Follicular and endocrine profiles associated with different GnRH-antagonist regimens: a randomized controlled trial.

This trial assessed the impact of early initiation of gonadotrophin-releasing hormone (GnRH) antagonist on follicular and endocrine profiles compared with the fixed GnRH-antagonist protocol. Eighty-five oocyte donors were randomized to GnRH antagonist starting in the mid-luteal phase of the prestimulation cycle (degarelix-ML group), on stimulation day 1 (early follicular phase, degarelix-EF group) or day 6 (fixed protocol) (mid-follicular phase, ganirelix-MF group). Subjects in the degarelix-EF and ganirelix-MF groups received placebo in the prestimulation cycle. At start of stimulation, serum concentrations of FSH (4.6 ± 2.3 versus 6.0 ± 1.8IU/l), LH (2.7 ± 1.4 versus 4.7 ± 1.9IU/l) and oestradiol (87 ± 35 versus 129 ± 50pmol/l) were markedly lower (P<0.001) in the degarelix-ML group than in the placebo group. The coefficients of variation of follicle size (36.7 ± 5.5% versus 39.2 ± 9.4%) were not significantly different. No differences in endometrial histology, embryo quality and pregnancy rates in recipient cycles were observed between the regimens. In conclusion, early administration of GnRH antagonist altered the endocrine profile without modifying the follicular synchrony for the majority of subjects. Whether patients with a more heterogeneous follicle size at start of stimulation may benefit from an earlier intervention remains to be proven.

Adnexal torsion: color Doppler and three-dimensional ultrasound.

OBJECTIVE: To correlate preoperative ultrasound and color Doppler findings in patients with surgically proven adnexal torsion. MATERIALS AND METHODS: A 5-year retrospective study included 36 patients with acute lower abdominal and/or pelvic pain. Twenty-four patients had complete adnexal torsion followed by adnexectomy. Twelve patients with partially twisted adnexa underwent detorsion and were followed by 3-D power Doppler US 1 and 3 months thereafter. RESULTS: 2-D color Doppler US detected the absence of blood flow signals in the pedicles of 21 patients with complete adnexal torsion. Presence of the arterial blood flow signals within the pedicle alone was detected in three patients and was predictive of a non-viable ovary. The ovarian artery and vein were demonstrated in 10 patients with partial torsion. Venous signals alone were isolated in two patients with partial adnexal torsion. 3-D power Doppler indices of partially twisted adnexa following detorsion have improved significantly 1 (P < 0.05) and 3 months (P < 0.05), respectively, reaching normal intra-ovarian perfusion values. CONCLUSIONS: 2-D color Doppler and 3-D power Doppler US are useful in early diagnosis of complete adnexal torsion and follow-up of the ovarian reperfusion after detorsion of the partially twisted adnexa.

2D and 3D hysterosalpingo-contrast-sonography in the assessment of uterine cavity and tubal patency.

OBJECTIVE: To demonstrate the diagnostic efficacy of 2D B-mode, color and pulsed Doppler Hy-Co-Sy and 3D B-mode and power Doppler Hy-Co-Sy. STUDY DESIGN AND METHODS: One hundred and fifty-two women were recruited into the 2D B-mode, color and pulsed Doppler Hy-Co-Sy study and 116 other women were recruited into the 3D B-mode and power Doppler Hy-Co-Sy study. We assessed the diagnostic performance (sensitivity, specificity, PPV and NPV) of 2D and 3D Hy-Co-Sy, compared to hysteroscopy, and laparoscopy and dye test in the assessment of uterine abnormalities and tubal patency, respectively. RESULTS: The sensitivity, specificity, PPV and NPV of 2D hysterosonography compared to hysteroscopy were 93.6, 97.3, 98.2 and 97.3%, respectively. The sensitivity, specificity, PPV and NPV of 3D hysterosonography compared to hysteroscopy were 97.9, 100, 97.9 and 100%, respectively. Addition of color and pulsed Doppler to 2D Hy-Co-Sy and power Doppler to 3D Hy-Co-Sy contributed to diagnostic precision in detection of tubal patency. The sensitivity, specificity, PPV and NPV of 3D power Doppler Hy-Co-Sy in detection of tubal patency compared to laparoscopy and dye intubation were 100, 99.1, 99.2 and 100%, respectively. CONCLUSION: 2D and 3D Hy-Co-Sy are accurate methods for evaluation of uterine abnormalities and tubal patency in infertile patients.

Assessment of placental vascularization by three-dimensional power Doppler "vascular biopsy" in normal pregnancies.

AIM: To describe the evolution of placental vascularization during a normal course of gestation and the blood flow 3D power Doppler indices obtained by "placental vascular biopsy." METHODS: A prospective study was carried out on 99 normal singleton pregnancies from 14 to 40 weeks. Placental vascularization was evaluated by 3D power Doppler ("placental biopsy"). The spherical volume acquired was analyzed using the VOCAL imaging program (Virtual Organ Computer-aided AnaLysis). Three vascular indices, vascularization index (VI), flow index (FI), and vascularization-flow index (VFI), were calculated. Equations and regression coefficients for placental volume and vascular indices (VI, FI, VFI) of the placental biopsy were calculated according to gestational age. Relationships between 3D placental flow indices and fetal growth parameters: biparietal diameter, head circumference, abdominal circumference, femur length, estimated fetal body weight, maximum systolic velocity (US), and resistance index in the umbilical artery (URI) were evaluated by calculating their correlation coefficients. RESULTS: All 3D Doppler indices had a significant relationship with gestational age. The most significant relationship was observed for FI, and the least significant for VI (r=0.58, r=0.29, respectively; P<0.01 for both). The FI increased linearly with gestation, whereas the VI showed a dispersion of values with a plateau from the 30th week onwards and a decrease from 37th week to the end of pregnancy. The VFI behaved as a combination of both VI and FI indices from which it was derived. All 3D Doppler indices were significantly related to fetal biometric parameters, except VI and fetal weight. A significant correlation was observed between 3D Doppler indices and maximum systolic velocity and URI. CONCLUSIONS: 3D power Doppler technique of placental vascular "biopsy" is an appropriate tool for routine evaluation of the human placental vascular tree during gestation. 3D Doppler indices change as pregnancy progresses and are significantly related with fetal biometry and umbilical artery Doppler velocimetry.

Influence of hormonal stimulation on in vitro fertilization/embryo transfer outcome.

OBJECTIVE: To compare efficacy and efficiency of ovarian stimulation therapy. STUDY DESIGN: Retrospective study compares ovarian response as number of retrieved oocytes, fertilization rates, endometrial patterns, number of pregnancies and pregnancy rates to different stimulation protocols. RESULTS: The least number of cancelled cycles was in long protocols with buserelin. There was no difference in overall number of retrieved oocytes between the rFSH and HMG protocols, but 75% of the patients undergoing both protocols had higher number of oocytes after rFSH. The highest pregnancy rate (35.13%) was with rFSH. There was no statistical correlation between endometrial pattern and type of protocol used. Data showed the 9 mm cut-off value for endometrial thickness, and RI = 0.58 for subendometrial blood flow between the pregnant and non-pregnant group of patients. Nitriderm patches significantly decreased (P < 0.05) subendometrial RI of the patients with impaired uterine perfusion, increased endometrial thickness and achieved better morphology. CONCLUSIONS: These findings demonstrate that rFSH alone and in long protocol gives better results in wide patient population. Nitriderm patches seem to have good impact on pregnancy rate, but further studies are necessary before making any statements.

Vaginal aplasia associated with anatomically and functionally normal uterus.

Maldevelopment of the vagina is usually combined with aplasia/hypoplasia of the uterus. Complete vaginal aplasia with a normally developed uterus and cervix is an extremely rare form of developmental failure. The accepted treatment for this kind of maldevelopment is hysterectomy plus creation of a neovagina. We present the case of 12-year-old girl with isolated complete vaginal aplasia. After the creation of a vagina during a first procedure and lysis of pericervical adhesions with implantation of skin graft in a second she now has regular menstrual bleeding.

B- and T-cells in the follicular fluid and peripheral blood of patients undergoing IVF/ET procedures.

PROBLEM: To analyse percentage of total and memory CD27(+) B-cells and other lymphocyte subpopulations in the peripheral blood (PB) and follicular fluid (FF) of infertile married couples. METHOD OF STUDY: Forty-eight couples from in vitro fertilization/embryo transfer (IVF/ET) programme were divided into four groups: patients with previous unsuccessful fertilization (n = 13), ectopic pregnancy (n = 8), multiple (at least three) failed IVF/ET (n = 18) and missed abortions (n = 9). Control group consisted of 15 married couples with healthy children. RESULTS: PB memory CD27(+) B-cells were significantly decreased in all groups of infertile patients compared with controls. First group had increased memory B-cells percentages compared with the second group. The differences in the percentages of PB memory B-cells in third and fourth group compared with the first group were not statistically significant. FF memory B-cells in the first and third group were significantly increased compared with second and fourth group. The percentage of total FF B-cells in all groups were significantly decreased compared with their percentage in PB. Male partners of women from the first group had had significantly increased percentages of memory B-cells compared with the partners of women from the second group. Percentage of total T- and B-cells, CD4+ and CD8+ T-cells, NK cells and activated HLA-DR(+) T-cells in all groups were not significantly different from controls. We found no statistically significant difference between immunoglobulin E levels in all groups of patients. We found lower levels of IgA and IgM in FF compared with serum in all groups. CONCLUSION: Infertile patients have significantly decreased percentage of CD27(+) B-cells in the PB. Abnormalities in the memory B-cell compartment may contribute to the pathogenesis of infertility. In the T-cell compartment abnormalities were not detected. It appears that hormonal stimulation did not influence cellular immunity parameters.

The detection of stage I ovarian cancer by three-dimensional sonography and power Doppler.

OBJECTIVE: The objective was to determine the diagnostic accuracy of three-dimensional (3D) sonography and 3D power Doppler imaging, used together with standard 2D transvaginal grayscale and color/power Doppler modalities, for preoperative sonographic assessment of suspected ovarian lesions. METHODS: Five-year retrospective analysis was performed by our experts on ultrasonography and surgery on the reports from 43 referred patients with suspected stage I ovarian cancer. All patients were evaluated during the week prior to surgery at our department. Preoperative sonographic assessment included careful examination of ovarian volume, morphology, and vascularity by four complementary sonographic methods. Scoring systems combining morphological and Doppler parameters were adopted for 2D and 3D sonographic examinations. Final diagnosis was confirmed by a histopathologist. RESULTS: Out of the 43 stage I ovarian cancers, 42 cases were successfully detected preoperatively by four complementary sonographic methods. Only 30 (69.8%) and 37 (86.1%) cases of stage I ovarian cancer were detected by 2D grayscale and combined 2D grayscale and color Doppler sonography, respectively. Morphological analysis obtained by 3D sonography alone detected 32 of 43 ovarian malignancies, reaching a diagnostic rate of 74.4%. Qualitative analysis of tumor vascularity architecture by 3D power Doppler significantly improved the sonographic management process and successfully detected 41 cases of stage I ovarian cancer (95.4%). When morphological features obtained by 3D sonography were added to 3D power Doppler findings, we achieved an even higher diagnostic accuracy of 97.7%. We found a statistically significant difference (P

Three-dimensional ultrasonographic ovarian measurements and in vitro fertilization outcome are related to age.

OBJECTIVE: To evaluate whether the number of ovarian antral follicles, ovarian volume, and ovarian stromal blood flow change with age and to prospectively analyze whether three-dimensional ultrasonographic measurements predict ovarian response and IVF outcome. DESIGN: Prospective analysis. SETTING: Assisted reproductive unit. PATIENT(S): Fifty-six consecutive women 22 to 43 years of age with normal basal serum FSH concentrations who were undergoing their first IVF cycle. MAIN OUTCOME MEASURE(S): Number of ovarian antral follicles, ovarian volume, and ovarian stromal flow index were determined by three-dimensional and power Doppler ultrasonography. Pretreatment measurements were compared with number of recovered oocytes, fertilization rates, and pregnancy rates. RESULT(S): As patient age increased, significant trends in ovarian volume, number of follicles, and stromal vascularity decreased. Three-dimensional ovarian measurements and fertilization rates differed significantly among age groups. For each age group, a higher number of antral follicles, greater ovarian volume, and favorable ovarian stromal vascularity was associated with higher number of retrieved oocytes and increased pregnancy rates. CONCLUSION(S): Increasing patient age is associated with poor ovarian response, as represented by smaller ovarian volume, lower antral follicle count, and poor stromal vascularity. Three-dimensional power Doppler ultrasonography can help to individualize IVF in patients regardless of age.

Fetal hand movements and facial expression in normal pregnancy studied by four-dimensional sonography.

AIM: To evaluate the developmental pattern of fetal hand movements and facial activity and expression during the second and third trimester of pregnancy by four-dimensional ultrasound (4D-US). SUBJECTS AND METHODS: A total of 25 fetuses in uncomplicated pregnancies were analyzed; 15 fetuses at 13 to 16 weeks and 10 fetuses at 30 to 33 weeks of gestation were studied with abdominal 4D-US. After standard assessment in two dimensional (2D) real-time B mode, a 4D mode was switched on. Further examination lasted a maximum of 15 minutes. RESULTS: Isolated hand movement and subtypes of hand movements were easily recognized by 4D-US. The sub-types of hand to head movement are: hand to head, hand to mouth, hand near mouth, hand to face, hand near face, hand to eye and hand to ear. All subtypes of hand to head movement can be seen from 13 weeks of gestation, with fluctuating incidence. Facial activities and different forms of expression are easily recognized by 4D-US. Among these, two types can be easily differentiated: smiling and scowling. CONCLUSIONS: 4D-US is superior over real-time two-dimensional ultrasound (2D-US) for qualitative, but inferior for quantitative analysis of hand movements. Thus 4D-US makes it possible to determine exactly the direction of the fetal hand, but the exact number of each type of hand movements can still not be determined. 4D-US is superior over two- and three-dimensional sonography in the evaluation of complex facial activity and expression. Among facial activities observed by 4D-US, simultaneous eyelid and mouthing movements dominate between 30 and 33 weeks of gestation. Pure mouth movements such as mouth opening, tongue expulsion, yawning and pouting are present, but at a significantly lower incidence. Facial expressions such as smiling and scowling can be precisely observed using 4D-US.

Preoperative assessment of ovarian tumors by CA 125 measurement and transvaginal color Doppler ultrasound.

The accuracy of combined use of serum CA 125 and transvaginal color Doppler for preoperative assessment of ovarian lesions in premenopausal patients was evaluated. Seventy-six ovarian lesions were analyzed the day before surgery using transvaginal color Doppler ultrasound. On the same day, serum CA 125 was measured in each patient. A novel index is proposed for the detection of ovarian malignancy combining resistance index (RI) obtained from newly formed vessels within the ovarian lesion and serum CA 125 level: (RI/CA 125) x 100. Values below the cut-off value of 1.5 were associated with a high risk of ovarian malignancy. Assessment of ovarian lesions by the novel index had a sensitivity and specificity of 94.44% and 100%, while positive and negative predictive values were 100% and 98.31%, respectively. The best prediction of ovarian malignancy was achieved by a combined use of transvaginal color Doppler ultrasound and serum CA 125 in the form of index: (RI/CA 125) x 100.

Ultrasonic assessment of the peri- and postmenopausal ovary.

OBJECTIVE: To analyze the role of B-mode ultrasound, color and power Doppler examination and three-dimensional ultrasound with and without power Doppler facilities in evaluation of the peri- and postmenopausal ovaries. METHODS: Review of the literature on ultrasonic assessment of the ovaries in postmenopausal patients. RESULTS: Ultrasound has assumed an increasing role in the evaluation of the peri- and postmenopausal ovaries. Ovarian lesions are a cause of great concern because of their malignant potential and the limited ability to distinguish accurately between benign and malignant lesions using morphological sonographic criteria alone. Superimposed color Doppler imaging enables the visualization of vascularization and blood flow characteristics of the ovaries and/or ovarian lesions. It becomes possible to detect normal, suspicious and pathologic blood flow characteristics even in small blood vessels. Owing to superb quality of the images, three-dimensional sonography enables precise assessment of the ovarian lesions. Three-dimensional power Doppler ultrasound permits effective targeting and rendering of ovarian tumor vasculature, thus providing new diagnostic possibilities for early detection of ovarian malignancy and differentiation of benign from malignant ovarian pathology. CONCLUSIONS: Further technological development will contribute to more objective evaluation of ovarian tumor morphology and vasculature which will give us tremendous support in clinical decision making and planning the management.

Ultrasonic assessment of the postmenopausal uterus.

OBJECTIVES: To assess the role of different forms of ultrasound in the evaluation of peri- and postmenopausal uterus. METHODS: B-mode ultrasound, colour and pulsed Doppler sonography, three-dimensional ultrasound and three-dimensional power Doppler sonography are non-invasive tools used repeatedly for assessing morphology and vascularity of the uterus and uterine lesions in peri- and postmenopausal patients. RESULTS: The application of transvaginal colour Doppler to the peri- and postmenopausal patients for the screening for endometrial and myometrial malignancy may be a viable option if combined with ovarian screening in the same scan. In this way the capital costs would be shared and oncological preventive medicine for postmenopausal women could be initiated. Three-dimensional and power Doppler ultrasound offers improved visualisation of uterine lesions, displays an entire volume, offers accurate volume estimation and enables retrospective review of stored data. Interactive rotation of power Doppler rendered images provides improved visualisation of the uterine vasculature. CONCLUSIONS: Further technological development of the ultrasound imaging techniques could result in reduction of both the potential risks and economic cost of the invasive diagnostic procedures in postmenopausal patients such as dilatation and curettage operations. Same techniques can be used for early detection of endometrial malignancy in asymptomatic postmenopausal women as well as for prediction of the depth of myometrial invasion.

Three-dimensional power Doppler in study of embryonic vasculogenesis.

Three-dimensional power Doppler sonography plays an important role in obstetrics, predominantly for assessing the relationship between fetal vascular system and surrounding organs. Presenting volume data in a standard anatomic orientation is valuable for assisting both ultrasonographers and pregnant patients to recognize anatomy more readily. This investigation was designed as an observational cross-sectional study. A group of 25 patients in gestational age of five to eleven weeks were recruited for the study. Architecture of the embryonic vessels was depicted by 3D power flow mapping and analyzed visually. Vascular 3D measurements were done through 3D color/power histogram and expressed by Vascularization Index (VI) and Vascularization Flow Index (VFI). Volume of the embryo increased exponentially throughout the observation period. The VI and VFI showed no change despite an exponential growth of embryonic volume. The findings of our study suggest that in cases of physiologic embryonic vasculogenesis there is a homeostatic steady state between tissue demands and blood supply given through the vascular network.

In vitro fertilization in spontaneous cycles--our experience.

OBJECTIVE: To study the efficacy of a simple protocol of natural cycle in vitro fertilization. METHOD: A retrospective study of 59 natural treatment cycles in 37 infertile couples with previous unsuccessful attempts of conventional in vitro fertilization. RESULTS: In 24% of cycles, the aspiration was cancelled because of inadequate visualization of follicles or because of preterm ovulation. Aspiration was performed in 45 cycles with oocyte retrieval of 82% per aspiration. Embryo transfer was performed in 30 cycles, pregnancy rate per pick-up was 15%. CONCLUSION: In vitro fertilization in a natural cycle is a simple, relatively cheap and comfortable procedure with reasonable results and can be offered to patients scheduled not only for in vitro fertilization because of tubal factor but also to patients with endometriosis or unexplained infertility.

Three-dimensional sonoembryology.

Three-dimensional (3D) ultrasound plays an important role in obstetrics, predominantly for assessing fetal anatomy. Presenting volume data in a standard anatomic orientation valuably assists both ultrasonographers and pregnant patients to recognize the anatomy more readily. Three-dimensional ultrasound is advantageous in studying normal embryonic and/or fetal development, as well as providing information for families at risk for specific congenital anomalies by confirming normality. This method offers advantages in assessing the embryo in the first trimester due to its ability to obtain multiplanar images through endovaginal volume acquisition. Rotation allows the systematic review of anatomic structures and early detection of fetal anomalies. Three-dimensional ultrasound imaging in vivo compliments pathologic and histologic evaluation of the developing embryo, giving rise to a new term: 3D sonoembryology. Rapid technological development will allow real-time 3D ultrasound to provide improved and expanded patient care on the one side, and increased knowledge of developmental anatomy on the other.

Screening for uterine abnormalities by three-dimensional ultrasound improves perinatal outcome.

The main goal of our study was to assess the true incidence of surgically correctable uterine abnormalities (congenital uterine anomalies, submucous leiomyoma, endometrial polyps and intrauterine synechiae) in the infertile population attending our tertiary infertility clinic. All of the infertile patients enrolled in the study were evaluated by three-dimensional ultrasound. Another objective was to assess pregnancy rates before and after operative hysteroscopy in patients affected by uterine causes of infertility. Good quality 3D images were obtained in all 3850 infertile patients, and in 23.2% of them 3D US revealed surgically correctable uterine abnormalities. The incidence of uterine septum in our general infertile population was 17.9%. Uterine septum was the most common uterine abnormality accounting for 77.1% of the intracavitary lesions. Out of 310 patients that were followed-up, 225 (72.6%) patients achieved pregnancy. The rate of term deliveries after septal incision was 57.7%, while 15.4% of patients had preterm deliveries. The rate of spontaneous abortions dropped from 41.7% before, to 11.9% after hysteroscopic resection of the septum. Three-dimensional ultrasound can be used as a screening method for detection of uterine abnormalities in patients suffering from infertility. We found significant improvement in reproductive outcome after operative hysteroscopy in secondary infertile patients with septate uterus and/or other uterine abnormalities.

Events from ovulation to implantation studied by three-dimensional ultrasound.

During the last decade transvaginal color Doppler has played an important role in increasing understanding of early human development. Although our knowledge of early pregnancy development has recently improved, little is known about the most critical period of human development: between conception and implantation. Recent advances in 3D ultrasound have made studies of follicular development, ovulation and uterine receptivity more accurate. The same method can be used for evaluation of the Fallopian tube patency and assessment of the ovarian and uterine causes of infertility which hamper processes of early human development. Storage capacities, reconstruction of the volume images and simultaneous viewing of all three orthogonal planes are the main advantages of this method. Introducing 3D ultrasound into assessment of early pregnancy has enabled visualization and volume estimation of the gestational sac, yolk sac and embryo. Switching on power Doppler superimposed to 3D gray scale can detect early vasculogenesis within the intervillous space and embryo/fetus. Here we review the potential application of this novel technique in monitoring the morphological and functional processes from ovulation towards implantation and early pregnancy.

Evaluation of serum CA 125 concentration before and during hormonal induced cycles as predictor of IVF/ET outcome.

PROBLEM: To evaluate the role of CA 125 in prediction of in vitro fertilization and embryo transfer (IVF/ET) outcome. METHOD OF STUDY: Serum CA 125 concentrations were evaluated in the spontaneous and stimulated cycles of 33 patients. CA 125 was measured using a microparticle enzyme immunoassay (MEIA) (Abbott, Diagnostics, USA). Follicular growth, endometrial thickness and subendometrial blood flow were evaluated by transvaginal color Doppler ultrasound. Statistical analysis was performed by Wilcoxon rank-sum test and Friedman test. RESULTS: There was no statistically significant difference (P > 0.05) of CA 125 values between spontaneous and stimulated cycles, and between pregnant and non-pregnant patients. A CA 125 rise from the late proliferative to the early secretory phase (P < 0.05) was obtained only in the stimulated cycles. There was no relationship between CA 125, follicle number, endometrial thickness and resistance index of the subendometrial vessels. CONCLUSION: CA 125 levels are not predictive of ovarian and endometrial response. Hormonal stimulation does not effect serum CA 125 concentration. There was no influence of CA 125 levels on IVF/ET outcome in stimulated cycles.