Premature Birth in Women with Endometriosis: a Systematic Review and Meta-analysis

The objective of this study is to verify the association between endometriosis and preterm birth through systematic review and meta-analysis. Is there an increased risk of premature birth in women with endometriosis compared to women without this diagnosis? The databases searched were PubMed, Medline, and LILACS in order to identify all studies published up to April 2020, using the keywords (prematurity OR preterm birth OR premature birth OR premature labor OR obstetric premature labor OR preterm labor OR premature obstetric labor) AND (endometriosis OR adenomyosis OR endometrioma OR endometriomas). A manual research was also performed through the analysis of theses, book chapters, reference references, guidelines, and reviews. All published prospective cohort studies that reported the prevalence of preterm delivery among women with endometriosis, adenomyosis, or endometrioma were included, comparing it to the control group of women without such diagnoses. The random-effects model, the calculation of relative risk, and the confidence interval of 95% were used to perform the meta-analysis. Three studies involving 10,111 patients were included. Compared to women without endometriosis, women with endometriosis present an increased risk of premature birth (RR: 2.68, 95% CI [1.19; 6.02], I2 = 91%). In the subgroup of women with spontaneous conception, endometriosis is also a risk factor for prematurity (RR: 3.26, 95% CI [2.09; 5.09], I2 = 0%, 2 studies, 682 participants). The evidence presented suggests that women with endometriosis should be alerted to a potential risk of preterm birth. PROSPERO registration number, CRD42020189451 Similar content being viewed by others Data Availability The data of this article are available with the corresponding author, by email [email protected]. Code Availability Not applicable.

Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447):1789–99. Gao X, Yeh YC, Outley J, Simon J, Botteman M, Spalding J. Health-related quality of life burden of women with endometriosis: a literature review. Curr Med Res Opin. 2006;22(9):1787–97. Missmer SA, Cramer DW. The epidemiology of endometriosis. Obstet Gynecol Clin North Am. 2003;30(1):1–19. Acién P, Velasco I. Endometriosis: a disease that remains enigmatic. ISRN Obstet Gynecol. 2013; 2013:242149. Petraglia F, Arcuri F, de Ziegler D, Chapron C. Inflammation: a link between endometriosis and preterm birth. Fertil Steril. 2012;98(1):36–40. Brosens I, Brosens JJ, Fusi L, Al-Sabbagh M, Kuroda K, Benagiano G. Risks of adverse pregnancy outcome in endometriosis. Fertil Steril. 2012;98(1):30–5. Romero R, Dey SK, Fisher SJ. Preterm labor: one syndrome, many causes. Science. 2014;345(6198):760–5. Borghese B, Zondervan KT, Abrao MS, Chapron C, Vaiman D. Recent insights on the genetics and epigenetics of endometriosis. Clin Genet. 2017;91(2):254–64. Saigal S, Doyle LW. An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet. 2008;371(9608):261–9. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009; 6(7):e1000100. Bonuccelli G, Ferreira R, Negrini R. Premature birth in women with endometriosis: a systematic review and meta-analysis. [online]. PROSPERO. 2020; crd42020189451. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020189451 [18 aug 2017] Zullo F, Spagnolo E, Saccone G, Acunzo M, Xodo S, Ceccaroni M, et al. Endometriosis and obstetrics complications: a systematic review and meta-analysis. Fertil Steril. 2017;108(4):667-72.e5. Lalani S, Choudhry AJ, Firth B, Bacal V, Walker M, Wen SW, et al. Endometriosis and adverse maternal, fetal and neonatal outcomes, a systematic review and meta-analysis. Hum Reprod. 2018;33(10):1854–65. Razavi M, Maleki-Hajiagha A, Sepidarkish M, Rouholamin S, Almasi-Hashiani A, Rezaeinejad M. Systematic review and meta-analysis of adverse pregnancy outcomes after uterine adenomyosis. Int J Gynaecol Obstet. 2019;145(2):149–57. Glavind MT, Mollgaard MV, Iversen ML, Arendt LH, Forman A. Obstetrical outcome in women with endometriosis including spontaneous hemoperitoneum and bowel perforation: a systematic review. Best Pract Res Clin Obstet Gynaecol. 2018;51:41–52. Kim SG, Seo HG, Kim YS. Primiparous singleton women with endometriosis have an increased risk of preterm birth: meta-analyses. Obstet Gynecol Sci. 2017;60(3):283–8. Tan J, Moriarty S, Taskin O, Allaire C, Williams C, Young P, et al. Reproductive outcomes after fertility-sparing surgery for focal and diffuse adenomyosis: a systematic review. J Minim Invasive Gynecol. 2018;25(4):608–21. Annicchino G, Malvezzi H, Piccinato CA, Podgaec S. Is there an increased risk for unfavorable obstetric outcomes in women with endometriosis? An evaluation of evidences. Rev Bras Ginecol Obstet. 2020;42(4):200–10. Maheshwari A, Gurunath S, Fatima F, Bhattacharya S. Adenomyosis and subfertility: a systematic review of prevalence, diagnosis, treatment and fertility outcomes. Hum Reprod Update. 2012;18(4):374–92. Cozzolino M, Basile F, Pontrelli G. Effects of adenomyosis on obstetric outcomes. Minerva Ginecol. 2019;71(2):146–54. Maggiore ULR, Ferrero S, Mangili G, Bergamini A, Inversetti A, Giorgione V, et al. A systematic review on endometriosis during pregnancy: diagnosis, misdiagnosis, complications and outcomes. Hum Reprod Update. 2016;22(1):70–103. Bruun MR, Arendt LH, Forman A, Ramlau-Hansen CH. Endometriosis and adenomyosis are associated with increased risk of preterm delivery and a small-for-gestational-age child: a systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2018;97(9):1073–90. Pérez-López FR, Villagrasa-Boli P, Muñoz-Olarte M, Morera-Grau Á, Cruz-Andrés P, Hernandez AV, et al. Association between endometriosis and preterm birth in women with spontaneous conception or using assisted reproductive technology: a systematic review and meta-analysis of cohort studies. Reprod Sci. 2018;25(3):311–9. Horton J, Sterrenburg M, Lane S, Maheshwari A, Li TC, Cheong Y. Reproductive, obstetric, and perinatal outcomes of women with adenomyosis and endometriosis: a systematic review and meta-analysis. Hum Reprod Update. 2019;25(5):592–632. Kobayashi H, Kawahara N, Ogawa K, Yoshimoto C. A relationship between endometriosis and obstetric complications. Reprod Sci. 2020;27(3):771–8. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. [online]. Ottawa: Ottawa Hospital Research Institute; 2000. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp [18 aug 2017] Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions: version 5.1.0. [online]. The Cochrane Collaboration; 2011. Available from: https://training.cochrane.org/handbook/archive/v5.1/ [18 aug 2017] Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60. Exacoustos C, Lauriola I, Lazzeri L, De Felice G, Zupi E. Complications during pregnancy and delivery in women with untreated rectovaginal deep infiltrating endometriosis. Fertil Steril. 2016;106(5):1129-35.e1. Porpora MG, Tomao F, Ticino A, Piacenti I, Scaramuzzino S, Simonetti S, et al. Endometriosis and pregnancy: a single institution experience. Int J Environ Res Public Health. 2020;17(2):401. Harada T, Taniguchi F, Onishi K, Kurozawa Y, Hayashi K, Harada T, et al. Obstetrical complications in women with endometriosis: a cohort study in Japan. PLoS One. 2016; 11(12):e0168476. Howson CP, Kinney MV, McDougall L, Lawn JE, Born Too Soon Preterm Birth Action Group. Born too soon: preterm birth matters. Reprod Health. 2013; 10(Suppl 1):S1. Palomba S, Homburg R, Santagni S, La Sala GB, Orvieto R. Risk of adverse pregnancy and perinatal outcomes after high technology infertility treatment: a comprehensive systematic review. Reprod Biol Endocrinol. 2016;14(1):76. Helmerhorst FM, Perquin DAM, Donker D, Keirse MJNC. Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. BMJ. 2004;328(7434):261. Kennedy S, Bergqvist A, Chapron C, D’Hooghe T, Dunselman G, Greb R, et al. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod. 2005;20(10):2698–704. Conti N, Cevenini G, Vannuccini S, Orlandini C, Valensise H, Gervasi MT, et al. Women with endometriosis at first pregnancy have an increased risk of adverse obstetric outcome. J Matern Fetal Neonatal Med. 2015;28(15):1795–8. Funding This work was supported by the authors. Author information Authors and Affiliations Contributions Giovana A. Bonuccelli: conceptualization, methodology, software, formal analysis, validation, writing—original draft preparation. Romulo Negrini: validation, data curation, writing—reviewing and editing, visualization. Raquel D. S. Ferreira: writing—reviewing and editing. Corresponding author Ethics declarations Ethics Approval This work was approved by research ethics committee of Hospital Central Santa Casa de Misericórdia de São Paulo. Consent to Participate Not applicable. Consent for Publication The authors and institution agreed with this publication, in with was used only data. Competing Interest The authors declare no competing interests. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions About this article Cite this article Bonuccelli, G.A., Negrini, R. & da Silva Ferreira, R.D. Premature Birth in Women with Endometriosis: a Systematic Review and Meta-analysis. Reprod. Sci. 29, 250–259 (2022). https://doi.org/10.1007/s43032-021-00712-1 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-021-00712-1