List of Abbreviations
IUS – intrauterine synechiae
IUD – intrauterine device
HSG – hysterosalpingography
Terms and Definitions
Intrauterine synechiae – obliteration of the uterine cavity caused by the presence of partial or complete fibrous intrauterine adhesions [1].
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
Intrauterine synechiae – obliteration of the uterine cavity caused by the presence of partial or complete fibrous intrauterine adhesions [1].
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
Endometrial trauma resulting from curettage for pregnancy termination, in the postpartum period, or during a spontaneous miscarriage; following surgeries accompanied by hysterotomy; as well as inflammatory uterine diseases and tuberculosis, is considered one of the main etiological factors in the development of intrauterine synechiae [2], [3]. Despite the numerous treatment options proposed, disease recurrence can reach 62%. Intrauterine synechiae associated with uterine artery embolization or prior uterine compression sutures (for postpartum hemorrhage) have a higher probability of recurrence [4], [5].
1.3 Epidemiology of the Disease or Condition
The frequency of secondary amenorrhea associated with intrauterine synechiae is approximately 3% [1].
1.4 Features of Coding the Disease or Condition
N85.6 – Intrauterine synechiae
N85.8 – Other specified noninflammatory disorders of uterus
1.5 Classification of the disease or condition
The American Fertility Society (AFS) and the European Society for Gynaecological Endoscopy (ESGE) provide classifications of intrauterine synechiae. The 1988 AFS classification for intrauterine synechiae used three criteria, including the extent of the cavity involved, the type of adhesions, and the menstrual pattern — Appendix A3 for the purpose of the following prognostic classification: stage I (mild), II (moderate), and III (severe) [6]. The ESGE classification includes grade I (thin or membranous adhesions, easily detached with a hysteroscopic introducer), II (single dense adhesions that cannot be detached with a hysteroscopic introducer, tubal ostia are visualized), IIa (occluding adhesions only in the internal os area with a normal uterine cavity), III (multiple dense adhesions connected to a separate cavity space and unilateral obliteration of tubal ostia), IV (extensive dense adhesion with partial occlusion of the cavity and tubal ostia), Va (extensive scarring and endometrial fibrosis combined with grade I or II adhesions accompanied by amenorrhea or marked hypomenorrhea), and Vb (extensive endometrial scarring and fibrosis combined with grade III or IV adhesion accompanied by amenorrhea), determined based on hysteroscopy and hysterosalpingography data [7], [8], [9], [10]. The classification was modified in 2017 (Appendix A3.1) [4].
1.6 Clinical presentation of the disease or condition
Intrauterine adhesions can be either asymptomatic or symptomatic, characterized by menstrual irregularities such as hypomenorrhea and amenorrhea, as well as reproductive disorders like recurrent pregnancy loss and infertility. Sex hormone and gonadotropin levels are within normal limits (normogonadotropic amenorrhea) [1].
2. Diagnostics, medical indications and contraindications for diagnostic methods
The diagnosis of intrauterine adhesions is established based on complaints, medical history, ultrasound examination, hysterosalpingography, sonohysterography, and hysteroscopy. Hysteroscopy is the most accurate diagnostic method for intrauterine adhesions.
2.1 Complaints and Anamnesis
The course of the disease can be asymptomatic and symptomatic. Symptoms of the disease include hypomenorrhea, amenorrhea, recurrent pregnancy loss, and infertility.
2.2 Physical Examination
It is recommended to perform a visual inspection of the external genitalia, a speculum examination of the cervix, and a bimanual pelvic examination in all patients to establish a diagnosis [1].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
2.3 Laboratory Diagnostics
It is recommended to review laboratory data to detect concomitant diseases, perform a preoperative evaluation, and determine management tactics in all patients with intrauterine adhesions [1].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
It is recommended to perform microscopic examination of vaginal smears in patients with intrauterine adhesions to rule out pelvic inflammatory disease [1].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
It is recommended to perform cytological examination of a cervical smear in patients with intrauterine adhesions to detect cervical intraepithelial neoplasia [1].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
2.4 Instrumental Diagnostics
It is recommended to perform hysterosalpingography (HSG) to diagnose intrauterine adhesions in patients with severe, dense adhesions [11].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: a high rate of false-positive results (up to 39%) limits its use; HSG does not detect endometrial fibrosis and does not allow assessment of the nature [12] and extent of intrauterine adhesions [13].
It is recommended to perform pelvic ultrasound (US) in all patients as the primary diagnostic method for intrauterine adhesions [11].
GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)
Comments: sonohysterography is effective in diagnosing intrauterine adhesions, with a sensitivity of 75%.
Three-dimensional ultrasonography may be more useful for assessing intrauterine adhesions, with a sensitivity of 87%.
It is recommended to perform hysteroscopy when intrauterine adhesions are suspected in patients with reproductive plans and symptoms [4].
GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5)
Comments: hysteroscopy more accurately confirms the presence, extent, and morphological characteristics of adhesions, as well as the condition of the endometrium. Hysteroscopy provides real-time visualization of the uterine cavity, allowing for precise description of the location and severity of adhesions, classification, and simultaneous surgical correction [4].
It is not recommended to use pelvic magnetic resonance imaging (MRI) for the routine diagnosis of intrauterine adhesions [11], [14].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
2.5 Other Procedures
Not provided
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
3.1 Conservative Treatment
It is recommended to insert solid barriers after hysteroscopic lysis of intrauterine adhesions [4], [15].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: copper-bearing and T-shaped IUDs cannot be recommended due to their inflammation-provoking properties and small surface area. An inert loop IUD is considered the most appropriate.
A Foley catheter may be used for 3–10 days after hysteroscopic lysis of intrauterine adhesions as a physical barrier [4], [16], [17].
It is recommended to insert semi-solid barriers after hysteroscopic lysis of intrauterine adhesions [4].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: a number of gel adhesion barriers (based on hyaluronic acid) successfully reduce the risk of adhesion recurrence after surgical treatment of intrauterine adhesions [18], [19], [20].
In cases of a thin endometrium following the lysis of extensive adhesions, several systematic reviews describe the use of autologous PRP for reparative tissue regeneration [21].
It is recommended to prescribe hormone replacement therapy with sex steroids (according to ATC – Natural and semisynthetic estrogens, Progestogens, Progestogens and estrogens, fixed combinations) in a cyclic regimen to patients after hysteroscopic lysis of intrauterine adhesions to restore the menstrual cycle in the absence of contraindications [22].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: hormone replacement therapy is carried out using oral or transdermal estrogen formulations at standard or high doses combined with progestogens in a cyclic regimen, including fixed-dose combinations [22], [23], [11], [24], [25], [26], [27], [28], [29].
3.2 Surgical Treatment
It is recommended to perform surgical treatment via hysteroscopic access (hysteroscopy) in patients with intrauterine adhesions who have reproductive plans and symptoms [4], [33], [34], [35], [36], [34].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
Comments: indications for surgical intervention include: hypomenorrhea, amenorrhea, as well as reproductive disorders such as recurrent pregnancy loss and infertility.
In severe forms of intrauterine adhesions with associated pathology, surgical treatment is performed via a combined approach (laparoscopy, hysteroscopy).
It is recommended to perform a second-look (control) hysteroscopy in patients with intrauterine adhesions to treat recurrence and evaluate the uterine cavity 2–3 months after surgery [4], [33], [34], [35].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
4. Medical Rehabilitation and Sanatorium-Resort Treatment
Specific rehabilitation has not been developed.
It is recommended that all patients undergo an examination (consultation) with a physical therapy doctor to determine a rehabilitation program [1], [35], [36].
GDR CLE 5Grade of recommendation C (level of evidence – 5)
5. Prevention and Dispensary Observation
Primary prevention of intrauterine adhesions: avoidance of abortions, avoiding rough and/or unjustified intrauterine interventions, diagnostic curettage without hysteroscopic control in endometrial pathology, reduction of electrosurgery usage, and minimization of endometrial and myometrial trauma [37].
Secondary prevention: use of biomaterials, barrier methods, and cell therapy after surgery [4], [37].
6. Organization of Medical Care
Indications for scheduled hospitalization in a medical organization:
1) Surgical treatment of intrauterine adhesions.
Criteria for Evaluating the Quality of Medical Care
№ | Quality criteria | Performance evaluation |
|---|---|---|
1. | Pelvic ultrasound performed | Yes/No |
2. | Surgical treatment via hysteroscopic access (hysteroscopy) was performed | Yes/No |
References
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Appendix A1. Working Group Composition
Leyla V. Adamyan – Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Deputy Director of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, Honored Worker of Science of Russia, Head of the Department of Reproductive Medicine and Surgery at the A.I. Evdokimov Moscow State University of Medicine and Dentistry of the Russian Ministry of Health, Chief Obstetrician-Gynecologist of the Russian Ministry of Health; member of the Society for Reproductive Medicine and Surgery, Russian Association of Gynecological Endoscopists, Russian Association for Endometriosis, and Russian Society of Obstetricians and Gynecologists.
Elena N. Andreeva – Doctor of Medical Sciences, Professor, Deputy Director – Director of the Institute of Reproductive Medicine, Head of the Department of Endocrine Gynecology, Professor of the Department of Endocrinology at the National Medical Research Center for Endocrinology of the Russian Ministry of Health, Professor of the Department of Obstetrics, Gynecology and Reproductive Medicine at the Russian University of Medicine, President of the International Association of Obstetricians, Gynecologists and Endocrinologists, member of the Russian Association of Gynecological Endoscopists, Russian Association for Endometriosis, Russian Society of Obstetricians and Gynecologists, and ROSGEM.
Natalya V. Artymuk – Doctor of Medical Sciences, Professor, Head of the Department of Obstetrics and Gynecology named after Professor G.A. Ushakova at Kemerovo State Medical University of the Russian Ministry of Health, Chief freelance specialist in obstetrics and gynecology of the Russian Ministry of Health in the Siberian Federal District, member of the Russian Society of Obstetricians and Gynecologists.
Tatyana E. Belokrinitskaya – Doctor of Medical Sciences, Professor, Head of the Department of Obstetrics and Gynecology at the Faculty of Postgraduate Education, Chita State Medical Academy of the Russian Ministry of Health, Honored Doctor of the Russian Federation, Chief freelance specialist of the Russian Ministry of Health in obstetrics, gynecology, and women's reproductive health in the Far Eastern Federal District (Chita).
Yulia E. Dobrohotova – Doctor of Medical Sciences, Professor, Head of the Department of Obstetrics and Gynecology at the Faculty of Medicine of the Pirogov Russian National Research Medical University of the Ministry of Health of Russia, Honored Physician of the RF, Honored Scientist of the RF, Laureate of the Government Prize of the RF, member of the Society for Reproductive Medicine and Surgery, Russian Association of Gynecologic Endoscopists, Russian Society of Obstetricians and Gynecologists.
Antonina A. Smetnik – Candidate of Medical Sciences, Head of the Department of Gynecological Endocrinology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health (Moscow), President of the Russian Society of Gynecological Endocrinology and Menopause Specialists.
Larisa V. Suturina – D.Sc. in Medicine, Professor, Head of the Department of Reproductive Health Protection, Scientific Centre for Family Health and Human Reproduction Problems (Irkutsk), member of the Association of Gynecological Endocrinologists of Russia, member of the Russian Society of Obstetricians and Gynecologists.
Gyuzal I. Tabeeva – Ph.D. in Medicine, Senior Research Associate, Department of Gynecological Endocrinology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, Scientific Secretary of the Russian Society of Gynecological Endocrinology and Menopause Specialists.
Narine M. Tonoyan – Candidate of Medical Sciences, Obstetrician-Gynecologist at the Department of Operative Gynecology of the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation.
Maria I. Yarmolinskaya – Professor of the Russian Academy of Sciences, D.Sc. in Medicine, Professor, Head of the Department of Gynecology and Reproductive Endocrinology, Research Institute of Obstetrics and Gynecology named after D.O. Ott, Professor of the Department of Obstetrics and Gynecology, North-Western State Medical University named after I.I. Mechnikov of the Russian Ministry of Health, member of the Russian Society of Obstetricians and Gynecologists.
Elena V. Uvarova – Corresponding Member of the Russian Academy of Sciences, D.Sc. in Medicine, Professor, Honored Scientist of the Russian Federation, Head of the 2nd Gynecological Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, Professor of the Department of Obstetrics, Gynecology and Reproductology, Institute of Professional Education, I.M. Sechenov First Moscow State Medical University (Sechenov University) of the Russian Ministry of Health, Chief Freelance Pediatric and Adolescent Gynecologist of the Russian Ministry of Health, President of the Association of Pediatric and Adolescent Gynecologists of Russia, member of the Russian Society of Obstetricians and Gynecologists
Conflict of interest:
All members of the working group declare no conflict of interest.
Appendix A2. Methodology for Developing Clinical Guidelines
Target audience for these clinical guidelines:
Obstetrician-gynecologists, general practitioners, family physicians;
Students, residents, postgraduate students;
Faculty members, researchers.
Table 1. Level of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)
LoE | Definition |
1 | Systematic reviews of studies with reference standard control or systematic reviews of randomized controlled trials with meta-analysis |
2 | Individual studies with reference standard control or individual randomized controlled trials and systematic reviews of studies of any design, except randomized controlled trials, with meta-analysis |
3 | Studies without consecutive reference standard control or studies with a reference standard not independent of the test method, or non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case report |
5 | Only justification of mechanism of action or expert opinion is available |
Table 2. Level of Evidence (LoE) grading scale for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)
LoE | Definitions |
1 | Systematic review of RCTs with meta-analysis |
2 | Individual RCTs and systematic reviews of studies of any design except RCTs, with meta-analysis |
3 | Non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case reports or case series, case-control studies |
5 | Only justification of the mechanism of action of the intervention (preclinical studies) or expert opinion is available |
Table 3. Grade of Recommendation (GoR) scale for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)
GoR | Definition |
A | Strong recommendation (all considered efficacy criteria (outcomes) are important, all studies are of high or acceptable methodological quality, and their conclusions on the outcomes of interest are consistent) |
B | Conditional recommendation (not all considered efficacy criteria (outcomes) are important, not all studies are of high or acceptable methodological quality, and/or their conclusions on the outcomes of interest are inconsistent) |
C | Weak recommendation (lack of adequate quality evidence (all considered efficacy criteria (outcomes) are unimportant, all studies are of low methodological quality, and their conclusions on the outcomes of interest are inconsistent) |
Procedure for updating clinical guidelines.
The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.
Appendix A3. Reference Materials
These clinical guidelines were developed taking into account the following regulatory legal documents:
Order of the Russian Ministry of Health No. 1130n dated October 20, 2020 "On Approval of the Procedure for Providing Medical Care in the Field of Obstetrics and Gynecology"
Order of the Russian Ministry of Health No. 803n dated July 31, 2020 "On the Procedure for Using Assisted Reproductive Technologies, Contraindications and Restrictions on Their Use."
Appendix A3.1 Classifications of Intrauterine Synechiae
March et al. [39] | Adhesions are classified as minimal, moderate, and severe based on hysteroscopic evaluation of the extent of uterine cavity involvement. |
Hamou et al. [34] | Based on hysteroscopy, adhesions are classified as isthmic, marginal, central, or severe. |
Valle and Sciarra [37] | Adhesions are classified as mild, moderate, or severe depending on hysteroscopic evaluation and the degree of occlusion (partial or complete) on hysterosalpingography (HSG). |
European Society for Hysteroscopy [40] | The comprehensive system classifies intrauterine adhesions (IAs) into grades I–IV with several subcategories and includes a combination of hysteroscopy and HSG findings, as well as clinical symptoms. |
American Fertility Society [6] | A comprehensive scoring system for mild, moderate, and severe IAs based on the degree of endometrial cavity obliteration, the appearance of adhesions, and the patient's menstrual characteristics derived from hysteroscopy or HSG evaluation. |
Donnez and Nisolle [41] | Adhesions are graded into 6 stages based on location, with the rate of postoperative pregnancy being the primary factor. Hysteroscopy or HSG is used for evaluation. |
Nasr et al. [42] | The comprehensive system generates a prognostic score by combining menstrual and obstetric history with IA findings from hysteroscopic evaluation. |
AAGL Practice Report: Practice Guidelines on Intrauterine Adhesions Developed in Collaboration With the European Society of Gynaecological Endoscopy (ESGE). J Minim Invasive Gynecol. 2017
Appendix B. Physician Action Algorithms
Appendix C. Patient Information
Intrauterine adhesions (synechiae), or the so-called Asherman syndrome (partial or complete obliteration of the uterine cavity), are considered one of the causes of menstrual and reproductive dysfunction.
Intrauterine adhesions (Asherman syndrome) are a consequence of frequent severe traumatic injuries to the endometrium or chronic endometritis.
Diagnosis is based on medical history—amenorrhea following various surgical interventions.
Intrauterine adhesions can be suspected based on transvaginal ultrasound findings.
The disease may be asymptomatic, but can cause amenorrhea, hypomenorrhea, or infertility.
Infertility in severe intrauterine adhesions is most commonly due to obliteration of the tubal ostia, a reduction in functional endometrial area, and mechanical obstacles to embryo implantation.
Surgery is performed to restore a normal menstrual cycle and fertility. The nature of the surgery and its efficacy depend on the type of intrauterine adhesions and the degree of uterine cavity occlusion.
Currently, the only treatment method for intrauterine adhesions is their transection under direct visual control using a hysteroscope without traumatizing the remaining endometrium.
Restoration of menstrual function and a normal uterine cavity is achieved in 79–90% of cases. Pregnancy occurs in 60–75% of cases.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
None.