A Study on Mullerian Duct Anamolies with Specific Mention of Meyer Rokitansky Kuster Hausen Syndrome

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International Journal of Current Medical And Applied Sciences, vol.6. Issue 2, April: 2015. PP: 114-118.

A study on Mullerian Duct Anamolies with Specific Mention of Meyer Rokitansky Kuster Hausen Syndrome. Vani Isukapalli*, Venkata Ram Prasad Kuppili** & T.Padmavathi* *Associate professor, Department of Obstetrics & Gynecology, **Associate professor, Department of Anatomy, Andhra Medical College, Visakhapatnam, Andhra Pradesh, India. Corresponding Email ID: [email protected] Research Article Subject: Obstetrics & Gynecology ------Abstract: Introduction: Mullerian duct anomalies are multifaceted defects Mullerian duct anomalies are fascinating disorders to involving the development of the female reproductive Obstetricians & Gynaecologists. In females, Mullerian duct system and the renal and skeletal systems to some extent is responsible for the development of fallopian tubes, .Majority of these anomalies are asymptomatic and pass uterus, cervix and the upper part of vagina. Defects in unnoticed. But a few of them are symptomatic and development range from anomalies of agenesis to present with amenorrhea, infertility, bad obstetric duplication and associated anomalies [1,2,3,4] of the history, difficulties in coital activity or pregnancy related renal, axial skeletal or cardiac systems. complications. This report is a review of the 23 patients MDA are classified [5] into the following categories as per with Mullerian duct anomalies who presented to our OPD the AFS classification (Figure 1). between January 2014 to December 2014. It discusses the  Segmental Mullerian hypoplasia or agenesis. embryology, various modes of presentation and  Unicornuate uterus with or without a rudimentary management with special emphasis on Meyer Rokitansky horn. Kuster Hausen syndrome (MRKH syndrome). Frank  Uterine Didelphis dilatation and McIndoe vaginoplasty appear to be the  Bicornuate uterus. acceptable means of therapy. The therapeutic success  Septate uterus depends to a large extent on the psychosocial adaptation  Arcuate uterus of the patient.  DES related Key Words: Amenorrhea, Bad obstetric history, Cryptomenorrhoea, Dyspareunia, MDA, Mullerian Duct, MRKH syndrome, Rudimentary horn, vaginal atresia. ------

Figure 1: Classification of MDA.

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The clinical presentation of MDA ranges from primary unfused upper ends; the renal system simultaneously amenorrhoea to menstrual irregularities, infertility to develops from the wolffian (mesonephric) ducts. Ovarian pregnancy complications like BOH, ectopic, preterm function is preserved because the ovaries originate within labour etc. Genetics plays a key role in the occurrence of the primitive ectoderm, independent of the MDA. Multifactorial autosomal dominant or autosomal mesonephros.The part of the vagina derived from recessive and X- linked inheritance are described by ectodermal origin is present. various authors for various conditions. Although Mayer-Rokitansky-Kuster-Hauser syndrome Meyer Rokitansky Kustner Hauser Syndrome (Mrkh was previously thought to be a sporadic anomaly, familial Syndrome): cases support the hypothesis of a genetic etiology. MRKH syndrome [6] is a congenital abnormality Although the precise gene has not yet been identified, this characterized by the absence of vagina, cervix and uterus. syndrome appears to be transmitted in an autosomal The reproductive abnormalities of MRKH syndrome are dominant fashion, with incomplete penetrance and due to incomplete development of the Müllerian variable expressivity.GALT (galactose/phosphate uredyl (paramesonephric) duct. The uterus, cervix, and upper transferase enzyme defect) [7], HOXA9, HOXA [8] and two thirds of the vagina form from the fused caudal ends WNT 4 genes are found to be associated with MDA. of the müllerian ducts. Fallopian tubes develop from the

Figure 2 : Karyotype of MRKH. Figure 3 : Pre-op MRKH showing a small blind vaginal depression

Figure 4 : Septate uterus on 3-D Ultrasound Figure : 5 . HSG of uterine didelphys.

Figure : 6. MRI of MRKH Syndrome showing absent uterus. Figure : 7.Laparoscopic picture of bicornuate uterus

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In this condition, individuals are phenotypically & EUA and laparoscopy (Fig.7) with or without genotypically female [9,10,11], with normally developed hysteroscopy was also done in clinically doubtful cases. In secondary sexual characters. Commonest presentation is all the cases, the presentation and interpretation was with primary amenorrhea. thoroughly analyzed. MRKH syndrome can manifest as 3 types. Observations & Results:  MRKH typical: Only isolated uterovaginal Out of the 15009 cases presenting to the OPD, 23 cases aplasia were diagnosed with Mullerian abnormalities and the  MRKH atypical: Associated with renal anomalies. following presentations were observed.  MR MURCS syndrome: MRKH + Urinary tract + Two patients presenting with amenorrhoea and pain Renal21+ Cardiac + Skeletal malformation abdomen were diagnosed to have cryptomenorrhea. They Prevalence: 1 in 10,000 [12]. had either a partial or complete vaginal atresia with a Treatment approaches are towards creating an artificial functioning uterus. Investigation protocol revealed vagina. Pregnancy is not possible due to absence of the haematocolpos & haematometra. Both the cases were uterus. But through oocyte , the woman can conceive by treated with Mc Indoe‘s vaginoplasty. ART -IVF technique with surrogacy. Four cases had a simple imperforate hymen and typically Materials and Methods: presented with cryptomenorrhoea, cyclical pain abdomen This study was conducted during the period January 2014 and a palpable uterus per abdomen. They were tackled to December 2014, wherein 15009 patients presented to with a cruciate incision over the bluish bulging the Department of Gynecology OPD, King George Hospital, membranes at the vaginal introitus. Visakhapatnam, Andhra Pradesh. The presentation of Two cases had complete transverse vaginal septae and patients to the Gynecology is with varied symptoms. A required septal excision. detailed screening of these cases for developmental Major group in the series presented with either infertility anomalies was done based on a detailed history including or bad Obstetric history. Only the cases with septate or a family history followed by a thorough clinical sub septate uterus could be surgically managed with examination along with pedigree charting. Cases septal excision. Rests of the other uterine anomalies were presenting with the same symptoms but due to various not amenable to surgical correction. pathological causes other than developmental defects Two cases in this group had a unicornuate uterus[18,19] were excluded from the study. A total number of 23 cases rudimentary horn and both presented with acute with Mullerian duct anomalies were identified. symptoms, one presenting with ruptured ectopic in a Ultrasound scan [13,14,15] of total abdomen (Figure 4) rudimentary horn with intra peritoneal haemorrhage and was performed on all the patients. Karyotyping (Figure 2), MR imaging [16.17] (Figure 6) and Intravenous the other with acute pain following failure of all pyelography, were done in relevant cases. Patients induction methods to terminate a mid trimester intra presenting with infertility in specific were subjected to uterine fetal death. HSG (Figure 5). Table 1: Showing the presentation of Mullerian duct anomalies: [15009 patients] S.No PRESENTATION CAUSE No. of Cases Percentage out of 15009 patients, 1. Amenorrhea or a. Imperforate Hymen 4 0.026% Cryptomenorrhoea b.Vaginal Atresia 2 0.013% c. Transverse Vaginal septum 2 0.013% d. MRKH Syndrome 2 0.013% 2. Infertility or BOH a. Uterine Didelphys 1 0.006% b.Bicornuate Uterus 2 0.013% c.Septate/ Subseptate uterus. 3 0.019% d. Unicornuate uterus with 2 0.013% rudimentary horn. 3. Difficulty during 2 0.013% coitus. b. Vaginal septum 2 0.013% 4. Difficulty during 1 0.006% Parturition 5. Abnormal uterine 1 0.006% bleeding. Total 23 0.153%

Vani Isukapalli, Venkata Ram Prasad Kuppili & T.Padmavathi

Table.2. Details of surgical procedures: PROCEDURE No. of Percentage out of 4622 cases Admitted patients Mc Indoe’s Vaginoplasty 2 0.043% Vaginal Septum Excision 4 0,086% Uterine Septum Excision 2 0.043% Imperforate Hymen Incision 4 0,086% Rudimentary Horn Excision 2 0.043% Total 14 0.302%

Discussion: In the present study as there were no DES exposed cases causing MDA, the involvement of DES in MDA in this The presentation of patients to the gynecological OPD is present era becomes a remote possibility. with varied symptoms, in which developmental anomalies of the Mullerian duct [20,21] need due Conclusion: consideration as they constitute 0.5 % of all gynecological admissions. The presentation of MDAs in the present MDA are not uncommon. Individuals present clinically at study show that majority present with infertility, various stages of life, with a variety of presentations. followed by a bad obstetric history in which Mullerian Thorough history, clinical examination should clinch the agenesis plays a major role. The rest of the cases diagnosis. USG, complemented by MR imaging are the presented with coital difficulty due to a complete best diagnostic tools. Corrective surgery is possible only transverse vaginal septum requiring a septal excision or a in select cases. primary amenorrhea which could be due to a imperforate References: hymen alleviated with a simple cruciate incision. A partial or a complete vaginal atresia or a MRKH which 1. Evans TN, Poland ML, Boving RL. Vaginal necessitates a Mc Indoe’s vaginoplasty[22,23,24] to malformations. Am J Obstet Gynecol 1981;141:910– atleast restore coital function is one area of prime 20. consideration. It should be noted that a clinical 2. Griffin JE, Edwards C, Madden JD, et al. Congenital absence of the vagina. The Mayer-Rokitansky-Kuster- examination is the mainstay of diagnosis and over Hauser syndrome. Ann Intern Med. Aug 1976; reliance on laboratory investigations is likely to miss the 85(2):224-36. condition. Mullerian duct anomalies need to be 3. Laufer MR. Structural abnormalities of the female considered in cases of ruptured ectopic and also in cases reproductive tract. In: Emans SJ, Laufer MR, editors. of a failed induction in Intra uterine fetal death, as an Emans,Laufer, Goldstein’s pediatric and adolescent underlying rudimentary horn may be the cause of gynecology. 6th ed. Philadelphia (PA): Wolters recurrence. Kluwer; Lippincott Williams & Wilkins; 2012. p. 188– Laboratory investigations including USG abdomen and 237. MR Imaging do play a role but mostly with anomalies 4. Murray JM, Gambrell RD Jr. Complete and partial vaginal agenesis. J Reprod Med. Feb 1979; 22(2):101- involving the upper part of the reproductive tract like a 5. septate and a bicornuate uterus, uterine didelphus etc. 5. Oppelt P, Renner SP, Kellermann A, Brucker S, Hauser out of which septate uterus can be managed with GA, Ludwig KS, et al. Clinical aspects of Mayer- hysteroscopic septolysis to improve the outcome of Rokitansky-Kuester-Hauser syndrome: pregnancy. It has been observed that, except for the cases recommendations for clinical diagnosis and staging. with septate or sub septate uterus which can be surgically Hum Reprod 2006; 21:792–7. managed with septal excision the other uterine anomalies 6. Morcel K, Camborieux L; Programme de Recherches were not amenable to surgical correction. HSG as such sur les Aplasies Müllériennes, Guerrier D. Mayer can be used as a complimentary diagnostic tool or as a Rokitansky-Küster-Hauser (MRKH) syndrome. Orphanet J Rare Dis. 2007 Mar 14; 2:13. primary tool in cases of infertility. Investigations in cases 7. Aughton DJ. Müllerian duct abnormalities and of imperforate hymen and vaginal atresias reveal galactosaemia heterozygosity: report of a family. Clin haematocolpos & haematometra for which Mc Indoe‘s Dysmorphol. Jan 1993; 2(1):55-61 vaginoplasty is the treatment of choice. 8. Taylor HS. Endocrine disruptors affect developmental programming of HOX gene expression. Fertil Steril. Feb 2008; 89(2):57-8.

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International Journal of Current Medical And Applied Sciences [IJCMAAS], volume.6. Issue 2. Page | 118