Publications
Cavadias, Iphigénie; Maitrot-Mantelet, Lorraine; Perol, Sandrine; Bourdon, Mathilde; Santulli, Pietro; Marcellin, Louis; Chapron, Charles; Plu-Bureau, Geneviève
In: Acta Obstet Gynecol Scand, vol. 105, no. 2, pp. 225–237, 2026, ISSN: 1600-0412.
@article{pmid41310987,
title = {Risk of cardiovascular disease and mortality among women with endometriosis: A systematic review and meta-analysis},
author = {Iphigénie Cavadias and Lorraine Maitrot-Mantelet and Sandrine Perol and Mathilde Bourdon and Pietro Santulli and Louis Marcellin and Charles Chapron and Geneviève Plu-Bureau},
doi = {10.1111/aogs.70104},
issn = {1600-0412},
year = {2026},
date = {2026-02-01},
journal = {Acta Obstet Gynecol Scand},
volume = {105},
number = {2},
pages = {225--237},
abstract = {INTRODUCTION: Endometriosis is a chronic and estrogen-dependent disorder that affects about 10% of women of reproductive age worldwide. Endometriosis has been associated with chronic inflammation and an atherogenic lipid profile, two conditions that increase the risk of atherothrombotic cardiovascular diseases.
MATERIAL AND METHODS: A literature search for relevant studies published from the earliest record to 31 March 2025 was conducted in MEDLINE and EMBASE databases. The following MESH terms were searched: "stroke," "cerebrovascular disease," "cardiovascular disease," "coronary heart disease," "ischemic heart disease," "mortality," and "endometriosis." The results of each study were pooled, and an overall estimate of relative risk was obtained with a random-effect model. Homogeneity between studies was analyzed using I statistics. This review was not registered.
RESULTS: Ten studies were eligible for inclusion in this meta-analysis. Five studies reported an increased risk of stroke with endometriosis, with a pooled risk of 1.18 (95% confidence intervals [95% CI] [1.13-1.22]). Four studies reported an increased risk of coronary heart disease with endometriosis, with a pooled risk of 1.36 (95% CI [1.32-1.40]). Four studies reported an increased risk of composite cardiovascular disease with endometriosis, with a pooled risk of 1.16 (95% CI [1.12-1.20]). Although the homogeneity is high in results, the confounding factors considered in the different studies vary. Thus, these results must be interpreted with caution.
CONCLUSIONS: Endometriosis is associated with an increased risk of cardiovascular disease. Further research is required to confirm these findings. However, these results highlight the importance of considering primary cardiovascular prevention strategies for women with endometriosis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
INTRODUCTION: Endometriosis is a chronic and estrogen-dependent disorder that affects about 10% of women of reproductive age worldwide. Endometriosis has been associated with chronic inflammation and an atherogenic lipid profile, two conditions that increase the risk of atherothrombotic cardiovascular diseases.
MATERIAL AND METHODS: A literature search for relevant studies published from the earliest record to 31 March 2025 was conducted in MEDLINE and EMBASE databases. The following MESH terms were searched: “stroke,” “cerebrovascular disease,” “cardiovascular disease,” “coronary heart disease,” “ischemic heart disease,” “mortality,” and “endometriosis.” The results of each study were pooled, and an overall estimate of relative risk was obtained with a random-effect model. Homogeneity between studies was analyzed using I statistics. This review was not registered.
RESULTS: Ten studies were eligible for inclusion in this meta-analysis. Five studies reported an increased risk of stroke with endometriosis, with a pooled risk of 1.18 (95% confidence intervals [95% CI] [1.13-1.22]). Four studies reported an increased risk of coronary heart disease with endometriosis, with a pooled risk of 1.36 (95% CI [1.32-1.40]). Four studies reported an increased risk of composite cardiovascular disease with endometriosis, with a pooled risk of 1.16 (95% CI [1.12-1.20]). Although the homogeneity is high in results, the confounding factors considered in the different studies vary. Thus, these results must be interpreted with caution.
CONCLUSIONS: Endometriosis is associated with an increased risk of cardiovascular disease. Further research is required to confirm these findings. However, these results highlight the importance of considering primary cardiovascular prevention strategies for women with endometriosis.
MATERIAL AND METHODS: A literature search for relevant studies published from the earliest record to 31 March 2025 was conducted in MEDLINE and EMBASE databases. The following MESH terms were searched: “stroke,” “cerebrovascular disease,” “cardiovascular disease,” “coronary heart disease,” “ischemic heart disease,” “mortality,” and “endometriosis.” The results of each study were pooled, and an overall estimate of relative risk was obtained with a random-effect model. Homogeneity between studies was analyzed using I statistics. This review was not registered.
RESULTS: Ten studies were eligible for inclusion in this meta-analysis. Five studies reported an increased risk of stroke with endometriosis, with a pooled risk of 1.18 (95% confidence intervals [95% CI] [1.13-1.22]). Four studies reported an increased risk of coronary heart disease with endometriosis, with a pooled risk of 1.36 (95% CI [1.32-1.40]). Four studies reported an increased risk of composite cardiovascular disease with endometriosis, with a pooled risk of 1.16 (95% CI [1.12-1.20]). Although the homogeneity is high in results, the confounding factors considered in the different studies vary. Thus, these results must be interpreted with caution.
CONCLUSIONS: Endometriosis is associated with an increased risk of cardiovascular disease. Further research is required to confirm these findings. However, these results highlight the importance of considering primary cardiovascular prevention strategies for women with endometriosis.
Ferreux, Lucile; Ducreux, Bastien; Firmin, Julie; Chargui, Ahmed; Pocate-Cheriet, Khaled; Maignien, Chloé; Santulli, Pietro; Borensztein, Maud; Fauque, Patricia; Patrat, Catherine
In: Hum Reprod Update, vol. 32, no. 1, pp. 33–57, 2026, ISSN: 1460-2369.
@article{pmid40891422,
title = {Transcript profiling and gene regulation of the human pre-implantation embryo: parental effects and impact of ARTs},
author = {Lucile Ferreux and Bastien Ducreux and Julie Firmin and Ahmed Chargui and Khaled Pocate-Cheriet and Chloé Maignien and Pietro Santulli and Maud Borensztein and Patricia Fauque and Catherine Patrat},
doi = {10.1093/humupd/dmaf022},
issn = {1460-2369},
year = {2026},
date = {2026-01-01},
journal = {Hum Reprod Update},
volume = {32},
number = {1},
pages = {33--57},
abstract = {BACKGROUND: Infertility is a growing global challenge, with ARTs significantly improving birth rates for infertile couples. However, ART conceptions are associated with a higher risk of negative obstetrical and perinatal outcomes, with potential long-term effects on offspring health. Many pre-implantation embryos exhibit abnormal morphokinetics, implantation failure, or arrested development. ART procedures and parental factors are suspected to perturb the embryonic transcriptome, potentially affecting molecular and epigenetic events during gametogenesis and early development. The timing and mechanisms of these perturbations remain unclear. Genome-wide transcriptomic misregulation in ART-conceived human pre-implantation embryos may provide important insights into observed differences between ART and naturally conceived offspring.
OBJECTIVE AND RATIONALE: This narrative review aims to explore how the transcriptome of the human pre-implantation embryo is influenced by parental characteristics, ART conditions, and embryonic factors, with the characterization of the temporal sequence of acquisition of lineage-specific markers at the blastocyst stage serving as a prerequisite. The primary objective is to compile changes in gene expression resulting from parental and intrinsic characteristics or from ART-specific interventions. A secondary aim is to identify common dysregulated molecular pathways across all factors studied.
SEARCH METHODS: A comprehensive PubMed search (up to December 2024) was conducted to identify studies assessing transcriptomic profiles in human blastocysts. Studies were included based on parental infertility characteristics (e.g. age, polycystic ovary syndrome (PCOS), endometriosis, diminished ovarian reserve (DOR), sperm alterations, unexplained infertility (UI), and obesity), ART interventions (e.g. hormonal stimulation, IVM, IVF, culture conditions, and vitrification), and intrinsic embryo factors (e.g. morphology, ploidy, sex, and developmental arrest). Differentially expressed genes between different embryo groups were compared across studies, and Gene Ontology analysis identified common or specific pathways. Single-cell RNA sequencing data were used to map lineage-specific transcriptomic patterns in human blastocysts, categorizing expression changes by cell lineages (epiblast, primitive endoderm, and trophectoderm). Where human data on blastocysts were limited, animal studies or other cleaved stages were discussed.
OUTCOMES: Maternal age was the most significant contributor to misregulated gene expression in human blastocysts, affecting metabolic and developmental processes. Variations in culture medium impacted cell cycle regulation, carbohydrate metabolism, and RNA biosynthesis. Blastocyst morphology mostly influenced metabolic process changes. Blastocyst aneuploidy induced significant changes in developmental pathways and pluripotency gene expression in the epiblast. Evidence on the effects of PCOS, endometriosis, DOR, sperm alterations, UI, and ART technologies remains limited. Dysregulated pathways commonly involve metabolic, cellular, reproductive, and developmental processes. Dysregulation of genomic imprinting and chromatin-modifier genes was also observed across at least two conditions.
WIDER IMPLICATIONS: This review highlights the complexity of interpreting gene expression in human pre-implantation embryos due to diverse influences, including parental age, ART conditions, developmental stage, and embryo sex. ART procedures may have cumulative effects on the blastocyst transcriptome. Modifiable factors, such as culture conditions, offer opportunities for improving IVF outcomes. Epigenetic modifications may also be sensitive to these diverse influences and involved in observed transcriptomic changes, opening further research investigation to clarify long-term health effects.
REGISTRATION NUMBER: n/a.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Infertility is a growing global challenge, with ARTs significantly improving birth rates for infertile couples. However, ART conceptions are associated with a higher risk of negative obstetrical and perinatal outcomes, with potential long-term effects on offspring health. Many pre-implantation embryos exhibit abnormal morphokinetics, implantation failure, or arrested development. ART procedures and parental factors are suspected to perturb the embryonic transcriptome, potentially affecting molecular and epigenetic events during gametogenesis and early development. The timing and mechanisms of these perturbations remain unclear. Genome-wide transcriptomic misregulation in ART-conceived human pre-implantation embryos may provide important insights into observed differences between ART and naturally conceived offspring.
OBJECTIVE AND RATIONALE: This narrative review aims to explore how the transcriptome of the human pre-implantation embryo is influenced by parental characteristics, ART conditions, and embryonic factors, with the characterization of the temporal sequence of acquisition of lineage-specific markers at the blastocyst stage serving as a prerequisite. The primary objective is to compile changes in gene expression resulting from parental and intrinsic characteristics or from ART-specific interventions. A secondary aim is to identify common dysregulated molecular pathways across all factors studied.
SEARCH METHODS: A comprehensive PubMed search (up to December 2024) was conducted to identify studies assessing transcriptomic profiles in human blastocysts. Studies were included based on parental infertility characteristics (e.g. age, polycystic ovary syndrome (PCOS), endometriosis, diminished ovarian reserve (DOR), sperm alterations, unexplained infertility (UI), and obesity), ART interventions (e.g. hormonal stimulation, IVM, IVF, culture conditions, and vitrification), and intrinsic embryo factors (e.g. morphology, ploidy, sex, and developmental arrest). Differentially expressed genes between different embryo groups were compared across studies, and Gene Ontology analysis identified common or specific pathways. Single-cell RNA sequencing data were used to map lineage-specific transcriptomic patterns in human blastocysts, categorizing expression changes by cell lineages (epiblast, primitive endoderm, and trophectoderm). Where human data on blastocysts were limited, animal studies or other cleaved stages were discussed.
OUTCOMES: Maternal age was the most significant contributor to misregulated gene expression in human blastocysts, affecting metabolic and developmental processes. Variations in culture medium impacted cell cycle regulation, carbohydrate metabolism, and RNA biosynthesis. Blastocyst morphology mostly influenced metabolic process changes. Blastocyst aneuploidy induced significant changes in developmental pathways and pluripotency gene expression in the epiblast. Evidence on the effects of PCOS, endometriosis, DOR, sperm alterations, UI, and ART technologies remains limited. Dysregulated pathways commonly involve metabolic, cellular, reproductive, and developmental processes. Dysregulation of genomic imprinting and chromatin-modifier genes was also observed across at least two conditions.
WIDER IMPLICATIONS: This review highlights the complexity of interpreting gene expression in human pre-implantation embryos due to diverse influences, including parental age, ART conditions, developmental stage, and embryo sex. ART procedures may have cumulative effects on the blastocyst transcriptome. Modifiable factors, such as culture conditions, offer opportunities for improving IVF outcomes. Epigenetic modifications may also be sensitive to these diverse influences and involved in observed transcriptomic changes, opening further research investigation to clarify long-term health effects.
REGISTRATION NUMBER: n/a.
OBJECTIVE AND RATIONALE: This narrative review aims to explore how the transcriptome of the human pre-implantation embryo is influenced by parental characteristics, ART conditions, and embryonic factors, with the characterization of the temporal sequence of acquisition of lineage-specific markers at the blastocyst stage serving as a prerequisite. The primary objective is to compile changes in gene expression resulting from parental and intrinsic characteristics or from ART-specific interventions. A secondary aim is to identify common dysregulated molecular pathways across all factors studied.
SEARCH METHODS: A comprehensive PubMed search (up to December 2024) was conducted to identify studies assessing transcriptomic profiles in human blastocysts. Studies were included based on parental infertility characteristics (e.g. age, polycystic ovary syndrome (PCOS), endometriosis, diminished ovarian reserve (DOR), sperm alterations, unexplained infertility (UI), and obesity), ART interventions (e.g. hormonal stimulation, IVM, IVF, culture conditions, and vitrification), and intrinsic embryo factors (e.g. morphology, ploidy, sex, and developmental arrest). Differentially expressed genes between different embryo groups were compared across studies, and Gene Ontology analysis identified common or specific pathways. Single-cell RNA sequencing data were used to map lineage-specific transcriptomic patterns in human blastocysts, categorizing expression changes by cell lineages (epiblast, primitive endoderm, and trophectoderm). Where human data on blastocysts were limited, animal studies or other cleaved stages were discussed.
OUTCOMES: Maternal age was the most significant contributor to misregulated gene expression in human blastocysts, affecting metabolic and developmental processes. Variations in culture medium impacted cell cycle regulation, carbohydrate metabolism, and RNA biosynthesis. Blastocyst morphology mostly influenced metabolic process changes. Blastocyst aneuploidy induced significant changes in developmental pathways and pluripotency gene expression in the epiblast. Evidence on the effects of PCOS, endometriosis, DOR, sperm alterations, UI, and ART technologies remains limited. Dysregulated pathways commonly involve metabolic, cellular, reproductive, and developmental processes. Dysregulation of genomic imprinting and chromatin-modifier genes was also observed across at least two conditions.
WIDER IMPLICATIONS: This review highlights the complexity of interpreting gene expression in human pre-implantation embryos due to diverse influences, including parental age, ART conditions, developmental stage, and embryo sex. ART procedures may have cumulative effects on the blastocyst transcriptome. Modifiable factors, such as culture conditions, offer opportunities for improving IVF outcomes. Epigenetic modifications may also be sensitive to these diverse influences and involved in observed transcriptomic changes, opening further research investigation to clarify long-term health effects.
REGISTRATION NUMBER: n/a.
Fauque, Patricia; Cottenet, Jonathan; Firmin, Julie; Pocate-Cheriet, Khaled; Ferreux, Lucile; Chargui, Ahmed; Tapia, Solène; Maignien, Chloé; Bourdon, Mathilde; Santulli, Pietro; Patrat, Catherine; Quantin, Catherine
In: Hum Reprod, 2025, ISSN: 1460-2350.
@article{pmid41453370,
title = {Obstetrical, perinatal, and children's health outcomes following fresh embryo transfer after extended embryo culture},
author = {Patricia Fauque and Jonathan Cottenet and Julie Firmin and Khaled Pocate-Cheriet and Lucile Ferreux and Ahmed Chargui and Solène Tapia and Chloé Maignien and Mathilde Bourdon and Pietro Santulli and Catherine Patrat and Catherine Quantin},
doi = {10.1093/humrep/deaf245},
issn = {1460-2350},
year = {2025},
date = {2025-12-01},
journal = {Hum Reprod},
abstract = {STUDY QUESTION: Does extended embryo culture (EEC) associate with an increased risk of obstetrical, perinatal, or children's health complications?nnSUMMARY ANSWER: After thorough adjustment, EEC was not associated with widespread increased risks, although a moderate excess risk persisted for a few specific outcomes, notably cardiac anomalies, whereas reduced risks were observed for gestational diabetes, small birthweight, and musculoskeletal-limb anomalies.
WHAT IS KNOWN ALREADY: EEC is increasingly used in IVF cycles. While blastocyst transfer (day-5/6) often improves birth rates, concerns remain about its impact on maternal and child health.
STUDY DESIGN, SIZE, DURATION: In this nationwide longitudinal cohort study, all live-born singletons conceived through IVF-with or without sperm microinjection-and following fresh embryo transfer between 2014 and 2019 in France were included and followed for up to 8 years.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were obtained from the French National Health System and the National Biomedicine Agency registries. A comparative study was conducted between singletons conceived at either day-2/3 (cleavage-stage embryos group) or day-5/6 (EEC group). Data from both registries were cross-linked to identify obstetrical, perinatal, and health outcomes, including major congenital malformations, hospitalizations, and surgical interventions. Multivariable logistic and survival models were used to adjust for maternal, paternal, and treatment-related factors.
MAIN RESULTS AND THE ROLE OF CHANCE: A total of 41 315 singletons were included (25 816 and 15 499 from day-2/3 and day-5/6 groups, respectively). Most outcomes were similar between groups, notably the incidence of global major congenital malformations. However, EEC was associated with increased risks of placenta praevia (aOR, 1.16; 95% CI, 1.02-1.30), admission in neonatal intensive care unit (aOR, 1.16; 95% CI, 1.05-1.29), and cardiac anomalies at age 3 years (aHR, 1.78; 95% CI, 1.21-2.60). Conversely, the risk of gestational diabetes (aOR, 0.94; 95% CI, 0.88-1.00; P = 0.041) and small birthweight (aOR, 0.94; 95% CI, 0.88-1.00, P = 0.039) was lower, as was the risk of musculoskeletal-limb anomalies (aHR, 0.63; 95% CI, 0.42-0.97)-a finding that persisted up to age 7. Other health outcomes were largely comparable.
LIMITATIONS, REASONS FOR CAUTION: One limitation of this study is that the data refer to live-born singletons, with stillbirths and medical terminations excluded from the analyses. Despite extensive adjustments, residual confounding cannot be excluded. Findings for specific pathologies/malformations should be interpreted with caution because the number of cases was small in some sub-groups.
WIDER IMPLICATIONS OF THE FINDINGS: In this large and unique study, after adjusting for multiple maternal, paternal, and cycle-related variables, our findings provide some reassurance regarding the safety of prolonged in vitro embryo culture. A moderate risk remained for a few maternal and child health conditions following EEC-warranting further investigation-whereas the risk was notably lower compared to short embryo culture, particularly for musculoskeletal-limb anomalies.
STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the AOI of University Hospital of Dijon. The authors have no competing interests to disclose.
TRIAL REGISTRATION NUMBER: N/A.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
STUDY QUESTION: Does extended embryo culture (EEC) associate with an increased risk of obstetrical, perinatal, or children’s health complications?nnSUMMARY ANSWER: After thorough adjustment, EEC was not associated with widespread increased risks, although a moderate excess risk persisted for a few specific outcomes, notably cardiac anomalies, whereas reduced risks were observed for gestational diabetes, small birthweight, and musculoskeletal-limb anomalies.
WHAT IS KNOWN ALREADY: EEC is increasingly used in IVF cycles. While blastocyst transfer (day-5/6) often improves birth rates, concerns remain about its impact on maternal and child health.
STUDY DESIGN, SIZE, DURATION: In this nationwide longitudinal cohort study, all live-born singletons conceived through IVF-with or without sperm microinjection-and following fresh embryo transfer between 2014 and 2019 in France were included and followed for up to 8 years.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were obtained from the French National Health System and the National Biomedicine Agency registries. A comparative study was conducted between singletons conceived at either day-2/3 (cleavage-stage embryos group) or day-5/6 (EEC group). Data from both registries were cross-linked to identify obstetrical, perinatal, and health outcomes, including major congenital malformations, hospitalizations, and surgical interventions. Multivariable logistic and survival models were used to adjust for maternal, paternal, and treatment-related factors.
MAIN RESULTS AND THE ROLE OF CHANCE: A total of 41 315 singletons were included (25 816 and 15 499 from day-2/3 and day-5/6 groups, respectively). Most outcomes were similar between groups, notably the incidence of global major congenital malformations. However, EEC was associated with increased risks of placenta praevia (aOR, 1.16; 95% CI, 1.02-1.30), admission in neonatal intensive care unit (aOR, 1.16; 95% CI, 1.05-1.29), and cardiac anomalies at age 3 years (aHR, 1.78; 95% CI, 1.21-2.60). Conversely, the risk of gestational diabetes (aOR, 0.94; 95% CI, 0.88-1.00; P = 0.041) and small birthweight (aOR, 0.94; 95% CI, 0.88-1.00, P = 0.039) was lower, as was the risk of musculoskeletal-limb anomalies (aHR, 0.63; 95% CI, 0.42-0.97)-a finding that persisted up to age 7. Other health outcomes were largely comparable.
LIMITATIONS, REASONS FOR CAUTION: One limitation of this study is that the data refer to live-born singletons, with stillbirths and medical terminations excluded from the analyses. Despite extensive adjustments, residual confounding cannot be excluded. Findings for specific pathologies/malformations should be interpreted with caution because the number of cases was small in some sub-groups.
WIDER IMPLICATIONS OF THE FINDINGS: In this large and unique study, after adjusting for multiple maternal, paternal, and cycle-related variables, our findings provide some reassurance regarding the safety of prolonged in vitro embryo culture. A moderate risk remained for a few maternal and child health conditions following EEC-warranting further investigation-whereas the risk was notably lower compared to short embryo culture, particularly for musculoskeletal-limb anomalies.
STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the AOI of University Hospital of Dijon. The authors have no competing interests to disclose.
TRIAL REGISTRATION NUMBER: N/A.
WHAT IS KNOWN ALREADY: EEC is increasingly used in IVF cycles. While blastocyst transfer (day-5/6) often improves birth rates, concerns remain about its impact on maternal and child health.
STUDY DESIGN, SIZE, DURATION: In this nationwide longitudinal cohort study, all live-born singletons conceived through IVF-with or without sperm microinjection-and following fresh embryo transfer between 2014 and 2019 in France were included and followed for up to 8 years.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were obtained from the French National Health System and the National Biomedicine Agency registries. A comparative study was conducted between singletons conceived at either day-2/3 (cleavage-stage embryos group) or day-5/6 (EEC group). Data from both registries were cross-linked to identify obstetrical, perinatal, and health outcomes, including major congenital malformations, hospitalizations, and surgical interventions. Multivariable logistic and survival models were used to adjust for maternal, paternal, and treatment-related factors.
MAIN RESULTS AND THE ROLE OF CHANCE: A total of 41 315 singletons were included (25 816 and 15 499 from day-2/3 and day-5/6 groups, respectively). Most outcomes were similar between groups, notably the incidence of global major congenital malformations. However, EEC was associated with increased risks of placenta praevia (aOR, 1.16; 95% CI, 1.02-1.30), admission in neonatal intensive care unit (aOR, 1.16; 95% CI, 1.05-1.29), and cardiac anomalies at age 3 years (aHR, 1.78; 95% CI, 1.21-2.60). Conversely, the risk of gestational diabetes (aOR, 0.94; 95% CI, 0.88-1.00; P = 0.041) and small birthweight (aOR, 0.94; 95% CI, 0.88-1.00, P = 0.039) was lower, as was the risk of musculoskeletal-limb anomalies (aHR, 0.63; 95% CI, 0.42-0.97)-a finding that persisted up to age 7. Other health outcomes were largely comparable.
LIMITATIONS, REASONS FOR CAUTION: One limitation of this study is that the data refer to live-born singletons, with stillbirths and medical terminations excluded from the analyses. Despite extensive adjustments, residual confounding cannot be excluded. Findings for specific pathologies/malformations should be interpreted with caution because the number of cases was small in some sub-groups.
WIDER IMPLICATIONS OF THE FINDINGS: In this large and unique study, after adjusting for multiple maternal, paternal, and cycle-related variables, our findings provide some reassurance regarding the safety of prolonged in vitro embryo culture. A moderate risk remained for a few maternal and child health conditions following EEC-warranting further investigation-whereas the risk was notably lower compared to short embryo culture, particularly for musculoskeletal-limb anomalies.
STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the AOI of University Hospital of Dijon. The authors have no competing interests to disclose.
TRIAL REGISTRATION NUMBER: N/A.
Anxiety and depression in women with endometriosis: a comparative study across fertility contexts
Bourdon, Mathilde; Bolac, Laure; Cervantes, Celie; Maignien, Chloé; Aoun-Clavel, Rhea; Reynaud, Marianne; Patrat, Catherine; Chapron, Charles; Santulli, Pietro
In: Fertil Steril, 2025, ISSN: 1556-5653.
@article{pmid41419108,
title = {Anxiety and depression in women with endometriosis: a comparative study across fertility contexts},
author = {Mathilde Bourdon and Laure Bolac and Celie Cervantes and Chloé Maignien and Rhea Aoun-Clavel and Marianne Reynaud and Catherine Patrat and Charles Chapron and Pietro Santulli},
doi = {10.1016/j.fertnstert.2025.12.011},
issn = {1556-5653},
year = {2025},
date = {2025-12-01},
journal = {Fertil Steril},
abstract = {OBJECTIVE: To assess the prevalence of anxiety and depression in women with endometriosis undergoing ovarian stimulation and oocyte retrieval for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) or fertility preservation (FP) compared with women without endometriosis.
DESIGN: Observational cohort study conducted in a university hospital-based research center.
SUBJECTS: Women who underwent ovarian stimulation and oocyte retrieval between November 2023 and May 2024 for IVF/ICSI or nononcological FP. Two populations were analyzed: (i) infertile women undergoing IVF/ICSI as part of a current family-building project, and (ii) women undergoing oocyte vitrification for FP.
EXPOSURE: Participants were classified as endometriosis (exposed) or disease-free (unexposed) based on imaging (transvaginal ultrasound and/or magnetic resonance imaging). All patients completed a 55-item questionnaire, including the validated Hospital Anxiety and Depression Scale (HADS), on the day of oocyte retrieval.
MAIN OUTCOME MEASURES: Prevalence of anxiety and depression, defined as a HADS-A or HADS-D score ≥11.
RESULTS: The study included 324 women: 196 IVF/ICSI patients (73 with endometriosis and 123 controls) and 128 FP patients (38 with endometriosis and 90 controls). Overall, 111/324 (34.3%) had endometriosis. Anxiety prevalence was higher in women with endometriosis in both populations, but did not reach significance. In patients undergoing IVF/ICSI, depression was significantly more frequent in those with endometriosis vs. controls (5.5% vs. 0.8%). In the FP population, women with endometriosis more often reported prior psychological support (21.1% vs. 4.4%) and psychotropic use (13.2% vs. 2.2%). Multivariate analysis identified severe deep dyspareunia as a factor independently associated with anxiety and/or depression (adjusted odds ratio 2.7; 95% confidence interval, 1.1-7.2).
CONCLUSION: Among patients undergoing IVF/ICSI, depression was significantly more prevalent in women with endometriosis, whereas no significant difference was observed in the FP population. These findings underscore the importance of integrating psychological support into assisted reproductive technology management for women with endometriosis, particularly those experiencing severe pain and/or infertility.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: To assess the prevalence of anxiety and depression in women with endometriosis undergoing ovarian stimulation and oocyte retrieval for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) or fertility preservation (FP) compared with women without endometriosis.
DESIGN: Observational cohort study conducted in a university hospital-based research center.
SUBJECTS: Women who underwent ovarian stimulation and oocyte retrieval between November 2023 and May 2024 for IVF/ICSI or nononcological FP. Two populations were analyzed: (i) infertile women undergoing IVF/ICSI as part of a current family-building project, and (ii) women undergoing oocyte vitrification for FP.
EXPOSURE: Participants were classified as endometriosis (exposed) or disease-free (unexposed) based on imaging (transvaginal ultrasound and/or magnetic resonance imaging). All patients completed a 55-item questionnaire, including the validated Hospital Anxiety and Depression Scale (HADS), on the day of oocyte retrieval.
MAIN OUTCOME MEASURES: Prevalence of anxiety and depression, defined as a HADS-A or HADS-D score ≥11.
RESULTS: The study included 324 women: 196 IVF/ICSI patients (73 with endometriosis and 123 controls) and 128 FP patients (38 with endometriosis and 90 controls). Overall, 111/324 (34.3%) had endometriosis. Anxiety prevalence was higher in women with endometriosis in both populations, but did not reach significance. In patients undergoing IVF/ICSI, depression was significantly more frequent in those with endometriosis vs. controls (5.5% vs. 0.8%). In the FP population, women with endometriosis more often reported prior psychological support (21.1% vs. 4.4%) and psychotropic use (13.2% vs. 2.2%). Multivariate analysis identified severe deep dyspareunia as a factor independently associated with anxiety and/or depression (adjusted odds ratio 2.7; 95% confidence interval, 1.1-7.2).
CONCLUSION: Among patients undergoing IVF/ICSI, depression was significantly more prevalent in women with endometriosis, whereas no significant difference was observed in the FP population. These findings underscore the importance of integrating psychological support into assisted reproductive technology management for women with endometriosis, particularly those experiencing severe pain and/or infertility.
DESIGN: Observational cohort study conducted in a university hospital-based research center.
SUBJECTS: Women who underwent ovarian stimulation and oocyte retrieval between November 2023 and May 2024 for IVF/ICSI or nononcological FP. Two populations were analyzed: (i) infertile women undergoing IVF/ICSI as part of a current family-building project, and (ii) women undergoing oocyte vitrification for FP.
EXPOSURE: Participants were classified as endometriosis (exposed) or disease-free (unexposed) based on imaging (transvaginal ultrasound and/or magnetic resonance imaging). All patients completed a 55-item questionnaire, including the validated Hospital Anxiety and Depression Scale (HADS), on the day of oocyte retrieval.
MAIN OUTCOME MEASURES: Prevalence of anxiety and depression, defined as a HADS-A or HADS-D score ≥11.
RESULTS: The study included 324 women: 196 IVF/ICSI patients (73 with endometriosis and 123 controls) and 128 FP patients (38 with endometriosis and 90 controls). Overall, 111/324 (34.3%) had endometriosis. Anxiety prevalence was higher in women with endometriosis in both populations, but did not reach significance. In patients undergoing IVF/ICSI, depression was significantly more frequent in those with endometriosis vs. controls (5.5% vs. 0.8%). In the FP population, women with endometriosis more often reported prior psychological support (21.1% vs. 4.4%) and psychotropic use (13.2% vs. 2.2%). Multivariate analysis identified severe deep dyspareunia as a factor independently associated with anxiety and/or depression (adjusted odds ratio 2.7; 95% confidence interval, 1.1-7.2).
CONCLUSION: Among patients undergoing IVF/ICSI, depression was significantly more prevalent in women with endometriosis, whereas no significant difference was observed in the FP population. These findings underscore the importance of integrating psychological support into assisted reproductive technology management for women with endometriosis, particularly those experiencing severe pain and/or infertility.
Oestradiol and reproductive outcomes in ART: when too much of a good thing hurts
Bourdon, Mathilde; Maignien, Chloé; Ouazana, Marion; Kefelian, Fleur; Marcellin, Louis; Patrat, Catherine; Pocate-Cheriet, Khaled; Chapron, Charles; Santulli, Pietro
In: Reprod Biomed Online, vol. 51, no. 6, pp. 105131, 2025, ISSN: 1472-6491.
@article{pmid41219022,
title = {Oestradiol and reproductive outcomes in ART: when too much of a good thing hurts},
author = {Mathilde Bourdon and Chloé Maignien and Marion Ouazana and Fleur Kefelian and Louis Marcellin and Catherine Patrat and Khaled Pocate-Cheriet and Charles Chapron and Pietro Santulli},
doi = {10.1016/j.rbmo.2025.105131},
issn = {1472-6491},
year = {2025},
date = {2025-12-01},
journal = {Reprod Biomed Online},
volume = {51},
number = {6},
pages = {105131},
abstract = {Oestradiol plays a crucial role in reproduction, particularly in assisted reproductive technology (ART), where it can reach supraphysiological concentrations. These fluctuations occur during ovarian stimulation in fresh embryo transfer cycles and during endometrial preparation for frozen embryo transfer, potentially impacting implantation and perinatal outcomes. Oestradiol influences endometrial proliferation, receptivity, implantation and placentation, with the sensitivity of the endometrium to systemic oestrogen emerging as a key determinant of reproductive success. In fresh embryo transfer cycles, ovarian stimulation induces histological, immunological and genetic changes in the endometrium, correlating with elevated oestradiol concentrations and possibly disrupting implantation. However, this adverse effect appears time-limited, as endometrial receptivity is restored in subsequent cycles. In FET cycles, both the duration and intensity of oestradiol exposure are critical, as excessive or prolonged exposure to exogenous oestradiol may impair reproductive outcomes. Despite these potential effects, strategies to regulate oestradiol concentrations in ART remain underexplored. This review examines the physiological and pathological roles of oestradiol in natural and ART cycles, emphasizing its impact on endometrial function, implantation and pregnancy outcomes. It highlights the need for further research to define optimal oestradiol thresholds and develop personalized ART protocols that consider both oestradiol concentrations and endometrial sensitivity to improve reproductive success and obstetric outcomes. Finally, it highlights strategies aimed at modulating oestradiol exposure to optimize reproductive success.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Oestradiol plays a crucial role in reproduction, particularly in assisted reproductive technology (ART), where it can reach supraphysiological concentrations. These fluctuations occur during ovarian stimulation in fresh embryo transfer cycles and during endometrial preparation for frozen embryo transfer, potentially impacting implantation and perinatal outcomes. Oestradiol influences endometrial proliferation, receptivity, implantation and placentation, with the sensitivity of the endometrium to systemic oestrogen emerging as a key determinant of reproductive success. In fresh embryo transfer cycles, ovarian stimulation induces histological, immunological and genetic changes in the endometrium, correlating with elevated oestradiol concentrations and possibly disrupting implantation. However, this adverse effect appears time-limited, as endometrial receptivity is restored in subsequent cycles. In FET cycles, both the duration and intensity of oestradiol exposure are critical, as excessive or prolonged exposure to exogenous oestradiol may impair reproductive outcomes. Despite these potential effects, strategies to regulate oestradiol concentrations in ART remain underexplored. This review examines the physiological and pathological roles of oestradiol in natural and ART cycles, emphasizing its impact on endometrial function, implantation and pregnancy outcomes. It highlights the need for further research to define optimal oestradiol thresholds and develop personalized ART protocols that consider both oestradiol concentrations and endometrial sensitivity to improve reproductive success and obstetric outcomes. Finally, it highlights strategies aimed at modulating oestradiol exposure to optimize reproductive success.
Microbiota insights in endometriosis
Parpex, Guillaume; Nicco, Carole; Chassaing, Benoît; Santulli, Pietro; Chouzenoux, Sandrine; Bourdon, Mathilde; Maignien, Chloé; Doridot, Ludivine; Batteux, Frédéric; Chapron, Charles; Marcellin, Louis
In: Microbiome, vol. 13, no. 1, pp. 251, 2025, ISSN: 2049-2618.
@article{pmid41345720,
title = {Microbiota insights in endometriosis},
author = {Guillaume Parpex and Carole Nicco and Benoît Chassaing and Pietro Santulli and Sandrine Chouzenoux and Mathilde Bourdon and Chloé Maignien and Ludivine Doridot and Frédéric Batteux and Charles Chapron and Louis Marcellin},
doi = {10.1186/s40168-025-02243-2},
issn = {2049-2618},
year = {2025},
date = {2025-12-01},
journal = {Microbiome},
volume = {13},
number = {1},
pages = {251},
abstract = {Endometriosis affects approximately 10% of women of reproductive age and is characterized by the presence of endometrial-like tissue outside the uterine cavity, leading to chronic pelvic pain, infertility, and a significant reduction in quality of life. Beyond its local manifestations, endometriosis is increasingly recognized as a systemic, immune-mediated condition with multifactorial origins. In this narrative review, we provide an updated and comprehensive overview of the disease, including its pathophysiology, clinical features, and evolving conceptual frameworks. Considering the frequent digestive symptoms observed in affected patients, we summarize key findings from both animal and human studies that investigate alterations in the gut microbiota. We also review the profound immune dysregulation associated with endometriosis and explore its potential bidirectional relationship with the microbiota. Furthermore, we examine recent insights into the endometrial microbiota-an emerging field of interest given its early involvement in the disease process and its strong interconnection with the vaginal microbiome. Lastly, we highlight studies exploring the gynecological microbiota and present an updated discussion of novel therapeutic strategies, including microbiota-targeted approaches that may shape future management of this complex disease. Video Abstract.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Endometriosis affects approximately 10% of women of reproductive age and is characterized by the presence of endometrial-like tissue outside the uterine cavity, leading to chronic pelvic pain, infertility, and a significant reduction in quality of life. Beyond its local manifestations, endometriosis is increasingly recognized as a systemic, immune-mediated condition with multifactorial origins. In this narrative review, we provide an updated and comprehensive overview of the disease, including its pathophysiology, clinical features, and evolving conceptual frameworks. Considering the frequent digestive symptoms observed in affected patients, we summarize key findings from both animal and human studies that investigate alterations in the gut microbiota. We also review the profound immune dysregulation associated with endometriosis and explore its potential bidirectional relationship with the microbiota. Furthermore, we examine recent insights into the endometrial microbiota-an emerging field of interest given its early involvement in the disease process and its strong interconnection with the vaginal microbiome. Lastly, we highlight studies exploring the gynecological microbiota and present an updated discussion of novel therapeutic strategies, including microbiota-targeted approaches that may shape future management of this complex disease. Video Abstract.
Fertility preservation in endometriosis: current strategies and outcomes
Bourdon, Mathilde; Fornelli, Gianfranco; Maignien, Chloé; Parpex, Guillaume; Marcellin, Louis; Melka, Léa; Patrat, Catherine; Chapron, Charles; Santulli, Pietro
In: Minerva Obstet Gynecol, 2025, ISSN: 2724-6450.
@article{pmid41424262,
title = {Fertility preservation in endometriosis: current strategies and outcomes},
author = {Mathilde Bourdon and Gianfranco Fornelli and Chloé Maignien and Guillaume Parpex and Louis Marcellin and Léa Melka and Catherine Patrat and Charles Chapron and Pietro Santulli},
doi = {10.23736/S2724-606X.25.05766-5},
issn = {2724-6450},
year = {2025},
date = {2025-12-01},
journal = {Minerva Obstet Gynecol},
abstract = {Endometriosis is a frequent chronic estrogen-dependent condition that can significantly impair fertility and reduce the quality of life in affected individuals. Women with endometriosis face a 30-50% risk of infertility. Multifactorial factors such as peritoneal inflammation, altered ovarian reserve, impaired tubal function and modified endometrial receptivity have been proposed to contribute to infertility. Endometriosis has been highlighted as a condition that may require a fertility preservation to safeguard reproductive potential. This review aims to provide a comprehensive update on fertility preservation for women with endometriosis. A comprehensive literature search was conducted using PubMed, focusing on peer-reviewed studies. Key words included "endometriosis," "fertility preservation," "oocytes," and "cryopreservation." Studies in English and French that delve into FP techniques, success factors, and risks were included. Several fertility preservation techniques are available, but oocyte cryopreservation following ovarian stimulation is the most common and effective option for women affected by endometriosis. Success rates depend on factors such as age and prior surgical history. Surgery for ovarian endometriomas may reduce ovarian reserve, underscoring the importance of considering fertility preservation before surgery. All of ovarian stimulation protocols can be used and may not increase the risk of disease progression or recurrence however the use of an antagonist protocol with GnRH agonist triggering could be particularly beneficial in this context, as it may help reduce pain and minimize the risk of ovarian hyperstimulation syndrome. The number of cryopreserved oocytes is directly correlated with pregnancy success. Multiple stimulation cycles can be performed to obtain a sufficient number of oocytes, increasing the chances of achieving a successful live birth in case of reuse. FP should be routinely discussed with women with endometriosis, particularly those who may undergo surgery, however, its implementation is not systematic and should be considered on a case-by-case basis. Further research is essential to tailor FP strategies for women with endometriosis optimizing both clinical outcomes and cost-effectiveness.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Endometriosis is a frequent chronic estrogen-dependent condition that can significantly impair fertility and reduce the quality of life in affected individuals. Women with endometriosis face a 30-50% risk of infertility. Multifactorial factors such as peritoneal inflammation, altered ovarian reserve, impaired tubal function and modified endometrial receptivity have been proposed to contribute to infertility. Endometriosis has been highlighted as a condition that may require a fertility preservation to safeguard reproductive potential. This review aims to provide a comprehensive update on fertility preservation for women with endometriosis. A comprehensive literature search was conducted using PubMed, focusing on peer-reviewed studies. Key words included “endometriosis,” “fertility preservation,” “oocytes,” and “cryopreservation.” Studies in English and French that delve into FP techniques, success factors, and risks were included. Several fertility preservation techniques are available, but oocyte cryopreservation following ovarian stimulation is the most common and effective option for women affected by endometriosis. Success rates depend on factors such as age and prior surgical history. Surgery for ovarian endometriomas may reduce ovarian reserve, underscoring the importance of considering fertility preservation before surgery. All of ovarian stimulation protocols can be used and may not increase the risk of disease progression or recurrence however the use of an antagonist protocol with GnRH agonist triggering could be particularly beneficial in this context, as it may help reduce pain and minimize the risk of ovarian hyperstimulation syndrome. The number of cryopreserved oocytes is directly correlated with pregnancy success. Multiple stimulation cycles can be performed to obtain a sufficient number of oocytes, increasing the chances of achieving a successful live birth in case of reuse. FP should be routinely discussed with women with endometriosis, particularly those who may undergo surgery, however, its implementation is not systematic and should be considered on a case-by-case basis. Further research is essential to tailor FP strategies for women with endometriosis optimizing both clinical outcomes and cost-effectiveness.
Agostini, Aubert; Legendre, Guillaume; Margueritte, François; Colas, Anaelle; Lamblin, Gery; Miguet-Bensouda, Chloé; Marcellin, Louis; Parpex, Guillaume; Boujenah, Jérémy; Astruc, Audrey; Bouet, Pierre-Emmanuel; Marret, Henri; Debras, Élodie; Huberlant, Stéphanie; Letouzey, Vincent; Adriamanjay, Dio; Chauvet, Pauline; Jegaden, Margaux; Vigoureux, Solène; Dion, Ludivine; Dabi, Yohann; Capmas, Perrine; Fernandez, Hervé
In: Gynecol Obstet Fertil Senol, 2025, ISSN: 2468-7189.
@article{pmid41183782,
title = {[Therapeutic management of tubal ectopic pregnancies: Clinical practice guidelines of CNGOF and SCGP]},
author = {Aubert Agostini and Guillaume Legendre and François Margueritte and Anaelle Colas and Gery Lamblin and Chloé Miguet-Bensouda and Louis Marcellin and Guillaume Parpex and Jérémy Boujenah and Audrey Astruc and Pierre-Emmanuel Bouet and Henri Marret and Élodie Debras and Stéphanie Huberlant and Vincent Letouzey and Dio Adriamanjay and Pauline Chauvet and Margaux Jegaden and Solène Vigoureux and Ludivine Dion and Yohann Dabi and Perrine Capmas and Hervé Fernandez},
doi = {10.1016/j.gofs.2025.10.023},
issn = {2468-7189},
year = {2025},
date = {2025-11-01},
journal = {Gynecol Obstet Fertil Senol},
abstract = {Ectopic Pregnancy is defined as the presence of a pregnancy or pregnancy residue outside the uterine cavity, with a prevalence of approximately 2%. Tubal ectopic pregnancy is defined as the presence of a pregnancy or pregnancy residue in the extra-myometrial portion of the fallopian tube (isthmus, ampulla, or fimbriae), and accounts for 96 to 99% of ectopic pregnancy locations. Management of tubal ectopic pregnancy should depend on both its activity and whether it is symptomatic or not. Regarding emergency management of tubal ectopic pregnancy, it is recommended not to consider expectant management for patients with symptomatic tubal ectopic pregnancy, nor for patients with active tubal ectopic pregnancy (Strong recommendation, low quality of evidence). It is recommended to offer expectant management as an alternative to medical treatment with MTX (methotrexate) for patients with non-active and asymptomatic tubal ectopic pregnancy (Strong recommendation, low quality of evidence). It is recommended to offer expectant management as an alternative to surgical treatment for patients with non-active and asymptomatic tubal ectopic pregnancy (Strong recommendation, very low quality of evidence). In cases of expectant management of tubal ectopic pregnancy, it is strongly recommended to systematically re-evaluate the patient clinically and biologically at 48hours (Strong recommendation, low quality of evidence). If hCG levels decrease by more than 15% at 48hours, it is recommended to continue monitoring weekly until negativity, provided there are no signs of symptomatic tubal ectopic pregnancy (Strong recommendation, very low quality of evidence). If an expectant approach is chosen, and there is an increase in hCG levels of more than 15% at 48hours or the tubal ectopic pregnancy becomes symptomatic, it is recommended to discontinue expectant management (Strong recommendation, low quality of evidence). Regarding medical treatment of tubal ectopic pregnancy, it is recommended not to favor a multi-dose protocol over a single-dose protocol to increase the success rate of MTX treatment (Strong recommendation, moderate quality of evidence). It is recommended to prefer the single-dose MTX protocol over the multi-dose protocol to limit the risk of adverse effects (Strong recommendation, high quality of evidence). It is also recommended not to systematically combine mifepristone treatment with an MTX injection to improve the efficacy of medical treatment for tubal ectopic pregnancy (Strong recommendation, high quality of evidence). Regarding surgical management, in a patient with tubal ectopic pregnancy, it is recommended to perform either salpingotomy or salpingectomy with regard to fertility (Strong recommendation, high quality of evidence). It is recommended not to perform tubal expression in order to reduce morbidity compared to salpingotomy (Strong recommendation, very low quality of evidence).},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Ectopic Pregnancy is defined as the presence of a pregnancy or pregnancy residue outside the uterine cavity, with a prevalence of approximately 2%. Tubal ectopic pregnancy is defined as the presence of a pregnancy or pregnancy residue in the extra-myometrial portion of the fallopian tube (isthmus, ampulla, or fimbriae), and accounts for 96 to 99% of ectopic pregnancy locations. Management of tubal ectopic pregnancy should depend on both its activity and whether it is symptomatic or not. Regarding emergency management of tubal ectopic pregnancy, it is recommended not to consider expectant management for patients with symptomatic tubal ectopic pregnancy, nor for patients with active tubal ectopic pregnancy (Strong recommendation, low quality of evidence). It is recommended to offer expectant management as an alternative to medical treatment with MTX (methotrexate) for patients with non-active and asymptomatic tubal ectopic pregnancy (Strong recommendation, low quality of evidence). It is recommended to offer expectant management as an alternative to surgical treatment for patients with non-active and asymptomatic tubal ectopic pregnancy (Strong recommendation, very low quality of evidence). In cases of expectant management of tubal ectopic pregnancy, it is strongly recommended to systematically re-evaluate the patient clinically and biologically at 48hours (Strong recommendation, low quality of evidence). If hCG levels decrease by more than 15% at 48hours, it is recommended to continue monitoring weekly until negativity, provided there are no signs of symptomatic tubal ectopic pregnancy (Strong recommendation, very low quality of evidence). If an expectant approach is chosen, and there is an increase in hCG levels of more than 15% at 48hours or the tubal ectopic pregnancy becomes symptomatic, it is recommended to discontinue expectant management (Strong recommendation, low quality of evidence). Regarding medical treatment of tubal ectopic pregnancy, it is recommended not to favor a multi-dose protocol over a single-dose protocol to increase the success rate of MTX treatment (Strong recommendation, moderate quality of evidence). It is recommended to prefer the single-dose MTX protocol over the multi-dose protocol to limit the risk of adverse effects (Strong recommendation, high quality of evidence). It is also recommended not to systematically combine mifepristone treatment with an MTX injection to improve the efficacy of medical treatment for tubal ectopic pregnancy (Strong recommendation, high quality of evidence). Regarding surgical management, in a patient with tubal ectopic pregnancy, it is recommended to perform either salpingotomy or salpingectomy with regard to fertility (Strong recommendation, high quality of evidence). It is recommended not to perform tubal expression in order to reduce morbidity compared to salpingotomy (Strong recommendation, very low quality of evidence).
Chardonnet, Antoine Gaudet; Borghese, Bruno; Alexandre, Jérôme; Richard, Camille; Métairie, Marie; Reilhac, Adele; Kime, Amel; Garinet, Simon; Parfait, Beatrice; Didelot, Audrey; Bourreau, Camille; Mulot, Claire; Abdelli, Justine; de Percin, Sixtine; Durdux, Catherine; Chapron, Charles; Goldwasser, François; Laurent-Puig, Pierre; Taly, Valérie; Beinse, Guillaume
In: Int J Gynecol Cancer, vol. 35, no. 10, pp. 101941, 2025, ISSN: 1525-1438.
@article{pmid40517131,
title = {Identification of a very-high risk subgroup of localized endometrial carcinoma before surgery using circulating tumor DNA: a proof-of-concept study},
author = {Antoine Gaudet Chardonnet and Bruno Borghese and Jérôme Alexandre and Camille Richard and Marie Métairie and Adele Reilhac and Amel Kime and Simon Garinet and Beatrice Parfait and Audrey Didelot and Camille Bourreau and Claire Mulot and Justine Abdelli and Sixtine de Percin and Catherine Durdux and Charles Chapron and François Goldwasser and Pierre Laurent-Puig and Valérie Taly and Guillaume Beinse},
doi = {10.1016/j.ijgc.2025.101941},
issn = {1525-1438},
year = {2025},
date = {2025-10-01},
journal = {Int J Gynecol Cancer},
volume = {35},
number = {10},
pages = {101941},
abstract = {OBJECTIVE: We aimed to study whether the detection of circulating tumor DNA (ctDNA) may predict the risk of early relapse for patients with localized endometrial carcinoma.
METHODS: Patients who underwent surgical resection at Cochin University Hospital (2021-2023) for International Federation of Gynecology and Obstetrics 2018 stage I to III endometrial carcinoma were prospectively included in a prospective biocollection cohort study. All patients had a plasma sample before surgery (EDTA collection tubes, 4-5 mL). After extraction and bisulfite-conversion of cell-free DNA, ctDNA was evaluated using a droplet-digital polymerase chain reaction assay targeting universally-hypermethylated positions in endometrial carcinoma (OXT, ZSCAN12 genes), and defined as significantly detected above the limit of detection. Patients were classified as high-risk based on 2022 European Society for Medical Oncology/European Society of Gynaecological Oncology/European Society of Pathology guidelines, or preoperative features (non-endometrioid histology, p53-abnormal tumors, or stage III). Events of interest were tumor progression or relapse (event-free survival). Adjusted-HR (aHR) was estimated using Cox regression.
RESULTS: Among 128 patients included with median follow-up of 26 months (interquartile range; 15-35), ctDNA was detected in 18 patients (14%). Patients with ctDNA had a 1-year event-free rate of 67% (95% CI [48% to 92%]), vs 91% [82% to 100%] among patients without ctDNA. The ctDNA was detected in 10 (29%) patients among those with preoperative high-risk features (N = 34, 1-year event-free rate = 60% [36%-100%]). ctDNA was associated with event-free survival independently of stage (aHR = 4.26 [1.68-10.8]), 2022 guidelines high-risk (aHR = 3.72 [1.57-8.87]), or preoperative high-risk features (aHR = 3.98 [1.65-9.60]).
CONCLUSIONS: Elevated ctDNA before surgery identifies a very high-risk subgroup of newly diagnosed endometrial carcinoma, suggestive of occult metastasis. Further studies are warranted to validate this finding and investigate the window of opportunity for neoadjuvant approaches.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: We aimed to study whether the detection of circulating tumor DNA (ctDNA) may predict the risk of early relapse for patients with localized endometrial carcinoma.
METHODS: Patients who underwent surgical resection at Cochin University Hospital (2021-2023) for International Federation of Gynecology and Obstetrics 2018 stage I to III endometrial carcinoma were prospectively included in a prospective biocollection cohort study. All patients had a plasma sample before surgery (EDTA collection tubes, 4-5 mL). After extraction and bisulfite-conversion of cell-free DNA, ctDNA was evaluated using a droplet-digital polymerase chain reaction assay targeting universally-hypermethylated positions in endometrial carcinoma (OXT, ZSCAN12 genes), and defined as significantly detected above the limit of detection. Patients were classified as high-risk based on 2022 European Society for Medical Oncology/European Society of Gynaecological Oncology/European Society of Pathology guidelines, or preoperative features (non-endometrioid histology, p53-abnormal tumors, or stage III). Events of interest were tumor progression or relapse (event-free survival). Adjusted-HR (aHR) was estimated using Cox regression.
RESULTS: Among 128 patients included with median follow-up of 26 months (interquartile range; 15-35), ctDNA was detected in 18 patients (14%). Patients with ctDNA had a 1-year event-free rate of 67% (95% CI [48% to 92%]), vs 91% [82% to 100%] among patients without ctDNA. The ctDNA was detected in 10 (29%) patients among those with preoperative high-risk features (N = 34, 1-year event-free rate = 60% [36%-100%]). ctDNA was associated with event-free survival independently of stage (aHR = 4.26 [1.68-10.8]), 2022 guidelines high-risk (aHR = 3.72 [1.57-8.87]), or preoperative high-risk features (aHR = 3.98 [1.65-9.60]).
CONCLUSIONS: Elevated ctDNA before surgery identifies a very high-risk subgroup of newly diagnosed endometrial carcinoma, suggestive of occult metastasis. Further studies are warranted to validate this finding and investigate the window of opportunity for neoadjuvant approaches.
METHODS: Patients who underwent surgical resection at Cochin University Hospital (2021-2023) for International Federation of Gynecology and Obstetrics 2018 stage I to III endometrial carcinoma were prospectively included in a prospective biocollection cohort study. All patients had a plasma sample before surgery (EDTA collection tubes, 4-5 mL). After extraction and bisulfite-conversion of cell-free DNA, ctDNA was evaluated using a droplet-digital polymerase chain reaction assay targeting universally-hypermethylated positions in endometrial carcinoma (OXT, ZSCAN12 genes), and defined as significantly detected above the limit of detection. Patients were classified as high-risk based on 2022 European Society for Medical Oncology/European Society of Gynaecological Oncology/European Society of Pathology guidelines, or preoperative features (non-endometrioid histology, p53-abnormal tumors, or stage III). Events of interest were tumor progression or relapse (event-free survival). Adjusted-HR (aHR) was estimated using Cox regression.
RESULTS: Among 128 patients included with median follow-up of 26 months (interquartile range; 15-35), ctDNA was detected in 18 patients (14%). Patients with ctDNA had a 1-year event-free rate of 67% (95% CI [48% to 92%]), vs 91% [82% to 100%] among patients without ctDNA. The ctDNA was detected in 10 (29%) patients among those with preoperative high-risk features (N = 34, 1-year event-free rate = 60% [36%-100%]). ctDNA was associated with event-free survival independently of stage (aHR = 4.26 [1.68-10.8]), 2022 guidelines high-risk (aHR = 3.72 [1.57-8.87]), or preoperative high-risk features (aHR = 3.98 [1.65-9.60]).
CONCLUSIONS: Elevated ctDNA before surgery identifies a very high-risk subgroup of newly diagnosed endometrial carcinoma, suggestive of occult metastasis. Further studies are warranted to validate this finding and investigate the window of opportunity for neoadjuvant approaches.
Endometriosis and comorbidities: molecular mechanisms and clinical implications
Petraglia, Felice; Vannuccini, Silvia; Donati, Chiara; Jeljeli, Maxime; Bourdon, Mathilde; Chapron, Charles
In: Trends Mol Med, 2025, ISSN: 1471-499X.
@article{pmid41038746,
title = {Endometriosis and comorbidities: molecular mechanisms and clinical implications},
author = {Felice Petraglia and Silvia Vannuccini and Chiara Donati and Maxime Jeljeli and Mathilde Bourdon and Charles Chapron},
doi = {10.1016/j.molmed.2025.09.002},
issn = {1471-499X},
year = {2025},
date = {2025-10-01},
journal = {Trends Mol Med},
abstract = {Endometriosis, traditionally viewed as a gynecological condition, is increasingly recognized as a systemic disease due to its frequent association with inflammatory and autoimmune comorbidities. Recent molecular and genetic insights reveal dysregulated hormone receptor signaling, heightened inflammatory responses, and immune dysfunction as central drivers of disease progression. These discoveries offer compelling explanations for extra-pelvic symptoms and open up avenues for targeted diagnostics and therapies. This review integrates emerging evidence to highlight endometriosis as a multisystem disorder, underscoring the need for multidisciplinary care. By redefining endometriosis beyond reproductive health, this perspective encourages a broader, systemic view of women's health and fosters innovation in precision medicine.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Endometriosis, traditionally viewed as a gynecological condition, is increasingly recognized as a systemic disease due to its frequent association with inflammatory and autoimmune comorbidities. Recent molecular and genetic insights reveal dysregulated hormone receptor signaling, heightened inflammatory responses, and immune dysfunction as central drivers of disease progression. These discoveries offer compelling explanations for extra-pelvic symptoms and open up avenues for targeted diagnostics and therapies. This review integrates emerging evidence to highlight endometriosis as a multisystem disorder, underscoring the need for multidisciplinary care. By redefining endometriosis beyond reproductive health, this perspective encourages a broader, systemic view of women’s health and fosters innovation in precision medicine.
