Serum vascular endothelial growth factor concentrations and ovarian stromal blood flow are increased in women with polycystic ovaries

The aim of this study was to determine basal serum vascular endothelial growth factor (VEGF) concentrations and Doppler blood flow changes within the ovarian stroma of women with polycystic ovaries (PCO) and women with normal ovaries. Pulsed and colour Doppler blood flows within the ovarian stroma were recorded, and serum VEGF concentrations measured, in the early follicular phase (days 2-3 of a menstrual cycle) in 60 women undergoing ovarian stimulation for in-vitro fertilization. 36 women had normal ovaries, 14 women had PCO as seen on pelvic ultrasound examination and 10 had polycystic ovarian syndrome (PCOS). Mean+/-SD serum VEGF concentrations were significantly higher (P < 0.001) in women with PCO and PCOS (3.4+/-0.7 and 3.2+/-0.66 ng/ml respectively) compared with women with normal ovaries (2.3+/-0.5 ng/ml). Mean peak systolic blood flow velocity (PSV) and time-averaged maximum flow velocity (TAMXV) were significantly higher (P < 0.001) in women with PCO and PCOS compared with women with normal ovaries. The mean PSV were 15+/-4 and 16+/-4 cm/s in women with PCO and PCOS respectively, compared with 9+/-2 cm/s in women with normal ovaries. The TAMXV were 9+/-3 and 11+/-3 cm/s in women with PCO and PCOS respectively compared with women with normal ovaries (5.8+/-1.5 cm/s). Serum VEGF concentrations were positively correlated with PSV (r=0.44, P=0.001) and TAMXV (r=0.45, P < 0.000) in all three groups of women. Higher serum concentrations of VEGF in women with PCO and PCOS may relate to the increased vascularity that underlies the increased blood flow demonstrated by Doppler blood flow velocity measurements in these women. The results may explain the higher risk of ovarian hyperstimulation syndrome in programmes of ovarian stimulation in patients with PCO compared with those with normal ovaries.      

Comparison of ovarian stromal blood flow between fertile women with normal ovaries and infertile women with polycystic ovary syndrome

BACKGROUND: Conflicting information exists in the literature with respect to ovarian stromal blood flow in women with polycystic ovary syndrome (PCOS). We compared the ovarian stromal blood flow and serum vascular endothelial growth factor (VEGF) concentration between fertile women with normal ovaries and infertile women with PCOS. METHODS: In the second to fourth day of the menstrual period, they underwent transvaginal scanning with three-dimensional (3D) power Doppler to determine total antral follicle count (AFC), total ovarian volume, total ovarian vascularization index (VI), flow index (VFI) and vascularization flow index (VFI). Serum FSH, LH and VEGF concentrations were also checked. RESULTS: 107 fertile controls and 32 PCOS women were recruited. Fertile controls and PCOS women had similar total ovarian VI/FI/VFI after controlling for age of the woman, although PCOS women had significantly higher total AFC, total ovarian volume and serum LH concentration than fertile controls. Total ovarian VI/FI/VFI were significantly higher in normal weight (BMI < 25 kg/m2) PCOS women than their overweight (> or = 25 kg/m2) counterparts. CONCLUSIONS: Fertile controls and PCOS women had similar total ovarian 3D power Doppler flow indices. Normal weight PCOS women had significantly higher total ovarian 3D power Doppler flow indices than their overweight counterparts.     

Ovarian stromal echogenicity in women with normal and polycystic ovaries

Since the widespread use of transvaginal ultrasound to diagnose polycystic ovary syndrome (PCOS), a cardinal feature has been shown to be the presence of a bright, highly echogenic stroma. This is usually assessed subjectively. The objective of this study was to determine whether ovarian stromal echogenicity when measured objectively actually differed between women with polycystic ovaries and those with normal ovaries. A total of 67 women underwent a detailed ultrasound assessment before considering assisted conception treatment. Ovarian morphology was assessed and total ovarian volume, stromal volume, peak stromal blood flow velocity and mean stromal echogenicity were measured. The stromal index (ratio of mean stromal echogenicity to mean echogenicity of the entire ovary) and total stromal echogenicity were also calculated. Ovarian volume, stromal volume, and stromal peak blood flow velocity were all significantly higher in ovaries from women with PCOS. There was no difference in the mean stromal echogenicity, although the stromal index was significantly greater in women with polycystic ovaries. The apparent subjective increase in stromal echogenicity in women with polycystic ovaries, as exemplified by the greater stromal index, is due to a combination of the increased volume of ovarian stroma and the significantly lower mean echogenicity of the entire ovary in these women.     

Contraception: Ovarian stromal blood flow in women with polycystic ovaries--a possible new marker for diagnosis?

Blood flow changes in the ovarian stroma of women embarkingon in-vitro fertilization treatment were assessed on day 2 or3 of the menstrual cycle using colour and pulsed Doppler ultrasound.Women were divided into three groups: group 1, 63 women withregular, ovulatory menstrual cycles and normal ovaries on ultrasoundscan; group 2, 13 women similar to group 1 but with polycysticovaries (PCO) on ultrasound scan; and group 3, 12 women withbiochemical evidence of previous anovulatory cycles and/or oligo-menorrhoeaand/or elevated serum luteinizing hormone concentrations (>10IU/1) in the early follicular phase together with PCO on ultrasoundscan. A subjective assessment of the intensity and quantityof coloured areas in the ovarian stroma appeared to be greaterin both groups 2 and 3 compared with group 1. Mean (SEM) ovarianstromal peak systolic blood flow velocity (V_max) was 16.88 (1.79)and 16.89 (2.36) cm/s in groups 2 and 3 respectively. Thesevelocities were significantly greater than the mean (SEM) ovarianstromal V_max of group 1; 8.74 (0.68) cm/s (P < 0.001). Mean(SEM) ovarian stromal time averaged maximum velocity (TAMX)was 10.55 (0.91) and 10.89 (1.80) cm/s in groups 2 and 3 respectively,both significantly greater than mean ovarian stromal TAMX ofgroup 1, (P < 0.001). There was no significant differencein pulsatility index (PI) between the three groups. There thusappears to be significantly greater ovarian stromal blood flowvelocity in women with polycystic ovaries as detected by colourand pulsed Doppler ultrasound. Increased ovarian stromal bloodvelocity may be a new parameter to assist in the ultrasounddiagnosis of PCO. The increase in stromal blood flow velocitymay help to explain the excessive response often seen duringgonadotrophin administration in women with PCO and is consistentwith the theory that the PCO may be a primary disorder of theovary.     

Quantification of Doppler signal in polycystic ovary syndrome using three-dimensional power Doppler ultrasonography: a possible new marker for diagnosis.

BACKGROUND: Differences in the ovarian stromal blood flow of women embarking on an IVF treatment, as assessed on day 2 or 3 of the menstrual cycle, using three-dimensional (3D) power Doppler ultrasonography to quantify the blood flow and vascularization, were compared. METHODS: The women were divided into two groups: group 1, 54 women with regular, ovulatory menstrual cycles and normal ovaries on ultrasound scan; and group 2, 25 women with polycystic ovary syndrome (PCOS). RESULTS: The quantification of Doppler signal in the ovarian stroma appeared to be greater in the PCOS group compared with the normal group. The mean of ovarian volume was significantly higher (P < 0.05) in women with PCOS compared with the normal ovaries. The vascularization flow index (VFI), flow index (FI), and vascularization index (VI), were significantly higher (P < 0.05) in the women with PCOS compared with the women with normal ovaries. CONCLUSIONS: This observation may help to explain the excessive response often seen during gonadotrophin administration in women with PCOS. We believe that a quantification study of the vascular flow, including the VI, FI, and VFI of the entire ovarian stroma using 3D power Doppler, is more accurate than the previously reported quantification analysis using 2D imaging, and may be a new parameter to assist in the ultrasound diagnosis of PCOS.     

Polycystic ovaries in childhood: a common finding in daughters of PCOS patients. A pilot study

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a controversial endocrine pathology and, recently, it has been suggested that the condition is hereditary. The aim of this study was to prospectively determine in daughters of patients with PCOS, by ultrasonographic (US) and colour Doppler analyses, the incidence of polycystic ovaries and search any correlation with specific hormonal parameters. METHODS: Fifteen prepubertal offspring (Group I) of patients with PCOS and 10 normal control prepubertal girls (Group II) were submitted to clinical, auxological, and basal hormonal assay. In addition all patients were submitted to US and colour Doppler ovarian and uterine evaluation. RESULTS: Among Group I girls the prevalence of polycystic ovaries was 93%, whereas no subjects among Group II had polycystic ovaries. The ovarian volume (2.76 +/- 1.21 ml versus 0.87 +/- 0.46 ml; P < 0.001) and the number of small sized follicles (5.36 +/- 2.2 versus 0.75 +/- 0.92; P < 0.001) were significantly higher in Group I than Group II patients. In addition, a normal stromal score and an absent stromal vascularization was observed in the control group. The hormone levels did not differ between the two groups. CONCLUSION: In conclusion we speculate that polycystic ovaries in childhood may be considered a sign of genetic predisposition to PCOS and that environmental factors may express the adult clinical and hormonal presentation of the syndrome.     

Three-dimensional ultrasound features of the polycystic ovary and the effect of different phenotypic expressions on these parameters

BACKGROUND: The aim of this study was to quantify the three-dimensional (3D) ultrasound characteristics of ovaries in Caucasian women with polycystic ovarian syndrome (PCOS) and to examine if these values differed between different phenotypic forms. METHODS: 3D pelvic ultrasound was performed in 40 women with PCOS and in 40 controls. Total ovarian volume, stromal volume and echogenicity and antral follicle count (AFC) were measured and ovarian blood flow was quantified using both 3D power Doppler and two-dimensional pulsed-wave Doppler. RESULTS: Women with PCOS had a higher AFC (median 16.3 versus 5.5 per ovary, P < 0.001) and ovarian volume (12.56 versus 5.66 ml, P < 0.001). Stromal volume (10.79 versus 4.69 ml, P < 0.001) and stromal vascularization (VI: 3.85 versus 2.79%, P < 0.001; VFI: 1.27 versus 0.85, P < 0.001) were also increased in women with PCOS. There were no significant differences in stromal echogenicity or pulsed-wave Doppler indices between women with PCOS and the controls. Among the women with PCOS, ovarian vascularity was significantly higher in 30 women who were hirsute compared with normoandrogenic women (FI: 33.94 versus 29.30, P < 0.05) and in 14 women with PCOS who were of normal weight compared with obese women (VI: 4.51 versus 3.25%, P < 0.05; VFI: 1.56 versus 1.22, P < 0.05). CONCLUSIONS: Based on 3D ultrasound, women with PCOS have an increased stromal volume and vascularity. Stromal vascularity is significantly higher in women with PCOS who are hirsute and of normal weight.     

A prospective study of predictive factors of ovarian response in 'standard' IVF/ICSI patients treated with recombinant FSH. A suggestion for a recombinant FSH dosage normogram

BACKGROUND: The aim was to identify independent predictors of ovarian response to recombinant (r)FSH through a multiple regression analysis. METHODS: Prospective study including 145 'standard' patients treated with 150 IU/day of rFSH during their first IVF/ICSI cycle. Down-regulation was achieved with long agonist protocol. The following were examined as possible predictive factors: age, body mass index, cycle length, smoking status and on day 2-5: total ovarian volume, total number of antral follicles (<10 mm), total Doppler score of the ovarian stromal blood flow, serum FSH, LH, estradiol, inhibin B, and testosterone. RESULTS: Total number of antral follicles, total Doppler score, serum FSH, LH, estradiol, inhibin B, smoking status and cycle length were independent predictors of the number of aspirated follicles. The number of oocytes was predicted by the total number of antral follicles, total Doppler score, serum testosterone and smoking status. In bivariate linear regression analyses ovarian volume was a highly significant predictor of both the number of follicles (P < 0.001) and the number of oocytes (P < 0.001). CONCLUSIONS: Among 12 investigated possible predictive factors in 'standard' patients, the total number of antral follicles and ovarian stromal blood flow assessed by total Power Doppler score are the two most significant predictors of ovarian response. Suggestion for an rFSH dosage normogram is presented.     

Effect of pituitary downregulation on antral follicle count, ovarian volume and stromal blood flow measured by three-dimensional ultrasound with power Doppler prior to ovarian stimulation

BACKGROUND: Despite the extensive use of gonadotrophin releasing hormone agonists (GnRH ag) for pituitary downregulation, the literature regarding their effect on ultrasound parameters for predicting ovarian responses are few and conflicting. The aim of this prospective study was to compare antral follicle count (AFC), ovarian volume and ovarian stromal blood flow measured by three-dimensional (3D) power Doppler ultrasound before and after pituitary downregulation. METHODS: All patients received a long protocol of intranasal Buserelin from the mid-luteal phase of the cycle. In the early follicular phase of the preceding cycle before downregulation and on the second day of the treatment cycle after downregulation, patients underwent a blood test for serum FSH, LH and estradiol and a transvaginal scanning with 3D power Doppler to determine AFC, ovarian volume and ovarian 3D power Doppler flow indices. RESULTS: Out of 104 women scanned, 85 women were analysed. Polycystic ovaries were encountered in 14 (16.5%) women. No significant differences in any of the ultrasound parameters were demonstrated before and after downregulation, in patients with normal ovaries or in those with polycystic ovaries. CONCLUSION: AFC, ovarian volume and ovarian 3D power Doppler flow indices did not significantly change after a short-term treatment of GnRH agonist for pituitary downregulation.     

Three-dimensional assessment of ultrasound features in women with clomiphene citrate-resistant polycystic ovarian syndrome (PCOS): ovarian stromal volume does not correlate with biochemical indices

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a heterogeneous endocrine disorder affecting women of reproductive age. The syndrome is characterized by a combination of polycystic ovarian morphology, clinical features and biochemical indices. The objective of this prospective observational study was to investigate the relationship between the total ovarian volume and the ovarian stromal volume, measured using a three-dimensional (3D) ultrasound scan, with biochemical indices of PCOS. METHODS: Twenty-three infertile women (mean age +/- SD: 31 +/- 3.1 years; range: 26-37) with clomiphene citrate-resistant PCOS were examined. Early follicular phase (days 2-4) serum FSH, LH and testosterone concentrations were measured following a withdrawal bleed. Total ovarian volume, stromal volume, pre-antral follicle (<10 mm) number and total follicular volume were measured by 3D transvaginal ultrasound. RESULTS: Total ovarian volume, follicular volume and follicle number correlated positively with serum FSH and LH, but not testosterone, concentrations. Ovarian stromal volume correlated strongly with total ovarian volume only, but not with serum FSH, LH or testosterone concentrations. CONCLUSIONS: These findings demonstrate an association of the total ovarian volume, pre-antral follicle number and total follicular volume with some of the biochemical indices of PCOS, but no association was observed between ovarian stromal volume and these indices.     

Ovarian stromal blood flow in the prediction of ovarian response during in vitro fertilization treatment

BACKGROUND: This study evaluated the role of ovarian stromal blood flow in the prediction of the ovarian response of infertile women by comparing age of women, body mass index (BMI), basal FSH concentration, antral follicle count (AFC) and ovarian stromal blood flow indices measured by power Doppler in two-dimensional ultrasound. Patients were aged <40 years with basal FSH <10 IU/l on recruitment for IVF treatment. METHODS: All received a standard regimen of ovarian stimulation in their first IVF cycle. AFC, pulsatility index, resistance index and peak systolic blood flow velocity of ovarian stromal vessels were determined on the second day of the treatment cycle prior to ovarian stimulation. Ovarian response was represented by the number of oocytes, serum oestradiol, and the duration and dosage of gonadotrophins. RESULTS: A total of 136 women were included in the analysis. Basal FSH concentration achieved the best predictive value in relation to the number of oocytes obtained, followed by AFC and BMI. AFC was the only predictive factor of serum oestradiol concentration on the day of HCG while BMI was predictive of the gonadotrophin dosage. CONCLUSION: Ovarian stromal blood flow indices measured by power Doppler ultrasound had no predictive value for the ovarian response.     

Effect of age on ovarian stromal flow measured by three-dimensional ultrasound with power Doppler in Chinese women with proven fertility

BACKGROUND: Increasing age is associated with reduced ovarian stromal blood flow detected by three-dimensional (3D) power Doppler ultrasound in infertile patients. However, little information exists in the literature regarding the effect of age on the ovarian stromal blood flow in fertile women. METHODS: On the second to fourth day of their menstrual cycle, fertile Chinese women who had regular monthly cycles and no history of tubal and ovarian surgery underwent a transvaginal scan with 3D power Doppler to determine total antral follicle count (AFC), total ovarian volume, total ovarian vascularization index (VI)/flow index (FI)/vascularization flow index (VFI). Serum FSH and vascular endothelial growth factor concentrations were checked. RESULTS: Out of 177 women scanned, 138 women were included in the final analysis. Total AFC and serum FSH were significantly different among four age groups (< or = 30, 31-35, 36-40 and > or = 41 years). Total ovarian VI and VFI were significantly lower in women aged > or = 41 years. AFC had the best correlation with the age of women, followed by serum FSH concentration and ovarian 3D power Doppler indices. The rate of decline of total ovarian VI was 0.18% per year. CONCLUSION: Ovarian stromal blood flow was significantly reduced only in women aged > or = 41 years.     

Colour Doppler analysis of ovarian and uterine arteries in women with hypoestrogenic amenorrhoea

BACKGROUND: This is a clinically-controlled study designed to investigate uterine and ovarian blood flow in patients with hypoestrogenic amenorrhoea. METHODS: Twelve women with hypoestrogenic amenorrhoea and 13 eumenorrhoeic subjects (controls) were enrolled. Colour and pulsed Doppler was used to visualize the uterine and ovarian arteries and the blood vessels within the ovarian stroma in both groups. Four blood flow indices were calculated: the pulsatility index, the resistance index, the peak systolic velocity and the end-diastolic velocity. RESULTS: Peak systolic velocity underwent the most significant change in amenorrhoeic patients, being significantly lower in comparison with that of controls, both in the uterine (P = 0.0009) and ovarian (P = 0.001) arteries. Compared with controls, the end-diastolic velocity of the ovarian artery was significantly lower (P = 0.039) in amenorrhoeic patients, and was also lower in the uterine artery (though not statistically significantly so). A reduction in blood flow was also evident in the ovarian stroma in amenorrhoeic patients. CONCLUSIONS: The significant reduction in blood flow observed in hypoestrogenic amenorrhoea suggests that estrogens play an important role in regulating both uterine and ovarian blood flow.     

Serum anti-Müllerian hormone levels remain high until late reproductive age and decrease during metformin therapy in women with polycystic ovary syndrome

BACKGROUND: Anti-Müllerian hormone (AMH) is secreted by granulosa cells of ovarian early developing follicles and its serum levels have been shown to correlate with small antral follicle number. Since the pronounced androgen secretion from follicles/stroma in women with polycystic ovary syndrome (PCOS) remains until late reproductive age, and since AMH reflects the number of antral follicles, it was of interest to study the possible age-related relationship between AMH, androgens and follicle number in women with PCOS and in control women. Moreover, the possible effect of metformin on serum AMH levels and the relationship to follicle count and volume were studied. METHODS: Forty-four healthy women (aged 21-44 years) and 65 women with previously diagnosed PCOS (aged 16-44 years) participated in the study. Serum basal AMH levels were correlated with those of serum androstenedione, testosterone, estradiol (E2), LH, FSH and inhibin B, and with follicle number. The effect of metformin on serum AMH concentrations, follicle number and ovarian volume was studied in 26 women (aged 20-41 years) with PCOS after 6 months of treatment. RESULTS: Serum AMH levels were 2- to 3- fold higher in PCOS women than in healthy women. In control women, serum AMH levels correlated positively with those of serum androstenedione (r = 0.564, P < 0.001) and testosterone (r = 0.328, P = 0.036) and negatively with serum FSH concentrations (r = -0.374, P = 0.012) and age (r = -0.691, P<0.001). In women with PCOS, serum AMH levels correlated positively with those of androstenedione (r = 0.311, P = 0.011) and testosterone (r = 0.310, P = 0.011) and with follicle count (r = 0.352, P = 0.012), and negatively with age (r = -0.300, P = 0.014). Serum AMH levels, the number of antral follicles and ovarian volume decreased significantly during metfromin treatment. CONCLUSIONS: Serum AMH levels decreased with age both in healthy women and in women with PCOS, although they were always 2- to 3-fold higher and remained elevated until 40 years of age in PCOS subjects. Thus, since serum AMH levels correlate well with antral follicle count and serum androgen levels, the measurement of AMH could be used as a tool to assess ovarian ageing, to diagnose polycystic ovaries/PCOS and to evaluate treatment efficacy.     

Quantification of ovarian stromal Doppler signals in postmenopausal women receiving hormone replacement therapy

OBJECTIVE: To investigate the effect of continuous-combined hormone replacement therapy (HRT) on ovarian circulation, we used three-dimensional power Doppler ultrasound to assess ovarian stromal blood flow in postmenopausal women. DESIGN: Forty healthy, postmenopausal women were enrolled in this prospective, controlled study. They were divided into two groups: the control group (20 patients with no HRT treatment) and the HRT group [initially 20 patients, but later 15 patients who completed the study, using continuous-combined conjugated equine estrogen (0.625 mg/day) plus medroxyprogesterone (5 mg/day)]. All patients underwent transvaginal three-dimensional power Doppler ultrasonography at the time of recruitment and 3 months later. The ovarian stromal flow indices, including vascularization-flow index (VFI), flow index (FI), and vascularization index (VI), were measured. Blood withdrawals for serum follicle-stimulating hormone and estrogen level testing were obtained before and after 3 months of treatment. RESULTS: All the variables in the hormone profile showed significant difference (P < 0.05) after 3 months of treatment in the HRT group. Of interest, the three-dimensional power Doppler indices of ovarian stromal flow, VFI (0.13 +/- 0.11 --> 0.59 +/- 0.49), FI (30.47 +/- 12.06 --> 38.41 +/- 10.21), and VI (0.31 +/- 0.27 --> 1.12 +/- 0.95) all showed significant increase (P < 0.05) after 3 months of HRT treatment. CONCLUSIONS: There was a significant increase in ovarian stromal flow indices after 3 months of treatment in the HRT group, but not in the controls. Monitoring the ovarian flow changes by three-dimensional power Doppler may be of clinical importance when HRT is given.     

Prevalence of polycystic ovaries in women with self-reported symptoms of oligomenorrhoea and/or hirsutism: Northern Finland Birth Cohort 1966 Study

BACKGROUND: The aim of this study was to investigate the prevalence of polycystic ovaries (PCO) among women with self-reported oligomenorrhoea and/or hirsutism and to see whether women with symptoms and PCO have less favourable levels of biochemical markers than controls or women with symptoms and normal ovaries. METHODS: The ultrasonographic ovarian morphology and the hormonal and metabolic profile of female cases with self-reported symptoms typical of polycystic ovary syndrome (PCOS) (n = 196) and asymptomatic controls (n = 67) at the age of 31 years were examined in a general population-based Northern Finland Birth Cohort 1966. RESULTS: The prevalence of PCO (37.3 versus 18.2%; P = 0.004) was significantly higher in the cases (oligomenorrhoea and/or hirsutism) than in the controls. PCO morphology was detected in 18.4% of those who reported only hirsutism, in 47.9% of those reporting only oligomenorrhoea, and in 70.4% of those reporting both symptoms. In the cases with PCO compared to (i) the controls and (ii) the cases without PCO, body mass index (P = 0.026 and P = 0.011), ovarian volume [right P = 0.001, left P = 0.208 (non-significant) and right P < 0.001, left P = 0.022], mean follicle number (P < 0.001 and P < 0.001), testosterone (P = 0.063 and P = 0.029), free androgen index (P = 0.007 and P = 0.013) and insulin (P = 0.033 and P = 0.040) were higher, and sex hormone-binding globulin (P = 0.039 and P = 0.068) and glucose:insulin ratio (P = 0.060 and P = 0.054) lower. Cases with PCO also had higher waist:hip ratio (P = 0.011), infertility rate (P = 0.005) and glucose (P = 0.045) and lower insulin-like growth factor-binding protein-1 (P = 0.012) than controls. The clinical, hormonal and metabolic characteristics did not differ significantly between cases without PCO and controls with the exception of infertility rate, which was significantly higher in the cases without PCO (26.4 vs. 10.0%; P = 0.009). CONCLUSIONS: In a general population, women with symptoms of oligomenorrhoea and/or hirsutism more often have PCO than asymptomatic women. Levels of biochemical and clinical markers in symptomatic women with PCO differed from and were less favourable than those in symptomatic women without PCO or asymptomatic women, implying an increased risk for health.     

Diurnal variation in uterine artery blood flow in post-menopausal women on oestrogen hormone replacement therapy.

Doppler ultrasound was used to investigate circadian variations in uterine artery blood flow in 20 post-menopausal women in the oestrogen-only phase of combined oestrogen hormone replacement therapy with cyclical oral norethisterone or dydrogesterone. All women were examined between 0800 and 0830 h and then again between 1800 and 1830 h on the same day. Mean arterial blood pressure, heart rate and a blood sample for measurement of serum oestradiol were taken at each visit. Indices of uterine artery blood flow included the pulsatility index, resistance index, peak systolic velocity and time-averaged maximum velocity. No significant differences in the mean arterial blood pressure, pulse rate and oestradiol concentrations were detected between morning and evening visits. Significant fluctuation was observed in the pulsatility index (P < 0. 001), resistance index (P < 0.001) and time-averaged maximum velocity (P < 0.01). The assessment of uterine artery blood flow in post-menopausal women should take into account the presence of circadian variations to ensure accuracy and reproducibility of Doppler investigations.     

Relationship of ovarian stromal volume to serum androgen concentrations in patients with polycystic ovary syndrome

The aim of this study was to investigate of the relationship of ovarian stromal volume, measured using three-dimensional ultrasound, to serum androgen concentrations in patients with polycystic ovaries. Serum gonadotrophin, oestradiol and androgen concentrations and ovarian volume measurements were obtained in the early follicular phase from 100 women undergoing assisted conception treatment cycles. Group 1 contained 50 women with regular menstrual cycles and normal ovarian morphology, group 2 contained 24 women with regular menstrual cycles and polycystic ovaries seen on ultrasound scan and group 3 contained 26 women with polycystic ovary syndrome. Statistical analysis included analysis of variance, Scheffe's procedure and Pearson's correlation. Total ovarian volume (15.7-16.1 versus 11 ml, P < 0.05), stromal volume (14.5 versus 9.4 ml, P < 0.05) and thecal steroid concentrations were significantly greater in groups 2 and 3. Stromal volume was positively correlated with serum androstenedione concentrations (r = 0.45, P = 0.0019 in group 3) but was not correlated with any other endocrine parameter. It was concluded that polycystic ovaries are characterized by increased ovarian stroma with associated overproduction of theca- derived steroids, particularly androstenedione.      

Do young women with polycystic ovary syndrome show early evidence of preclinical coronary artery disease?

BACKGROUND: It is thought that women with polycystic ovary syndrome (PCOS) are at increased risk of developing cardiovascular diseases. METHODS: In this study, we used transthoracic echocardiography to measure coronary flow reserve (CFR) in 28 women with PCOS and in 26 healthy women. RESULTS: The PCOS and the control groups were similar in terms of age (27.1 +/- 4.5 versus 28.8 +/- 4.4 years) and BMI (26.6 +/- 5.7 versus 24.7 +/- 4.4 kg/m2). Fasting insulin levels and homeostasis model assessment insulin resistance index were higher in the PCOS group. LH, the LH/FSH ratio, total testosterone, free testosterone and androstenedione were higher in the PCOS group. FSH, estradiol, prolactin, progesterone, cholesterol, triglyceride and high-sensitive C-reactive protein were similar between the two groups, but homocysteine levels were higher in the PCOS group. Baseline diastolic peak f low velocity (DPFV) (25.0 +/- 4.6 versus 23.3 +/- 2.7 cm/s, P > 0.05), hyperaemic DPFV (71.2 +/- 12.8 versus 73.0 +/- 12.9 cm/s, P > 0.05) and CFR (2.8 +/- 0.8 versus 3.2 +/- 0.8 cm/s, P > 0.05) of the left anterior descending coronary artery were similar between the two groups. CONCLUSION: We conclude that in young women with PCOS and without cardiovascular risk factors, CFR is preserved.     

A comparative randomized multicentric study comparing the step-up versus step-down protocol in polycystic ovary syndrome

BACKGROUND: The aim of the study was to evaluate follicular development and ovulation comparing the low-dose step-up and the step-down protocols, in women with clomiphene citrate (CC)-resistant polycystic ovaries. METHODS: Eighty-three women were randomized, and treated with recombinant (r) FSH (Puregon) using either the step-up (n=44) or step-down (n=39) protocol. They were followed up for three cycles unless pregnancy occurred. RESULTS: Monofollicular development occurred in 68.2% of the 85 cycles in the step-up group, as compared with 32% of the 72 cycles in the step-down group (P<0.0001). Hyperstimulation was statistically less frequent using the step-up procedure (4.7 versus 36%, P<0.0001). Both protocols used the same number of FSH units per cycle (951+/-586 versus 967+/-458 in step-up and step-down respectively, P=not significant). However, the duration of ovarian stimulation was statistically different (15.2+/-7.0 days in step-up versus 9.7+/-3.1 in step-down, P<0.001). Ovulation was observed in 70.3% of the cycles using the step-up procedure as compared with 51.3% using the step-down procedure (P<0.01). The cumulative rate of clinical gestations during the study did not differ between the two groups (38.6% in the step-up versus 30.8% in the step-down procedure). CONCLUSIONS: The step-up protocol using rFSH (Puregon), is more efficient in obtaining a monofollicular development and ovulation than the step-down protocol, in women with CC-resistant polycystic ovaries. Although the duration of stimulation is longer, the rate of ovarian hyperstimulation is much lower using the step-up protocol.