Raman Spectroscopy Detects Early Cervical Changes During Pregnancy

By Pooja Toshniwal PahariaReviewed by Lexie CornerJun 23 2025

A recent study published in npj Women’s Health used Raman spectroscopy to investigate biochemical changes in the human cervix during early pregnancy.

The findings show that the cervix becomes more vascular and less stiff as pregnancy progresses, due to a reduction in structural proteins and collagen cross-linking. These changes begin within six to eight weeks of conception.

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The study demonstrates that Raman spectroscopy can non-invasively detect these early changes, offering a new way to monitor cervical remodeling. This approach could help clinicians assess cervical health and identify complications early in pregnancy.

The research focused on women undergoing intrauterine insemination (IUI), which may support the development of more personalized fertility treatments, particularly for patients in non-traditional family structures.

Background

The cervix plays a key role in supporting pregnancy and undergoes significant remodeling in response to hormonal changes. It shifts from a firm to a soft, flexible structure over the course of pregnancy. However, early-stage cervical changes remain poorly understood.

Most current research relies on animal models, engineered tissues, or ex vivo human samples, which do not fully capture in vivo cervical changes during the earliest phases of pregnancy. While previous studies have used Raman spectroscopy to examine the cervix in later trimesters or postpartum, early pregnancy changes remain underexplored.

About the Study

This study examined cervical remodeling at the transition from the non-pregnant to pregnant state. Researchers enrolled 53 individuals aged 23 to 37 (mean BMI: 30.15 kg/m²) who were undergoing IUI treatment, with or without ovulation induction. Most participants used donor sperm.

Of the participants, one conceived naturally and nine conceived following ovulation induction—five with letrozole (LTZ) and four with clomiphene citrate (CC). Among these ten, pre-conception cervical measurements were taken within the menstrual cycle in which pregnancy was established, allowing direct comparison before and after conception.

Raman spectroscopy was used to analyze cervical biochemical changes in vivo during 10 IUI cycles that resulted in pregnancy. Fifteen individuals underwent multiple IUI cycles.

Findings

Spectral analysis of the cervix revealed significant biochemical changes during the early stages of pregnancy. The molecular fingerprint region (980–1700 cm⁻¹) showed increases in blood-related spectral peaks (1560–1620 cm⁻¹) after conception, suggesting enhanced vascularity. Meanwhile, spectral peaks related to actin (1430–1460 cm⁻¹) and collagen (1630–1670 cm⁻¹) decreased, indicating reduced structural protein content and collagen cross-linking.

The ratio of mature collagen to phenylalanine at 1003 cm⁻¹ supported these findings. Although not statistically significant, glycogen levels were slightly higher in early pregnancy compared to the pre-conception period, potentially reflecting increased energy demands for tissue remodeling.

Hormonal treatments also appeared to affect spectral readings. CC users showed lower collagen and actin peaks in the pre-conception phase, while blood-related peaks remained stable. LTZ users had higher intensities for water and protein than CC users, though the small sample size limited statistical conclusions.

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Conclusions

The study supports the use of Raman spectroscopy as a non-invasive tool to monitor early biochemical changes in the uterine cervix. Within six to eight weeks of pregnancy, the cervix shows increased vascularity and reduced structural proteins and collagen cross-linking, all of which are part of the preparation for labor.

These findings may help establish baselines for distinguishing normal from abnormal cervical remodeling. This could inform early diagnosis of complications such as ectopic pregnancy, miscarriage, or preterm birth. Larger studies involving different hormonal treatments could further improve fertility treatment strategies and patient outcomes.

Journal Reference

Spurlin, EE., et al. (2025). In vivo Raman spectroscopy reveals biochemical changes in the human cervix with pregnancy establishment. npj Women's Health, 3, 32, DOI: 10.1038/s44294-025-00083-x, https://www.nature.com/articles/s44294-025-00083-x