Gynecol Surg (2014) 11:129–138

DOI 10.1007/s10397-014-0837-5

REVIEW ARTICLE

Septate uterus: nosographic overview and endoscopic treatment

Antonio Perino & Francesco Forlani & Antonio Lo Casto &
Giuseppe Calì & Gloria Calagna & Stefano Rotolo &
Gaspare Cucinella

Received: 9 October 2013 / Accepted: 10 February 2014 / Published online: 26 February 2014
# Springer-Verlag Berlin Heidelberg 2014

Abstract To comment on the prevalence, diagnosis, and Introduction

treatment of the septate uterus, with special reference to hys-
teroscopic metroplasty and its effect on reproductive outcome, Septate uterus results from the incomplete or completely failed
we searched publications in PubMed and Embase. Original fusion of Müllerian ducts and is the most common type among
articles, meta-analysis, reviews, and opinion articles were congenital uterine anomalies [1, 2]. Two types of septate
selected. The studies suggest that the prevalence of the septate uterus are described: the complete septate uterus, in which
uterus is increased in women with repeated pregnancy loss the septum divides the whole uterine cavity, and the
and infertility. Reliable diagnosis depends on accurate assess- subseptate uterus, in which a partial separation of uterine
ment of the uterine fundal contour and uterine cavity by means cavity does not reach the cervix (Fig. 1a, b). Failure of fusion
of magnetic resonance and three-dimensional ultrasound. Per- may even occur at a lower level, so that two cervices and even
tinent published data comparing pregnancy outcome before a vaginal septum may be present [3–6] (Fig. 1, d). The
and after hysteroscopic metroplasty indicated a marked im- European Society of Human Reproduction and Embryology
provement after surgery. Magnetic resonance and three- (ESHRE) and the European Society for Gynecological En-
dimensional ultrasound represent the gold standard for diag- doscopy (ESGE) developed a new updated classification sys-
nosis of septate uterus. Hysteroscopic metroplasty with its tem of congenital uterine anomalies [7]. The uterus septum
simplicity, minimal postoperative sequelae, and improved (category U2) was defined as the uterus with normal outline
reproductive outcome is the gold standard for treatment, not and an internal indentation at the fundal midline exceeding
only in patients with recurrent pregnancy loss and premature 50 % of the uterine wall thickness. This indentation is char-
labor but also in patients with infertility, especially if in vitro acterized as septum and could divide partly or completely the
fertilization is being contemplated. uterine cavity, including in some cases cervix and/or vagina
(cervical and vaginal coexistent anomalies). The true preva-
lence of Müllerian anomalies in the general population re-
Keywords Septate uterus . Miscarriage . Infertility . mains unknown. Mainly based on clinical exam, early inves-
Hysteroscopy . Metroplasty tigations on congenital uterine anomalies were limited by the
lack of diagnostic tools. A meta-analysis of 94 observational
studies comprising nearly 90,000 women indicated a preva-
A. Perino : F. Forlani (*) : G. Calagna : S. Rotolo : G. Cucinella lence of 5.5 % in the unselected population, 8.0 % in infertile
Department of Obstetrics and Gynecology, University Hospital “P. women, 13.3 % in those with a history of miscarriage, and
Giaccone”, Palermo, Italy 24.5 % in those with miscarriage and infertility [8]. Further-
e-mail: [email protected]
more, canalization defects (subseptate or septate uteri) had a
A. Lo Casto prevalence of 2.3 % in the unselected population but were
Department of Radiological Sciences, DIBIMEF, University encountered significantly more frequently in women with
Hospital “P. Giaccone”, Palermo, Italy previous miscarriage (5.3 %) [8]. In addiiton, septate uterus
is associated with higher first and second trimester abortion
G. Calì
Department of Obstetrics and Gynecology, ARNAS Civico, Di rates, preterm labor, abnormal labor, intrauterine growth re-
Cristina e Benfratelli, Palermo, Italy striction, and infertility. These conditions may be attributed to
130 Gynecol Surg (2014) 11:129–138

Fig. 1 Sepatate uterus: partial (a)

and complete (b). Uterine septum
involving the cervix (c) and
vagina (d)

several factors, as diminished blood supply [9], distortion of Methods

the uterine cavity, increased intrauterine pressure with resul-
tant cervical incompetence [10], and altered estrogen and The authors performed a comprehensive search on the
progesterone receptor expression [11]. Thus, surgical correc- PubMed and EMBASE database for published studies with
tion of septate uterus should be considered a first-line treat- the following keywords: “septate uterus,” “hysteroscopic
ment whenever indications are present. metroplasty,” “uterine anomalies,” “infertility,” and “recurrent
Currently, surgical treatment of septate uterus has been miscarriage.” We selected studies evaluating diagnosis, im-
significantly simplified by the introduction of hysteroscopic pact on fertility, hysteroscopic treatment of septate uterus
metroplasty, which has almost completely replaced the ab- including original articles, meta-analysis, reviews, and opin-
dominal approach. Although the reproductive outcome of ion articles published up to August 2013. The authors ana-
abdominal and hysteroscopic procedures is similar [12, 13], lyzed embryology, diagnosis, and role of surgical correction
the latter is associated with a reduced complication rate and on reproductive outcome.
shorter hospital stay. Therefore, hysteroscopic metroplasty is
currently considered the gold standard of these uterine anom-
alies, as it increases the reproductive outcome with less cost in
terms of risk of complications and outflow of resources. Findings
Nonetheless, currently available data come mainly from un-
controlled retrospective studies, and to date no randomized Embryology and genetics
trials have been conducted. Considering the resulting lack of
evidence, analysis regarding the efficacy of hysteroscop- In the embryo of 5 to 6 weeks of gestational age, the Müllerian
ic metroplasty cannot be considered conclusive. Herein, ducts become apparent. They stem from the urogenital ridge
we want to focus on the most relevant literature find- as a groove of the coelomic epithelium, growing caudally their
ings about diagnosis and management of the uterine medial walls fuse in the midline around 9 weeks and finally
septum; we also want to analyze the impact of this join the endodermal evaginations of the urogenital sinus. The
disease on reproductive outcome. process concludes at the end of the first trimester with the
Gynecol Surg (2014) 11:129–138 131

resorption of the septum, around 19–20 weeks of gestation uterine outline. Being economic and reproducible, its use is
[14]. widespread but accuracy chiefly depends on the clinician’s
Studies conducted on women affected by genetic syn- experience [23–25]. Sensitivity of 2D US ranges from 88 to
dromes, including Müllerian anomalies and knockout mouse 93 % and specificity from 94 to 99 %, with a positive predic-
models, have allowed the identification of several genes, tive value around 50–55 % and a negative predictive value
which play a significant role in the development of the female ranging between 88 and 100 % [26–30]. In addition,
reproductive system and in the pathogenesis of uterine sonohysterography in which a transonic means expands the
malformations [15]. An altered expression of the Bcl-2 gene uterine cavity enhances ultrasound accuracy in the identifica-
in uterine septum may prevent apoptosis and uterine septum tion of uterine anomalies providing more detailed information
regression [16]. Mikkilä et al. described an X-linked laterality about uterine cavity contour [31–37].
sequence, in which obligate carrier females had uterine sep- Hysteroscopy offers a direct visual inspection of the cervi-
tum and hypertelorism [17]. Ergün et al. reported a rare cal canal and uterine cavity. Modern mini-hysteroscopy, com-
familial aggregation in three sisters with different degrees of bining miniaturization with adequate image quality, has been
septate uterus [18]. widely used as a screening tool [38, 39]. However, it cannot
Despite advances in molecular biology and genetics, the provide any information about uterine wall or external uterine
precise pathophysiology of septate uterus remains unveiled. outline. The combined hysteroscopic–laparoscopic approach
The majority of the authors agree that the origin of nearly all is considered the best approach in the assessment of women
uterine malformations is consistent with a polygenic/ with congenital reproductive malformations, as both internal
multifactorial etiology [18, 19]. and external aspect of the uterus can be explored [40]. In
addition, coexistent tubal and ovarian anomalies, peritoneal
adhesion, or endometriosis can be identified and treated.
Diagnosis Nonetheless, like diagnostic tools, this combined approach
cannot provide objective measurable data as diagnosis relies
Congenital uterine anomalies are usually asymptomatic and on the subjective impression of the examiner. Furthermore,
may present with delayed menarche, primary infertility, or because of the invasive nature, it should not be used as a
recurrent pregnancy loss. Although diagnosis of reproductive primary diagnostic tool. The techniques so far described are
malformations can be made during gynecological examina- widely used in the study of Müllerian anomalies, but, if they
tion if obvious anomalies of the vagina and cervix are present, are considered separately, none is able to provide adequate
the identification of uterine malformations mainly depends on data on both the uterine cavity and external contour of the
imaging findings. Furthermore, surgical treatment produces uterus. Currently, magnetic resonance imaging (MRI) and
clear benefits in terms of reproductive outcome only in the three-dimensional ultrasound (3D US) are the only techniques
case of a septate uterus; therefore, it is crucial to differentiate that can assess both aspects contemporarily.
this condition from other uterine anomalies [1–8, 20]. An ideal As MRI accuracy in diagnosis of uterine malformations has
diagnostic tool should assess two main key points: the shape been demonstrated by several studies [41–44], 3D US repre-
of the uterine cavity (with the position of tubal ostium) and the sents a good, emerging alternative as it provides image quality
external uterine outline. Gubbini et al. proposed a simple, similar to that of MRI, being better tolerated by patients and
systematic, and reproducible subclassification system for uter- cheaper. A recently introduced MR technique, 3D
ine anomalies previously classified by the American Ferility fastrecovery fast spin-echo (FRFSE) cube can be used to
Society as classes V and VI, to achieve a precise definition of produce high-resolution volumetric image sets. The image
each uterine anomaly and determine the specific surgical data can be reformatted in any plane eliminating the possibil-
management [21]. ity of suboptimal plane prescription using 2D FRFSE tech-
Hysterosalpingography has been the primary diagnostic nique, regardless of the prescribed plane during the image
tool used to detect uterine cavity malformations and is still acquisition (Fig. 2). This is advantageous because variable
currently indicated in the early stages of evaluation of the uterine anatomy in case of Müllerian anomaly may obstacle a
infertile couple. Despite being able to supply important infor- correct choice of cross sectional planes in 2D imaging. Fur-
mation regarding tubal patency, it does not provide any infor- thermore, acquiring just one image volumetric sequence in-
mation on uterine wall or external uterine contour. Moreover, stead of multiple sequences on different planes decreases the
this technique is not reproducible and is not free from risks MR exam acquisition time with a positive impact on patient
arising from radiating exposure and/or upper reproductive comfort [45].
tract infection [22]. Ghi et al. [46] demonstrated the efficacy of 3D US in
Two-dimensional ultrasound (2D US) mainly performed differentiating arcuate, subseptate, septate, and bicornuate
through an endovaginal approach, offers clear information uterus by analysis of the outer profile of the uterus in coronal
about the uterine cavity, internal uterine walls, and external plane scans. A bicornuate uterus is diagnosed if a fundal
132 Gynecol Surg (2014) 11:129–138

Fig. 2 A case of septate uterus. Axial reformatted 3D FRFSE cube T2 fat-saturated image (b). Agenesia of the left kidney with hypertrophy of
image (a): two distinguished uterine horns (asterisk) with an interposed, the right kidney (k). 3D ultrasonography image of septate uterus (c, d)
complete septum (s) reaching the internal os are depicted. Coronal GE T2

external indentation higher than or equal to 10 mm divides 3D sonohysterography when endometrium appears thin or
two separated uterine cornua; conversely, septate, subseptate, irregular or if other uterine pathologies coexist.
and arcuate uteri present a convex fundal outline or a fundal Thus, clinical assessment of women with suspected
indentation inferior than 10 mm. While in the septate uterus Müllerian anomalies should be addressed with 3D US, espe-
the septum completely divides the cavity from fundus to cially before the surgery. With regard to MRI, its high costs
cervix, in the subseptate and arcuate uteri the septum is
bulging inside the uterine cavity drawing an acute or obtuse
angle at its central point, respectively.
Bermejo et al. [44] found a high degree of concordance
between 3D US and MRI in the diagnosis and classification of
uterine malformations [47]. To differentiate bicornuate from
septate uteri using 3D US, they used a formula to analyze
coronal plane scans, proposed by Troiano and McCarthy [48]:
if a line passing through tubal ostia crosses the fundus or its
distance from the fundus is less than or equal to 5 mm, it is a
bicornuate uterus; if distance is more than 5 mm, it is consid-
ered septate uterus, regardless of fundus shape (Fig. 3). Faivre
et al. [49] following the diagnostic criteria proposed by the
American Fertility Society (AFS) [50] and previously used by
Woefler et al. [51] experienced higher diagnostic accuracy of
3D US in detecting septate uterus and differentiating septate
from bicornuate uterus, compared with hysteroscopy and Fig. 3 Septate uterus: the fundus is more than 5 mm (arrow) above the
MRI. Moreover, the same authors have proposed the use of line passing through tubal ostia
Gynecol Surg (2014) 11:129–138 133

together with the need of uterine malformation experienced as gonadotropin-releasing hormone analog (GnRH-a) prior to
clinicians, limit its use to doubtful or complex cases. surgery. The surgical technique consists briefly in the incision
of the septum, beginning from its inferior apex and proceeding
slowly toward the fundus; after, the septum is thinned from
Surgical technique both sides under vision while continuously monitoring the
position of the ostia, it is then incised in the midsection. As
Historically, metroplasty for septate uterus has been the septum is cut transversely, both edges will retract anteri-
approached by laparotomic hysterotomy and only in the case orly and posteriorly.
of recurrent pregnancy loss. Although both Tompkins and The most critical step of this procedure is determining the
Jones’ procedure provided quite good results [52, 53], these end point of the resection: if keeping the incision too superfi-
were highly morbid procedures, resulting in a long time before cial, it may result in a residual septum and eventually will
conception and a subsequent cesarean delivery [54]. require an additional operation, whereas, carrying the resec-
In 1974, Edstrom first described the hysteroscopic resec- tion too deep into the fundus, it can lead to intraoperative
tion of the uterine septum [55]. Since then, the hysteroscopic uterine perforation or uterine rupture during labor or, worse,
surgical technique have been refined and so have been signif- during subsequent pregnancies.
icant diffusion, technical developments have led to miniatur- The procedure usually ends when both ostia are clearly
ization and improvement of endoscopes resulting in a safer, visible from a panoramic view of the uterine cavity and the tip
less-invasive diagnostic and therapeutic tool [56]. Currently, of the instrument can be moved freely from one side to the
two types of instrument are available for the procedure, name- other, otherwise, when the septum has been adequately
ly resectoscope and mini-hysteroscopy, both supporting bipo- resected and minimal bleeding coming from myometrial ves-
lar and monopolar cautery (Fig. 4). It is best to perform sels appears from the bottom of the incision. A few months
metroplasty in the follicular phase when the endometrium is after surgery, a hysteroscopic evaluation of the uterine cavity
thin; otherwise, it is possible to administer hormonal therapy may be performed to reveal potential postoperative adhesions

Fig. 4 Septate uterus with double cervix (a, b). Resettoscopic metroplasty with monopolar electrode (c). Small-diameter hysteroscopy with VersaPoint
bipolar system (d)
134 Gynecol Surg (2014) 11:129–138

or a residual septum thicker than 1 cm. The majority of the terms of reproductive outcome, the choice of either depends
authors agree that a residual septum inferior to 1 cm does not on the costs of the instrumentation, the availability of the
worsen the reproductive outcome [57]. operating room, operative time and complication rate.
The use of laparoscopy, once considered mandatory both The advantages of classic resectoscopy include availability
during diagnosis (mainly to differentiate the septate from and low cost instruments. Conversely, considering the advan-
bicornuate uterus) and during surgery (to reveal the relative tages in terms of operative time, increased safety and higher
thickness of the remaining myometrium, through transillumi- feasibility, mini-hysteroscopy is a viable alternative to tradi-
nation) has now become quite uncommon. Laparoscopy is tional resectoscopy and therefore should be preferred in case
occasionally used to conclude a diagnostic work-up in infertile of subseptate uterus (class Vb).
women and is mainly reserved to treat coexisting pathologies. Only in the case of septate uterus (septum extends up to the
Traditional resectoscopic techniques make use of 22 or 26 cervix) should the use of the classic resectoscope be preferred,
Fr endoscope equipped with a monopolar or bipolar 90° loop. as a continuous loss of distension medium through a widely
The procedure is usually performed in the operating theater patent cervical canal may occur; this can lead to insufficient
under general or locoregional anesthesia and is preceded by expansion of the uterine cavity and hence a suboptimal view
the dilatation of the cervical canal and distension of the uterine of the surgical field.
cavity with a non-electrolytic medium if monopolar cautery is
used, or with saline solution if bipolar loop is used. It is well
known that bipolar energy reduces thermal injury to adjacent
tissue compared with monopolar cautery, allowing the use of Septate uterus and reproductive outcome
saline solution as distension media at the same time, which
may provide a greater margin in fluid intravasation. Obstetric complications Approximately 20–25 % women
A further advance in the hysteroscopic approach to septate with septate uterus experience obstetric complications and,
uterus has been achieved in the last decade thanks to the among these, recurrent miscarriage and preterm labor are the
miniaturization of hysteroscopes that allows diagnosis and most common [59].
treatment in the same operative session, with the so-called A retrospective review conducted in 2001 on 198 women
"see-and-treat" hysteroscopy. with septate uterus and a total of 499 pregnancies, indicated a
Currently, operative hysteroscopes of small diameter prevalence of 44.1 % of miscarriage, 22.3 % of preterm labor,
with continuous flow features and operative sheaths are and 32.9 % for term delivery [60]. Similar results have been
available. Such hysteroscopes allow the use of reported by other authors during the last years, confirming
microscissors or 5 Fr bipolar electrodes. No cervical dila- poor pregnancy outcome related to the presence of uterine
tation is needed, thus reducing cervical trauma, operating septum. Therefore, reproductive outcome in women with
time, risk of uterine perforation, and subsequent cervical septate uterus is the reference parameter used to assess the
incompetence, especially in nulliparous infertile women efficacy of hysteroscopic metroplasty. Numerous studies have
[58]. In addition, numerous studies indicate the possibility already demonstrated a significant decrease of abortion and
to perform the "office" procedure with a short intravenous preterm labor rate in women treated with hysteroscopic
sedation or no analgesia [53–55]. The efficacy and safety metroplasty [61–69]. In a series of 366 pregnancies following
of office hysteroscopy with a VersaPoint device were hysteroscopic septum resection, just 60 cases of recurrent
assessed by two major studies that compared this tech- abortion (16.4 %) and 25 cases of preterm labor (6.8 %) were
nique with traditional monopolar [54–57]. Although repro- observed. These results were significantly improved when
ductive outcomes (pregnancy rate, live births rate, and compared with preoperative rates, 86.4 % for miscarriage
miscarriages rate) were similar in both techniques, hyster- and 9.8 % for preterm labor [60].
oscopy performed with VersaPoint was found to be safer The prophylactic role of metroplasty in asymptomatic or
and easier (as no dilatation was needed). Furthermore, it nulliparous women is still debated. The increased risk of
granted better haemostasis and could be used both in uterine rupture in subsequent pregnancies and the need for a
nulligravide and in women with stenosis of the cervical cesarean section would limit the surgical removal of the
canal. Colacurci et al. [54] in a randomized, multicentre septum only to symptomatic women [59, 70]. Conversely,
trial found no difference in reproductive outcomes between scientific evidence indicates a clear association between sep-
women treated by a bipolar microelectrode and those tate uterus and poor pregnancy outcome and a significant
treated by resectoscope with monopolar knife, whereas improvement of the reproductive outcome after resection.
operative time, fluid absorption, and complication rates Considering the safety and feasibility of hysteroscopic
were higher with resectoscopy. metroplasty in the hands of an experienced surgeon, several
Although, “office” hysteroscopic metroplasty with bipolar authors have taken into account the possibility of using it as a
electrodes is fully equivalent to monopolar resectoscope in prophylactic tool [71].
Gynecol Surg (2014) 11:129–138 135

Infertility During the last two decades, contradictory results Table 1 Pregnancy rate after hysteroscopic metroplasty for the septate
uterus in women with primary infertility
about the role of uterine malformations in fertility have been
reported [23, 60, 72, 73]. Although uterine malformations Author No. of patients who No. of patients Pregnancy
may interfere with embryonic implantation and placentation underwent hysteroscopic with primary rate (%)
[67], a review by Grimbizis et al. [60] found a similar preva- metroplasty for infertility
septate uterus
lence of uterine malformations in infertile women and in the
general population. These findings were confirmed by other Fayez [11] 19 7 36
authors [20, 66]. Thus, a direct correlation between uterine Perino [54] 24 8 33
malformations and infertility should be excluded. Conversely, Daly [55] 70 15 21
arcuate uterus is the most common uterine malformation in the Marabini [74] 40 14 35
fertile population and, in addition, the prevalence of septate Pabuccu [75] 59 10 16
uterus among infertile women is twice as high as that observed Colacurci [76] 69 21 30
in the general population. These data support a relation be- Venturoli [77] 69 36 52
tween septate uterus and female infertility [74], especially in Pabuccu [71] 61 25 40
secondary infertility [66]. Colacurci [52] 35 26 74
The discrepancy of data available in literature is reflected in Mollo[69] 44 17 38
clinical practice when metroplasty is used in cases of unex- Wang [78] 6 2 33
plained female infertility, to improve pregnancy rates. Still, Pai [79] 64 33 51
data available are not conclusive, coming mostly from retro- Tongue [80] 102 44 43
spective studies, conducted over small numbers of patients,
Total 662 258 39
often selected by different criteria.
A systematic review conducted by Homer et al.
found a pregnancy rate of 48 % after resection in
women with primary sterility and thereby supporting fertilization (IVF) or intracytoplasmic sperm injection, signif-
the use of hysteroscopic metroplasty in these cases icantly increased pregnancy rates and live birth rates [75].
[69]. The first prospective study on the use of Therefore, in accordance with Homer [69], they conclude that
metroplasty in infertile women was published in 2004 hysteroscopic correction of uterine abnormalities is a feasible,
by Pabuccu et al. [73], reporting a postoperative spon- safe technique that improves reproductive outcome not only in
taneous pregnancy rate of 41 % in women with infer- women with recurrent pregnancy loss and preterm labor but
tility of unknown cause. These results were confirmed also in infertile women, especially if IVF is being
by prospective controlled trial by Mollo et al. on 44 contemplated.
women affected by septate uterus and otherwise unex-
plained infertility and 132 women with unexplained
infertility as control [71]; the authors found a signifi-
cantly higher pregnancy rate (38.6 vs 20.4 %) and live Conclusions
birth rate (34.1 vs 18.9 %) in the metroplasty group
than in the control group. Similar outcome is achieved Septate uterus results from the incomplete or completely
from a study by Shokeir et al. in 2011 [34], highlight- failed fusion of Müllerian ducts. Approximately 20–
ing a postoperative pregnancy rate of 40.7 % with 80 % 25 % of women with septate uterus experience obstetric
spontaneous conceptions. Although there are no ran- complications that required a hysteroscopic surgery. Al-
domized controlled trials, published data from 1986 to though obstetric complications represent the main indi-
2011 of hysteroscopic metroplasty in patients with pri- cations for metroplasty, a possible negative role of uter-
mary infertility showed a pregnancy rate of about 40 % ine septum in case of otherwise unexplained infertility
(16–74 %) (Table 1). cannot be excluded. The scientific evidence does not
With regard to the need for metroplasty prior to a program show a direct etiological nexus but are not conclusive
for assisted reproduction (hence consisting of an infertile and require further study. According to the latest data,
female population), most authors agree with the benefits of considering the simplicity and safety of hysteroscopic
hysteroscopic resection of endometrial polyps, submucous metroplasty, it seems safe to indicate the use in infertile
fibroids, and uterine septum in terms of reproductive outcome. women, especially if nulliparous over 35 years of age
Tomazevic et al. studied approximately 2,500 patients affected [23] or who intend to undergo a program of PMA [59].
by septate uterus (complete, subseptate uterus, and arcuate
uterus) and undergoing an assisted reproduction program.
They found that hysteroscopic metroplasty prior to in vitro Conflict of interest The authors declare no conflict of interest.
136 Gynecol Surg (2014) 11:129–138

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