Corpus luteal insufficiency

The corpus luteum is controlled by luteinizing hormone (LH) and intraovarian morphofunctional specialization and autocrine/paracrine mechanisms. Corpus luteal insufficiency produces luteal phase defects (LPD). The poor precision and validation of endometrial histologic dating and single or random multiple serum progesterone measurements produce widely variable diagnoses. The true prevalence rate of LPD may be only 3-5% similar to that due to chance. The role of LPD in causing infertility can be challenged because the diagnosis is not predictive of recurrence in subsequent cycles, and other causes of infertility are not controlled for. Intraobserver and interobserver variability, uterine site of biopsy, luteal phase length, time of ovulation, and luteal phase timing of biopsy have been examined and have confirmed the imprecision of dating as a sensitive and reliable assessment of luteal insufficiency. There is support for either early or late luteal phase biopsy. Endometrial dating using LH timing as a reference point is relatively more reliable. Integrated luteal progesterone is the only currently accurate assessment of luteal sufficiency. Clomiphene does not increase LPD but increases serum progesterone, integrated progesterone, corpus luteum LH/human chorionic gonadotropin (hCG), and insulin-like growth factor-1 (IGF-1) receptors, all of which promote increased progesterone production and do not affect endometrial estrogen and progesterone receptors. hCG is more likely to stimulate progesterone production if given at the mid rather than early luteal phase corresponding to the phase with highest total and available (unoccupied) corpus luteal LH receptors. Careful analysis of published studies on treatment of LPD revealed only one randomized controlled study, and, statistically, all studies revealed no better outcome with progesterone treatment.