Christopher V. Steer

Transvaginal colour flow imaging: a possible new screening technique for ovarian cancer.

OBJECTIVE--To assess whether changes in the intraovarian vasculature or blood flow impedance can be used to identify potentially malignant masses. DESIGN--Open, non-comparative prospective study. SETTING--Ovarian screening clinics at Kings College Hospital and the Hallam Medical Centre. SUBJECTS--50 Women selected on the basis of their medical history and the result of a previous transvaginal ultrasound scan. Thirty women (10 premenopausal (scan taken on days 1 to 8 of the menstrual cycle) and 20 postmenopausal) had normal ovaries, and 20 had at least one ovary with an abnormal morphology or volume, or both. INTERVENTIONS--Women with a positive result on screening were referred for laparotomy. MAIN OUTCOME MEASURES--Presence or absence of coloured areas (neovascularisation) and the pulsatility index within each ovary. The pulsatility index is a measure of the impedance to blood flow, a low value indicating decreased impedance and a high value increased impedance to blood flow. RESULTS--Two women with a positive result on screening had hydrosalpinges, 10 a benign tumour or a tumour-like condition, and eight primary ovarian cancers. No areas of neovascularisation were seen in the 30 women with morphologically normal ovaries and the two patients with hydrosalpinges; the pulsatility index ranged from 3.1 to 9.4. Similarly, nine patients (10 affected ovaries) with a non-malignant mass had no signs of neovascularisation and the pulsatility index varied from 3.2 to 7.0. One patient with bilateral dermoid cysts containing nests of thyroid-like cells had vascular changes and pulsatility index values of 0.4 and 0.8. Seven patients (eight ovaries) with primary ovarian cancer (one stage IV, four stage II, and two stage Ia) showed clear evidence of neovascularisation and pulsatility index values were from 0.3 to 1.0. One patient with an intraepithelial serous cystadenocarcinoma in a small ovary (less than 5 ml volume) had no signs of any vascular change and the pulsatility index was 5.5. CONCLUSION--Transvaginal colour flow imaging may be used to identify potentially malignant ovarian masses and help elucidate the early stages of tumorigenesis. The routine application of this technique may reduce the rate of false positive results of an ultrasonography based screening procedure.

Vaginal color Doppler assessment of uterine artery impedance correlates with immunohistochemical markers of endometrial receptivity required for the implantation of an embryo

OBJECTIVE To investigate the correlation between uterine artery impedance with immunohistochemical histologic, and ultrasonographic markers of uterine receptivity. DESIGN A prospective study of subfertile women undergoing a frozen embryo replacement cycle. SETTING A tertiary infertility clinic. PATIENTS The study was based on 86 patients who had failed to become pregnant during a standard IVF treatment cycle and who had at least two good quality embryos cryopreserved. INTERVENTIONS All patients had pituitary desensitization with the GnRH analogue buserelin acetate, followed by E2 and P replacement therapy. Vaginal color Doppler images of both uterine arteries were obtained on days 7, 14, and 21 of the first (trial) cycle. On day 21, an endometrial biopsy was taken for dating a 24-kd protein, placental protein 14, and E2 receptor assessment. After a menstrual bleed had been induced, administration of estrogen and P was reinstituted and embryos transferred to the uterus on the 3rd or 4th day of P administration. MAIN OUTCOME MEASURES The mean pulsatility index of the left and right uterine arteries, a semiquantitative score of endometrial 24-kd protein, PP14, and E2 receptor assessment, endometrial histologic dating, and pregnancy outcome. RESULTS Nineteen of 76 patients who had a successful ET became pregnant. The pulsatility index on day 14 of both the trial and ET cycles was significantly lower in those who achieved pregnancy as compared with those who did not conceive: 2.65 (range 1.3 to 3.4) versus 3.85 (1.8 to 6.8) and 2.85 (1.4 to 3.6) versus 4.15 (2.1 to 6.8), respectively. There were significant correlations between pulsatility index and 24-kd protein, E2 receptor, and endometrial histology but not with PP14 and endometrial thickness. CONCLUSIONS Uterine artery impedance has a significant correlation with biochemical markers of uterine receptivity and accurately predicts the probability of pregnancy in frozen embryo replacement cycles. It is a useful method for assessing uterine receptivity in assisted conception programs.

Detection of endometrial cancer by transvaginal ultrasonography with color flow imaging and blood flow analysis: a preliminary report

A prospective study was undertaken to assess whether changes in uterine blood flow could be used to detect endometrial cancer in 138 selected postmenopausal women (34 had uterine bleeding, 17 with endometrial cancer; 104 did not have uterine bleeding; 1 had endometrial cancer). Thirty-five of the asymptomatic women were receiving estrogen replacement therapy (ERT). The endpoints were endometrial (including tumoral) thickness and a pulsatility index (PI) derived from flow velocity waveforms recorded from both uterine arteries and from within a tumor. We found an overlap in endometrial thickness between those women with endometrial cancer and those without. The mean arterial PI value was invariably lower in women with postmenopausal bleeding and endometrial cancer (mean 0.91, range 0.31-1.49) than in those with other reasons for the blood loss (mean 3.83, range 1.95-6.40). The index was 1.10 in the woman with endometrial cancer but no sign of postmenopausal bleeding. Blood flow impedance was inversely related to stage of cancer. PI values in healthy women tended to increase slightly with age, but decrease during ERT. The detection rate was 100% within the limitations of the study design, and the false-positive rate was 1% for all women not receiving ERT and 11% for patients receiving ERT. Malignant tumors show signs of altered vascularization and a low PI (mean 0.49, range 0.29-0.92). We conclude that transvaginal ultrasonography, with or without color flow imaging, and blood flow analysis can be used to detect endometrial cancer in women with postmenopausal bleeding. A screening procedure for asymptomatic women must allow for changes in uterine blood flow during ERT.

Detection of endometrial cancer in postmenopausal women by transvaginal ultrasonography and colour flow imaging.

About 3700 new cases of endometrial cancer are reported in the United Kingdom each year. The incidence of the disease increases considerably during the fifth decade of life and reaches a peak between the ages of 60 and 65. Uterine bleeding is the most common initial symptom after the menopause and necessitates invasive investigation (for example, dilatation and curettage). About a tenth of women with postmenopausal bleeding have endometrial cancer. A less invasive technique with a high rate of detection of the disease and a low rate of false positive diagnoses would be of value for selecting those women who require diagnostic surgery. Pelvic ultrasonography yields detailed images of the uterus. Although a thick endometrium may be a sign of pathological processes, no morphological features that are unique to malignant disease have been identified.1 Recently the use of transvaginal pulsed Doppler probes, with and without colour flow imaging, has shown that uterine blood flow changes during the menstrual cycle.2 Furthermore, trans vaginal ultra? sonography with colour flow imaging has shown that the presence of intratumoral vascularisation with a low impedance to blood flow can be used as an end point in screening programmes for early ovarian cancer.34 We report the use of these techniques to measure the impedance to uterine arterial and intra? tumoral blood flow and hence detect endometrial cancer in women with postmenopausal bleeding.

Ovarian cyst aspiration and the outcome of in vitro fertilization

This study was designed to ascertain whether any benefit would be derived from aspirating ovarian cysts identified before ovarian stimulation in patients undergoing in vitro fertilization. Thirty-seven patients who had ovarian cysts were categorized into two groups: group A (n = 14) with baseline ovarian cysts and group B (n = 23) with ovarian cysts that developed during pituitary suppression with the gonadotropin-releasing hormone analog. Each group was prospectively randomized into two subgroups depending on whether the ovarian cysts were aspirated or not. In group A, there was a significantly greater number of follicles and oocytes in the ovaries in which cysts were aspirated. However, there was no significant difference in the total number of follicles, oocytes retrieved and fertilized, or in the final outcome. In group B, there was no significant difference in folliculogenesis between the aspirated and nonaspirated subgroups. These observations suggest that the presence of a baseline ovarian cyst may reduce folliculogenesis but do not support routine cyst aspiration if the patient has two functional ovaries.

The clinical outcome of reinsemination of human oocytes fertilized in vitro

To assess the value of reinseminating human oocytes, the results of 1,662 embryo transfers were analyzed. In 1,460 transfers embryos arose from oocytes that had fertilized and cleaved after initial insemination. The pregnancy rate was significantly higher than in transfers of embryos (n = 76) resulting solely from reinseminated oocytes (27% versus 3%). Adding reinseminated embryos to those fertilizing on initial insemination at transfer failed to raise the pregnancy rate. Only 2 of 158 (1.3%) reinseminated embryos implanted compared with 540 of 4,181 (12.9%) fertilized and cleaved on initial insemination (P less than 0.001). Reinseminated embryos do occasionally produce viable pregnancies. It is therefore worth considering replacement of these embryos if initial fertilization has entirely failed. Patients should be counseled as to the low chance of implantation with these embryos.

Outcome of triplet pregnancies resulting from IVF at Bourn Hallam 1984-1987.

43 consecutive sets of triplet pregnancies progressing beyond 16 weeks and conceived following in vitro fertilisation at the Bourn Hallam Centre between 1984-1987 were included in the study. Follow-up information was available in the 31 sets born to United Kingdom residents. 91 live births resulted at an average gestation of 33 weeks and 2 days (range 26-38 weeks). All but one of the deliveries was by Caesarean section. The average birth weight was 1.85 kg and was significantly higher in the first-born triplet than in the third (1.93 kg versus 1.74 kg, respectively). The perinatal mortality rate amongst the triplets was 32.26 per thousand births, and the neonatal death rate was 21.98 per thousand live births. This compares favourably with the latest published data on perinatal mortality rates in triplets.

Transvaginal peritoneal oocyte and sperm transfer for the treatment of nontubal infertility

OBJECTIVE To investigate if peritoneal oocyte and sperm transfer (POST) performed transvaginally is an effective treatment for nontubal infertility. DESIGN, SETTING, AND PATIENTS Prospective study of 18 patients (4 with unexplained infertility, 13 with failed donor insemination, and 1 with male factor infertility) having 20 cycles of transvaginal POST in a specialist infertility unit. INTERVENTIONS Ovarian stimulation was achieved with human menopausal gonadotropin (hMG) alone, hMG and clomiphene citrate, or gonadotropin-releasing hormone agonist with hMG. Oocyte recovery was performed transvaginally under ultrasound guidance, the pouch of Douglas rinsed repeatedly and an embryo transfer catheter used to transfer 4 x 10(6) progressively motile sperm in 1 mL and up to four oocytes into the pouch of Douglas. Luteal support was provided with human chorionic gonadotropin injections given 2 and 5 days later. RESULTS The mean age of the patients was 32.65 +/- 5.0, and the mean length of infertility 5.07 +/- 2.32 years. The mean number of oocytes transferred was 3.53 +/- 0.87. Three pregnancies were achieved in the failed donor insemination group and 1 each in those with unexplained and male factor infertility, giving overall clinical pregnancy and live birth rates of 25% and 20% per initiated cycle. All pregnancies were achieved in those who had three or four oocytes transferred. CONCLUSION Transvaginal POST is a useful assisted conception technique for the treatment of nontubal infertility.

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.