Pregnancy outcomes and obstetrical complications of twin pregnancies with endometriosis: A single center cohort study

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However, there was limited evidence of twin pregnancies with endometriosis. The objective of this study was to compare the pregnancy outcomes and obstetrical complications in twin pregnancies with endometriosis or without endometriosis in single institution. Methods: Between January 2011 and July 2022, a cohort of twin pregnancies delivered at single institution was retrospectively analyzed. Patients who underwent surgical treatment before pregnancy and had histological confirmation; had visual or histological confirmation during cesarean section; and those with antenatal ultrasonographic findings of typical ovarian endometriosis and underwent vaginal delivery were included in the endometriosis group. Pregnancy outcomes and obstetrical complications were compared between the two groups. Results: A total of 1,951 patients were examined, of whom 143 (7.3%) were included in the endometriosis group. Maternal body mass index (BMI) was significantly lower in the endometriosis group (p<0.001). However, there were no significant differences in maternal age, mode of conception, and chorionicity. There were also no significant differences in pregnancy outcomes: gestational age at delivery (p=0.619), rate of delivery before 37weeks (p=0.728), and mode of delivery (p=0.698). However, some obstetrical complications showed significantly higher rates in the endometriosis group: placenta previa (p=0.038), small for gestational age <10% (p=0.039), and postpartum hemorrhage (p=0.006). Logistic regression analyses performed after adjusted for BMI showed that patient with endometriosis had a higher risk of developing placenta previa (odds ratios (OR) 2.191; 95% confidence intervals (CI) 1.051-4.568), and postpartum hemorrhage (OR, 2.506; 95% CI, 1.444-4.348). After multivariable analyses, postpartum hemorrhage was significantly higher in patients with endometriosis (OR, 2.264; 95% CI, 1.265-4.054). Conclusions: Twin pregnancies with endometriosis had a significantly higher risk of postpartum hemorrhage. To confirm these outcomes, further large prospective studies are required. Trial registration : retrospectively registered Twin pregnancy endometriosis pregnancy outcome placenta previa small for gestational age postpartum hemorrhage Figures Figure 1 Background Endometriosis, defined as the presence of endometrial tissue outside of the uterus, is a chronic, estrogen-dependent inflammatory disorder ( 1 ). It is a common gynecologic condition that occurs in approximately 10–20% of women of reproductive age ( 2 ) and up to 50% of women with infertility ( 3 ). Pregnancy had beneficial effects on endometriosis due to various pregnancy related metabolic, hormonal, immunologic and angiogenetic changes ( 4 ). However, according to a report by Leeners et al., during pregnancy, 15–50% of lesions disappeared completely, 34-64.7% regressed, 25% remained stable, and 8.8–39% progressed ( 5 ). Additionally, in women with endometriosis, the risk of first trimester miscarriage and ectopic pregnancy were increased ( 4 ), and there was a possible increased risk of obstetrical complications of singleton pregnancies with endometriosis, such as preterm birth, preeclampsia, placenta previa, peripartum hemorrhage, and small for gestational age ( 6 – 10 ). However, limited studies are available on twin pregnancies with endometriosis-related pregnancy outcomes and obstetrical complications. Therefore, this study aimed to compare the pregnancy outcomes and obstetrical complications in twin pregnancies with or without endometriosis at a single institution. Methods Inclusion and exclusion criteria We performed a retrospective review of patients who delivered twins at CHA Gangnam Medical Center between January 2011 and July 2022. Inclusion criteria were as follows: (1) twin deliveries at ≥ 24 weeks of gestational age, (2) initial ≥ triplet pregnancy, which was reduced to twin pregnancy at the time of delivery due to missed abortion or selective abortion of fetus(es) before 14weeks. During antenatal ultrasound examinations, the presence of typical ovarian endometrioma was evaluated. The endometriosis group included patients who underwent surgical treatment before pregnancy and had histological confirmation; visual or histological confirmation during cesarean section; and antenatal ultrasonographic findings that showed typical ovarian endometriosis, for patients who underwent vaginal delivery. Exclusion criteria were as follows: patients with (1) monochorionic monoamniotic twins; (2) previous cervical conization; (3) associated uterine anomalies, such as didelphys, septate, unicornuate, and bicornuate uterus; and (4) unknown chorionicity or mode of pregnancy. All twin pregnancies were managed according to a standardized institutional protocol. During the first trimester, we confirmed the gestational age, chorionicity, and adnexal lesions by using transvaginal ultrasonography. If the patient first visited the clinic after late second trimester and the chorionicity was unclear, we confirmed the chorionicity using pathological examination of the placenta. However, some emergency cases were excluded from the study due to missed placenta pathology. Ethical approval and informed consent for study. The study protocol was approved by the Institutional Review Board (IRB) of CHA Gangnam Medical Center (GCI-2022-11-001). Data were anonymized and de-identified before analysis; therefore, informed consent was not required, and the IRB agreed for the study to be conducted without informed consent from patients. The requirement for informed consent was waived by the IRB of CHA Gangnam Medical Center because of the retrospective nature of the study. All procedures for patients were conducted in accordance with the approved protocol at CHA Gangnam Medical Center. Patient characteristics and clinical definitions The following data were extracted from the patients’ medical records: maternal age at delivery; body mass index (BMI) at delivery; pre-pregnancy history of hypertension or diabetes mellitus; parity; mode of conception; chorionicity; gestational age at delivery; delivery mode; birth weight of newborns; and obstetric complications, such as preterm labor, premature rupture of membranes, preeclampsia, gestational diabetes, placenta previa, incompetent internal os of cervix (IIOC), intrauterine fetal death (IUFD) after the second trimester, small for gestational age (SGA: defined as neonatal birth weight in the <10th percentile for gestational age) (11), placenta abruption, postpartum hemorrhage (estimated blood loss over 500ml during vaginal delivery, and over 1000ml during cesarean delivery), peripartum transfusion, and peripartum intensive care unit admission. The sum of birth weights of twins and weight difference were calculated in patients without IUFD. Statistical analysis Statistical analyses were performed using SPSS 26.00 (IBM, Armonk, NY, USA). Descriptive data are expressed as mean ± standard deviation and median, range. Chi-square and Fisher’s exact tests were used to analyze categorical variables. Quantitative variables were compared using the Mann-Whitney U test according to the Shapiro-Wilk test for normal distribution. Logistic regression was used to calculate the odds ratio (OR), presented with 95% confidence intervals (CI), to evaluate the association between endometriosis and pregnancy outcomes and obstetrical complications, before and after adjustment for BMI. Variables with a p-value < 0.05, identified using univariable analysis, were subjected to multiple logistic regression. A p-value of < 0.05 was considered statistically significant. Results A total of 1,951 twin pregnancies met the inclusion criteria (Figure 1), and the endometriosis group comprised 143 (7.3%) patients. Baseline characteristics of patients with or without endometriosis were compared in Table 1. Maternal BMI was significantly lower in the endometriosis group (p<0.001). However, there were no significant differences in maternal age, pre-pregnancy medical history, parity, mode of conception, and chorionicity. Pregnancy outcomes and obstetric complications are compared in Table 2. There were no significant differences in pregnancy outcomes: gestational age at delivery (p=0.619), rate of delivery before 37weeks (p=0.728), and mode of delivery (p=0.698). However, some obstetrical complications showed significantly higher rates in the endometriosis group: placenta previa (p=0.038), SGA <10% (p=0.039), and postpartum hemorrhage (p=0.006). Table 3 shows the results of the univariable logistic regression analyses: placenta previa (crude OR, 2.314; 95% CI, 1.115-4.802; p=0.024), SGA (crude OR, 1.610; 95% CI, 1.035-2.505; p=0.035), and postpartum hemorrhage (crude OR, 2.257; 95% CI, 1.309-3.889; p=0.003) were higher in endometriosis group. After adjusting for BMI, patients with endometriosis had a higher risk of developing placenta previa (OR, 2.191; 95% CI, 1.051-4.568), and postpartum hemorrhage (OR, 2.506; 95% CI, 1.444-4.348). After multivariable analyses, postpartum hemorrhage was significantly higher in patients with endometriosis (OR, 2.264; 95% CI, 1.265-4.054) (Table 4). Discussion Compared with singleton pregnancy, twin pregnancies are widely known to significantly increase the risk of pre-eclampsia, preterm labor, placenta previa, and postpartum hemorrhage. Therefore, twin pregnancy alone was considered a confounding factor for the analysis of pregnancy outcomes in endometriosis and resulted in limited data for twin pregnancy outcomes with endometriosis. Our study, which was the largest cohort study of twin pregnancies with endometriosis, suggested that the endometriosis was related to adverse effects, such as postpartum hemorrhage; however, there was no relationship with preterm birth, preeclampsia, placenta previa, and SGA. There were several possible mechanisms for preterm delivery in endometriosis. Increased levels of prostaglandins and cytokines, indicating the presence of inflammatory markers, have been found in peritoneal fluid (12). Significantly increased levels of prostaglandin E 2 , cyclooxygenase 2, and various cytokines have been found in endometriotic tissue than in normal endometrium (13). These increased inflammatory markers may stimulate myometrial contractions and cervical ripening, leading to preterm labor. The eutopic endometrium in the patients with endometriosis also showed aberrant expression of integrins and HOX-genes, which may affect endometrial receptivity and subsequent placentation (13, 14). The junctional zone also showed abnormal molecular and functional levels, such as progesterone resistance, which lead to impairment of endometrial growth, maturation and decidualization, conversion of the uterine spiral arteries into uteroplacental vessels, and deep placentation (15-17). Abnormal placentation may cause increased risks of antepartum hemorrhage and placental complications. Moreover, the normal frequency and amplitude of uterine contractions are altered in women with endometriosis, this uterine dysperistalsis changes embryo transportation and implantation and increases the risk of placenta previa (18, 19). In vitro fertilization procedures due to endometriosis-related infertility are also related to the risk of placenta previa in singleton pregnancy (20). Defective artery remodeling is related to preeclampsia, preterm labor, and SGA (15, 16). However, in our study, there were no statistical differences in the rate of preterm labor and preeclampsia in patients with or without endometriosis. It is well known that endometriosis is a hormone responsive disease, and an anti-estrogenic environment suppresses disease progression. Therefore, the possibility of elevated levels of steroid hormones in twin pregnancies overcomes the negative effect of endometriosis in preterm labor and preeclampsia. In our study, patients with twin pregnancy with endometriosis had a lower BMI than those without endometriosis, which correlated with a study by Stepahnsson et al. on singleton pregnancy with endometriosis (21). In a crude univariable analysis, placenta previa, SGA, and postpartum hemorrhage were significant obstetrical complications in twin pregnancies with endometriosis. Due to a lower BMI related to SGA, SGA was excluded as obstetrical complications in twin pregnancies with endometriosis, after adjusting for BMI. Endometriosis increased the risk of postpartum hemorrhage in this study, which may have resulted from the stretching and tearing of endometriosis related adhesions during delivery. Additionally, decidualized endometriosis tissue in the pelvic cavity is usually friable and showed easy touch bleeding. A major strength of our study was the inclusion of a large cohort of twin patients. Furthermore, this study was the first comparative study on twin pregnancy with or without endometriosis. However, this study had some limitations. First, the diverse characteristics of endometriosis, including location, stage, and cyst size (in cases of ovarian endometriosis) were not compared. Due to the small sample size of twin pregnancies with endometriosis, the definitive conclusion of obstetric outcomes in twin pregnancy with endometriosis was difficult to determine. Second, the data were collected retrospectively, an inherent bias was present. Patients with a history of gynecologic surgery, such as myomectomy or ovarian cystectomy, had a possibility of combined pelvic endometriosis. However, the exact surgical findings were not identified in all patients, which may have resulted in selection bias. Third, we did not evaluate the first trimester pregnancy loss rates. Many clinicians and patients have been interested in the possibility of implantation failure and early pregnancy loss in the first trimester with endometriosis. However, this data retrospectively obtained from the twin delivery registry of our hospital; therefore, accurate data related to early pregnancy loss could not be obtained. Additionally, twin pregnancy alone had a higher risk of early pregnancy loss than singleton pregnancies. Future, prospective study can overcome these limitations of the important issue. Conclusions Overall, our study suggests that endometriosis was related to significantly higher risks of postpartum hemorrhage in patients with twin pregnancy. Endometriosis alone was related to infertility; therefore, the possibility of requiring assisted reproductive technology (ART) and subsequent increase of twin pregnancies was increased. Our data can be used to provide adequate intrapartum management plans of twin pregnancies with endometriosis. Additional large-scaled multicenter studies may be required to confirm our results. Abbreviations IRB : Institutional Review Board BMI : body mass index IIOC : incompetent internal os of cervix IUFD : intrauterine fetal death SGA : small for gestational age OR : odds ratio CI : confidence intervals ART : assisted reproductive technology Declarations Conflict of interest: The authors report no conflict of interest. Financial Disclosure: none Acknowledgements We would like to thank Statisticspanda for responsible for statistical analysis (https://blog.naver.com/dltpwns85) Authors’ contributions JSS and SJK were involved in the data collection or management, data analysis, manuscript writing/editing. JYC, KH were involved in the data collection or management, manuscript editing. SS and YWJ were involved in the statistical analysis. SJS and HSJ were involved in the protocol/project development and manuscript editing. MLK was designed study protocol/project development, supervised manuscript writing and editing. All authors contributed to the interpretation, commented on multiple versions, and approved the final manuscript. Funding No specific funding obtained. Availability of data and materials Data will be available upon reasonable request from the corresponding author. However, the data cannot be made public to maintain women’s privacy and legal reasons as it contains private health information along with identifiers. Ethics approval and consent to participate The study protocol was approved by the Institutional Review Board on the CHA Gangnam Medical Center (GCI-2022-11-0001). Data were anonymized and deidentified before analysis, and therefore, informed consent was not required and IRB agreed to conduct the study without informed consent from the patients. The requirement for informed consent was waived by the IRB of CHA Gangnam Medical Center because of the retrospective nature of the study. All procedures for patients were conducted in accordance with the approved protocol at CHA Gangnam Medical Center. Consent for publication Not applicable Competing interests The all authors did not report any potential conflicts of interest. References Giudice LC. Clinical practice. Endometriosis. N Engl J Med. 2010;362:2389–98. Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am. 1997;24:235–58. Meuleman C, Vandenabeel B, Fieuws S, Spiessens C, Timmerman D, D’Hooghe T. High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Fertil Steril. 2009;92:68–74. Leone Roberti Maggiore U, Ferrero S, Mangili G, Bergamini A, Inversetti A, Giorgione V, et al. A systematic review on endometriosis during pregnancy: diagnosis, misdiagnosis, complicaitons and outcomes. Hum Reprod Update. 2016;22:70–103. Leeners B, Damaso F, Ochsenbein-Kolble N, et al. The effect of pregnancy on endometriosis-facts or fiction? 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Assisted reproductive technology and the risk of pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies: a metaanalysis of cohort studies. Fertil Steril. 2016;105:73–85.e1. Stephansson O, Kieler H, Granath F, Falconer H. Endometriosis, assisted reproduction technology, and risk of adverse pregnancy outcome. Hum Reprod. 2009;24:2341–7. Tables Table 1. Patient’s characteristics between with or without endometriosis groups in twin pregnancy With endometriosis group (n=143) Without endometriosis group (n=1808) P value Maternal age (year) a BMI at delivery (kg/m 2 ) a Medical history, n(%) Prepregnancy HTN b Prepregnancy Diabetes b Primiparity b Mode of conception c Natural or TI, COH+TI IUI or COH+IUI IVF or T-ET Chorionicity b MCDA DCDA 35.1±2.9 (35, 30-43) 26.2±2.8 (25.7,20.4-36.9) 1 (0.7%) 0 (0%) 126 (88.1%) 12 (8.4%) 8 (5.6%) 123 (86.0%) 12 (8.4%) 131 (91.6%) 34.6±3.3 (35, 19-48) 27.2±3.3 (26.8, 18.0-41.0) 15 (0.8%) 10 (0.6%) 1556 (86.1%) 260 (14.4%) 129 (7.1%) 1419 (78.5%) 161 (8.9%) 1647 (91.1%) 0.123 <0.001 1.000 1.000 0.614 0.09 1.000 a Mann-Whitney U test, b Fisher’s exact test, c Chi-square test BMI=body mass index; HTN=hypertension; TI=timed intercourse; COH=controlled ovarian hyperstimulation; IUI=intrauterine insemination; IVF=in vitro fertilization; T-ET=thawing-embryo transfer; MCDA=monochorionic diamniotic; DCDA=dichorionic diamniotic Table 2. Pregnancy outcomes and obstetric complications With endometriosis Group (n=143) Without endometriosis Group (n=1808) P value GA at delivery (weeks) a Delivery mode b NSVD Cesarean section Sum of birth weight of twin (except IUFD case) a Weight difference of twin (except IUFD case) a Delivery <37weeks b GA at delivery c Full term 34~<37weeks 2 nd trimester IUFD b SGA (<10%) b (excluded IUFD case) Placenta abruption b Placenta accreta b Postpartum hemorrhage b Peripartum transfusion b Postpartum ICU care b 36.3±1.7 (36.9, 29.7-39) 6 (4.2%) 137 (95.8%) 4796.9±734.7(4850, 2530-6780) (n=141) 290.6±245.0(260, 0-1370) (n=141) 78 (54.5%) 65 (45.5%) 63 (44.0%) 15 (10.5%) 56 (39.2%) 16 (11.2%) 11 (7.7%) 16 (11.2%) 9 (6.3%) 6 (4.2%) 2 (1.4%) 27 (19.1%) (n=141) 1 (0.7%) 3 (2.1%) 17 (11.9%) 19 (13.3%) 13 (9.1%) 36.2±1.9 (36.9, 24.4-39.7) 98 (5.4%) 1710 (94.6%) 4857.4±791.0(4960, 1280-6920) (n=1778) 287.8±229.4(240, 0-1390) (n=1778) 957 (52.9%) 851 (47.1%) 776 (42.9%) 181 (10.0%) 763 (42.2%) 285 (15.8%) 116 (6.4%) 174 (9.6%) 51 (2.8%) 202 (11.2%) 30 (1.7%) 228 (12.8%) (n=1778) 10(0.6%) 64 (3.5%) 102 (5.6%) 177 (9.8%) 184 (10.2%) 0.619 0.698 0.113 0.900 0.728 0.931 0.538 0.185 0.097 0.557 0.038 0.091 1.000 0.039 0.568 0.478 0.006 0.192 0.774 a Mann-Whitney U test, b Fisher’s exact test, c Chi-square test GA=gestational age; IUFD=intrauterine fetal death; d/t=due to; PPROM=preterm premature rupture of membranes; IIOC=incompetent internal os of cervix; SGA=small for gestational age; ICU=intensive care unit Table 3. Crude and adjusted ORs for obstetrical complication of twin pregnancies associated endometriosis Univariable analysis Adjusted for BMI Crude OR (95% CI) p-value Adjusted OR (95% CI) p-value PIH 1.183 (0.687-2.036) 0.544 1.345 (0.776-2.331) 0.291 GDM 0.534 (0.268-1.065) 0.075 0.557 (0.279-1.113) 0.098 Placenta previa 2.314 (1.115-4.802) 0.024 2.191 (1.051-4.568) 0.036 IIOC 0.971 (0.416-2.269) 0.946 0.897 (0.382-2.104) 0.802 Preterm labor 0.882 (0.622-1.249) 0.478 0.783 (0.548-1.118) 0.178 Premature rupture of membranes 0.673 (0.394-1.150) 0.147 0.625 (0.365-1.071) 0.087 >2 nd trimester IUFD 0.841 (0.199-3.554) 0.813 0.806 (0.190-3.420) 0.770 Preterm delivery 0.937 (0.666-1.319) 0.710 1.008 (0.714-1.425) 0.962 NSVD vs C/S 1.309 (0.564-3.039) 0.532 1.394 (0.599-3.244) 0.441 SGA 1.610 (1.035-2.505) 0.035 1.509 (0.967-2.355) 0.070 Postpartum hemorrhage 2.257 (1.309-3.889) 0.003 2.506 (1.444-4.348) 0.001 Placenta abruption 1.266 (0.161-9.962) 0.823 0.869 (0.110-6.871) 0.894 Perioperative transfusion 1.412 (0.850-2.345) 0.183 0.680 (0.408-1.132) 0.138 Placenta accreta 1.713 (0.531-5.521) 0.368 1.718 (0.532-5.551) 0.366 Postpartum ICU care 0.883 (0.489-1.592) 0.678 0.946 (0.523-1.712) 0.855 OR=odd ratio; CI=confidence interval; BMI=body mass index; PIH=preeclampsia; GDM=gestational diabetes mellitus; IIOC=incompetent internal os of cervix; IUFD=intrauterine fetal death; NSVD=normal spontaneous vaginal birth; vs=versus; C/S=cesarean section; SGA=small for gestational age; ICU=intensive care unit Table 4 . Multivariable analysis after adjusted for BMI for obstetrical complication of twin pregnancies associated endometriosis Univariable analysis after adjusted for BMI Multivariable analysis after adjusted for BMI Adjusted OR (95% CI) p-value Adjusted OR (95% CI) p-value Placenta previa 2.191 (1.051-4.568) 0.036 1.614 (0.738-3.531) 0.231 Postpartum hemorrhage 2.506 (1.444-4.348) 0.001 2.264 (1.265-4.054) 0.006 OR=odd ratio; CI=confidence interval; BMI=body mass index Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 01 Jan, 2024 Read the published version in Yonsei Medical Journal → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2376445","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":162903463,"identity":"85487672-fa6e-45e0-aabb-e3fffbf58de3","order_by":0,"name":"Joong Sik Shin","email":"","orcid":"","institution":"CHA Gangnam Medical Center, CHA University","correspondingAuthor":false,"prefix":"","firstName":"Joong","middleName":"Sik","lastName":"Shin","suffix":""},{"id":162903466,"identity":"ff0a8b93-d056-4a56-9e82-88d41f48558f","order_by":1,"name":"Sujin Kim","email":"","orcid":"","institution":"Dong-A University Hospital, Dong-A University 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University","correspondingAuthor":false,"prefix":"","firstName":"Hye","middleName":"Sun","lastName":"Jun","suffix":""},{"id":162903484,"identity":"e5eb5b6c-7dc8-43e0-9c2b-3d1978c72454","order_by":8,"name":"Mi-La Kim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAArklEQVRIiWNgGAWjYDACZuYG5j8VNiRpYWxg4DmTRpI1QC28LYdJ0KDbztj4QbLhfB7/jORjHxhqbKIJajE7zNgsYbjjdrHEjbTkGQzH0nIbiNDSIJF45nZiw5kzxkBHHiZKS/OPg23nEuefOf+ZaC1tko1tBxI3HO9hJl6LNcOZ5MSNx9uMGRKI8sv5w4dvM1TYJc47zPyY4UONDWEtqCCBNOWjYBSMglEwCnABADqWQjyL0fbWAAAAAElFTkSuQmCC","orcid":"","institution":"CHA Gangnam Medical Center, CHA University","correspondingAuthor":true,"prefix":"","firstName":"Mi-La","middleName":"","lastName":"Kim","suffix":""}],"badges":[],"createdAt":"2022-12-14 06:29:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2376445/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2376445/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.3349/ymj.2023.0099","type":"published","date":"2024-01-01T07:09:28+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":31030170,"identity":"3d19ce0a-36cd-45f4-b585-3ca4ce24ba55","added_by":"auto","created_at":"2023-01-03 15:00:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":150640,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of patient selection process\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-2376445/v1/b922568ddd3f802379b25aa8.png"},{"id":56761817,"identity":"dace1304-8a91-4dae-8716-e60ce8b10425","added_by":"auto","created_at":"2024-05-20 07:09:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":762227,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2376445/v1/1d746db3-9b5f-4086-976b-0686794e1e02.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pregnancy outcomes and obstetrical complications of twin pregnancies with endometriosis: A single center cohort study","fulltext":[{"header":"Background","content":"\u003cp\u003eEndometriosis, defined as the presence of endometrial tissue outside of the uterus, is a chronic, estrogen-dependent inflammatory disorder (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It is a common gynecologic condition that occurs in approximately 10\u0026ndash;20% of women of reproductive age (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) and up to 50% of women with infertility (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Pregnancy had beneficial effects on endometriosis due to various pregnancy related metabolic, hormonal, immunologic and angiogenetic changes (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). However, according to a report by Leeners et al., during pregnancy, 15\u0026ndash;50% of lesions disappeared completely, 34-64.7% regressed, 25% remained stable, and 8.8\u0026ndash;39% progressed (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Additionally, in women with endometriosis, the risk of first trimester miscarriage and ectopic pregnancy were increased (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e), and there was a possible increased risk of obstetrical complications of singleton pregnancies with endometriosis, such as preterm birth, preeclampsia, placenta previa, peripartum hemorrhage, and small for gestational age (\u003cspan additionalcitationids=\"CR7 CR8 CR9\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). However, limited studies are available on twin pregnancies with endometriosis-related pregnancy outcomes and obstetrical complications. Therefore, this study aimed to compare the pregnancy outcomes and obstetrical complications in twin pregnancies with or without endometriosis at a single institution.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eInclusion and exclusion criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe performed a retrospective review of patients who delivered twins at CHA Gangnam Medical Center between January 2011 and July 2022. Inclusion criteria were as follows: (1) twin deliveries at\u0026nbsp;\u0026ge;\u0026nbsp;24 weeks of gestational age, (2) initial\u0026nbsp;\u0026ge;\u0026nbsp;triplet pregnancy, which was reduced to twin pregnancy at the time of delivery due to missed abortion or selective abortion of fetus(es) before 14weeks. During antenatal ultrasound examinations, the presence of typical ovarian endometrioma was evaluated. The endometriosis group included patients who underwent surgical treatment before pregnancy and had histological confirmation; visual or histological confirmation during cesarean section; and antenatal ultrasonographic findings that showed typical ovarian endometriosis, for patients who underwent vaginal delivery. Exclusion criteria were as follows: patients with (1) monochorionic monoamniotic twins; (2) previous cervical conization; (3) associated uterine anomalies, such as didelphys, septate, unicornuate, and bicornuate uterus; and (4) unknown chorionicity or mode of pregnancy. All twin pregnancies were managed according to a standardized institutional protocol. During the first trimester, we confirmed the gestational age, chorionicity, and adnexal lesions by using transvaginal ultrasonography. If the patient first visited the clinic after late second trimester and the chorionicity was unclear, we confirmed the chorionicity using pathological examination of the placenta. However, some emergency cases were excluded from the study due to missed placenta pathology.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and informed consent for study.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the Institutional Review Board (IRB) of CHA Gangnam Medical Center (GCI-2022-11-001). Data were anonymized and de-identified before analysis; therefore, informed consent was not required, and the IRB agreed for the study to be conducted without informed consent from patients.\u0026nbsp;The requirement for informed consent was waived by the IRB of CHA Gangnam Medical Center because of the retrospective nature of the study. All procedures for patients were conducted in accordance with the approved protocol at CHA Gangnam Medical Center.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient characteristics and clinical definitions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe following data were extracted from the patients\u0026rsquo; medical records: maternal age at delivery; body mass index (BMI) at delivery; pre-pregnancy history of hypertension or diabetes mellitus; parity; mode of conception; chorionicity; gestational age at delivery; delivery mode; birth weight of newborns; and obstetric complications, such as preterm labor, premature rupture of membranes, preeclampsia, gestational diabetes, placenta previa, incompetent internal os of cervix (IIOC), intrauterine fetal death (IUFD) after the second trimester, small for gestational age (SGA: defined as neonatal birth weight in the \u0026lt;10th percentile for gestational age) (11), placenta abruption, postpartum hemorrhage (estimated blood loss over 500ml during vaginal delivery, and over 1000ml during cesarean delivery), peripartum transfusion, and peripartum intensive care unit admission. The sum of birth weights of twins and weight difference were calculated in patients without IUFD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using SPSS 26.00 (IBM, Armonk, NY, USA). Descriptive data are expressed as mean \u0026plusmn; standard deviation and median, range. Chi-square and Fisher\u0026rsquo;s exact tests were used to analyze categorical variables. Quantitative variables were compared using the Mann-Whitney U test according to the Shapiro-Wilk test for normal distribution. Logistic regression was used to calculate the odds ratio (OR), presented with 95% confidence intervals (CI), to evaluate the association between endometriosis and pregnancy outcomes and obstetrical complications, before and after adjustment for BMI. Variables with a p-value \u0026lt; 0.05, identified using univariable analysis, were subjected to multiple logistic regression. A p-value of \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u0026nbsp;A total of 1,951 twin pregnancies met the inclusion criteria (Figure 1), and the endometriosis group comprised 143 (7.3%) patients.\u003c/p\u003e\n\u003cp\u003eBaseline characteristics of patients with or without endometriosis were compared in Table 1. Maternal BMI was significantly lower in the endometriosis group (p\u0026lt;0.001). However, there were no significant differences in maternal age, pre-pregnancy medical history, parity, mode of conception, and chorionicity.\u003c/p\u003e\n\u003cp\u003ePregnancy outcomes and obstetric complications are compared in Table 2. There were no significant differences in pregnancy outcomes: gestational age at delivery (p=0.619), rate of delivery before 37weeks (p=0.728), and mode of delivery (p=0.698). However, some obstetrical complications showed significantly higher rates in the endometriosis group: placenta previa (p=0.038), SGA \u0026lt;10% (p=0.039), and postpartum hemorrhage (p=0.006).\u003c/p\u003e\n\u003cp\u003eTable 3 shows the results of the univariable logistic regression analyses: placenta previa (crude OR, 2.314; 95% CI, 1.115-4.802; p=0.024), SGA (crude OR, 1.610; 95% CI, 1.035-2.505; p=0.035), and postpartum hemorrhage (crude OR, 2.257; 95% CI, 1.309-3.889; p=0.003) were higher in endometriosis group. After adjusting for BMI,\u0026nbsp;patients with endometriosis had\u0026nbsp;a higher risk of developing placenta previa (OR, 2.191; 95% CI, 1.051-4.568), and postpartum hemorrhage (OR, 2.506; 95% CI, 1.444-4.348).\u003c/p\u003e\n\u003cp\u003eAfter multivariable analyses, postpartum hemorrhage was significantly higher in patients with endometriosis (OR, 2.264; 95% CI, 1.265-4.054) (Table 4).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCompared with singleton pregnancy, twin pregnancies are widely known to significantly increase the risk of pre-eclampsia, preterm labor, placenta previa, and postpartum hemorrhage. Therefore, twin pregnancy alone was considered a confounding factor for the analysis of pregnancy outcomes in endometriosis and resulted in limited data for twin pregnancy outcomes with endometriosis. Our study, which was the largest cohort study of twin pregnancies with endometriosis, suggested that the endometriosis was related to adverse effects, such as postpartum hemorrhage; however, there was no relationship with preterm birth, preeclampsia, placenta previa, and SGA.\u003c/p\u003e\n\u003cp\u003eThere were several possible mechanisms for preterm delivery in endometriosis. Increased levels of prostaglandins and cytokines, indicating the presence of inflammatory markers, have been found in peritoneal fluid (12). Significantly increased levels of prostaglandin E\u003csub\u003e2\u003c/sub\u003e, cyclooxygenase 2, and various cytokines have been found in endometriotic tissue than in normal endometrium (13). These increased inflammatory markers may stimulate myometrial contractions and cervical ripening, leading to preterm labor.\u003c/p\u003e\n\u003cp\u003eThe eutopic endometrium in the patients with endometriosis also showed aberrant expression of integrins and HOX-genes, which may affect endometrial receptivity and subsequent placentation (13, 14). The junctional zone also showed abnormal molecular and functional levels, such as progesterone resistance, which lead to impairment of endometrial growth, maturation and decidualization, conversion of the uterine spiral arteries into uteroplacental vessels, and deep placentation (15-17). Abnormal placentation may cause increased risks of antepartum hemorrhage and placental complications. Moreover, the normal frequency and amplitude of uterine contractions are altered in women with endometriosis, this uterine dysperistalsis changes embryo transportation and implantation and increases the risk of placenta previa (18, 19). In vitro fertilization procedures due to endometriosis-related infertility are also related to the risk of placenta previa in singleton pregnancy (20). Defective artery remodeling is related to preeclampsia, preterm labor, and SGA (15, 16).\u003c/p\u003e\n\u003cp\u003eHowever, in our study, there were no statistical differences in the rate of preterm labor and preeclampsia in patients with or without endometriosis. It is well known that endometriosis is a hormone responsive disease, and an anti-estrogenic environment suppresses disease progression. Therefore, the possibility of elevated levels of steroid hormones in twin pregnancies overcomes the negative effect of endometriosis in preterm labor and preeclampsia.\u003c/p\u003e\n\u003cp\u003eIn our study, patients with twin pregnancy with endometriosis had a lower BMI than those without endometriosis, which correlated with a study by Stepahnsson et al. on singleton pregnancy with endometriosis (21). In a crude univariable analysis, placenta previa, SGA, and postpartum hemorrhage were significant obstetrical complications in twin pregnancies with endometriosis. Due to a lower BMI related to SGA, SGA was excluded as obstetrical complications in twin pregnancies with endometriosis, after adjusting for BMI.\u003c/p\u003e\n\u003cp\u003eEndometriosis increased the risk of postpartum hemorrhage in this study, which may have resulted from the stretching and tearing of endometriosis related adhesions during delivery. Additionally, decidualized endometriosis tissue in the pelvic cavity is usually friable and showed easy touch bleeding.\u003c/p\u003e\n\u003cp\u003eA major strength of our study was the inclusion of a large cohort of twin patients. Furthermore, this study was the first comparative study on twin pregnancy with or without endometriosis. However, this study had some limitations. First, the diverse characteristics of endometriosis, including location, stage, and cyst size (in cases of ovarian endometriosis) were not compared. Due to the small sample size of twin pregnancies with endometriosis, the definitive conclusion of obstetric outcomes in twin pregnancy with endometriosis was difficult to determine. Second, the data were collected retrospectively, an inherent bias was present. Patients with a history of gynecologic surgery, such as myomectomy or ovarian cystectomy, had a possibility of combined pelvic endometriosis. However, the exact surgical findings were not identified in all patients, which may have resulted in selection bias. Third, we did not evaluate the first trimester pregnancy loss rates. Many clinicians and patients have been interested in the possibility of implantation failure and early pregnancy loss in the first trimester with endometriosis. However, this data retrospectively obtained from the twin delivery registry of our hospital; therefore, accurate data related to early pregnancy loss could not be obtained. Additionally, twin pregnancy alone had a higher risk of early pregnancy loss than singleton pregnancies. Future, prospective study can overcome these limitations of the important issue.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOverall, our study suggests that endometriosis was related to significantly higher risks of postpartum hemorrhage in patients with twin pregnancy. Endometriosis alone was related to infertility; therefore, the possibility of requiring assisted reproductive technology (ART) and subsequent increase of twin pregnancies was increased. Our data can be used to provide adequate intrapartum management plans of twin pregnancies with endometriosis. Additional large-scaled multicenter studies may be required to confirm our results.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eIRB : Institutional Review Board\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBMI : body mass index\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIIOC : incompetent internal os of cervix\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIUFD : intrauterine fetal death\u003c/p\u003e\n\u003cp\u003eSGA : small for gestational age\u003c/p\u003e\n\u003cp\u003eOR : odds ratio\u003c/p\u003e\n\u003cp\u003eCI : confidence intervals\u003c/p\u003e\n\u003cp\u003eART : assisted reproductive technology\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest:\u0026nbsp;\u003c/strong\u003eThe authors report no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial Disclosure:\u0026nbsp;\u003c/strong\u003enone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Statisticspanda for responsible for statistical analysis (https://blog.naver.com/dltpwns85)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJSS and SJK were involved in the data collection or management, data analysis, manuscript writing/editing. JYC, KH were involved in the data collection or management, manuscript editing. SS and YWJ were involved in the statistical analysis. SJS and HSJ were involved in the protocol/project development and manuscript editing. MLK was designed study protocol/project development, supervised manuscript writing and editing. All authors contributed to the interpretation, commented on multiple versions, and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo specific funding obtained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData will be available upon reasonable request from the corresponding author. However, the data cannot be made public to maintain women’s privacy and legal reasons as it contains private health information along with identifiers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the Institutional Review Board on the CHA Gangnam Medical Center (GCI-2022-11-0001). Data were anonymized and deidentified before analysis, and therefore, informed consent was not required and IRB agreed to conduct the study without informed consent from the patients.\u0026nbsp;The requirement for informed consent was waived by the IRB of CHA Gangnam Medical Center because of the retrospective nature of the study. All procedures for patients were conducted in accordance with the approved protocol at CHA Gangnam Medical Center.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe all authors did not report any potential conflicts of interest.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eGiudice LC. Clinical practice. Endometriosis. N Engl J Med. 2010;362:2389\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eEskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am. 1997;24:235\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eMeuleman C, Vandenabeel B, Fieuws S, Spiessens C, Timmerman D, D\u0026rsquo;Hooghe T. High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Fertil Steril. 2009;92:68\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLeone Roberti Maggiore U, Ferrero S, Mangili G, Bergamini A, Inversetti A, Giorgione V, et al. A systematic review on endometriosis during pregnancy: diagnosis, misdiagnosis, complicaitons and outcomes. Hum Reprod Update. 2016;22:70\u0026ndash;103.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLeeners B, Damaso F, Ochsenbein-Kolble N, et al. The effect of pregnancy on endometriosis-facts or fiction? Hum Reprod Update. 2018;24:290\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003ePerez-Lopez FR, Villagrasa-Boli P, Munoz-Olarte M, Morera-Grau A, Cruz-Andres P, Hernandez AV. Association between endometriosis and preterm birth in women with spontaneous conception or using assisted reproductive technology: a systematic review and meta-analysis of cohort studies. Reprod Sci. 2018;25:311\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eHorton J, Sterrenburg M, Lane S, Maheshwari A, Li TC, Cheong Y. Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis. Hum Reprod Update. 2019;25:592\u0026ndash;632.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eKim SG, Seo HG, Kim YS. Primiparous singleton women with endometriosis have an increased risk of preterm birth: Meta-analyses. Obstet Gynecol Sci. 2017;60:283\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBerlac JF, Hartwell D, Skovlund CW, Langhoff-Roos J, Lidegaard O. Endometriosis increases the risk of obstetrical and neonatal complicaitons. Acta Obstet Gynecol Scand. 2017;96:751\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLalani S, Choudhry AJ, Firth B, Bacal V, Walker M, Wen SW, et al. Endometriosis and adverse maternal, fetal and neonatal outcomes, a systematic review and meta-analysis. Hum Reprod. 2018;33:1854\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAnanth CV, Vintzileos AM, Shen-Schwarz S, Smulian JC, Lai YL. Standards of birth weight in twin gestations stratified by placental chorionicity. Obstet Gynecol. 1998; 91;917 \u0026ndash; 24.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003ePizzo A, Salmeri FM, Ardita FV, Sofo V, Tripepi M, Marsico S. Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis. Gynecol Obstet Invest. 2002;54:82\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eZanatta A, Pereira RM, Rocha AM, Cogliati B, Baracat EC, Taylor HS, et al. 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Am J Obstet Gynecol. 2011;204:193\u0026ndash;201.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eFarella M, Chanavaz-Lacheray I, Verspick E, Merlot B, Klapczynski C, Hennetier C, et al. Pregnancy outcomes in women with history of surgery for endometriosis. Fertil Steril. 2020;113:996\u0026ndash;1004.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eKunz G, Beil D, Huppert P, Leyendecker G. Structural abnormalities of the uterine wall in women with endometriosis and infertility visualized by vaginal sonography and magnetic resonance imaging. Hum Reprod. 2000;15:76\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eAguilar HN, Mitchell BP. Physiological pathways and molecular mechanisms regulating uterine contractility. Hum Reprod Update. 2010;16:725\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eQin J, Liu X, Sheng X, Wang H, Gao S. Assisted reproductive technology and the risk of pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies: a metaanalysis of cohort studies. Fertil Steril. 2016;105:73\u0026ndash;85.e1.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eStephansson O, Kieler H, Granath F, Falconer H. Endometriosis, assisted reproduction technology, and risk of adverse pregnancy outcome. Hum Reprod. 2009;24:2341\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Patient\u0026rsquo;s characteristics between with or without endometriosis groups in twin pregnancy\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"593\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.342327150084316%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.17369308600337%\"\u003e\n \u003cp\u003eWith endometriosis\u003c/p\u003e\n \u003cp\u003egroup (n=143)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.354131534569984%\"\u003e\n \u003cp\u003eWithout endometriosis\u003c/p\u003e\n \u003cp\u003egroup (n=1808)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.129848229342327%\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.342327150084316%\"\u003e\n \u003cp\u003eMaternal age (year)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eBMI at delivery (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eMedical history, n(%)\u003c/p\u003e\n \u003cp\u003ePrepregnancy HTN\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003ePrepregnancy Diabetes\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003ePrimiparity\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eMode of conception\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eNatural or TI, COH+TI\u003c/p\u003e\n \u003cp\u003eIUI or COH+IUI\u003c/p\u003e\n \u003cp\u003eIVF or T-ET\u003c/p\u003e\n \u003cp\u003eChorionicity\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eMCDA\u003c/p\u003e\n \u003cp\u003eDCDA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.17369308600337%\"\u003e\n \u003cp\u003e35.1\u0026plusmn;2.9 (35, 30-43)\u003c/p\u003e\n \u003cp\u003e26.2\u0026plusmn;2.8 (25.7,20.4-36.9)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (0.7%)\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003cp\u003e126 (88.1%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12 (8.4%)\u003c/p\u003e\n \u003cp\u003e8 (5.6%)\u003c/p\u003e\n \u003cp\u003e123 (86.0%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12 (8.4%)\u003c/p\u003e\n \u003cp\u003e131 (91.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.354131534569984%\"\u003e\n \u003cp\u003e34.6\u0026plusmn;3.3 (35, 19-48)\u003c/p\u003e\n \u003cp\u003e27.2\u0026plusmn;3.3 (26.8, 18.0-41.0)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15 (0.8%)\u003c/p\u003e\n \u003cp\u003e10 (0.6%)\u003c/p\u003e\n \u003cp\u003e1556 (86.1%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e260 (14.4%)\u003c/p\u003e\n \u003cp\u003e129 (7.1%)\u003c/p\u003e\n \u003cp\u003e1419 (78.5%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e161 (8.9%)\u003c/p\u003e\n \u003cp\u003e1647 (91.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.129848229342327%\"\u003e\n \u003cp\u003e0.123\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003cp\u003e0.614\u003c/p\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003eMann-Whitney U test, \u003csup\u003eb\u003c/sup\u003e Fisher\u0026rsquo;s exact test, \u003csup\u003ec\u003c/sup\u003e Chi-square test\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBMI=body mass index; HTN=hypertension; TI=timed intercourse; COH=controlled ovarian hyperstimulation; IUI=intrauterine insemination; IVF=in vitro fertilization; T-ET=thawing-embryo transfer; MCDA=monochorionic diamniotic; DCDA=dichorionic diamniotic\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Pregnancy outcomes and obstetric complications\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.3953488372093%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.239202657807308%\"\u003e\n \u003cp\u003eWith endometriosis\u003c/p\u003e\n \u003cp\u003eGroup (n=143)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.069767441860463%\"\u003e\n \u003cp\u003eWithout endometriosis Group (n=1808)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.295681063122924%\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.3953488372093%\"\u003e\n \u003cp\u003eGA at delivery (weeks)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eDelivery mode\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eNSVD\u003c/p\u003e\n \u003cp\u003eCesarean section\u003c/p\u003e\n \u003cp\u003eSum of birth weight of twin\u003c/p\u003e\n \u003cp\u003e(except IUFD case)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eWeight difference of twin\u003c/p\u003e\n \u003cp\u003e(except IUFD case)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eDelivery \u0026lt;37weeks\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eGA at delivery \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eFull term\u003c/p\u003e\n \u003cp\u003e34~\u0026lt;37weeks\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt;34weeks\u003c/p\u003e\n \u003cp\u003ePreterm labor\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003ePROM\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003ePre-eclampsia\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eGestational diabetes\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003ePlacenta previa\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eIIOC\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u0026gt;2\u003csup\u003end\u003c/sup\u003e trimester IUFD\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eSGA (\u0026lt;10%)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e(excluded IUFD case)\u003c/p\u003e\n \u003cp\u003ePlacenta abruption\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003ePlacenta accreta\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003ePostpartum hemorrhage\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003ePeripartum transfusion\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003ePostpartum ICU care\u003csup\u003eb\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.239202657807308%\"\u003e\n \u003cp\u003e36.3\u0026plusmn;1.7 (36.9, 29.7-39)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (4.2%)\u003c/p\u003e\n \u003cp\u003e137 (95.8%)\u003c/p\u003e\n \u003cp\u003e4796.9\u0026plusmn;734.7(4850, 2530-6780) (n=141)\u003c/p\u003e\n \u003cp\u003e290.6\u0026plusmn;245.0(260,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0-1370) (n=141)\u003c/p\u003e\n \u003cp\u003e78 (54.5%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e65 (45.5%)\u003c/p\u003e\n \u003cp\u003e63 (44.0%)\u003c/p\u003e\n \u003cp\u003e15 (10.5%)\u003c/p\u003e\n \u003cp\u003e56 (39.2%)\u003c/p\u003e\n \u003cp\u003e16 (11.2%)\u003c/p\u003e\n \u003cp\u003e11 (7.7%)\u003c/p\u003e\n \u003cp\u003e16 (11.2%)\u003c/p\u003e\n \u003cp\u003e9 (6.3%)\u003c/p\u003e\n \u003cp\u003e6 (4.2%)\u003c/p\u003e\n \u003cp\u003e2 (1.4%)\u003c/p\u003e\n \u003cp\u003e27 (19.1%)\u003c/p\u003e\n \u003cp\u003e(n=141)\u003c/p\u003e\n \u003cp\u003e1 (0.7%)\u003c/p\u003e\n \u003cp\u003e3 (2.1%)\u003c/p\u003e\n \u003cp\u003e17 (11.9%)\u003c/p\u003e\n \u003cp\u003e19 (13.3%)\u003c/p\u003e\n \u003cp\u003e13 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.069767441860463%\"\u003e\n \u003cp\u003e36.2\u0026plusmn;1.9 (36.9, 24.4-39.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e98 (5.4%)\u003c/p\u003e\n \u003cp\u003e1710 (94.6%)\u003c/p\u003e\n \u003cp\u003e4857.4\u0026plusmn;791.0(4960, 1280-6920) (n=1778)\u003c/p\u003e\n \u003cp\u003e287.8\u0026plusmn;229.4(240,\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0-1390) (n=1778)\u003c/p\u003e\n \u003cp\u003e957 (52.9%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e851 (47.1%)\u003c/p\u003e\n \u003cp\u003e776 (42.9%)\u003c/p\u003e\n \u003cp\u003e181 (10.0%)\u003c/p\u003e\n \u003cp\u003e763 (42.2%)\u003c/p\u003e\n \u003cp\u003e285 (15.8%)\u003c/p\u003e\n \u003cp\u003e116 (6.4%)\u003c/p\u003e\n \u003cp\u003e174 (9.6%)\u003c/p\u003e\n \u003cp\u003e51 (2.8%)\u003c/p\u003e\n \u003cp\u003e202 (11.2%)\u003c/p\u003e\n \u003cp\u003e30 (1.7%)\u003c/p\u003e\n \u003cp\u003e228 (12.8%)\u003c/p\u003e\n \u003cp\u003e(n=1778)\u003c/p\u003e\n \u003cp\u003e10(0.6%)\u003c/p\u003e\n \u003cp\u003e64 (3.5%)\u003c/p\u003e\n \u003cp\u003e102 (5.6%)\u003c/p\u003e\n \u003cp\u003e177 (9.8%)\u003c/p\u003e\n \u003cp\u003e184 (10.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.295681063122924%\"\u003e\n \u003cp\u003e0.619\u003c/p\u003e\n \u003cp\u003e0.698\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.113\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.900\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.728\u003c/p\u003e\n \u003cp\u003e0.931\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.538\u003c/p\u003e\n \u003cp\u003e0.185\u003c/p\u003e\n \u003cp\u003e0.097\u003c/p\u003e\n \u003cp\u003e0.557\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.038\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0.091\u003c/p\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.039\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.568\u003c/p\u003e\n \u003cp\u003e0.478\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e0.192\u003c/p\u003e\n \u003cp\u003e0.774\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003eMann-Whitney U test, \u003csup\u003eb\u003c/sup\u003e Fisher\u0026rsquo;s exact test, \u003csup\u003ec\u003c/sup\u003e Chi-square test\u003c/p\u003e\n\u003cp\u003eGA=gestational age; IUFD=intrauterine fetal death; d/t=due to; PPROM=preterm premature rupture of membranes; IIOC=incompetent internal os of cervix; SGA=small for gestational age; ICU=intensive care unit\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eCrude and adjusted ORs for\u0026nbsp;obstetrical complication of twin pregnancies associated endometriosis\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"661\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariable analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"34.24242424242424%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted for BMI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.87878787878788%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCrude OR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10%\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.696969696969695%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted OR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.545454545454545%\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003ePIH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.87878787878788%\"\u003e\n \u003cp\u003e1.183 (0.687-2.036)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10%\"\u003e\n \u003cp\u003e0.544\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.696969696969695%\"\u003e\n \u003cp\u003e1.345 (0.776-2.331)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.545454545454545%\"\u003e\n \u003cp\u003e0.291\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003eGDM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.87878787878788%\"\u003e\n \u003cp\u003e0.534 (0.268-1.065)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10%\"\u003e\n \u003cp\u003e0.075\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.696969696969695%\"\u003e\n \u003cp\u003e0.557 (0.279-1.113)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.545454545454545%\"\u003e\n \u003cp\u003e0.098\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003ePlacenta previa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.87878787878788%\"\u003e\n \u003cp\u003e2.314 (1.115-4.802)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10%\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.696969696969695%\"\u003e\n \u003cp\u003e2.191 (1.051-4.568)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.545454545454545%\"\u003e\n \u003cp\u003e0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003eIIOC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.87878787878788%\"\u003e\n \u003cp\u003e0.971 (0.416-2.269)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10%\"\u003e\n \u003cp\u003e0.946\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.696969696969695%\"\u003e\n \u003cp\u003e0.897 (0.382-2.104)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.545454545454545%\"\u003e\n \u003cp\u003e0.802\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003ePreterm labor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.87878787878788%\"\u003e\n \u003cp\u003e0.882 (0.622-1.249)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10%\"\u003e\n \u003cp\u003e0.478\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.696969696969695%\"\u003e\n \u003cp\u003e0.783 (0.548-1.118)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.545454545454545%\"\u003e\n \u003cp\u003e0.178\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003ePremature rupture of membranes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.87878787878788%\"\u003e\n \u003cp\u003e0.673 (0.394-1.150)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10%\"\u003e\n \u003cp\u003e0.147\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.696969696969695%\"\u003e\n \u003cp\u003e0.625 (0.365-1.071)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.545454545454545%\"\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003e\u0026gt;2\u003csup\u003end\u003c/sup\u003e trimester IUFD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.87878787878788%\"\u003e\n \u003cp\u003e0.841 (0.199-3.554)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10%\"\u003e\n \u003cp\u003e0.813\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.696969696969695%\"\u003e\n \u003cp\u003e0.806 (0.190-3.420)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.545454545454545%\"\u003e\n \u003cp\u003e0.770\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003ePreterm delivery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.87878787878788%\"\u003e\n \u003cp\u003e0.937 (0.666-1.319)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10%\"\u003e\n \u003cp\u003e0.710\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.696969696969695%\"\u003e\n \u003cp\u003e1.008 (0.714-1.425)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.545454545454545%\"\u003e\n \u003cp\u003e0.962\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003eNSVD vs C/S\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.87878787878788%\"\u003e\n \u003cp\u003e1.309 (0.564-3.039)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10%\"\u003e\n \u003cp\u003e0.532\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.696969696969695%\"\u003e\n \u003cp\u003e1.394 (0.599-3.244)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.545454545454545%\"\u003e\n \u003cp\u003e0.441\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003eSGA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.87878787878788%\"\u003e\n \u003cp\u003e1.610 (1.035-2.505)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10%\"\u003e\n \u003cp\u003e0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.696969696969695%\"\u003e\n \u003cp\u003e1.509 (0.967-2.355)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.545454545454545%\"\u003e\n \u003cp\u003e0.070\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003ePostpartum hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.87878787878788%\"\u003e\n \u003cp\u003e2.257 (1.309-3.889)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10%\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.696969696969695%\"\u003e\n \u003cp\u003e2.506 (1.444-4.348)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.545454545454545%\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003ePlacenta abruption\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.87878787878788%\"\u003e\n \u003cp\u003e1.266 (0.161-9.962)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10%\"\u003e\n \u003cp\u003e0.823\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.696969696969695%\"\u003e\n \u003cp\u003e0.869 (0.110-6.871)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.545454545454545%\"\u003e\n \u003cp\u003e0.894\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003ePerioperative transfusion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.87878787878788%\"\u003e\n \u003cp\u003e1.412 (0.850-2.345)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10%\"\u003e\n \u003cp\u003e0.183\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.696969696969695%\"\u003e\n \u003cp\u003e0.680 (0.408-1.132)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.545454545454545%\"\u003e\n \u003cp\u003e0.138\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003ePlacenta accreta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.87878787878788%\"\u003e\n \u003cp\u003e1.713 (0.531-5.521)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10%\"\u003e\n \u003cp\u003e0.368\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.696969696969695%\"\u003e\n \u003cp\u003e1.718 (0.532-5.551)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.545454545454545%\"\u003e\n \u003cp\u003e0.366\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"32.878787878787875%\"\u003e\n \u003cp\u003ePostpartum ICU care\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"22.87878787878788%\"\u003e\n \u003cp\u003e0.883 (0.489-1.592)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10%\"\u003e\n \u003cp\u003e0.678\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.696969696969695%\"\u003e\n \u003cp\u003e0.946 (0.523-1.712)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.545454545454545%\"\u003e\n \u003cp\u003e0.855\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eOR=odd ratio; CI=confidence interval; BMI=body mass index; PIH=preeclampsia; GDM=gestational diabetes mellitus; IIOC=incompetent internal os of cervix; IUFD=intrauterine fetal death; NSVD=normal spontaneous vaginal birth; vs=versus; C/S=cesarean section; SGA=small for gestational age; ICU=intensive care unit\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u003c/strong\u003e. Multivariable analysis after adjusted for BMI for\u0026nbsp;obstetrical complication of twin pregnancies associated endometriosis\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.602564102564102%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"35.8974358974359%\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariable analysis after adjusted for BMI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"37.5%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariable analysis after adjusted for BMI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.64526484751204%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.52166934189406%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted OR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.43338683788122%\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.96629213483146%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted OR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.43338683788122%\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.64526484751204%\"\u003e\n \u003cp\u003ePlacenta previa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.52166934189406%\"\u003e\n \u003cp\u003e2.191 (1.051-4.568)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.43338683788122%\"\u003e\n \u003cp\u003e0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.96629213483146%\"\u003e\n \u003cp\u003e1.614 (0.738-3.531)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.43338683788122%\"\u003e\n \u003cp\u003e0.231\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.64526484751204%\"\u003e\n \u003cp\u003ePostpartum hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.52166934189406%\"\u003e\n \u003cp\u003e2.506 (1.444-4.348)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.43338683788122%\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.96629213483146%\"\u003e\n \u003cp\u003e2.264 (1.265-4.054)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.43338683788122%\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003eOR=odd ratio; CI=confidence interval; BMI=body mass index\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Twin pregnancy, endometriosis, pregnancy outcome, placenta previa, small for gestational age, postpartum hemorrhage","lastPublishedDoi":"10.21203/rs.3.rs-2376445/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2376445/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eThere are many studies regarding the increased relationship between pregnancy outcomes and obstetrical complications of singleton with endometriosis such as preterm birth, preeclampsia, placenta previa, and small for gestational age. However, there was limited evidence of twin pregnancies with endometriosis. The objective of this study was to compare the pregnancy outcomes and obstetrical complications in twin pregnancies with endometriosis or without endometriosis in single institution.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eBetween\u003cstrong\u003e \u003c/strong\u003eJanuary 2011 and July 2022,\u003cstrong\u003e \u003c/strong\u003ea cohort of twin pregnancies delivered at single institution was retrospectively analyzed. Patients who underwent surgical treatment before pregnancy and had histological confirmation; had visual or histological confirmation during cesarean section; and those with antenatal ultrasonographic findings of typical ovarian endometriosis and underwent vaginal delivery were included in the endometriosis group. Pregnancy outcomes and obstetrical complications were compared between the two groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eA total of 1,951 patients were examined, of whom 143 (7.3%) were included in the endometriosis group. Maternal body mass index (BMI) was significantly lower in the endometriosis group (p\u0026lt;0.001). However, there were no significant differences in maternal age, mode of conception, and chorionicity. There were also no significant differences in pregnancy outcomes: gestational age at delivery (p=0.619), rate of delivery before 37weeks (p=0.728), and mode of delivery (p=0.698). However, some obstetrical complications showed significantly higher rates in the endometriosis group: placenta previa (p=0.038), small for gestational age \u0026lt;10% (p=0.039), and postpartum hemorrhage (p=0.006). Logistic regression analyses performed after adjusted for BMI showed that patient with endometriosis had a higher risk of developing placenta previa (odds ratios (OR) 2.191; 95% confidence intervals (CI) 1.051-4.568), and postpartum hemorrhage (OR, 2.506; 95% CI, 1.444-4.348). After multivariable analyses, postpartum hemorrhage was significantly higher in patients with endometriosis (OR, 2.264; 95% CI, 1.265-4.054).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eTwin pregnancies with endometriosis had a significantly higher risk of postpartum hemorrhage. To confirm these outcomes, further large prospective studies are required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration : \u003c/strong\u003eretrospectively registered\u003c/p\u003e","manuscriptTitle":"Pregnancy outcomes and obstetrical complications of twin pregnancies with endometriosis: A single center cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-01-03 15:00:09","doi":"10.21203/rs.3.rs-2376445/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"446721af-c4d0-4fac-b449-7d32d969d139","owner":[],"postedDate":"January 3rd, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-05-20T07:09:28+00:00","versionOfRecord":{"articleIdentity":"rs-2376445","link":"https://doi.org/10.3349/ymj.2023.0099","journal":{"identity":"yonsei-medical-journal","isVorOnly":true,"title":"Yonsei Medical Journal"},"publishedOn":"2024-01-01 07:09:28","publishedOnDateReadable":"January 1st, 2024"},"versionCreatedAt":"2023-01-03 15:00:09","video":"","vorDoi":"10.3349/ymj.2023.0099","vorDoiUrl":"https://doi.org/10.3349/ymj.2023.0099","workflowStages":[]},"version":"v1","identity":"rs-2376445","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2376445","identity":"rs-2376445","version":["v1"]},"buildId":"WvIrzKhiLBfengagbw6Ux","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}