Quantification of blood volume and vascular perfusion in the corpus luteum of rhesus macaques during the menstrual cycle

Abstract

OBJECTIVE: To determine changes to luteal vascular flow and volume in rhesus monkeys using dynamic contrast enhanced ultrasound (d-CEU). DESIGN: In vivo, repeated measures. MATERIALS AND METHODS: Hormonal status of 8 adult cycling female macaques was monitored to detect the day of ovulation. D-CEU with Definity (Lantheus) microbubble perfusion was performed on the corpus luteum (CL) at the early, mid, mid-late and late luteal phase (LP; Mol Reprod Dev, 76: 367-378, 2009), as recently described for the uterus (Fertil Steril 95:1316, 2011). Vascular parameters were quantified in d-CEU video captures using a region of interest (ROI) focused on the CL. Video intensity (VI) was normalized to brachial artery flow to provide an estimate of blood volume (BV); change in VI (DVI/sec) was used to determine vascular perfusion rate (VP). RESULTS: Significant changes in BVand VP (P<001 and P1⁄40.07) were observed between stages of the LP. BV was negatively correlated with luteal day (P<0.02). In contrast, serum progesterone (P) levels correlated positively with BV (P1⁄40.04) and VP (P1⁄40.001). P area under curve (AUC) also positively correlated with AUC for BV (P1⁄40.03). In typical LPs, BV was highest during the early LP, before decreasing 3-fold in late LP CL. In contrast, VP peaked at mid LP, with values 5 and 11-fold greater than early and late LP, respectively. Two females were identified with luteal insufficiency based on peak P levels during the mid and mid-late LP (2.3 0.2 ng/ml), whereas 5 had normal LPs (6.2 1.2 ng/ml). Another female was identified with a luteal cyst on the contralateral ovary, and a functional CL that regressed before P levels declined. Insufficient LPs trended toward lower peak BVand VP, compared to typical LPs. CONCLUSION: D-CEU provides a non-invasive measurement of the dynamics of CL blood volume and flow during the luteal lifespan in the menstrual cycle. Reduced vascular perfusion is evident in animals with reduced P secretion and in animals with aberrant luteal function. Supported by: P51OD011092, R01HD020869 (RLS).