Timothy J.B. Crayford

Differential effects of transdermal estradiol and sequential progestogens on impedance to flow within the uterine arteries of postmenopausal women

OBJECTIVE To investigate the relationship between estradiol (E2), progestogen, and impedance to blood flow in the uterine artery. SUBJECTS Twelve postmenopausal women treated for two cycles with transdermal E2, 0.05 mg/d, with either norethindrone acetate, 0.7 mg, or medroxyprogesterone acetate, 10 mg added sequentially. MEASUREMENTS Transvaginal ultrasonography and color flow imaging were used to measure the pulsatility index in the uterine arteries before and during the E2-only and combined E2/progestogen phases. RESULTS The mean pulsatility index fell to 53% of its pretreatment value within 12 days E2 administration (P < or = 0.0001) and was 66% of its pretreatment value in the combined phase (P < 0.005). Similar changes were seen in cycle 2. Time since menopause was correlated with the pretreatment pulsatility index (r = 0.674, P < 0.05) and change in pulsatility index on treatment (r = 0.856, P < 0.001). CONCLUSION Gonadal hormones have a profound effect on arterial tone in postmenopausal women; this action may help explain some of the beneficial effects of estrogen on arterial disease risk.

Effects of indomethacin on follicular structure, vascularity, and function over the periovulatory period in women * †

OBJECTIVE To assess the effect of indomethacin (taken at defined times) on follicular rupture, indexes of intrafollicular blood flow, and steroidogenesis. PARTICIPANTS Six healthy volunteers awaiting treatment for infertility by IVF-ET during subsequent natural cycles. INTERVENTIONS All women were examined (at least every 8 hours) by transvaginal ultrasonography with color Doppler imaging and had samples of blood taken for hormone analysis. A self-test for urinary LH was performed before each scan. Indomethacin was first taken (50 mg three times per day) according to the maximum follicular diameter (first four women) or when the LH dipstick gave a positive result; the drug was taken for > or = 3 days. RESULTS Follicular rupture was delayed in five of six cases (by 2 to 12 days). There was a reduction in intrafollicular peak systolic velocity before and after the positive urinary LH test compared with historical controls. Three follicles (50% of women) with the highest peak systolic velocity had an hemorrhagic appearance and persisted longer. There was no significant effect on menstrual cycle length or the levels of circulating FSH, E2, LH, or P. CONCLUSION Indomethacin administered at the time of a positive self-test for urinary LH can delay follicular rupture with an associated reduction in intrafollicular blood flow but with no apparent effects on hormonal or menstrual status.

Screening for early familial ovarian cancer with transvaginal ultrasonography and color blood flow imaging

BMJ 1993;306:1025-9 Abstract Objective?To assess the value of transvaginal ultrasonography with colour blood flow imaging in detecting early ovarian cancer in women with a family history of the disease. Design?Study of self referred symptomless women with a close relative who had developed the disease. Each woman was screened to detect per? sistent lesions and defined changes in ovarian volume. Morphological score and pulsatility index were recorded. Setting?Ovarian screening clinic. Subjects?1601 self referred women. Interventions?Women with a positive screening result were recommended to have further investi? gations. Main outcome measures?Findings at surgery and histology of abnormal ovaries. Morphological score ^ 5 and pulsatility index < 1 *0 at last scan. Results?Women were aged 17 to 79 (mean 47) years; 959 (60%) were premenopausal, 469 (29%) were naturally postmenopausal, and 173 (11%) had had a hysterectomy. 157 women had a pedigree suggestive of the site specific ovarian cancer syn? drome and 288 of multiple site cancers. 61 women had a positive screening result (3*8%, 95% confidence interval 2*9 to 4*9%), six of whom had primary ovarian cancer detected at surgery (five stage la, one stage III). Use of a high morphological score or a low pulsatility index increased the odds of finding ovarian cancer from 1:9 to about 2:5 (1:1 in the highest risk groups). Five interval cancers were reported (three ovarian and two peritoneal). Eight of the 11 cancers developed in women with pedigrees suggestive of inherited cancer. Conclusions?Transvaginal ultrasonography with colour flow imaging can effectively detect early ovarian cancer in women with a family history of the disease. The screening interval should be less than two years.

The potential role of serum CA 125 in an ultrasound‐based screening program for familial ovarian cancer

We have assessed the potential role of a test based upon the measurement of serum CA 125 in an ultrasound-based screening program for familial ovarian cancer. A sample of peripheral blood was taken from 1502 self-referred, asymptomatic women whose pedigree showed that at least one close relative had developed the disease. All women in the study underwent one screening by transvaginal ultrasonography (consisting of one or more scans) to detect any persistent lesion and a change in ovarian volume. Women with a positive result were referred for surgery. The concentration of serum CA 125 was measured in all samples at the end of the study. Seven ovarian cancers (4 invasive and 3 of borderline malignancy; 5 FIGO stage Ia, 1 stage IIa, 1 stage III) and 55 benign lesions were detected. We calculated the effect that a prescreening test (based on different threshold values for serum CA 125) would have had on the number of women entering the ultrasound-based screening program, and on the detection rate and false-positive rate of the overall procedure. There was a direct relationship between the number of women referred for ultrasound screening and the detection rate. The use of a threshold value for serum CA 125 > or = 20 U/ml would have meant that 380 women (25.3%) were referred for ultrasonography and 5 out of 7 cancers (71%) would have been detected with a false-positive rate of 1.1%. The odds of a woman with a positive screening result having cancer at surgery would have been about 1:3 (which would improve to about 1:1 if observational indices of color Doppler imaging and a morphological score had been used throughout). We concluded that a prescreening immunochemical test based on the measurement of serum CA 125 (with a threshold value of > or = 20 U/ml) would increase the prior odds for familial ovarian cancer by 2.8, but would lower the overall detection rate by 29% at the prevalence screening.

Transvaginal color blood flow imaging of the periovulatory follicle

OBJECTIVE To assess intrafollicular blood flow in relation to ovarian morphology and function during the periovulatory period. DESIGN A prospective, longitudinal study of random, natural ovarian cycles. SETTING The Ovarian Screening Clinic and Endocrine Laboratory of the Department of Obstetrics and Gynaecology, Kings College Hospital, London, United Kingdom. PATIENTS Women with apparently normal ovarian function awaiting treatment for infertility by IVF-ET during subsequent natural cycles. INTERVENTIONS All women were examined by transvaginal ultrasonography with color flow imaging and had a sample of peripheral venous blood taken at each scan for hormone analysis. MAIN OUTCOME MEASURES The minimum pulsatility index (PI) and maximum peak systolic velocity from vessels within the dominant follicle; the maximum follicular diameters (and hence volume); serum FSH, E2, LH, and P. RESULTS The dominant follicle ruptured in 10 of 11 women. The median interval between the two scans that delineated the time of follicular rupture was 9.5 hours (range, 0.0 to 24.5 hours). These cycles appeared to be morphologically and endocrinologically normal. There was an apparent increase in intrafollicular blood flow over the periovulatory period with an insignificant trend toward lower values for the mean PI and a significant increase in the peak systolic velocity. These changes appeared to follow the rise in circulating LH. CONCLUSION Indexes of blood flow at a given site within the leading follicle can be monitored by transvaginal ultrasonography with color Doppler imaging over the periovulatory period. The increase in the peak systolic velocity and the relatively constant PI suggest a marked increase in blood flow at this time during the ovarian cycle.

The use of transvaginal color flow imaging after in vitro fertilization to identify optimum uterine conditions before embryo transfer**Presented at the 46th Annual Meeting of The American Fertility Society, Washington D.C., October 6 to 11, 1990.

OBJECTIVE To assess whether a measure of uterine blood flow impedance (the pulsatility index, PI) as determined by transvaginal ultrasonography with color blood flow imaging, may be used to assess endometrial receptivity immediately before the time of embryo transfer (ET) after assisted conception. DESIGN A prospective study of infertile women who had undergone treatment to induce multiple follicular development followed by ultrasound-guided oocyte retrieval. The oocytes were fertilized in vitro. SETTING The Hallam Medical Centre. PATIENTS Eight-two women (22 to 44 years of age) who all had three or four good quality embryos available for transfer to the uterus. INTERVENTIONS All women were examined by transvaginal ultrasonography, with color flow imaging and blood flow analysis, immediately before ET. MAIN OUTCOME MEASURES The mean PI of the left and right uterine arteries, the pregnancy rate (PR) (%), the embryo implantation rate (%), and the multiple PR (%). RESULTS The patients were grouped according to whether the PI was low (1.00 to 1.99), medium (2.00 to 2.99), or high (3+). There were 27 women in the low PI group, 36 in the medium, and 19 in the high. The PR (%), embryo implantation rate (%), and multiple PR (%) were 41%, 15.3%, and 27.3% for the low PI group and 47%, 22.2%, and 47.1% for the medium PI group. There were no pregnancies in the high PI group. Thus 35% (19/54) of women who failed to become pregnant had a PI value greater than 3.0. CONCLUSIONS These data suggest that the PI value on the day of ET could be used to: (1) increase the implantation rate by showing which embryos should be cryopreserved until the uterus is more receptive and (2) reduce the multiple PR by indicating that the number of embryos transferred should be limited when the uterus is most receptive.