Introduction

In recent years there has been increasing concern about a possible decline in reproductive health. It is estimated that one in seven couples worldwide have problems conceiving and there is increasing demand for fertility treatments. These include intracytoplasmic sperm injection (ICSI) and in vitro fertilisation. In some European countries, such as Denmark, more than 6% of children are born after assisted reproduction. Sperm counts in many European countries are declining by around 2% per year.

Although human infertility rates are high and increasing, our understanding of the genetic pathways and basic molecular mechanisms involved in gonadal development and function is limited. In this overview, we examine the various forms of infertility and the evidence that there is a genetic component, and discuss in some detail the known genetic causes of infertility.

Female infertility

The main causes of female infertility are anovulation and anatomical causes such as obstruction in the genital tract (ovulatory infertility). About one-third of all cases of female infertility are due to obstruction in the genital tract. The obstruction can be in the fallopian tubes, uterus, cervix or vagina. Uterine abnormalities include congenitally absent (Mayer–Rokitansky–Küster–Hauser [MRKH] syndrome), bicornuate or double uterus, leiomyomas and Asherman syndrome.

Endometriosis is an estrogen-dependent inflammatory disease that affects 5–10% of women of reproductive age in the USA. Its defining feature is the presence of endometrium-like tissue in sites outside the uterine cavity, primarily on the pelvic peritoneum and ovaries.