
Publications
Serum progesterone levels on fresh blastocyst transfer day: a key determinant of live birth rates
Maignien, Chloé; Fornelli, Gianfranco; Bourdon, Mathilde; Melka, Léa; Marcellin, Louis; Laguillier-Morizot, Christelle; Firmin, Julie; Patrat, Catherine; Santulli, Pietro
Dans: Hum Reprod, vol. 40, no. 9, p. 1651–1659, 2025, ISSN: 1460-2350.
@article{pmid40639805,
title = {Serum progesterone levels on fresh blastocyst transfer day: a key determinant of live birth rates},
author = {Chloé Maignien and Gianfranco Fornelli and Mathilde Bourdon and Léa Melka and Louis Marcellin and Christelle Laguillier-Morizot and Julie Firmin and Catherine Patrat and Pietro Santulli},
doi = {10.1093/humrep/deaf138},
issn = {1460-2350},
year = {2025},
date = {2025-09-01},
journal = {Hum Reprod},
volume = {40},
number = {9},
pages = {1651--1659},
abstract = {STUDY QUESTION: Is there an association between mid-luteal serum progesterone (P) levels on the day of fresh embryo transfer (ET) at the blastocyst stage and the live birth rate (LBR)?nnSUMMARY ANSWER: Serum P levels between 46.6 and 72.3 ng/ml on the day of fresh ET are associated with the highest LBR.
WHAT IS KNOWN ALREADY: Luteal phase monitoring is a standard practice in frozen ET cycles to personalize luteal phase support. However, the role of serum P levels in fresh ET cycles remains underexplored and inconsistent, with some studies suggesting a link to outcomes while others show no association.
STUDY DESIGN, SIZE, DURATION: This retrospective, single-center cohort study included all single autologous Day-5 blastocyst fresh ETs performed between June 2020 and March 2023. Serum P levels were measured on the day of ET.
PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 874 patients underwent ovarian stimulation according to standardized protocols, with ovulation triggered by human chorionic gonadotropin. All patients received the same luteal phase support regimen of vaginal micronized P (800 mg/day). Serum P levels were measured on the morning of ET in a single laboratory, with clinicians blinded to the results. Patients were divided into four quartiles based on their serum P levels: Q1 (10.2-46.5 ng/ml), Q2 (46.6-72.3 ng/ml), Q3 (72.4-106.9 ng/ml), and Q4 (107.0-364.8 ng/ml). The primary outcome was the LBR, with secondary outcomes including clinical pregnancy rates, early miscarriage rates, and neonatal outcomes (birth weight and gestational age at delivery). Univariate and multivariate logistic regression analyses were performed to identify factors associated with LBR.
MAIN RESULTS AND THE ROLE OF CHANCE: The median serum P level on ET day for the entire study population was 72.3 ng/ml (range: 46.5-106.9), with a minimum value of 10.2 ng/ml and a maximum value of 364.8 ng/ml. The overall LBR was 29.4% (260/874), ranging from 21.0% in Q1 to 38.1% in Q2, 29.5% in Q3, and 30.3% in Q4. A significant association between serum P levels and LBR was observed, with Q1 showing the lowest LBR and Q2 the highest (P < 0.001). Multivariate logistic regression indicated that serum P levels in Q1, Q3, and Q4 were associated with significantly lower LBRs compared to Q2, with adjusted odds ratios of 0.52 (95% CI: 0.32-0.82, P = 0.005), 0.55 (95% CI: 0.36-0.86, P = 0.010), and 0.54 (95% CI: 0.34-0.85, P = 0.010), respectively. For secondary outcomes, clinical pregnancy rates were significantly lower in Q1 (29.2% vs 44.1%, P < 0.001). Early miscarriage rates were higher in Q3 (38.5%) and Q4 (35.6%) compared to Q2 (12.3%, P < 0.001). Preterm birth was significantly more frequent in Q1 than in Q2 (15.2% vs 3.6%, P = 0.010).
LIMITATIONS, REASONS FOR CAUTION: The study's retrospective design is a key limitation, introducing potential selection and confounding biases, despite efforts to mitigate these using multivariable analysis.
WIDER IMPLICATIONS OF THE FINDINGS: These findings highlight the need for prospective studies to validate the association between serum P levels and pregnancy outcomes in fresh ET cycles. Such studies could explore the benefits of personalizing luteal phase support based on serum P levels, including the potential for enhanced P supplementation in low P cases or a freeze-all approach for those with elevated P levels, to improve LBRs and optimize treatment outcomes.
STUDY FUNDING/COMPETING INTEREST(S): This study received no external funding. The authors have no conflicts of interest to declare.
TRIAL REGISTRATION NUMBER: N/A.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
WHAT IS KNOWN ALREADY: Luteal phase monitoring is a standard practice in frozen ET cycles to personalize luteal phase support. However, the role of serum P levels in fresh ET cycles remains underexplored and inconsistent, with some studies suggesting a link to outcomes while others show no association.
STUDY DESIGN, SIZE, DURATION: This retrospective, single-center cohort study included all single autologous Day-5 blastocyst fresh ETs performed between June 2020 and March 2023. Serum P levels were measured on the day of ET.
PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 874 patients underwent ovarian stimulation according to standardized protocols, with ovulation triggered by human chorionic gonadotropin. All patients received the same luteal phase support regimen of vaginal micronized P (800 mg/day). Serum P levels were measured on the morning of ET in a single laboratory, with clinicians blinded to the results. Patients were divided into four quartiles based on their serum P levels: Q1 (10.2-46.5 ng/ml), Q2 (46.6-72.3 ng/ml), Q3 (72.4-106.9 ng/ml), and Q4 (107.0-364.8 ng/ml). The primary outcome was the LBR, with secondary outcomes including clinical pregnancy rates, early miscarriage rates, and neonatal outcomes (birth weight and gestational age at delivery). Univariate and multivariate logistic regression analyses were performed to identify factors associated with LBR.
MAIN RESULTS AND THE ROLE OF CHANCE: The median serum P level on ET day for the entire study population was 72.3 ng/ml (range: 46.5-106.9), with a minimum value of 10.2 ng/ml and a maximum value of 364.8 ng/ml. The overall LBR was 29.4% (260/874), ranging from 21.0% in Q1 to 38.1% in Q2, 29.5% in Q3, and 30.3% in Q4. A significant association between serum P levels and LBR was observed, with Q1 showing the lowest LBR and Q2 the highest (P < 0.001). Multivariate logistic regression indicated that serum P levels in Q1, Q3, and Q4 were associated with significantly lower LBRs compared to Q2, with adjusted odds ratios of 0.52 (95% CI: 0.32-0.82, P = 0.005), 0.55 (95% CI: 0.36-0.86, P = 0.010), and 0.54 (95% CI: 0.34-0.85, P = 0.010), respectively. For secondary outcomes, clinical pregnancy rates were significantly lower in Q1 (29.2% vs 44.1%, P < 0.001). Early miscarriage rates were higher in Q3 (38.5%) and Q4 (35.6%) compared to Q2 (12.3%, P < 0.001). Preterm birth was significantly more frequent in Q1 than in Q2 (15.2% vs 3.6%, P = 0.010).
LIMITATIONS, REASONS FOR CAUTION: The study’s retrospective design is a key limitation, introducing potential selection and confounding biases, despite efforts to mitigate these using multivariable analysis.
WIDER IMPLICATIONS OF THE FINDINGS: These findings highlight the need for prospective studies to validate the association between serum P levels and pregnancy outcomes in fresh ET cycles. Such studies could explore the benefits of personalizing luteal phase support based on serum P levels, including the potential for enhanced P supplementation in low P cases or a freeze-all approach for those with elevated P levels, to improve LBRs and optimize treatment outcomes.
STUDY FUNDING/COMPETING INTEREST(S): This study received no external funding. The authors have no conflicts of interest to declare.
TRIAL REGISTRATION NUMBER: N/A.
The endocrine aspects of endometriosis
Petraglia, Felice; Vannuccini, Silvia; Dolmans, Marie-Madeleine; Speciale, Anna Rosa; Bourdon, Mathilde; Marcellin, Louis; Donnez, Jacques; Chapron, Charles
Dans: Eur J Endocrinol, vol. 193, no. 4, p. R17–R30, 2025, ISSN: 1479-683X.
@article{pmid40982542,
title = {The endocrine aspects of endometriosis},
author = {Felice Petraglia and Silvia Vannuccini and Marie-Madeleine Dolmans and Anna Rosa Speciale and Mathilde Bourdon and Louis Marcellin and Jacques Donnez and Charles Chapron},
doi = {10.1093/ejendo/lvaf192},
issn = {1479-683X},
year = {2025},
date = {2025-09-01},
journal = {Eur J Endocrinol},
volume = {193},
number = {4},
pages = {R17--R30},
abstract = {Endometriosis is a chronic gynecologic disease of reproductive-age women, causing menstrual pain and infertility. Endocrine and inflammatory mechanisms drive its development, with estrogen/progesterone imbalance contributing to extrauterine implantation and persistence of ectopic endometrial cells. Chronic pain also induces stress-related disorders, worsening the quality of life. Infertility results from inflammatory, ovarian, and endometrial changes, and adverse pregnancy outcomes are reported. Diagnosis of endometriosis is clinical and imaging based. Furthermore, gastrointestinal, urinary, or autoimmune comorbidities complicate endometriosis management. Hormonal treatments, including progestins, estro-progestins, gonadotropin-releasing hormone analogs (GnRH-a), or oral antagonists, suppress menstruation and relieve pain. The relevant endocrine aspects and the systemic comorbidities make endometriosis a syndrome that requires a multidisciplinary diagnostic and therapeutic approach.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Maignien, Chloé; Jobin, Timon; Bourdon, Mathilde; Melka, Léa; Marcellin, Louis; Laguillier-Morizot, Christelle; Chargui, Ahmed; Patrat, Catherine; Chapron, Charles; Santulli, Pietro
Dans: Hum Reprod, vol. 40, no. 5, p. 876–884, 2025, ISSN: 1460-2350.
@article{pmid40052481,
title = {High serum estradiol levels on the day of frozen blastocyst transfer are associated with increased early miscarriage rates in artificial cycles using transdermal estrogens},
author = {Chloé Maignien and Timon Jobin and Mathilde Bourdon and Léa Melka and Louis Marcellin and Christelle Laguillier-Morizot and Ahmed Chargui and Catherine Patrat and Charles Chapron and Pietro Santulli},
doi = {10.1093/humrep/deaf037},
issn = {1460-2350},
year = {2025},
date = {2025-05-01},
journal = {Hum Reprod},
volume = {40},
number = {5},
pages = {876--884},
abstract = {STUDY QUESTION: Do serum estradiol (E2) levels on the day of frozen blastocyst transfer (FBT) affect pregnancy outcomes in hormonal replacement therapy (HRT) cycles using transdermal estrogens?nnSUMMARY ANSWER: E2 levels ≥313 pg/ml on the day of FBT are associated with increased early miscarriage rates (EMRs), but do not significantly impact the live birth rate (LBR).
WHAT IS KNOWN ALREADY: E2 plays a crucial role in endometrial receptivity and placentation. The effect of serum E2 levels measured around the time of FBT in HRT cycles remains debated, with some studies indicating a negative impact of high E2 levels and others finding no significant difference. Currently, no studies focus exclusively on HRT cycles using transdermal estrogens, which are considered safer regarding thromboembolic complications.
STUDY DESIGN, SIZE, DURATION: This retrospective cohort study analyzed 2364 patients undergoing HRT-FBT cycles at a university hospital between January 2019 and December 2022. Each patient was included only once during the study period.
PARTICIPANTS/MATERIALS, SETTING, METHODS: The study involved patients undergoing single autologous FBT under HRT with transdermal estrogens and vaginal micronized progesterone. Serum E2 levels were measured in the morning of the FBT at a single laboratory. Primary outcomes included the LBR, with secondary outcomes encompassing clinical pregnancy rates, EMRs, and neonatal outcomes (birth weight and term of delivery). Patients were categorized into three groups based on E2 levels: <25th centile (<122 pg/ml), between 25th and 75th centile (122-312 pg/ml), and >75th centile (≥313 pg/ml), and analyzed using univariate and multivariate logistic regression models.
MAIN RESULTS AND THE ROLE OF CHANCE: Of the 2364 patients, 590 were in the '<122 pg/ml' group, 1184 in the '122-312 pg/ml' group, and 590 in the '≥313 pg/ml' group. The median (interquartile range) E2 level in the entire study population was 195.3 pg/ml (122.1-312.8). The LBRs across the E2 level groups were 33.7%, 31.6%, and 31.0%. Crude and adjusted odds ratios (ORs) showed no significant differences in LBR between the '<122 pg/ml' and '≥313 pg/ml' groups compared to the '122-312 pg/ml' reference group (adjusted OR 0.9, 95% CI 0.72-1.14 and 0.9, 95% CI 0.69-1.09, respectively). The EMRs for the groups were 25.5%, 24.6%, and 30.3%, respectively. While crude analysis showed no differences between the groups, the multivariable analysis indicated that the '≥313 pg/ml' group had a significantly higher risk of early miscarriage compared to the reference group (adjusted OR 1.5, 95% CI 1.06-2.18). No significant differences were observed in clinical pregnancy rates or neonatal outcomes.
LIMITATIONS, REASONS FOR CAUTION: The primary limitation is the study's retrospective design, which introduces risks of selection and confusion bias, although multivariable analysis was employed to mitigate these issues.
WIDER IMPLICATIONS OF THE FINDINGS: Managing high serum E2 levels on the day of the FBT may enhance ART outcomes. Future research should aim to define optimal E2 thresholds for HRT-FBT cycles and develop personalized treatment protocols that account for individual patient variability.
STUDY FUNDING/COMPETING INTEREST(S): No funding was received. The authors have no conflicts of interest.
TRIAL REGISTRATION NUMBER: N/A.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
WHAT IS KNOWN ALREADY: E2 plays a crucial role in endometrial receptivity and placentation. The effect of serum E2 levels measured around the time of FBT in HRT cycles remains debated, with some studies indicating a negative impact of high E2 levels and others finding no significant difference. Currently, no studies focus exclusively on HRT cycles using transdermal estrogens, which are considered safer regarding thromboembolic complications.
STUDY DESIGN, SIZE, DURATION: This retrospective cohort study analyzed 2364 patients undergoing HRT-FBT cycles at a university hospital between January 2019 and December 2022. Each patient was included only once during the study period.
PARTICIPANTS/MATERIALS, SETTING, METHODS: The study involved patients undergoing single autologous FBT under HRT with transdermal estrogens and vaginal micronized progesterone. Serum E2 levels were measured in the morning of the FBT at a single laboratory. Primary outcomes included the LBR, with secondary outcomes encompassing clinical pregnancy rates, EMRs, and neonatal outcomes (birth weight and term of delivery). Patients were categorized into three groups based on E2 levels: <25th centile (<122 pg/ml), between 25th and 75th centile (122-312 pg/ml), and >75th centile (≥313 pg/ml), and analyzed using univariate and multivariate logistic regression models.
MAIN RESULTS AND THE ROLE OF CHANCE: Of the 2364 patients, 590 were in the ‘<122 pg/ml' group, 1184 in the '122-312 pg/ml' group, and 590 in the '≥313 pg/ml' group. The median (interquartile range) E2 level in the entire study population was 195.3 pg/ml (122.1-312.8). The LBRs across the E2 level groups were 33.7%, 31.6%, and 31.0%. Crude and adjusted odds ratios (ORs) showed no significant differences in LBR between the '<122 pg/ml' and '≥313 pg/ml' groups compared to the '122-312 pg/ml' reference group (adjusted OR 0.9, 95% CI 0.72-1.14 and 0.9, 95% CI 0.69-1.09, respectively). The EMRs for the groups were 25.5%, 24.6%, and 30.3%, respectively. While crude analysis showed no differences between the groups, the multivariable analysis indicated that the '≥313 pg/ml' group had a significantly higher risk of early miscarriage compared to the reference group (adjusted OR 1.5, 95% CI 1.06-2.18). No significant differences were observed in clinical pregnancy rates or neonatal outcomes.
LIMITATIONS, REASONS FOR CAUTION: The primary limitation is the study’s retrospective design, which introduces risks of selection and confusion bias, although multivariable analysis was employed to mitigate these issues.
WIDER IMPLICATIONS OF THE FINDINGS: Managing high serum E2 levels on the day of the FBT may enhance ART outcomes. Future research should aim to define optimal E2 thresholds for HRT-FBT cycles and develop personalized treatment protocols that account for individual patient variability.
STUDY FUNDING/COMPETING INTEREST(S): No funding was received. The authors have no conflicts of interest.
TRIAL REGISTRATION NUMBER: N/A.
Reduced live birth rates following ART in adenomyosis patients: a matched control study
Bourdon, M; Mimouni, A; Maignien, C; Casalechi, M; Vigano, P; Bordonne, C; Millisher, A E; Patrat, C; Marcellin, L; Chapron, C; Santulli, P
Dans: Hum Reprod, vol. 40, no. 5, p. 855–864, 2025, ISSN: 1460-2350.
@article{pmid40159349,
title = {Reduced live birth rates following ART in adenomyosis patients: a matched control study},
author = {M Bourdon and A Mimouni and C Maignien and M Casalechi and P Vigano and C Bordonne and A E Millisher and C Patrat and L Marcellin and C Chapron and P Santulli},
doi = {10.1093/humrep/deaf052},
issn = {1460-2350},
year = {2025},
date = {2025-05-01},
journal = {Hum Reprod},
volume = {40},
number = {5},
pages = {855--864},
abstract = {STUDY QUESTION: How does adenomyosis affect live birth rates (LBRs) in women undergoing ART compared to a matched control population?nnSUMMARY ANSWER: Women with adenomyosis, matched with controls for age, blastocyst count, and top-quality blastocyst count, exhibited reduced LBR following IVF/ICSI treatment.
WHAT IS KNOWN ALREADY: Adenomyosis, a benign uterine disorder, is believed to hinder implantation due to anatomical, hormonal, and immune disruptions. Its precise impact on LBRs following ART, however, remains controversial, with studies presenting inconsistent outcomes. It is uncertain whether adenomyosis directly reduces ART success or if confounding factors such as age or embryo quality play a more significant role.
STUDY DESIGN, SIZE, DURATION: This observational study included women aged 18-42 years undergoing IVF/ICSI treatments with a freeze-all strategy from 1 January 2018 to 31 December 2022, each having at least one available blastocyst for transfer. The adenomyosis group consisted of patients with a confirmed diagnosis through pelvic MRI, interpreted by gynecologic radiologists. The control group included women without adenomyosis, who had idiopathic, tubal, and/or male factor infertility.
PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 285 women with adenomyosis were included. These patients were matched 1:1 with controls based on age, the number of cryopreserved blastocysts, and the number of top-quality blastocysts. The primary outcome was the cumulative LBR per patient following a single oocyte retrieval, with secondary outcomes including clinical pregnancy rate (CPR) and early miscarriage rate (EMR). Both univariate and multivariate analyses were conducted.
MAIN RESULTS AND THE ROLE OF CHANCE: In this study, 285 women with adenomyosis were matched with 285 controls. The mean age was 35.4 ± 3.3 and 35.5 ± 3.4 years, respectively, with an average of 3.5 ± 2.5 and 3.6 ± 2.6 cryopreserved blastocysts and 0.4 ± 0.7 and 0.4 ± 0.5 top-quality blastocysts, respectively. In the adenomyosis group, MRI revealed internal diffuse adenomyosis in 73.7% of patients, adenomyoma in 3.5%, and external adenomyosis lesions in 46.7%. The cumulative LBR was significantly lower in the adenomyosis group compared to controls (41.4% versus 51.9%; odds ratio = 0.65, 95% CI [0.47-0.91]; P = 0.012). Similarly, the CPR was reduced in the adenomyosis group (53.3% versus 63.9%; P = 0.011). No significant difference was found in the EMR. Multivariate analysis, adjusted for confounders such as freeze-all indication, AMH levels, BMI, infertility type, and ART procedure (IVF versus ICSI), identified adenomyosis as an independent risk factor for reduced LBR (OR = 0.7, 95% CI [0.4-0.9]). These findings indicate that adenomyosis is associated with lower ART success rates.
LIMITATIONS, REASONS FOR CAUTION: Patients included in this study were from a specialized referral center focusing on the management of endometriosis and adenomyosis, potentially introducing selection bias, as these women may have more severe forms of adenomyosis.
WIDER IMPLICATIONS OF THE FINDINGS: For infertile women, it is crucial for practitioners to conduct comprehensive clinical and imaging assessments to detect adenomyosis. Continued research is needed to refine and personalize ART management strategies for patients affected by this condition.
STUDY FUNDING/COMPETING INTEREST(S): No external funding was received. P.V. is the co-editor-in-chief of the Journal of Endometriosis and Uterine Disorders. C.M. has received payments to her institution from Merck, Ferring, Theramex, Gedeon Richer, and Besins, as well as direct payments to her from Gedeon Richter and Ferring and honoraria from Merck Serono, Ferring, Besins, IBSA, and Organon and meeting/travel support but no payment from Ferring, Besins, and Gedeon Richter. C.C. has received grants from Merck, Ferring, Theramex, Gedeon Richter, and Besins, which were paid to his institution, and honoraria from Merck, Besins, Gedeon Richter, and Theramex, which he received directly. He has also received support for attending meetings from Besins, Gedeon Richter, and Merck but no payment. He is a founder and past-president of the Society for Endometriosis and Uterine Disorders (SEUD), an unpaid role. P.S. received grants or contracts from Merck, Ferring, Theramex, Gedeon Richter, Besins, paid to his institution, and direct payment to him for presentations and lectures from Merck, Ferring, Besins, Gedeon Richter, Theramex, IBSA, and General Electric Medical Systems. He also received travel support but no payment from Merck, Ferring, Besins, Gedeon Richter, Theramex, and IBSA. P.S. is a board member of the SEUD and an editorial board member of RBMO and GOF. C.P. has received payment for lectures and presentations from Ferring and support but no payment for attending meetings from Ferring. M.B. has received grants from Merck, Ferring, Theramex, Gedeon Richter, and Besins, which were paid to her institution, and direct payment from Merck, Ferring, Gedeon Richter, Theramex, IBSA, and Organon for lectures/presentations. She has also received support but not payment for attending meetings from Ferring and Gedeon Richter.
TRIAL REGISTRATION NUMBER: Not applicable.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
WHAT IS KNOWN ALREADY: Adenomyosis, a benign uterine disorder, is believed to hinder implantation due to anatomical, hormonal, and immune disruptions. Its precise impact on LBRs following ART, however, remains controversial, with studies presenting inconsistent outcomes. It is uncertain whether adenomyosis directly reduces ART success or if confounding factors such as age or embryo quality play a more significant role.
STUDY DESIGN, SIZE, DURATION: This observational study included women aged 18-42 years undergoing IVF/ICSI treatments with a freeze-all strategy from 1 January 2018 to 31 December 2022, each having at least one available blastocyst for transfer. The adenomyosis group consisted of patients with a confirmed diagnosis through pelvic MRI, interpreted by gynecologic radiologists. The control group included women without adenomyosis, who had idiopathic, tubal, and/or male factor infertility.
PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 285 women with adenomyosis were included. These patients were matched 1:1 with controls based on age, the number of cryopreserved blastocysts, and the number of top-quality blastocysts. The primary outcome was the cumulative LBR per patient following a single oocyte retrieval, with secondary outcomes including clinical pregnancy rate (CPR) and early miscarriage rate (EMR). Both univariate and multivariate analyses were conducted.
MAIN RESULTS AND THE ROLE OF CHANCE: In this study, 285 women with adenomyosis were matched with 285 controls. The mean age was 35.4 ± 3.3 and 35.5 ± 3.4 years, respectively, with an average of 3.5 ± 2.5 and 3.6 ± 2.6 cryopreserved blastocysts and 0.4 ± 0.7 and 0.4 ± 0.5 top-quality blastocysts, respectively. In the adenomyosis group, MRI revealed internal diffuse adenomyosis in 73.7% of patients, adenomyoma in 3.5%, and external adenomyosis lesions in 46.7%. The cumulative LBR was significantly lower in the adenomyosis group compared to controls (41.4% versus 51.9%; odds ratio = 0.65, 95% CI [0.47-0.91]; P = 0.012). Similarly, the CPR was reduced in the adenomyosis group (53.3% versus 63.9%; P = 0.011). No significant difference was found in the EMR. Multivariate analysis, adjusted for confounders such as freeze-all indication, AMH levels, BMI, infertility type, and ART procedure (IVF versus ICSI), identified adenomyosis as an independent risk factor for reduced LBR (OR = 0.7, 95% CI [0.4-0.9]). These findings indicate that adenomyosis is associated with lower ART success rates.
LIMITATIONS, REASONS FOR CAUTION: Patients included in this study were from a specialized referral center focusing on the management of endometriosis and adenomyosis, potentially introducing selection bias, as these women may have more severe forms of adenomyosis.
WIDER IMPLICATIONS OF THE FINDINGS: For infertile women, it is crucial for practitioners to conduct comprehensive clinical and imaging assessments to detect adenomyosis. Continued research is needed to refine and personalize ART management strategies for patients affected by this condition.
STUDY FUNDING/COMPETING INTEREST(S): No external funding was received. P.V. is the co-editor-in-chief of the Journal of Endometriosis and Uterine Disorders. C.M. has received payments to her institution from Merck, Ferring, Theramex, Gedeon Richer, and Besins, as well as direct payments to her from Gedeon Richter and Ferring and honoraria from Merck Serono, Ferring, Besins, IBSA, and Organon and meeting/travel support but no payment from Ferring, Besins, and Gedeon Richter. C.C. has received grants from Merck, Ferring, Theramex, Gedeon Richter, and Besins, which were paid to his institution, and honoraria from Merck, Besins, Gedeon Richter, and Theramex, which he received directly. He has also received support for attending meetings from Besins, Gedeon Richter, and Merck but no payment. He is a founder and past-president of the Society for Endometriosis and Uterine Disorders (SEUD), an unpaid role. P.S. received grants or contracts from Merck, Ferring, Theramex, Gedeon Richter, Besins, paid to his institution, and direct payment to him for presentations and lectures from Merck, Ferring, Besins, Gedeon Richter, Theramex, IBSA, and General Electric Medical Systems. He also received travel support but no payment from Merck, Ferring, Besins, Gedeon Richter, Theramex, and IBSA. P.S. is a board member of the SEUD and an editorial board member of RBMO and GOF. C.P. has received payment for lectures and presentations from Ferring and support but no payment for attending meetings from Ferring. M.B. has received grants from Merck, Ferring, Theramex, Gedeon Richter, and Besins, which were paid to her institution, and direct payment from Merck, Ferring, Gedeon Richter, Theramex, IBSA, and Organon for lectures/presentations. She has also received support but not payment for attending meetings from Ferring and Gedeon Richter.
TRIAL REGISTRATION NUMBER: Not applicable.
Characteristics and outcomes in endometrioma infections: a cohort of 94 cases
Parpex, Guillaume; Belan, Martin; Tazi, Asmaa; Campin, Laetitia; Ganancia, Simon; Canouï, Etienne; Bourdon, Mathilde; Chapron, Charles; Marcellin, Louis; Charlier, Caroline
Dans: Fertil Steril, vol. 123, no. 4, p. 724–726, 2025, ISSN: 1556-5653.
@article{pmid39521112,
title = {Characteristics and outcomes in endometrioma infections: a cohort of 94 cases},
author = {Guillaume Parpex and Martin Belan and Asmaa Tazi and Laetitia Campin and Simon Ganancia and Etienne Canouï and Mathilde Bourdon and Charles Chapron and Louis Marcellin and Caroline Charlier},
doi = {10.1016/j.fertnstert.2024.11.002},
issn = {1556-5653},
year = {2025},
date = {2025-04-01},
journal = {Fertil Steril},
volume = {123},
number = {4},
pages = {724--726},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Systematic review on the DNA methylation role in endometriosis: current evidence and perspectives
Ducreux, Bastien; Patrat, Catherine; Firmin, Julie; Ferreux, Lucile; Chapron, Charles; Marcellin, Louis; Parpex, Guillaume; Bourdon, Mathilde; Vaiman, Daniel; Santulli, Pietro; Fauque, Patricia
Dans: Clin Epigenetics, vol. 17, no. 1, p. 32, 2025, ISSN: 1868-7083.
@article{pmid39985111,
title = {Systematic review on the DNA methylation role in endometriosis: current evidence and perspectives},
author = {Bastien Ducreux and Catherine Patrat and Julie Firmin and Lucile Ferreux and Charles Chapron and Louis Marcellin and Guillaume Parpex and Mathilde Bourdon and Daniel Vaiman and Pietro Santulli and Patricia Fauque},
doi = {10.1186/s13148-025-01828-w},
issn = {1868-7083},
year = {2025},
date = {2025-02-01},
journal = {Clin Epigenetics},
volume = {17},
number = {1},
pages = {32},
abstract = {BACKGROUND: Endometriosis appears to have a multilayered etiology, with genetic and epigenetic factors each contributing half of the pathogenesis. The molecular processes that underlie the onset of endometriosis are yet unclear, but it is assumed that an important contributor in the etiopathology of the disease is DNA methylation.
METHODS: We conducted a systematic review of the literature regarding DNA methylation in endometriosis following PRISMA guidelines. Records were obtained from PubMed and Web of Science on May 31, 2024. Original research articles analyzing regional or genome-wide DNA methylation in patients with confirmed endometriosis (by surgery and/or histological examination) were given consideration for inclusion. Only human studies were included, and there were no restrictions on the types of tissue that was analyzed (i.e., endometrium, blood, or fetal tissue). The study selection process was run by two manual reviewers. In parallel, an adapted virtual artificial intelligence-powered reviewer operated study selection and results were compared with the manual reviewers' selection. Studies were divided into targeted (e.g., single gene or region level) and epigenome-wide association studies. For each, we extracted a list of genes studied with precise location of CpGs analyzed and the DNA methylation status according to the groups compared. Quality assessment of studies was performed following the Newcastle-Ottawa scale. Quality of evidence was graded following the Grading of Recommendations Assessment, Development and Evaluation.
RESULTS: A total of 955 studies were screened, and 70 were identified as relevant for systematic review. Our analyses displayed that endometriosis could be polyepigenetic and with alterations in specific genes implicated in major signaling pathways contributing to the disease etiopathology (cell proliferation, differentiation, and division [PI3K-Akt and Wnt-signaling pathway], cell division [MAPK pathway], cell adhesion, cell communication, developmental processes, response to hormone, apoptosis, immunity, neurogenesis, and cancer).
CONCLUSION: Our systematic review indicates that endometriosis is associated with DNA methylation modifications at specific genes involved in key endometrial biological processes, particularly in the ectopic endometrium. As DNA methylation appears to be an integral component of the pathogenesis of endometriosis, the identification of DNA methylation biomarkers would likely help better understand its causes and aggravating factors as well as potentially facilitate its diagnosis and support the development of new therapeutic approaches.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
METHODS: We conducted a systematic review of the literature regarding DNA methylation in endometriosis following PRISMA guidelines. Records were obtained from PubMed and Web of Science on May 31, 2024. Original research articles analyzing regional or genome-wide DNA methylation in patients with confirmed endometriosis (by surgery and/or histological examination) were given consideration for inclusion. Only human studies were included, and there were no restrictions on the types of tissue that was analyzed (i.e., endometrium, blood, or fetal tissue). The study selection process was run by two manual reviewers. In parallel, an adapted virtual artificial intelligence-powered reviewer operated study selection and results were compared with the manual reviewers’ selection. Studies were divided into targeted (e.g., single gene or region level) and epigenome-wide association studies. For each, we extracted a list of genes studied with precise location of CpGs analyzed and the DNA methylation status according to the groups compared. Quality assessment of studies was performed following the Newcastle-Ottawa scale. Quality of evidence was graded following the Grading of Recommendations Assessment, Development and Evaluation.
RESULTS: A total of 955 studies were screened, and 70 were identified as relevant for systematic review. Our analyses displayed that endometriosis could be polyepigenetic and with alterations in specific genes implicated in major signaling pathways contributing to the disease etiopathology (cell proliferation, differentiation, and division [PI3K-Akt and Wnt-signaling pathway], cell division [MAPK pathway], cell adhesion, cell communication, developmental processes, response to hormone, apoptosis, immunity, neurogenesis, and cancer).
CONCLUSION: Our systematic review indicates that endometriosis is associated with DNA methylation modifications at specific genes involved in key endometrial biological processes, particularly in the ectopic endometrium. As DNA methylation appears to be an integral component of the pathogenesis of endometriosis, the identification of DNA methylation biomarkers would likely help better understand its causes and aggravating factors as well as potentially facilitate its diagnosis and support the development of new therapeutic approaches.
Chapron, Charles; Reis, Fernando M; Santulli, Pietro; Marcellin, Louis; Bourdon, Mathilde; Maignien, Chloé; Chapron, Charles
Dans: Gynecol Obstet Invest, vol. 90, no. 5, p. 447–452, 2025, ISSN: 1423-002X.
@article{pmid39978328,
title = {Clinical Characteristics of Women with Surgical Signs of Superficial Peritoneal Endometriosis but a Negative Histology: A Nested Case-Control Study},
author = {Charles Chapron and Fernando M Reis and Pietro Santulli and Louis Marcellin and Mathilde Bourdon and Chloé Maignien and Charles Chapron},
doi = {10.1159/000543910},
issn = {1423-002X},
year = {2025},
date = {2025-01-01},
journal = {Gynecol Obstet Invest},
volume = {90},
number = {5},
pages = {447--452},
abstract = {OBJECTIVES: The aim of this study was to investigate the clinical characteristics of women with superficial peritoneal endometriosis (SUP) diagnosed by surgery and not confirmed by histology, compared with histologically proven SUP.
DESIGN: This was a single-center, nested case-control study. Participants/Materials: Patients with a surgical report of SUP (n = 390), comprising a subgroup with histological confirmation of endometriosis (n = 245) and a subgroup without it (n = 145). In addition, we enrolled a control group (n = 390) among nonpregnant patients submitted to a laparoscopy or laparotomy for a benign gynecologic condition without any macroscopic sign of endometriosis.
SETTING: The review was conducted in the University hospital.
METHODS: Data synthesis, descriptive statistics, chi-square test, and one-way analysis of variance followed by Tukey's test.
RESULTS: All groups had similar age, body mass index, smoking prevalence, serum anti-müllerian hormone levels and menstrual cycle patterns. However, the two SUP subgroups had the same prevalence and intensity of endometriosis symptoms. The SUP/histology-negative subgroup was more likely to have a familial history of endometriosis (14% vs. 1%) or a personal history of primary infertility (29% vs. 19%) or primary dysmenorrhea (50% vs. 33%) compared to the control group (all p <0.01). The intensity scores for dysmenorrhea, deep dyspareunia, and non-cyclic chronic pelvic pain were severer in both SUP subgroups than in the control group (p < 0.05).
LIMITATIONS: The participants underwent surgery, so their symptoms may not represent groups with initial or mild disease that responded to medical treatments. Due to the retrospective design, performance bias cannot be ruled out.
CONCLUSIONS: Patients with suspected SUP lesions and a negative histology had clinical characteristics resembling those with proven endometriosis. Further characterization with molecular biomarkers is needed to explain why these women are so symptomatic in the absence of histological hallmarks of the disease.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
DESIGN: This was a single-center, nested case-control study. Participants/Materials: Patients with a surgical report of SUP (n = 390), comprising a subgroup with histological confirmation of endometriosis (n = 245) and a subgroup without it (n = 145). In addition, we enrolled a control group (n = 390) among nonpregnant patients submitted to a laparoscopy or laparotomy for a benign gynecologic condition without any macroscopic sign of endometriosis.
SETTING: The review was conducted in the University hospital.
METHODS: Data synthesis, descriptive statistics, chi-square test, and one-way analysis of variance followed by Tukey’s test.
RESULTS: All groups had similar age, body mass index, smoking prevalence, serum anti-müllerian hormone levels and menstrual cycle patterns. However, the two SUP subgroups had the same prevalence and intensity of endometriosis symptoms. The SUP/histology-negative subgroup was more likely to have a familial history of endometriosis (14% vs. 1%) or a personal history of primary infertility (29% vs. 19%) or primary dysmenorrhea (50% vs. 33%) compared to the control group (all p <0.01). The intensity scores for dysmenorrhea, deep dyspareunia, and non-cyclic chronic pelvic pain were severer in both SUP subgroups than in the control group (p < 0.05).
LIMITATIONS: The participants underwent surgery, so their symptoms may not represent groups with initial or mild disease that responded to medical treatments. Due to the retrospective design, performance bias cannot be ruled out.
CONCLUSIONS: Patients with suspected SUP lesions and a negative histology had clinical characteristics resembling those with proven endometriosis. Further characterization with molecular biomarkers is needed to explain why these women are so symptomatic in the absence of histological hallmarks of the disease.
Parpex, Guillaume; Chassaing, Benoît; Bourdon, Mathilde; Santulli, Pietro; Doridot, Ludivine; Thomas, Marine; Batteux, Frédéric; Chouzenoux, Sandrine; Chapron, Charles; Nicco, Carole; Marcellin, Louis
Dans: BMC Med, vol. 22, no. 1, p. 513, 2024, ISSN: 1741-7015.
@article{pmid39501247,
title = {Western diet promotes endometriotic lesion growth in mice and induces depletion of Akkermansia muciniphila in intestinal microbiota},
author = {Guillaume Parpex and Benoît Chassaing and Mathilde Bourdon and Pietro Santulli and Ludivine Doridot and Marine Thomas and Frédéric Batteux and Sandrine Chouzenoux and Charles Chapron and Carole Nicco and Louis Marcellin},
doi = {10.1186/s12916-024-03738-9},
issn = {1741-7015},
year = {2024},
date = {2024-11-01},
journal = {BMC Med},
volume = {22},
number = {1},
pages = {513},
abstract = {BACKGROUND: Endometriosis, affecting 10% of women in their reproductive years, remains poorly understood. Both individual and environmental unexplained factors are implicated in this heterogenous condition. This study aims to examine the influence of a Western diet on endometriosis lesion development in mice and to uncover the mechanisms involved.
METHODS: Mice were fed either a control diet or a Western diet (high in fatty acids and low in fiber) for 4 weeks. Endometriosis was then surgically induced, and lesion development was monitored by ultrasound. After 7 weeks, the mice were sacrificed for analysis of lesion characteristics through RT-qPCR, immunohistochemistry, and flow cytometry. Additionally, the intestinal microbiota was assessed using 16S rRNA gene sequencing.
RESULTS: Mice on the Western diet developed lesions that were significantly twice as large compared to those on the control diet. These lesions exhibited greater fibrosis and proliferation, alongside enhanced macrophage activity and leptin pathway expression. Changes in the intestinal microbiota were significantly noted after endometriosis induction, regardless of diet. Notably, mice on the Western diet with the most substantial lesions showed a loss of Akkermansia Muciniphila in their intestinal microbiota.
CONCLUSIONS: A Western diet significantly exacerbates lesion size in a mouse model of endometriosis, accompanied by metabolic and immune alterations. The onset of endometriosis also leads to substantial shifts in intestinal microbiota, suggesting a potential link between diet, intestinal health, and endometriosis development.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
METHODS: Mice were fed either a control diet or a Western diet (high in fatty acids and low in fiber) for 4 weeks. Endometriosis was then surgically induced, and lesion development was monitored by ultrasound. After 7 weeks, the mice were sacrificed for analysis of lesion characteristics through RT-qPCR, immunohistochemistry, and flow cytometry. Additionally, the intestinal microbiota was assessed using 16S rRNA gene sequencing.
RESULTS: Mice on the Western diet developed lesions that were significantly twice as large compared to those on the control diet. These lesions exhibited greater fibrosis and proliferation, alongside enhanced macrophage activity and leptin pathway expression. Changes in the intestinal microbiota were significantly noted after endometriosis induction, regardless of diet. Notably, mice on the Western diet with the most substantial lesions showed a loss of Akkermansia Muciniphila in their intestinal microbiota.
CONCLUSIONS: A Western diet significantly exacerbates lesion size in a mouse model of endometriosis, accompanied by metabolic and immune alterations. The onset of endometriosis also leads to substantial shifts in intestinal microbiota, suggesting a potential link between diet, intestinal health, and endometriosis development.


