Hormonal profile during the follicular phase in cycles stimulated with a combination of human menopausal gonadotrophin and gonadotrophin-releasing hormone antagonist (Cetrorelix)

A third generation gonadotrophin-releasing hormone antagonist (Cetrorelix) was used during ovarian stimulation in 32 patients undergoing assisted reproduction, in order to prevent the premature luteinizing hormone (LH) surge. In all patients, ovarian stimulation was carried out with two or three ampoules of human menopausal gonadotrophin (HMG), starting on day 2 of the menstrual cycle. In addition, 0.5 mg of Cetrorelix was administered daily from day 6 of HMG treatment until the day of ovulation induction by human chorionic gonadotrophin (HCG). A significant drop in plasma LH concentration was observed within a few hours of the first administration of Cetrorelix (P < 0.005). Moreover, no LH surge was detected at any point in the treatment period in any of the 32 patients. A mean oestradiol concentration of 2111 +/- 935 ng/l was observed on the day of the HCG administration, indicating normal folliculogenesis. Like LH, progesterone concentration also dropped within a few hours of the first administration of Cetrorelix (P < 0.005). A 0.5 mg daily dose of Cetrorelix prevented a premature LH surge in all the 32 patients treated.     

A new mutation, 3905insT, accounts for 4.8% of 1173 CF chromosomes in Switzerland and causes a severe phenotype

The objective of this study was to determine the predictive value of the number of follicles seen by transvaginal ultrasound before gonadotrophin stimulation on the ovarian responsiveness of 166 infertile women undergoing in-vitro fertilization (IVF) treatment. The main variables were patient age, ovarian volume and number of ovarian follicles measuring 2-5 mm on transvaginal ultrasound before gonadotrophin stimulation. Based on the sum of ovarian follicles in both ovaries the patients were divided into three groups of inactive (<5 follicles), normal (5-15 follicles) or polycystic (PCO)-like ovaries (>15 follicles). The main outcome measure was the number of recovered oocytes. The number of follicles was correlated more strongly with the number of recovered oocytes (r2 = 0.131; P = 0.0001) than age alone (r2 = -0.053; P = 0.005). Fewer oocytes were recovered from patients with inactive ovaries (5.4 +/- 2.5; P = 0.006) than with normal (7.5 +/- 4.5) or PCO-like ovaries (10.5 +/- 5.1). Ovarian volume was correlated with the number of follicles before stimulation (P = 0.0001), but not with the number of oocytes. The number of small follicles present before ovarian stimulation was a better predictor of the outcome than ovarian volume or age alone. Patients can be identified with inactive ovaries which will have a poor response to IVF treatment, a key factor for counselling couples and optimizing resources.     

Improved oocyte quality is obtained with follicle stimulating hormone alone than with follicle stimulating hormone/human menopausal gonadotrophin combination

The aim of this study was to compare the efficacy of pure follicle stimulating hormone (FSH) with that of FSH/human menopausal gonadotrophin (HMG) combination in downregulated cycles. A total of 357 patients was evaluated retrospectively. Sixty percent of patients in the FSH group and 55% in the FSH/HMG group were new; the others were repeat patients. Ovulation was suppressed with leuprolide acetate in all patients, followed by either FSH (n = 218) or FSH/HMG (n = 119). There was no difference in patients' age, infertility factors, number of ampoules used, length of stimulation, oestradiol levels on day of human chorionic gonadotrophin (HCG) administration, number of oocytes recovered or the number of embryos transferred. Also, nuclear maturity at aspiration and fertilization rates were not different between the two groups. FSH stimulation resulted in a significantly higher percentage of mature oocytes that showed the typical 'mature' morphological characteristics (P < 0.0001). The clinical pregnancy rates per transfer were 40 and 28% in patients stimulated with pure FSH and FSH/HMG respectively (P < 0.05). The significantly higher number of immature oocytes matured in vitro in the FSH/HMG group (P = 0.001) suggests a possible effect on in-vitro maturation, due to luteinizing hormone present in HMG. The difference in mature oocyte quality may be an important determinant in the higher pregnancy rates for the FSH-stimulated patients.     

Endometrial stripe thickness as a predictor of ectopic pregnancy

We have examined the efficacy of highly purified follicle stimulating hormone (FSH-HP) for controlled ovarian stimulation in our in-vitro fertilization (IVF) programme, and compared the results obtained with this preparation with those using human menopausal gonadotrophin (HMG) in 15 patients who had received treatment with both FSH-HP and HMG in consecutive cycles (n = 39). No differences were found in the duration of stimulation, which was 13.9 days (HMG) as compared with 14.3 days (FSH-HP). However, in the FSH-HP-treated cycles we found a striking difference in the rise of serum oestradiol, which was significantly lower than in HMG-treated cycles (2953 +/- 938 pmol/l as compared with 6349 +/- 3683 pmol/l on the day before ovum retrieval). Number and size of follicles were similar in the two groups, as were oocyte characteristics. Increase in endometrial thickness at two days prior to ovum retrieval was slightly higher after HMG. The results indicate that in combination with a long gonadotrophin-releasing hormone agonist (GnRHa) protocol, pure FSH is sufficient for adequate follicle recruitment and growth. However, since FSH-HP resulted in markedly reduced concentrations of serum oestradiol as compared to HMG cycles, IVF programmes using repeated oestradiol measurements to decide the day of ovum retrieval must take this into consideration in order not to prolong the stimulation unnecessarily.     

Reducing the dose of gonadotrophin-releasing hormone agonist on starting ovarian stimulation: effect on ovarian response and in-vitro fertilization outcome

The aim of this study was to examine if lowering the dose of gonadotrophin-releasing hormone agonist (GnRHa) on starting ovarian stimulation could be beneficial in in-vitro fertilization (IVF) programmes. A total of 64 normally ovulating patients entering an IVF programme were randomized to receive GnRHa (nafarelin acetate/Synarel) as an intranasal spray commencing in the midluteal phase, either at a dosage of 200 microg three times daily until the day of human chorionic gonadotrophin (HCG) administration, or to be reduced to 200 microg twice daily as ovarian stimulation was initiated. Patients in both groups were below 35 years with a body mass index below 30. All patients received three ampoules of Metrodin HP per day. Blood samples were taken on the day of HCG administration to measure luteinizing hormone (LH), oestradiol, and progesterone. LH and oestradiol were found to be significantly higher in the lower Synarel dose group. Our results show that reducing the GnRHa dose during ovarian stimulation in IVF might be beneficial in terms of significantly more oocytes recovered, and significantly greater number of embryos available for transfer and freezing, with no incidence of premature luteinization.     

Serum progesterone at the time of human chorionic gonadotrophin does not predict pregnancy in in-vitro fertilization and embryo transfer

Controversy exists as to whether the serum concentration of progesterone on the day of human chorionic gonadotrophin (HCG) administration following ovarian stimulation for in-vitro fertilization (IVF) and embryo transfer can be used to predict the likelihood of success. This retrospective study was undertaken to answer this question by analysing a large population of IVF and embryo transfer cycles (n = 756). In addition to the concentration of progesterone on the day of HCG administration, all variables known to impact on IVF and embryo transfer success (such as patient age), indication for IVF and embryo transfer, number of oocytes retrieved and the number of embryos generated and transferred were examined. There was a significant increase in the number of oocytes retrieved with increasing progesterone concentration at the time of HCG administration. However, there was no correlation of progesterone concentration at HCG administration with pregnancy and implantation rates. It is concluded that previous reports associating a slight elevation of progesterone in gonadotrophin-releasing hormone agonist ovarian stimulation cycles for IVF and embryo transfer may be misleading because of a small sample size or the presence of confounding variables that affect IVF and embryo transfer success.     

Outcome from consecutive in-vitro fertilization/intracytoplasmic sperm injection attempts in the final group treated with urinary gonadotrophins and the first group treated with recombinant follicle stimulating hormone

In the absence of specific dose equivalency data, the aim of this study was to compare the clinical results during the cross-over from menopausal urinary products (human menopausal gonadotrophin; HMG) to recombinant follicle stimulating hormone (FSH) follitrophin beta (FSHr) in order to determine whether the manufacturer's recommendation for equivalence of ampoule to ampoule (50 IU FSHr:75 IU HMG) would prove clinically correct. A total of 353 consecutive in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment cycles was studied between 1st September 1996 and mid-February 1997. This included cycles in the last 191 women receiving HMG and the first 162 taking FSHr. All were down-regulated using a gonadotrophin releasing hormone (GnRH) agonist long protocol method from day 1 of the cycle. Greater efficacy was seen in the HMG group in terms of days of stimulation required, need to increase dosage, cycle discontinuation, number of follicles punctured, the numbers of oocytes retrieved and their quality. The hormonal response to stimulation assessed by oestradiol concentrations on days 5, 8 and day of human chorionic gonadotrophin (HCG) was significantly lower in the FSHr group. The ratio of oestradiol per follicle and per oocyte was significantly lower in the FSHr group. There was a highly significant increase in cost with FSHr therapy. Clinical pregnancy rates were 14% per cycle with FSHr and 20% per cycle with HMG.     

Internal jugular vein thrombosis caused by resistance to activated protein C as a complication of ovarian hyperstimulation after in-vitro fertilization

We present a case of a 24 year old woman who became pregnant (twins) after human menopausal gonadotrophin (HMG)-induced ovarian stimulation, in-vitro fertilization (IVF) and subsequent embryo transfer. She developed a right internal jugular vein thrombosis as a complication of severe ovarian hyperstimulation syndrome (OHSS) 28 days after embryo transfer. The thrombosis developed in spite of anticoagulation with low-dose heparin. Later a resistance to activated protein C (APC) or Dahlb?ck disease was diagnosed. Due to a new test procedure (accelerin inactivation test), the diagnosis was possible even under anticoagulation treatment. The coincidence of hyperstimulation and internal jugular vein thrombosis with the concurrent diagnosis of resistance to APC has not been published previously. The benefit of general screening for resistance to APC before admission to the IVF programme should be weighed. Targeted selection of a group of high-risk women would therefore be made possible.     

Endometrial thickness as a predictor of pregnancy after in-vitro fertilization but not after intracytoplasmic sperm injection

An ultrasonographic evaluation of the endometrium was performed in 158 patients undergoing ovarian stimulation for an in-vitro assisted reproduction programme. Endometrial thickness was evaluated in 109 patients undergoing in-vitro fertilization (IVF) for female indications and in 49 patients undergoing intracytoplasmic sperm injection (ICSI) for male indications. The maximal endometrial thickness was measured on the day of human chorionic gonadotrophin (HCG) administration by longitudinal scanning of the uterus on the frozen image using electronic callipers placed at the junction of the endometrium-myometrium interface at the level of the fundus. Cases in which the endometrial thickness was >/=10 mm were included in group A; cases in which the endometrial thickness was <10 mm were assigned to group B. The age of the patients, serum 17-beta oestradiol concentrations on the day of HCG administration, the length of follicular stimulation, the number of follicles, 17-beta oestradiol concentrations per follicle on the day of HCG and the number of embryos transferred were analysed in each case. When comparing endometrial thickness and results in IVF and ICSI patients, an endometrium <10 mm predominated in IVF patients (27.5%) compared with those undergoing ICSI (16.7%) (P = 0.05); conversely an endometrium >=10 mm was more frequent in ICSI than in IVF patients. The incidence of pregnancy was higher in IVF group A patients (32/79; 41%) than in IVF group B patients (5/30; 17%) (P = 0.03), whereas no significant difference was found between ICSI group A (13/42; 31%) and ICSI group B (3/7; 43%) patients. Thus, a higher percentage of IVF patients had thin endometrium when compared with ICSI patients; thin endometrium was a prognostic indicator of pregnancy only in the case of a female indication for infertility (IVF). A thin endometrium in cases of female infertility may reflect a previous or present uterine pathology, whereas in indications of male infertility (i.e. cases using ICSI), in the absence of any associated uterine pathology, the presence of a thin endometrium is not predictive.     

Purified urinary follicle stimulating hormone induces different hormone profiles compared with menotrophins, dependent upon the route of administration and endogenous luteinizing hormone activity

The effects of treatment of patients with gonadotrophin-releasing hormone analogue (GnRHa) combined with purified follicle stimulating hormone (FSH) for in-vitro fertilization (IVF) were investigated in detail to determine the influences of different administration routes and the degree of suppression of luteinizing hormone (LH). Responses to exogenous gonadotrophins were studied in infertile women (n = 60) with normal menstrual rhythm whose endogenous gonadotrophin activity was suppressed using a GnRHa in a long protocol. They were randomized to receive i.m. administration of human menopausal gonadotrophins (HMGim, Pergonal) or purified follicle stimulating hormone (FSH, Metrodin High Purity) administered either i.m. (MHPim) or s.c. (MHPsc). Responses were assessed by measuring plasma FSH, LH, oestradiol, testosterone and progesterone. After stimulation day 4, the MHPsc group showed significantly higher circulating concentrations of FSH than either the MHPim or HMGim group. However, the HMG group showed significantly higher oestradiol concentrations after stimulation day 5 than either MHP group. The differences in circulating oestradiol concentrations in the MHP-treated patients appeared to be strongly influenced by the mean circulating concentrations of LH in the follicular phase. The patients who showed mean follicular phase LH concentrations of < 1 IU/l showed longer follicular phases, lower circulating oestradiol and testosterone concentrations and also lower follicular fluid concentrations of oestradiol and testosterone, indicating a reduction in the normal follicular metabolism of progesterone to androgens and oestrogens under these conditions. This group of patients also showed longer follicular phases, which may have consequences for future clinical management.     

Increased anticardiolipin antibodies are positively related to the uterine artery pulsatility index in unexplained infertility

The objective of the study was to evaluate, in patients with unexplained infertilty, the possible relationship between anticardiolipin antibodies and indices of uterine artery Doppler measurements. A total of 46 infertile women participated in the study and underwent ovarian stimulation. Transvaginal ultrasonography and colour Doppler were performed on the day of embryo transfer and patients were divided on the basis of pulsatility index (PI): group I, PI <2.5; group II, PI 2.5-3.0; and group III, PI >3.0. On the same day that Doppler analysis took place, peripheral blood was obtained and circulating anticardiolipin antibodies were assayed. The response to ovarian stimulation was similar in the three studied groups. No significant differences in oestradiol and ultrasonographic parameters were observed between the groups. A significant increase in anticardiolipin antibodies was observed in those patients with higher resistance to flow at the level of the uterine artery. A significant relationship was found between the uterine artery PI and anticardiolipin immunoglobulin G class (F = 14.35; P = 0.001), and immunoglobulin M class (F = 5.88; P = 0.020). It is concluded that, in unexplained infertility, anticardiolipin antibodies may be involved in uterine vascular modifications and that Doppler flow analysis of uterine arteries may be an important tool in the assessment and management of ovarian stimulation.     

Induction of the endogenous gonadotrophin surge for oocyte maturation with intra-nasal gonadotrophin-releasing hormone analogue (buserelin): effective minimal dose

From 1985-1987, a total of 34 couples undergoing superovulation for a single in-vitro fertilization (IVF) cycle with clomiphene citrate and purified follicle stimulating hormone (FSH) or human menopausal gonadotrophin (HMG) were randomly allocated doses of intra-nasal buserelin to induce an endogenous gonadotrophin surge, prior to oocyte collection. The doses ranged from a single 25 microg dose to 100 microg every 4 h for 20 h. In three cycles the treatment was abandoned because of a poor ovarian response. In the remaining 31 cycles buserelin was given to induce the endogenous gonadotrophin surge, but there was evidence of premature luteinization in eight cycles and a premature gonadotrophin surge in four cycles. Although a single dose as low as 40 microg induced a surge and resulted in a pregnancy, a single dose of 50 microg proved the most effective minimal dose consistently to induce a gonadotrophin surge and oocyte maturation. Recent reports using gonadotrophin-releasing hormone (GnRH) analogues to induce a gonadotrophin surge has prompted publication of this previously unpublished data.     

Endometrial fluid collection in women with hydrosalpinx after human chorionic gonadotrophin administration: a report of two cases and implications for management

The impact of hydrosalpinx (HSPX) on in-vitro fertilization (IVF) outcome has recently been the subject of intense debate. Most, but not all, studies have reported decreased implantation and pregnancy rates and increased early pregnancy loss in HSPX patients. This has led to prophylactic salpingectomies prior to IVF in HSPX patients despite the lack of any prospective studies to suggest that any improvement will occur. Women with HSPX constitute a heterogeneous population because some conceive easily with IVF while others do not until after surgical correction. HSPX also increases in size with ovarian stimulation, and can cause implantation failure by fluid reflux into the uterine cavity. Careful assessment of the endometrial lining is mandatory in HSPX to rule out fluid reflux from the HSPX. We present two case reports of patients whose HSPX enlarged with ovarian stimulation, causing fluid reflux into the uterine cavity which was only noted after human chorionic gonadotrophin (HCG) administration.     

Short-term GnRH-analogue administration in patients with PCOS and its impact on hemodynamics and hormonal profile

PURPOSE: The ovarian response to 14 days of GnRH-analogue (GnRHa) application in patients with polycystic ovary syndrome (PCOS) was evaluated by measuring hemodynamic parameters and hormonal profile. METHODS: Twenty patients with PCOS represented the study group, and 22 patients with normal menstrual cycle (NMC) the reference group. The resistance index (RI) of uteroovarian arterial blood flow and serum level of LH and androstendione were measured on days 4, 13, and 22 of the cycle and after 14 days of GnRHa administration. RESULTS: On day 22 of the cycle the RI in the uterine artery was 0.86 in the PCOS and 0.82 in the NMC group. Throughout the cycle the ovarian arterial blood flow in both ovaries in the PCOS group was similar to that in inactive ovaries in the NMC group. After the 14-day GnRHa administration the RI of uteroovarian blood flow and the serum level of androstenedione remained unchanged in the PCOS group. CONCLUSIONS: RI in the uteroovarian blood flow and serum androstendione level in the PCOS group are not affected by 14-day GnRHa administration.     

Morphometric study of the placental vessels and its correlation with umbilical artery Doppler flow

OBJECTIVE: To determine the changes in the vessel-wall thickness and the radius of the lumen in tertiary-stem villi of the placenta with advancing gestational duration and their relationship to umbilical artery Doppler flow studies. METHODS: Placentas from 63 miscarriages and preterm and term deliveries (between 19 and 40 weeks) were used for morphometric study of the tertiary-stem villi vessels. Each woman had undergone Doppler flow study of the umbilical artery. The resistance index (RI) was determined from the Doppler flow velocity waveform. Placental paraffin sections of 4-micron thickness were stained with hematoxylin and eosin and with periodic acid-Schiff reagents. The tertiary-stem villi and their vessels were examined microscopically and assessed morphometrically using a personal computer with math co-processor and a touch-sensitive screen overlying a video monitor. The monitor received microscopic images from a video camera that was mounted on a microscope. We determined vessel-wall thickness by tracing the outer and inner circumferences of digitized vessel-wall images. RESULTS: Wall thickness, but not lumen size, of the tertiary-stem villi vessels decreased significantly overall at a rate of 0.63micron/week (P < .001). The rate of decrease was 0.64micron/week (P < .001) during the second trimester and 0.50micron/week (P < .001) during the third trimester. There was a significant correlation between the decrease in thickness and in RI (r = 0.83 [P < .001], r = 0.78 [P < .001] in the second and third trimesters, respectively). Resistance indices were all within normal limits. CONCLUSIONS: Placental tertiary-stem villi vessel-wall thickness decreases with advancing gestational age. There is a correlation between the changes in RI of the umbilical artery Doppler flow and the changes in mean wall thickness of the placental vessels.     

Anti-GBM glomerulonephritis in mice lacking nitric oxide synthase type 2

To determine the relationship between quantitative Doppler parameters of portal, hepatic, and splanchnic circulation and hepatic venous pressure gradient (HVPG), variceal size, and Child-Pugh class in patients with alcoholic cirrhosis, we studied forty patients with proved alcoholic cirrhosis who underwent Doppler ultrasonography, hepatic vein catheterization, and esophagoscopy. The following Doppler parameters were recorded: time-averaged mean blood velocity, volume flow of the main portal vein flow, and resistance index (RI) of the hepatic and of the superior mesenteric artery. Doppler findings were compared with HVPG, presence and size of esophageal varices, and Child-Pugh class. There was a significant inverse correlation between portal velocity and HVPG (r = -.69), as well as between portal vein flow and HVPG (r = -.58). No correlation was found between RI in the hepatic artery or superior mesenteric artery and HVPG. No correlation was found between portal vein measurements and presence and size of varices. Severe liver failure was associated with lower portal velocity and flow. In patients with alcoholic cirrhosis, only portal vein blood velocity and flow, but neither hepatic nor mesenteric artery RI, are correlated to the severity of portal hypertension and to the severity of liver failure.     

The first three weeks assessed by transvaginal color Doppler

Transvaginal color Doppler has made possible to study ovarian and uterine perfusion in non-pregnant and pregnant patients, thus advancing the understanding of the early human development. RI of follicular blood flow starts decreasing prior to ovulation reaching its nadir at ovulation. It is considered that apart from hormonal factors the angiogenesis is also involved. The mature corpus luteum shows increased blood flow velocity in relation to preovulatory follicle. Comparing RI values of luteal blood flow of normal and ectopic pregnancy no difference was found. But in threatened, incomplete and missed abortions the resistance and pulsatility indices were significantly higher than in normal pregnancy. The follow up of the luteal flow might have a prognostic value in a group of patients with threatened abortion. In women with spontaneous cycles the day preceding the ovulation impedance to uterine flow velocity starts decreasing. Alterations in flow velocity patterns of the radial and spiral arteries in spontaneous ovulatory cycles are paralleling blood flow dynamics of the uterine arteries. In stimulated cycles RI increases the day before ovulation in both the uterine arteries and their branches. It seems that endometrial perfusion presents more accurate noninvasive assay of uterine receptivity than uterine artery perfusion alone. Endometrial receptivity is maximum during the time of peak luteal function during which implantation is most likely to occur. During the pregnancy impedance to blood flow decrease from the main uterine to the spiral arteries as well as with the advancing gestational age. The spiral arteries in pregnancy become the vessels with completely different haemodynamic characteristics in relation to other arteries of uteroplacental circulation. Color Doppler adds new information on perfusion and pathophysiological changes connected with the ectopic trophoblast implantation.     

Beta-chemokines MCP-1 and RANTES are selectively increased in cerebrospinal fluid of patients with human immunodeficiency virus-associated dementia

OBJECTIVE: To compare the endocrine responses of patients who first received hMG plus FSH, then were treated in a subsequent cycle with FSH alone. DESIGN: Retrospective study. SETTING: An academic research environment. PATIENT(S): Ninety-six women with pituitary down-regulation who underwent two sequential IVF treatments, the first with combined hMG and FSH and the second with FSH alone. MAIN OUTCOME MEASURE(S): Duration of stimulation, serum estradiol level on the day of hCG administration, amount of gonadotropin used, number of oocytes retrieved, number of oocytes fertilized, and selected preembryo morphologic features. RESULT(S): No difference in the mean duration of stimulation was observed between the treatment cycles among patients who received hMG and FSH (11.9 days) followed by FSH alone (11.7 days). The mean number of oocytes retrieved, the mean number of oocytes fertilized, the percentage of preembryo fragmentation, and the preembryo cell number at transfer did not differ significantly between the stimulation protocols. The cumulative amount of gonadotropin used during stimulation was slightly greater in the cycles stimulated with FSH alone, but this difference was not significant (29.4 ampules of hMG plus FSH versus 31.8 ampules of FSH alone). Serum estradiol levels measured on the day of hCG administration during stimulation with hMG and FSH (1,382 pg/mL) were higher than those measured during stimulation with FSH alone (1,149 pg/mL). CONCLUSION(S): Follicular response and preembryo quality were not significantly different when patients were treated first with hMG and FSH and then with FSH alone in a subsequent cycle. Similarities in ovarian response and preembryo characteristics, as well as differences in estradiol patterns seen in each stimulation setting, should be anticipated when patients receive these protocols.     

Color Doppler ultrasound pulsatile flow signals of thoracic lesions: comparison of lung cancers and benign lesions

Color Doppler ultrasound (US) was performed in 153 patients (including 102 with lung cancer and 51 with benign lesions) to assess pulsatile flow signals in thoracic lesions. The values of resistive index (RI) and pulsatility index (PI) of color Doppler US pulsatile flow signals in lung cancers and benign lesions were measured, analyzed, and compared. In the enrolled 153 patients with thoracic lesions, 61 lung cancers and 34 benign lesions had detectable color Doppler US pulsatile flow signals, and lung cancers had lower RI and PI values than benign lesions (RI: 0.70+/-0.03 vs. 0.79+/-0.04, p < 0.05; PI: 1.61+/-0.15 vs. 2.44+/-0.25, p < 0.005). However, overlapping RI and PI values in lung cancers and benign lesions somewhat limited color Doppler US pulsatile flow signals to differentiate lung cancers from benign lesions. Further analysis of RI and PI values in subgroups of lung cancers [squamous cell carcinoma (SCC, n = 34), adenocarcinoma (AC, n = 18), and small-cell lung cancer (SCLC, n = 6)] and benign lesions [cavitary benign lesions (CBL, n = 8), and noncavitary benign lesions (NCBL, n = 26)] revealed that all different cell types of lung cancers (SCC, AC, and SCLC), indeed, had lower RI and PI values than NCBL (for RI, all p < 0.01; for PI, all p< or =0.001). Moreover, the mean RI and PI values showed a significant incremental decrease from NCBL (mean RI, PI = 0.88, 2.94) toward SCC and AC (for SCC, mean RI, PI = 0.71, 1.68; for AC, mean RI, PI = 0.68, 1.67) and, finally, to SCLC (mean RI, PI = 0.62, 1.05). In contrast, CBL had relatively lower RI and PI values than AC and SCLC (for CBL, mean RI, PI = 0.53, 0.80; both p > 0.05 for RI and PI), and even a significant difference from SCC (p < 0.05 for RI and PI). We conclude that color Doppler US pulsatile flow signal is somewhat limited to differentiate lung cancers from benign lesions, but provides a noninvasive in vivo model to assess the neovascularity intensity of lung cancers.