Pietro Santulli1, Louis Marcellin2, Sophie Menard3, Thibault Thubert3, Babak Khoshnood4, Vanessa Gayet3, Francois Goffinet5, Pierre-Yves Ancel4, Charles Chapron2. 1. Department of Gynaecology Obstetrics II and Reproductive Medicine, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre, Centre Hospitalier Universitaire (CHU) Cochin, Paris, France Institut Cochin, INSERM U1016, Laboratoire d'immunologie, Université Paris Descartes, Sorbonne Paris Cité, Paris, France Département de 'Génetique, Développement et Cancer', Institut Cochin, Inserm, U1016, Université Paris Descartes, Sorbonne Paris Cité, Paris, France pietro.santulli@cch.aphp.fr pietrosantulli@hotmail.com. 2. Department of Gynaecology Obstetrics II and Reproductive Medicine, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre, Centre Hospitalier Universitaire (CHU) Cochin, Paris, France Institut Cochin, INSERM U1016, Laboratoire d'immunologie, Université Paris Descartes, Sorbonne Paris Cité, Paris, France Département de 'Génetique, Développement et Cancer', Institut Cochin, Inserm, U1016, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 3. Department of Gynaecology Obstetrics II and Reproductive Medicine, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre, Centre Hospitalier Universitaire (CHU) Cochin, Paris, France. 4. INSERM, U_1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center, Obstetrical, Perinatal and Pediatric Epidemiology Team, Maternité Port-Royal, 53 avenue de l'Observatoire, 75014 Paris, France. 5. INSERM, U_1153, Epidemiology and Biostatistics Sorbonne Paris Cité Center, Obstetrical, Perinatal and Pediatric Epidemiology Team, Maternité Port-Royal, 53 avenue de l'Observatoire, 75014 Paris, France Department of Obstetrics and Gynaecology I, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre, Centre Hospitalier Universitaire (CHU) Cochin, Paris, France.
Abstract
STUDY QUESTION: Were spontaneous miscarriages more frequent in women with histologically proven endometriosis when compared with endometriosis-free controls? SUMMARY ANSWER: Endometriosis-affected women display a significantly higher rate of previous spontaneous miscarriages than endometriosis-free controls. WHAT IS KNOWN ALREADY: The association between endometriosis and miscarriages has long been debated without reaching a consensus. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study comparing exposed women (endometriosis) and control (without endometriosis) regarding the incidence of miscarriages. All study participants underwent surgery for benign gynaecological conditions in a tertiary-care university hospital between January 2004 and March 2013. After thorough surgical examination of the abdominopelvic cavity, 870 women with histologically proven endometriosis were allocated to the endometriosis group and 981 unaffected women to the control group. Only previously pregnant women were finally included for the study analysis: 284 women in the endometriosis group and 466 in the control group. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected preoperatively using a structured questionnaire. Among women with at least one pregnancy before the surgery, the type and number of the different previous first trimester pregnancies outcomes were studied. Previous history of miscarriage was studied according to the existence of previous infertility history and the disease severity (revised American Fertility Society and surgical classification). MAIN RESULTS AND THE ROLE OF CHANCE: Four hundred and seventy-eight pregnancies in endometriosis-affected women and 964 pregnancies in controls were analysed. The previous miscarriage rate was significantly higher in women with endometriosis compared with the controls (139/478 [29] versus 187/964 [19%], respectively; ITALIC! P < 0.001). After a subgroup analysis, the miscarriage rates of women with endometriosis and the controls were, respectively: 20 versus 12% ( ITALIC! P = 0.003) among women without a previous history of infertility and 53 versus 30% ( ITALIC! P < 0.001) for women with a previous history of infertility. After using a random-effects Poisson regression and adjusting for confounding factors, we found a significantly increased incidence rate ratio (IRR) for miscarriages in women with endometriosis (adjusted IRR: 1.70, 95% confidence interval: 1.34-2.16). LIMITATIONS, REASONS FOR CAUTION: There is a possible selection bias due to the specificity of the study design which included only surgical patients. In the control group, certain of the surgical gynaecological conditions, such as fibroids, ovarian cysts or tubal pathologies, might be associated with higher spontaneous miscarriage rates. In the endometriosis group, asymptomatic women were less likely to be referred for surgery and might therefore be underrepresented. WIDER IMPLICATIONS OF THE FINDINGS: This study opens the doors to future, more mechanistic studies to establish the exact link between endometriosis and spontaneous miscarriage rates. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. The authors have no conflicts of interest to declare.
STUDY QUESTION: Were spontaneous miscarriages more frequent in women with histologically proven endometriosis when compared with endometriosis-free controls? SUMMARY ANSWER: Endometriosis-affected women display a significantly higher rate of previous spontaneous miscarriages than endometriosis-free controls. WHAT IS KNOWN ALREADY: The association between endometriosis and miscarriages has long been debated without reaching a consensus. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study comparing exposed women (endometriosis) and control (without endometriosis) regarding the incidence of miscarriages. All study participants underwent surgery for benign gynaecological conditions in a tertiary-care university hospital between January 2004 and March 2013. After thorough surgical examination of the abdominopelvic cavity, 870 women with histologically proven endometriosis were allocated to the endometriosis group and 981 unaffected women to the control group. Only previously pregnant women were finally included for the study analysis: 284 women in the endometriosis group and 466 in the control group. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected preoperatively using a structured questionnaire. Among women with at least one pregnancy before the surgery, the type and number of the different previous first trimester pregnancies outcomes were studied. Previous history of miscarriage was studied according to the existence of previous infertility history and the disease severity (revised American Fertility Society and surgical classification). MAIN RESULTS AND THE ROLE OF CHANCE: Four hundred and seventy-eight pregnancies in endometriosis-affected women and 964 pregnancies in controls were analysed. The previous miscarriage rate was significantly higher in women with endometriosis compared with the controls (139/478 [29] versus 187/964 [19%], respectively; ITALIC! P < 0.001). After a subgroup analysis, the miscarriage rates of women with endometriosis and the controls were, respectively: 20 versus 12% ( ITALIC! P = 0.003) among women without a previous history of infertility and 53 versus 30% ( ITALIC! P < 0.001) for women with a previous history of infertility. After using a random-effects Poisson regression and adjusting for confounding factors, we found a significantly increased incidence rate ratio (IRR) for miscarriages in women with endometriosis (adjusted IRR: 1.70, 95% confidence interval: 1.34-2.16). LIMITATIONS, REASONS FOR CAUTION: There is a possible selection bias due to the specificity of the study design which included only surgical patients. In the control group, certain of the surgical gynaecological conditions, such as fibroids, ovarian cysts or tubal pathologies, might be associated with higher spontaneous miscarriage rates. In the endometriosis group, asymptomatic women were less likely to be referred for surgery and might therefore be underrepresented. WIDER IMPLICATIONS OF THE FINDINGS: This study opens the doors to future, more mechanistic studies to establish the exact link between endometriosis and spontaneous miscarriage rates. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. The authors have no conflicts of interest to declare.
Authors: Creighton E Likes; Leah J Cooper; Jessica Efird; David A Forstein; Paul B Miller; Ricardo Savaris; Bruce A Lessey Journal: J Assist Reprod Genet Date: 2019-01-04 Impact factor: 3.412
Authors: Marlene Hager; René Wenzl; Sonja Riesenhuber; Julian Marschalek; Lorenz Kuessel; Daniel Mayrhofer; Robin Ristl; Christine Kurz; Johannes Ott Journal: J Clin Med Date: 2019-08-14 Impact factor: 4.241
Authors: Anne Elodie Millischer; Louis Marcellin; Pietro Santulli; Chloe Maignien; Mathilde Bourdon; Bruno Borghese; François Goffinet; Charles Chapron Journal: PLoS One Date: 2019-10-04 Impact factor: 3.240