Pregnancy outcomes of infertile women with co-existing endometriosis and adenomyosis after laparoscopic surgery: a long-term follow-up

Pregnancy outcomes of infertile women with co-existing endometriosis and adenomyosis after laparoscopic surgery: a long-term follow-up | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Pregnancy outcomes of infertile women with co-existing endometriosis and adenomyosis after laparoscopic surgery: a long-term follow-up Jinghua Shi, Yi Dai, Junji Zhang, Xiaoyan Li, Shuangzhen Jia, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-85435/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 20 You are reading this latest preprint version Abstract Background: Adenomyosis and endometriosis are often co-existent. Laparoscopic surgery is one of the main methods to diagnose and treat these conditions. However, very few studies have been done that concentrate on the pregnancy outcomes of infertile women with both adenomyosis and endometriosis after laparoscopic surgery, as well as the relevant influential factors. Methods : This is a retrospective, cross-sectional study including infertile women diagnosed with endometriosis and adenomyosis. All patients had undergone laparoscopic surgery and were divided into two groups according to pregnancy outcomes. Demographic data, operation records, and pregnancy outcomes were collected. Results: Ninety-seven patients had live births, including 81 full-term and 16 preterm deliveries. The biochemical pregnancy, clinical pregnancy, and live birth rates were 80.87%, 67.4, and 55.11% respectively. One hundred thirty-five patients received IVF with 70 (51.85%) patients having live births. Age, size of endometrioma, and size of uterus were significantly lower in those who had a successful delivery. There was no statistical difference in symptoms except anemia (13.40% vs. 25.32%, p=0.044). The group that failed to have a live birth had a higher percentage of ovarian and peritoneal endometriosis (P<.05), while the distribution of deep infiltrating endometriosis and adenomyosis types were similar. Mean uterus diameter (OR: 0.636, 95% CI: 0.434-0.932, p = 0.020) and endometriosis fertility index (EFI) (OR:1.299, 95% CI: 1.101-1.531, p = 0.002) were significantly correlated with live births in the multivariate analysis. Conclusions: Endometriosis and adenomyosis have an adverse effect on fertility. IVF is an important technology improving pregnancy rate even after surgery. The size of the uterus and EFI were independent risk factors for pregnancy outcomes. Sexual & Reproductive Medicine Maternal & Fetal Medicine Adenomyosis Endometriosis Infertility Laparoscopic surgery Pregnancy outcome Figures Figure 1 Introduction Adenomyosis (AM) and endometriosis (EM) are benign conditions of the uterus, defined by the presence of endometrial glands and stroma within the myometrium and outside of the uterus. Histological diagnosis is the most accurate method to identify these conditions, but they can also be diagnosed clinically when patients are presenting with symptoms. These symptoms include dysmenorrhea, dyspareunia, abnormal uterine bleeding, and infertility. AM shares some pathogenic mechanisms with EM[ 1 ]. Our center reported that 39.9% of women with endometrioma also had AM[ 2 ], while 33.3%[ 3 ] of 72 patients histologically diagnosed with AM had concomitant EM. Chapron et al. [ 4 ] reported that the coexistence rate could be as high as 87.4%. AM and EM both have adverse effects on fertility, making treatment more complicated. In addition to the impacts on reproductive performance (infertility and miscarriage) and pregnancy outcomes (preterm labor, fetal growth restriction, placenta previa and even uterine rupture) are also affected by AM[ 5 , 6 ] and EM[ 7 ]. Laparoscopic surgery is one of the main ways to diagnose as well as treat these uterine conditions, but it is difficult to predict pregnancy outcomes in infertile women diagnosed with both AM and EM. The endometriosis fertility index (EFI) has been proven to be a useful model to predict pregnancy outcomes[ 8 ]. However, adenomyosis is not included. Additionally, the effect of the removal of coexisting adenomyosis on fertility outcomes is not fully evaluated and few studies have specifically concentrated on this field. In this study we aimed to explore pregnancy outcomes and use long term follow up to analyze factors relating to fertility outcomes of infertile women with both adenomyosis and endometriosis after laparoscopic surgery. Material And Methods Ethical approval and informed consent for study This study was approved by the Ethics Committee of Peking Union Medical College Hospital (S-K1055), and all procedures involving human participants followed the ethical standards of the IRB from the study center. Informed consent was obtained from all patients at their follow-up interviews. Patient population We identified all the patients who underwent laparoscopic surgery for the first time in our hospital diagnosed with both EM and AM between January 2013 and December 2017. Among them, 226 patients were infertile and wished to conceive after surgery. During the surgery, endometriomas were removed and peritoneal endometrial tissue was coagulated. Deep infiltrating endometriosis and adenomyoma were resected if patients had severe symptoms or repeated IVF-ET failure due to unknown reasons. Pre-surgical symptoms and surgical data, including postoperative complications, were retrieved from patient admission and operative databases. The revised American Fertility Society (rAFS) score revised American Society for Reproductive Medicine (rASRM) staging, and EFI score were collected according to surgical records and infertility history. Post-surgical symptoms and pregnancy outcomes were collected from follow up interviews with outpatients. Ultrasonographic exams were performed after the menstrual cycle that occurred most recently before surgery. Features on ultrasounds that suggested AM are as follows: asymmetrical myometrial thickening, myometrial cysts, linear striations, hyperechoic islands, or an irregular and thickened endometrial–myometrial junctional zone[ 9 ]. If more than two features were present and the lesions were located in only one part of the uterine wall, a diagnosis of focal AM was made. Diffuse AM was diagnosed as lesions in more than one site within the myometrium, more often being widely spread rather than forming a confined lesion[ 10 ]. Endometriosis was visually inspected by laparoscopy and histologically confirmed. Deep infiltrating endometriosis was diagnosed as the presence of one or more endometriotic nodules deeper than 5 mm. The exclusion criteria were as follows: (1) age 40 years; (2) patient underwent a bilateral oophorectomy or hysterectomy; (3) intraoperative conversion to a laparotomy; (4) concomitant diseases that clearly affect fertility, such as submucosal fibroids, premature ovarian failure, systemic lupus erythematosus, malignant tumors, etc. Statistical analysis Continuous data were presented as median (interquartile range) or mean ± SD and compared using t-tests or ANOVA tests. Categorical data were described by the number of cases (including percentages) and compared with Fisher’s exact or chi-square tests. Potential risk factors (p < 0.2) were identified using univariate analysis and multivariate, logistic regression analysis (Stepwise). The odds ratio (OR) and 95% confidence interval (CI) were calculated as a measure of the impact on live births. All analyses used a two-tailed α of 0.05 and were performed using software SPSS (Version 20.0, IBM Corp., Armonk, NY, USA). Results Patient characteristics During the study period, 226 infertile patients with AM and EM were identified. 43 patients were excluded due to an elderly age (n = 32) or insufficient follow-up data (n = 11). Here we define a successful delivery as the patient having a live birth. To report the factors associated with successful live births, we divided the 176 women into two groups: Group A (n = 97) contained 81 full-term infants and 16 preterm infants, and Group B (n = 79) contained those who didn’t get live birth. The remaining seven patients were still pregnant and were excluded. Details regarding the flowchart of the group selection process for the patients are provided in Fig. 1 . Basic characteristics of both groups are presented in Table 1 . Table 1 Population characteristics of the live birth and non-live birth group Group A Group B p value Women who had a successful delivery(n = 97) Women who did not have a successful delivery(n = 79) Age (years) 32.52 ± 3.20 33.53 ± 3.95 0.046* BMI (kg/m 2 ) 21.74 ± 2.78 20.51 ± 4.72 0.033* Type of Infertility Primary infertility Secondary infertility 60 37 52 27 NS Gravida 0(0–5) 0(0–5) NS Parity 0(0–1) 0(0–2) NS Abortion 19(19.58%) 23(29.11%) NS Previous ART 21(21.65%) 14(17.72%) NS Duration of infertility(years) 3(1–8) 2(1–11) NS Length of period(day) 5.88 ± 1.86 6.22 ± 2.04 NS Menstrual cycle(day) 28.94 ± 6.17 28.94 ± 9.35 NS Duration of dysmenorrheal(years) 5.33 ± 5.77 6.30 ± 6.29 NS Dysmenorrhea (VAS) 4.22 ± 3.59 4.58 ± 3.49 NS Anemia 13(13.40%) 20(25.32%) 0.044* CA125(U/ml) 80.67 ± 92.47 109.57 ± 98.48 NS FSH(IU/l) 7.12 ± 2.21 8.43 ± 2.81 0.005* E2(pg/ml) 53.69 ± 41.14 48.88 ± 21.85 NS Mean uterus diameter (cm) 4.91 ± 0.79 5.42 ± 1.20 0.001* Mean cyst diameter (cm) 2.63 ± 3.43 4.38 ± 4.00 0.002* Note:Data are presented as mean ± SD or n (%); NS, not significant; BMI, body mass index; ART assisted reproductive technology; VAS, visual analog scale; CA125,cancer antigen 125; FSH, follicle stimulating hormone; E2, estrogen. Surgical findings Compared to the women who did not have a successful delivery, the women who had a successful delivery had significantly lower rAFS scores (33.62 ± 33.53 vs. 47.56 ± 38.22, p = 0.011) and higher EFI scores (6.87 ± 2.04 vs. 5.67 ± 2.09, p = 0.001). Blood loss during the laparoscopy in group A was also less than group B (46.03 ± 51.80 ml vs 84.08 ± 114.39 ml, p = 0.009) and so was surgical time (56.60 ± 21.42 min vs. 65.76 ± 27.34 min, p = 0.022). This study also found that the non-live birth group had a significantly higher proportion of OEM (ovarian endometriosis) and PEM (peritoneal endometriosis). However, there were no statistical difference in DIE (deep infiltrating endometriosis), leiomyoma, endometrial polyps, or obstruction of oviduct (Table 2 ). Table 2 Surgical findings between live birth and non-live birth groups Group A(n = 97) Group B(n = 79) p value Ovarian endometriosis 49(50.52%) 57(72.15%) 0.004* Peritoneal endometriosis 65(67.01%) 40(72.15%) 0.028* Deep infiltrating endometriosis 35(36.08%) 22(27.85%) NS AM type Diffuse Local 52(53.61%) 45(46.39%) 43(54.43%) 36(45.57%) NS Leiomyoma 29(29.90%) 18(22.78%) NS Obstruction of oviduct 22(22.68%) 23(29.11%) NS Endometrial polyps 31(31.96%) 25(31.64%) NS Note:Data are presented as mean ± SD or n (%); NS, not significant. Fertility results and pregnancy outcomes After a long term follow up (median 47 months, range 20–80 months), 35 (19.13%) patients failed to conceive and 13 (7.10%) patients stopped trying to conceive: four due to disease relapses, two due to cases of depression, four due to premature ovarian failures (POF), one case due to endometrial intraepithelial neoplasia (EIN), and two due to repeated in vitro fertilization (IVF) failures. One hundred thirty five (73.77%) patients received IVF, among which four patients lacked follow up data and 70 patients had live births (51.85%). The mean time from surgery to pregnancy was 12.89 ± 8.66 months and the mean time from stopping contraception after surgery to pregnancy was 8.56 ± 8.48 months.148(80.87%) patients got a positive pregnancy test, clinical pregnancy rate, or presence of a fetal heartbeat at 12 weeks of gestation, was 67.4%, and 55.11% ultimately achieved a successful delivery. Forty (27.03%) patients experienced natural abortions, two (1.35%) had an ectopic pregnancy, and five (3.38%) had intrauterine deaths (fetal death at or after the 20th week of gestation). Ninety five (51.91%) patients took their babies home, among which 16 (16.84%) had preterm labor and 12 (12.63%) had abnormal placentae (seven placenta previa, four placenta acrreta, and one placenta increta). To determine the factors associated with a successful delivery, univariate analysis and multivariate logistic regression analysis were performed. Variables showing a tendency of association with live birth rates (p values < 0.20) in the univariate analysis were included in the multivariate model. When two variables were highly correlated, we introduced only one of them into the model and suppressed the other; for example when examining age and FSH levels, the latter was suppressed. Surgical time (p = 0.016) and blood loss (p = 0.011) showed a tendency of association, but they were excluded as they were highly correlated with the AFS score and type of AM. EFI includes age, infertility type, years of infertility, function of tube/fimbria/ovaries, and AFS and therefore, they wouldn’t be included as candidate factors. EFI (p = 0.00), anemia (p = 0.047),VAS (p = 0.112) ,CA125 (p = 0.093), mean uterine diameter (p = 0.002), assisted reproductive technology (ART) (p = 0.122), and medical history (p = 0.017) were included as covariates in the final model. AM type (p = 0.159) and AM surgery (p = 0.110) were also included as they were reported to be related to the pregnancy rate[ 11 ]. Table 3 presents the estimated ORs with the standard errors (SE) and 95% CIs between live birth rates and significantly relevant confounders. Other variables had no significant relationship with live births. Table 3 Significant prognostic factors of live birth rate after multivariate analysis Characteristics OR SE 95% CI P- value Mean uterus diameter 0.636 0.195 0.434–0.932 0.020* EFI 1.299 0.084 1.101–1.531 0.002* Note: OR: odds ratio; SE: standard error; CI: confidential interval Discussion In this study, 176 infertile women with both EM and AM had laparoscopic surgery and completed an outpatient follow up. Few studies have concentrated on the pregnancy outcomes of women with both AM and EM; most research reported only EM or AM patients or grouped the two diseases together. Chloé Maignien et al.[ 12 ] studied 359 infertile EM patients and the pregnancy and live birth rates were 44% and 32%, respectively. Our results were a bit higher, perhaps because of the longevity of our follow up. Some patients were able to have a natural live birth even after repeated IVF-ET failure. EM phenotypes seemed to impact pregnancy outcomes, as there were significant differences between the live-birth group and stillbirth group. Our previous results verified the presence of follicles in the cyst walls of the endometrioma in paraffin sections[ 13 ] and that FSH levels were significantly decreased after laparoscopic bilateral ovary endometrioma resection[ 14 ]. Vercellini et al. retrospectively analyzed 419 patients who achieved natural conception and divided them into four groups according to the type of EM. The total pregnancy loss rate was 20.8%, which was close to ours (20.03%). They also observed a higher miscarriage rate in women with ovarian endometriomas (26%) than in those with the peritoneal type (12%)[ 15 ]. However, these findings were contrary to the report done by Chloé Maignien et al.[ 12 ]. In his study, the live birth rates per cycle were 13.7%, 16.5,% and 16% in peritoneal, ovarian, and deep infiltrating EM subgroups (p = 0.82), respectively. In addition to the reduced oocyte yield, reduced fertilization rate (FR), and increased miscarriage rate, AM and EM were also reported to be related to several obstetrical and fetal complications. However, the evidence is still scanty and conflicting. A meta-analysis in 2019[ 16 ] including 104 papers demonstrated that EM could be associated with preterm delivery (OR 1.38, CI 1.01–1.89), caesarean section delivery (OR 1.98 CI 1.64–2.38), and neonatal unit admission following delivery (OR 1.29, CI 1.07–1.55). It is noteworthy that no OR exceeded three. Two other systematic reviews failed to draw conclusions on obstetrical complications related to EM except for preterm delivery[ 17 ] and placenta previa[ 18 ]. The results of this study showed a preterm birth rate of 16.84% and placenta previa rate of 7.36%, which are findings slightly higher than in Benaglia L’s report. In his retrospective, matched, case-control study[ 19 ], the rate of preterm birth was similar between the EM and non-EM groups (14% and 14%, respectively, p = 0.89), while placenta previa was more common in women with EM than in the control group (6% versus 1%, respectively; p = 0.006, OR 4.8, 95% CI: 1.4–17.2). A possible explanation for this might be that our cases had patients with both EM and AM. In a multicenter, retrospective, questionnaire survey[ 20 ] including 272 pregnant women with AM from 65 facilities, the preterm delivery rate was reported to be as high as 24.4%. Several studies further analyzed the clinical factors that affect pregnancy outcomes. In a retrospective study of 631 women with EM who became pregnant by ART [ 21 ], the reported incidence of preterm delivery or abnormal placental positioning didn’t increase in stages I–III, but increased significantly in stage IV. Dr. Kim and colleagues[ 22 ] reported a preterm labor rate of 24.56% in a retrospective study and found that uterine wall thickness in the second trimester was related to subsequent preterm delivery. In our study, the size of uterus was also found to be significantly different between the two groups. The etiology of infertility might include disordered inflammatory factors like prostaglandin (PG) production (PGE2 and PGF2a), cyclooxygenase 2 (COX-2)[ 23 ], abnormal ER- and PR-mediated signaling pathways associated with progesterone resistance[ 24 ], impaired trophoblast invasiveness, and uterine contractility[ 25 ]. These can also be related to failure of the physiologic transformation of spiral arteries in the inner myometrial segment, or junctional zone (JZ). Alterations of the JZ in women with EM and AM can influence vascular resistance of JZ spiral arteries at the onset of decidualization[ 25 ] and lead to incomplete spiral artery remodeling and the reduction of placental blood flow[ 26 ]. The mechanism is complex, and the existing results are debatable. The influence of co-existing EM and AM on pregnancy is not simply superimposed, but rather the two diseases interact with each other. The strength of this study is its diagnosis. The golden standard of AM diagnosis is based on histological specimens, which is an invasive technique and has a potential of uterine rupture during pregnancy and delivery. Therefore, non-invasive technics like ultrasound and MRI are preferred. MRI, with a sensitivity from 78–88% and specificity from 67–93% [ 27 ], was traditionally considered to be more accurate than ultrasound. However, with the development of high-quality transvaginal ultrasound (TVUS), a systematic review including 10 studies (1168 records) proved that the two techniques are comparable[ 28 ]. The accuracy of the ultrasound in AM diagnoses is high with a mean sensitivity of 0.72 (95% CI: 0.65–0.79), specificity of 0.81 (95% CI: 0.77–0.85), and area under the curve (AUC) of 0.85[ 29 , 30 ]. Additionally, ultrasounds are much cheaper and more convenient. The diagnoses of EM and its subtypes are based on laparoscopic surgery, which is the gold standard and quite reliable. However, women referred to our hospital may have had particularly severe forms of AM, EM, or repeated IVF failure, which introduces potential selection and comparison bias. Second, the follow up didn’t include an analysis of IVF details. Most patients went to their local ART center for controlled ovarian stimulation and IVF-ET and could hardly recall the details, remembering only the final results. There are several other limitations to these results. First, our study is retrospective. Second, the number of cases was limited and we could not perform subtype analyses according to the obstetric complications. Third, other disputed factors were not included, such as the excision of DIE[ 31 ], use of GnRHa[ 32 ], and complete removal of endometrial lesions [ 33 ]. Fourth, this study only includes patients that needed laparoscopic surgery. Although dysmenorrhea, metrorrhagia, chronic pelvic pain, dyspareunia, and infertility often occur, a third of the women were asymptomatic[ 27 ] and we are worried about the extent to which this will affect our fertility and sterility rates. Conclusions Overall, our study suggests that co-existing EM and AM has adverse effects on both reproductive performance and the outcome of pregnancy. Age, BMI, and size of endometrioma and the uterus were related to the prognosis. IVF is an important technique in improving the pregnancy rate following surgery. These findings may prove useful in daily practice for offering optimal infertility consultation to women with both EM and AM. Further prospective studies with larger sample sizes are still needed to draw firmer conclusions. Declarations Acknowledgments We appreciate the whole stuff at Peking Union Medical College Hospital (PUMCH) for their clinical work and data recording about the cases we reported in this article. Author contribution JH-S and JH-L designed the study. XY-L, SZ-J, and J-J Zhang retrieved the data and performed the data analysis. JH-S and Y-D drafted the manuscript. All the authors participated in the discussion of the results and critically revised the manuscript. Compliance with Ethical Standards: Funding: This study was funded by the National Key R&D Program of China (No. 2017YFC1001200), National Natural Science Foundation of China (No. 81541016) Conflict of interest: All authors declared that they have no conflict of interest related to the topic to declare. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: Informed consent was obtained from all individual participants included in the study. References Brosens, I., G. Kunz, and G. Benagiano, Is adenomyosis the neglected phenotype of an endomyometrial dysfunction syndrome? Gynecol Surg, 2012. 9 (2): p. 131-137. Li, X.Y., et al., Risk factors for postoperative recurrence of ovarian endometriosis: long-term follow-up of 358 women. J Ovarian Res, 2019. 12 (1): p. 79. Lv, Y., et al., The medium to long term clinical outcomes of laparoscopic conservative surgery on adenomyomas. CHINESE JOURNAL OF PRACTICAL GYNECOLOGY AND OBSTETRICS, 2011. 27 (10): p. 753-756. Chapron, C., et al., Relationship between the magnetic resonance imaging appearance of adenomyosis and endometriosis phenotypes. Hum Reprod, 2017. 32 (7): p. 1393-1401. Mochimaru, A., et al., Adverse pregnancy outcomes associated with adenomyosis with uterine enlargement. Journal of Obstetrics and Gynaecology Research, 2014. 41 . Razavi, M., et al., Systematic review and meta-analysis of adverse pregnancy outcomes after uterine adenomyosis. Int J Gynaecol Obstet, 2019. 145 (2): p. 149-157. Harada, T., et al., Adverse obstetrical outcomes for women with endometriosis and adenomyosis: A large cohort of the Japan Environment and Children's Study. PLoS One, 2019. 14 (8): p. e0220256. Maheux-Lacroix, S., et al., Endometriosis fertility index predicts live births following surgical resection of moderate and severe endometriosis. Hum Reprod, 2017. 32 (11): p. 2243-2249. Lazzeri, L., et al., Preoperative and Postoperative Clinical and Transvaginal Ultrasound Findings of Adenomyosis in Patients With Deep Infiltrating Endometriosis. Reprod Sci, 2014. 21 (8): p. 1027-1033. Van den Bosch, T., et al., Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group. Ultrasound Obstet Gynecol, 2015. 46 (3): p. 284-98. Tan, J., et al., Reproductive Outcomes after Fertility-Sparing Surgery for Focal and Diffuse Adenomyosis: A Systematic Review. J Minim Invasive Gynecol, 2018. 25 (4): p. 608-621. Maignien, C., et al., Prognostic factors for assisted reproductive technology in women with endometriosis-related infertility. Am J Obstet Gynecol, 2017. 216 (3): p. 280.e1-280.e9. Shi, J., et al., Follicle loss after laparoscopic treatment of ovarian endometriotic cysts. Int J Gynaecol Obstet, 2011. 115 (3): p. 277-81. Shi, J.H., et al., Influence of Laparoscopic Cystectomy on Ovarian Reserve Function and Pregnantic Outcome in Women with Ovarian Endometriotic Cyst. MEDICAL JOURNAL OF PEKING UNION MEDICAL COLLEGE HOSPITAL, 2011. 002 (2): p. 20-24. Vercellini, P., et al., Pregnancy outcome in women with peritoneal, ovarian and rectovaginal endometriosis: a retrospective cohort study. Bjog, 2012. 119 (12): p. 1538-43. Horton, J., et al., Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis. Human reproduction update, 2019. 25 . Vigano, P., L. Corti, and N. Berlanda, Beyond infertility: obstetrical and postpartum complications associated with endometriosis and adenomyosis. Fertil Steril, 2015. 104 (4): p. 802-812. Leone Roberti Maggiore, U., et al., A systematic review on endometriosis during pregnancy: diagnosis, misdiagnosis, complications and outcomes. Human Reproduction Update, 2015. 22 (1): p. 70-103. Benaglia, L., et al., Pregnancy outcome in women with endometriosis achieving pregnancy with IVF. Hum Reprod, 2016. 31 (12): p. 2730-2736. Tamura, H., et al., Complications and outcomes of pregnant women with adenomyosis in Japan. Reprod Med Biol, 2017. 16 (4): p. 330-336. Fujii, T., et al., Assisted reproductive technology pregnancy complications are significantly associated with endometriosis severity before conception: a retrospective cohort study. 14 (1): p. 73. Kim, Y.-M., et al., Uterine wall thickness at the second trimester can predict subsequent preterm delivery in pregnancies with adenomyosis. Taiwanese Journal of Obstetrics and Gynecology, 2019. 58 : p. 598-603. Vannuccini, S., et al., Infertility and reproductive disorders: impact of hormonal and inflammatory mechanisms on pregnancy outcome. Hum Reprod Update, 2016. 22 (1): p. 104-15. Lessey, B.A. and S.L. Young, Homeostasis imbalance in the endometrium of women with implantation defects: the role of estrogen and progesterone. Semin Reprod Med, 2014. 32 (5): p. 365-75. Aguilar, H.N. and B.F. Mitchell, Physiological pathways and molecular mechanisms regulating uterine contractility. Hum Reprod Update, 2010. 16 (6): p. 725-44. Hashimoto, A., et al., Impact of endometriosis and adenomyosis on pregnancy outcomes. Hypertension Research in Pregnancy, 2019. 7 (2): p. 50-55. Graziano, A., et al., Diagnostic findings in adenomyosis: a pictorial review on the major concerns. Eur Rev Med Pharmacol Sci, 2015. 19 (7): p. 1146-54. Tellum, T., S. Nygaard, and M. Lieng, Noninvasive Diagnosis of Adenomyosis: A Structured Review and Meta-analysis of Diagnostic Accuracy in Imaging. J Minim Invasive Gynecol, 2019. Champaneria, R., et al., Ultrasound scan and magnetic resonance imaging for the diagnosis of adenomyosis: systematic review comparing test accuracy. Acta Obstet Gynecol Scand, 2010. 89 (11): p. 1374-84. Van den Bosch, T. and D. Van Schoubroeck, Ultrasound diagnosis of endometriosis and adenomyosis: State of the art. Best Pract Res Clin Obstet Gynaecol, 2018. 51 : p. 16-24. Vercellini, P., et al., Adenomyosis and reproductive performance after surgery for rectovaginal and colorectal endometriosis: a systematic review and meta-analysis. Reprod Biomed Online, 2014. 28 (6): p. 704-13. Younes, G. and T. Tulandi, Effects of adenomyosis on in vitro fertilization treatment outcomes: a meta-analysis. Fertil Steril, 2017. 108 (3): p. 483-490.e3. Bianchi, P.H.M., et al., Extensive Excision of Deep Infiltrative Endometriosis before In Vitro Fertilization Significantly Improves Pregnancy Rates. Journal of Minimally Invasive Gynecology, 2009. 16 (2): p. 174-180. 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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-85435","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":2961596,"identity":"325c8449-a6f6-47a4-ad08-3d4e7b90a5b0","order_by":0,"name":"Jinghua Shi","email":"","orcid":"https://orcid.org/0000-0001-5267-9092","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jinghua","middleName":"","lastName":"Shi","suffix":""},{"id":2961597,"identity":"1fe495c4-a5c0-4549-9a24-035a343f909c","order_by":1,"name":"Yi Dai","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Dai","suffix":""},{"id":2961598,"identity":"d8cb1765-0e13-442c-b0fd-3a3397675746","order_by":2,"name":"Junji Zhang","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Junji","middleName":"","lastName":"Zhang","suffix":""},{"id":2961599,"identity":"2032cdcc-902e-4dc2-be9d-3c068b417d69","order_by":3,"name":"Xiaoyan Li","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiaoyan","middleName":"","lastName":"Li","suffix":""},{"id":2961600,"identity":"df08743f-6817-461d-9f03-cd5bb26bbb37","order_by":4,"name":"Shuangzhen Jia","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shuangzhen","middleName":"","lastName":"Jia","suffix":""},{"id":2961601,"identity":"6ff5711c-ee0c-4e29-abb3-5c8a8d869f4e","order_by":5,"name":"Jinhua Leng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/klEQVRIiWNgGAWjYBACPhAhASLYGxgOACkeglrY4Fp4DpCiBQwkEoh0GBt77+EXFhV38gxuvjE8XMBQJ2POfoDxw8ccPFp4zqVZSJx5VmxwO8fg8AyGwzyWPQnMkjO34dEikWNmINl2OHHD7bSEwzwMB3gMDiSwMfPi0yL/BqjlH1DLzWMgLXU8BucfENAiwWP8QLIBqOUG8wGgFmYegxuEbOHJMWOQOHY4ceaZ5AOHZxgcBmp52IzXL/zsZ4w/S9QcTuw7frD5c0FFnb3B+eSDHz7i0QKySBoUlQoHGBiYGQxAAowNeNUDAfPHD0BSvgGkZRSMglEwCkYBFgAAH95SKTIkkKQAAAAASUVORK5CYII=","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":true,"prefix":"","firstName":"Jinhua","middleName":"","lastName":"Leng","suffix":""}],"badges":[],"createdAt":"2020-09-29 15:18:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-85435/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-85435/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":2814032,"identity":"077ee35d-b81b-42e4-a97c-6c03843a678a","added_by":"auto","created_at":"2020-10-06 19:36:41","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":74227,"visible":true,"origin":"","legend":"Flowchart of patients’ selection","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-85435/v1/3049107884a8e409dbcf6c33.jpg"},{"id":13600177,"identity":"8ecf72c1-ce87-4e04-b8d8-45181ba80f7f","added_by":"auto","created_at":"2021-09-17 05:42:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":383180,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-85435/v1/1c2e342d-8794-4846-9992-3f2dba4f4218.pdf"}],"financialInterests":"","formattedTitle":"Pregnancy outcomes of infertile women with co-existing endometriosis and adenomyosis after laparoscopic surgery: a long-term follow-up","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAdenomyosis (AM) and endometriosis (EM) are benign conditions of the uterus, defined by the presence of endometrial glands and stroma within the myometrium and outside of the uterus. Histological diagnosis is the most accurate method to identify these conditions, but they can also be diagnosed clinically when patients are presenting with symptoms. These symptoms include dysmenorrhea, dyspareunia, abnormal uterine bleeding, and infertility. AM shares some pathogenic mechanisms with EM[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e]. Our center reported that 39.9% of women with endometrioma also had AM[\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e], while 33.3%[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e] of 72 patients histologically diagnosed with AM had concomitant EM. Chapron et al. [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e] reported that the coexistence rate could be as high as 87.4%.\u003c/p\u003e\n\u003cp\u003eAM and EM both have adverse effects on fertility, making treatment more complicated. In addition to the impacts on reproductive performance (infertility and miscarriage) and pregnancy outcomes (preterm labor, fetal growth restriction, placenta previa and even uterine rupture) are also affected by AM[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e] and EM[\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eLaparoscopic surgery is one of the main ways to diagnose as well as treat these uterine conditions, but it is difficult to predict pregnancy outcomes in infertile women diagnosed with both AM and EM. The endometriosis fertility index (EFI) has been proven to be a useful model to predict pregnancy outcomes[\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, adenomyosis is not included. Additionally, the effect of the removal of coexisting adenomyosis on fertility outcomes is not fully evaluated and few studies have specifically concentrated on this field. In this study we aimed to explore pregnancy outcomes and use long term follow up to analyze factors relating to fertility outcomes of infertile women with both adenomyosis and endometriosis after laparoscopic surgery.\u003c/p\u003e"},{"header":"Material And Methods","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and informed consent for study\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Peking Union Medical College Hospital (S-K1055), and all procedures involving human participants followed the ethical standards of the IRB from the study center. Informed consent was obtained from all patients at their follow-up interviews.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe identified all the patients who underwent laparoscopic surgery for the first time in our hospital diagnosed with both EM and AM between January 2013 and December 2017. Among them, 226 patients were infertile and wished to conceive after surgery. During the surgery, endometriomas were removed and peritoneal endometrial tissue was coagulated. Deep infiltrating endometriosis and adenomyoma were resected if patients had severe symptoms or repeated IVF-ET failure due to unknown reasons. Pre-surgical symptoms and surgical data, including postoperative complications, were retrieved from patient admission and operative databases. The revised American Fertility Society (rAFS) score revised American Society for Reproductive Medicine (rASRM) staging, and EFI score were collected according to surgical records and infertility history. Post-surgical symptoms and pregnancy outcomes were collected from follow up interviews with outpatients.\u003c/p\u003e\n\u003cp\u003eUltrasonographic exams were performed after the menstrual cycle that occurred most recently before surgery. Features on ultrasounds that suggested AM are as follows: asymmetrical myometrial thickening, myometrial cysts, linear striations, hyperechoic islands, or an irregular and thickened endometrial\u0026ndash;myometrial junctional zone[\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]. If more than two features were present and the lesions were located in only one part of the uterine wall, a diagnosis of focal AM was made. Diffuse AM was diagnosed as lesions in more than one site within the myometrium, more often being widely spread rather than forming a confined lesion[\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]. Endometriosis was visually inspected by laparoscopy and histologically confirmed. Deep infiltrating endometriosis was diagnosed as the presence of one or more endometriotic nodules deeper than 5\u0026nbsp;mm.\u003c/p\u003e\n\u003cp\u003eThe exclusion criteria were as follows: (1) age\u0026thinsp;\u0026lt;\u0026thinsp;20 or \u0026gt;\u0026thinsp;40 years; (2) patient underwent a bilateral oophorectomy or hysterectomy; (3) intraoperative conversion to a laparotomy; (4) concomitant diseases that clearly affect fertility, such as submucosal fibroids, premature ovarian failure, systemic lupus erythematosus, malignant tumors, etc.\u003c/p\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContinuous data were presented as median (interquartile range) or mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD and compared using t-tests or ANOVA tests. Categorical data were described by the number of cases (including percentages) and compared with Fisher\u0026rsquo;s exact or chi-square tests. Potential risk factors (p\u0026thinsp;\u0026lt;\u0026thinsp;0.2) were identified using univariate analysis and multivariate, logistic regression analysis (Stepwise). The odds ratio (OR) and 95% confidence interval (CI) were calculated as a measure of the impact on live births. All analyses used a two-tailed \u0026alpha; of 0.05 and were performed using software SPSS (Version 20.0, IBM Corp., Armonk, NY, USA).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatient characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring the study period, 226 infertile patients with AM and EM were identified. 43 patients were excluded due to an elderly age (n\u0026thinsp;=\u0026thinsp;32) or insufficient follow-up data (n\u0026thinsp;=\u0026thinsp;11). Here we define a successful delivery as the patient having a live birth. To report the factors associated with successful live births, we divided the 176 women into two groups: Group A (n\u0026thinsp;=\u0026thinsp;97) contained 81 full-term infants and 16 preterm infants, and Group B (n\u0026thinsp;=\u0026thinsp;79) contained those who didn\u0026rsquo;t get live birth. The remaining seven patients were still pregnant and were excluded. Details regarding the flowchart of the group selection process for the patients are provided in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Basic characteristics of both groups are presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003ePopulation characteristics of the live birth and non-live birth group\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGroup A\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGroup B\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ep value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWomen who had a successful delivery(n\u0026thinsp;=\u0026thinsp;97)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWomen who did not have a successful delivery(n\u0026thinsp;=\u0026thinsp;79)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge (years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32.52\u0026thinsp;\u0026plusmn;\u0026thinsp;3.20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33.53\u0026thinsp;\u0026plusmn;\u0026thinsp;3.95\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.046*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.74\u0026thinsp;\u0026plusmn;\u0026thinsp;2.78\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20.51\u0026thinsp;\u0026plusmn;\u0026thinsp;4.72\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.033*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eType of Infertility\u003c/p\u003e\n\u003cp\u003ePrimary infertility\u003c/p\u003e\n\u003cp\u003eSecondary infertility\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60\u003c/p\u003e\n\u003cp\u003e37\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52\u003c/p\u003e\n\u003cp\u003e27\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGravida\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0(0\u0026ndash;5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0(0\u0026ndash;5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eParity\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0(0\u0026ndash;1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0(0\u0026ndash;2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAbortion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19(19.58%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23(29.11%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePrevious ART\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21(21.65%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14(17.72%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDuration of infertility(years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3(1\u0026ndash;8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2(1\u0026ndash;11)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLength of period(day)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.88\u0026thinsp;\u0026plusmn;\u0026thinsp;1.86\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.22\u0026thinsp;\u0026plusmn;\u0026thinsp;2.04\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMenstrual cycle(day)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28.94\u0026thinsp;\u0026plusmn;\u0026thinsp;6.17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28.94\u0026thinsp;\u0026plusmn;\u0026thinsp;9.35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDuration of dysmenorrheal(years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.33\u0026thinsp;\u0026plusmn;\u0026thinsp;5.77\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.30\u0026thinsp;\u0026plusmn;\u0026thinsp;6.29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDysmenorrhea (VAS)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.22\u0026thinsp;\u0026plusmn;\u0026thinsp;3.59\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.58\u0026thinsp;\u0026plusmn;\u0026thinsp;3.49\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAnemia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13(13.40%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20(25.32%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.044*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCA125(U/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e80.67\u0026thinsp;\u0026plusmn;\u0026thinsp;92.47\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e109.57\u0026thinsp;\u0026plusmn;\u0026thinsp;98.48\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFSH(IU/l)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.12\u0026thinsp;\u0026plusmn;\u0026thinsp;2.21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.43\u0026thinsp;\u0026plusmn;\u0026thinsp;2.81\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.005*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eE2(pg/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e53.69\u0026thinsp;\u0026plusmn;\u0026thinsp;41.14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e48.88\u0026thinsp;\u0026plusmn;\u0026thinsp;21.85\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean uterus diameter (cm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.42\u0026thinsp;\u0026plusmn;\u0026thinsp;1.20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.001*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean cyst diameter (cm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.63\u0026thinsp;\u0026plusmn;\u0026thinsp;3.43\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.38\u0026thinsp;\u0026plusmn;\u0026thinsp;4.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.002*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\"\u003eNote:Data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or \u003cem\u003en\u003c/em\u003e (%); NS, not significant; BMI, body mass index; ART assisted reproductive technology; VAS, visual analog scale; CA125,cancer antigen 125; FSH, follicle stimulating hormone; E2, estrogen.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurgical findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCompared to the women who did not have a successful delivery, the women who had a successful delivery had significantly lower rAFS scores (33.62\u0026thinsp;\u0026plusmn;\u0026thinsp;33.53 vs. 47.56\u0026thinsp;\u0026plusmn;\u0026thinsp;38.22, p\u0026thinsp;=\u0026thinsp;0.011) and higher EFI scores (6.87\u0026thinsp;\u0026plusmn;\u0026thinsp;2.04 vs. 5.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.09, p\u0026thinsp;=\u0026thinsp;0.001). Blood loss during the laparoscopy in group A was also less than group B (46.03\u0026thinsp;\u0026plusmn;\u0026thinsp;51.80\u0026nbsp;ml vs 84.08\u0026thinsp;\u0026plusmn;\u0026thinsp;114.39\u0026nbsp;ml, p\u0026thinsp;=\u0026thinsp;0.009) and so was surgical time (56.60\u0026thinsp;\u0026plusmn;\u0026thinsp;21.42\u0026nbsp;min vs. 65.76\u0026thinsp;\u0026plusmn;\u0026thinsp;27.34\u0026nbsp;min, p\u0026thinsp;=\u0026thinsp;0.022). This study also found that the non-live birth group had a significantly higher proportion of OEM (ovarian endometriosis) and PEM (peritoneal endometriosis). However, there were no statistical difference in DIE (deep infiltrating endometriosis), leiomyoma, endometrial polyps, or obstruction of oviduct (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eSurgical findings between live birth and non-live birth groups\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGroup A(n\u0026thinsp;=\u0026thinsp;97)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGroup B(n\u0026thinsp;=\u0026thinsp;79)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOvarian endometriosis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e49(50.52%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e57(72.15%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.004*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePeritoneal endometriosis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e65(67.01%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e40(72.15%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.028*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDeep infiltrating\u003c/p\u003e\n\u003cp\u003eendometriosis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e35(36.08%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e22(27.85%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAM type\u003c/p\u003e\n\u003cp\u003eDiffuse\u003c/p\u003e\n\u003cp\u003eLocal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52(53.61%)\u003c/p\u003e\n\u003cp\u003e45(46.39%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e43(54.43%)\u003c/p\u003e\n\u003cp\u003e36(45.57%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLeiomyoma\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e29(29.90%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e18(22.78%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eObstruction of oviduct\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e22(22.68%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e23(29.11%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEndometrial polyps\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e31(31.96%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e25(31.64%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\"\u003eNote:Data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or \u003cem\u003en\u003c/em\u003e (%); NS, not significant.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFertility results and pregnancy outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter a long term follow up (median 47 months, range 20\u0026ndash;80 months), 35 (19.13%) patients failed to conceive and 13 (7.10%) patients stopped trying to conceive: four due to disease relapses, two due to cases of depression, four due to premature ovarian failures (POF), one case due to endometrial intraepithelial neoplasia (EIN), and two due to repeated in vitro fertilization (IVF) failures. One hundred thirty five (73.77%) patients received IVF, among which four patients lacked follow up data and 70 patients had live births (51.85%). The mean time from surgery to pregnancy was 12.89\u0026thinsp;\u0026plusmn;\u0026thinsp;8.66 months and the mean time from stopping contraception after surgery to pregnancy was 8.56\u0026thinsp;\u0026plusmn;\u0026thinsp;8.48 months.148(80.87%) patients got a positive pregnancy test, clinical pregnancy rate, or presence of a fetal heartbeat at 12 weeks of gestation, was 67.4%, and 55.11% ultimately achieved a successful delivery. Forty (27.03%) patients experienced natural abortions, two (1.35%) had an ectopic pregnancy, and five (3.38%) had intrauterine deaths (fetal death at or after the 20th week of gestation). Ninety five (51.91%) patients took their babies home, among which 16 (16.84%) had preterm labor and 12 (12.63%) had abnormal placentae (seven placenta previa, four placenta acrreta, and one placenta increta).\u003c/p\u003e\n\u003cp\u003eTo determine the factors associated with a successful delivery, univariate analysis and multivariate logistic regression analysis were performed. Variables showing a tendency of association with live birth rates (p values\u0026thinsp;\u0026lt;\u0026thinsp;0.20) in the univariate analysis were included in the multivariate model. When two variables were highly correlated, we introduced only one of them into the model and suppressed the other; for example when examining age and FSH levels, the latter was suppressed. Surgical time (p\u0026thinsp;=\u0026thinsp;0.016) and blood loss (p\u0026thinsp;=\u0026thinsp;0.011) showed a tendency of association, but they were excluded as they were highly correlated with the AFS score and type of AM. EFI includes age, infertility type, years of infertility, function of tube/fimbria/ovaries, and AFS and therefore, they wouldn\u0026rsquo;t be included as candidate factors. EFI (p\u0026thinsp;=\u0026thinsp;0.00), anemia (p\u0026thinsp;=\u0026thinsp;0.047),VAS (p\u0026thinsp;=\u0026thinsp;0.112) ,CA125 (p\u0026thinsp;=\u0026thinsp;0.093), mean uterine diameter (p\u0026thinsp;=\u0026thinsp;0.002), assisted reproductive technology (ART) (p\u0026thinsp;=\u0026thinsp;0.122), and medical history (p\u0026thinsp;=\u0026thinsp;0.017) were included as covariates in the final model. AM type (p\u0026thinsp;=\u0026thinsp;0.159) and AM surgery (p\u0026thinsp;=\u0026thinsp;0.110) were also included as they were reported to be related to the pregnancy rate[\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e]. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e presents the estimated ORs with the standard errors (SE) and 95% CIs between live birth rates and significantly relevant confounders. Other variables had no significant relationship with live births.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eSignificant prognostic factors of live birth rate after multivariate analysis\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOR\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSE\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e95% CI\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP- value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean uterus diameter\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.636\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.195\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.434\u0026ndash;0.932\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.020*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEFI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.299\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.084\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.101\u0026ndash;1.531\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.002*\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003eNote: OR: odds ratio; SE: standard error; CI: confidential interval\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, 176 infertile women with both EM and AM had laparoscopic surgery and completed an outpatient follow up.\u003c/p\u003e\n\u003cp\u003eFew studies have concentrated on the pregnancy outcomes of women with both AM and EM; most research reported only EM or AM patients or grouped the two diseases together. Chlo\u0026eacute; Maignien et al.[\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e] studied 359 infertile EM patients and the pregnancy and live birth rates were 44% and 32%, respectively. Our results were a bit higher, perhaps because of the longevity of our follow up. Some patients were able to have a natural live birth even after repeated IVF-ET failure.\u003c/p\u003e\n\u003cp\u003eEM phenotypes seemed to impact pregnancy outcomes, as there were significant differences between the live-birth group and stillbirth group. Our previous results verified the presence of follicles in the cyst walls of the endometrioma in paraffin sections[\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e] and that FSH levels were significantly decreased after laparoscopic bilateral ovary endometrioma resection[\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. Vercellini et al. retrospectively analyzed 419 patients who achieved natural conception and divided them into four groups according to the type of EM. The total pregnancy loss rate was 20.8%, which was close to ours (20.03%). They also observed a higher miscarriage rate in women with ovarian endometriomas (26%) than in those with the peritoneal type (12%)[\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, these findings were contrary to the report done by Chlo\u0026eacute; Maignien et al.[\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e]. In his study, the live birth rates per cycle were 13.7%, 16.5,% and 16% in peritoneal, ovarian, and deep infiltrating EM subgroups (p\u0026thinsp;=\u0026thinsp;0.82), respectively.\u003c/p\u003e\n\u003cp\u003eIn addition to the reduced oocyte yield, reduced fertilization rate (FR), and increased miscarriage rate, AM and EM were also reported to be related to several obstetrical and fetal complications. However, the evidence is still scanty and conflicting. A meta-analysis in 2019[\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e] including 104 papers demonstrated that EM could be associated with preterm delivery (OR 1.38, CI 1.01\u0026ndash;1.89), caesarean section delivery (OR 1.98 CI 1.64\u0026ndash;2.38), and neonatal unit admission following delivery (OR 1.29, CI 1.07\u0026ndash;1.55). It is noteworthy that no OR exceeded three. Two other systematic reviews failed to draw conclusions on obstetrical complications related to EM except for preterm delivery[\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e] and placenta previa[\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e]. The results of this study showed a preterm birth rate of 16.84% and placenta previa rate of 7.36%, which are findings slightly higher than in Benaglia L\u0026rsquo;s report. In his retrospective, matched, case-control study[\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e], the rate of preterm birth was similar between the EM and non-EM groups (14% and 14%, respectively, p\u0026thinsp;=\u0026thinsp;0.89), while placenta previa was more common in women with EM than in the control group (6% versus 1%, respectively; p\u0026thinsp;=\u0026thinsp;0.006, OR 4.8, 95% CI: 1.4\u0026ndash;17.2). A possible explanation for this might be that our cases had patients with both EM and AM. In a multicenter, retrospective, questionnaire survey[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e] including 272 pregnant women with AM from 65 facilities, the preterm delivery rate was reported to be as high as 24.4%. Several studies further analyzed the clinical factors that affect pregnancy outcomes. In a retrospective study of 631 women with EM who became pregnant by ART [\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e], the reported incidence of preterm delivery or abnormal placental positioning didn\u0026rsquo;t increase in stages I\u0026ndash;III, but increased significantly in stage IV. Dr. Kim and colleagues[\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e] reported a preterm labor rate of 24.56% in a retrospective study and found that uterine wall thickness in the second trimester was related to subsequent preterm delivery. In our study, the size of uterus was also found to be significantly different between the two groups.\u003c/p\u003e\n\u003cp\u003eThe etiology of infertility might include disordered inflammatory factors like prostaglandin (PG) production (PGE2 and PGF2a), cyclooxygenase 2 (COX-2)[\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e], abnormal ER- and PR-mediated signaling pathways associated with progesterone resistance[\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e], impaired trophoblast invasiveness, and uterine contractility[\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]. These can also be related to failure of the physiologic transformation of spiral arteries in the inner myometrial segment, or junctional zone (JZ). Alterations of the JZ in women with EM and AM can influence vascular resistance of JZ spiral arteries at the onset of decidualization[\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e] and lead to incomplete spiral artery remodeling and the reduction of placental blood flow[\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e]. The mechanism is complex, and the existing results are debatable. The influence of co-existing EM and AM on pregnancy is not simply superimposed, but rather the two diseases interact with each other.\u003c/p\u003e\n\u003cp\u003eThe strength of this study is its diagnosis. The golden standard of AM diagnosis is based on histological specimens, which is an invasive technique and has a potential of uterine rupture during pregnancy and delivery. Therefore, non-invasive technics like ultrasound and MRI are preferred. MRI, with a sensitivity from 78\u0026ndash;88% and specificity from 67\u0026ndash;93% [\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e], was traditionally considered to be more accurate than ultrasound. However, with the development of high-quality transvaginal ultrasound (TVUS), a systematic review including 10 studies (1168 records) proved that the two techniques are comparable[\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e]. The accuracy of the ultrasound in AM diagnoses is high with a mean sensitivity of 0.72 (95% CI: 0.65\u0026ndash;0.79), specificity of 0.81 (95% CI: 0.77\u0026ndash;0.85), and area under the curve (AUC) of 0.85[\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e]. Additionally, ultrasounds are much cheaper and more convenient. The diagnoses of EM and its subtypes are based on laparoscopic surgery, which is the gold standard and quite reliable. However, women referred to our hospital may have had particularly severe forms of AM, EM, or repeated IVF failure, which introduces potential selection and comparison bias. Second, the follow up didn\u0026rsquo;t include an analysis of IVF details. Most patients went to their local ART center for controlled ovarian stimulation and IVF-ET and could hardly recall the details, remembering only the final results. There are several other limitations to these results. First, our study is retrospective. Second, the number of cases was limited and we could not perform subtype analyses according to the obstetric complications. Third, other disputed factors were not included, such as the excision of DIE[\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e], use of GnRHa[\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e], and complete removal of endometrial lesions [\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e]. Fourth, this study only includes patients that needed laparoscopic surgery. Although dysmenorrhea, metrorrhagia, chronic pelvic pain, dyspareunia, and infertility often occur, a third of the women were asymptomatic[\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e] and we are worried about the extent to which this will affect our fertility and sterility rates.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOverall, our study suggests that co-existing EM and AM has adverse effects on both reproductive performance and the outcome of pregnancy. Age, BMI, and size of endometrioma and the uterus were related to the prognosis. IVF is an important technique in improving the pregnancy rate following surgery. These findings may prove useful in daily practice for offering optimal infertility consultation to women with both EM and AM. Further prospective studies with larger sample sizes are still needed to draw firmer conclusions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe appreciate the whole stuff at Peking Union Medical College Hospital (PUMCH) for their clinical work and data recording about the cases we reported in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJH-S and JH-L designed the study. XY-L, SZ-J, and J-J Zhang retrieved the data and performed the data analysis. JH-S and Y-D drafted the manuscript. All the authors participated in the discussion of the results and critically revised the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompliance with Ethical Standards:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the National Key R\u0026amp;D Program of China (No. 2017YFC1001200), National Natural Science Foundation of China (No. 81541016)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declared that they have no conflict of interest related to the topic to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all individual participants included in the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBrosens, I., G. Kunz, and G. Benagiano, \u003cem\u003eIs adenomyosis the neglected phenotype of an endomyometrial dysfunction syndrome?\u003c/em\u003e Gynecol Surg, 2012. \u003cstrong\u003e9\u003c/strong\u003e(2): p. 131-137.\u003c/li\u003e\n\u003cli\u003eLi, X.Y., et al., \u003cem\u003eRisk factors for postoperative recurrence of ovarian endometriosis: long-term follow-up of 358 women.\u003c/em\u003e J Ovarian Res, 2019. \u003cstrong\u003e12\u003c/strong\u003e(1): p. 79.\u003c/li\u003e\n\u003cli\u003eLv, Y., et al., \u003cem\u003eThe medium to long term clinical outcomes of laparoscopic conservative surgery on adenomyomas.\u003c/em\u003e CHINESE JOURNAL OF PRACTICAL GYNECOLOGY AND OBSTETRICS, 2011. \u003cstrong\u003e27\u003c/strong\u003e(10): p. 753-756.\u003c/li\u003e\n\u003cli\u003eChapron, C., et al., \u003cem\u003eRelationship between the magnetic resonance imaging appearance of adenomyosis and endometriosis phenotypes.\u003c/em\u003e Hum Reprod, 2017. \u003cstrong\u003e32\u003c/strong\u003e(7): p. 1393-1401.\u003c/li\u003e\n\u003cli\u003eMochimaru, A., et al., \u003cem\u003eAdverse pregnancy outcomes associated with adenomyosis with uterine enlargement.\u003c/em\u003e Journal of Obstetrics and Gynaecology Research, 2014. \u003cstrong\u003e41\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eRazavi, M., et al., \u003cem\u003eSystematic review and meta-analysis of adverse pregnancy outcomes after uterine adenomyosis.\u003c/em\u003e Int J Gynaecol Obstet, 2019. \u003cstrong\u003e145\u003c/strong\u003e(2): p. 149-157.\u003c/li\u003e\n\u003cli\u003eHarada, T., et al., \u003cem\u003eAdverse obstetrical outcomes for women with endometriosis and adenomyosis: A large cohort of the Japan Environment and Children's Study.\u003c/em\u003e PLoS One, 2019. \u003cstrong\u003e14\u003c/strong\u003e(8): p. e0220256.\u003c/li\u003e\n\u003cli\u003eMaheux-Lacroix, S., et al., \u003cem\u003eEndometriosis fertility index predicts live births following surgical resection of moderate and severe endometriosis.\u003c/em\u003e Hum Reprod, 2017. \u003cstrong\u003e32\u003c/strong\u003e(11): p. 2243-2249.\u003c/li\u003e\n\u003cli\u003eLazzeri, L., et al., \u003cem\u003ePreoperative and Postoperative Clinical and Transvaginal Ultrasound Findings of Adenomyosis in Patients With Deep Infiltrating Endometriosis.\u003c/em\u003e Reprod Sci, 2014. \u003cstrong\u003e21\u003c/strong\u003e(8): p. 1027-1033.\u003c/li\u003e\n\u003cli\u003eVan den Bosch, T., et al., \u003cem\u003eTerms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group.\u003c/em\u003e Ultrasound Obstet Gynecol, 2015. \u003cstrong\u003e46\u003c/strong\u003e(3): p. 284-98.\u003c/li\u003e\n\u003cli\u003eTan, J., et al., \u003cem\u003eReproductive Outcomes after Fertility-Sparing Surgery for Focal and Diffuse Adenomyosis: A Systematic Review.\u003c/em\u003e J Minim Invasive Gynecol, 2018. \u003cstrong\u003e25\u003c/strong\u003e(4): p. 608-621.\u003c/li\u003e\n\u003cli\u003eMaignien, C., et al., \u003cem\u003ePrognostic factors for assisted reproductive technology in women with endometriosis-related infertility.\u003c/em\u003e Am J Obstet Gynecol, 2017. \u003cstrong\u003e216\u003c/strong\u003e(3): p. 280.e1-280.e9.\u003c/li\u003e\n\u003cli\u003eShi, J., et al., \u003cem\u003eFollicle loss after laparoscopic treatment of ovarian endometriotic cysts.\u003c/em\u003e Int J Gynaecol Obstet, 2011. \u003cstrong\u003e115\u003c/strong\u003e(3): p. 277-81.\u003c/li\u003e\n\u003cli\u003eShi, J.H., et al., \u003cem\u003eInfluence of Laparoscopic Cystectomy on Ovarian Reserve Function and Pregnantic Outcome in Women with Ovarian Endometriotic Cyst.\u003c/em\u003e MEDICAL JOURNAL OF PEKING UNION MEDICAL COLLEGE HOSPITAL, 2011. \u003cstrong\u003e002\u003c/strong\u003e(2): p. 20-24.\u003c/li\u003e\n\u003cli\u003eVercellini, P., et al., \u003cem\u003ePregnancy outcome in women with peritoneal, ovarian and rectovaginal endometriosis: a retrospective cohort study.\u003c/em\u003e Bjog, 2012. \u003cstrong\u003e119\u003c/strong\u003e(12): p. 1538-43.\u003c/li\u003e\n\u003cli\u003eHorton, J., et al., \u003cem\u003eReproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis.\u003c/em\u003e Human reproduction update, 2019. \u003cstrong\u003e25\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eVigano, P., L. Corti, and N. Berlanda, \u003cem\u003eBeyond infertility: obstetrical and postpartum complications associated with endometriosis and adenomyosis.\u003c/em\u003e Fertil Steril, 2015. \u003cstrong\u003e104\u003c/strong\u003e(4): p. 802-812.\u003c/li\u003e\n\u003cli\u003eLeone Roberti Maggiore, U., et al., \u003cem\u003eA systematic review on endometriosis during pregnancy: diagnosis, misdiagnosis, complications and outcomes.\u003c/em\u003e Human Reproduction Update, 2015. \u003cstrong\u003e22\u003c/strong\u003e(1): p. 70-103.\u003c/li\u003e\n\u003cli\u003eBenaglia, L., et al., \u003cem\u003ePregnancy outcome in women with endometriosis achieving pregnancy with IVF.\u003c/em\u003e Hum Reprod, 2016. \u003cstrong\u003e31\u003c/strong\u003e(12): p. 2730-2736.\u003c/li\u003e\n\u003cli\u003eTamura, H., et al., \u003cem\u003eComplications and outcomes of pregnant women with adenomyosis in Japan.\u003c/em\u003e Reprod Med Biol, 2017. \u003cstrong\u003e16\u003c/strong\u003e(4): p. 330-336.\u003c/li\u003e\n\u003cli\u003eFujii, T., et al., \u003cem\u003eAssisted reproductive technology pregnancy complications are significantly associated with endometriosis severity before conception: a retrospective cohort study.\u003c/em\u003e \u003cstrong\u003e14\u003c/strong\u003e(1): p. 73.\u003c/li\u003e\n\u003cli\u003eKim, Y.-M., et al., \u003cem\u003eUterine wall thickness at the second trimester can predict subsequent preterm delivery in pregnancies with adenomyosis.\u003c/em\u003e Taiwanese Journal of Obstetrics and Gynecology, 2019. \u003cstrong\u003e58\u003c/strong\u003e: p. 598-603.\u003c/li\u003e\n\u003cli\u003eVannuccini, S., et al., \u003cem\u003eInfertility and reproductive disorders: impact of hormonal and inflammatory mechanisms on pregnancy outcome.\u003c/em\u003e Hum Reprod Update, 2016. \u003cstrong\u003e22\u003c/strong\u003e(1): p. 104-15.\u003c/li\u003e\n\u003cli\u003eLessey, B.A. and S.L. Young, \u003cem\u003eHomeostasis imbalance in the endometrium of women with implantation defects: the role of estrogen and progesterone.\u003c/em\u003e Semin Reprod Med, 2014. \u003cstrong\u003e32\u003c/strong\u003e(5): p. 365-75.\u003c/li\u003e\n\u003cli\u003eAguilar, H.N. and B.F. Mitchell, \u003cem\u003ePhysiological pathways and molecular mechanisms regulating uterine contractility.\u003c/em\u003e Hum Reprod Update, 2010. \u003cstrong\u003e16\u003c/strong\u003e(6): p. 725-44.\u003c/li\u003e\n\u003cli\u003eHashimoto, A., et al., \u003cem\u003eImpact of endometriosis and adenomyosis on pregnancy outcomes.\u003c/em\u003e Hypertension Research in Pregnancy, 2019. \u003cstrong\u003e7\u003c/strong\u003e(2): p. 50-55.\u003c/li\u003e\n\u003cli\u003eGraziano, A., et al., \u003cem\u003eDiagnostic findings in adenomyosis: a pictorial review on the major concerns.\u003c/em\u003e Eur Rev Med Pharmacol Sci, 2015. \u003cstrong\u003e19\u003c/strong\u003e(7): p. 1146-54.\u003c/li\u003e\n\u003cli\u003eTellum, T., S. Nygaard, and M. Lieng, \u003cem\u003eNoninvasive Diagnosis of Adenomyosis: A Structured Review and Meta-analysis of Diagnostic Accuracy in Imaging.\u003c/em\u003e J Minim Invasive Gynecol, 2019.\u003c/li\u003e\n\u003cli\u003eChampaneria, R., et al., \u003cem\u003eUltrasound scan and magnetic resonance imaging for the diagnosis of adenomyosis: systematic review comparing test accuracy.\u003c/em\u003e Acta Obstet Gynecol Scand, 2010. \u003cstrong\u003e89\u003c/strong\u003e(11): p. 1374-84.\u003c/li\u003e\n\u003cli\u003eVan den Bosch, T. and D. Van Schoubroeck, \u003cem\u003eUltrasound diagnosis of endometriosis and adenomyosis: State of the art.\u003c/em\u003e Best Pract Res Clin Obstet Gynaecol, 2018. \u003cstrong\u003e51\u003c/strong\u003e: p. 16-24.\u003c/li\u003e\n\u003cli\u003eVercellini, P., et al., \u003cem\u003eAdenomyosis and reproductive performance after surgery for rectovaginal and colorectal endometriosis: a systematic review and meta-analysis.\u003c/em\u003e Reprod Biomed Online, 2014. \u003cstrong\u003e28\u003c/strong\u003e(6): p. 704-13.\u003c/li\u003e\n\u003cli\u003eYounes, G. and T. Tulandi, \u003cem\u003eEffects of adenomyosis on in vitro fertilization treatment outcomes: a meta-analysis.\u003c/em\u003e Fertil Steril, 2017. \u003cstrong\u003e108\u003c/strong\u003e(3): p. 483-490.e3.\u003c/li\u003e\n\u003cli\u003eBianchi, P.H.M., et al., \u003cem\u003eExtensive Excision of Deep Infiltrative Endometriosis before In Vitro Fertilization Significantly Improves Pregnancy Rates.\u003c/em\u003e Journal of Minimally Invasive Gynecology, 2009. \u003cstrong\u003e16\u003c/strong\u003e(2): p. 174-180.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Adenomyosis, Endometriosis; Infertility, Laparoscopic surgery, Pregnancy outcome","lastPublishedDoi":"10.21203/rs.3.rs-85435/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-85435/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eAdenomyosis and endometriosis are often co-existent. Laparoscopic surgery is one of the main methods to diagnose and treat these conditions. However, very few studies have been done that concentrate on the pregnancy outcomes of infertile women with both adenomyosis and endometriosis after laparoscopic surgery, as well as the relevant influential factors.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: This is a retrospective, cross-sectional study including infertile women diagnosed with endometriosis and adenomyosis. All patients had undergone laparoscopic surgery and were divided into two groups according to pregnancy outcomes. Demographic data, operation records, and pregnancy outcomes were collected.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Ninety-seven patients had live births, including 81 full-term and 16 preterm deliveries. The biochemical pregnancy, clinical pregnancy, and live birth rates were 80.87%, 67.4, and 55.11% respectively. One hundred thirty-five patients received IVF with 70 (51.85%) patients having live births. Age, size of endometrioma, and size of uterus were significantly lower in those who had a successful delivery. There was no statistical difference in symptoms except anemia (13.40% vs. 25.32%, p=0.044). The group that failed to have a live birth had a higher percentage of ovarian and peritoneal endometriosis (P\u0026lt;.05), while the distribution of deep infiltrating endometriosis and adenomyosis types were similar. Mean uterus diameter (OR: 0.636, 95% CI: 0.434-0.932, p = 0.020) and endometriosis fertility index (EFI) (OR:1.299, 95% CI: 1.101-1.531, p = 0.002) were significantly correlated with live births in the multivariate analysis.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eEndometriosis and adenomyosis have an adverse effect on fertility. IVF is an important technology improving pregnancy rate even after surgery. The size of the uterus and EFI were independent risk factors for pregnancy outcomes.\u003c/p\u003e","manuscriptTitle":"Pregnancy outcomes of infertile women with co-existing endometriosis and adenomyosis after laparoscopic surgery: a long-term follow-up","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-10-06 19:36:40","doi":"10.21203/rs.3.rs-85435/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-12-13T00:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-11-22T01:00:00+00:00","index":7,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-11-22T00:00:00+00:00","index":7,"fulltext":"Recommendation: Accept after discretionary revisions\nForm responses:\n---\n\nComments to Author:\n---\nThe paper is well written and easy to understand.\n\nThe first point to make is that this paper will be mainly of interest to gynaecologists, and as an obstetrician, I am not familiar with the literature on endometriosis and adenomyosis. Accordingly, I was not aware how frequently there is a combination of endometriosis and adenomyosis, or what proportion of the total population of women with endometriosis this might represent. The authors say that it is about 30 to 40%, which I presume makes it of significant importance to gynaecologists. I already knew that both conditions were likely to be associated with infertility and so the figure that about half of women treated who wish to have a family will succeed in becoming pregnant is useful for counselling. I am not aware if this information was available before, but it is likely to have been. There appears to be little practical value in the findings other than for counselling.\n\nThe outcomes of the pregnancy do not seem to be very unusual, but there is no control group so it is difficult to be sure. The incidence of abnormal placentation appears to be higher than one would have expected (the authors say that this has been reported before), although there is no information given about previous Caesarean sections, which would be relevant (some of the women were parous).\n\nI have a few minor comments. Given the relatively small number of patients studied (less than 200), there is no need to give percentages to 4 significant figures, and a similarly giving time durations to an accuracy of 0.01 (about six hours) is unnecessary. In the abstract, there is a mention of the different rate of anaemia in the two groups but it is not clear which group has the higher rate of anaemia until one reads the table of results. This should be made clear in the abstract.\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"editorInvitedReview","content":"","date":"2020-11-22T00:00:00+00:00","index":6,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nThis is a retrospective cross-sectional study evaluating pregnancy outcomes of women with infertility and adenomyosis and endometriosis who have had laparoscopic surgery as predicted by the endometriosis fertility index and revised American Fertility Society score. \n\n(Line numbers do not correlate to lines in text so therefore not used to reference suggested edits.)\n\n* Consider exchanging \"infertile women\" to \"women with infertility\" throughout, including title.\n* How was infertility defined for the purposes of this study?\n\nIntroduction\n* Consider changing to \"Our center reported that 39.9% of women with an endometrioma also had AM...\"\n* Second paragraph second sentence is not grammatically correct\n\nMethods\n* How long were patients followed after they received surgery? How was the study period defined?\n* Long term follow up should be mentioned here in the methods section as well (appears for the first time in the results section)\n* Which patients had failed IVF prior to laparoscopy?\n\nResults\n* Consider \"were excluded due to age criteria\" thus avoiding use of \"elderly\". Why was 40 years old used as a cutoff? AMA and very AMA designations are 35 and 45 respectively.\n* Consider placing definition of \"successful delivery\" under materials and methods, rather than results\n* Consider changing \"Group B contained those who didn't get live birth\" to \"Group B consisted of those patient's not achieving successful delivery\"\n* It is unclear which patient's had IVF versus which patients conceived spontaneously after surgery (with regards to the live birth outcome). It is important to perform analysis on these groups separately.\n* Graphical representation of long term follow up might be helpful, especially given the variation in length of follow up among these patients\n\n\nComment\n* It is important to investigate predictors of live birth success rates among patients with concomitant endometriosis and adenomyosis and it seems as though the authors have an adequate database available to analyze for contribution to the literature on this topic. However, this paper as written is hard to follow grammatically. There is a lack of clarity in the description of the patient populations, definitions of categorical designations, and in the description of the analyses performed. For example, it is unclear which patients had IVF versus which conceived spontaneously after surgery. Those conceived by IVF should be analyzed separately from those that conceived spontaneously. This paper needs major revision before it can be considered for publication. \n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **No**\n* Are the methods sufficiently described to allow the study to be repeated?: **No**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **No**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2020-11-22T00:00:00+00:00","index":6,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-11-01T00:00:00+00:00","index":4,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nI read with great interest the Manuscript titled \"Pregnancy outcomes of infertile women with co-existing endometriosis and adenomyosis after laparoscopic surgery: a long-term follow-up\" (PRCH-D-20-02066).\nThe study is well written, has important clinical message, and should be of great interest to the readers of BMC Pregnancy and Childbirth. The Manuscript can be further expanded and improved, and reference list can be updated by citing recent studies about the topic.\nAccording to my opinion, only a few small improvements are needed, as suggested below:\n- The Manuscript should be further revised by a native English speaker.\n- The Authors did not mention the sample size calculation for their study. It is essential to specify this data in order to guarantee an adequate significance of the results obtained by the Authors.\n- In the Results section, the Authors have simply reported the p values from which however it is not possible to deduce the real clinical relevance of the highlighted statistical significance. In order to better understand the results obtained, I strongly suggest reporting not only the p values but also the corresponding confidence intervals.\n- It would be interesting to briefly discuss clinical features and treatment of endometriosis, mentioning these recent studies about the topic: doi:10.1038/nrendo.2013.255; doi: 10.2147/JPR.S207599; doi:10.1093/humrep/det457.\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"editorInvitedReview","content":"","date":"2020-11-01T00:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nThis paper examines the outcomes of 176 women between the ages of 20 and 40 after laparoscopic surgery for endometriosis/adenomyosis. The paper does not say anything new, but confirms what is already known about endometriosis and adenomyosis. \n\nThe paper needs to add to the abstract that the study looks at 176 women after laparoscopic surgery for endometriosis/adenomyosis who wished to have a live birth.\n\nThe researchers did long term follow up, but states that it excluded 7 women (4%) of women because they had not delivered yet. It is stated: \"The remaining seven patients were still pregnant and were excluded\" It is\nnot logical that 4% of the women were excluded because they didnt want to wait a couple of months for the end of their pregnancies, since the follow up of the women was for \"median 47 months, range 20-80 months\". Could the authors clarify why they excluded 7 pregnant women? why couldnt they wait 2-4 months until 4% of the women delivered?\n\n\" Our results were a bit higher, perhaps because of the longevity of our follow up.\" The authors should add to this conclusion and to the abstract that their results are also better because\nthey eliminated the highest risk women- who are aged 40 and over.\n\nIVF was used more frequently and more rounds of IVF were offered.\n\nThere were women with BMI over 24 in the study. Average BMI = 21\n\nThese 3 points should also appear in the abstract, since they are very interesting. For example, No American study has a study group with average BMI = 21.\n\n\nAlso, in Figure one- the authors should make it clear that the 31 women who were eliminated from the study was because they were not interested in getting pregnant.\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **No competing interests.\nHave never received any reimbursements, fees or funding and none coming in the future.\nNo stocks. No shares,\nNo patents.\nNo reimbursements, fees or funding from any patents ever.\nNo financial competing interests.\nNo non-financial competing interests. I declare i have no competing interests.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please publish my name with my report.**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"editorInvitedReview","content":"","date":"2020-11-01T00:00:00+00:00","index":5,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\n1) page 4 line 28, should have a comma instead of and before pregnancy outcomes\n2) Page 5 line 38, instead of \"most recently before surgery\" would read better as \"immediately prior to surgery\"\n3) It would be helpful to put in the population based numbers for the adverse pregnancy outcomes that you describe, especially as you don't have a control group. For example an early loss rate of 27% is likely similar to the population based rate but a 16% preterm labour rate is likely higher in your population than the general pregnancy population\n4) as laparoscopic surgery for adenomysis is quite rare, at least here in Canada, can you please describe at some point what may have been done during those procedures, I would imaging a hysterotomy would have needed to be done\n5) Page 9 line 13 should read scant rather than scanty\n6) It would be nice to see what was done at the surgeries and how many of the patients needed surgery for adenomyosis. Your conclusion that the co-existence of the diseases worsens outcomes but many of the obstetrical outcomes that you listed (preterm labour, previa, abnormal placentation) are more linked to AM and it would be good to know how many patients received surgery for this.\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **No**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"editorInvitedReview","content":"","date":"2020-11-01T00:00:00+00:00","index":3,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nThank you for the opportunity to review the paper which I was excited to read. However I would recommend these changes be considered before possible publication\nTitle: The title indicates that this study is a long-term prospective cohort study but when you get to methods it is a retrospective cross-sectional study. Which is it? Are the women 'infertile' or are they women who are having their fertility investigated? The main challenge I have is with the term 'infertile women'. These women were having their fertility investigated and were found to have EM and AM. Please remove the term 'infertile from the title and abstract and refer to these women were undergoing laparoscopy to investigate causation of infertility.\nWhat is the novelty of this study? I am not sure how it contributes greatly to our current understanding of pregnancy outcomes as we know little about spontaneous pregnancy and no detail on the IVF treatment undertaken. I did not get a sense that any pregnancy outcomes can be predicted from this data in women who have AM or EM. How many women had both? The conclusion really speaks for itself. There were likely too many limitations to this study to make this a valuable contribution to our current prediction models of these risk factors and likely live birth outcomes.\nAbstract\nLine 1 Delete the word 'are' where highlighted\nMethods in Abstract\nIndicate what the pregnancy outcome is in the abstract. Are we talking live birth or clinical pregnancy? Biochemical pregnancies is not a good marker for a pregnancy outcome\nPlease indicate the total number investigated first then break it down as I don't know how many didn't have IVF\nInsert the word 'and' under Results in Abstract where highlighted\nIndicate what type of anaemia and which group had higher anaemia levels please\nDon't use the term 'failed' to have a live birth. Say the group were a live birth did not occur or did not proceed to a live birth. Or some other word not seen as potentially emotive\nConclusion\nTalk about live birth as outcome please and add an 's' to pregnancy rates\n\nIntroduction\nLine 7 , add the word respectively so readers can differentiate which definition belongs to adeno and which is endo\nLine 30, doesn't make sense, looks like you didn't complete the sentence\nPlease use different headings for Methods, it didn't appear differentiated for me\nMethods\nPage 4, Line 5, what does IRB stand for. Spell it out the first time and then use acronym please\nPage 4, Line 13, please tell us the number who underwent laparoscopic surgery over that time and what percentage of that population was diagnosed\nPage 4, line 15, Please give us the number of women who underwent surgery in this time period so we have a denominator. This gives some context to the prevalence of the problem\nPage 4, Line 17, what is the definition of infertile here (please define this as it can be different in different countries and practices)\nPage 4, Line 21 What do you mean by 'coagulation' here. Is this the correct context and grammar/word? Perhaps you need a small section clearly outlining the sample processing protocols\nPage 4, Line 60, why was laparotomy excluded?\nPage 5, line 2. Don't use the word etc. Please list all the exclusions to make the population group more transparent (a table may be advisable)\nStatistical analysis\nPage 5, Line 17. What is this p value for Is this the power of the study? If this is a statistical significance it is not appropriate. Less than .05 is better, do you mean .02?\nResults\nPage 5, Line 33. Never start a sentence with a number, you need to use the word of the number, ie Forty-three.\nPage 5, Line 35, add the word 'either'. This way we see where the 43 comes from\nPage 5, Line 40, where are the other 7 women? Oh yes, maybe just put this in the earlier line so people can clearly see the sequence of exclusion\nLine 44 replace 'get' with 'experience' a live birth\nSurgical findings\nPage 6, Line 4. Group A had higher EFI but shorter surgery and Group B had higher rates of ovarian and peritoneal infiltration so why didn't they get higher EFI? Is EFI calculated before surgery OR at surgery?\nI think you need to define how EFI is calculated so the reader can understand the impact of the surgical findings\nPage 6, Line 7, differences needs a plural\nFertility results and pregnancy outcomes\nPage 6, Line 31. Don't start a sentence with a number\nPage 7, Line 4, a p value of \u003c.00 is usually reported as \u003c.001\nPage 7, line 6, please identify the anaemia\nPage 7, line 6, is diameter endometrial thickness? I haven't heard this term but it may be appropriate, please identify exactly what it was you were measuring\nDiscussion\nPage 8, line 21- why is it noteworthy that the OR never reached 3. I don't understand this, could you please provide some context to this statement\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **No**\n* Are the methods sufficiently described to allow the study to be repeated?: **No**\n* Is the use of statistics and treatment of uncertainties appropriate?: **No**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2020-10-31T00:00:00+00:00","index":5,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-10-28T12:00:00+00:00","index":4,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-10-28T12:00:00+00:00","index":3,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-10-18T12:00:00+00:00","index":1,"fulltext":"Recommendation: Reject\nForm responses:\n---\n\nComments to Author:\n---\nThank you for inviting me to review this work\n1-trial registration number is not included\n2-type of study design no mentioned in the title\n3-aim of work not mentioned on abstract\n4-cross section study could not considered a retrospective on* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **No**\n* Are the methods sufficiently described to allow the study to be repeated?: **No**\n* Is the use of statistics and treatment of uncertainties appropriate?: **No**\n* Is the presentation of the work clear?: **No**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **No**\n"},{"type":"reviewerAgreed","content":"","date":"2020-10-07T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-10-07T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-10-07T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-09-25T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-09-24T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-09-24T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2020-09-23T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"11b4439a-db4e-425d-ac82-932435eba907","owner":[],"postedDate":"October 6th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":673706,"name":"Sexual \u0026 Reproductive Medicine"},{"id":673707,"name":"Maternal \u0026 Fetal Medicine"}],"tags":[],"updatedAt":"2021-01-03T23:48:01+00:00","versionOfRecord":[],"versionCreatedAt":"2020-10-06 19:36:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-85435","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-85435","identity":"rs-85435","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}