The role of progesterone/estradiol ratio in exploring the mechanism of late follicular progesterone elevation in low ovarian reserve women

Late follicular progesterone (P) elevation continues to complicate a significant part of assisted reproductive technologies (ART) cycles, despite the ardent employment of gonadotropin releasing hormone (GnRH) analogues. In women with good ovarian reserve, late follicular P elevation is believed to be the result of the controlled ovarian stimulation (COS) itself, multiple follicular development and excessive ovarian steroidogenic activity. These mechanisms do not seem to be plausible in women with low ovarian reserve. In these women, excessive COS achieve a small number of pre-ovulatory follicles, which is not coupled to considerable ovarian steroidogenic activity. Therefore, other mechanisms should be pursued and explored. Delicate paracrine and autocrine mechanisms within the oocyte-cumulus complex were suggested to preserve the integrity of the pre-ovulatory follicle, including inhibition of P increase and follicular luteinization. However, clinical studies to demonstrate the disruption of these mechanisms in cases with low ovarian reserve and ageing oocytes are still lacking. Late follicular progesterone/estradiol (P/E-2) ratio was introduced into clinical practice as a more appropriate way to analyze P rise in women undergoing COS to control for the E-2 increase. The current hypothesis claims that in a follicular environment were the mechanism that prevent premature luteinization is disrupted, independent to LH surge; P rise at the late follicular phase may relatively bypass normal E-2 production, at the pre-ovulatory stage of steroidogenesis, causing a rise in the P/E-2 ratio. Therefore, in women with low ovarian reserve and few pre-ovulatory follicles, undergoing conventional COS, a negative (reverse) correlation between number of maturing follicles and P/E-2 ratio may support the existence of such a mechanism as its disruption, while a no or a positive correlation may disapprove it.