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Gonadotrophin-releasing hormone agonist (GnRHa)-induced ovulation after gonadotrophin ovarian stimulation is used to prevent ovarian hyperstimulation syndrome and multiple pregnancy in polyfollicular cycles. However, one of the major problems to be resolved is corpus luteum function after follicular maturation and ovulation by mid-cycle GnRHa administration. The present report investigated the luteal phase in non-conceptual polyfollicular cycles in 26 patients (group 1) receiving a single dose of 0.5 mg leuprolide acetate to induce ovulation and in a control group of patients (n = 26) (group 2) who were given human chorionic gonadotrophin (HCG) (10,000 IU i.m.) for ovulation induction. All of them were normal ovulatory women undergoing gonadotrophin ovarian stimulation because of unexplained infertility or male factor. In both groups of patients two doses of 2500 IU HCG i.m. were given 6 and 10 days after the ovulatory dose of HCG or GnRHa to support the luteal phase. All cycles were ovulatory as shown by mid-luteal serum progesterone concentrations >10 ng/ml. Mean serum progesterone concentrations were 62% higher in group 2 than in group 1, but this difference was not statistically significant. The mean length of the luteal phase was similar in groups 1 and 2. It is concluded that HCG luteal support is a useful tool to overcome the luteal phase inadequacy that characterizes GnRHa-triggered cycles after gonadotrophin stimulation. [ABSTRACT FROM AUTHOR]

Integrins have recently been proposed as having a major role in endometrial receptivity. Different patterns of integrin expression have been described during the normal endometrial cycle, and the co-expression of several integrins, mainly α1, α4 and β3 has been considered as specific to the 'window of implantation'. In the present study 55 infertile patients underwent two endometrial biopsies during a single menstrual cycle. An early biopsy was done on postovulatory days 6-8, and a late biopsy was performed on postovulatory days 10 to 12. Histological dating as well as immunohistochemical evaluation of α1, α4, β1, β3, β5, αvβ3 integrin expression and oestrogen and progesterone receptors were determined in all endometrial biopsies. Oestradiol and progesterone serum concentrations in serum were evaluated on the same days of the endometrial samplings. Nine out of the 55 midluteal biopsies (16.4%) showed out-of-phase endometria, but all biopsies were in phase in the late luteal phase. Differences in integrin expression between in- and out-of-phase biopsies were observed only for αvβ3 integrin glandular expression during the midluteal phase. αvβ3 integrin glandular expression was found in all late luteal phase biopsies. αvβ3 expression was closely correlated with histological maturation of the endometrium appearing suddenly at postovulatory day 6-7 and being expressed by all endometria dated as postovulatory day ≥8, irrespective of midluteal endometrial biopsies being in phase or out of phase. No differences in integrin expression were detected between patients with or without endometriosis or between patients who became spontaneously pregnant and those who did not. In conclusion, further studies are necessary before patterns of integrin expression may offer an alternative to predict uterine receptivity and implantation potential. [ABSTRACT FROM PUBLISHER]

At present, it is well accepted that maternal recognition of paternally derived fetal antigens occurs during normal pregnancy and may be beneficial for implantation and maintenance of gestation. Thus, we have investigated the compatibility of human leukocyte antigens (HLA) in couples with successive failed in-vitro fertilization (IVF) cycles. Study group 1 included 50 couples with prior primary infertility who had not achieved a pregnancy after 3 (range 3-7, mean 3.7) IVF cycles where at least two embryos (mean 3.3, range 2-4) were transferred in each attempt. An infertile control group (group 2) included 50 infertile couples undergoing IVF with the same indications as couples in group 1, who achieved a viable pregnancy with their first IVF attempt. The results were compared with those found in a population sample including 100 men and 100 women from the local population (group 3). We found a statistically significant (P <0.05) excess of HLA sharing (2 antigens) between partners in group 1 as compared to groups 2. There was a trend toward increased HLA sharing in group 1 when groups 1 and 3 were compared. We conclude that some cases of implantation failure after IVF and embryo transfer might be caused by underlying close histocompatibility between partners. [ABSTRACT FROM PUBLISHER]

Objective: To describe sequential changes in uterine artery waveform between the first and second trimesters of gestation and to analyze their association with the subsequent risk of hypertensive disorders and fetal growth restriction (IUGR)., Methods: Sequential uterine artery Doppler recordings were obtained in a final cohort of 870 singleton pregnancies over two gestational age intervals: 11-14 weeks and 19-22 weeks. The left and right uterine arteries were examined by color and pulsed Doppler and the mean pulsatility index (PI) as well as the presence of a bilateral protodiastolic notch were recorded during both intervals. Pregnancies were followed for occurrence of hypertensive disorders and IUGR., Results: Mean uterine artery PI showed a significant linear decrease within each of the two intervals considered, while the prevalence of a bilateral notch showed decreasing values only throughout 11-14 weeks of gestation. Sixty-four (7.3%) pregnancies developed a hypertensive disorder and/or IUGR, including three (0.34%) cases of gestational hypertension, 24 cases of pre-eclampsia (2.75%) and 37 (4.25%) of IUGR. Compared with pregnancies with a normal outcome, complicated pregnancies showed a significantly higher prevalence of a bilateral notch and a higher mean PI in each of the two intervals studied. Compared with normal pregnancies, complicated pregnancies had a significantly higher persistence of a bilateral notch (30% vs. 8%), a higher proportion of women with an abnormal first-trimester uterine artery PI shifting to normal in the second trimester (14% vs. 4%) and a higher incidence of a normal first-trimester mean PI that shifted to abnormal in the second trimester (13% vs. 4%). Persistence of an abnormal mean PI from the first to the second trimester identified the group with the greatest risk for adverse perinatal outcome (OR, 10.7; 95% CI, 3.7-30.9). In addition, women in whom the uterine artery mean PI shifted from abnormal to normal between the two trimesters and women in whom the reverse shift occurred showed a similar intermediate risk (OR, 5; 95% CI, 2.1-10.6), comparable to that in women with persistence of a bilateral notch (OR, 5.6; 95% CI, 2.9-10.7)., Conclusions: The sequence of changes in uterine flow between the first and second trimesters correlates with the subsequent development of hypertensive disorders and IUGR. Women with a persistent abnormal mean PI represent the group with the greatest risk for adverse perinatal outcome., (Copyright (c) 2006 ISUOG.)

Background: Treatment of poor-responder patients to controlled ovarian stimulation for assisted reproduction, who have normal basal FSH concentrations, is one of the most difficult challenges in reproductive medicine. This study investigated the usefulness of testosterone pretreatment in such patients., Methods: Prospective, therapeutic, self-controlled clinical trial including 25 consecutive infertile patients who had a background of the first and second IVF treatment cycle cancellations due to poor follicular response, in spite of vigorous gonadotrophin ovarian stimulation and having normal basal FSH levels. In the third IVF attempt, all patients received transdermal testosterone treatment (20 microg/kg per day) during the 5 days preceding gonadotrophin treatment., Results: Twenty patients (80%) showed an increase of over fivefold in the number of recruited follicles, produced 5.8+/-0.4 (mean+/-SEM) oocytes, received two or three embryos and achieved a clinical pregnancy rate of 30% per oocyte retrieval. There were 20% cancelled cycles., Conclusion: Pretreatment with transdermal testosterone may be a useful approach for women known to be low responders on the basis of a poor response to controlled ovarian stimulation but having normal basal FSH concentrations.

Objective: To evaluate the effects of recombinant human luteinizing hormone (rhLH) supplementation on ovarian stimulation and implantation rate in down-regulated women of advanced reproductive age., Design: Prospective randomized study., Setting: University teaching hospital., Patient(s): A total of 120 consecutive normogonadotropic infertile women > or = 35 years old undergoing their first cycle of IVF or intracytoplasmic sperm injection (ICSI) treatment., Intervention(s): Ovarian stimulation in a long agonist protocol with a combination of recombinant human follicle-stimulating hormone (rhFSH) and rhLH (group 1, n = 60) starting on day 6 of FSH stimulation until hCG at a daily fixed dose of 150 IU of rhLH, or with rhFSH alone (group 2, n = 60)., Main Outcome Measure(s): Ovarian stimulation characteristics, ovum retrieval, and IVF/ICSI outcome., Result(s): The mean number of intermediate (10-14 mm) and large (> 14- < 18 mm) but not leading (> or = 18 mm) follicles was significantly lower in group 1 on the day of hCG injection. The oocyte yield and maturity as well as the number of oocytes fertilized were significantly higher in group 2 than in group 1. However, the number of patients having embryo transfer (n = 55 in both treatment groups), the number and quality of embryos replaced, the implantation rate (20.6% vs. 21.7%) and clinical pregnancy rates per embryo transfer (44% vs. 45%) were similar in groups 1 and 2., Conclusion(s): The rhLH supplementation does not increase ovarian response and implantation rates in patients of older reproductive age stimulated with rhFSH under pituitary suppression for assisted reproductive technologies (ARTs).

Background: Pre-eclampsia and/or fetal death have increased sharply in HIV-infected pregnant women receiving HAART., Methods: The occurrence of pre-eclampsia or fetal death was analysed in women who delivered after at least 22 weeks of gestation for all women (January 2001 until July 2003) and for HIV-infected women (November 1985 until July 2003)., Results: In 2001, 2002 and 2003, the rates per 1000 deliveries of pre-eclampsia and fetal death, respectively, remained stable in all pregnant women at 25.4, 31.9 and 27.7 (P = 0.48) and 4.8, 5.8, and 5.0 (P = 0.89) (n = 8768). In 1985-2000 (n = 390) to 2001-2003 (n = 82), rates per 1000 deliveries in HIV-infected women rose from 0.0 to 109.8 (P < 0.001) for pre-eclampsia and from 7.7 to 61.0 (P < 0.001) for fetal death. In all pregnant women, factors associated with pre-eclampsia or fetal death were multiple gestation [adjusted odds ratio (OR) 3.6; 95% confidence interval (CI), 2.3-5.6; P < 0.001], HIV infection (adjusted OR, 4.9; 95% CI, 2.4-10.1; P < 0.001), multiparity (adjusted OR, 0.76; 95% CI, 0.58-0.98; P = 0.040) and tobacco smoking (adjusted OR, 0.65; 95% CI, 0.46-0.90; P = 0.010). The use of HAART prior to pregnancy (adjusted OR, 5.6; 95% CI, 1.7-18.1; P = 0.004) and tobacco smoking (adjusted OR, 0.183; 95% CI, 0.054-0.627; P = 0.007) were risk factors in HIV-infected women., Conclusions: HIV infection treated with HAART prior to pregnancy was associated with a significantly higher risk for pre-eclampsia and fetal death.

The objective of this study was to determine the value of myometrial invasion by magnetic resonance imaging (MRI), histologic typing and grading by endometrial biopsy, and the intraoperative evaluation of both parameters by frozen section in the evaluation of endometrial cancer. The preoperative and intraoperative records of 180 patients with endometrial cancer were used to compare the preoperative endometrial biopsy, the myometrial invasion by MRI, and the intraoperative frozen sections, with the final histopathologic findings. The preoperative endometrial biopsy gave us the tumor histologic type and grade. MRI gave us the depth of myometrial invasion. The evaluation of intraoperative frozen sections gave us the tumor histologic type, the tumor grade, and also the myometrial invasion. Patients were classified as low risk (grade 1 and 2, and myometrial invasion <50%) and high risk (grade 3 or myometrial invasion >50%). Standard statistical calculations were used. Evaluation of the tumor grade by preoperative biopsy has a sensitivity and a specificity of 75% and 95%, respectively. Evaluation of the tumor grade by intraoperative biopsy has a sensitivity and a specificity of 40% and 98%, respectively. Evaluation of the depth of myometrial invasion with MRI has a sensitivity and a specificity of 79% and 82%, respectively. Evaluation of the depth of myometrial invasion with intraoperative frozen sections has a sensitivity and a specificity of 74% and 95%, respectively. Evaluation of all four of the parameters together has a sensitivity and a specificity of 80% and 82%, respectively with a kappa of 0.621. In our opinion, the combination of preoperative biopsy and intraoperative frozen section is the best way to decide whether a lymphadenectomy is necessary with a low rate of understaging patients. MRI would have a fringe benefit in these patients.

Background. Intensity of exercise and low energy consumption, specific type and amount of training, early age at initiation, previous menstrual dysfunctions, low body mass index (BMI) or percentage body fat, pathological feeding habits and psychological stress have been suggested as potential factors accountable for menstrual irregularities in female athletes.Aim. To evaluate the influence of intensive training and of dietetic and anthropometric factors on menstrual cycles in female ballet dancers.Method. A case-control study, in which a structured interview and physical examination were carried out in two groups of teenagers aged between 12 and 18 years. The study included a total of 115 adolescent girls distributed in two groups: dancers (group B, n = 38) and girls of the same age not engaged in any sports activity (group C, n = 77).Results. Early starting high-intensity training delayed the onset of menarche ( p < 0.001). Dancers had a higher prevalence of oligomenorrhea and amenorrhea than control girls ( p = 0.004). Additionally, the dancers had lower scores in anthropometric variables: breast circumference 80 cm vs. 86.6 cm for controls ( p = 0.0001), low weight in 18% of dancers vs. 2.6% of controls ( p = 0.0001), and low height in 18% of dancers vs. 9% of controls ( p = 0.016). In addition, in dancers, low BMI was observed in 21% compared with 13% of controls ( p = 0.0001). Finally, 32% of the dancers were on a weight-control diet while this percentage decreased to 12% for the girls in control group (odds ratio = 3.49, 95% confidence interval = 1.31-9.25).Conclusions. In ballet dancers, high-intensity training was associated with late onset of menarche, menstrual disorders, lower weight and height development, and abnormal feeding behaviors.

We report the case of a 19-year-old pregnant woman who presented with a nipple tumor. The lesion consisted in a spindle-cell proliferation with histologic features similar to those of fibrous histiocytoma, with a highly vascularized stroma. Although it showed low mitotic activity, scattered marked atypical cells with prominent nucleoli were identified, thus raising concern about the benign nature of the tumor. Immunohistochemical evaluation revealed that the spindle cells were diffusely positive for vimentin, focally positive for CD68, and negative for all the other tested antibodies. The patient had a total excision of the lesion and she is free of disease after 30 months. To our knowledge this is the first reported case of a lesion of this type in the nipple after body-piercing., (Int J Surg Pathol 14(1):89-93, 2006.)

Objective: To evaluate the effectiveness of the addition of first-trimester biochemistry to fetal nuchal translucency (NT) measurement in the Combined Test when screening for trisomy 21 in twin pregnancies., Methods: Maternal serum free beta-hCG and PAPP-A were determined at 8 to 12 weeks and fetal NT was measured at 11 to 14 weeks. The individual risks were estimated for each of the fetuses using both NT screening alone and the Combined Test. An invasive diagnostic procedure was offered when the risk was 1:250 or over in either one of the fetuses. In the first period, only the results of NT screening were clinically applied. After previous analysis, the Combined Test was introduced into clinical practice., Results: In the two-and-a-half-year study period, a complete follow-up was obtained in 100 twin pregnancies. Three fetuses (two pregnancies) with trisomy 21 were detected by both methods. The false-positive rate achieved by NT screening (14.3% of pregnancies and 8.6% of fetuses) was substantially reduced when first-trimester biochemistry was added in the Combined Test (5.1% of pregnancies and 3.6% of fetuses)., Conclusion: The Combined Test appears to maintain the detection rate achieved by NT screening for trisomy 21 in twin pregnancies, but false-positive rates and invasive diagnostic procedures are reduced., (Copyright 2005 John Wiley & Sons, Ltd)

Objectives: To establish reference values for the first-trimester uterine artery (UtA) pulsatility index (PI) and to investigate the role of UtA Doppler in the early prediction of hypertensive disorders and their associated complications in an unselected Mediterranean population., Methods: A prospective study including 1091 consecutive singleton pregnancies undergoing routine early ultrasound screening at 11-14 weeks of gestation was performed. The left and right UtA were examined by color and pulsed Doppler transvaginally. The mean PI and the presence of bilateral protodiastolic notching were cross-sectionally recorded. Reference ranges were calculated and the pregnancies were followed for occurrence of pre-eclampsia, gestational hypertension, intrauterine growth restriction, placental abruption and stillbirth. The sensitivity and predictive values of a mean UtA-PI>95th percentile and the presence of bilateral notching in the prediction of these pregnancy complications were calculated., Results: A total of 999 women were finally included. Both the mean UtA-PI and the prevalence of bilateral notches showed a significant linear decrease between 11 and 14 weeks' gestation. Sixty-seven (6.7%) pregnancies developed at least one of the formerly described complications, including 22 (2.2%) cases of pre-eclampsia and 37 (3.7%) cases with intrauterine growth restriction. Compared with women with a normal outcome, complicated pregnancies showed a significantly higher mean PI (2.04 vs. 1.75; P<0.05, t-test) and a higher prevalence of bilateral notching (58% vs. 41%; P<0.05, Chi-square test). Using the 95th percentile in mean UtA-PI as a cut-off, 23.9% (95% CI, 13.7-34.1) of complicated pregnancies and 30.8% (95% CI, 5.68-55.85) of severe cases were identified., Conclusions: Our results suggest that pregnancies with an increased risk of developing hypertensive disorders and related complications already have an abnormally increased UtA-PI in early pregnancy. However, the use of a single uterine Doppler measurement for screening purposes in unselected early pregnancy populations has limited clinical value. The use of UtA-PI combined with other screening tests needs to be determined by further investigation., (Copyright (c) 2005 ISUOG.)

Purpose: The aim of this study was to evaluate the frequency of false-negative (FN) sentinel node procedures in patients with breast cancer and the subsequent clinical outcome in such patients., Methods: A total of 325 breast cancer patients underwent sentinel lymph node biopsy at our institution between June 1998 and May 2004. A 2-day protocol was used to localise the sentinel node with the injection of 99mTc-nanocolloid. There were two phases in the study: the learning phase (105 patients) and the application phase (220 patients). In the learning phase, a complete lymphadenectomy was always performed. In the application phase, sentinel nodes were studied intraoperatively and lymphadenectomy was performed when considered warranted by the pathological intraoperative results., Results: The median follow-up duration in the 220 patients studied during the application phase was 21.2 months (range 4-45 months). In this phase a total of 427 sentinel nodes were obtained (range 1-5 per patient, median 1.99), with 66 positive sentinel nodes in 56 patients (26%). The lymphadenectomies performed were also positive in 25% of cases (14 patients). We observed a total of two false-negative sentinel lymph node results (3.45%). One of them was found during the surgical excision of non-sentinel nodes, and the other presented as an axillary recurrence 17 months postoperatively (1.72% clinical false-negative rate). The latter patient died 1 year after the first recurrence., Conclusion: After a median follow-up of 21.2 months we observed only one clinical recurrence among 220 patients. Our results indicate that adequate local control is achieved by application of the sentinel node protocol.

Background: Anti-Müllerian hormone (AMH) has been recently proposed as a marker for ovarian ageing and poor ovarian response to controlled ovarian hyperstimulation in assisted reproduction cycles. The present study was undertaken to investigate the usefulness of baseline cycle day 3 AMH levels and AMH serum concentrations obtained on the fifth day of gonadotropin therapy in predicting ovarian response and pregnancy in women undergoing ovarian stimulation with FSH under pituitary desensitization for assisted reproduction., Methods: A total of 80 women undergoing their first cycle of IVF/intracytoplasmic sperm injection (ICSI) treatment were studied. Twenty consecutive cycles which were cancelled because of a poor follicular response were initially selected. As a control group, 60 women were randomly selected from our assisted reproduction programme matching by race, age, body mass index, basal FSH and indication for IVF/ICSI to those in the cancelled group. For each cancelled patient, three IVF/ICSI women who met the matching criteria were included., Results: Basal and day 5 AMH serum concentrations were significantly lower in the cancelled than in the control group. Receiver-operating characteristic (ROC) analysis showed that the capacity of day 5 AMH in predicting the likelihood of cancellation in an assisted reproduction treatment programme was significantly higher than that for basal AMH measurement. However, the predictive capacity of day 5 AMH was not better than that provided by day 5 estradiol. In addition, neither basal nor day 5 AMH or estradiol measurements were useful in the prediction of pregnancy after assisted reproductive treatment., Conclusions: AMH concentrations obtained early in the follicular phase during ovarian stimulation under pituitary suppression for assisted reproduction are better predictors of ovarian response than basal AMH measurements. However, AMH is not useful in the prediction of pregnancy. Definite clinical applicability of AMH determination as a marker of IVF outcome remains to be established.

Background: There is scanty information analysing the predictive value of a poor response, in terms of cancellation of the IVF cycle because of poor follicular development, as a predictor of ovarian response in a subsequent treatment cycle. This study, where logistic regression analysis was used, was undertaken to investigate the relative power of the woman's age, basal FSH, and previous cycle cancellation both as single and combined predictors of ovarian response in an IVF program where pituitary desensitization is routinely used., Methods: One hundred and twenty-nine consecutive patients having their first cycle of IVF/ICSI treatment cancelled because of poor follicular response and undergoing a second attempt within 6 months after the failed treatment cycle were initially selected (group 1). Group 2 comprised 129 patients undergoing the first cycle of IVF/ICSI treatment and who were randomly selected from our assisted reproductive treatment program matching by BMI and indication for IVF/ICSI to those in group 1., Results: Cancellation rate was significantly higher but ovarian response significantly lower in group 1 as compared with group 2. As indicated by the AUC(ROC) determined with ROC analysis, such a poor outcome in patients having a previous IVF/ICSI cycle cancelled due to poor response was observed whatever the level of basal FSH. In a logistic regression analysis and according to the odds ratio values, the predictive capacity of a previous poor response was 9 and 7.6 times higher than the predictive capacity of age and basal FSH, respectively. Any two or all three variables studied did not improve the predictive value of previous cycle cancellation alone., Conclusions: The history of an IVF/ICSI cancelled cycle due to poor follicular response in a standard stimulation protocol is a better predictor of cancellation in subsequent treatment cycles than age or FSH. The poor ovarian response associated with previous cycle cancellation occurs whatever the level of basal FSH.

Halving the standard daily dose of triptorelin at the start of ovarian stimulation in down-regulated women stimulated with recombinant FSH is enough for pituitary suppression and was associated with higher LH serum concentrations in the follicular phase. However, this did not translate into higher serum concentrations of androstenedione and E2 and had no significant effect on ovarian response and the outcome of IVF/intracytoplasmic sperm injection.

Purpose: To prospectively compare unenhanced power Doppler sonographic findings of arterial vascularization of invasive breast carcinoma with histopathologic and immunohistochemical parameters and to determine whether tumor arterial vascularization contributes to prediction of axillary node status., Materials and Methods: Ethics committee approval and informed consent were obtained. A total of 97 invasive breast carcinomas were prospectively studied with unenhanced power Doppler sonography before surgery. Lumpectomy or mastectomy with full axillary nodal dissection was performed. Sonographic tumor size and number of tumor arteries were correlated with axillary nodal status by means of logistic regression analysis. Tumor microvascularization was immunohistochemically assessed in a subset of 55 carcinomas. Sonographic variables were correlated with tumor arteries with a diameter larger than 300 mum and with the density and area of microvascularization. The kappa statistic and Bland-Altman agreement limits were used to measure agreement between techniques., Results: Good agreement of sonographic and histologic findings regarding number of tumor arteries (kappa= 0.66, P < .001) and tumor size (P = .012) was observed. Multivariate analysis showed an independent relationship between probability of axillary metastasis, number of tumor arteries (P = .016), and sonographic tumor size (P = .035). A predictive model of axillary status was developed. The receiver operating characteristic curve was used to determine 0.2324 as the score to classify axillary nodal status. This score indicated high sensitivity (96.1%), low specificity (53.0%), and high negative predictive value (96.1%)., Conclusion: The number of arteries in invasive breast carcinoma detected with unenhanced power Doppler sonography and sonographic tumor size are independent predictors of axillary nodal status; these variables could contribute to reliable prediction of absence of axillary involvement on the basis of a mathematic model., ((c) RSNA, 2004.)

Background: Although studies have reported good results with laparoscopic-assisted vaginal hysterectomy (LAVH) to treat endometrial cancer, it has been associated with recurrent disease at trocar insertion sites. Long-term follow-up is necessary to detect possible adverse effects of this technique., Cases: We present two case reports of stage IIB endometrial cancer with port-site metastasis 39 and 48 months after initial surgery with LAVH., Conclusion: Although LAVH is a good technique to treat patients with endometrial cancer, port-site metastasis is a possible complication and should be taken into consideration until a randomized study shows the long-term benefits and risks of laparoscopic over standard treatment.

Objective: To construct normal ranges for umbilical artery pulsatility index (UA PI), middle cerebral artery pulsatility index (MCA PI) and cerebroplacental ratio (CPR) in prolonged pregnancies according to strict methodological criteria using polynomial regression analysis., Methods: This was a retrospective, cross-sectional observational study involving 140 women, 10 women for each gestational day between 287 and 300 days of gestation. Fetal Doppler parameters were assessed to construct normal reference ranges for UA PI and MCA PI. CPR was calculated as a ratio of MCA PI/UA PI., Results: Mathematical modeling of the data demonstrated that the optimal fit was a linear polynomial one. Mean, 5th and 95th centiles were calculated for UA, MCA and CPR and centile curves from the regression analysis were constructed., Conclusions: Reference ranges for UA PI, MCA PI and CPR in prolonged pregnancies have been constructed. MCA PI shows a wider range than previously reported in the literature.

Objectives: To assess the value of middle cerebral artery Doppler indices obtained from different sampling sites in predicting umbilical cord gases at delivery in prolonged pregnancies., Methods: This was a prospective study of consecutive pregnant women referred for prolonged-pregnancy surveillance. The predictive value of distal and proximal middle cerebral artery Doppler indices for cord blood gases was evaluated in women who delivered within 48 h of their last antenatal test using stepwise multiple regression., Results: There was a significant linear correlation between proximal and distal middle cerebral artery pulsatility indices (R = 0.777; P < 0.0001), the mean values being 1.49 (SD, 0.45) and 1.56 (SD, 0.47), respectively. There was also a linear correlation between proximal and distal cerebroplacental ratios (R = 0.68; P < 0.0001), the mean values being 1.85 (SD, 1.96) and 1.92 (SD, 1.89), respectively. The stepwise multiple regression analysis for umbilical artery pH showed that once the distal middle cerebral artery pulsatility index was introduced into the model, the addition of any variable did not result in a significant improvement of the predictive capacity. The model showed a coefficient of determination (R(2)) of 0.079. There was a significant correlation between umbilical artery pO(2) and both proximal middle cerebral artery pulsatility index (positive) and the occurrence of elective Cesarean section (negative). This model accounted for 21% of the variance (R(2) = 0.21). No other variables added any significant prediction for pO(2)., Conclusions: In post-term pregnancies the proximal middle cerebral artery pulsatility index significantly predicts umbilical artery pO(2) at delivery but does not predict pH. There is a weak association between distal middle cerebral artery pulsatility index and pH but, as this only explains 8% of the variance, it is of little clinical value.

Objective: To investigate the oocyte quality in patients with severe ovarian hyperstimulation syndrome (OHSS)., Design: Self-controlled clinical study., Setting: University teaching hospital., Patient(s): Twenty-two patients from our assisted reproductive technology (ART) program who developed severe OHSS during their first controlled ovarian hyperstimulation for IVF or intracytoplasmic sperm injection (ICSI) (OHSS cycles) during a period of 10 years and had a second ART attempt performed in our center in which OHSS did not develop (control cycles)., Intervention(s): IVF and ICSI., Main Outcome Measure(s): Oocyte yield and quality, fertilization rate, embryo yield and quality, implantation rate, and pregnancy rate., Result(s): The total number of oocytes retrieved and the mean number of metaphase II oocytes were significantly higher in patients with OHSS than in control cycles. Fertilization rates were similar in both groups of ART cycles, and thus the number of viable embryos were significantly higher in OHSS cycles. Implantation and pregnancy rates were similar in OHSS and control cycles. Oocyte and embryo yield and quality were similar in early and late OHSS. Oocyte yield and quality, embryological outcome, and implantation and pregnancy rates were similar in patients with and without polycystic ovarian syndrome (PCOS) both in cycles developing OHSS and control cycles., Conclusion(s): Oocyte quality is not compromised in severe OHSS cycles irrespective of whether patients had or did not have PCOS.

Objective: To assess the effectiveness of the Combined Test in the prenatal detection of trisomy 21 in the general pregnant population using a new timing for the screening approach., Methods: First-trimester maternal serum biochemical markers (pregnancy-associated plasma protein-A and free-beta hCG) were determined in maternal serum at 7 to 12 weeks. Fetal nuchal translucency and gestational age were assessed at the 10- to 14-week ultrasound scan. A combined risk was estimated and delivered to the women the same day. When the risk was 1:250 or above, chorionic villus sampling was offered., Results: Mean gestational age at biochemistry was 9.4 weeks, being 12.3 at ultrasound. In the 2780 studied pregnancies with a complete follow-up, observed detection rates were 88% (7/8) for trisomy 21 and 75% (3/4) for trisomy 18, with a 3.3% (92/2765) false-positive rate., Conclusion: The Combined Test, assessing biochemistry and ultrasound at individually optimal ages in the first trimester, showed an 88% detection rate for trisomy 21 with a remarkably reduced false-positive rate (3.3%)., (Copyright 2004 John Wiley and Sons, Ltd.)

Objective: To investigate the effect on embryo transfer (ET) success of air loaded into the transfer catheter to bracket the embryo-containing medium., Design: Prospective, randomized study., Setting: University teaching hospital., Patient(s): One hundred two consecutive patients undergoing ET after IVF., Intervention(s): In group 1 (n = 52), embryos were loaded as follows: 200 microL of air in the syringe, 100-125 microL of air in the proximal part of the catheter, 20-25 microL of medium containing the embryos to be transferred, and 10 microL of air at the tip of the catheter. In group 2 (n = 50), the syringe and the entire catheter were filled with medium and the embryo-containing medium (20-25 microL) was aspirated without being bracketed by air spaces., Main Outcome Measure(s): Implantation and pregnancy rates., Result(s): No differences were found between groups 1 and 2 with respect to implantation and pregnancy rates., Conclusion(s): The air loaded into the transfer catheter to bracket the embryo-containing medium has no negative effect on ET success.

Recent advances in manufacturing procedures for r-hFSH have resulted in a preparation (follitropin alfa) that is highly consistent in both isoform profile and glycan species distribution. As a result, follitropin alfa can be reliably quantified and vials can be filled by mass. This study compared the clinical results in a well-established assisted reproduction programme during the crossover from standard follitropin alfa filled-by-bioassay (FSH-bio) to follitropin alfa filled-by-mass (FSH-mass). The study included the last 125 patients treated with FSH-bio and the first 125 patients receiving FSH-mass for ovarian stimulation in their first assisted reproduction treatment cycle. Patient baseline characteristics were almost identical in the two groups. The duration of ovarian stimulation was significantly shorter in the FSH-mass group. The number of patients receiving the HCG injection and undergoing oocyte retrieval, follicular development and the serum concentration of oestradiol on the day of HCG injection were similar for the two treatment groups. The oocyte yield and the fertilization rates were similar in both groups of patients. However, embryo quality and implantation rates were significantly higher in the FSH-mass group. Accordingly, in spite of the mean number of embryos transferred being significantly lower in the FSH-mass group, there was a trend for higher clinical pregnancy rates in this group of patients. It is concluded that the new formulation of FSH-mass is more effective than the standard FSH-bio in terms of embryo quality, implantation rates, and number of days of stimulation.

Background: Human follicular fluid contains several substances, such as cytokines and growth factors, which may affect follicular growth and maturation. The present study examines the relative contribution of macrophages and granulosa cells in the production of vascular endothelial growth factor (VEGF) and adrenomedullin in the human ovulatory follicle., Methods: Both follicular fluid samples and blood samples were obtained at the time of oocyte retrieval following ovarian stimulation from 20 women undergoing IVF treatment because of male infertility. Human follicular fluid macrophages and luteinized granulosa cells were obtained from pooled follicular fluid of individual patients. Accumulation of VEGF and adrenomedullin in the culture medium of the isolated macrophages and human granulosa cells was determined at variable time intervals ranging from 0 to 48 h. Plasma and follicular fluid concentrations of VEGF and adrenomedullin were also measured., Results: The follicular fluid concentrations of VEGF and adrenomedullin were significantly higher than those found in plasma. After 48 h, accumulation of VEGF in the culture medium of follicular fluid macrophages was significantly higher than that released in the culture medium of luteinized granulosa cells. In contrast, the production rate of adrenomedullin by follicular fluid macrophages was similar to that found in granulosa cells. VEGF secreted by follicular fluid macrophages increased progressively within 48 h of cell culture. A similar response pattern was observed with the culture medium of luteinized granulosa cells, but with lower production rates., Conclusions: This study suggests for the first time that both luteinized granulosa cells and macrophages actively secrete VEGF and adrenomedullin into follicular fluid in the human ovary.

The most commonly used biomarker tests of ovarian reserve are basal hormone measurements during the early follicular phase, including mainly FSH but also oestradiol, FSH:LH ratio, and inhibin B. This study was designed to assess prospectively the intra- and inter-cycle variability of serum values of those hormone biomarkers in the early follicular phase of consecutive cycles in a group of women candidates for assisted reproduction. Fifty eumenorrhoeic women underwent blood sampling for hormone measurement on cycle day 3 for three consecutive cycles, and during the first study cycle, daily samples were obtained on cycle days 2, 3, 4 and 5. No significant difference was detected among FSH concentrations and FSH:LH ratios during cycle days 2-5; in contrast, oestradiol and inhibin B were not constant through the early follicular phase. No difference in FSH or inhibin B serum concentrations and FSH:LH ratio on cycle day 3 during three consecutive cycles was noted; however, significant inter-cycle variability for oestradiol serum concentration on cycle day 3 was detected. FSH and inhibin serum concentrations, and FSH:LH ratio varied significantly less than oestradiol on cycle day 3, but inter-cycle variability was similar for the first three hormonal biomarkers of ovarian reserve. There was significantly less intra-cycle variability of FSH serum concentration and FSH:LH ratio than oestradiol and inhibin B serum concentrations. Basal FSH serum concentrations (or FSH:LH ratio) during the early follicular phase showed neither significant inter-cycle nor intra-cycle variability when measured during 3 consecutive months in an assisted reproduction patient population, thus offering greater flexibility of pretreatment sampling.

Background: There has been much debate about the effect of 'residual' LH levels in normogonadotrophic women undergoing assisted reproduction with GnRH agonist down-regulation and recombinant FSH ovarian stimulation. The aim of this prospective study, where receiver-operating characteristic (ROC) analysis was used, was to assess further the usefulness of serum LH levels as predictors of ovarian response, assisted reproduction treatment outcome, and the outcome of pregnancy when measured throughout the ovarian stimulation period in a large cohort of such assisted reproduction treatment women., Methods: A total of 246 consecutive women undergoing their first cycle of IVF or ICSI treatment were included in this study. Blood samples for hormone analyses were obtained on day S0 (the day when pituitary suppression was evidenced) and every other day from stimulation day 5 (S5) until the day of hCG injection., Results: LH serum levels throughout ovarian stimulation treatment were similar for cancelled (n =32) versus non-cancelled (n = 214) cycles, non-conception (n = 132) versus conception (n = 82) cycles, and ongoing pregnancy (n = 66) versus early pregnancy loss (n = 16) groups. There was no correlation between LH serum levels in non-cancelled cycles and parameters of ovarian response and assisted reproduction treatment outcome. ROC analysis showed that serum LH concentration during ovarian stimulation was unable to discriminate between cancelled and non-cancelled cycles, conception versus non-conception cycles, or early pregnancy loss versus ongoing pregnancy groups., Conclusions: Serum LH measurements during ovarian stimulation with recombinant FSH under pituitary suppression in normogonadotrophic women undergoing assisted reproduction treatment cannot predict ovarian response, IVF/ICSI outcome, implantation, and the outcome of pregnancy. Thus, there is little underlying physiological support for the addition of LH in stimulation protocols if daily doses of an appropriate GnRH agonist (leuprolide or triptorelin having lower potency than buserelin) and a step-down regimen of recombinant FSH administration are used.

Purpose: To investigate the relative power of HCG, estradiol, and progesterone determinations in the prediction of pregnancy outcome after IVF. These prognostic hormonal factors were studied as single and combined predictors., Methods: Serum concentrations of beta-HCG, progesterone, and estradiol were measured 12-13 days after embryo transfer (study point 1) and 7 days later (study point 2) in a series of 20 consecutive infertile patients having a first-trimester spontaneous clinical abortion after an IVF-embryo transfer cycle. As a control group (n = 60), the next three IVF-embryo transfer cycles resulting in an ongoing pregnancy after each miscarried IVF cycle in our assisted reproduction program was used. The discrimination attained between the two study groups (ongoing pregnancies and miscarriages) was evaluated by logistic regression and receiver operating characteristic (ROC) curve analysis., Results: Mean hormone concentrations at study points 1 and 2 were higher in the ongoing pregnancy than in the abortion group. Regarding pregnancy outcome the percentage increment of HCG serum levels (> or = 1321%), with an accuracy (predictive value of pregnancy outcome) of 81.2% (sensitivity 98%, specificity 50%), had the best prognostic reliability but no significant differences were found when this parameter was compared with the predictive value of HCG concentration (> or = 72 IU/l) at study point 1 (diagnostic accuracy 80.5%; sensitivity 70%; specificity 80%). When ROC analysis was used, the best predictor of ongoing pregnancy according to the AUC(ROC) was HCG concentration at study point 2 but again no significant differences were found when this parameter was compared with the predictive value of HCG serum levels at study point 1. A multiple marker strategy did not help distinguish viable from nonviable pregnancies., Conclusion: A single, early (days 12-13 after embryo transfer) HCG quantitative serum measurement in IVF cycles not only is diagnostic but also has good predictive value for pregnancy outcome.

Purpose: To investigate endometrial receptivity in terms of pinopode formation and alphavbeta3 integrin expression in infertile women with endometriosis during natural cycles., Methods: We investigated the expression of alphavbeta3 integrin and pinopode formation in the endometrium of 12 infertile patients with stage I or II endometriosis as the only cause of infertility, 12 infertile patients having unexplained infertility, and 12 fertile women who were undergoing tubal sterilization. Two endometrial biopsies (postovulatory day +7 to +8 and 4 days later) were performed during a single menstrual cycle in each subject., Results: No statistically significant difference regarding alphavbeta3 integrin expression and pinopode formation was found between infertile patients with endometriosis and the two control groups., Conclusion: alphavbeta3 integrin expression and pinopode formation are not reduced during the window of implantation in patients with stage I-II endometriosis. Whether these results imply normal endometrial receptivity in such patients or add to the increasing uncertainty about the clinical value of assessing the endometrium with those markers of implantation, warrants further studies.

Problem: The majority of women with recurrent miscarriage have no discernible cause but it has been postulated that immunologic aberrations may be the cause in most of such cases. Also, it has been stressed that deliberate modification of the maternal host defense system can improve the chances of success. We tested the hypothesis that it is possible to potentiate maternal immune functions so as to improve reproductive performance by replacing several embryos into the uterus, thus favoring the recognition of fetal antigens., Method of Study: A total of 57 couples with three or more (mean 5.52; range 3-12) consecutive first-trimester spontaneous clinical abortions of unknown etiology were treated with in vitro fertilization (IVF) and embryo transfer for a total of 84 cycles. Patients underwent IVF after combined gonadotropin-releasing hormone agonist/gonadotropin treatment for ovarian stimulation, and up to four embryos were replaced into the uterus., Results: There were 32 pregnancies (three of them after frozen-thawed embryo transfers) and 26 (81%) of them were viable gestations. Overall, patients had a previous obstetric history of 315 pregnancy losses and 15 live-born babies. Thus, the probability of having a live baby before treatment was 4.54% (95% CI, 2.78-7.36) a figure significantly lower (P < 0.0001) than that observed under IVF treatment (81%; 95% CI, 64.53-91.01). None of selected variables potentially related with the outcome of pregnancy after IVF and embryo transfer in recurrent aborters (including pre-implantation genetic diagnosis) was found to be associated with miscarriage., Conclusions: This study shows that replacement of several embryos after IVF is a useful treatment in the prevention of unexplained recurrent spontaneous abortion thus providing further evidence for immunologically modifiable pregnancy loss.

Objective: To describe the time sequence of changes in cardiac function in intrauterine growth restriction., Study Design: This was a prospective longitudinal study on 22 singleton pregnancies with growth-restricted fetuses. Pulsatility indices of fetal arterial and venous Doppler waveforms, systolic peak velocity in the aorta and pulmonary artery, right and left ventricular shortening fraction and atrioventricular flow E/A ratio were assessed at each monitoring session. Logistic regression was used for modeling the probability of abnormality of a variable in relation to the time interval before delivery. Trends over time were analyzed by Mann-Withney U-test., Results: Umbilical artery pulsatility index was the first variable to become abnormal, followed by the middle cerebral artery, right diastolic indices (right E/A, ductus venosus), right systolic indices and, finally, both diastolic and systolic left cardiac indices., Conclusion: We have found an earlier and more pronounced right than left and diastolic than systolic fetal cardiac function deterioration in growth restricted fetuses monitored longitudinally.

At present, there is considerable debate about the utility of supplemental LH in assisted reproduction treatment. In order to explore this, the present authors used a depot gonadotrophin-releasing hormone agonist (GnRHa) protocol combined with recombinant human FSH (rhFSH) or human menopausal gonadotrophin (HMG) in patients undergoing intracytoplasmic sperm injection (ICSI). The response to either rhFSH (75 IU FSH/ampoule; group rhFSH, 25 patients) or HMG (75 IU FSH and 75 IU LH/ampoule; group HMG, 25 patients) was compared in normo-ovulatory women suppressed with a depot triptorelin injection and candidates for ICSI. A fixed regimen of 150 IU rhFSH or HMG was administered in the first 14 days of treatment. Treatment was monitored with transvaginal pelvic ultrasonographic scans and serum measurement of FSH, LH, oestradiol, androstenedione, testosterone, progesterone, inhibin A, inhibin B and human chorionic gonadotrophin (HCG) at 2-day intervals. Although oestradiol serum concentrations on the day of HCG injection were similar, both the duration of treatment and the per cycle gonadotrophin dose were lower in group HMG. In the initial 16 days of gonadotrophin treatment, the area under the curve (AUC) of LH, oestradiol, androstenedione and inhibin B were higher in group HMG; no differences were seen for the remaining hormones measured, including the inhibin B:inhibin A ratio. The dynamics of ovarian follicle development during gonadotrophin treatment were similar in both study groups, but there were more leading follicles (>17 mm in diameter) on the day of HCG injection in the rhFSH group. The number of oocytes, mature oocytes and good quality zygotes and embryos obtained were significantly increased in the rhFSH group. It is concluded that in IVF patients undergoing pituitary desensitization with a depot agonist preparation, supplemental LH may be required in terms of treatment duration and gonadotrophin consumption. However, both oocyte, embryo yield and quality were significantly higher with the use of rhFSH.

Background: Different hormonal replacement regimens are used for treating climacteric complaints; however, not all of them have the same clinical profile. Cardiovascular disease (CVD) is a major health problem and tibolone, raloxifene, estradiol (alone or with cyproterone acetate) have been added to cholesterol-fed rabbits to study atherosclerosis., Methods: A total of 48 cholesterol-fed New Zealand white rabbits were studied for 4 months. Forty rabbits underwent bilateral ovariectomy and the other eight were sham operated (group S). The ovariectomized rabbits were allocated to five groups of eight animals each receiving tibolone (Group T, 6 mg/day), raloxifene (R, 35 mg/day), estradiol valerate (E, 3 mg/day), estradiol valerate plus cyproterone acetate (EC, 3+0.5 mg/day, respectively), and no treatment for the control group (C). The sham group received no treatment too., Results: After 4 months the percentage of the extent of atherosclerosis in the aorta was 30.4% in C group, 24.5% in S group, 10.2% in T group, 30.3% in R group, 17.9% in E group and 28.1% in EC group (P<0.05 T vs. C, R, EC). The aortic cholesterol content compared with aortic weight was 8.55 microg/mg in C group, 11.97 microg/mg in S group, 1.86 microg/mg in T group, 3.82 microg/mg in R group, 2.86 microg/mg in E group and 5.24 microg/mg in EC group (P<0.05 T vs. EC, C, S; R vs. C, S; E vs. C, S). Uterine weights in grams were: 1.89 (C group), 2.24 (S), 7.38 (T), 1.94 (R), 9.92 (E), and 5.94 (EC); P<0.05 (C, S, R, vs. T, E, EC; T vs. E; EC vs. T, E)., Conclusion: Our study showed a decrease in the extent of aortic atherosclerosis in oophorectomized cholesterol-fed rabbits treated with tibolone or estradiol, and a decrease in aortic cholesterol content in rabbits treated with tibolone, raloxifene and estradiol. However, rabbits treated with tibolone showed an increased uterine weight, which is contrary to that observed in humans.

Background: Integrin expression and pinopode formation have been proposed as a means of distinguishing receptive endometrium from non-receptive in clinical practice, thus offering new directions for the development of contraceptive approaches targeted to the endometrium as well as a better understanding of occult causes of infertility in women. The aim of the present study was to investigate the effect of ovulation induction, oral contraception, treatment with dehydrogesterone, and different regimens of hormone replacement therapy on endometrial alphavbeta3 integrin expression and pinopode formation using a prospective, controlled study design., Methods: Histological dating, alphavbeta3 integrin expression and pinopode formation were evaluated in control and treated cycles in six groups of women including eight subjects per group and who received clomiphene citrate, ovarian stimulation for IVF, oral contraception, dehydrogesterone for endometrial luteal phase defect, or two different regimens of hormone replacement therapy. Twelve healthy fertile women served as a general control group., Results: Alphavbeta3 integrin expression and pinopode formation in the human endometrium were closely related to endometrial maturation as defined by histological dating and this was irrespective of endometria being in-phase or out-of-phase and the hormonal treatment received. Only for clomiphene citrate did a direct effect with reduction in pinopode formation in the midluteal phase seem to exist., Conclusion: Alphavbeta3 integrin expression and pinopode formation in the human endometrium are processes closely related to endometrial maturation and this is irrespective of endometria being in-phase or out-of-phase and the hormonal treatment received. The potential usefulness of those two so-called endometrial markers of implantation as targets for contraceptive approaches or fertility-promoting strategies seems unlikely.

Objective: To investigate the predictive value of ultrasonographic parameters as prognostic indicators of implantation after IVF when measured on the day of embryo transfer., Design: Comparative, observational study., Setting: University teaching hospital., Patient(s): Two hundred eighty patients undergoing IVF., Intervention(s): Ovarian stimulation, IVF., Main Outcome Measure(s): Variables related to patients' clinical characteristics, treatment characteristics, ovarian response, ovum retrieval, outcome of IVF and ICSI, embryo transfer, ultrasonographic and Doppler endometrial measurements, and uterine blood flow that have been proposed as potential predictive factors of implantation. All transvaginal ultrasonographic assessments were performed on the day of embryo transfer., Result(s): Among 240 patients finally evaluable, 67 (group 1) became pregnant after IVF, and 173 (group 2) failed to conceive. The 111 nonpregnant patients who had the same embryo score per replacement (group 3) as did patients in group 1 were selected for comparison purposes. The only significant differences between groups 1 and 3 were the type A endometrium and the absence of a protodiastolic notch in the uterine arteries, both of which were more frequently found in group 1. However, a considerable overlap existed between conception and nonconception cycles regarding both variables., Conclusion(s): Ultrasonographic parameters as predictors of implantation in assisted reproduction have a limited value in the clinical setting.

Background: Tibolone is a synthetic steroid effective for the treatment of climacteric symptoms and osteoporosis. Long term treatment with tibolone is associated with a significant decrease in cholesterol levels due to a parallel decrease in high-density lipoprotein. However, the effect of these changes on atherogenesis is not known., Objective: To investigate the effect of tibolone therapy on aorta atherogenesis., Material and Methods: Thirty-two New Zealand white rabbits were fed cholesterol-rich feed and studied for four months. The rabbits underwent laparotomy and were randomly assigned to four groups. Twenty-four rabbits underwent bilateral ovariectomy; of these, eight received tibolone (group T), eight received estradiol valerate (group E), eight received placebo after sterilization (group C), and eight were sham operated (group S)., Results: After receiving the cholesterol-rich diet, total levels of cholesterol increased in group C from 3.17+/-0.72 mmol/L to 35.36+/-9.01 mmol/L, in group S from 2.88+/-0.9 mmol/L to 28.76+/-9.442 mmol/L, in group E from 1.69+/-0.44 mmol/L to 1.69+/-0.44 mmol/L and in group T from 2.03+/-0.22 mmol/L to 26.33+/-13.45 mmol/L (no significant differences were observed among the groups at the end of the study). At four months, the cholesterol- rich diet caused atherosclerotic lesions in both treated and untreated rabbits, affecting 30.47+/-12.2%, 24.51+/-16.1%, 17.91+/-10.19% and 10.21+/-6.8% of the aortic surface for groups C, S, E and T, respectively (P<0.01 for treated groups)., Conclusion: The principal result from this study was that treatment with tibolone in cholesterol-fed ovariectomized rabbits reduces aortic atherosclerotic lesion formation and that this reduction is not related to plasma lipid levels.

Objective: To compare Doppler evaluation of the ductus venosus and contraction stress test (CST) in the prediction of adverse perinatal outcome in growth-restricted fetuses with evidence of hemodynamic redistribution and a non-reactive non-stress test (NST)., Methods: Data were collected from all singleton pregnancies seen in our Fetal Surveillance Unit who underwent antenatal monitoring for fetal growth restriction, non-reactive NST and arterial redistribution beyond 26 weeks of pregnancy. Patients were divided into four groups based on their CST and ductus venosus waveform results. Perinatal outcome was evaluated by means of four variables: the need for admission to the neonatal intensive care unit (NICU), need for neonatal intubation, an umbilical artery pH < 7.10 and significant neonatal morbidity. Outcome was compared among fetuses delivered within 3 days of their antenatal test. Logistic regression analysis was used to analyze the relation between predictive and outcome variables., Results: Sixty-eight women met the inclusion criteria for the study. The positive predictive value of the CST was 45% for admission to the NICU, 13% for significant neonatal morbidity, 26% for need of neonatal intubation and 29% for umbilical artery pH < 7.10. The positive predictive values of abnormal ductus venosus waveform (ADVW) were 81.5%, 26%, 48% and 55%. Groups with ADVW showed significantly poorer neonatal outcome. No significant differences were observed when CST results were compared. Logistic regression analysis showed that both gestational age at delivery and ADVW significantly predict the occurrence of adverse perinatal outcome., Conclusion: In growth-restricted fetuses with hemodynamic redistribution and a non-reassuring NST, Doppler assessment of the ductus venosus correlates with adverse perinatal outcome. In this clinical situation there is no benefit of CST in terms of prediction., (Copyright 2003 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: To compare the safety of recombinant human luteinizing hormone (LH) with that of urinary hCG in terms of the hemodynamic changes when they are used to induce final follicular maturation in patients undergoing in vitro fertilization (IVF). A secondary end point was efficacy in terms of IVF outcome., Design: Prospective, randomized clinical trial., Setting: University teaching hospital., Patient(s): Thirty IVF patients., Intervention(s): Ovarian stimulation was induced with FSH under pituitary suppression. Patients were randomized to receive either hCG or recombinant human LH as a trigger of oocyte maturation (5,000 IU) and for luteal phase support (5,000 IU, 2,500 IU, and 2,500 IU on the day of follicular aspiration, 2 days later, and 5 days later, respectively)., Main Outcome Measure(s): Mean arterial pressure, cardiac output, peripheral vascular resistance, and serum levels of progesterone, plasma concentrations of aldosterone, norepinephrine, and plasma renin activity were measured in all patients on postovulatory day 7 of the spontaneous menstrual cycle preceding IVF (baseline) and 7 days after the hCG/recombinant human LH ovulatory injection during the IVF cycle., Result(s): Ovarian response and IVF outcome (pregnancy rate, 60%) were similar in both treatment groups. On the seventh day after hCG/recombinant human LH administration, the peripheral vascular resistance was significantly lower and serum progesterone concentrations significantly higher in the hCG group as compared with the recombinant human LH group. The percentage change from baseline values during IVF cycles in all hemodynamic and neurohormonal variables investigated was higher (albeit not statistically different) in the group treated with hCG vs. the group treated with recombinant human LH., Conclusion(s): Recombinant human LH is associated with less intense circulatory changes than hCG when it is given to induce final follicular maturation and luteal phase support in IVF procedures.

It is accepted that approximately 50% of embryos obtained after IVF arrest during the first week. Traditionally, chromosome abnormality and suboptimal culture conditions have been proposed as factors commonly associated with embryo arrest. However, even when considering 'ideal' conditions and embryos of only excellent morphology in vitro, there is still a significant incidence of embryonic arrest. There is considerable evidence that the nuclear protein p27, a member of the Cip/Kip family of CDK inhibitors, plays an important role in multiple fundamental cellular processes, including cell proliferation, cell differentiation, and apoptosis. The present investigation, using immunocytochemical techniques coupled with confocal microscopy, was undertaken to determine whether p27 could play a role in the arrest of 4-8-cell human embryos. A total of 28 preimplantation embryos at the 4-8-cell stage were investigated. Of these, 16 were diploid embryos showing cleavage arrest with no further progression, and 12 were normally developing embryos. There was a 2-fold increased expression of the cell-cycle inhibitor p27 in arrested embryos compared with control normally developing embryos. This study represents the first demonstration of an increased expression of p27 in cleavage-stage human arrested embryos.

Background: There is scanty and contradictory information regarding the comparison of traditional histological dating criteria of the endometrium with the expression of the new markers of endometrial receptivity such as alphavbeta3 integrin and pinopods. Also, definite data with respect to the potential correlation existing between these different new markers in defining the putative window of implantation are lacking., Methods: The temporal relationship between alphavbeta3 integrin expression and pinopod formation in normal and out-of-phase endometrial biopsies from normal healthy women (n = 12) and infertile patients (n = 36) was investigated. Two endometrial biopsies (postovulatory day +7 to +8 and 4 days later) were performed during a single menstrual cycle in each subject. Estradiol and progesterone serum concentrations were quantified on the same days as endometrial sampling., Results: No statistically significant difference regarding alphavbeta3 integrin expression, pinopod formation, and hormone concentrations was found between fertile controls and infertile patients irrespective of endometria being in-phase or out-of-phase. Although a coordinate high level of expression of alphavbeta3 integrin and pinopod on postovulatory days 7-8 was observed, there was an evident lack of temporal co-expression of these markers over the luteal phase in the endometrial samples investigated., Conclusions: There is a clear dissociation in the temporal expression of the most cited markers postulated to frame the window of implantation. The functional significance (if any) of these new markers remains to be established.

It has been recently proposed that the immunohistochemical evaluation of alphavbeta3 integrin in combination with histologic dating in midluteal endometrial biopsy specimens should be performed to evaluate the endometrial receptivity in the infertile patient. However, no studies have attempted to correlate these findings with subsequent fecundity. In 100 consecutive infertile patients (mean age 31.9+/-3.4 years) undergoing a routine work-up, two endometrial biopsies were performed during a single menstrual cycle: a midluteal biopsy on postovulatory days 6 to 8 and another biopsy 4 days later. Histological dating and immunohistochemical evaluation of alphavbeta3 integrin expression were done in all endometrial biopsy specimens. All patients were followed without treatment during 18 to 24 months (mean 23.5+/-1.4, range 18 to 24). Twenty-five midluteal biopsies showed out-of-phase endometria, whereas all but one late-luteal biopsy specimens were in-phase. Glandular alphavbeta3 integrin expression was observed in 50% of midluteal specimens with this expression being significantly more frequent among in-phase (63%) than among out-of-phase (12%) specimens (p<0.001). However, all late-luteal specimens strongly expressed this integrin. Thirty-eight women became spontaneously pregnant during the follow-up period, 32 ended in a live birth and 6 in first trimester spontaneous abortion. The Cox regression method showed no differences between the hazard of pregnancy when the alphavbeta3 integrin-positive and -negative groups were compared (odds ratio 1.25; 95% confidence interval [CI] 0.66-2.36; p=0.49) or when patients with in-phase endometria were compared with those with delayed endometrial maturation (odds ratio 1.12; 95% CI 0.53-2.37; p=0.76). In conclusion, neither midluteal histological evaluation nor alphavbeta3 integrin expression in mid- or late-luteal endometrial biopsy specimens correlated with outcome for subsequently untreated infertile women.

Objective: To characterize the chronology of hemodynamic changes in in vitro fertilization (IVF) cycles and its relationship with circulating ovarian steroids, cytokines, and their mediator nitric oxide., Design: Prospective, cross-sectional study., Setting: University teaching hospital., Patient(s): Eighty-eight IVF patients., Intervention(s): Ovarian stimulation with FSH under pituitary suppression., Main Outcome Measure(s): Circulating levels of estradiol, progesterone, nitrite/nitrate, interleukin-6, vascular endothelial growth factor, tumor necrosis factor alpha, aldosterone, norepinephrine, as well as measurements of plasma renin activity and mean arterial pressure., Result(s): The maximal stimulation of the renin-aldosterone and sympathetic nervous systems was seen 7 days after hCG administration, although values still remained elevated over normal control values on day of hCG + 11. Mean arterial pressure in IVF patients remained significantly reduced throughout the luteal phase. Changes in the stimulation of the renin-aldosterone system correlated temporally with progesterone but not estradiol levels. No significant changes were observed in circulating concentrations of cytokines investigated or nitric oxide., Conclusion(s): The circulatory changes and the homeostatic activation of the renin-aldosterone system and sympathetic nervous system that consistently develop in patients undergoing controlled ovarian hyperstimulation for IVF is a feature associated with the luteinization process. These hemodynamic changes occur in the absence of variations in the circulating levels of cytokines potentially involved in ovarian hyperstimulation syndrome.

Mesonephric (wolffian) neoplasms of the female genital tract are infrequent and found in sites where embryonic remnants of wolffian origin are usually detected, such as the uterine cervix, broad ligament, mesosalpinx, and ovary. Their diagnosis is difficult because of the absence of specific immunohistochemical markers for mesonephric derivatives. We present the first report of adenocarcinoma of mesonephric type arising as a purely myometrial mass without endometrial or cervical involvement in the uterine corpus of a 33-year-old woman. The tumor showed a combination of patterns, with retiform areas, ductal foci, and small tubules with eosinophilic secretion, which merged with solid sheets of cells with a sarcomatoid appearance. Immunohistochemically, neoplastic cells were diffusely positive for cytokeratin 7, epithelial membrane antigen, and CD15 and focally positive for BerEP4 and vimentin. A hitherto unreported feature was the positivity for CD10 in neoplastic cells, which was also present in a large number of control tissues obtained from male mesonephric derivatives and female mesonephric remnants and tumors. Furthermore, CD10 was negative in controls from müllerian epithelia of the female genital tract and in their corresponding tumors. Therefore, the expression of CD10 by mesonephric remnants may be useful in establishing the diagnosis of tumors with mesonephric differentiation.

Objective: The aim of the present study was to determine whether assignment to continuous estrogen-progestin therapy is more effective in protecting against bone loss than assignment to a sequential regimen., Study Design: A total of 104 postmenopausal women were randomly assigned to one of two groups of treatment, Conjugated Equine Estrogens and Medroxyprogestin without interruption (continuous group) and Conjugated Equine Estrogens over 25 days with Medroxyprogestin beyond the 14th day (sequential group). Bone mineral density (BMD) was measured at inclusion, 12 and 24 months later by dual energy X-ray absorptiometry., Results: among women completing the 2-year treatment period, continuous and sequential regimens yielded results significantly different from baseline values, but not significantly different from each other at the 12-month (4.2 and 4%) or 24-month visits (6.6 and 6.3%). In the intention-to-treat analysis, the results with both regimens also differed from baseline values; additionally, the continuous group showed a greater increase in BMD than the sequential group at the 12-month (3.5 and 3%) and at the 24-month visits (5.5 versus 4.6%)., Conclusion: assignment to continuous administration seems to be more effective in increasing bone density than the sequential regimen. Thus, combined continuous estrogen therapy would seem to be the most effective regimen for those women requiring long-term hormone replacement therapy.