Uterine factors in recurrent pregnancy losses

Congenital and acquired uterine anomalies are associated with recurrent pregnancy loss (RPL). Relevant congenital Müllerian tract anomalies include unicornuate, bicornuate septate, and arcuate uterus. Recurrent pregnancy loss has also been associated with acquired uterine abnormalities that distort the uterine cavity such as, notably, intrauterine adhesions, polyps, and submucosal myomas. Initial evaluation of women with RPLs should include an assessment of the uterine anatomy. Even if proof of efficacy of surgical management of certain uterine anomalies is often lacking for managing RPLs, surgery should be encouraged in certain circumstances for improving subsequent pregnancy outcome. Uterine anomalies such as uterine septa, endometrial polyps, intrauterine adhesions, and submucosal myomas are the primary surgical indications for managing RPLs. Congenital and acquired uterine anomalies are associated with recurrent pregnancy loss (RPL). Relevant congenital Müllerian tract anomalies include unicornuate, bicornuate septate, and arcuate uterus. Recurrent pregnancy loss has also been associated with acquired uterine abnormalities that distort the uterine cavity such as, notably, intrauterine adhesions, polyps, and submucosal myomas. Initial evaluation of women with RPLs should include an assessment of the uterine anatomy. Even if proof of efficacy of surgical management of certain uterine anomalies is often lacking for managing RPLs, surgery should be encouraged in certain circumstances for improving subsequent pregnancy outcome. Uterine anomalies such as uterine septa, endometrial polyps, intrauterine adhesions, and submucosal myomas are the primary surgical indications for managing RPLs. Discuss: You can discuss this article with its authors and other readers at There is no general consensus for defining recurrent pregnancy loss (RPL) and its management (1Youssef A. Vermeulen N. Lashley E. Goddijn M. van der Hoorn M.L.P. Comparison and appraisal of (inter)national recurrent pregnancy loss guidelines.Reprod Biomed Online. 2019; 39: 497-503Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar). Classically, RPL is defined by the occurrence of three or more miscarriages—consecutive or not—occurring before 20 weeks of gestation, that is, before fetal viability (2Rock J.A. Zacur H.A. The clinical management of repeated early pregnancy wastage.Fertil Steril. 1983; 39: 123-140Abstract Full Text PDF PubMed Google Scholar). In spite of this commonly accepted idea, it has been recently suggested that it is appropriate to start investigating infertile women—particularly if they are young—after two miscarriages (3Bender Atik R. Christiansen O.B. Elson J. Kolte A.M. Lewis S. et al.ESHRE Guideline Group on RPLESHRE guideline: recurrent pregnancy loss.Hum Reprod Open. 2018; 2018hoy004Crossref PubMed Google Scholar, 4van Dijk M.M. Kolte A.M. Limpens J. Kirk E. Quenby S. van Wely M. et al.Recurrent pregnancy loss: diagnostic workup after two or three pregnancy losses? A systematic review of the literature and meta-analysis.Hum Reprod Update. 2020; 26: 356-367Crossref PubMed Scopus (37) Google Scholar). The American Society for Reproductive Medicine (ASRM) does not mention a threshold number of miscarriages in the context of RPL (5Practice Committee of the American Society for Reproductive MedicineDefinitions of infertility and recurrent pregnancy loss: a committee opinion.Fertil Steril. 2013; 99: 63Abstract Full Text Full Text PDF PubMed Scopus (581) Google Scholar). It is generally accepted that RPL occurs in 1%–3% of couples who try to conceive (3Bender Atik R. Christiansen O.B. Elson J. Kolte A.M. Lewis S. et al.ESHRE Guideline Group on RPLESHRE guideline: recurrent pregnancy loss.Hum Reprod Open. 2018; 2018hoy004Crossref PubMed Google Scholar). The prevalence of anatomical uterine anomalies in women experiencing RPL varies from 15% to 42% according to different studies (6Medrano-Uribe F.A. Enriquez-Perez M.M. Reyes-Munoz E. [Prevalence of uterine anatomical anomalies in Mexican women with recurrent pregnancy loss (RPL)].Gac Med Mex. 2016; 152: 163-166PubMed Google Scholar, 7Galamb A. Petho B. Fekete D. Petranyi G. Pajor A. [Uterine anomalies in women with recurrent pregnancy loss].Orv Hetil. 2015; 156: 1081-1084Crossref PubMed Scopus (5) Google Scholar, 8Ono S. Yonezawa M. Watanabe K. Abe T. Mine K. Kuwabara Y. et al.Retrospective cohort study of the risk factors for secondary infertility following hysteroscopic metroplasty of the uterine septum in women with recurrent pregnancy loss.Reprod Med Biol. 2018; 17: 77-81Crossref PubMed Scopus (7) Google Scholar, 9Seckin B. Sarikaya E. Oruc A.S. Celen S. Cicek N. Office hysteroscopic findings in patients with two, three, and four or more, consecutive miscarriages.Eur J Contracept Reprod Health Care. 2012; 17: 393-398Crossref PubMed Scopus (11) Google Scholar, 10Hooker A.B. Lemmers M. Thurkow A.L. Heymans M.W. Opmeer B.C. Brolmann H.A. et al.Systematic review and meta-analysis of intrauterine adhesions after miscarriage: prevalence, risk factors and long-term reproductive outcome.Hum Reprod Update. 2014; 20: 262-278Crossref PubMed Scopus (213) Google Scholar). Congenital uterine anomalies are associated with 7%–28% of RPL (6Medrano-Uribe F.A. Enriquez-Perez M.M. Reyes-Munoz E. [Prevalence of uterine anatomical anomalies in Mexican women with recurrent pregnancy loss (RPL)].Gac Med Mex. 2016; 152: 163-166PubMed Google Scholar, 7Galamb A. Petho B. Fekete D. Petranyi G. Pajor A. [Uterine anomalies in women with recurrent pregnancy loss].Orv Hetil. 2015; 156: 1081-1084Crossref PubMed Scopus (5) Google Scholar, 8Ono S. Yonezawa M. Watanabe K. Abe T. Mine K. Kuwabara Y. et al.Retrospective cohort study of the risk factors for secondary infertility following hysteroscopic metroplasty of the uterine septum in women with recurrent pregnancy loss.Reprod Med Biol. 2018; 17: 77-81Crossref PubMed Scopus (7) Google Scholar, 9Seckin B. Sarikaya E. Oruc A.S. Celen S. Cicek N. Office hysteroscopic findings in patients with two, three, and four or more, consecutive miscarriages.Eur J Contracept Reprod Health Care. 2012; 17: 393-398Crossref PubMed Scopus (11) Google Scholar, 10Hooker A.B. Lemmers M. Thurkow A.L. Heymans M.W. Opmeer B.C. Brolmann H.A. et al.Systematic review and meta-analysis of intrauterine adhesions after miscarriage: prevalence, risk factors and long-term reproductive outcome.Hum Reprod Update. 2014; 20: 262-278Crossref PubMed Scopus (213) Google Scholar). These mainly include septate uteri and more rarely arcuate or bicorporeal uteri. Acquired uterine anomalies are associated with 6%–15% of RPL (6Medrano-Uribe F.A. Enriquez-Perez M.M. Reyes-Munoz E. [Prevalence of uterine anatomical anomalies in Mexican women with recurrent pregnancy loss (RPL)].Gac Med Mex. 2016; 152: 163-166PubMed Google Scholar, 7Galamb A. Petho B. Fekete D. Petranyi G. Pajor A. [Uterine anomalies in women with recurrent pregnancy loss].Orv Hetil. 2015; 156: 1081-1084Crossref PubMed Scopus (5) Google Scholar, 8Ono S. Yonezawa M. Watanabe K. Abe T. Mine K. Kuwabara Y. et al.Retrospective cohort study of the risk factors for secondary infertility following hysteroscopic metroplasty of the uterine septum in women with recurrent pregnancy loss.Reprod Med Biol. 2018; 17: 77-81Crossref PubMed Scopus (7) Google Scholar, 9Seckin B. Sarikaya E. Oruc A.S. Celen S. Cicek N. Office hysteroscopic findings in patients with two, three, and four or more, consecutive miscarriages.Eur J Contracept Reprod Health Care. 2012; 17: 393-398Crossref PubMed Scopus (11) Google Scholar, 10Hooker A.B. Lemmers M. Thurkow A.L. Heymans M.W. Opmeer B.C. Brolmann H.A. et al.Systematic review and meta-analysis of intrauterine adhesions after miscarriage: prevalence, risk factors and long-term reproductive outcome.Hum Reprod Update. 2014; 20: 262-278Crossref PubMed Scopus (213) Google Scholar). These include submucosal myomas, intrauterine adhesions (IUAs), and endometrial polyps. Endometrial polyps are commonly found in both fertile and infertile women. Therefore, it must be acknowledged that their mere presence observed on uterine imaging or during hysteroscopies does not necessarily imply a specific negative impact on fertility. Because clinicians may not know when these findings negatively impact early pregnancy development, endometrial polyps are commonly removed when identified. To determine which of the abovementioned entities are likely to impair pregnancy development and which are just innocent bystanders unrelated to RPL, clinicians must perform a thorough uterine assessment in concordance with the international guidelines. Yet the investigations recommended slightly vary according to the different published guidelines (Table 1). The Royal College of Obstetricians and Gynaecologists recommends first performing a classical two-dimensional (2D) pelvic ultrasound. When uterine anomalies are suspected on regular ultrasound, further explorations are then recommended, including three-dimensional (3D) pelvic ultrasound, hysteroscopy, sonohysterography (SHG), and laparoscopy (11The Royal College of Obstetricians and GynaecologistsThe investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage.Green-top Guideline. 2011; (no. 17)Google Scholar). However, the European Society of Human Reproduction and Embryology (ESHRE) recommends first performing transvaginal 3D ultrasound as the primary examination of uterine anatomy (3Bender Atik R. Christiansen O.B. Elson J. Kolte A.M. Lewis S. et al.ESHRE Guideline Group on RPLESHRE guideline: recurrent pregnancy loss.Hum Reprod Open. 2018; 2018hoy004Crossref PubMed Google Scholar). In contrast, the ASRM guidelines recommend performing SHG or hysteroscopy (12Practice Committee of the American Society for Reproductive MedicineEvaluation and treatment of recurrent pregnancy loss: a committee opinion.Fertil Steril. 2012; 98: 1103-1111Abstract Full Text Full Text PDF PubMed Scopus (638) Google Scholar). The French Collège National des Gynécologues et Obstétriciens recommends performing 2D or 3D ultrasound, magnetic resonance imaging (MRI), hysteroscopy, and/or SHG depending on the diagnostic measures available (13Huchon C. Deffieux X. Beucher G. Capmas P. Carcopino X. Costedoat-Chalumeau N. et al.Pregnancy loss: French clinical practice guidelines.Eur J Obstet Gynecol Reprod Biol. 2016; 201: 18-26Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar).Table 1Comparison of the recurrent pregnancy loss guidelines.ESHRE (3Bender Atik R. Christiansen O.B. Elson J. Kolte A.M. Lewis S. et al.ESHRE Guideline Group on RPLESHRE guideline: recurrent pregnancy loss.Hum Reprod Open. 2018; 2018hoy004Crossref PubMed Google Scholar)ASRM (5Practice Committee of the American Society for Reproductive MedicineDefinitions of infertility and recurrent pregnancy loss: a committee opinion.Fertil Steril. 2013; 99: 63Abstract Full Text Full Text PDF PubMed Scopus (581) Google Scholar, 12Practice Committee of the American Society for Reproductive MedicineEvaluation and treatment of recurrent pregnancy loss: a committee opinion.Fertil Steril. 2012; 98: 1103-1111Abstract Full Text Full Text PDF PubMed Scopus (638) Google Scholar)RCOG (11The Royal College of Obstetricians and GynaecologistsThe investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage.Green-top Guideline. 2011; (no. 17)Google Scholar)CNGOF (13Huchon C. Deffieux X. Beucher G. Capmas P. Carcopino X. Costedoat-Chalumeau N. et al.Pregnancy loss: French clinical practice guidelines.Eur J Obstet Gynecol Reprod Biol. 2016; 201: 18-26Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar)Year of publication20172012–1320112016Anatomical assessment2D ultrasoundSHG, hysteroscopyPelvic ultrasound first. If suspected anomalies: hysteroscopy, laparoscopy or 3D pelvic ultrasound2D or 3D ultrasound, SHG, hysteroscopy, or MRI depending on availabilityCongenital anomaliesInsufficient evidence; section of uterine septum in trialsSection of uterine septumInsufficient evidenceSection of uterine septumAcquired anomaliesInsufficient evidenceInsufficient evidenceInsufficient evidenceResection of endometrial polyps, submucosal myomas Section of IUAs2D = two-dimensional; 3D = three-dimensional; ASRM = American Society for Reproductive Medicine; CNGOF = Collège National des Gynécologues et Obstétriciens Français; ESHRE = European Society of Human Reproduction and Embryology; IUAs = intrauterine adhesions; MRI = magnetic resonance imaging; RPL = recurrent pregnancy loss; RCOG = Royal College of Obstetricians and Gynaecologists; SHG = sonohysterography. Open table in a new tab 2D = two-dimensional; 3D = three-dimensional; ASRM = American Society for Reproductive Medicine; CNGOF = Collège National des Gynécologues et Obstétriciens Français; ESHRE = European Society of Human Reproduction and Embryology; IUAs = intrauterine adhesions; MRI = magnetic resonance imaging; RPL = recurrent pregnancy loss; RCOG = Royal College of Obstetricians and Gynaecologists; SHG = sonohysterography. The risk of RPL is increased in women with congenital uterine malformations (14Rikken J.F. Kowalik C.R. Emanuel M.H. Mol B.W. Van der Veen F. van Wely M. et al.Septum resection for women of reproductive age with a septate uterus.Cochrane Database Syst Rev. 2017; 1CD008576PubMed Google Scholar). The two most widely used classifications are provided by ASRM (15The American Fertility Society classifications of adnexal adhesions, distal tubal occlusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, Mullerian anomalies and intrauterine adhesions.Fertil Steril. 1988; 49: 944-955Abstract Full Text PDF PubMed Google Scholar) and ESHRE/European Society for Gynecological Endoscopy. The latter classification system of female genital tract congenital anomalies—used in the present article—is illustrated in Figure 1 (16Grimbizis G.F. Gordts S. Di Spiezio Sardo A. Brucker S. De Angelis C. Gergolet M. et al.The ESHRE/ESGE consensus on the classification of female genital tract congenital anomalies.Hum Reprod. 2013; 28: 2032-2044Crossref PubMed Scopus (402) Google Scholar). The septate uterus is the congenital malformation most commonly associated with RPL, being found in 6%–16% of cases (6Medrano-Uribe F.A. Enriquez-Perez M.M. Reyes-Munoz E. [Prevalence of uterine anatomical anomalies in Mexican women with recurrent pregnancy loss (RPL)].Gac Med Mex. 2016; 152: 163-166PubMed Google Scholar, 7Galamb A. Petho B. Fekete D. Petranyi G. Pajor A. [Uterine anomalies in women with recurrent pregnancy loss].Orv Hetil. 2015; 156: 1081-1084Crossref PubMed Scopus (5) Google Scholar, 9Seckin B. Sarikaya E. Oruc A.S. Celen S. Cicek N. Office hysteroscopic findings in patients with two, three, and four or more, consecutive miscarriages.Eur J Contracept Reprod Health Care. 2012; 17: 393-398Crossref PubMed Scopus (11) Google Scholar). Septate uteri (class U2) result from partial or complete failure of resorption of the medial septum between the two Müllerian ducts during fetal life. The degree of indentation of the protruding medial portion defines the two conditions known as septate and arcuate uterus, with different cutoffs ranging from 10 to 15 mm reported in the literature (15The American Fertility Society classifications of adnexal adhesions, distal tubal occlusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, Mullerian anomalies and intrauterine adhesions.Fertil Steril. 1988; 49: 944-955Abstract Full Text PDF PubMed Google Scholar, 17Ludwin A. Martins W.P. Nastri C.O. Ludwin I. Coelho Neto M.A. Leitao V.M. et al.Congenital Uterine Malformation by Experts (CUME): better criteria for distinguishing between normal/arcuate and septate uterus?.Ultrasound Obstet Gynecol. 2018; 51: 101-109Crossref PubMed Scopus (67) Google Scholar). While the pathophysiology by which this disorder interferes with early pregnancy development is not entirely known, hypotheses have been formulated. Miscarriages in case of septate uteri likely result from inadequate implantation of the embryo on a poorly vascularized septum. Furthermore, the septum could alter the pre- and postovulatory changes of the endometrium under the influence of estradiol and progesterone, uterine contractibility, and/or disruption of the physiology of endometrial factors such as, notably, vascular endothelial growth factor (18Rikken J. Leeuwis-Fedorovich N.E. Letteboer S. Emanuel M.H. Limpens J. van der Veen F. et al.The pathophysiology of the septate uterus: a systematic review.Br J Obstet Gynecol. 2019; 126: 1192-1199Crossref Scopus (13) Google Scholar). Other congenital disorders, in particular, unicornuate (class U4), arcuate (class U2), and bicornuate uteri (class U3), are reported in only 0.5%–2% of cases of RPL (6Medrano-Uribe F.A. Enriquez-Perez M.M. Reyes-Munoz E. [Prevalence of uterine anatomical anomalies in Mexican women with recurrent pregnancy loss (RPL)].Gac Med Mex. 2016; 152: 163-166PubMed Google Scholar, 7Galamb A. Petho B. Fekete D. Petranyi G. Pajor A. [Uterine anomalies in women with recurrent pregnancy loss].Orv Hetil. 2015; 156: 1081-1084Crossref PubMed Scopus (5) Google Scholar). The presence of congenital malformations can be suspected with traditional 2D transvaginal ultrasounds. The sensitivity of 2D ultrasounds is, however, low (60%–80%) for detecting uterine malformations. Conversely, 3D transvaginal ultrasounds have the highest overall diagnostic sensitivity and accuracy (19Grimbizis G.F. Di Spiezio Sardo A. Saravelos S.H. Gordts S. Exacoustos C. Van Schoubroeck D. et al.The Thessaloniki ESHRE/ESGE consensus on diagnosis of female genital anomalies.Gynecol Surg. 2016; 13: 1-16Crossref PubMed Scopus (51) Google Scholar), especially for distinguishing between septate and bicornuate uteri (20Saravelos S.H. Cocksedge K.A. Li T.C. Prevalence and diagnosis of congenital uterine anomalies in women with reproductive failure: a critical appraisal.Hum Reprod Update. 2008; 14: 415-429Crossref PubMed Scopus (394) Google Scholar). The coronal—frontal view—of the uterus is ideal for diagnosing congenital uterine anomalies (Fig. 1A and 1B). The uterine cavity can be further explored with SHG and/or hysteroscopy. In contrast, hysterosalpingography is not very effective for assessing uterine malformations. Hysteroscopy only offers mediocre accuracy for distinguishing septate from arcuate uteri with poor interobserver agreement on final diagnosis. Hence, hysteroscopy per se is insufficient as a single tool for appropriately diagnosing uterine malformations and deciding on the appropriate treatment, notably, the need for resection—metroplasty—of septate uteri (21Smit J.G. Overdijkink S. Mol B.W. Kasius J.C. Torrance H.L. Eijkemans M.J. et al.The impact of diagnostic criteria on the reproducibility of the hysteroscopic diagnosis of the septate uterus: a randomized controlled trial.Hum Reprod. 2015; 30: 1323-1330Crossref PubMed Scopus (19) Google Scholar). Combining both hysteroscopy and laparoscopy remains the gold standard for diagnosing uterine malformations because it offers a simultaneous internal and external view of the uterus. Yet this dual approach is invasive. This has led researchers to seek simpler approaches using 2D or 3D SHG, which ultimately have great value for diagnosing the most commonly encountered congenital uterine anomalies. In particular, SHG allows the delineation of the internal contours of the uterine cavity as well as the surface of the uterus (22Ludwin A. Pitynski K. Ludwin I. Banas T. Knafel A. Two- and three-dimensional ultrasonography and sonohysterography versus hysteroscopy with laparoscopy in the differential diagnosis of septate, bicornuate, and arcuate uteri.J Minim Invasive Gynecol. 2013; 20: 90-99Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar). Pelvic MRI may be helpful in complicated cases associated with complex anatomical defects like rudimentary cavities but is not routinely necessary (3Bender Atik R. Christiansen O.B. Elson J. Kolte A.M. Lewis S. et al.ESHRE Guideline Group on RPLESHRE guideline: recurrent pregnancy loss.Hum Reprod Open. 2018; 2018hoy004Crossref PubMed Google Scholar, 19Grimbizis G.F. Di Spiezio Sardo A. Saravelos S.H. Gordts S. Exacoustos C. Van Schoubroeck D. et al.The Thessaloniki ESHRE/ESGE consensus on diagnosis of female genital anomalies.Gynecol Surg. 2016; 13: 1-16Crossref PubMed Scopus (51) Google Scholar). When class U3 and U5 malformations are diagnosed, it is recommended to investigate the kidneys and urinary tract as well for possible associated malformations (3Bender Atik R. Christiansen O.B. Elson J. Kolte A.M. Lewis S. et al.ESHRE Guideline Group on RPLESHRE guideline: recurrent pregnancy loss.Hum Reprod Open. 2018; 2018hoy004Crossref PubMed Google Scholar). Hysteroscopic metroplasty is the most commonly preferred approach for resecting the uterine septum. A 15 French gauge (FR) hysteroscope with a 5 FR operative channel allows the use of instruments (including bipolar and monopolar electrodes and cold scissors). Alternatively, a 15–26 FR resectoscope (hysteroscope with cauterization loop) equipped with bipolar or monopolar cautery or laser can be used with comparable results (23Daniilidis A. Kalpatsanidis A. Kalkan U. Kasmas S. Pados G. Angioni S. Reproductive outcome after operative hysteroscopy for uterine septum: scissors or diathermy?.Minerva Ginecol. 2020; 72: 36-42Crossref PubMed Scopus (5) Google Scholar). This procedure has been determined to be safe and effective, although this determination was based on nonrandomized and mainly retrospective trials only (14Rikken J.F. Kowalik C.R. Emanuel M.H. Mol B.W. Van der Veen F. van Wely M. et al.Septum resection for women of reproductive age with a septate uterus.Cochrane Database Syst Rev. 2017; 1CD008576PubMed Google Scholar). Observational studies report important improvements in pregnancy chances when comparing before and after septum resection in observational studies, which are highly susceptible to various biases (24Pang L.H. Li M.J. Li M. Xu H. Wei Z.L. Not every subseptate uterus requires surgical correction to reduce poor reproductive outcome.Int J Gynaecol Obstet. 2011; 115: 260-263Crossref PubMed Scopus (25) Google Scholar, 25Sugiura-Ogasawara M. Lin B.L. Aoki K. Maruyama T. Nakatsuka M. Ozawa N. et al.Does surgery improve live birth rates in patients with recurrent miscarriage caused by uterine anomalies?.J Obstet Gynaecol. 2015; 35: 155-158Crossref PubMed Scopus (21) Google Scholar, 26Homer H.A. Li T.C. Cooke I.D. The septate uterus: a review of management and reproductive outcome.Fertil Steril. 2000; 73: 1-14Abstract Full Text Full Text PDF PubMed Scopus (493) Google Scholar, 27Gundabattula S.R. Joseph E. Marakani L.R. Dasari S. Nirmalan P.K. Reproductive outcomes after resection of intrauterine septum.J Obstet Gynaecol. 2014; 34: 235-237Crossref PubMed Scopus (11) Google Scholar). First among the possible biases is the fact that participants with RPL treated by hysteroscopic metroplasty have commonly served as their own controls. A meta-analysis showed that hysteroscopic removal of a septum was associated with reduced probability of spontaneous abortion (28Venetis C.A. Papadopoulos S.P. Campo R. Gordts S. Tarlatzis B.C. Grimbizis G.F. Clinical implications of congenital uterine anomalies: a meta-analysis of comparative studies.Reprod Biomed Online. 2014; 29: 665-683Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar). The ASRM and French guidelines recommend septum resection in case of septate uteri associated with RPL (12Practice Committee of the American Society for Reproductive MedicineEvaluation and treatment of recurrent pregnancy loss: a committee opinion.Fertil Steril. 2012; 98: 1103-1111Abstract Full Text Full Text PDF PubMed Scopus (638) Google Scholar, 13Huchon C. Deffieux X. Beucher G. Capmas P. Carcopino X. Costedoat-Chalumeau N. et al.Pregnancy loss: French clinical practice guidelines.Eur J Obstet Gynecol Reprod Biol. 2016; 201: 18-26Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar). However, the Royal College of Obstetricians and Gynaecologists concludes that there is insufficient evidence for justifying surgical correction of septate uteri (11The Royal College of Obstetricians and GynaecologistsThe investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage.Green-top Guideline. 2011; (no. 17)Google Scholar). Likewise, the ESHRE guidelines conclude that the net value of septum resection should be evaluated in randomized controlled trials (RCTs) (16Grimbizis G.F. Gordts S. Di Spiezio Sardo A. Brucker S. De Angelis C. Gergolet M. et al.The ESHRE/ESGE consensus on the classification of female genital tract congenital anomalies.Hum Reprod. 2013; 28: 2032-2044Crossref PubMed Scopus (402) Google Scholar). In fact, an international RCT (the TRUST trial) comparing septum resection versus no resection in women with a history of RPL is currently in progress (29Rikken J.F.W. Kowalik C.R. Emanuel M.H. Bongers M.Y. Spinder T. de Kruif J.H. et al.The randomised uterine septum transsection trial (TRUST): design and protocol.BMC Womens Health. 2018; 18: 163Crossref PubMed Scopus (27) Google Scholar). Some investigators have proposed additional morphologic criteria beyond those proposed by the American Fertility Society for better characterizing the differences between septate and arcuate uteri (30Pfeifer S. Butts S. Dumesic D. Gracia C. Vernon M. Fossum G. et al.Uterine septum: a guideline.Fertil Steril. 2016; 106: 530-540Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar). These investigators also define the role played by the angle existing at the tip of the septum protruding in the cavity. Following this approach, a closed angle between the two uterine horns is characteristic of the arcuate configuration (31Woelfer B. Salim R. Banerjee S. Elson J. Regan L. Jurkovic D. Reproductive outcomes in women with congenital uterine anomalies detected by three-dimensional ultrasound screening.Obstet Gynecol. 2001; 98: 1099-1103Crossref PubMed Scopus (204) Google Scholar). Furthermore, emphasis is put on the length of the septum, which in the case of arcuate uterus ranges between 10 and 15 mm (32Ludwin A. Ludwin I. Banas T. Knafel A. Miedzyblocki M. Basta A. Diagnostic accuracy of sonohysterography, hysterosalpingography and diagnostic hysteroscopy in diagnosis of arcuate, septate and bicornuate uterus.J Obstet Gynaecol Res. 2011; 37: 178-186Crossref PubMed Scopus (45) Google Scholar). The lack of a universally accepted standard definition of septate uterus may add variability in diagnostic classifications and affect the actual incidence of surgical metroplasties (33Ludwin A. Ludwin I. Comparison of the ESHRE-ESGE and ASRM classifications of Müllerian duct anomalies in everyday practice.Hum Reprod. 2014; 30: 569-580Crossref PubMed Scopus (85) Google Scholar). Surgical and obstetrical complications of hysteroscopic metroplasty have been described. These include perforation of the uterus, postoperative IUAs, cervical laceration (34Litta P. Spiller E. Saccardi C. Ambrosini G. Caserta D. Cosmi E. Resectoscope or Versapoint for hysteroscopic metroplasty.Int J Gynaecol Obstet. 2008; 101: 39-42Crossref PubMed Scopus (39) Google Scholar), and an increased rate of cesarean sections due to dystocic obstetrical presentations (35Agostini A. De Guibert F. Salari K. Crochet P. Bretelle F. Gamerre M. Adverse obstetric outcomes at term after hysteroscopic metroplasty.J Minim Invasive Gynecol. 2009; 16: 454-457Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar). Some cases of uterine rupture during subsequent pregnancies have also been reported (35Agostini A. De Guibert F. Salari K. Crochet P. Bretelle F. Gamerre M. Adverse obstetric outcomes at term after hysteroscopic metroplasty.J Minim Invasive Gynecol. 2009; 16: 454-457Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar, 36Sentilhes L. Sergent F. Berthier A. Catala L. Descamps P. Marpeau L. [Uterine rupture following operative hysteroscopy].Gynecol Obstet Fertil. 2006; 34: 1064-1070Crossref PubMed Scopus (37) Google Scholar). Abdominal ultrasound guidance during surgery, the use of barrier gels, and postoperative hysteroscopies are options aimed at reducing postoperative complications (37Sebbag L. Even M. Fay S. Naoura I. Revaux A. Carbonnel M. et al.Early second-look hysteroscopy: prevention and treatment of intrauterine post-surgical adhesions.Front Surg. 2019; 6: 50Crossref PubMed Scopus (20) Google Scholar). However, no evidence of a benefit of surgical treatment for arcuate, bicornuate, or unicornuate uterus has been shown (25Sugiura-Ogasawara M. Lin B.L. Aoki K. Maruyama T. Nakatsuka M. Ozawa N. et al.Does surgery improve live birth rates in patients with recurrent miscarriage caused by uterine anomalies?.J Obstet Gynaecol. 2015; 35: 155-158Crossref PubMed Scopus (21) Google Scholar). Data about uterine enlargement metroplasty for dysmorphic uteri (class U1) are controversial in the case of RPL (38Sanchez-Santiuste M. Rios M. Calles L. Cuesta R. Engels V. Pereira A. et al.Dysmorphic uteri: obstetric results after hysteroscopic office metroplasty in infertile and recurrent pregnancy loss patients: a prospective observational study.J Clin Med. 2020; 9Crossref PubMed Scopus (1) Google Scholar, 39De Franciscis P. Riemma G. Schiattarella A. Cobellis L. Colacurci N. Vitale S.G. et al.Impact of hysteroscopic metroplasty on reproductive outcomes of women with a dysmorphic uterus and recurrent miscarriages: a systematic review and meta-analysis.J Gynecol Obstet Hum Reprod. 2020; 49: 101763Crossref PubMed Scopus (8) Google Scholar, 40Garzon S. Lagana A.S. Di Spiezio Sardo A. Alonso P