# Effect of alpha‐lipoic acid and myoinositol on endometrial inflammation in women with unexplained recurrent pregnancy loss

**Authors:** Chiara Tersigni, Maria Elisabeth Street, Roberta Castellani, Fiorella Di Nicuolo, Marianna Onori, Cecilia Catellani, Greta Barbaro, Carlo Ticconi, Nicoletta Di Simone

PMC · DOI: 10.1007/s00404-026-08365-8 · Archives of Gynecology and Obstetrics · 2026-02-25

## TL;DR

This study shows that a combination of alpha-lipoic acid and myo-inositol can reduce inflammation in women with unexplained recurrent pregnancy loss.

## Contribution

The study demonstrates that ALA and Myo can modulate inflammatory markers in uRPL patients.

## Key findings

- uRPL women had higher serum and endometrial HMGB-1 levels compared to controls.
- ALA and Myo treatment significantly reduced NLRP-3 and HMGB-1 levels in uRPL women.
- Post-treatment levels in uRPL women became similar to those in controls.

## Abstract

The aim of this study was to investigate the effect of oral administration of a combination of alpha- lipoic acid (ALA) and myo-inositol (Myo) on serum and endometrial inflammation of women with unexplained recurrent pregnancy loss (uRPL).

Serum and endometrial levels of Nacht leucine-rich-repeat protein-3 (NLRP-3) and High Mobility Group Box 1 (HMGB-1) were analyzed by ELISA in women with unexplained Recurrent Pregnancy Loss (uRPL) (n = 31) and in control women who had had at least one uncomplicated pregnancy at term (n = 10) before and after daily oral administration of a commercial combination of ALA and Myo.

uRPL women had higher serum levels (p < 0.01) and endometrial content (p < 0.0001) of HMGB-1 than controls while no difference was observed regarding NALP3. Oral administration of ALA and Myo for three months significantly decreased pre-treatment serum levels of NLRP-3 (p < 0.0001) and HMGB-1 (p < 0.0001), as well as endometrial content of NLRP-3 (p < 0.001) and HMGB-1 (p < 0.0001) in uRPL women, similar to those found in controls.

Women with uRPL have increased systemic and endometrial inflammation than controls. Oral administration of ALA and Myo could modulate serum and endometrial levels of NLRP-3 and HMGB-1 in uRPL women.

## Linked entities

- **Genes:** NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548], HMGB1 (high mobility group box 1) [NCBI Gene 3146]
- **Chemicals:** alpha-lipoic acid (PubChem CID 864), myo-inositol (PubChem CID 892)

## Full-text entities

- **Genes:** Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, Hmgb1 (high mobility group box 1) [NCBI Gene 25459] {aka Ac2-008, Hmg1}, Tlr2 (toll-like receptor 2) [NCBI Gene 24088] {aka Ly105}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, Casp1 (caspase 1) [NCBI Gene 12362] {aka ICE, Il1bc}, Hmgb1 (high mobility group box 1) [NCBI Gene 15289] {aka HMG-1, Hmg1, SBP-1, p30}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, HMGB1 (high mobility group box 1) [NCBI Gene 3146] {aka HMG-1, HMG1, HMG3, SBP-1}
- **Diseases:** pregnancy failure (MESH:D051437), sperm anomalies (MESH:C567467), immune (MESH:D007154), RPL (MESH:D000026), insulin resistance (MESH:D007333), endometrial inflammation (MESH:D007249), hyperglycemic (MESH:D006944), PCOS (MESH:D011085), necrosis (MESH:D009336), endometrial polyp (MESH:D014591), Pregnancy Loss (MESH:D000022)
- **Chemicals:** ALA (MESH:D008063), vitamin E (MESH:D014810), Ala (MESH:D000409), Myo-inositol (-), leupeptin (MESH:C032854), vitamin C (MESH:D001205), LH (MESH:D007986), MYO (MESH:D007294), glutathione (MESH:D005978)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12935864/full.md

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Source: https://tomesphere.com/paper/PMC12935864