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Главная / Архив / 2023 год / MEDICUS № 2 (50), March / THE REVIEW OF CONGENITAL MALFORMATIONS OF THE UTERUS AS A FERTILITY DETERMINING FACTOR

THE REVIEW OF CONGENITAL MALFORMATIONS OF THE UTERUS AS A FERTILITY DETERMINING FACTOR

Дата публикации: 21.03.2023

UDC 618.1-007

 

THE REVIEW OF CONGENITAL MALFORMATIONS

OF THE UTERUS AS A FERTILITY DETERMINING FACTOR

 

Veronica Lipciu, Student

Department of Gynecology, Obstetrics and Human Reproduction

Nicolae Testemitsanu State University of Medicine and Pharmacy,

(MD-2004, the Republic of Moldova, Chisinau, Stefan cel Mare Boulevard, 165)

Email: veronica.lipciu@gmail.com

 

Natalia Corolcova, Doctor of Medical Sciences, University Lecturer

Department of Gynecology, Obstetrics and Human Reproduction

Nicolae Testemitsanu State University of Medicine and Pharmacy,

(MD-2004, the Republic of Moldova, Chisinau, Stefan cel Mare Boulevard, 165)

Email: veronica.lipciu@gmail.com

 

Mihaela Burac, University Assistant

Department of Gynecology, Obstetrics and Human Reproduction

Nicolae Testemitsanu State University of Medicine and Pharmacy,

(MD-2004, the Republic of Moldova, Chisinau, Stefan cel Mare Boulevard, 165)

Email: veronica.lipciu@gmail.com

 

Abstract. Congenital uterine anomalies are relatively rare. Many of them are asymptomatic and are associated with normal reproductive outcomes, but others involve complications during pregnancy or during delivery. The overlap of the mullerian anomalies with the patient's fertility is an controversial issue, and the appropriate management of infertile women with many forms of these anomalies is challenging [16]. There is insufficient existing literature on the frequency and likely causes of infertility among women with congenital uterine anomalies to permit broad conclusions. The lack of objective diagnostic criteria for different types of abnormalities and the heterogeneity of study designs have conducted to conflicting results regarding the prevalence of the pathology among infertile and fertile women [25]. However, emerging evidence in the recent literature suggests causal associations between mullerian anomalies (especially septate uterus) and infertility and demonstrates significant improvements in reproductive function in women with septate uterus and unexplained infertility after hysteroscopic hysteroplasty interventions. This literature review provides a critical update on the knowledge of congenital uterine anomalies, as well as the understanding of their effect on fertility and how they can be managed from a reproductive perspective [33].

Keywords: uterus, infertility, congenital anomalies, Mullerian anomalies, uterine myoma, endometrial polyp, chronic endometritis, intrauterine adhesions.

 

Introduction:

Uterus is the organ responsible for the most important stages of the reproductive process such as: sperm migration, embryo implantation, fetal feeding, development and growth and, last but not least, labor and birth, processes that are based on the existence of a structural uterus normal and functionally competent. The endometrium is a complex functional tissue, hormonally dependent, which undergoes cyclical and structural changes under the influence of sex hormones. The optimal morphofunctional characteristics of the endometrium are the basic elements in the occurrence and development of pregnancy [5, 7]. The pathological processes of the pelvic organs have both a direct and indirect effect on the state of the endometrium and their structural and functional changes cause infertility, spontaneous abortions and implantation defects [14, 21, 22].

 

Embryogenesis.

Embryos of both sexes initially present two pairs of genital ducts: the Wolff mesonephric ducts and the Müller paramesonephric ducts. The paramesonephric duct is in the form of a longitudinal invagination of the epithelium on the antero-lateral surface of the urogenital ridge. The duct opens in the cranial part into the abdominal cavity and has a conical shape [23]. The paramesonephric duct, in the caudal part, descends laterally from the mesonephric duct, intersecting it on the ventral side and continues its path in the caudo-medial direction. At the level of the median line, it comes into close contact with the paramesonephric duct on the opposite side [2]. The two ducts are initially separated by a septum but later merge and form the uterine canal. The caudal extremity of the two associated ducts projects into the posterior wall of the urogenital sinus, causing small protrusions that constitute the paramesonephric tubercle (Müller). The mesonephric ducts open into the urogenital sinus, on either side of Müller's tubercle.

Development of the genital tract in female embryos.

The paramesonephric ducts in female embryos give rise to the main genital tracts. Each duct has three portions: a vertical cranial segment, which communicates with the abdominal cavity, a horizontal segment that crosses the mesonephric duct and a vertical caudal segment that fuses with the homologous segment on the opposite side. After the descent of the ovary, the first two segments form the fallopian tube, and the fused caudal segments form the uterine canal. By moving in the medio-caudal direction of the middle segments of the paramesonephric ducts, the urogenital ridges are positioned in the transverse plane. The fusion of the ducts on the midline determines the formation of a wide transverse pelvic envelope that extends between the lateral faces of the fused paramesonephric ducts and the walls of the pelvic cavity and is called the broad ligament of the uterus. The fallopian tubes are located in the upper edges of this ligament and the ovary is located on its posterior surface. The uterus and the broad ligament divide the pelvic cavity into the recto-uterine recess (the bottom of the Douglas sac) and the utero-vesical recess. Through the fusion of the para-mesonephric ducts, the body and the cervix are born, surrounded by a layer of mesenchymal tissue that forms the muscular layer of the uterus, the myometrium, and the overlying peritoneal membrane, the perimetrium [9]. The fallopian tubes are located in the upper edges of this ligament and the ovary is located on its posterior surface. The uterus and the broad ligament divide the pelvic cavity into the recto-uterine recess (the bottom of the Douglas sac) and the utero-vesical recess. Through the fusion of the para-mesonephric ducts, the body and the cervix are born, surrounded by a layer of mesenchymal tissue that forms the muscular layer of the uterus, the myometrium, and the overlying peritoneal membrane, the perimeter. The fallopian tubes are located in the upper edges of this ligament and the ovary is located on its posterior surface. The uterus and the broad ligament divide the pelvic cavity into the recto-uterine recess (the bottom of the Douglas sac) and the utero-vesical recess. Through the fusion of the para-mesonephric ducts, the body and the cervix are born, surrounded by a layer of mesenchymal tissue that forms the muscular layer of the uterus, the myometrium, and the overlying peritoneal membrane, the perimeter [6].

Müllerian development occurs separately from gonadal development, and women with Müllerian abnormalities usually have normal ovaries and normal ovarian hormone production [29]. In contrast, Müllerian development occurs in close association with urinary tract development, and renal abnormalities are frequently identified in women with Müllerian anomalies [7, 14].

Congenital uterine malformations.

Uterine malformations are part of the category of Mullerian malformations, along with renourinary malformations, having a common origin, namely the Mullerian ducts. In addition, these abnormalities may be isolated or may be part of a complex syndrome that affects other organs and therefore may have other implications, for example, Müllerian agenesis syndrome, renal anomalies, and syndrome of vertebral anomalies, atresia of the anus, trachea, esophagus, which are associated with unicornuate uterus with non-communicating horn [21, 39].

Congenital uterine abnormalities may result from: failure to develop one or both Müllerian ducts (eg. agenesis, hypoplasia or unicornuate uterus without a rudimentary horn), inability to channel one or both ducts (eg. rudimentary uterus or a unicornuate uterus with a rudimentary horn), failure of migration or abnormal fusion of the ducts (eg. didelphis uterus or bicornuate uterus) and failure of resorption of the intermediate septum (eg. septate uterus or an arcuate uterus) [15,30]. The last two groups constitute lateral fusion defects, which is the most common form of Müllerian defects [24]. In addition, vertical fusion defects can result from the abnormal fusion of the Müllerian ducts with the urogenital sinus or from the lack of a vaginal canalization process [33]. However, the most complex malformations are mesonephric anomalies [1, 17]. The Wolffian ducts are a precursor and inducer of Müllerian development and are required for the formation of the lower vagina, and by supplying the ureteral buds at their distal ends, they play a crucial role in kidney development, so mesonephric abnormalities are mostly associated with uterine malformations as well as with ipsilateral blind hemivagin and renal abnormalities (mostly renal agenesis, cystic renal dysplasia, ectopic ureters and bifurcated collecting systems) [20, 34]. The ipsilateral blind hemivagina may or may not communicate with the bicornuate or septate uterus (with or without communicating uterus) depending on the coexistence of cervical or cervicovaginal atresia [12, 44] or it may be associated with the unicornuate uterus with a rudimentary horn in cases of additional atresia or hypoplasia of the corresponding hemiuterus [19, 48].

Classification of congenital anomalies of the uterus.

 

Table 1

Clinical and embryological classification of malformations of the female genital tract [11]

Classes

Description

1

Agenesis or hypoplasia of an entire urogenital ridge: unicorn uterus with uterine, tubal,

ovarian and renal agenesis on the contralateral side

2

 

 

 

2b

2c

 

 

2d

Mesonephric anomalies with the absence of the Wolffian duct opening to the urogenital sinus and

the absence of budding of the ureteral buds (and therefore renal agenesis occurs), the "inducing" function of the Wolffian duct on the Müllerian duct is also failed, and uterovaginal duplicity plus ipsilateral blind hemivagina with renal agenesis is usually seen, which presents clinically as:

– Large unilateral hematocolpos;

– Gartner pseudocyst on the anterolateral wall of the vagina;

– Partial reabsorption of the intervaginal septum, seen as a "buttonhole" on the anterolateral wall

of the normal vagina.

– Complete unilateral vaginal or cervicovaginal agenesis, which is ipsilateral to the renal agenesis and without or with communication between both hemiuteri (communicating uteri)

3

3a

 

3b

3c

Isolated Müllerian anomalies affecting:

–Müllerian ducts: the most common uterine malformations including unicornuate uterus (generally with a rudimentary uterine horn), bicornuate, septate and didelphis uterus;

–Müllerian tubercle: cervicovaginal atresia and segmental anomalies such as a transverse vaginal septum;

–Both Müllerian tubercle and ducts: (uni- or bilateral) Mayer-Rokitansky-Kuster-Hauser syndrome

4

Anomalies of the urogenital sinus: cloacal and other anomalies

5

Malformative combinations: Wolfian, Müllerian and cloacal anomalies

 

These types of malformations can be associated with an ectopic vaginal ureter and interseptal or interuterine communication [1].

The classification proposed by the American Fertility Society in 1988 was the most recognized and used, even if it suffered some criticism [15].

Class I – Müllerian agenesis (absent uterus). The uterus is not present, the vagina is only rudimentary or absent. The condition is also called Mayer-Rokitansky-Kuster-Hauser syndrome. The patient with MRKH syndrome will have primary amenorrhea.

Class II – Unicornuate uterus (a unilateral uterus). Only part of the Müllerian duct is formed. The uterus has a typical "banana shape" on imaging screenings.

Class III – Didelphys uterus, (double uterus). Both Müllerian ducts develop but fail to fuse, so the patient has a "double uterus". This may be a condition with a double cervix and vaginal division or the fused inferior Müllerian system in its unpaired state.

Class IV – Bicornuate uterus (uterus with two horns). Only the upper part of that part of the Müllerian system which forms the uterus fails to fuse, thus the caudal part of the uterus is normal, the cranial part is bifurcated. The uterus is "heart shaped".

Class V – Septate uterus (uterine septum). The two Müllerian ducts have fused, but the septum between them is still present, dividing the system into two parts. With a complete septum, the vagina, cervix, and uterus can be partitioned. Usually, the septum affects only the cranial part of the uterus. A uterine septum is the most common uterine malformation and a cause of miscarriages. It is diagnosed by medical imaging techniques, i.e. ultrasound or MRI. MRI is considered the modality of choice due to its multiplanar capabilities as well as its ability to assess the uterine contour, junctional area, and other pelvic anatomy. A hysterosalpingogram is not considered useful due to the technique's inability to assess the outer contour of the uterus and distinguish between a bicornuate and septate uterus.

Class VI – DES uterus. Hysterosalpingography of a T-shaped uterus The uterine cavity is "T-shaped" as a result of fetal exposure to diethylstilbestrol. An additional variant is the arched uterus in which there is a concave dimple in the uterine fundus within the cavity. The distinction between an arched uterus and a septate uterus is not standardized. A rudimentary uterus is a uterine remnant that is not connected to the cervix and vagina and can be found on the other side of a unicorn uterus. Patients with uterine abnormalities may have associated renal abnormalities, including unilateral renal agenesis [16, 21].

 

 

Fig. 1. Classification of Müllerian duct abnormalities according to AFS and correlation with ESHRE/ESGE classification [14]

 

Diagnostic methods.

The gynecological examination is the first and most important method of diagnosis, although in many cases of malformations of the genital organs it cannot be done completely or will not be sufficiently informative. In cases of primary amenorrhea, the external genitalia should be carefully examined to assess the distal vaginal third. The initial paraclinical diagnostic method is two-dimensional ultrasound, but three-dimensional ultrasound, MRI, hysterosalpingography with contrast, video-hysteroscopy and video-laparoscopy are also used.

Treatment.

Some Müllerian malformations are curable by surgery, and the success of the treatment depends on the accurate diagnosis and the choice of the best technique [12].

Vaginal agenesis can be treated by dilation or vaginoplasty. In 2002 ACOG recommended dilation as the first-line method, given the high success rate and lack of complications [3]. The most common technique is the Frank technique [31, 18], which consists in the daily self-application of rigid vaginal dilators, with a progressive increase in their length and width, for 30 to 120 min, over several months. The best anatomical results and the lowest complication rates are recorded in patients who perform coitus dilatation.

Congenital cervical and vaginal atresia is controversial in terms of treatment because there are no guidelines or randomized trials.

Unicornuate uterus is an indication for surgical treatment only if there is a rudimentary uterine horn not communicating with the cavity, which will require resection if it causes pain resulting from obstruction of menstrual flow. In some cases, its muscle mass is reduced, and it can cause isthmo-cervical incompetence that would imply the need for cerclage in a future pregnancy [29]. The didelphis uterus is a malformation with a good reproductive prognosis and requires intervention only in cases of HWW syndrome, which involves obliterated one of the vaginas and the septum between them must be resected to drain the hematocolpos and hematometra, as well as to allow the normal outflow of menstrual flow [27]. The bicornuate uterus does not present a cause of infertility, but rather the presence of recurrent spontaneous abortions in the 2nd trimester of pregnancy and preterm birth. When no other cause is identified, Strassman metroplasty can be recommended, with good results and a 90 % complete pregnancy rate [43]. The septate uterus is the most common müllerian malformation, with the worst prognosis for reproduction, which is frequently associated with spontaneous abortion in the first and second trimesters of pregnancy, although the treatment is relatively easy. The treatment of choice is hysteroscopy with uteroplasty, which shows good results [49].

Conclusions.

Congenital uterine anomalies can present themselves in various forms and in different periods of a woman's life. A careful history and a complete clinical examination play a fundamental role in deciding on the best diagnostic methods and choosing the right treatment. The two main classifications currently in use, that of AFS-ASRM [13] and ESHRE/ESGE [14], encompass the majority of cases of congenital anomalies, although there are others that are not yet included in the classification. There are unique cases of Müllerian malformations that do not fit into any of the classifications proposed so far. Women with more obvious symptoms, such as primary amenorrhea, inability to have vaginal intercourse, or pelvic pain due to obstruction of menstrual flow, are diagnosed earlier because they seek for medical help. Accordingly, those women who experience reproductive problems, such as recurrent pregnancy loss, premature birth, and infertility, are diagnosed in the process of elucidating the causes of these infertility. Imaging diagnosis is indispensable, ultrasound is used very frequently for the first examination, and MRI is considered by specialists as the gold standard in the diagnosis of these anomalies.

Because they are rare pathologies, most of the studies found in the literature are made up of case reports, small series of clinical cases, comparative studies, and most of the authors report their own experience in different institutions where they work. To be able to understand and treat these unique cases, studies involving genetics and embryology as well as randomized trials are needed to have a complete picture.

 

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REFERENCES

  1. Acien P.A. M.-F. (2004). Complex malformations of the female genital tract.New types and revision of classification. Hum. Reprod., 19, 2377-2384 (In English).
  2. Aplin J. Uterus – Endometrium. In: Spencer T, J. F. (2018). Female reproduction. Elsevier Online; (Skinner M, editor. Encyclopedia of reproduction, 2nd ed.; vol. 2) (In English).
  3. Auflage. Berlin: Ullstein Mosby. Standring, S. B. (2008). Embryonic Development and Fehlbildungen des Menschen. Anatomy and Clinic, 10 (In English).
  4. Bendarska-Czerwińska A. Z.-M. (2023). Endocrine disorders and fertility and pregnancy: an update. Frontiers in endocrinology, 13, 970439 (In English).
  5. Care A. C. (2002). Nonsurgical diagnosis and management of vaginal agenesis. ACOG Committee Opinion Number 274. Obstet Gynecol, 100:213e6 (In English).
  6. Churchill Livingstone/Elsevier. Ulijaszek S.J. (2000). Encyclopedia of Human Growth and Development. Gray's anatomy: the anatomical basis of clinical practice. 40th ed., anniversary (In English).
  7. Constantin H. (1966). Ureteral ectopy, hydrocolpos and uterine didelphi. JAMA 197, 54-56 (In English).
  8. Critchley H. M. (2020). Physiology of the endometrium and regulation of menstruation. Physiological Reviews, 100(3), 1149-1179 (In English).
  9. Davies MC, C. S. (2005). Pitfalls of vaginal construction. BJU Int, 95:1293e8 (In English).
  10. Devi Wold AS, P. N. (2006). natomical factors in recurrent pregnancy loss. Seed. Play Med. , 24, 25-32 (In English).
  11. DK. E. (2003). Congenital malformations of the genital tract and their management. Best Pract Res Clin Obstet Gynaecol, 17(1):19e40 (In English).
  12. Dominique de Ziegler P. P. (2016). Optimal uterine anatomy and physiology necessary for normal implantation and placentation. Fertility and Sterility, Volume 105, Issue 4, Pages 844-854 (In English).
  13. Grimbizis GF, C. M. (1998). Hysteroscopic septal resection in patients with recurrent miscarriages and infertility. Hum. Reprod. 13, 1188-1193 (In English).
  14. Grimbizis G.G. (2013). The ESHRE/ESGE consensus on the classification of congenital anomalies of the female genital tract. Human Reproduction (Oxford, England),, 28(8), 2032–2044 (In English).
  15. GS, L. (1998). Structural abnormalities and reproductive failure: Effective diagnostic and management techniques. Blackwell Science, NY, USA (In English).
  16. GS., L. (2011). Management of congenital uterine anomalies. Reprod Biomed Online, ;23(1):40e52 (In English).
  17. Hannema SE, H. I. (2007). Regulation of Wolffian duct development. Horm. Res. 67, 142-151 (In English).
  18. Hayashida SA, S. J. (2015). Clinical, structural, and biological features of neovagina: a comparison of the Frank and McIndoe techniques. Eur J Obstet Gynecol Reprod Biol , 186:12e6 (In English).
  19. Hofstetter G, C. N. (2008). : Genetic analyzes in a variant of Mayer-RokitanskyKuster-Hauser syndrome (MURCS association). Vienna. Klin. Wochenschr. , 120(13-14), 435-439 (In English).
  20. Ispas, A. e. (2005). Embryology. Guide to Microscopy Practical Papers. Year I. "Carol Davila" 2nd University Publishing House, Bucharest. Lazar (In English).
  21. Iverson RE, D. A. (2007). Clinical manifestations and diagnosis of congenital anomalies of the uterus. In: Up to date. Rose BD (Ed.). Waltham, MA, USA (In English).
  22. Jayaprakasan K. (2022). Diagnoses of congenital uterine anomalies: practical considerations. Journal of clinical medicine,, 11 (5), 1251 (In English).
  23. Joshi B.K. (2021). Prevalenza ed esito della gravidanza delle anomalie mulleriane nelle donne donne infertile: uno study retrospettivo. Journal of Human Reproductive Sciences, 14 (4), 431-435 (In English).
  24. Kapczuk K, F. Z. (2018). Obstructive müllerian anomalies in menstruating adolescent girls: a report of 22 cases. J Pediatr Adolesc Gynecol, 31(3):252e7 (In English).
  25. KL, P. T. (2009). General embryology. Timişoara: Mirton Publishing House (In English).
  26. Ludwin A.L. (2019). Utero setto according to the definitions of ESHRE/ESGE, ASRM and CME: association with infertility and spontaneous abortion, costs and warnings for health systems. Ultrasound in obstetrics and gynecology: la rivista ufficiale della Società internazionale di ultrasound in obstetrics and gynecology,, 54 (6), 800-814 (In English).
  27. Magee MC, L.D. (1979). A new embryologic classification for urogynecologic malformations: mesonephric duct syndromes induced Mullerian malformations. J. Urol, 121, 265-267 (In English).
  28. Marshall FF, B.D. (1978). Association of uterine and renal anomalies. Obstet. Gynecologist, 51, 559-562 (In English).
  29. Moreno I, C. E.-G. (2018). Diagnosis of chronic endometritis in asymptomatic infertile women: a comparative study of histology, microbial cultures, hysteroscopy and molecular microbiology. Am J Obstet Gynecol, 218(6):602.e1-602.e16 (In English).
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  31. Nunes N, K.S. (2009). VATER/VACTERL syndrome (vertebra/anus/cardiac/trachea/esophagus/radius/renal/limb abnormalities) with a functional noncommunicating uterine horn and a unicornuate uterus : a case report. Fertile. Steril., 91(5), 1957.E11-E12 (In English).
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Материал поступил в редакцию 28.02.23

 

 

ОБЗОР ВРОЖДЕННЫХ ПОРОКОВ РАЗВИТИЯ

МАТКИ КАК ФАКТОРА, ОПРЕДЕЛЯЮЩЕГО ФЕРТИЛЬНОСТЬ

 

Вероника Липчиу, студент

Кафедра гинекологии, акушерства и репродукции человека

Государственный университет медицины и фармакологии имени Николая Тестемицану

(MD-2004, Республика Молдова, г. Кишинёв, бул. Штефана чел Маре, 165)

Email: veronica.lipciu@gmail.com

 

Наталия Королкова, доктор медицинских наук, преподаватель

Кафедра гинекологии, акушерства и репродукции человека

Государственный университет медицины и фармакологии имени Николая Тестемицану

(MD-2004, Республика Молдова, г. Кишинёв, бул. Штефана чел Маре, 165)

Email: veronica.lipciu@gmail.com

 

Михаэла Бурак, ассистент

Кафедра гинекологии, акушерства и репродукции человека

Государственный университет медицины и фармакологии имени Николая Тестемицану

(MD-2004, Республика Молдова, г. Кишинёв, бул. Штефана чел Маре, 165)

Email: veronica.lipciu@gmail.com

 

Аннотация. Врожденные аномалии развития матки встречаются относительно редко. Многие из них протекают бессимптомно и не влияют на репродуктивные исходамы, но другие могут вызывать осложнения во время беременности или родов. Связь аномалий Мюллера с фертильностью пациентки является спорным вопросом, и надлежащее ведение бесплодных женщин со многими формами этих аномалий является сложной задачей [16]. Существующей литературы о частоте и вероятных причинах бесплодия среди женщин с врожденными аномалиями матки недостаточно, чтобы можно было делать общие выводы. Отсутствие объективных диагностических критериев для различных типов аномалий и неоднородность исследований привели к противоречивым результатам относительно распространенности патологии среди бесплодных и фертильных женщин [25]. Однако данные, недавно появившиеся в литературе, указывают на причинно-следственную связь между аномалиями Мюллера (особенно перегородкой матки) и бесплодием и демонстрируют значительное улучшение репродуктивной функции у женщин с перегородкой матки и необъяснимым бесплодием после гистероскопических вмешательств по гистеропластике. Это дает важную обновленную информацию о врожденных аномалиях матки, а также понимание их влияния на фертильность и того, как ими можно управлять с репродуктивной точки зрения [33].

Ключевые слова: матка, бесплодие, врожденные аномалии, аномалии Мюллера, миома матки, полип эндометрия, хронический эндометрит, внутриматочные спайки.