervix Between Non-Pregnant and Early Pregnancy States

Saturday, October 26, 2024
10:00 AM - 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Early pregnancy failure is a common complication in the first trimester; however, limited understanding of abnormal pregnancies hampers diagnosis and effective treatments. Early identification of conditions like ectopic pregnancy is crucial for timely intervention. Current biomarkers, such as beta human chorionic gonadotropin and serum progesterone levels, have limitations in accurately distinguishing between normal and abnormal pregnancies. The uterine cervix, composed primarily of a dense extracellular matrix (notably collagen I), is an under-researched organ that could provide insights into infertility and early pregnancy failure. The cervix undergoes substantial structural and biochemical changes that are driven by hormonal fluctuations during pregnancy, such as collagen reorganization and a reduction in collagen cross-linking. Raman spectroscopy (RS) is a non-invasive, light-based technique that provides molecular fingerprints unique to different tissues, offering quantitative information about tissue composition. RS has been effective in monitoring cervical biochemical changes in later pregnancy stages, and holds promise for detecting early cervical changes. RS utilizes light to provide unique tissue spectra and quantitative data on tissue composition. Previous studies using RS have successfully differentiated normal cervical tissue from abnormal conditions like precancers and cancers. Longitudinal analyses using RS have demonstrated decreases in collagen and increases in blood-associated peaks as pregnancy progresses. Using RS, we aimed to characterize normal cervical changes that occur between non-pregnant and early pregnant states. The information collected will set the stage for future studies that work to identify differences that occur with abnormally developing pregnancies.

Materials and

Methods:  In this study, we recruited patients undergoing intrauterine insemination (IUI), a fertility treatment in which sperm is injected into the uterus with the goal of the patient becoming pregnant. All patients had RS measurements taken at the time of IUI (non-pregnant) and during the patients’ first obstetric ultrasound in successful IUI trials (4-8 weeks pregnant). Measurements were collected using a portable RS system comprising a handheld fiber optic Raman probe, imaging spectrograph, dual wavelength diode laser, CCD camera, and laptop. The cervix was visualized with a speculum by a trained provider and RS measurements were collected at 680 nm (high-wavenumber RS region) and 785 nm (fingerprint RS region) on the ectocervix. For analysis presented herein, only the spectra of patients with successful IUIs was included. The mean and standard deviation of Raman shift frequencies for non-pregnant versus early pregnancy measurements were plotted for the fingerprint and high wavenumber regions. Raman spectral peak intensities and ratios were calculated to normalize data and enable comparison across varied signal-to-noise datasets. Paired t-tests at a significance level of 0.05 were used to identify significant spectral differences between pre-pregnancy and early pregnancy. Non-negative least squares analysis (NNLS) that used actin, blood, cholesterol, collagen I, glycogen, and water as base spectra facilitated accurate quantification of these components' abundances. Paired t-tests were performed to identify significant changes that occurred in NNLS components between pre-pregnancy and early pregnancy.

Results, Conclusions, and Discussions: Ten of the enrolled subjects that underwent IUI became pregnant and their data were used for subsequent Raman spectral analysis. Mean and standard deviation plots of fingerprint spectra from non-pregnant and early pregnancy showed notable increases in blood-specific peaks (1560-1620 cm⁻¹) during early pregnancy, indicating heightened vascularization of the cervical tissue. Conversely, peaks associated with extracellular matrix (ECM) proteins (1430-1460 cm⁻¹ and 1630-1670 cm⁻¹) showed decreased intensity in early pregnancy, suggesting decreases in cervix ECM proteins. Spectral plots from the high wavenumber region showed an overall decrease in intensity between non-pregnant and pregnant states.

In the fingerprint region, quantitative analysis of a peak ratio that includes a collagen cross-linking peak and a general protein peak revealed a statistically significant reduction in the collagen cross-linking ratio (p=0.01), indicating a shift towards decreased tissue stiffness in early pregnancy. NNLS analysis followed by paired t-tests revealed elevated levels of blood (p=0.04) and glycogen (p=0.03) during early pregnancy compared to pre-pregnancy levels.

In the high wavenumber region, which is uniquely sensitive to water, no statistically significant differences were observed in any peaks (~2800-3700 cm⁻¹) or peak ratios. This indicates that changes in this region were highly variable across patients.

These findings offer valuable insights into the dynamic biochemical processes occurring within the cervix during early pregnancy. The observed increase in vascularization and glycogen accumulation, alongside altered collagen structure, signifies early stages of cervical remodeling essential for supporting pregnancy. This underscores RS as a powerful non-invasive tool for monitoring these physiological changes. Moving forward, further research could refine Raman spectral analysis to enhance its diagnostic potential in obstetrics, particularly for early detection of conditions such as early pregnancy loss, ectopic pregnancy, and preterm birth. This study contributes significantly to advancing our understanding of cervical dynamics throughout pregnancy, complementing traditional diagnostic methods like ultrasound and physical examinations.

Acknowledgements (Optional):