CHANGES IN ANGIOGENESIS AND BLOOD FLOW IN THE HUMAN CORPUS LUTEUM THROUGHOUT THE MENSTRUAL CYCLE AND DURING EARLY PREGNANCY

We have reported that angiogenesis is important for development of the corpus luteum and maintenance of luteal function. To maintain progesterone production for successful pregnancy, not only high vascularization but also adequate blood flow in the corpus luteum is necessary to provide luteal cells with large amounts of cholesterol needed for progesterone synthesis and for the delivery of progesterone to the circulation. The present study was undertaken to investigate a relationship between angiogenesis and blood flow in the human corpus luteum throughout the menstrual cycle and during early pregnancy. Changes in numbers of blood vessels were examined in the corpus luteum during the menstrual cycle [early stage of the early luteal phase:1–2 days after ovulation (D1–2), late stage of the early luteal phase:D3–4, mid-luteal phase:D5–8, late luteal phase:D10–14, with day 1 being the day of ovulation confirmed by urinary LH] and in early pregnancy (6–8 weeks). The number of blood vessels in the corpus luteum, determined by immunohistochemistry for CD34, expressed per 100 luteal cells was used as a vascular index. Vascular index significantly increased from the early stage to the late stage during the early luteal phase. Vascular index in the late stage of the early luteal phase was the same level as that in the midluteal phase, and significantly decreased in the late luteal phase. In the corpus luteum of early pregnancy, vascular index was significantly larger than that in the mid-luteal phase, suggesting that angiogenesis is activated again by pregnancy. Changes in blood flow impedance in the preovulatory follicle and in the corpus luteum were assessed by transvaginal color and pulsed Doppler ultrasound during the menstrual cycle and in early pregnancy. Blood flow impedance was expressed as resistance index (RI), which was calculated from curves fitted to flow velocity waveforms according to the formula (ratio between the systolic peak velocity and end-diastolic velocity). Color flow was detected in the follicular wall and in the peripheral area of the corpus luteum. RI in the preovulatory follicle rapidly declined after ovulation. Then, RI in the corpus luteum further declined from the early stage to the late stage during the early luteal phase. RI in the corpus luteum of the mid-luteal phase was the same level as the late stage of the early luteal phase, and thereafter increased in the late luteal phase. In the corpus luteum of early pregnancy, RI remained the same level as the mid-luteal phase until 7 weeks of gestation. In conclusions, the present study showed the change in luteal blood flow throughout the menstrual cycle and during early pregnancy. The change in luteal blood flow is closely associated with angiogenesis and blood vessel regression during the divergent phases of luteal formation, luteal regression, and luteal rescue by pregnancy. (platform)