New adverse obstetrics outcomes associated with endometriosis: a retrospective cohort study

Purpose The main aim of this study was to evaluate the incidence of endometriosis and intrahepatic cholestasis (ICP) and induction of labor in pregnant women with endometriosis compared with women without endometriosis. The secondary aim was to confirm increased incidence of already known endometriosis-related pregnancy complications in these patients.

This is a retrospective cohort study performed at a tertiary hospital between January 2009 and December 2014 to compare obstetrics outcome between women with endometriosis and women without endometriosis. Pregnant patients with endometriosis were included in the study group. Patients were divided in the following subgroups: patients with deep infiltrating endometriosis (DIE subgroup) and patients without deep infiltrating endometriosis (non-DIE subgroup); patients with singleton pregnancy and spontaneous conception (subgroup A) and patients with multiple pregnancy and/or patients who underwent assisted reproductive technology (subgroup B). To form a control group, for each patient with endometriosis, two patients without endometriosis were selected as the control group by means of matched sample.

The study population included 262 pregnant women with endometriosis and 524 controls. Patients of the study population had significantly increased risks of placenta praevia (p < 0.05), ICP (p < 0.01), induction of labor (p < 0.01) and preterm birth (p < 0.01). DIE patients had a significantly higher percentage only of preterm birth (p < 0.01), while in non-DIE group all complications had a higher incidence except for placenta praevia, which did not differ with control. Subgroup A had a statistically higher incidence of placenta praevia (p < 0.01), ICP (p < 0.01), induction of labor (p < 0.01) and preterm birth (p < 0.01) compared to its control subgroup. There was no difference in distribution of pregnancy complications between subgroup B and control subgroup.

Our results showed for the first time that women with endometriosis are at higher risk of developing ICP and experiencing an induced labor. Further studies are warranted to clarify whether the history of endometriosis might be taken into account in the antenatal care of these patients. Access this article We’re sorry, something doesn't seem to be working properly. Please try refreshing the page. If that doesn't work, please contact support so we can address the problem. Similar content being viewed by others

Eskenazi B, Warner ML (1997) Epidemiology of endometriosis. Obstet Gynecol Clin North Am 24:235–258 Braundmeier AG, Fazleabas AT (2009) The non-human primate model of endometriosis: research and implications for fecundity. Mol Hum Reprod 15:577–586. doi:10.1093/molehr/gap057 Templeman C, Marshall SF, Ursin G, Horn-Ross PL, Clarke CA, Allen M, Deapen D, Ziogas A, Reynolds P, Cress R, Anton-Culver H, West D, Ross RK, Bernstein L (2008) Adenomyosis and endometriosis in the California Teachers Study. Fertil Steril 90:415–424 Benagiano G, Brosens I (2014) In utero exposure and endometriosis. J Matern Fetal Neonatal Med 27:303–308. doi:10.3109/14767058.2013.814630 Brosens I, Brosens JJ, Benagiano G (2012) The eutopic endometrium in endometriosis: are the changes of clinical significance? Reprod Biomed Online 24:496–502. doi:10.1016/j.rbmo.2012.01.022 Carvalho L, Podgaec S, Bellodi-Privato M, Falcone T, Abrão MS (2011) Role of eutopic endometrium in pelvic endometriosis. J Minim Invasive Gynecol 18:419–427. doi:10.1016/j.jmig.2011.03.009 Leone Roberti Maggiore U, Ferrero S, Mangili G, Bergamini A, Inversetti A, Giorgione V, Viganò P, Candiani M (2016) A systematic review on endometriosis during pregnancy: diagnosis, misdiagnosis, complications and outcomes. Hum Reprod Update 22:70–103. doi:10.1093/humupd/dmv045 Cha J, Sun X, Dey SK (2012) Mechanisms of implantation: strategies for successful pregnancy. Nat Med 18:1754–1767. doi:10.1038/nm.3012 European IVF-Monitoring Consortium (EIM), European Society of Human Reproduction and Embryology (ESHRE), Kupka MS, D’Hooghe T, Ferraretti AP, de Mouzon J, Erb K, Castilla JA, Calhaz-Jorge C, De Geyter Ch, Goossens V (2016) Assisted reproductive technology in Europe, 2011: results generated from European registers by ESHRE†. Hum Reprod 31:233–248. doi:10.1093/humrep/dev319 Ohlsson Teague EM, Van der Hoek KH, Van der Hoek MB, Perry N, Wagaarachchi P, Robertson SA, Print CG, Hull LM (2009) MicroRNA-regulated pathways associated with endometriosis. Mol Endocrinol 23:265–275. doi: 10.1210/me.2008-0387 Guo SW (2009) Epigenetics of endometriosis. Mol Hum Reprod 15:587–607. doi:10.1093/molehr/gap064 Fambrini M, Sorbi F, Bussani C, Cioni R, Sisti G, Andersson KL (2013) Hypermethylation of HOXA10 gene in mid-luteal endometrium from women with ovarian endometriomas. Acta Obstet Gynecol Scand 92:1331–1334. doi:10.1111/aogs.12236 Benagiano G, Brosens I, Habiba M (2014) Structural and molecular features of the endomyometrium in endometriosis and adenomyosis. Hum Reprod Update 20:386–402. doi:10.1093/humupd/dmt052 Du Y, Gao M, Shi Y, Sun Z, Wang J (2013) Endocrine and inflammatory factors and endometriosis-associated infertility in assisted reproduction techniques. Arch Gynecol Obstet 287:123. doi:10.1007/s00404-012-2567-0 Kamada Y, Nakatsuka M, Asagiri K, Noguchi S, Habara T, Takata M, Kudo T (2000) GnRH agonist-suppressed expression of nitric oxide synthases and generation of peroxynitrite in adenomyosis. Hum Reprod 15(12):2512–2519 Ota H, Igarashi S, Kato N, Tanaka T (2000) Aberrant expression of glutathione peroxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis. Fertil Steril 74:313–318 Giudice LC (2010) Clinical practice. Endometriosis. N Engl J Med 362:2389–2398. doi:10.1056/NEJMcp1000274 Petraglia F, Arcuri F, de Ziegler D, Chapron C (2013) Inflammation: a link between endometriosis and preterm birth. Fertil Steril 98:36–40. doi:10.1016/j.fertnstert.2012.04.051 Kokcu A (2013) Possible effects of endometriosis-related immune events on reproductive function. Arch Gynecol Obstet 287:1225. doi:10.1007/s00404-013-2767-2 Perez MJ, Macias RI, Marin JJ (2006) Maternal cholestasis induces placental oxidative stress and apoptosis. Protective effect of ursodeoxycholic acid. Placenta 27:34–41 Du Q, Pan Y, Zhang Y, Zhang H, Zheng Y, Lu L, Wang J, Duan T, Chen J (2014) Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation. BMC Med Genom 7:42. doi:10.1186/1755-8794-7-42 Marschall HU, Wikström Shemer E, Ludvigsson JF, Stephansson O (2013) Intrahepatic cholestasis of pregnancy and associated hepatobiliary disease: a population-based cohort study. Hepatology 58(4):1385–1391. doi:10.1002/hep.26444 Lin L, Zhang LJ (2008) Role of CD4 + CD25 high regulatory T cells in the pathogenesis of intrahepatic cholestasis of pregnancy. Zhonghua Fu Chan Ke Za Zhi 43:900–903 Yayi H, Danqing W, Shuyun L, Jicheng L (2010) Immunologic abnormality of intrahepatic cholestasis of pregnancy. Am J Reprod Immunol 63:267–273. doi:10.1111/j.1600-0897.2009.00798.x He P, Wang F, Jiang Y, Zhong Y, Lan Y, Chen S (2014) Placental proteome alterations in women with intraepathic cholestasis of pregnancy. Int J Gynaecol Obstet 126:256–259. doi:10.1016/j.ijgo.2014.03.035 Zakar T, Hertelendy F (2007) Progesterone withdrawal: key to parturition. Am J Obstet Gynecol 196:289–296 Stephansson O, Kieler H, Granath F, Falconer H (2009) Endometriosis, assisted reproduction technology, and risk of adverse pregnancy outcome. Hum Reprod 24:2341–2347. doi:10.1093/humrep/dep186 Healy DL, Breheny S, Halliday J, Jaques A, Rushford D, Garrett C, Talbot JM, Baker HW (2010) Prevalence and risk factors for obstetric haemorrhage in 6730 singleton births after assisted reproductive technology in Victoria Australia. Hum Reprod 25:265–274. doi:10.1093/humrep/dep376 Kuivasaari-Pirinen P, Raatikainen K, Hippeläinen M, Heinonen S (2012) Adverse outcomes of IVF/ICSI pregnancies vary depending on aetiology of infertility. ISRN Obstet Gynecol 2012:451915. doi:10.5402/2012/451915 Vercellini P, Parazzini F, Pietropaolo G, Cipriani S, Frattaruolo MP, Fedele L (2012) Pregnancy outcome in women with peritoneal, ovarian and rectovaginal endometriosis: a retrospective cohort study. BJOG 119:1538–1543. doi:10.1111/j.1471-0528.2012.03466.x Fernando S, Breheny S, Jaques AM, Halliday JL, Baker G, Healy D (2009) Preterm birth, ovarian endometriomata, and assisted reproduction technologies. Fertil Steril 91:325–330. doi:10.1016/j.fertnstert.2008.01.096 Stern JE, Luke B, Tobias M, Gopal D, Hornstein MD, Diop H (2015) Adverse pregnancy and birth outcomes associated with underlying diagnosis with and without assisted reproductive technology treatment. Fertil Steril 103:1438–1445. doi:10.1016/j.fertnstert.2015.02.027 Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest The authors declare that they have no conflict of interest. Authors state that they have had full control of all primary data and that they agree to allow the Journal to review their data if requested. Research involving human participants and/or animals 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. Rights and permissions About this article Cite this article Mannini, L., Sorbi, F., Noci, I. et al. New adverse obstetrics outcomes associated with endometriosis: a retrospective cohort study. Arch Gynecol Obstet 295, 141–151 (2017). https://doi.org/10.1007/s00404-016-4222-7 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00404-016-4222-7