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Circulating MMP-7 and VEGF as potential predictive biomarkers for recurrent implantation failures

Published online by Cambridge University Press:  19 March 2021

Mustapha Benkhalifa ,
Wiem Zidi ,
Hatem Bahri ,
Sami Mahjoub ,
Khaled Boudhraa ,
Haifa Sanhaji ,
Hafida Khorsi-Cauet ,
Moncef Feki ,
Moncef Benkhalifa Open the ORCID record for Moncef Benkhalifa [Opens in a new window]  and
Monia Allal-Elasmi Open the ORCID record for Monia Allal-Elasmi [Opens in a new window]
Mustapha Benkhalifa
Affiliation:
LR99ES11, Department of Biochemistry, La Rabta Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia Faculty of Sciences of Bizerte, University of Carthage, Tunis, Tunisia
Wiem Zidi
Affiliation:
LR99ES11, Department of Biochemistry, La Rabta Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia Faculty of Sciences of Bizerte, University of Carthage, Tunis, Tunisia
Hatem Bahri
Affiliation:
Alyssa Fertility Group Center, Alyssa Clinic, Les Berges du Lac, Tunis, Tunisia
Sami Mahjoub
Affiliation:
Alyssa Fertility Group Center, Alyssa Clinic, Les Berges du Lac, Tunis, Tunisia
Khaled Boudhraa
Affiliation:
Alyssa Fertility Group Center, Alyssa Clinic, Les Berges du Lac, Tunis, Tunisia
Haifa Sanhaji
Affiliation:
LR99ES11, Department of Biochemistry, La Rabta Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
Hafida Khorsi-Cauet
Affiliation:
PERITOX-UMR-I 01 CURS, Picardie University Jules Verne, Amiens, France
Moncef Feki
Affiliation:
LR99ES11, Department of Biochemistry, La Rabta Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
Moncef Benkhalifa
Affiliation:
PERITOX-UMR-I 01 CURS, Picardie University Jules Verne, Amiens, France Reproductive Medicine, Reproductive Biology and Genetics, University Hospital and School of Medicine Picardie University Jules Verne, Amiens, France
Monia Allal-Elasmi*
Affiliation:
LR99ES11, Department of Biochemistry, La Rabta Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia
*
Author for correspondence: Monia Allal-Elasmi. LR99ES11, Department of Biochemistry, Rabta Hospital, 1007 Jebbari, Tunis, Tunisia. Tel: +216 98425496. Fax: +216 71561912. E-mails: monia.elasmi@fmt.utm.tn; monia_elasmi@yahoo.fr
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Summary

Recurrent implantation failure (RIF) is considered to be one of the major limiting factors of assisted reproductive technology (ART) programme success. The current study focused on the investigation of matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), cytokines and cell adhesion molecules in peripheral blood (PB) and follicular fluid (FF) obtained from 44 women aged between 25 and 39 years old and undergoing intracytoplasmic sperm injection (ICSI). These women were divided into two groups: 22 RIF women with embryo implantation failures after the transfer of at least four fresh or frozen–thawed good quality embryos in a minimum of three ICSI cycles, and 22 ICSI success women (controls) who achieved a clinical pregnancy at their first ICSI attempt. The PB and FF samples were obtained from each patient on the day of oocyte retrieval. MMP-1, -2, -3, -7, -9, TIMP-1, -2, vascular endothelial growth factor (VEGF), leukaemia inhibitory factor (LIF), vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecules 1 (ICAM1) were analyzed using enzyme-linked immunosorbent assay of PB and FF. Our results showed significant decreases in PB MMP-7 and PB VEGF in the RIF group compared with controls [281.11 (33–614) pg/ml vs 119.92 (27–441) pg/ml; P-value = 0.030] and [82.54 (25.94–210.20) pg/ml vs 30.93 (13.62–193.33) pg/ml; P-value = 0.022; respectively]. Receiver operating characteristic (ROC) curve analysis showed informative area under the curve values for PB MMP-7, as well as for PB VEGF, making them able to be proposed as biomarkers of the RIF. Therefore, circulating MMP-7 and VEGF seem to play an interesting role in embryo implantation in in vitro fertilization (IVF)/ICSI cycles and could be proposed as circulating biomarkers of the RIF. These results could be helpful for clinicians and patients to choose the best rescue strategy and treatment to minimize implantation failure in women undergoing IVF/ICSI procedures after the first attempt.

Keywords

Assisted reproductive technologyMatrilysinMatrix metalloproteinasesRecurrent implantation failureVascular endothelial growth factor

Information

Type
Research Article
Information
Zygote , Volume 29 , Issue 5 , October 2021 , pp. 365 - 371
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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