Diagnosis and Therapy of Female Genital Malformations (Part 2). Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/052, May 2019)

Abstract

Objectives Female genital malformations may be present in the form of individual entities, they may involve neighboring organs or they may occur in the context of complex syndromes. Given the anatomical structures of the vulva, vagina, uterus and uterine appendages, the clinical picture of malformations varies greatly.

Methods This S2k-guideline was developed by representative members from different medical specialties and professions as part of the guidelines program of the DGGG, SGGG and OEGGG. The recommendations and statements were developed and voted on using a structured consensus process with neutral moderation.

Recommendations This guideline is the first comprehensive summary of female genital malformations from infancy to adulthood which covers clinical examinations, diagnostic workups and treatment options. Additional chapters have been included on complex urogenital malformations, vascular malformations, psychosomatic care, and tumor risk.

Key words

guideline - genital malformations - subseptate uterus - septate uterus - bicornuate uterus - unicornuate uterus - malformations of the uterine adnexa - uterine vascular malformations

I  Guideline Information

Guidelines program of the DGGG, OEGGG and SGGG

For information on the guidelines program, please refer to the end of this guideline.

Citation format

Diagnosis and Therapy of Female Genital Malformations (Part 2). Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/052, May 2019). Geburtsh Frauenheilk 2021; 81: 1329–1347

Guideline documents

The complete German-language long version of this guideline and a slide version of these guidelines as well as a list of the conflicts of interest of all of the authors are available on the homepage of the AWMF: http://www.awmf.org/leitlinien/detail/ll/015-052.html

Guideline authors

See [Tables 1] and [2].

Table 1 Lead author and/or coordinating guideline author.

Author	AWMF professional society
Prof. Dr. Peter Oppelt	Arbeitsgemeinschaft gynäkologische Endoskopie in DGGG [Gynecologic Endoscopy Working Group of the DGGG], Österreichische Gesellschaft für Gynäkologie & Geburtshilfe [Austrian Society of Gynecology and Obstetrics]

Table 2 Contributing guideline authors.

Author Mandate holder	DGGG working groups/AWMF/non-AWMF professional society/organization/association
Binder Helge, Prof. Dr.	Arbeitsgemeinschaft gyn. Endoskopie in DGGG [Gynecologic Endoscopy Working Group of the DGGG]
Birraux Jacques, Dr.	Schweizerische Gesellschaft für Kinderchirurgie [Swiss Society for Pediatric Surgery]
Brucker Sara, Prof. Dr.	Arbeitsgemeinschaft gyn. Endoskopie in DGGG [Gynecologic Endoscopy Working Group of the DGGG]
Dingeldein Irene, Dr.	Schweizerische Gesellschaft für Gynäkologie und Geburtshilfe [Swiss Society of Gynecology and Obstetrics]
Draths Ruth, Dr.	Schweizerische Arbeitsgemeinschaft für Kinder- und Jugendgynäkologie [Swiss Working Group on Pediatric and Adolescent Gynecology]
Eckoldt Felicitas, Prof. Dr.	Deutsche Gesellschaft für Kinderchirurgie [German Society for Pediatric Surgery]
Füllers Ulrich, Dr.	Arbeitsgemeinschaft gyn. Endoskopie in DGGG [Gynecologic Endoscopy Working Group of the DGGG]
Hiort Olaf, Prof. Dr.	Deutsche Gesellschaft für Kinder- und Jugendmedizin [German Society of Pediatrics and Adolescent Medicine]
Hoffmann Dorit, Dr.	Schweizerische Gesellschaft für Pädiatrie [Swiss Society of Pediatrics]
Hoopmann Markus, PD Dr.	Arbeitsgemeinschaft für Ultraschalldiagnostik in DGGG [Working Group for Ultrasound Diagnostics in the DGGG]
Hucke Jürgen, Prof. Dr.	Arbeitsgemeinschaft gyn. Endoskopie in DGGG [Gynecologic Endoscopy Working Group of the DGGG]
Korell Matthias, PD Dr.	Arbeitsgemeinschaft gyn. Endoskopie in DGGG [Gynecologic Endoscopy Working Group of the DGGG]
Kühnert Maritta, Prof. Dr.	Arbeitsgemeinschaft Geburtshilfe & Pränatalmedizin in DGGG [Obstetrics and Prenatal Medicine Working Group of the DGGG]
Ludwikowski Barbara PD Dr.	Deutsche Gesellschaft für Kinderchirurgie [German Society for Pediatric Surgery]
Mentzel Hans-Joachim, Prof. Dr.	Gesellschaft für Pädiatrische Radiologie [Society for Pediatric Radiology]
OʼDey Dan mon, PD Dr.	Deutsche Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen [Geman Society of Plastic, Reconstructive and Aesthetic Surgeons]
Rall Katharina, Dr.	AG Kinder- und Jugendgynäkologie in DGGG [Pediatric and Adolescent Gynecology Working Group of the DGGG]
Riccabona Michael, Univ.-Prof. Dr.	Gesellschaft für Pädiatrische Radiologie [Society for Pediatric Radiology]
Rimbach Stefan, PD Dr.	Arbeitsgemeinschaft gyn. Endoskopie in DGGG [Gynecologic Endoscopy Working Group of the DGGG]
Schäffeler Norbert, Dr.	Deutsches Kollegium für Psychosomatische Medizin [German Collegium of Psychosomatic Medicine]
Shavit Sandra, Dr.	Schweizerische Gesellschaft für Kinderchirurgie [Swiss Society for Pediatric Surgery]
Stein Raimund, Prof. Dr.	Deutsche Gesellschaft für Urologie [German Society of Urology]
Utsch Boris, PD Dr.	Deutsche Gesellschaft für Kinder- und Jugendmedizin [German Society of Pediatrics and Adolescent Medicine]
Wenzl Rene, Prof. Dr.	Österreichische Gesellschaft für Gynäkologie & Geburtshilfe [Austrian Society of Gynecology and Obstetrics]
Wieacker Peter, Prof. Dr.	Deutsche Gesellschaft für Humangenetik [German Society of Human Genetics]
Zeino Mazen, Dr.	Schweizerische Gesellschaft für Kinderurologie [Swiss Society for Pediatric Urology]

The guideline was moderated by Dr. med. Monika Nothacker (AWMF-certified guideline moderator).

II  Guideline Application

Purpose and objectives

This guideline aims to present feasible diagnostic and therapeutic approaches for patients with congenital malformations of the female genital tract.

Targeted areas of patient care

1. Hospital care

2. Outpatient care

3. Day-patient care

4. Senior consultant/medical specialist care

Target user group/target audience

This guideline is aimed at the following groups of people:

• Practice-based gynecologists

• Hospital-based gynecologists

• Practice-based physicians of pediatric and adolescent medicine

• Hospital-based physicians of pediatric and adolescent medicine

• Practice-based pediatric surgeons

• Hospital-based pediatric surgeons

• Practice-based pediatric radiology physicians

• Hospital-based pediatric radiology physicians

• Practice-based pediatric urologists

• Hospital-based pediatric urologists

• Practice-based physicians of psychosomatic medicine and psychologists

• Hospital-based physicians of psychosomatic medicine and psychologists

The guideline also aims to provide information to other medical professionals who care for female patients with genital malformations, e.g., nursing staff.

Adoption and period of validity

The validity of this guideline was confirmed by the executive boards/heads of the participating medical professional societies, working groups, organizations and associations as well as the boards of the DGGG, the DGGG guidelines commission, the SGGG and the OEGGG in the 4th quarter of 2019 and was thus approved in its entirety. This guideline is valid from 1st May 2019 through to 30th May 2024. Because of the contents of this guideline, this period of validity is only an estimate.

III  Methodology

Basic principles

The method used to prepare this guideline was determined by the class to which this guideline was assigned. The AWMF Guidance Manual (version 1.0) has set out the respective rules and requirements for different classes of guidelines. Guidelines are differentiated into lowest (S1), intermediate (S2), and highest (S3) class. The lowest class is defined as consisting of a set of recommendations for action compiled by a non-representative group of experts. In 2004, the S2 class was divided into two subclasses: a systematic evidence-based subclass (S2e) and a structural consensus-based subclass (S2k). The highest S3 class combines both approaches.

This guideline has been classified as: S2k

Grading of recommendations

The grading of evidence based on the systematic search, selection, evaluation and synthesis of an evidence base which is then used to grade recommendations is not envisaged for S2k guidelines. The different individual statements and recommendations are only differentiated linguistically, not by the use of symbols ([Table 3]):

Table 3 Grading of recommendations (based on Lomotan et al., Qual Saf Health Care 2010)).

Description of binding character	Expression
Strong recommendation with highly binding character	must/must not
Regular recommendation with moderately binding character	should/should not
Open recommendation with limited binding character	may/may not

Statements

Expositions or explanations of specific facts, circumstances or problems without any direct recommendations for action included in this guideline are referred to as “statements”. It is not possible to provide any information about the grading of evidence for these statements.

Achieving consensus and level of consensus

At structured NIH-type consensus-based conferences (S2k/S3 level), authorized participants attending the session vote on draft statements and recommendations. The process is as follows. A recommendation is presented, its contents are discussed, proposed changes are put forward, and finally, all proposed changes are voted on. If a consensus (> 75% of votes) is not achieved, there is another round of discussions, followed by a repeat vote. Finally, the extent of consensus is determined based on the number of participants ([Table 4]).

Table 4 Level of consensus based on extent of agreement.

Symbol	Level of consensus	Extent of agreement in percent
+++	Strong consensus	> 95% of participants agree
++	Consensus	> 75 – 95% of participants agree
+	Majority agreement	> 50 – 75% of participants agree
–	No consensus	< 51% of participants agree

Expert consensus

As the term already indicates, this refers to consensus decisions taken specifically with regard to recommendations/statements issued without a prior systematic search of the literature (S2k) or where evidence is lacking (S2e/S3). The term “expert consensus” (EC) used here is synonymous with terms used in other guidelines such as “good clinical practice” (GCP) or “clinical consensus point” (CCP). The strength of the recommendation is graded as previously described in the chapter on the grading of recommendations but without the use of symbols; it is only expressed semantically (“must”/“must not” or “should”/“should not” or “may”/“may not”).

IV  Guideline

9  Malformations of the uterus

Arcuate uterus/subseptate uterus/septate uterus

(VCUAM U1a – c; ESHRE/ESGE Class U 1 – 2)

9.1  Definition

Fusion of the Mullerian ducts has occurred but in cases with a single uterus, resorption of the sagittal septum either did not occur or was only partial. A subseptate uterus is defined as an outwardly almost normally shaped, often slightly wider uterus with a sagittal septum which does not create a separation across the entire length of the uterine cavity. A subseptate septum is longer than the indentation occurring with an arcuate uterus but shorter than the septum of a septate uterus. Septate uterus is used to describe a uterus in which the septum separates more than half of the uterine cavity, often extending down to the uterine cervix.

9.2  Diagnostic imaging

The initial suspicion of uterine malformation is often based on two-dimensional ultrasound. A more precise differentiation can be obtained with 3D vaginal sonography and magnetic resonance imaging (MRI). Invasive diagnostic methods include hysteroscopy and laparoscopy. The outer contour of the uterus, thickness of the myometrial wall, a thickened fundus of uterus, the presence and extent of the central fundal indentation and the shape of the uterine cavity are diagnostic criteria. The key concern is to differentiate this malformation from bicornuate uterus.

9.3  Arcuate uterus

(VCUAM U1a; ESHRE/ESGE Class U1)

Arcuate uterus may also be interpreted as the smallest manifestation of a uterine septum.

9.3.1  Specific features

There are no confirmed data on whether an arcuate uterus may cause sterility.

9.3.2  Therapy

Surgical correction of an arcuate uterus should be carried out in patients with recurrent miscarriage. The procedure consists of a median incision of a wide septum using hysteroscopic scissors or the needle electrode of a resectoscope.

9.4  Subseptate uterus

(VCUAM U1b; ESHRE/ESGE Class U2)

9.4.1  Specific features

A subseptate uterus has a negative impact on fertility due to increased rates of early and late miscarriage. This is compounded by higher numbers of cases with malpresentation and higher rates of fetal growth restriction, stillbirth and dystocia. Women with a septate uterus and idiopathic sterility benefit from dissection of the septum.

9.4.2  Specific diagnostic workup

3D ultrasound and MRI are non-invasive methods which can be used to obtain a differential diagnosis. Hysteroscopy is used to assess the size of the intracavitary septum. A laparoscopy to obtain an external evaluation of the uterus and differentiate it from bicornuate uterus is recommended.

9.4.3  Therapy

As hysteroscopy for surgical correction is now a simple procedure, a preventive incision of the septum should be considered in women wanting to have children. The dissection should be carried out before starting assisted reproductive technology procedures and in cases with recurrent miscarriage. The septum is incised using hysteroscopic scissors or the needle electrode of a resectoscope. The incision should be extended until the shape of the uterine cavity appears normal. Whether this is carried out under simultaneous laparoscopic monitoring depends on the surgeonʼs experience. Dissection is recommended in cases with a low proliferative endometrium.

9.4.4  Specific follow-up care

Special follow-up care after surgical correction is not necessary. Reliable contraception for the duration of the healing period of three months is advised.

9.5  Septate uterus

(VCUAM U1c; ESHRE/ESGE Class U2)

9.5.1  Specific features

A septate uterus has a negative impact on fertility due to the increased rates of early and late miscarriage. In addition, higher numbers of cases with malpresentation, higher rates of fetal growth restriction, stillbirth and dystocia are observed in these patients. There are no confirmed data but some indications that a septate uterus may cause sterility. As noted above for subseptate uterus, the data is limited.

9.5.2  Specific diagnostic workup

3D ultrasound and MRI are non-invasive methods used to obtain a differential diagnosis which differentiates between septate and bicornuate uterus. Direct visualization is possible with a hysteroscopy. A laparoscopy to obtain an external assessment of the uterus and differentiate this malformation from bicornuate uterus is strongly recommended.

9.5.3  Therapy

Compared to a subseptate uterus (9.4.3), the septum in a septate uterus usually extends from the fundus down to the cervix. The cervical part of the septum should not be dissected as cervical insufficiency in a subsequent pregnancy is possible. It requires particular skill on the part of the surgeon to find the correct level of dissection when the contralateral cavity cannot be visualized. To avoid complications, carrying out this procedure under laparoscopic control is strongly recommended. The procedure should be carried out in a low proliferative endometrium. If necessary, prior hormone suppressive treatment using a GnRH agonist or ovulation inhibitors should be considered at the time of the surgical procedure. Abdominal metroplasty has been entirely replaced by surgical hysteroscopy and the technique is therefore obsolete.

9.5.4  Specific follow-up care

Special follow-up care after surgical correction is not necessary. Reliable contraception for the duration of the healing period of three months is advised. The fetus may be delivered vaginally. The medical center where the patient gives birth must be informed about the surgical intervention.

9.6  Bicornuate uterus

(VCUAM U2; ESHRE/ESGE Class U 3)

9.6.1  Specific features

Formation of a bicornuate unicollis or bicollis uterus with or without vaginal duplication is the result of impairment in the fusion of the two Mullerian ducts. Bicornuate unicollis uterus is the most common anomaly.

9.6.2  Specific diagnostic workup

The same diagnostic methods are used to diagnose subseptate and septate uterus. The use of 3D ultrasound and MRI are non-invasive methods to obtain a differential diagnosis which differentiates between septate and bicornuate uterus. A laparoscopy for external assessment of the uterus is strongly recommended.

9.6.3  Therapy

9.7  Unicornuate uterus

(VCUAM U4a; ESHRE/ESGE Class U 4)

9.7.1  Specific features

Unicornuate uterus may be associated with impaired fertility. Treatment depends in the first instance on the specific features of the rudimentary horn. If a communicating or noncommunicating rudimentary horn with endometrial tissue is present, it must be resected. Pregnancy in a rudimentary horn often has dramatic consequences, with uterine rupture occurring in the 2nd trimester of pregnancy; this is a potentially life-threatening situation for the patient.

10  Malformations of the uterine adnexa

(ESHRE/ESGE free description; VCUAM A1 – 3)

11  Complex urogenital malformations

This chapter deals with female genital malformations in infants. The chapter covers malformations of the urogenital sinus, cloacal malformation and bladder exstrophy-epispadias complex, from their epidemiology to their treatment and follow-up care. For more details on Chapter 11, please refer to the long German-language version available on the homepage of the AWMF.

12  Congenital vascular malformations

13  Associated malformations

Because the developmental processes of the paramesonephric (Mullerian) ducts, mesonephric (Wolffian) ducts and the urogenital sinus are interconnected, malformations of the Mullerian ducts lead to associated malformations [1], [2].

The mechanisms of female urogenital development are based on a complex signal transduction system. Wnt and Hox genes along with BMP (bone morphogenetic protein) and WT-1 (Wilmsʼ tumor) suppressor genes play a key role [3], [4], [5]. The mesonephric ducts and their interaction with the urogenital sinus over time affect the correct development of the paramesonephric ducts and their anatomical relationship to the urinary tract. Developmental disorders can lead to a large number of associated malformations, for example, of the kidneys, urinary tract, bladder and skeletal system as well as anorectal malformations.

14  Obstetric management

In patients with genital anomalies, the question arises whether vaginal delivery is feasible. In many cases, spontaneous delivery is possible. The general rule is that the obstetrician must decide on the delivery mode together with the pregnant patient. The specific individual circumstances of the malformation and the extent of the malformation must be taken into account, and the obstetric management must be adapted accordingly. Below are statements and recommendations on the obstetric management of various malformations [4], [6], [7].

14.1  Cloaca

14.2  Bladder exstrophy

14.3  Congenital anomalies of the vulva

14.4  Vagina

14.5  Congenital anomalies of the uterus

15  Psychosomatic care

15.1  Quality of life, psychological comorbidities, stressful issues

15.2  Psychosomatic considerations during diagnosis and treatment

15.3  Psychosomatic diagnosis

15.4  Special approach/situation: children and adolescents

Age-appropriate and repeated discussions of the diagnosis with children and adolescents are important, and the approach which is taken will differ depending on the timepoint when the diagnosis is made and the impact of the malformation.

15.5  Malformation of the external genitalia

Because of its external visibility, early diagnosis of this type of malformation is possible, usually in early childhood. In this case, continuous age-appropriate support is required.

15.6  Genital malformations affecting puberty and/or sexuality

These are usually only diagnosed at a late stage (in puberty). When the diagnosis is dicussed, the meeting should be attended by someone the patient trusts. The patient may often wish to include her partner and the inclusion of the partner is often experienced as positive.

15.7  Special approach/situation: surgical treatment to create a vagina

Emotional/sexual maturity are important preconditions for the surgical creation of a vagina. The suitable age for this appears to be 16 – 18 years.

15.8  Psychosomatic interventions

While in retrospect, affected patients talk about having a great need of support after receiving the diagnosis, the obstacles to availing themselves of this support at the time of diagnosis appear to be high. Providing information on available psychosomatic counseling and support services as part of the standard care offered to affected patients and facilitating contacts to other affected (same-age) girls or women appears to be helpful [8], [9].

15.9  Self-help groups/networks

16  Tumor risk

Risk of bladder tumors in patients with bladder exstrophy

Tumor risk associated with disorders of sex development (DSD)

Conflict of Interest/Interessenkonflikt

The conflicts of interest of all of the authors are listed in the German-language long version of the guideline./Die Interessenkonflikte der Autoren sind in der Langfassung der Leitlinie aufgelistet.

• References/Literatur

• 1 Hall-Craggs MA, Kirkham A, Creighton SM. Renal and urological abnormalities occurring with Mullerian anomalies. J Pediatr Urol 2013; 9: 27-32
• 2 Wu CQ, Childress KJ, Traore EJ. et al. A Review of Mullerian Anomalies and Their Urologic Associations. Urology 2020; DOI: 10.1016/j.urology.2020.04.088.
• 3 Ledig S, Wieacker P. Clinical and genetic aspects of Mayer-Rokitansky-Küster-Hauser syndrome. Med Genet 2018; 30: 3-11
• 4 Oppelt P, von Have M, Paulsen M. et al. Female genital malformations and their associated abnormalities. Fertil Steril 2007; 87: 335-342
• 5 Carlson BM. Human Embryology and developmental Biology. 6th ed. St. Louis, MO: Elsevier; 2019
• 6 Edmonds DK. Congenital malformations of the genital tract and their management. Best Pract Res Clin Obstet Gynaecol 2003; 17: 19-40
• 7 Acién P, Acién M. The presentation and management of complex female genital malformations. Hum Reprod Update 2016; 22: 48-69
• 8 Weijenborg PT, ter Kuile MM. The effect of a group programme on women with the Mayer-Rokitansky-Küster-Hauser syndrome. BJOG 2000; 107: 365-368
• 9 Heller-Boersma JG, Schmidt UH, Edmonds DK. A randomized controlled trial of a cognitive-behavioural group intervention versus waiting-list control for women with uterovaginal agenesis (Mayer-Rokitansky-Küster-Hauser syndrome: MRKH). Hum Reprod 2007; 22: 2296-2301

Publication History

Received: 28 March 2021
Received: 02 December 2020

Accepted: 28 March 2021

Article published online:
08 December 2021