Molecular Basis of Müllerian Agenesis Causing Congenital Uterine Factor Infertility-A Systematic Review

Abstract

Infertility affects around 1 in 5 couples in the world. Congenital absence of the uterus results in absolute infertility in females. Müllerian agenesis is the nondevelopment of the uterus. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a condition of uterovaginal agenesis in the presence of normal ovaries and the 46 XX Karyotype. With advancements in reproductive techniques, women with MA having biological offspring is possible. The exact etiology of MA is unknown, although several genes and mechanisms affect the development of Müllerian ducts. Through this systematic review of the available literature, we searched for the genetic basis of MA. The aims included identification of the genes, chromosomal locations, changes responsible for MA, and fertility options, in order to offer proper management and counseling to these women with MA. A total of 85 studies were identified through searches. Most of the studies identified multiple genes at various locations, although the commonest involved chromosomes 1, 17, and 22. There is also conflicting evidence of the involvement of various candidate genes in the studies. The etiology of MA seems to be multifactorial and complex, involving multiple genes and mechanisms including various mutations and mosaicism.

Keywords: Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome; Müllerian agenesis (MA); genetics; molecular; uterine agenesis; uterine aplasia.

Figure 1

Prisma flow diagram for study inclusions.