MESTRADO INTEGRADO EM MEDICINA Congenital uterine ...
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MESTRADO INTEGRADO EM MEDICINA Congenital uterine anomalies: the role of surgery Maria Carolina Fernandes Lamouroux Barroso M 2021
Transcript of MESTRADO INTEGRADO EM MEDICINA Congenital uterine ...
MESTRADO INTEGRADO EM MEDICINA
Congenital uterine anomalies: the role
of surgery
Maria Carolina Fernandes Lamouroux Barroso
M 2021
Congenital uterine anomalies: the role of surgery
Dissertação de candidatura ao grau de Mestre em Medicina, submetida ao Instituto de Ciências
Biomédicas Abel Salazar – Universidade do Porto
Maria Carolina Fernandes Lamouroux Barroso
Aluna do 6º ano profissionalizante de Mestrado Integrado em Medicina
Afiliação: Instituto de Ciências Biomédicas Abel Salazar – Universidade do Porto
Endereço: Rua de Jorge Viterbo Ferreira nº228, 4050-313 Porto
Endereço eletrónico: [email protected]; [email protected]
Orientador: Dra. Márcia Sofia Alves Caxide e Abreu Barreiro
Diretora do Centro de Procriação Medicamente Assistida e do Banco Público de Gâmetas do
Centro Materno-Infantil do Norte
Assistente convidada, Instituto de Ciências Biomédicas Abel Salazar – Universidade do Porto.
Afiliação: Instituto de Ciências Biomédicas Abel Salazar – Universidade do Porto
Endereço: Largo da Maternidade de Júlio Dinis 45, 4050-651 Porto
Endereço eletrónico: [email protected]
Coorientador: Prof. Doutor Hélder Ferreira
Coordenador da Unidade de Cirurgia Minimamente Invasiva e Endometriose do Centro Materno-
Infantil do Norte
Professor associado convidado, Instituto de Ciências Biomédicas Abel Salazar – Universidade do
Porto.
Afiliação: Instituto de Ciências Biomédicas Abel Salazar – Universidade do Porto
Endereço: Rua Júlio Dinis 230, B-2, 9º Esq, Porto
Endereço eletrónico: [email protected]
Junho 2021
Porto, junho de 2021
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(Assinatura da estudante)
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(Assinatura da orientadora)
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(Assinatura do coorientador)
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ACKNOWLEDGEMENTS
À Dra. Márcia Barreiro, ao Dr. Luís Castro e ao Prof. Doutor Hélder Ferreira, por toda a
disponibilidade e empenho dedicado à realização deste trabalho.
Aos meus pais, irmão e avós, pela participação que desde sempre tiveram na minha
formação, e pelo carinho e apoio incondicional.
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ABSTRACT When disturbances occur in normal uterine embryogenesis, different uterine congenital
malformations, defined as deviations from the normal anatomy of the uterus, can occur. While a
variety of etiological factors are related, among them: teratogenic agents, genetic, environmental,
and multifactorial factors, there is still no concrete documentation on its influence or form of
action.
Although there is no universally accepted classification for congenital uterine anomalies,
the ESHRE/ESGE classification is a recent and clear system, enabling physicians to organize any
anomaly. Based on this classification system, protocols for an efficient diagnostic and treatment
approach are developed for each type of malformation.
These anomalies are often related to adverse reproductive outcomes, representing great
relevance in clinical practice. They are usually only diagnosed when the woman reaches adulthood
coinciding with the occurrence of these events. Infertility, repeated abortions (in the first or
beginning of the second trimesters) and preterm births are common manifestations.
This systematic review was carried out using the PubMed and Google Scholar databases,
the research was based on the combination of the Medical Subject Headings (MeSH) terms defined.
Scientific articles, written in English since 2010 were included, as well as older relevant articles by
cross referencing. The Female Genital Tract Congenital Malformations: Classification, Diagnosis and
Management, a 2015 published book, and the ESHRE/ESGE guidelines were also complementary
research tools.
Since it is currently accepted that the need for correction of uterine malformations varies
from case to case, not being mandatory and depending on many variables such as: the clinical
presentation, the degree of anomaly, the woman's history especially in terms of obstetric
complications, her age, and her reproductive plans, the goal of this dissertation is to discuss in which
situations surgery (restorage of the uterine architecture) plays an important role. It is also reviewed
various surgical techniques and the post-surgery results for each class of anomaly, respectively,
although it is notorious that large randomized controlled trials with consistent results are lacking,
which may lead to contradictory bibliography.
Keywords: Uterine anomalies, malformations, congenital, classification, diagnosis, infertility,
abortion, hysteroscopy, laparoscopy, surgery, dysmorphic, septate, bicorporeal, hemi-uterus,
aplasia.
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RESUMO Quando ocorrem distúrbios na embriogénese uterina, diferentes malformações congénitas
uterinas, definidas como desvios da anatomia normal do útero, surgem. Embora diversos fatores
etiológicos estejam relacionados, nomeadamente: agentes teratogénicos, fatores genéticos,
ambientais e multifatoriais, ainda não há documentação concreta sobre sua influência ou
mecanismo de ação.
Embora não haja uma classificação universalmente aceite para as anomalias uterinas
congénitas, a classificação ESHRE/ESGE é um sistema recente e claro, permitindo aos médicos
organizar qualquer anomalia. Com base nesse sistema de classificação, são desenvolvidos
protocolos para uma abordagem diagnóstica e de tratamento eficiente para cada tipo de
malformação.
Muitas vezes, essas anomalias estão relacionadas a desfechos reprodutivos adversos,
apresentando grande relevância na prática clínica. Geralmente, são diagnosticados apenas quando
a mulher atinge a idade adulta coincidindo com a ocorrência desses eventos. Infertilidade, abortos
repetidos (no primeiro ou início do segundo trimestre) e partos prematuros são manifestações
comuns.
Esta revisão sistemática foi realizada através das bases de dados PubMed e Google Scholar.
A pesquisa foi baseada na combinação dos termos do Medical Subject Headings (MeSH) definidos.
Artigos científicos, escritos em inglês desde 2010, foram incluídos, bem como artigos relevantes
mais antigos por referências cruzadas. The Female Genital Tract Congenital Malformations:
Classification, Diagnosis and Management, livro publicado em 2015, e as diretrizes ESHRE / ESGE
também foram ferramentas complementares de pesquisa.
Visto que atualmente é aceite que a necessidade de correção das malformações uterinas
varia conforme a doente, não sendo obrigatória e dependendo de muitas variáveis como: a
apresentação clínica, o grau de anomalia, a sua história médica passada principalmente em termos
de complicações obstétricas, a sua idade, e os seus planos reprodutivos, o objetivo desta
dissertação é discutir em quais situações a cirurgia de restauração da arquitetura uterina
desempenha um papel importante. Também são revisadas várias técnicas cirúrgicas e os resultados
pós-cirúrgicos para cada classe de anomalia, respetivamente, embora seja notório a falta de
grandes ensaios clínicos randomizados com resultados consistentes, o que pode levar a bibliografia
contraditória.
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Palavras-chave: Anomalias uterinas, malformações, congénitas, classificação, diagnóstico,
infertilidade, abortamento, histeroscopia, laparoscopia, cirurgia, dismórfico, septado, bicorpóreo,
hemi-útero, aplasia.
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ABBREVIATIONS
2D Two dimensional 3D Three dimensional AFS American Fertility Society AMH Anti-Müllerian hormone ASRM American Society of Reproductive Medicine CUA Congenital uterine anomaly DES Diethylstilbestrol ESGE European Society for Gynaecological Endoscopy ESHRE European Society of Human Reproduction and Embryology GnRH Gonadotropin-releasing hormone HSG Hysterosalpingography IUA Intrauterine adhesions IUGR Intrauterine growth restriction IVF In-vitro fertilization MA Müllerian aplasia MRI Magnetic resonance imaging MRKH Mayer-Rokitansky-Kuster-Hauser syndrome RCT Randomized controlled trial TRUST The Randomised Uterine Septum Transsection Trial TVS Transvaginal scanning US Ultrasonography
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LIST OF FIGURES Figure 1: Embryology of the female genito-urinary tract (frontal view). ......................................... 27
Figure 2: ESHRE/ESGE classification of uterine anomalie ................................................................ 28
Figure 3: Scheme for the classification of female genital tract anomalies according to the new
ESHRE/ESGE classification system. ................................................................................................... 29
Figure 4: Diagram of the incisions in dysmorphic uterus surgery. ................................................... 30
Figure 5: Surgical Technique of the Jones Procedure ...................................................................... 32
Figure 6: Surgical Technique of the Tompkins Procedure ................................................................ 34
Figure 7: Surgical Technique of the Strassman Metroplasty............................................................ 35
LIST OF TABLES Table I: Estimates of prevalence of different genital tract malformations using the new
ESGE/ESHRE classification ............................................................................................................... 36
Table II: Variants of bicorporeal uterus and their surgical treatment ............................................. 36
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INDEX
Acknowledgements ............................................................................................................................. i
Abstract ...............................................................................................................................................ii
Resumo ............................................................................................................................................... iii
Abbreviations ...................................................................................................................................... v
List of Figures ..................................................................................................................................... vi
List of Tables ....................................................................................................................................... vi
Introduction ....................................................................................................................................... 1
Material and Methods ....................................................................................................................... 2
Embryology ........................................................................................................................................ 3
Etiology ............................................................................................................................................... 5
Classification....................................................................................................................................... 7
Prevalence ........................................................................................................................................ 11
Clinical Presentation ......................................................................................................................... 13
Diagnosis .......................................................................................................................................... 16
Surgical Management ...................................................................................................................... 18
Class U1 (ESHRE/ESGE classification): Dysmorphic Uterus .......................................................... 18
Class U2 (ESHRE/ESGE classification): Septate Uterus ................................................................. 20
Class U3 (ESHRE/ESGE Classification): Bicorporeal Uterus .......................................................... 23
Classes U4a and U5a (ESHRE/ESGE classification): Rudimentary Horns with Cavity ................... 24
Conclusion ........................................................................................................................................ 26
Appendix 1 ....................................................................................................................................... 27
Appendix 2 ....................................................................................................................................... 36
References ........................................................................................................................................ 37
1
INTRODUCTION Disturbances of development, canalization, fusion or reabsorption of paired Müller
channels and urogenital sinus may lead to many congenital anomalies of the uterus, cervix, vagina,
and fallopian tubes. The prevalence of these malformations in unselected population is
approximately 5%, while women with reproductive issues are more commonly affected with
prevalence of 8% in infertile women and 13% in women with past miscarriages.1 Congenital uterine
anomalies (CUA) may cause no symptoms or can implicate severe health consequences and
diminish reproductive functions. It is described that morphologically identical defects have similar
embryologic origin and may be related with similar clinical expression. 2 Several attempts have been
made to label and organize these disorders of the Müller channels and establish definitions of
specific types of malformations according to morphologic resemblance, embryologic origin, and
suitable management. 3
During the past decade, classification systems and definitions of malformations have been
established, altered, or clarified, although implications of these adjustments for patient
management are not universally accepted and defined. 4 In this review, the recent European Society
of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy
(ESGE) classification 5 is used as reference since it characterizes the uterine anomalies in a clear and
objective way.
Current non-invasive or minimally invasive diagnostic methods have become generally
accessible and are now used for classification and surgical planning. These tools have replaced
classic diagnostic tools such as hysterosalpingography, two-dimensional (2D) ultrasound, diagnostic
hysteroscopy alone and hysteroscopy with laparoscopy. 4,6,7
Classically, corrective surgery of CUAs was performed in patients with specific clinical
presentation: infertility, history of poor obstetrical outcomes, and recurrent miscarriages. It is now
known the clinical implication of each type of anomaly and impact of surgery on fertility and
obstetrical results are not the same for all defects. There have been many advances in the
management of these patients including presurgical qualification, intraoperative imaging tools,
surgical approaches, and postoperative care. 8
2
MATERIAL AND METHODS An online search was performed at Pubmed and Google Scholar, using the following
Medical Subject Headings (MeSH) terms: uterine anomalies, congenital, Mullerian, abnormalities,
malformations, etiology, classification, clinical presentation, diagnosis, surgery, hysteroscopy,
laparoscopy, infertility, abortion, arcuate uterus, dysmorphic uterus, septate uterus, bicorporeal
uterus, hemi-uterus, aplastic uterus, and the UpToDate database using congenital uterine
anomalies as keywords.
The selection took place between September and April 2021 and the following inclusion
criteria were used: scientific articles, published since 2010, in English. After reading and critically
analysing the abstracts and conclusions, the bibliographic review articles, systematic reviews,
prospective studies, case reports, meta-analysis and clinical trials whose content was found to be
relevant to the topics covered in this review were considered.
At a later stage, cross references of relevant articles published prior to 2010 were also
included, when information on the subject was limited in the recent bibliography.
The Female Genital Tract Congenital Malformations: Classification, Diagnosis and
Management, a 2015 published book, and the ESHRE/ESGE guidelines were also complementary
research tools.
3
EMBRYOLOGY Up to the sixth week of embryogenesis, the urogenital system remains indifferent in both
sexes. Two pairs of genital systems are present: the mesonephric (Wolffian duct) and
paramesonephric (Müllerian duct). Further differentiation of the gonads is dependent on the
presence or absence of the SRY gene on the Y chromosome, which stimulates differentiation of the
testes in male individuals. In female individuals, the lack of anti-Müllerian hormone (AMH) allows
differentiation of the paramesonephric ducts into the female internal organs, and estrogen drives
the differentiation of female external genitalia (labia majora, labia minora and clitoris). The
testosterone insufficiency prevents the differentiation of the mesonephric ducts in female
individuals. 9,10
At week 6, the mesonephric ducts will develop from the mesoderm and span from the
mesonephros (where the future gonad will be located) to the cloaca (which will originate the
anorectal canal and the urogenital sinus). Until the eighth week, the paramesonephric ducts
appear, through the longitudinal invagination of the celomic epithelium on the antero-external face
of the mesonephros, parallel and externally to the mesonephric channels. During this week of
embryogenesis, the Müller channels begin to move towards the midline, while the consequent
degeneration of the male Wolff channels occurs. 10
The Müller channels eventually merge in the cranio-caudal direction, during week 10,
forming the uterus-vaginal canal. However, its proximal portion remains separate as it will develop
into the fallopian tubes, forming the fimbriae which derives from the tip of this structure, remaining
open and acquiring a funnel shape.
The fused caudal end gives origin to the left and right parts of what will ultimately become
the uterus. This structure contains mesoderm that will form the endometrium and myometrium. It
also remains divided by the inter-Müllerian septum, which is reabsorved during 11th week of
gestation.11 If this midline septum is not completely reabsorbed by the twelfth week, it will persist
and produce a septate uterus.
A continuous differentiation of structures occurs up until week 40, namely differentiation
of the uterine wall, cervix, and loss of the "V" shape of the uterus.
From the fusion of the sinus-vaginal bulbs along with the caudal end of the two Mullerian
ducts, the vaginal plaque is formed which, after bidirectional growth and central degeneration,
allows cavitation, which is completed by the 20th week, constituting the lower third of the vagina.
Thus, when disturbances in any of the steps in normal uterine embryogenesis occur,
different uterine abnormalities will result. Therefore, 4 major developmental defects are
considered:10
4
• Failure of one or both Müllerian ducts to form results in hemi-uterus without
rudimentary cavity or aplastic uterus, respectively. Aplastic uterus is the most
severe Müllerian defect. Cervical and vaginal aplasia frequently co-exist, and this is
known as Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome or Müllerian aplasia
(MA).
• Abnormal canalization of the Müllerian ducts results in hemi-uterus with
rudimentary cavity.
• Fusion of both Müllerian ducts leads to formation of a uterus and upper vagina.
o Horizontal fusion or unification (lower segments of paired müllerian duct
fuse to form uterus, cervix and upper vagina)–defects, depending on the
degree, lead to partial fusion or unification defect (bicorporeal uterus) or
complete fusion or unification defect.
o Vertical fusion (between the descending müllerian duct and ascending
urogenital sinus to form vaginal canal)–defects cause an imperforate
hymen or a transverse vaginal septum.
• Septal reabsorption involves the reabsorption of the horizontally fused Müllerian
ducts leading to development of the uterine cavity. A failure of this mechanism
results in a septate uterus. 12
All these malformations can be segmental, partial, or complete, related to the vagina, the
cervix, the uterine fundus, the fallopian tubes, or can be associated. Therefore, congenital uterine
anomalies may have characteristic features of various defects.11
Since the development of the genital and urinary systems are strongly associated, as both
depend on the correct maturation of the mesonephric system, it should be noted that in case of
interference of one of these systems, the other may also be affected. Therefore, it is imperative
that, after the diagnosis of one of the two types of abnormalities, uterine or renal, the existence of
the other is investigated. 13 This is widely documented in the literature, with studies indicating a
coexistence of congenital uterine and renal abnormalities in about 30–50%. Heinonen et al.14
concluded that the unilateral renal agenesis was the most frequent renal tract malformation in
women with Müllerian channel anomalies and renal malformations were more common in the main
groups of uterine anomalies, especially in patients with concomitant cervical and vaginal
obstructive anomaly. 14
If any factor causes disturbance at some point in the development of Müllerian channels,
the malformations will correspond to the week in which there was exposure to this etiological
factor. An exception is the exposure to Diethylstilbestrol (DES) in utero.
5
ETIOLOGY The occurrence of the malformations previously described are related to disturbances in
normal embryogenesis however, the exact etiology remains unknown. There are several theories
about possible causes and their form of action, namely teratogenic agents, genetic, chromosomal,
environmental, and multifactorial factors, that together can create a favourable environment for
the anomaly. 11,15
The karyotype is generally normal. However, some familiar cases are linked to a recessive
autosomal gene and others to a dominant autosomal one. Currently, only a small number of genes
(HNF1B, WNT4, WNT7A, HOXA13) have assembled a strong evidence of causality, mainly in
syndromic presentations. The sequencing of candidate genes in series of individuals with isolated
uterine abnormalities has been able to suggest an association for several genes, but confirmation
of a strong causative effect is still missing for most of them. 16
According to Hammoud et al. 17 nearly 10% of patients with Müllerian anomalies seem to
be accountable to a familiar association. They conclude that Müllerian anomalies have a strong
familiar aggregation and follow a polygenic and multifactorial inheritance.17
Nevertheless, the familiar association is hard to research. Uterine ultrasounds have not
usually been performed in extended family members with asymptomatic anomalies. Although in
many families recurrences tend to repeat the same type of uterine malformation, recurrences with
variable types of uterine maldevelopment have also been reported in several families suggesting
that similar genetic background could still induce different types of uterine malformation with
variable penetrance and expressivity. 16
It is implied that several cases of fetal genital tract defects are associated with a history of
exposure, intra and extrauterine, to certain environmental factors. Apart from the DES syndrome,
other teratogenic drugs, malnutrition, metabolic alterations, viral infections, and placental
anomalies have been implied. Numerous reports of discordant phenotypes in monozygotic twins
(e.g., MRKH syndrome vs. normal uterus) argue against strong heritability and suggest that post-
zygotic somatic mutations or non-genetic mechanisms including epigenetic or microenvironmental
factors regulate the occurrence of congenital uterine malformations. 18,19
The uterus exposed to DES in utero undergoes several changes in its development, having
a characteristic aspect: uterus with "T" shaped cavity, usually hypoplastic, with widening of its lower
segment, presence of median constricting bands and irregular endometrial edges.20 DES has been
used by women for several years, since it was thought that it could reduce the risk of spontaneous
abortions. However, it was discontinued in 1971, after perceived increased risk of developing clear
cell adenocarcinoma of the lower genital tract (cervix and vagina) in women exposed in utero.21
6
Nevertheless, this dysmorphic T-shaped uterus can also be found in DES non-exposed
patients, which is consistent with the idea that CUA are influenced by multifactorial, polygenic and
familiar mechanisms that together can create a favourable environment for the anomaly, but in
most patients there is no evident cause or association.
7
CLASSIFICATION Classifications are fundamental in medicine since they allow a systematization of medical
knowledge and facilitate communication between physicians. Until today, there is no universally
acknowledged classification system for CUAs, which is critical due to their prevalence and clinical
relevance.22 The existing about an efficient classification emerge diagnostic and treatment
difficulties.
An ideal classification system includes a clear description of each class and subclass,
allowing objective identification of each anatomical variation. It should also enable the inclusion of
new classes, if new anomalies are detected. Finally, the correlation between the various classes and
subclasses with the respective clinical presentations, treatment options and prognosis is crucial.
Thus, it would allow the determination of obstetric and fertility impacts inherent to each anomaly
and the therapeutic strategies that would improve them. 22
The first classifications for CUAs were carried out according to the descriptions of
Cruveilher, Foerster and von Rokitansky in the mid-19th century. However, the first description to
be widely recognised was published by Buttram and Gibbons in 1979, which was later revised and
modified by the American Fertility Society (AFS), now known as the American Society of
Reproductive Medicine (ASRM). This has been the most used classification over the past three
decades. In 1988 the AFS published their classification scheme 23 for mechanical problems
associated with poor reproductive outcomes. The Müllerian anomalies were classified as follows:
(I) agenesis and hypoplasias;
(II) unicornuate uterus;
(III) didelphic uterus;
(IV) bicornuate uterus;
(V) septate uterus;
(VI) arcuate uterus;
(VII) anomalies related to DES syndrome.
The goal of this classification was to provide an easy and reliable system to allow physicians
to group cases, and for future patients to be counselled accurately and effectively. Nevertheless,
this classification has several disadvantages, including the lack of strict morphometric criteria and
the subjective description of the anomalies since there are no standardized diagnostic criteria.
There was also no apparent definition of normal uterus. For these reasons, additional
morphometric criteria were endorsed by ASRM in 2016 , which reported Class VI (arcuate uterus)
as a normal variant, not clinically relevant. This leaves a grey zone between normal/arcuate and
septate where some women will not meet the criteria for either diagnoses.
8
Another limitation is that the AFS classification only refers to Müllerian anomalies and is
mainly focused on the uterus. Therefore, an embryologic-clinic classification was suggested by
Acién et al. 3 which considers all female genitourinary malformations and their embryologic origin.
Another group described the vagina, cervix, uterus, adnexa, and associated malformations
(VCUAM) system influenced by the TNM oncology system.24 These two systems, although very
understandable, are complex and not user friendly, for physicians.
The ESHRE/ESGE developed in 2013 (figure 2) a “uterus-cervix-vagina” classification
system5. Anatomy is the foundation for the systematic categorization of anomalies so deviations of
uterine anatomy deriving from the same embryological origin are the basis for the design of the
main classes. The sub-classes are based on the different degrees of uterine deformity, while cervical
and vaginal anomalies are classified in independent supplementary sub-classes. Anomalies are
sorted in the classes and sub-classes of the system according to increasing severity of the
anatomical deviation. 5
All cases with normal uterus are classified in Class U0. A normal uterus is defined as any
uterus having either straight or curved interostial line but with an internal indentation at the fundal
midline not exceeding 50% of the uterine wall thickness. The arcuate uterus is now considered a
normal variant, since it is the mildest form of uterine septum 5,25, resulting from anomalies at the
end of resorption of the inter-Müllerian septum7,26. Patients are asymptomatic, have no
compromise of fertility, and similar pregnancy outcomes as those in the general obstetric
population. In imaging it appears as a minimal myometrial prominence at the fundus, there is
deviation less than 1 cm fundal indentation and an angle of indentation greater than 90º.6
Dysmorphic uterus (Class U1) refers to all cases with normal uterine outer configuration
but with an abnormal shape of the uterine cavity excluding septa. It is subdivided into three
categories:
T-shaped uterus (Class U1a) represents a narrow uterine cavity due to thickened
lateral walls with a ratio of 2/3 uterine corpus to 1/3 cervix.
Uterus infantilis (Class U1b) characterized also by a narrow uterine cavity without
lateral wall thickening and an inverse ratio of 1/3 uterine body and 2/3 cervix.
Others (Class U1c) include minor deformities of the uterine cavity including those
with an inner indentation at the fundal midline level of <50% of the uterine wall
thickness. This clearly differentiates them from patients with septate uterus.
The Septate uterus (Class U2) includes all cases with normal fusion of the Müller channels
and abnormal absorption of the midline septum.27 The uterus presents with normal outline and an
internal indentation at the fundal midline exceeding 50% of the uterine wall thickness.28 The
septum is usually vascularized fibromuscular and it could divide partly or completely the uterine
9
cavity including in some cases cervix and/or vagina. The thickness and composition of the septum,
the relative amounts of fibrous and muscular tissue, and the degree of vascularization from the
adjacent uterine wall may also vary.27 No classification system standardizes all these variations. The
anomalies are divided in two sub-class according to the degree of the uterine corpus deformity:
Partial septate uterus (Class U2a) which has a septum dividing partly the uterine
cavity above the level of the internal cervical ostium.
Complete septate uterus (Class U2b) is characterized by the presence of a septum
fully dividing the uterine cavity up to the level of the internal cervical ostium.
Patients with complete septate uterus (ClassU2b) could have or not cervical (e.g.
bicervical septate uterus) and/or vaginal defects.
The Bicorporeal uterus (Class U3) occurs due to incomplete or partial fusion of both Müller
channels.29 As bicorporeal is defined the uterus with an abnormal fundal outline, it is characterized
by the presence of an external indentation at the fundal midline exceeding 50% of the uterine wall
thickness. It also correlates with an inner indentation at the midline level that divides the cavity as
the septate uterus. The degree of uterine corpus deformity divides this anomaly into three sub-
classes:
Partial bicorporeal uterus (Class U3a) when an external fundal indentation partly
divides the uterine corpus above the cervix.
Complete bicorporeal uterus (Class U3b) characterized by an external fundal
indentation completely dividing the uterine corpus. These patients could have
coexistent cervical defects, for instance double cervix (formerly didelphys uterus)
and/or vaginal anomalies as an obstructive or non-obstructive septum. In some
cases, duplication of other structures such as bladder, vagina or anus are
present.(29)
Bicorporeal septate uterus (Class U3c) characterized by the presence of an
absorption defect combined with the main fusion defect. In patients with this
anomaly, the width of the midline fundal indentation exceeds by 150% the uterine
wall thickness.
The Hemi-uterus (Class U4) is defined as a unilateral uterine development, while the
contralateral part could be either incompletely formed or absent. The need to classify it in a
different class than that of aplastic uterus (formation defect) is due to the existence of a fully
developed functional uterine hemi-cavity. It is further divided into two sub-classes depending on
the presence or not of a functional rudimentary cavity, since it changes the clinical presentation
and treatment:
10
Hemi-uterus with a rudimentary cavity (Class U4a) which can be a communicating
or noncommunicating functional contralateral horn.
Hemi-uterus without rudimentary cavity (Class U4b) characterized either by the
presence of non-functional contralateral uterine horn or by aplasia of the
contralateral part.
The Aplastic uterus (Class U5) means the absence of any fully or unilaterally developed
uterine cavity due to defects during the initial development of the Müller channels. Some co-
existent anomalies, as vaginal aplasia or MRKH Syndrome could be present. This class is further
divided into two sub-classes depending on the presence or not of a functional cavity in an existent
rudimentary horn:
Class U5a or aplastic uterus with rudimentary (functional) cavity characterized by
the presence of bi- or unilateral functional horn.
Class U5b or aplastic uterus without rudimentary (functional) cavity characterized
either by the presence of uterine remnants or by full uterine aplasia.
Class U6 is kept for unclassified cases. Current imaging technology grants objective
evaluations of uterine anatomy for the differential diagnosis among the six groups. However,
infrequent anomalies, subtle changes or combined anomalies could not be allocated correctly to
one of the group. The system is designed to include cases resulting from formation, fusion or
absorption defects of normal embryological development. Duplication defects or ectopic Müllerian
tissue anomalies, if existing, could not be described. These anomalies could be put in this class.
This classification also has autonomous categories to classify vaginal and cervical defects
that could be associated with the uterine defects. Figure 3 demonstrates the classification and
description of the different types of vaginal and cervical anomalies.
11
PREVALENCE Malformations of the female genital tract are common but not always identified. CUA are
the most frequent ones, being significant in the population with adverse reproductive history.
The prevalence of female genital tract malformations in different populations of women
has been exceedingly difficult to estimate in the past few decades owing to the lack of indispensable
factors (a clear definition and selection of the populations examined; the use of a clear and
consistent classification of the malformations; the use of accurate investigations to make the
correct diagnosis of the malformations) explaining the notable difference of these values between
them. 30–32
In an initial review by Grimbizis et al. 33 the prevalence of uterine anomalies was found to
be around 4% in the general population, 4% in patients with infertility, and 12% in patients with
recurrent abortions. This study has various limitations such as the retrospective design of the
studies included, and diagnostic methods used in different studies included were not the same and
of low accuracy.
Recent systematic reviews 1,30 estimate the prevalence to be 5.5–6.7% for the general
population, 7.3–8.0% for the infertile population and 13.3–16.7% for the recurrent miscarriage and
poor reproductive outcome population and 24.5 % in those with miscarriage and infertility. Overall,
the prevalence of major congenital anomalies appears to be at least three times higher in women
with poor reproductive outcome compared with the general population. 30
The commonest malformations appeared to be the Class U2 septate/subseptate uteri,
followed by the class U3 bicorporeal uteri. Class U1 dysmorphic uteri, Class U4 hemi-uteri and Class
U5 aplastic uteri all had a prevalence of less than 1%. 1,30 However, Class U2 uteri may be
overrepresented since some arcuate uteri which will fall in the Class U2 septate/subseptate
category may in fact be normal uterine variants according to the new ESGE/ESHRE classification. 5
Usually, the diagnosis is done after imaging tests in response to signs or symptoms
presented by the patient. However, these can exist without clinical manifestations, with benign
evolution and reproductive success, remaining asymptomatic. Thus, no clinical detection is ever
made, or it is done unintentionally, so it is estimated that the prevalence of these anomalies is
slightly higher than what has been reported. 34
On the other hand, in addition to hysterosalpingography (HSG), the increasing and everyday
use of high-accuracy imaging techniques such as 3D ultrasound (3D US), magnetic resonance
imaging (MRI) and the application of minimally invasive surgical procedures (hysteroscopy and
laparoscopy) resulted in a more accurate diagnosis and in an observed increase in their prevalence.
30
12
With increased accessibility through imaging techniques, and therefore higher detection
rates, an emerging question is: “What is clinically significant and requires intervention versus what
may be ignored as a subtle and normal variant?” 15 This question acknowledges the issue of when
intervention improves outcomes.
13
CLINICAL PRESENTATION Congenital uterine anomalies are frequently related to adverse reproductive outcomes
with the leading clinical presentations being infertility, conflicting obstetric events (repetitive
abortions especially during the first or beginning of the second trimester, preterm delivery, fetal
malpresentation and intrauterine growth restriction [IUGR]), menstrual disorders and dyspareunia.
2,15,34 These women are also reported to have increased rates of pre-eclampsia and stillbirth. 35
Currently, it is established, the close association between the specific type of malformation and the
respective clinical presentation, including reproductive results. 34
The factors that negatively influence fertility, include changes in morphology, volume,
thickness, organization and function of the endometrium and myometrium, which may be
associated with cervical incompetence or changes in uterine vascularization, according to each
specific anomaly. Usually, the myometrium of congenitally abnormal uteri are thinner than normal
and mural thickness diminishes as pregnancy advances, causing inconsistencies over different
aspects of the uterus. 34
As cases of infertility are generally associated with other etiological factors, these must be
excluded before proceeding to the treatment of uterine malformations. 15
While most cases are diagnosed during adulthood, certain groups of malformations are
associated with primary amenorrhea without impuberism, making it possible to for the detection
to be made at a younger age. The MRKH syndrome being an example. 15
Chan et al. 36 reviewed 3805 women with CUAs and reported that abortion rates resulting
from all causes range between 21–50%, with a decrease in birth rates of about half in comparison
to the general population. This author describes that those with septate and partial septate uteri,
seem to have the worst reproductive performance, with a smaller conception rate (OR 0.86; 95%
CI 0.77–0.96) and increased probability of first-trimester miscarriage (OR 2.89; 95% CI 2.02–4.14),
preterm birth (OR 2.14; 95% CI 1.48–3.11), and fetal malpresentation at delivery (OR 6.24; 95% CI
4.05–9.62). Compared with those with a partial septate uterus, women with a septate uterus have
poorer outcomes throughout their pregnancies. 35
Various hypothesis have been suggested, such as vascular abnormalities, since the septum
is composed of fibroelastic tissue with inadequate vascularization and consequent imbalance in its
relationship between the myometrium and the endometrium. This imbalance may cause
disturbances in the implantation of the embryo and in the response of the septal endometrial
mucosa to estrogen, with little proliferation and estrogenic maturation. Here an additional
mechanism is identified, the inadequate growth of deciduous. Uncoordinated uterine contractions
14
or reduced uterine capacity are other factors that may contribute to the suboptimal reproductive
performance. 36
The bicorporeal uterus and hemi-uterus do not appear to reduce fertility but are associated
with increased risks of adverse outcomes during pregnancy. These patients have an increased risk
of first trimester miscarriage (OR 3.4; 95% CI 1.18–9.76 and OR 2.15; 95% CI 1.03–4.47 respectively),
preterm birth (OR 2.55; 95% CI 1.57–4.17 and OR 3.47; 95% CI 1.94–6.22 respectively) and fetal
malpresentation (OR 5.38; 95% CI 3.15–9.19 and OR 2.74; 95% CI 1.3–5.77 respectively). 36
Vascularization may be deficient in some uterine malformations, due to its absence or the
presence of abnormal uterine or ovarian vessels. This mechanism may explain possible IUGR or
spontaneous abortions. There are also less endothelial growth factors, which are essential for the
growth of the vascular network needed for embryo/fetus nutrition and development. In the hemi-
uterus, the severe lack of volume and distorted morphology, which, throughout a pregnancy, will
progressively cause a decrease in wall thickness the presence of a single uterine artery causes
important lack in vascularization. While in the bicorporeal uterus, there is a poor vascularization of
the medial endometrium, which is shared between the two semi-cavities. 34
The dysmorphic uterus is characterized by abnormal morphology (T-shaped or a infantilis
uterus). Fernandez et al. 37 presented a retrospective study on 97 women with a T-shaped uterus;
while 63 had a history of DES exposure, the remaining 35% had either a congenital malformation
attributable to other causes or an acquired T-shaped malformation. On a total of 78 pregnancies
before hysteroscopic metroplasty the miscarriage prevalence is 78.2 %, ectopic pregnancy 17.9 %,
preterm delivery 3.8 % with all neonatal deaths and no live birth.37
Cervical insufficiency seems to be an important cause of poor reproductive results in cases
of Müllerian anomalies, not due to the existence of malformations in the neck itself, but, according
to several researchers, due to the imbalance between the amount of muscle fibres and connective
tissue, which exists in less quantity. 38,39 In addition to this different composition, the forces exerted
by the uterine content during pregnancy are also distinct, being asymmetrical and being increased
in the presence of uterine malformations, which causes premature relaxation of the hypermuscular
neck. Thus, a way to improve reproductive results in cases of uterine congenital anomalies may
involve prophylactic cervical cerclage, as has been successfully tested. 4011[NO_PRINTED_FORM]
15CUAs may also entail severe health conditions or have serious consequences that
endanger the woman's life. 34 Regarding the obstructive anomalies, the uterus has a functioning
endometrium with no communication (Classes U4 and U5) or is associated with aplasia or dysplasia
of the cervix and/or vagina (Co-existing classes C1, C3, C4, V2, V3 and V4). These patients are
asymptomatic until they reach puberty, then their main presenting symptom is amenorrhea (with
normal secondary sexual characteristics) and cyclical abdominal pain (due to the retention of
15
menstruation and eventually leading to hematometra and hematocolpus) which may be followed
by constant pain. These women are at increased risk for: endometriosis due to retromenstruation;
abnormal uterine bleeding or discharge; infections secondary to vaginal micro perforations;
possible inability to establish a sexual life; reproductive difficulties (even under medically assisted
procreation treatments).30
Considering pregnant patients, fertilization can occur in a functional non-communicating
(rudimentary) uterine horn (Class U4a) by transmigration of sperm, however the exact incidence
remains unknown. The eventual15 rupture and haemorrhage of this cavity corresponds
almost15always to an emergency. 15
It 34is important to understand the negative psychological impact that these types of
anomalies may have. The psychologic support of these adolescents will reduce the anxiety and
depression they experience, will help them to adapt better to their congenital abnormality and help
to prepare better for the appropriate surgical management.
Finally, an idea to keep in mind is the possibility that the obstetric results presented are
biased, and correspond to ‘worst-case scenarios’, due to the selection of symptomatic cases. It is
estimated that there is an important number of undiagnosed cases, as they are asymptomatic and
have reproductive success.
16
DIAGNOSIS The diagnostic work-up for female genital tract anomalies continues to represent a great
challenge for the gynaecologist due to the presence of various techniques available for the
diagnosis that differ in their invasiveness, availability, needs for training and, more importantly,
diagnostic accuracy. It seems that, despite advances in ultrasound and new pelvic imaging
techniques, late diagnosis of female genital tract anomalies remains frequent.
Correct evaluation of the internal and external outlines of the uterus is essential for correct
diagnosis and classification of CUAs. Formerly, the gold standard has been a combination of
laparoscopy and hysteroscopy, since it also offers the advantage of concurrent treatment, as in the
case of a uterine septum resection. However, imaging techniques that are non-invasive, easily
accessible, and well-accepted from the patients such as ultrasonography (US),
hysterosalpingography (HSG), sonohysterography and magnetic resonance imaging (MRI) are the
choice to screen, diagnose and classify CUAs. 7 While conventional two-dimensional (2D)
transvaginal US and HSG are suitable for screening for uterine anomalies, three-dimensional (3D)
transvaginal US and MRI can accurately classify them. 41–43Clique ou toque aqui para introduzir
texto.
Conventional 2D transvaginal US is minimally invasive, available, and can give reliable,
reproducible, and measurable information on uterine anatomy, leading to the exact diagnosis as
well as the differential diagnosis between the different categories. However, it has a lower
diagnostic accuracy in comparison with the other sonographic techniques. 6 Scanning in the second
half of the menstrual cycle (the secretory phase) provides more accurate visualization of the
endometrium and is therefore appropriate for assessment. Visualization of two endometrial
cavities on a transverse plane indicates anomaly.
3D transvaginal US, by its unique feature of providing the coronal plane of the uterus,
facilitates simultaneous visualization of both external (serosal surface) and internal (uterine cavity)
outlines of the uterine fundus, being important for the correct classification of the partial
bicorporeal, septate and partial septate uteri. 44 Complete bicorporeal, also demonstrates two
endometrial cavities in the transverse plane of conventional 2D US, but 3D US, along with a clinical
manifestation of two cervices or two vaginas on speculum examinations, can confirm the diagnosis.
In cases of hemi-uterus, a normal long axis of the uterus is demonstrated on one side only of the
pelvis. The parallel side is characterized by the lack of, or a rudimentary, uterine shadow. A banana-
shaped uterine cavity and single interstitial portion of fallopian tube in the coronal plane is seen
using 3D ultrasound. Saline infusion sonography has been suggested as a method for diagnosing
17
rudimentary horns, as saline can evidently be seen in the hemi-uterus, with absence of flow into
the rudimentary horn, if it is non-communicating. 41
Currently, 3D transvaginal US is considered the gold standard for the assessment of CUAs
as it is less invasive and can classify the varying types of uterine anomalies correctly. Criteria for the
classification of uterine anomalies based on 3D ultrasound have been described in the Thessaloniki
ESHRE/ESGE consensus on diagnosis of female genital anomalies. 41
MRI of the pelvis is sensitive and specific for diagnosis of uterine malformations, as it
outlines the endometrium and has the capacity to detect uterine horns. It also defines any
abnormal gonadal location or renal anatomy.45 It is a less invasive modality than combined
laparoscopy and hysteroscopy. While MRI is not routinely recommended in all women with a
suspected CUA, it is useful for those women with unconfirmed diagnosis on 3D ultrasound, those
with suspected complex anomalies, and for those who decline or are uncomfortable by internal
examinations. 41
A urinary tract ultrasound scan, MRI or intravenous pyelogram is recommended in all
women diagnosed with a uterine anomaly, choosing the most appropriate method accordingly. 14
18
SURGICAL MANAGEMENT
The purpose of CUA management relies on treating anatomical deformities associated with
obstructive anomalies for symptomatic relief (therefore improving quality of life) and to avoid long-
term health and reproductive adverse consequences. Relatively to non-obstructive anomalies, the
goal is to improve reproductive outcomes in infertile women or women who have history of
recurrent miscarriages. The fundamental intention is increasing live births at term, with an
associated reduction in long term neonatal morbidity and mortality, therefore surgical application
is dependent on its efficacy to reverse the reproductive consequences. 46,47
The need for treatment to correct uterine malformations varies from case to case,
depending on the clinical presentation, the degree of change in the anatomy of the uterus, the
woman's past medical history, especially in terms of obstetric complications, her age, and her
reproductive plans. Intervention is not mandatory. The role of surgical treatment in incidentally
diagnosed non-obstructive uterine anomalies to improve reproductive outcomes remains
debatable. 15
CLASS U1 (ESHRE/ESGE CLASSIFICATION): DYSMORPHIC UTERUS There are no standardized criteria for reconstructive surgery of a T-shaped uterus (Class
U1a), since many of these patients are asymptomatic and are able to carry a pregnancy to term 48,
however some authors 37,49 are proposing hysteroscopic metroplasty as potential treatment,
especially regarding repeated miscarriage, preterm deliveries, long-term infertility, implantation
failures, or an upcoming IVF treatment (although prospective randomized controlled trials are
lacking to give a firm recommendation). 47 This procedure can be performed in ambulatory setting,
with the patient in conscient sedation.
For patients with a dysmorphic uterus U1b (infantilis uterus), there is currently no
indication for reconstructive surgery, according to Grimbizis et. al. 50
The aim of the metroplasty is the restorage of the normal triangular anatomy of the uterine
cavity through incisions in the lateral walls of the dysmorphic uterus and, if necessary, in the fundus,
as seen in Figure 4. 47 Hysteroscopic scissors, monopolar or bipolar resectoscope, mini-
hysteroscopes with 5 Fr needles, or micro-scissors could be used for the enlargement of the
endometrial cavity by successive incisions along an initial incision line from each tubal ostium to
the isthmus uteri. Fundal incision should be made if there is a coexisting fundal indentation
(especially if thickness greater than 11mm). A vaginoscopic approach is suggested to reduce the
risk of unnecessary trauma or uterine perforations.
19
The complication rate during and after this hysteroscopic procedure is low. They include
intraoperative (uterine perforation and haemorrhage) and postoperative complications
(intrauterine adhesions [IUA], cervical insufficiency and abnormal placentation in a future
pregnancy). In the literature there is only one case of uterine perforation and one case of
haemorrhage after T-uterus surgery reported 37, while the postoperative complications are more
common. Fernandez et al. using different surgical approaches reports an incidence of 5% of
adhesions 37. To prevent IUA, a collagen gel barrier is advised to be inserted into the endometrial
cavity. Use of estrogen as perioperative adjuvant therapy has been suggested for preventing
recurrent IUA, based on its critical role in stimulating and enhancing endometrial growth via
angiogenesis. However, according to the literature, 50 in case of normal endocrinological profile
with regular menstrual cycles no adjuvant estrogen therapy is recommended. Although antibiotic
is still used widely after hysteroscopic surgery recent randomised trials do not find evidence of
benefit and recommend not to implement it, since it does not reduce the risk of infection. 51,52 The
result of this surgery is usually assessed after two menstrual bleedings by hysteroscopy.
Regarding abnormal placentation after surgical correction, three cases of placental
retention described by Di Spiezio et al. 53 The depth of the myometrial incisions and altered
vascularization in these patients could play a role in the pathophysiology. Cervical insufficiency is
not as much established in the literature. Although Fernandez et al. 37 reported ten cases of cerclage
after surgery in 97 women, five of them had previous history of cervical incompetence.
Confounding factors are the use of cervical dilatation and the antecedent to DES-exposure that are
related to cervical insufficiency.
Fernandez et al. 37 noted ~50% of pregnancy rate after the hysteroscopic metroplasty with
a mean time until the first conception of 10.5 months. Miscarriage rate was 36.8% and 8 pregnant
women delivered before 30 weeks of gestation. Among those with secondary infertility, the first
trimester miscarriage rate decreased from 78.2% to 26.9% and the live birth rate increased to 73%
after the reconstructive surgery. Meier et al. 49 in a pool of 100 women without DES-exposure,
reported 57% of pregnancy rates, with the median time to the first pregnancy of 4 months.
Miscarriage rate was 16%, and no ectopic pregnancy was reported, while 36 deliveries were at
term. Di Spiezio et al. 53 out of 214 patients with a dysmorphic uterus, metroplasty was completed
in all cases, resulting in a significant increase of uterine cavity volume (100%) and optimization of
uterine morphology in 211 of 214 women (98.6%). After 60 months, the overall clinical pregnancy
rate was 72.9% and the live birth rate was 80.1%. Specifically, 74 of 156 women (47.4%) conceived
spontaneously (with a median time to pregnancy of 5.5 months), of whom 32.4% had previously
failed 1 or more attempts at in vitro fertilization/intracytoplasmic sperm injection.
20
It seems that the surgery improves or normalizes the reproductive results, although this
evidence is mainly based on retrospective studies, none of which had a control group of untreated
women for comparison. Nowadays, patients with dysmorphic uterus and history of recurrent
pregnancy loss, preterm delivery or before entering an assisted reproductive programme could
benefit from a hysteroscopic correction. For an experienced surgeon, using a small diameter
hysteroscope and the micro scissors, excellent anatomical results are obtained in a simple
ambulatory procedure with low complication rate. 50
Neto et. al 54, however states that the benefits of surgical treatment for this anomaly seem
to be largely exaggerated and the current evidence available lack quality. They also emphasize that
until randomized controlled trials (RCTs) demonstrate the benefit of this surgery, expectant
management is the most appropriate choice in daily practice for women with a T-shaped uterus.
CLASS U2 (ESHRE/ESGE CLASSIFICATION): SEPTATE UTERUS The resection of the septum is a viable procedure which can be easily performed by
hysteroscopy, currently considered the gold-standard. 15 Compared with a transabdominal
approach (Jones or Tompkins metroplasty, demonstrated in figures 5 and 6, respectively), benefits
include lower perioperative morbidity, avoidance of potential pregnancy complications related to
transmyometrial incisions, and faster return to normal activity. The transcervical approach reduces
the risk of pelvic infection and formation of intra-abdominal adhesions, which may cause future
infertility or small bowel obstruction. Patients may attempt pregnancy sooner after a transcervical
approach than a transabdominal approach, and future vaginal delivery is not contraindicated. 55
Transcervical resection of a septum is easier when the endometrium is thin since a
thickened endometrium limits visualization. Therefore, typically the aim is to schedule the
procedure in the early follicular phase, also decreasing the risk of undiagnosed pregnancy.
Alternatively, a thinner endometrium can be accomplished by pre-treatment with a continuous
estrogen/progestin contraceptive, progestin-only pill or a gonadotropin-releasing hormone (GnRH)
agonist. Use of danazol is slightly preferable to use of a GnRH agonist because of lower cost and
side effects. Furthermore, the use of a GnRH agonist may decrease the size of the uterine cavities,
limiting the ability to perform the procedure. 47
When the preoperative imaging study clearly establishes the diagnosis and the septum is
small, a hysteroscopic metroplasty is performed. However, when the imaging study does not clearly
establish the diagnosis or the septum is large (extending from the fundus to the internal cervical
os), a simultaneous laparoscopy is needed to evaluate the external uterus and observe the serosa
during the procedure to help decrease the risk of perforation.
21
Various techniques and instruments can be used for incision or resection, including scissors,
electrosurgical electrodes guided through the hysteroscope, resectoscopy, or fibre lasers. The
resectoscope is widely used and its energy source can be monopolar or bipolar. When bipolar
energy is used, the distention medium of the cavity is isotonic saline solution, and therefore, the
risk of complications due to intravasation are low. Non-ionic low viscosity fluid such as Dextran or
Glycin in case monopolar energy is used. 47
The goal of the procedure is reducing the septal surface area. A partial septum may require
only incision of the septum, while a large septum requires resection, starting from the distal part of
the septum. During surgery, the tubal ostia are the surgical landmarks for decent guidance. The
septum incision is made equidistant from the anterior and posterior uterine wall and the procedure
is completed when there is a good view of a restored triangular cavity, with free movement of the
hysteroscope between the two ostia and exposure of the muscle fibres of the fundus. Using a
graduated intrauterine palpator to objectively check the portion of septum resected, is an
alternative that verifies completion of resection.56 It is of extreme importance to leave a safety
thickness of 10 mm of the fundal wall, in order to avoid possible future uterine ruptures. 47
The small diameter hysteroscopes do not require general anaesthesia or even a local one.
Several authors favour this “vaginoscopic” technique due to the accessible entry of the uterus,
without cervical dilatation, use of saline solution as the distension medium and, according to their
studies, low risk of uterine perforation and thermal trauma. Since the visualization of the cavity is
not as broad as in the resectoscopic technique, two incisions, as landmarks, must be done at both
sides of the septum before starting the incision. The incision can be done by cold scissors or electric
devices.
Potassium-titan-phosphate (KTP-532), Fibeoptic Nd:YAG or argon lasers are other viable
techniques although their use has markedly decreased due to their cost and the simplification of
electrosurgery using vaporizing and bipolar electrodes. 57
A cervical septum (class U2C1) or a double cervix (class U2C2) might also be present.
Incision of a coexisting cervical septum can be performed, although potential cervical weakness
after surgery must be considered. There are authors that defend the unification of the cavity should
only be performed from the isthmus up to the fundus, while the repair of the cervical deformity
should be avoided since it is too traumatic for the cervix and associated with cervical insufficiency
in a subsequent pregnancy. In order to achieve this, a Foley balloon catheter is inserted into the
uterus transcervically, slightly inflated, and pulled down against the internal ostium to prevent
leakage of the distension media. Placing a flexible hysteroscope into the second cervix or instilling
blue dye can be helpful for identifying when the hysteroscope has entered the second cavity. The
22
challenge in these cases is placing the first incision so it passes from one side of the septum to the
other and does not compromise the internal cervical ostium of either cervix.
A 2D or 3D ultrasound or a hysterosalpingogram can be performed two months
postoperatively to assess results. Ideally, over 90% of the septum should have been removed. If
there is a significant residual septum remaining, which happens occasionally, further resection of
the septum is necessary.
When the procedure is deemed adequate, a recent observational study 58, suggests that
patients can begin attempting to conceive two months postoperatively. However, there not enough
evidence to advocate a specific length of time before a woman should conceive after the procedure.
Clinical results of hysteroscopic metroplasties are generally good and seem to be
independent from the tools, the type of energy and the techniques used.
In the past two systematic reviews 33,59 reported significant decrease in miscarriage rates
(from 86.4 - 88% before to 16.4 - 14% after hysteroscopic incision) and an increase in term delivery
rates (from 3 - 3.4% before to 76.2 - 80% after).
A more recent review by Nouri et al. 60 analysed the accomplishment of pregnancy in
infertile women after septum incision: they reported ~60% pregnancy rate and ~45% live birth rate.
All studies indicating a positive effect of surgery although these are heterogeneous in population
and in definition of uterine septum.
Gergolet et al. 26 prospectively compared the reproductive outcome in patients with small
(group A) and large (group B) septa who underwent metroplasty. Miscarriage rates dropped from
94.9% to 82.1% in groups A and B, respectively, before treatment to 11.1% and 14.0% after
treatment. Delivery rates were 2.6% and 15.7%, respectively, before operation and 88.9% and
84.2% after surgery. It seems, therefore, that the length of the septum does not play a role in
reproductive outcome, either before or after hysteroscopic metroplasty. Similar results were
reported by Paradisi et al. 61 in women with small (<2.5 cm) and large partial uterine septum (>2.5
cm), and by Tomazevic et al. 62 who found that the clinical pot-surgery result of women with small
septa is not different from that of women with large septa.
A systematic review and meta-analysis of controlled studies 2 reported a decreased
probability of spontaneous miscarriages (both first and second trimester) in women treated with
hysteroscopic resection of septum compared with women who were not treated (RR 0.37, 95% CI
0.25–0.55). There was no difference in conception rates (RR 1.14, 95% CI 0.79–1.65) and preterm
delivery rates (RR 0.66, 95% CI 0.29–1.49) among the hysteroscopic resection and control groups.
RCTs are needed to confirm the beneficial effects of metroplasty reported by numerous
publications. 63 The Randomised Uterine Septum Transsection Trial (TRUST)64 to assess whether
hysteroscopic septum resection improves reproductive outcomes in women with a septate uterus
23
and a history of (recurrent) miscarriage, subfertility or preterm birth is a multicentre study in the
Netherlands, Iran and USA. Recruitment has started since October 2009 and is ongoing, since the
authors are experiencing difficulty in recruiting women and clinicians to participate. 64 Women are
aware of all these of non-randomized publications which confirm the improvement of pregnancy
and live birth rates after metroplasty. Also, the lack of uniformity in the distinction between a
normal uterine cavity and a small septate uterus. The new ESHRE/ESGE classification 5 is a helpful
tool to reach a greater homogeneity of studies and interpretation of uterine imaging procedures
since the terminology “arcuate” uterus has been abandoned by this classification.
CLASS U3 (ESHRE/ESGE CLASSIFICATION): BICORPOREAL UTERUS The necessity of surgical repair for this anomaly is currently arguable, varying according to
each subclass, as shown in table 2. 47
Since patients with a partial bicorporeal uterus (Class U3a) do not have an increased risk of
adverse pregnancy outcomes, they do not benefit from surgical intervention.
Traditionally, Strassman metroplasty by laparotomy was the gold standard for surgical
correction of the complete bicorporeal uterus (Classes U3bC0 and U3bC2) 65. The technique, as
shown in Figure 7, involves a single transverse incision across the uterine fundus from one cornua
to the other so that both uterine cavities can be visualized. Then, eversion of each horn is made,
and a single layer of interrupted figure-of-eight sutures is placed to form a single uterine cavity
beginning from the posterior and continuing with the anterior wall. 65
However, whether surgical correction of bicorporeal uterus with Strassman metroplasty is
necessary is highly controversial given that fertility rates are not significantly reduced and
successful pregnancies without surgical correction intervention are common. 50 Thus, it should be
avoided as a prophylactic procedure.
Laparoscopic unification of bicorporeal uterus with normal (class U3bC0) or double cervix
(class U3bC2) has been reported 13, but it is technically challenging. Laparoscopic subtotal
hysterectomy in a woman with U3bC2 uterus due to abnormal uterine bleeding has been recently
described as well. 66 The surgical steps of the procedure were similar to those of laparoscopic
subtotal hysterectomy performed in morphologically normal uteri. 66
Counseling pregnant women with bicorporeal uterus, either surgically repaired or not,
about the necessity of a cesarean section is crucial since the risk of uterine rupture is increased. 34
Cervical cerclage might be considered because cervical incompetence is an issue in these patients,
however it is not clear at which week of pregnancy it should be performed.
24
Depending on the anatomical status of cervix and/or vagina, bicorporeal uterus could be
presented in some uncommon variants. Surgical treatment is necessary and laparoscopic
management feasible in these rare subclasses which present with obstructing symptoms.
Patients with bicorporeal uterus, double cervix, and longitudinal obstructing vaginal
septum (Class U3bC2V2) should be treated surgically by cutting or resecting the vaginal septum.
This is necessary to alleviate vaginal and hemi-uterine obstruction by restoring continuity. 67
In cases of bicorporeal uterus with unilateral cervical aplasia (class U3bC3), removal of the
obstructed hemi-uterus is indicated, since it might act as a rudimentary horn and has therefore
similar clinical manifestation.13 Restoration of utero-vagina continuity of the obstructed hemi-
uterus is an alternative technique either by laparoscopically assisted cervicoplasty in cases of
cervical atresia or by isthmo-vagina anastomosis. In these types of malformation, the risk of
complications such as ectopic pregnancy should be addressed to the patients before surgical
management. 67
Finally, patients with a bicorporeal septate uterus (class U3c) represent a challenging
management. A 2011 study 68 reported that hysteroscopic metroplasty (by incising the septate part
of the indentation) improved reproductive outcome in 80% of the patients and dysmenorrhea also
remarkably improved. 68
Larger number of patients and well-designed studies are essential to draw accurate
conclusions. RCTs comparing the pregnancy outcomes between cases treated and not treated by
metroplasty among patients with poor obstetric history are needed because it is not yet established
whether surgery alone could improve live birth rate.
CLASSES U4A AND U5A (ESHRE/ESGE CLASSIFICATION): RUDIMENTARY HORNS WITH CAVITY
While a hemi-uterus does not warrant surgical intervention, functioning rudimentary
uterine horns, frequently attached, have strong surgical indications. They can be excised by
laparotomy, but currently, laparoscopic removal is the usual gold-standard, along with excision of
the ipsilateral fallopian tube. This technique has been reported for over a decade already. 69
Preoperative treatment with a GnRH-analogue or danazol has been suggested aiming to
reduce the size of hematometra before surgery.
The surgeon must avoid damage of the remaining unicorporeal uterus, especially in
patients with large attachment between the unicorporeal body and the rudimentary horn. Scissors,
electrosurgery ultracision energy, and endoscopic staplers have been reported as tools to remove
the rudimentary horn, while the simultaneous use of hysteroscopy to separate the two horns is also
described. 70
25
Regarding class U5a, prophylactic excision of the rudimentary horn is still controversial. It
is certain that laparoscopic excision is the preferred management if the patient is symptomatic with
cyclic pelvic pain and/or hematocavity in whom other underlying causes of pain have been
excluded.71
In cases of MRKH patients with rudimentary functional uterine horns an different surgical
approach can be offered: the uterovaginal anastomosis with restoration of menstrual function,
which has been documented in the past.72 It involves neovagina creation, metroplasty (incision of
the uterine bulbs, surgical consolidation of the uterine horns and creation of a large uterine cavity)
and utero-neovaginal anastomosis can lead not only in the function of the horn but in successful
reproductive outcome as well.
A two-step surgery, combining a laparoscopic Davidov’s vaginoplasty with abdominal
isthmo-neovagina anastomosis, has been reported recently.73 The anatomic restoration of the
genital tract in these women appears to have good outcomes and leads to functional
menstruation and restitution of the sexual life.73,74
26
CONCLUSION The new ESHRE/ESGE Classification, which has been recently published, seems to be a new,
clear, and systematic categorization of CUA.
Based on the best currently available evidence, it seems that surgical treatment is indicated
in women presenting with symptoms related to specific uterine anomalies and it also improves or
normalizes the reproductive results, although this evidence is mainly based on retrospective
studies, being a relevant limitation. Many issues are still controversial among scientists, and
prospective studies should be performed for a more reliable evaluation of outcomes of the
proposed surgical techniques.
Nowadays, patients with a dysmorphic (class U1 in ESHRE/ESGE Classification), septate
(class U2 in ESHRE/ESGE Classification), or bicorporeal septate (class U3 in ESHRE/ESGE
Classification) uterus presenting with infertility, poor reproductive outcomes, or before entering an
assisted reproductive programme could benefit from a hysteroscopic correction. Excellent
anatomical results are obtained in a simple ambulatory procedure with low complication rate.
Surgical removal of the rudimentary horns with cavity (ESHRE/ESGE class U4a/U5a) appears
to be the established method of treatment of rudimentary horns for symptoms relief and avoidance
of complications. Another surgical treatment alternative in highly selected cases is restoration of
continuity. The therapeutic objectives should always be pain relief and preservation of sexual and
reproductive function, if possible.
27
APPENDIX 1
FIGURE 1: EMBRYOLOGY OF THE FEMALE GENITO-URINARY TRACT (FRONTAL VIEW). THE FORMATION OF THE UTERINE
PRIMORDIUM AND THE OPENING OF THE MESONEPHRIC DUCTS INTO THE UROGENITAL SINUS ARE SHOWN. MÜLLERIAN TUBERCLE
CAN BE SEEN BETWEEN BOTH WOLFFIAN DUCTS AND THE URETERAL BUDS SPROUTING FROM THE OPENING OF THE WOLFFIAN DUCT
INTO THE UROGENITAL SINUS. MD, MÜLLERIAN DUCTS; WD, WOLFFIAN DUCTS; K, KIDNEY; MT, MÜLLERIAN TUBERCLE; US,
UROGENITAL SINUS.75
28
FIGURE 2: ESHRE/ESGE CLASSIFICATION OF UTERINE ANOMALIES5
29
FIGURE 3: SCHEME FOR THE CLASSIFICATION OF FEMALE GENITAL TRACT ANOMALIES ACCORDING TO THE NEW
ESHRE/ESGE CLASSIFICATION SYSTEM.5
30
FIGURE 4: DIAGRAM OF THE INCISIONS IN DYSMORPHIC UTERUS SURGERY.50 (A) LATERAL INCISION IN SUBTYPE U1A; (B)
LATERAL AND FUNDAL INCISIONS IN SUBTYPE U1C
A B
31
32
FIGURE 5: SURGICAL TECHNIQUE OF THE JONES PROCEDURE ADAPTED FROM UPTODATE: (A) IN THE JONES
PROCEDURE, THE COMMON CAVITY IS INITIALLY REACHED THROUGH A WEDGE RESECTION OF THE SEPTUM. (B) THE SEPTUM IS
TOTALLY REMOVED AS THE TWO CAVITIES ARE UNROOFED. (C) UTERINE CLOSURE IS BEGUN IN THE LOWER PORTION OF THE CAVITY. THE ANTERIOR AND THEN THE POSTERIOR WALLS ARE CLOSED, INCLUDING THE ENDOMETRIUM AND A SMALL PORTION OF THE
MYOMETRIUM. THE SUTURE MAY BE CONTINUOUS OR INTERRUPTED. (D) BEGINNING INFERIORLY, A ROW OF INTERRUPTED
SUTURES IS THEN PLACED IN THE REMAINING THICKNESS OF THE UTERINE WALL. (E) USING THE LIGHTEST POSSIBLE SUTURE, THE
THIRD LAYER APPROXIMATES THE SUPERFICIAL MYOMETRIUM AND SEROSA. THE ROUGH EDGES SHOULD BE IMBRICATED AS MUCH
AS POSSIBLE TO PREVENT ADHESIONS ALONG THE SUTURE LINE.
E
33
34
FIGURE 6: SURGICAL TECHNIQUE OF THE TOMPKINS PROCEDURE ADAPTED FROM UPTODATE: (A) IN THE TOMPKINS
PROCEDURE, THE SEPTUM IS INCISED, BUT NOT REMOVED. AN INITIAL INCISION IS MADE DOWN THE MIDDLE OF THE SEPTUM UNTIL
THE COMMON CAVITY IS REACHED. (B) THE SEPTAL TISSUE IS INCISED BILATERALLY TO UNROOF THE TWO CAVITIES. (C) REPAIR
THEN PROCEEDS AS IN THE JONES TECHNIQUE, WITH THE ANTERIOR AND THE POSTERIOR ASPECTS BEING APPROXIMATED WITH
CONTINUOUS OR INTERRUPTED SUTURES. (D) THE DEEP MYOMETRIUM IS REPAIRED. (E) AFTER WHICH THE SUPERFICIAL
MYOMETRIUM AND SEROSA ARE CLOSED WITH AN IMBRICATING SUTURE.
35
FIGURE 7: SURGICAL TECHNIQUE OF THE STRASSMAN METROPLASTY50 (A) BICORPOREAL UTERUS (B) INCISION FROM ONE
CORNUA TO THE OTHER (C) POSTERIOR UTERINE WALL CLOSURE (D) ANTERIOR UTERINE WALL CLOSURE (E) SEROSAL CLOSURE
36
APPENDIX 2 TABLE I: ESTIMATES OF PREVALENCE OF DIFFERENT GENITAL TRACT MALFORMATIONS USING THE NEW
ESGE/ESHRE CLASSIFICATION 1,30
TABLE II: VARIANTS OF BICORPOREAL UTERUS AND THEIR SURGICAL TREATMENT50
37
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