Blood flow velocity in the uterine and ovarian arteries during menstruation.

Eleven healthy women with regular menstrual cycles were examined with a combination of two-dimensional real-time ultrasound and color and spectral Doppler techniques on the 7th day after follicular rupture, and on the 1st, 2nd, 3rd and 4th days of menstrual bleeding. Both uterine arteries, arteries in the stroma and hila of both ovaries, in the wall of the largest follicle of the non-dominant ovary and in the wall of the corpus luteum were examined with the Doppler technique. The pulsatility index (PI) and the time-averaged maximum velocity were calculated. In the uterine arteries, the PI was highest on the first day of menstrual bleeding (median PI 3.2 for the dominant and 3.0 for the non-dominant uterine artery), after which it decreased to its lowest values on the second day (median PI 2.1 and 1.8, respectively) and third day (median PI 2.2 and 2.1, respectively). The time-averaged maximum velocity reached its highest value on the second and third days of menstruation. The corpus luteum was still visible on the first day of menstrual bleeding in all women, and on the second day in five. It was indistinguishable on the third and fourth days of menstruation in all women. In the dominant ovary, the time-averaged maximum velocity of flow in the arteries in the ovarian hilum decreased during menstrual bleeding and was lower during menstruation than in the preceding luteal phase. In the non-dominant ovary, neither the PI nor the time-averaged maximum velocity manifested any consistent changes during the period studied. We conclude that substantial changes in PI and time-averaged maximum velocity occur in the uterine arteries and in the arteries of the dominant ovary during menstruation.     

Assessment of changes in endometrial and subendometrial volume and vascularity during the normal menstrual cycle using three-dimensional power Doppler ultrasound.

OBJECTIVES: To describe changes in endometrial and subendometrial volume and vascularity during the normal menstrual cycle using three-dimensional (3D) power Doppler ultrasonography. METHODS: Fourteen healthy volunteers, 24-44 years old with regular menstrual cycles, underwent serial transvaginal 3D power Doppler ultrasound examinations of the uterus on cycle day 2, 3 or 4, then daily from cycle day 9 until follicular rupture and 1, 2, 5, 7 and 12 days after follicular rupture. Endometrial and subendometrial volume (cm3), vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were calculated using the VOCAL (Virtual Organ Computer-aided AnaLysis) software. RESULTS: Endometrial and subendometrial vascularity indices increased throughout the follicular phase, decreased to a nadir 2 days after follicular rupture and then increased again during the luteal phase. Endometrial and subendometrial volume increased rapidly during the follicular phase and then remained almost unchanged during the luteal phase. CONCLUSIONS: Substantial changes occur in endometrial volume and vascularization during the normal menstrual cycle. There is the potential for 3D power Doppler ultrasonography to become a useful tool for assessing pathological changes associated with female subfertility and abnormal uterine bleeding.     

Intrafollicular blood flow during human ovulation.

Transvaginal ultrasonography with color flow mapping has been used to study changes in intrafollicular blood flow and morphology during follicular rupture and presumed ovulation in one human volunteer. Detailed monitoring started on day 11 of the menstrual cycle and the follicle began to rupture at 14.30 on day 13. This event was preceded by a defined rise and peak in the level of immunoreactive serum luteinizing hormone (LH) by 42 h and 17 h 20 min, respectively. Blood vessels were clearly visible in the inner ring of the follicle (the granulosa layer) at the time of the LH peak and part of the granulosa (probably containing the oocyte) started to detach before the follicle ruptured. The maximum value for the peak blood velocity in the inner vessels was observed 10 s after the start of follicular rupture and there was a concurrent increase in the impedance to blood flow, as reflected by the resistance index and the pulsatility index. The follicle took 14 min 29 s to empty and the corpus haemorrhagicum started to form about 1 min later. These preliminary data suggest that intrafollicular angiogenesis and changes in blood flow can be monitored by a relatively non-invasive technique. Changes in vascularity might be used to predict imminent ovulation and could possibly be identified or modified biochemically to help achieve or avoid a pregnancy.     

Physiology of the menstrual cycle by ultrasonography.

The aim of this was to study the physiologic changes occurring during the menstrual cycle in 39 healthy women as they appear ultrasonographically. We investigated the following parameters: serum progesterone level, endometrial thickness, and uterine artery pulsatility index. Endometrial thickness was measured at the widest point in the longitudinal plane, including all of the highly reflective endometrium. Uterine arterial Doppler velocimetry was evaluated at the level of the uterine cornua by the pulsatility index. Ovulation was documented by transvaginal determinations of follicle development and progesterone level in each cycle. This prospective study shows that ultrasonographically determined endometrial thickness and uterine artery pulsatility index depend on the phase of the menstrual cycle. Endometrial thickness steadily increases throughout the menstrual cycle whereas the pulsatility index of both uterine arteries tends to decrease after ovulation. This decrease is larger in the uterine artery ipsilateral to the site where ovulation took place.     

Basic review: endocrinology of the normal menstrual cycle

(1) The normal menstrual cycle depends on hormonal relationships between the hypothalamus, pituitary, and ovary. The mechanisms of hormonal control involve both long-looped feedback control (i.e., E2 feedback to the hypothalamus) and local control (i.e., internal ovary). A hormone may have different effects depending on concentration and timing of appearance during the menstrual cycle. (2) There is a single gonadotropin-releasing hormone that governs both FSH and LH release from the pituitary. FSH and LH release is governed by both the concentration and timing of the hypothalamic-releasing factor, GNRH. (3) The follicular or proliferative phase of the menstrual cycle is characterized by the selective development of a dominant follicle. The follicular phase biochemistry is notable for increasing estradiol production, which inhibits GNRH secretion but increases the gonadotropin pool and prepares the follicle for LH influence by stimulating LH receptors. (4) Ovulation occurs secondary to LH surge triggered by increasing levels of E2 acting in a positive feedback loop on the pituitary. (5) Corpus luteum development is signaled by increasing serum progesterone and is largely an autonomous ovarian phenomenon not subject to a great deal of control by hypothalamic or pituitary hormonal controls, because high levels of progesterone inhibit GNRH and gonadotropins.     

Three-dimensional sonographic and power Doppler characterization of ovaries in late follicular phase.

OBJECTIVE: To determine ovarian blood flow characteristics using three-dimensional power Doppler ultrasound. METHODS: We examined 30 patients (30 cycles) prior to the start of their in vitro fertilization treatment in the late follicular phase using three-dimensional power Doppler ultrasound. The volume, vascularization index, flow index, vascularization flow index, mean grayness and the presence of the dominant follicle were determined for each ovary separately. RESULTS: The dominant follicle could be detected in 24 out of 30 cycles (80.0%). The volume of the dominant ovary was 9.9 (standard deviation, 4.0) cm3 and the volume of the non-dominant ovary 6.8 (standard deviation, 2.8) cm3 (P < 0.001). Mean grayness in the dominant ovary was 43.3 (standard deviation, 5.0) and in the non-dominant 47.2 (standard deviation, 4.0) (P < 0.001), but no other differences could be observed between dominant and non-dominant ovaries. The shell with a diameter of 2 mm surrounding the dominant follicle had a higher vascularization index (mean, 9.0; standard deviation, 5.9) and vascularization flow index (mean, 4.2; standard deviation, 2.8) than the whole dominant ovary (mean, 5.5; standard deviation, 2.5 and mean, 2.5; standard deviation, 1.3, respectively) (P = 0.003 and 0.002, respectively). In the cycles without a dominant follicle (n = 6), flow index (mean, 50.0; standard deviation, 5.9) and vascularization flow index (mean, 7.3; standard deviation, 6.2) on the left side were higher than on the right side (mean, 40.2; standard deviation, 3.1; mean, 1.5; standard deviation, 1.4; P-values 0.013 and 0.046, respectively). CONCLUSION: In the dominant ovary, the volume was higher and mean grayness lower than in the non-dominant ovary. The vascularization index in the shell surrounding the dominant follicle was higher than the average vascularization index in the whole dominant ovary. In addition, there were differences in the vascularization and flow indices between right and left ovaries, which may be related to the anatomical difference in the venous drainage between right and left ovaries.     

Intraovarian Doppler velocimetry in ovulatory, dysovulatory and anovulatory cycles.

We have evaluated 48 spontaneous ovarian cycles in 23 women by transabdominal Doppler ultrasound. A total of 1064 intraovarian flow velocity waveform recordings were obtained. The ultrasound assessment of follicular growth, and changes in the concentrations of urinary luteinizing hormone and serum progesterone were used to classify the cycles. After follicular rupture (and presumed ovulation) in 30 cycles, the intraovarian flow velocity waveform (dominant ovary) showed a turbulent flow during the luteal phase ('luteal conversion'). The maximal resistance index was lower compared to values obtained during the follicular phase, and from the contralateral ovary. The intraovarian flow velocity waveform from 12 abnormal cycles showed similar quantitative and qualitative changes. When ovulation did not occur (three cases of the luteinized unruptured follicle syndrome, three anovulatory cycles), there was no evidence of 'luteal conversion' and the velocimetry values were similar throughout the study. Intraovarian Doppler velocimetry makes it possible to distinguish between ovulatory and anovulatory cycles, and provides a non-invasive diagnosis of the luteinized unruptured follicle syndrome.     

Doppler study of arterial and venous intraovarian blood flow in stimulated cycles.

OBJECTIVE: To evaluate arterial and venous intraovarian blood flow in follicle stimulating hormone-stimulated cycles. SUBJECTS AND METHODS: This was a prospective study of 76 follicle stimulating hormone-stimulated cycles carried out in 39 infertile patients who were included in a timed intercourse or intrauterine insemination program in a referral center for assisted reproduction. Transvaginal color and pulsed Doppler measurements of the follicular and luteal phase resistance index, pulsatility index, peak systolic velocity and maximum venous velocity were made and serum progesterone levels during the mid-luteal phase were recorded. Velocimetric parameters were established and then used to classify ovarian function as having a normal ovulatory cycle, or a cycle in which there was either luteal phase deficiency or a luteinized unruptured follicle. RESULTS: In 52 normal ovulatory cycles, the luteal phase peak systolic and maximum venous velocities were significantly higher and resistance and pulsatility indices were significantly lower than those found in the follicular phase. In 15 women with luteal phase deficiency we did not find any differences in arterial velocimetric parameters when compared with normal ovulatory cycles. However, luteal phase maximum venous velocities were lower in the luteal phase deficiency cycles and there was a significant correlation between luteal phase maximum venous velocity and serum progesterone levels (r = 0.36). Luteinized unruptured follicle cycles (n = 9) did not show significant changes during the ovarian cycle and no 'luteal conversion' of the Doppler signal was identified. CONCLUSIONS: Follicle stimulating hormone-stimulated cycles in infertile patients can have a high percentage of abnormal functional responses that can be diagnosed only by sonographic assessment, Doppler and the appropriate hormonal follow-up. Arterial and venous intraovarian blood flow remain unaltered during luteinized unruptured follicle cycles and serum progesterone levels correlated with luteal phase maximum venous velocity, which makes Doppler a potentially useful non-invasive test to assess ovulation and luteal function.     

经阴道彩色多普勒超声对输卵管妊娠中妊娠黄体的临床研究

目的探讨妊娠黄体在超声诊断输卵管妊娠(TP)中的临床意义。方法临床拟诊宫外孕患者50例,于术前行经阴道超声(TVS)检查。在确定TP包块的同时,对妊娠黄体进行观察,CDFI显示双侧子宫动脉输卵管支血流,检测收缩期最大流速(PSV)、舒张末期流速(EDV)、平均流速(TAmax)、搏动指数(PI)及阻力指数(RI),并进行统计学处理。结果在确诊为TP的40例中,超声诊断符合38例。妊娠黄体的声像图表现可分为:薄壁囊肿型、薄壁囊肿内部光点型、厚壁囊肿型、实质低回声型四种类型。超声显示妊娠黄体38例(95.0%),黄体与TP同侧33例(86.8%);与TP非同侧5例(13.2%)。黄体与TP同侧时,患侧输卵管动脉血流EDV、TAmax明显高于健侧,PI、RI则明显低于健侧(P<0.05),PSV双侧无统计学差异(P>0.05);黄体与TP非同侧时,双侧血流参数均无统计学意义(P>0.05)。结论妊娠黄体在超声诊断早期TP时具有重要的定位作用。     

Endovaginal doppler flow measurements of the ovarian artery in patients with a normal menstrual cycle and with polycystic ovary syndrome during in vitro fertilization

Women with a normal menstrual cycle (n = 21, controls), polycystic ovary syndrome (n = 10) and hypogonadotropic amenorrhea (n = 3) were stimulated with clomiphen-citrate (4th day to 8th day of the cycle) and with human menopausal gonadotropin (8th day to 11th day). The vascular impedance of the ovary carrying the dominant follicles was monitored by endovaginal pulsed Doppler flow measurement. Simultaneously, serum levels of LH, E₂ and 17-OHP were assayed. Contrary to controls, women with polycystic ovary syndrome or hypogonadotropic amenorrhea showed decreased hormone levels and no lowering of the vascular impedance. In controls, the lower pulsatility index is caused by neovascularization around the dominant follicle and by E₂-induced vasodilatation in the ovarian artery. © 1993 by John Wiley & Sons.     

经阴道彩色多普勒超声监测卵泡发育及观察子宫内膜血流变化

目的　观察卵泡发育成熟度及子宫内膜厚度和子宫螺旋动脉血流阻力指数的相互关系。方法 应用经阴道超声监测56例正常月经周期的卵泡发育情况、子宫内膜增殖期厚度及子宫螺旋动脉各项参数。结果　排卵前卵泡直径平均2.1cm,并移至卵巢表面,距卵巢包膜≤1.0cm时即将排卵。子宫内膜相应增厚（达1.4cm),螺旋动脉阻力指数降低(0.45±0.03)。结论　经阴道超声多普勒监测卵泡生长发育,观察子宫内膜厚度及螺旋动脉血流阻力指数,可指导临床提高受孕率。     

Physiology of ovarian function

The ovarian function including follicular maturation, ovulation and corpus luteum formation is regulated by a complex control system composed of hypothalamus, pituitary and the ovary itself. These organs communicate via positive and negative feedback loops and can be considered as a functional entity. Special neurons in the hypothalamus produce gonadotropin-releasing hormone (GnRH) being delivered to the anterior pituitary lobe by the pituitary portal vessels. GnRH binds to specific receptors inducing synthesis and release of the gonadotropins FSH and LH into the circulation. After binding to their specific receptors at the ovary FSH and LH induce follicular maturation, ovulation and corpus luteum formation. The ovary responds to gonadotropin stimulation in dual fashion: secretion of sexsteroids and the liberation of a fertilizable oocyte. In addition the ovary is also able to secrete peptide-hormones such as inhibin and activin. Sexsteroids and inhibin modulate the pulsatile secretion of GnRH and gonadotropins. Cooperation of theca- and granulosa cells at the ovarian level and the corpus luteum formation are described and the significance of growth factors and cytocines is emphasized. The effects of estradiol and progesterone are highlighted by the morphological response of the endometrium. The ovary is actively involved in maintaining cyclicity, as reflected by the processes of follicular growth, follicle rupture and formation of the corpus luteum with the dramatic morphological changes involved.     

Change in retrobulbar circulation during menstrual cycle assessed by Doppler ultrasound

Our purpose was to study the hemodynamic changes in the ophthalmic, central retinal and posterior ciliary arteries during the normal menstrual cycle and to relate the vascular changes to menstrual cycle. A total of 23 healthy women underwent serial color Doppler ultrasonography at least six times during a normal menstrual cycle, twice each in follicular, ovulatory and luteal phases. Pulsatility and resistance index and peak systolic velocity of the each arteries were assessed with color Doppler imaging. There was no statistical difference in any of the parameters during the menstrual cycle. This was supposed to be because generalized hormonal effects on heart rate, blood pressure, blood volume, cardiac output and on the diameter of the vessel cancel each other and this effect maintains the same ocular blood flow and perfusion during the menstrual cycle.     

经阴道彩色多普勒超声检查对卵巢储备功能下降患者卵巢基础状态的评价

目的采用经阴道彩色多普勒超声检查探讨卵巢基础状态与卵巢储备功能的关系,评价其对卵巢储备功能的预测价值。方法 74例不孕患者于自然月经周期第2～3天测定基础性激素水平,同时经阴道彩色多普勒超声检测卵巢最大平面平均直径(MOD)、窦卵泡数(AFC)、卵巢间质动脉峰值流速(PSV)、阻力指数(RI)、搏动指数(PI),并于同一周期行克罗米芬刺激实验(CCCT),应用人绒毛膜促性腺激素(hCG)诱导成熟卵泡排卵,指导同房或行宫腔内人工受精(IUI)。超声监测卵泡发育,同时计数注射hCG日优势卵泡数。结果依据基础性激素测定及CCCT结果将患者分为卵巢储备功能正常组和下降组。卵巢储备功能下降组AFC和PSV值均显著低于正常组(P<0.001),卵巢储备功能下降组MOD低于正常组,但二者差异无统计学意义(P>0.05);卵巢储备功能下降组注射hCG日所获优势卵泡数少,妊娠率低于正常组,二者差异有统计学意义(P=0.021)。卵巢间质动脉PSV与注射hCG日优势卵泡数呈正相关(r=0.432,P=0.014)。结论卵巢基础窦卵泡数和PSV值与卵巢储备功能密切相关,可作为临床预测卵巢储备功能的有效指标。     

Utility of color Doppler indices of dominant follicular blood flow for prediction of clinical factors in in vitro fertilization-embryo transfer cycles.

OBJECTIVE: To investigate the relationship between color Doppler indices of dominant follicular blood flow and clinical factors in in vitro fertilization-embryo transfer cycles. SUBJECTS AND METHODS: This was a prospective study involving 26 patients completing a total of 33 in vitro fertilization cycles. Dominant follicular blood flow indices, peak systolic velocities, the resistance index and the pulsatility index were evaluated using transvaginal color Doppler. The indices were compared to the clinical outcomes of in vitro fertilization-embryo transfer. RESULTS: There was a significant correlation between dominant follicular peak systolic velocities and the number of oocytes retrieved, as well as the number of mature oocytes obtained. There was no significant correlation between dominant follicular resistance index or pulsatility index and the number of follicles > 10 mm in diameter, the number of oocytes retrieved or the number of mature oocytes. There were no significant differences between dominant follicular peak systolic velocities, resistance index or pulsatility index, and fertilization rate or the ratio of good quality embryos. However, significant differences were found between the number of oocytes retrieved, as well as the number of mature oocytes for those patients in which the peak systolic velocity was below 25 cm/s. CONCLUSIONS: Doppler assessment of dominant follicle blood flow alone is useful for predicting the number of retrievable oocytes. However, morphological quality of the embryo produced or the pregnancy rate cannot be predicted by this method.     

Ovulation and corpus luteum formation observed by ultrasonography

Ultrasonic observation of the ovary at 8–12 hr intervals reveals typical appearances when ovulation has take place. Shortly after ovulation there is an increase in solid echoes as the cystic follicle decreases in size until a small, less intense echogenic area (“cystic or structural loosening”) stays visible within the ovary. This either stays unchanged during the luteal phase or increases up to a cystic corpus luteum. Premensturally, the ovary regains its more homogenous solid structure. When cystic alteration has taken place, solid echoes invade the cystic corpus luteum which continuously decreases in size once menstruation has started. A cystic structure, similar to a cystic corpus luteum, in the second part of the menstrual cycle possibly signifies luteinisation of the unruptured follicle when no collapse of the follicle is observed before. After multifollicular development, the collapse of the predominant follicle may be difficult to outline when, simultaneous to ovulation, other follicles enlarge as in patients treated with gonadotrophins.     

Longitudinal doppler sonographic measurements of vascular impedance in the central and peripheral spiral arteries throughout pregnancy

PURPOSE: We assessed vascular impedance in the spiral arteries in the central and peripheral placental bed throughout uncomplicated pregnancies. METHODS: Transabdominal color Doppler sonography was used to measure the pulsatility index (PI), resistance index (RI), and peak systolic velocity in the central and peripheral spiral arteries in 94 women with uncomplicated singleton pregnancies. Sonographic examinations took place approximately every 5 weeks from 10 to 40 weeks' menstrual age. RESULTS: PI, RI, and peak systolic velocity were not different in the central versus the peripheral segments of the spiral arteries. The PI and RI values of central spiral arteries after 25 weeks' menstrual age. The PI and RI values of peripheral arteries decreased after 20 weeks' menstrual age. CONCLUSIONS: Additional subjects are needed to clarify changes in the impedance of central and peripheral spiral arteries over the course of normal and complicated pregnancies.     

Paracetamol-associated luteinized unruptured follicle syndrome: effect on intrafollicular blood flow.

We are using transvaginal ultrasonography with color Doppler imaging to study changes in intrafollicular blood flow over the periovulatory period. We report here the findings from one volunteer (subject 9), who took two tablets of paracetamol (1000 mg) twice daily (between 07.00 and 08.00, and 18.00 and 19.00) for 2 consecutive menstrual cycle days (12 and 13) to alleviate a headache, which was shown retrospectively to have occurred within the duration of the luteinizing hormone (LH) surge in peripheral plasma. The drug appeared to have a profound effect on peak systolic blood velocity within the preovulatory follicle. Color (an index of blood velocity) disappeared and flow velocity waveforms were not detectable for at least 4 h. Color then re-appeared, but the peak systolic blood velocity had reduced by 69.8% (from 18.2 to 5.5 cm/s). The peak systolic blood velocity recovered subsequently to 16.3 cm/s, but the follicle did not rupture and continued to grow to a maximum diameter > 59 mm. There was no apparent effect of the drug on expected changes in the circulating levels of estradiol, LH, follicle stimulating hormone or progesterone. The secretory phase of the menstrual cycle lasted 13 days (i. e. day of LH peak to day of next menses minus one). We suggest that paracetamol taken at the time of the LH surge may affect intrafollicular peak systolic blood velocity and might inhibit ovulation. Possible molecular mechanisms are discussed.     

Subendometrial arterial spectral doppler assessment during IVF cycles and its correlation with treatment outcome

The influence of blood flow impedance in subendometrial arteries on embryo implantation rate was investigated by transvaginal sonographic examination in in vitro fertilization (IVF) cycles. A total of 39 women undergoing IVF treatment were evaluated along the treatment cycle. Power and spectral Doppler studies of subendometrial arteries were performed to calculate the pulsatility index (PI), resistance index (RI) and systolic:diastolic ratio (S:D). The correlation between these parameters and pregnancy achievement was analyzed. Patients were grouped according to whether pregnancy was achieved or not. RI and S:D did not differ between the groups along the course of treatment. In pregnant patients, the PI was significantly lower in the beginning of the cycle than on the preovulation day and ovum pickup day. PI in the beginning of the treatment was significantly lower in pregnancy cycles than in nonpregnancy ones. A lower PI on day 1 was correlated with a better chance for pregnancy.     

Assessment of luteal blood flow in normal early pregnancy.

A cross-sectional study was performed in 85 low-risk singleton first trimester pregnancies to assess corpus luteum blood flow during this period. Gestational age, established by measuring crown-rump length, ranged from 6 to 12 weeks. All cases were studied by transvaginal color velocity imaging and pulsed Doppler ultrasonography. After corpus luteum blood flow was identified by color velocity imaging, the resistive index and pulsatility index were calculated to assess vascular resistance. Overall, detection rate of corpus luteum blood flow was 75.2%. No statistical differences were found in mean resistive index and pulsatility index among gestational weeks studied. Linear regression analysis showed that nonsignificant changes in resistive and pulsatility indices occur during the first weeks of normal early pregnancy (R2 = 0.0059 for resistive index, R2 = 0.0008 for pulsatility index). In conclusion, luteal blood flow is constant during normal early pregnancy.