Study Background: The relationship between systemic inflammation and female fertility is becoming a research area of great interest, given the rising prevalence of infertility and the need to further investigate its underlying causes. Available studies and the increasing use of assisted reproductive technology (ART) have contributed to hypothesizing a potential association between chronic inflammation and fertility. Study Aim: The study aims to evaluate the possible association between chronic endometritis (CE) and a systemic inflammatory profile and alterations in the renin–angiotensin–aldosterone system (RAAS), through the assessment of circulating levels of IL-6, renin, aldosterone, the aldosterone-to-renin ratio (ARR), as well as sodium and potassium levels. The rationale is based on the pro-inflammatory activity of aldosterone and the expression of mineralocorticoid receptors (MR) in the endometrium. It is therefore hypothesized that aldosterone-mediated activation of MR may contribute to the inflammatory mechanisms associated with chronic endometritis. Materials and Methods: This is a single-center observational study conducted at the Infertility and Assisted Reproduction Unit (UOSD PMA) of the Padua University Hospital, involving 40 female patients evaluated for infertility. For each patient, an endometrial biopsy and two blood samples (during and 48 hours before biopsy) were obtained. Systemic inflammation was assessed by measuring the following parameters: renin (mIU/L), aldosterone (pmol/L), aldosterone-to-renin ratio (ARR), IL-6 (ng/L), as well as sodium (mmol/L) and potassium (mmol/L) ion concentrations. BMI was also recorded, given that obesity is associated with systemic inflammation. To evaluate ovarian function and fertility status, anti-Müllerian hormone (AMH, ng/mL), progesterone (PG, nmol/L), and thyroid-stimulating hormone (TSH, mIU/L) were measured. Statistical analysis was performed using Microsoft Excel software. Results: Dividing the sample between patients who tested positive for chronic endometritis (> 5 plasma cells) and those who tested negative (< 5 plasma cells), no statistically significant differences were observed regarding systemic inflammatory markers. Therefore, it was evaluated whether changes occurred with an increasing count of positive plasma cells by stratifying the sample based on a cutoff of below or above 20 positive plasma cells; in this case as well, no statistically significant differences emerged. Finally, potential differences were analyzed between patients who achieved resolution of chronic endometritis following therapy and those with persistently positive biopsy findings: again, this analysis revealed no statistically significant differences among the evaluated biochemical parameters. Conclusions: In this study, no statistically significant differences were observed in the analyzed parameters between patients with or without chronic endometritis, nor in relation to an increasing plasma cell count or following the resolution of the condition. However, since the systemic RAAS serves as an indicator of systemic inflammation, these results suggest that chronic endometritis is predominantly a local inflammatory phenomenon. Indeed, a local renin-angiotensin system is present at the endometrial and uterine levels, which in turn regulates local aldosterone levels; this system warrants further investigation to elucidate the actual correlation between chronic endometritis, local inflammation, and female infertility.
Presupposti dello studio: La relazione tra infiammazione sistemica e fertilità femminile sta diventando un'area di ricerca di grande interesse, data la crescente prevalenza dell’infertilità e la necessità di approfondirne le cause. Gli studi condotti e il crescente ricorso alle tecniche di riproduzione assistita (ART) hanno contribuito a ipotizzare una potenziale associazione tra infiammazione cronica e fertilità. Scopo dello studio: Lo studio si propone di valutare la possibile associazione tra l’endometrite cronica (CE) e un quadro di infiammazione sistemica e di alterazioni del sistema renina-angiotensina-aldosterone (RAAS), attraverso la valutazione dei livelli circolanti di IL-6, renina, aldosterone, del rapporto aldosterone/renina (ARR), nonché dei livelli di sodio e potassio. Il razionale si basa sull’attività pro-infiammatoria dell’aldosterone e sull’espressione dei recettori dei mineralcorticoidi (MR) a livello endometriale. Si ipotizza pertanto che l’attivazione del MR da parte dell’aldosterone possa contribuire ai meccanismi infiammatori associati all’endometrite cronica. Materiali e Metodi: Si tratta di uno studio osservazionale monocentrico condotto presso l’UOSD PMA dell’Azienda Ospedale-Università di Padova, nel quale sono stati raccolti i dati relativi a 40 pazienti seguite dal centro per problemi di fertilità. Per ciascuna paziente sono state effettuate una biopsia endometriale e due prelievi ematochimici (uno contestualmente alla biopsia e uno 48 ore prima). L’infiammazione sistemica è stata analizzata valutando i seguenti parametri: renina (mIU/L), aldosterone (pmol/L), ARR, IL-6 (ng/L), e gli ioni sodio (mmol/L) e potassio (mmol/L). È stato inoltre rilevato il BMI, poiché a uno stato di obesità corrisponde una condizione di infiammazione sistemica. Per valutare la funzionalità ovarica sono stati dosati anche l'AMH (ng/mL), il progesterone (PG, nmol/L) e il TSH (mIU/L). L’analisi statistica è stata condotta mediante l'utilizzo del software Excel. Risultati: Suddividendo il campione tra le pazienti risultate positive per la CE (> 5 plasmacellule) e quelle risultate negative, non sono emerse differenze statisticamente significative per quanto riguarda gli indicatori di infiammazione sistemica. Si è valutato, pertanto, se si verificassero variazioni all’aumentare del numero di plasmacellule positive, stratificando il campione in base al riscontro di un valore inferiore o superiore a 20 PC; anche in questo caso, non sono emerse differenze statisticamente significative. Infine, si è analizzata l'eventuale presenza di differenze tra le pazienti che hanno presentato la risoluzione dell'endometrite cronica dopo la terapia e quelle con biopsia persistentemente positiva: anche in questa analisi non sono emerse differenze statisticamente significative tra i parametri biochimici valutati. Conclusioni: In questo studio non sono emerse differenze statisticamente significative nei parametri analizzati tra le pazienti con o senza CE né in relazione all’aumentare del numero di plasmacellule o all'avvenuta risoluzione del quadro clinico. Tuttavia, poiché il RAAS rappresenta un indicatore di infiammazione sistemica, i risultati suggeriscono che la CE sia un fenomeno infiammatorio prevalentemente locale. A livello endometriale e uterino è infatti descritto un sistema renina-angiotensina locale, deputato a sua volta alla regolazione dell’aldosterone; tale sistema merita ulteriori approfondimenti futuri per chiarire l’effettiva correlazione tra endometrite cronica, infiammazione locale e infertilità.
Endometrite cronica e infiammazione sistemica: analisi del coinvolgimento del sistema RAAS
LONGO, ALISSA
2025/2026
Abstract
Study Background: The relationship between systemic inflammation and female fertility is becoming a research area of great interest, given the rising prevalence of infertility and the need to further investigate its underlying causes. Available studies and the increasing use of assisted reproductive technology (ART) have contributed to hypothesizing a potential association between chronic inflammation and fertility. Study Aim: The study aims to evaluate the possible association between chronic endometritis (CE) and a systemic inflammatory profile and alterations in the renin–angiotensin–aldosterone system (RAAS), through the assessment of circulating levels of IL-6, renin, aldosterone, the aldosterone-to-renin ratio (ARR), as well as sodium and potassium levels. The rationale is based on the pro-inflammatory activity of aldosterone and the expression of mineralocorticoid receptors (MR) in the endometrium. It is therefore hypothesized that aldosterone-mediated activation of MR may contribute to the inflammatory mechanisms associated with chronic endometritis. Materials and Methods: This is a single-center observational study conducted at the Infertility and Assisted Reproduction Unit (UOSD PMA) of the Padua University Hospital, involving 40 female patients evaluated for infertility. For each patient, an endometrial biopsy and two blood samples (during and 48 hours before biopsy) were obtained. Systemic inflammation was assessed by measuring the following parameters: renin (mIU/L), aldosterone (pmol/L), aldosterone-to-renin ratio (ARR), IL-6 (ng/L), as well as sodium (mmol/L) and potassium (mmol/L) ion concentrations. BMI was also recorded, given that obesity is associated with systemic inflammation. To evaluate ovarian function and fertility status, anti-Müllerian hormone (AMH, ng/mL), progesterone (PG, nmol/L), and thyroid-stimulating hormone (TSH, mIU/L) were measured. Statistical analysis was performed using Microsoft Excel software. Results: Dividing the sample between patients who tested positive for chronic endometritis (> 5 plasma cells) and those who tested negative (< 5 plasma cells), no statistically significant differences were observed regarding systemic inflammatory markers. Therefore, it was evaluated whether changes occurred with an increasing count of positive plasma cells by stratifying the sample based on a cutoff of below or above 20 positive plasma cells; in this case as well, no statistically significant differences emerged. Finally, potential differences were analyzed between patients who achieved resolution of chronic endometritis following therapy and those with persistently positive biopsy findings: again, this analysis revealed no statistically significant differences among the evaluated biochemical parameters. Conclusions: In this study, no statistically significant differences were observed in the analyzed parameters between patients with or without chronic endometritis, nor in relation to an increasing plasma cell count or following the resolution of the condition. However, since the systemic RAAS serves as an indicator of systemic inflammation, these results suggest that chronic endometritis is predominantly a local inflammatory phenomenon. Indeed, a local renin-angiotensin system is present at the endometrial and uterine levels, which in turn regulates local aldosterone levels; this system warrants further investigation to elucidate the actual correlation between chronic endometritis, local inflammation, and female infertility.| File | Dimensione | Formato | |
|---|---|---|---|
|
Longo_Alissa.pdf
Accesso riservato
Dimensione
765.54 kB
Formato
Adobe PDF
|
765.54 kB | Adobe PDF |
The text of this website © Università degli studi di Padova. Full Text are published under a non-exclusive license. Metadata are under a CC0 License
https://hdl.handle.net/20.500.12608/116081