Should the Treatment of Patients with Repeated Embryo Implantation Failure Be Adapted as a Function of the Endometrial Cytokine Profile? A Single-Center Experience
Repeated embryo implantation failures (RIF) is a source of distress and frustration for patients and clinicians alike. Today’s approaches for treating RIF are largely empirical and have limited effectiveness. The main causes of RIF are poor endometrial receptivity and poor-quality embryos. Recent st...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/3/817 |
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| author | Bérangère Coutanceau Esther Dos Santos Nelly Swierkowski Blanchard Anne Sanchez Louboutin Florence Boitrelle François Margueritte François Vialard Valérie Serazin Khadija Fathallah |
| author_facet | Bérangère Coutanceau Esther Dos Santos Nelly Swierkowski Blanchard Anne Sanchez Louboutin Florence Boitrelle François Margueritte François Vialard Valérie Serazin Khadija Fathallah |
| author_sort | Bérangère Coutanceau |
| collection | DOAJ |
| description | Repeated embryo implantation failures (RIF) is a source of distress and frustration for patients and clinicians alike. Today’s approaches for treating RIF are largely empirical and have limited effectiveness. The main causes of RIF are poor endometrial receptivity and poor-quality embryos. Recent studies have suggested the involvement of immune dysregulation due to an imbalance between T-helper (Th) 1 and Th2 cytokines; this opens up perspectives for treating women with RIF and increasing the implantation rate. We conducted an interventional, longitudinal, prospective cohort study of the impact of correcting the cytokine imbalance on the clinical pregnancy rate in women with RIF. Seventy-seven women with RIF underwent an endometrial biopsy during the implantation window. The cytokine profile was evaluated by studying the activation and maturation of uterine natural killer (uNK) cells, the IL-15/Fn-14 mRNA ratio (a biomarker of uNK activation/maturation), and the IL-18/TWEAK mRNA ratio (a marker of angiogenesis and the Th1/Th2 balance). Personalized treatment was initiated for women with an abnormal endometrial cytokine profile (hyper-activation or hypo-activation). We documented the clinical pregnancy rate after subsequent embryo transfers. In total, 72.7% (56/77) of patients had an abnormal endometrial cytokine profile (hyper-activation in 68.8% (n = 53) and hypo-activation in 3.9% (n = 3). After treatment (or not) as a function of the endometrial profile, the overall clinical pregnancy rate was 30.2%. Our results indicated a potential positive effect of appropriate treatment on the ongoing pregnancy rate in women with RIF, despite the small number of cases analyzed. The results must now be validated in randomized studies with larger numbers of well-characterized patients. By applying a previously published decision tree, this treatment approach could be implemented in clinics worldwide. |
| first_indexed | 2024-03-11T06:53:32Z |
| format | Article |
| id | doaj.art-62330231dc524fe8b17b7f8ef0443013 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T06:53:32Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-62330231dc524fe8b17b7f8ef04430132023-11-17T09:46:04ZengMDPI AGBiomedicines2227-90592023-03-0111381710.3390/biomedicines11030817Should the Treatment of Patients with Repeated Embryo Implantation Failure Be Adapted as a Function of the Endometrial Cytokine Profile? A Single-Center ExperienceBérangère Coutanceau0Esther Dos Santos1Nelly Swierkowski Blanchard2Anne Sanchez Louboutin3Florence Boitrelle4François Margueritte5François Vialard6Valérie Serazin7Khadija Fathallah8Department of Obstetrics and Gynaecology, Poissy-Saint-Germain-en-Laye Hospital, 78300 Poissy, FranceMedical Biology Laboratory, Poissy-Saint-Germain-en-Laye Hospital, 78300 Poissy, FranceDepartment of Obstetrics and Gynaecology, Poissy-Saint-Germain-en-Laye Hospital, 78300 Poissy, FranceDepartment of Anatomy and Pathology, Poissy-Saint-Germain-en-Laye Hospital, 78300 Poissy, FranceReproductive Biology Department, Poissy-Saint-Germain-en-Laye Hospital, 78300 Poissy, FranceDepartment of Obstetrics and Gynaecology, Poissy-Saint-Germain-en-Laye Hospital, 78300 Poissy, FranceRhUMA Team, UMR-BREED (INRAE, UVSQ, ENVA), UFR Simone Veil-Santé, 78180 Montigny le Bretonneux, FranceMedical Biology Laboratory, Poissy-Saint-Germain-en-Laye Hospital, 78300 Poissy, FranceDepartment of Obstetrics and Gynaecology, Poissy-Saint-Germain-en-Laye Hospital, 78300 Poissy, FranceRepeated embryo implantation failures (RIF) is a source of distress and frustration for patients and clinicians alike. Today’s approaches for treating RIF are largely empirical and have limited effectiveness. The main causes of RIF are poor endometrial receptivity and poor-quality embryos. Recent studies have suggested the involvement of immune dysregulation due to an imbalance between T-helper (Th) 1 and Th2 cytokines; this opens up perspectives for treating women with RIF and increasing the implantation rate. We conducted an interventional, longitudinal, prospective cohort study of the impact of correcting the cytokine imbalance on the clinical pregnancy rate in women with RIF. Seventy-seven women with RIF underwent an endometrial biopsy during the implantation window. The cytokine profile was evaluated by studying the activation and maturation of uterine natural killer (uNK) cells, the IL-15/Fn-14 mRNA ratio (a biomarker of uNK activation/maturation), and the IL-18/TWEAK mRNA ratio (a marker of angiogenesis and the Th1/Th2 balance). Personalized treatment was initiated for women with an abnormal endometrial cytokine profile (hyper-activation or hypo-activation). We documented the clinical pregnancy rate after subsequent embryo transfers. In total, 72.7% (56/77) of patients had an abnormal endometrial cytokine profile (hyper-activation in 68.8% (n = 53) and hypo-activation in 3.9% (n = 3). After treatment (or not) as a function of the endometrial profile, the overall clinical pregnancy rate was 30.2%. Our results indicated a potential positive effect of appropriate treatment on the ongoing pregnancy rate in women with RIF, despite the small number of cases analyzed. The results must now be validated in randomized studies with larger numbers of well-characterized patients. By applying a previously published decision tree, this treatment approach could be implemented in clinics worldwide.https://www.mdpi.com/2227-9059/11/3/817embryo implantationin vitro fertilizationendometriumcytokine profile |
| spellingShingle | Bérangère Coutanceau Esther Dos Santos Nelly Swierkowski Blanchard Anne Sanchez Louboutin Florence Boitrelle François Margueritte François Vialard Valérie Serazin Khadija Fathallah Should the Treatment of Patients with Repeated Embryo Implantation Failure Be Adapted as a Function of the Endometrial Cytokine Profile? A Single-Center Experience Biomedicines embryo implantation in vitro fertilization endometrium cytokine profile |
| title | Should the Treatment of Patients with Repeated Embryo Implantation Failure Be Adapted as a Function of the Endometrial Cytokine Profile? A Single-Center Experience |
| title_full | Should the Treatment of Patients with Repeated Embryo Implantation Failure Be Adapted as a Function of the Endometrial Cytokine Profile? A Single-Center Experience |
| title_fullStr | Should the Treatment of Patients with Repeated Embryo Implantation Failure Be Adapted as a Function of the Endometrial Cytokine Profile? A Single-Center Experience |
| title_full_unstemmed | Should the Treatment of Patients with Repeated Embryo Implantation Failure Be Adapted as a Function of the Endometrial Cytokine Profile? A Single-Center Experience |
| title_short | Should the Treatment of Patients with Repeated Embryo Implantation Failure Be Adapted as a Function of the Endometrial Cytokine Profile? A Single-Center Experience |
| title_sort | should the treatment of patients with repeated embryo implantation failure be adapted as a function of the endometrial cytokine profile a single center experience |
| topic | embryo implantation in vitro fertilization endometrium cytokine profile |
| url | https://www.mdpi.com/2227-9059/11/3/817 |
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