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Article

Exploring the Association Between Gut Microbiota and Infertility in Women with Multiple Implantation Failures: An Exploratory Study

1
PhD School of Applied Medical-Surgical Sciences, Tor Vergata University of Rome, 00133 Rome, Italy
2
School of Specialization in Food Science, Tor Vergata University of Rome, 00133 Rome, Italy
3
Department of Biomedicine and Prevention, University of Tor Vergata, 00133 Rome, Italy
4
IVIRMA Global Research Alliance, IVIRMA Italia, Reproductive Health Unit, 00197 Rome, Italy
5
Unit of Cardiology, Istituto Dermatopatico Dell’immacolata (IDI)—IRCCS, Via Monti di Creta, 00167 Rome, Italy
6
Department of Biology, Centro di Bioinformatica Molecolare, Tor Vergata University of Rome, 00133 Rome, Italy
7
Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, 27100 Pavia, Italy
8
IVIRMA Global Research Alliance, IVIRMA Italia, 00197 Rome, Italy
9
IVIRMA Global Research Alliance, Genera, Clinica Valle Giulia, 00197 Roma, Italy
10
Section of Food, Clinical Nutrition and Pharmaceutica Science, Department of Biomedicine and Prevention, Tor Vergata University of Rome, 00133 Rome, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors also contributed equally to this work.
Microorganisms 2026, 14(6), 1334; https://doi.org/10.3390/microorganisms14061334 (registering DOI)
Submission received: 6 May 2026 / Revised: 8 June 2026 / Accepted: 12 June 2026 / Published: 14 June 2026
(This article belongs to the Special Issue State-of-the-Art Medical Microbiology in Italy (2025, 2026))

Abstract

Implantation failure remains a major challenge in IVF, and the contribution of the gut microbiota to implantation success is still poorly defined. We conducted a pilot matched case–control study (February 2023–December 2024) to compare gut microbiota profiles between women with RIF (defined according to ESHRE good practice recommendations) and fertile controls with documented fertility (≥1 prior spontaneous pregnancy). All participants underwent standardized clinical and nutritional assessment of medical history, dietary habits, anthropometry, and body composition. Stool samples were collected for 16S rRNA gene sequencing. In women with RIF, sampling occurred within 1 year after the last failed embryo transfer. Of 45 enrolled women, 41 completed the study (20 RIF and 21 controls; mean age 38.46 ± 4.53 years), with no significant between-group age differences. Women with RIF showed reduced alpha diversity (Shannon p = 0.003; inverse Simpson p = 0.002) and a distinct community structure versus controls (Bray–Curtis PERMANOVA F = 7.16; R2 = 0.16; p = 0.001), which remained significant after adjustment for clinical covariates including waist-to-hip ratio (p = 0.018). At the phylum level, women with RIF had fewer Firmicutes (52.7% vs. 65.0%; p = 0.012) and more Proteobacteria (9.1% vs. 3.6%; p < 0.001). These findings support an association between gut dysbiosis and a history of implantation failures and warrant confirmation in larger, longitudinal cohorts.
Keywords: infertile women; implantation failures; gut microbiota composition; comparison infertile women; implantation failures; gut microbiota composition; comparison

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MDPI and ACS Style

La Placa, G.; Fabozzi, G.; Pala, B.; Peluso, D.; Cimadomo, D.; Vaiarelli, A.; Gualtieri, P.; Di Renzo, L. Exploring the Association Between Gut Microbiota and Infertility in Women with Multiple Implantation Failures: An Exploratory Study. Microorganisms 2026, 14, 1334. https://doi.org/10.3390/microorganisms14061334

AMA Style

La Placa G, Fabozzi G, Pala B, Peluso D, Cimadomo D, Vaiarelli A, Gualtieri P, Di Renzo L. Exploring the Association Between Gut Microbiota and Infertility in Women with Multiple Implantation Failures: An Exploratory Study. Microorganisms. 2026; 14(6):1334. https://doi.org/10.3390/microorganisms14061334

Chicago/Turabian Style

La Placa, Giada, Gemma Fabozzi, Barbara Pala, Daniele Peluso, Danilo Cimadomo, Alberto Vaiarelli, Paola Gualtieri, and Laura Di Renzo. 2026. "Exploring the Association Between Gut Microbiota and Infertility in Women with Multiple Implantation Failures: An Exploratory Study" Microorganisms 14, no. 6: 1334. https://doi.org/10.3390/microorganisms14061334

APA Style

La Placa, G., Fabozzi, G., Pala, B., Peluso, D., Cimadomo, D., Vaiarelli, A., Gualtieri, P., & Di Renzo, L. (2026). Exploring the Association Between Gut Microbiota and Infertility in Women with Multiple Implantation Failures: An Exploratory Study. Microorganisms, 14(6), 1334. https://doi.org/10.3390/microorganisms14061334

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