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A population-based study of the incidence of müllerian aplasia in Finland

2001; Elsevier BV; Volume: 76; Issue: 3 Linguagem: Inglês

10.1016/s0015-0282(01)01963-x

1556-5653

Kristiina Aittomäki, Hille Eroila, Pauli Kajanoja,

Urological Disorders and Treatments

Congenital absence of the vagina and functional uterus are the primary features of müllerian aplasia. Most women with müllerian aplasia are otherwise healthy and have normal female chromosome constitution, hormonally active functioning ovaries, and normal female secondary sexual characteristics. However, müllerian aplasia also occurs in specific syndromes such as androgen insensitivity. The etiology of müllerian aplasia is not known. There are some reports of familial occurrence, but these seem to be scarce and therefore, the mostly favored hypothesis in the majority of patients is multifactorial inheritance (1Simpson J.L. Genetics of the female reproductive ducts.Am J Med Genet (Semin Med Genet). 1999; 89: 224-239Crossref PubMed Scopus (95) Google Scholar). There are two forms of müllerian aplasia, Mayer-Rokitansky-Küster syndrome and total absence of müllerian derivatives (absence of the uterus, fallopian tubes, and vagina) and the etiology of these two may be different. The Mayer-Rokitansky-Küster syndrome is characterized by a rudimentary uterus, which consists of two remnant buds of uterine horns with either normal or hypoplastic fallopian tubes. A broad peritoneal fold replacing the normal uterine corpus connects these uterine buds. Urinary tract anomalies are known to occur in one-third and skeletal anomalies in a smaller proportion of patients with müllerian aplasia (2Griffin J.E. Edwards C. Madden J.D. Harrod M.J. Wilson J.D. Congenital absence of the vagina. The Mayer-Rokitansky-Kuster-Hauser syndrome.Ann Intern Med. 1976; 85: 224-236Crossref PubMed Scopus (306) Google Scholar). The incidence of vaginal aplasia has not been adequately studied. It is mostly given as a proportion of gynecological admissions to a specific hospital. The previous estimations of the incidence vary between 1:1,250 and 1:30,000. The most cited incidence is the one reported by Engstad in 1917 stating "I myself have found nine in my private praxis. From my own experience I should judge that we might expect to find one case in about 5,000" (3Engstad J. Artificial vagina.J Lancet. 1917; 37: 329-331Google Scholar). The only population-based evaluation of the incidence we are aware of is the one reported by Evans et al. (4Evans T. Poland M. Boving R. Vaginal malformations.Am J Obstetrics. 1981; 141: 910-920PubMed Scopus (138) Google Scholar). They estimated that vaginal agenesis occurred in 1:10,558 female births in Michigan during the period from 1953 to 1957. Furthermore, it is important to note that when calculating the incidence, most reports only refer to "congenital absence of vagina." This may include specific syndromes such as androgen insensitivity. As müllerian aplasia is a major malformation with unknown frequency, this was studied in Finland with an ethnically homogeneous population of 5.5 million inhabitants. A well-organized public health care service and a nation-wide system of keeping patient records enables population-based studies on frequencies of diseases and anomalies such as müllerian aplasia. The country is divided into five university hospital regions. These hospitals constitute the tertiary level of referral where all patients with clinically significant anomalies are referred to for diagnosis and treatment. To calculate the incidence of müllerian aplasia, the hospital records of the five university hospitals were studied for patients treated for vaginal or uterine anomalies in the 15-year period from 1978 to 1993. Computer-based patient files were screened for these anomalies using ICD-9 based codes: 7521A, 7522A, 7523A, and 7524A. Clinical data including the specific type of anomaly and karyotype were collected for each patient. Only patients with congenital aplasia of the vagina and uterus were included in the series. All patients with other vaginal or uterine anomalies or 46,XY karyotype were excluded. The approval of the institutional review board was obtained for the study. Annual incidence of vaginal aplasia was determined by calculating the ratio of affected patients per all females born each year in the entire country. To ensure as high patient ascertainment as possible and reliability, a period of 10 years was finally chosen for the calculation of the incidence. This included females born in 1960 to 1969. Altogether 161 patients with congenital absence of vagina and uterus without a known cause were identified in the entire period of 15 years. Detailed information on whether the fallopian tubes were present (Mayer-Rokitansky-Küster syndrome) or absent (total müllerian aplasia) was not available for all patients, but at least 99 of the 161 had the Mayer-Rokitansky-Küster syndrome. The number of patients and newborn girls and the calculated annual incidence for each year from 1960 to 1969 are shown in Table 1. The incidence varied from 1:3,803 to 1:7,530 during the study period. The incidence of vaginal aplasia calculated for the entire 10-year period was 1 in 4,961 newborn girls.TABLE 1The incidence of vaginal aplasia in the population of Finland in the 10-year period of 1960 to 1969. legendThe number of new cases, newborn girls, and the calculated incidence are shown separately for each year and for the entire period., legendAittomäki. Incidence of müllerian aplasia. Fertil Steril 2001.Year of birthNo. of patientsNo. of newborn girlsIncidence1960940,1011:4,4551961940,1281:4,4581962839,7411:4,9761963840,1211:5,0151964839,2191:4,90219651038,0311:3,8031966838,1461:4,7681967537,6501:7,5301968736,0531:5,1501969532,8331:6,5661960–196977382,0231:4,961legend The number of new cases, newborn girls, and the calculated incidence are shown separately for each year and for the entire period.legend Aittomäki. Incidence of müllerian aplasia. Fertil Steril 2001. Open table in a new tab The study was conducted using patient records from five university hospitals for patient ascertainment. Although these university hospitals together service the entire county of Finland, we may not have been able to find all patients. It is unlikely that anyone who actually has attended these hospitals would not have been identified, but it is possible that all women with vaginal aplasia would not be referred to a university hospital as all patients do not need medical procedures to obtain a functional vagina. Due to this, it is possible that the true frequency of vaginal aplasia may actually be higher than determined here. It is controversial who should be included in the patient series when calculating the incidence of müllerian aplasia. The condition is etiologically heterogeneous and the similar clinical phenotype of müllerian aplasia may be caused by different etiological factors, genetic or environmental. As the etiology is mostly unknown, we have only excluded the patients with 46,XY karyotype. The incidence of müllerian aplasia was 1 in 5,000 in this study. As the etiology of this condition is multifactorial, however, it is plausible that the underlying genes may not be the same in all populations and the incidence may vary. This is actually suggested by the finding that in some studies most patients have had total müllerian aplasia, whereas most Finnish patients had Mayer-Rokitansky-Küster syndrome. Therefore, it is important that the frequency and clinical phenotype of this anomaly be studied in other populations. At present, we are performing genealogical studies in this series of 161 patients as an attempt to obtain further information on the genetic background of müllerian aplasia.