Contemporary issues in primary amenorrhea.

Reproductive medicine has changed dramatically since the 1981 publication of the study of patients presenting with pubertal amenorrhea. The breakdown of causes likely remains unchanged, with the four most common causes of primary amenorrhea being ovarian failure (48.5%), congenital absence of the uterus and vagina (16.2%), GnRH deficiency (8.3%), and constitutional delay of puberty (6.0%). In the study of patients reported by Reindollar, 60% of patients had barriers to reproduction. Since its publication over 15 years ago, developments in assisted reproductive technologies have enabled pregnancy in many of these patients. Women with ovarian failure may gestate pregnancies from donated oocytes. Women with congenital absence of the uterus and vagina may have their fetuses carried in a surrogate uterus. During this period, the advances of molecular medicine have provided a better understanding of the etiologies of many of these disorders, including Turner's syndrome; 46,XY gonadal dysgenesis; 46,XX gonadal dysgenesis; hypogonadotropic hypogonadism; enzyme-deficient states; gonadotropin resistance; and androgen insensitivity. Contemporary issues related to these disorders involve information about molecular defects and outcome of pregnancies for patients previously considered sterile. Largely, this information has been extremely helpful and reassuring. However, the reported deaths of patients with Turner's syndrome who become pregnant by donor oocyte should remind us to proceed cautiously as new reproductive avenues are opened for these patients.

Analysis of cystic fibrosis transmembrane conductance regulator gene mutations in patients with congenital absence of the uterus and vagina.

The relationship between cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations and congenital absence of the uterus and vagina (CAUV) was examined. CFTR mutations have previously been associated with congenital bilateral absence of the vas deferens (CBAVD). CBAVD is caused by a disruption in the vas deferens, a Wolffian duct derivative. Because the embryologic development of the Müllerian ducts directly depends on the prior normal development of the Wolffian ducts, the same gene products may be necessary for normal embryologic development of both ductal systems. This study evaluated the role of CFTR mutations in the development of CAUV. DNA samples from 25 patients with CAUV were tested for the presence of 33 of the most common CFTR mutations. Protein-coding DNA fragments from the CFTR gene were amplified in vitro by the polymerase chain reaction (PCR) and analyzed for mutations using allele-specific oligonucleotide (ASO) probes. Two patients were heterozygous for CFTR mutations. One was heterozygous for the W1282X mutation and the other was heterozygous for the DeltaF508 mutation. The incidence of the 33 CFTR mutations found in the patients with CAUV (8%) was twice that found in the general population (4%), but much less than the incidence of CFTR mutations in men with CBAVD (80%). This data suggests that it is unlikely for CFTR mutations to cause CAUV in females as they cause CBAVD in some males. Furthermore, the data suggest that CAUV in females may be the same disorder as CBAVD in males who do not have CFTR mutations.