Investigations leave us with unexplained infertility.How can this be?

What is unexplained infertility?

'Unexplained infertility' is an arbitrary diagnosis derived by exclusion according to the protocols of the investigating department. It may be frustrating for an infertile couple concluding their initial set of infertility investigations to learn that no explanation has been detected. We try to take a more positive attitude on the situation, for eventual success is more likely, even with low-tech treatment, than when infertility is attributable to male factor or tubal factor. The average spontaneous pregnancy rate with unexplained infertility over three years is 60%.

We regard infertility as being unexplained if there is a normal semen analysis, reasonable follicular development (>12mm) on the twelfth day of the menstrual cycle and a mid-luteal progesterone of at least 30 nmol/l, a normal hysterosalpingogram and a positive post-coital test. Depending on the criteria employed, it is believed that infertility cannot be explained for between 10% and 25% of couples.

Recurrent failure of implantation of an embryo in some women suggests that the endometrium may be an infertility factor. Immunological differences between the endometrium of women with unexplained infertility compared to fertile women has led to the suggestion that this could account for some cases of unexplained infertility. Antiphospholipid antibodies (Q12.17), notably lupus anticoagulant and anticardiolipin, are more prevalent in women with unexplained infertility. It may be that we should consider investigating prolonged unexplained infertility with antiphospholipid antibody studies and chromosome analysis but this approach has not been widely adopted.

Arguably the most significant cause of infertility is implantation failure. From a practical point of view, the next area for significant development in the treatment of infertility lies in our understanding of embryo implantation. Only 12% of embryos transferred during IVF result in a live birth although implantation is probably around 25% in natural conception. Further research is required to improve our understanding in this critical area of fertility investigation but successful treatment for implantation problems remains elusive.

A successful outcome of assisted fertility treatment is reduced to about 30% in women over forty which contrasts to 50% in younger women. The reduction in fertility with age could be related to oocytes or to uterine factors.

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