Ovarian follicular dynamics: from basic science to clinical practice.
The management of low responders (LR) to ovarian stimulation in cycles of assisted reproduction (AR) is a difficult challenge. Aging of the ovary and LR are coincidental in many situations, but LR is also present in young patients undergoing AR. In fact, today it is a recognized cause of infertility. When the aged ovary is considered, there is evidence that the functioning of the granulosa cells as well as the quality of the oocytes and resulting embryos are affected. Similarly, in young LR, the production of inhibin is affected. However, there is no evidence that the quality of the oocyte and/or the resulting embryo is affected. In this study, we have retrospectively analyzed our files and observed that the quality of the oocytes and embryos was similar between younger and older LR and normal responders (NR). Studies using color Doppler vaginal ultrasound have shown that the pulsatility index (PI) and the resistance index (RI) were increased in LR as compared with NR, suggesting that there was some degree of vascular resistance to flow. Treatment of LR is also a difficult challenge. Ovum donation is a successful treatment for LR, since cumulative birth rates are > 85% with four attempts of embryo transfer. The future may be promising for LR once new technologies are introduced into clinical practice. The use of recombinant gonadotropins and genetically engineered human gonadotropin derivatives may be of considerable help for LR. Similarly, non-gonadotropin hormones, such as cytokines or growth factors, may be shown to play a role in the stimulation of the ovary in the near future, and may therefore open new frontiers for treatment of LR.