To the best of our knowledge, this study represents the largest cohort of 284 women with MRKH syndrome diagnosed with evaluated and standardized diagnostic procedures and grouped according to a defined classification system. There is a unique occurrence in malformations of the distal genital system; vagina, cervix and uterus. The spectrum of variations accumulates in the more proximal part of the female genital system with a variety of adnexal and associated malformations. Most associated malformations were found in the renal system along with additional numerous combinations of different malformations (see Figure1).
Examination of women with MRKH syndrome revealed according to the definition of MRKH syndrome an absence or severe hypoplasia of the upper vagina as well as uterine agenesis. In the present study 100% of MRKH women showed a complete atresia of vagina, although 1–3 cm of the lower vagina can be present. We found in 100% of patients an aplasia of the cervix (Table2). In our study 87.3% of patients showed normal adnexa (stage A0), ten (3.5%) showed stage 2a (unilateral hypoplasia), seven (2.5%) showed 1b (bilateral tubal malformation) and six women (2.1%) showed stage 3a (unilateral aplasia). Two women (0.7%) showed stage 2b (bilateral hypoplasia/gonadal streak) and one women (0.4%) stage 1a (unilateral tubal malformation). One woman (0.4%) showed other malformations (Table2). We did not find a tendency toward polycystic ovaries as some authors reported [7, 21, 22]. We agree with Rokitansky, Bompiani and Oppelt et al. who described hypoplastic or aplastic ovaries only in a few cases [3, 5, 23]. Characteristic for all MRKH patients is the unilateral or bilateral hypoplasia of the uterus. In our study 84.2% showed bilaterally rudimentary or aplastic uterus, in 9.5% a unilaterally rudimentary or aplastic uterus was diagnosed. Two (0.7%) women had a hypoplastic uterus (Table2). These proportions of the uterus developmental state in MRKH patients was similar to Guerrier et al. .
The present analysis showed that 44.4% of the patients were affected by associated malformations. Excluding women which were not classifiable (M#) (0.7%), we found associated malformations in 44.7% of patients (Table3). The rate of associated malformations in patients with MRKH syndrome reported in the literature was between 53%  and 64% . Although MRKH patients have a normal female karyotype, in case of severe hormonal alterations, like the androgen insensitivity syndrome, it is recommended that patients should be analysed for chromosomal changes. In our study we focused more on the examination of the renal system, where every woman received an examination by laparoscopy and ultrasound and/or MRI. No direct symptoms of skeletal malformations like dorsal pain, scoliosis etc. excluded MRI analysis. An open inguinal canal was often found during laparoscopy, but only women with an operated inguinal hernia were classified as M+. Malformations of the renal system were seen in up to 32% of the patients and represented the largest proportion of affected organs . 29.6% of our cohort (284 patients) had renal malformations, confirming this as the most frequent associated malformation with MRKH (Table3). The most frequent renal malformation was a renal agenesis (64.4%).
Furthermore, we support that the associated renal malformations with MRKH can be explained due to the close link between genital and urinary embryonal development.
The human genital tracts are undifferentiated until the 8th week of gestation and are referred to as “bipotential or indifferent” gonads. At this time both the male and female embryo have two symmetrical paired genital ducts: the mesonephric (Wolffian) and the paramesonephric (Müllerian) ducts, which originate from the intermediate mesoderm. Together with the urogenital sinus they provide the bases for internal and external genital development. Only one of the two ductal systems will normally develop further, depending on whether differentiation of a testis or ovary has begun. The distal mesonephric duct is the starting point for a pair of ureteric buds, which grow into the cloaca and induces the overlying metanephros to develop into the primitive kidneys. The ureteric buds and distal portions of the mesonephric ducts are later incorporated into the wall of the primitive bladder to develop into ureters, trigone and bladder neck. In the female embryo, the mesonephric duct regresses completely and the paramesonephric (Müllerian) duct develops into the fallopian tubes, uterus, cervix and upper part of the vagina. Importantly, ovaries originate within the primitive ectoderm, thus are independent of the mesonephros. In the male embryo, testosterone and androstenedione stimulates mesonephric duct development to form the epididymi, vasa deferentia and seminal vesicles, while the Müllerian duct regresses in response to anti-Müllerian-hormone, which is secreted from the Sertoli cells. The disappearance of the Müllerian ducts in the male fetus is completed by 9 to 10 weeks of gestation [26–28].
It is interesting to note that in the general population, urinary tract defects occur in as many as 1:100 live births and constitute the most frequent cause of chronic kidney disease in children . Considering the incidence of MRKH in ~1:4,500 live female births, congenital renal malformations (as well as unilateral renal agenesis) in MRKH patients are higher compared to the general population. This is not surprising due to the association and interaction of the two ductal systems for normal genital and renal development. Combined urogenital malformations are common with estimations of 10 in 100 cases and account for over 30% of all congenital malformations . Malformations of the genital and renal axis are common, e.g. 35% of females where unilateral renal agenesis showed partial or complete duplication of the genital tract ; renal agenesis was present in 43% of patients with uterus didelphys and 10% of patients with other genital tract abnormalities had an abnormal or ectopic kidney . As a matter of course all patients with genital malformations should be evaluated for renal abnormalities, may be patients with renal abnormalities should also be assessed for genital malformations.