Saline contrast hysterosonography in infertile patients and in women with abnormal uterine bleeding.

OBJECTIVE: We conducted this prospective study to evaluate saline contrast hysterosonography (SCHS) as a diagnostic modality for intrauterine lesions in comparison to hysteroscopy and endometrial biopsy. MATERIALS AND METHODS: We included 135 patients, of whom 70 presented with abnormal uterine bleeding and 65 with subfertility problems. All cases were examined with conventional transvaginal sonography and were further investigated with SCHS using saline as contrast medium, and finally hysteroscopy with endometrial biopsy that was used as the reference test. RESULTS: SCHS revealed the presence of intrauterine pathology in 23 cases and failed in three (4.2%). SCHS had a sensitivity of 94%, a specificity of 71%, a positive predictive value of 76% and a negative predictive value of 95% in the abnormal uterine group. In subfertile patients, SCHS revealed the presence of intrauterine pathology in 34 cases and had a sensitivity of 96%, a specificity of 74%, a positive predictive value of 79% and a negative predictive value of 95%. CONCLUSIONS: We found that SCHS is an extremely accurate modality for the diagnosis of focal endometrial pathology, compared to diagnostic hysteroscopy.

Small doses of LH activity are needed early in ovarian stimulation for better quality oocytes in IVF-ET.

OBJECTIVE: To examine whether exogenous LH administration has a beneficial effect on the quality of oocytes, fertilization potential, as well as pregnancy rate in IVF-ET cycles. A randomized trial comparing r-FSH versus r-FSH and LH was employed. STUDY DESIGN: Forty-six infertile couples entering IVF-ET for the first time (either tubal or male factor) were divided after prospective randomization into two groups. In both groups the long protocol with GnRH-analogs was used. In group A, ovarian stimulation started with r-FSH (200 IU/day) for the first four days. In group B, the stimulation protocol started with one amp hMG (75 IU FSH + 75 IU LH activity) daily for four days, with simultaneous administration of r-FSH (150 IU/day). The outcome was compared. RESULTS: Statistical difference was observed in the number of mature oocytes, the number of fertilized oocytes as well as the number of transferable embryos. In all cases, results were statistically significantly better (p < 0.05) in group B. Clinical pregnancy rate, finally, was similar in the two groups. CONCLUSION: The relatively small sample size does not allow a definitive conclusion for the important role of LH during early oocyte maturation. Our results, however, indicate a beneficial effect when small doses of LH are used for ovarian stimulation in IVF-ET cycles. This effect may be more important in cases in which few embryos are available for transfer.

Comparison between "short" and "long" protocols in an ICSI programme.

In the present retrospective study we compare the efficacy of gonadotropin-releasing hormone (GnRH) agonist in a long protocol and a GnRH agonist in a short protocol administration for controlled ovarian hyperstimulation (COH) in an ICSI program. A total of 424 consecutive patients with a history of male factor were included in the present study. Three hundred and three patients were included in the long protocol and 121 in the short protocol. Patients treated with the short protocol were stimulated in a shorter time and achieved lower estradiol levels. A significantly higher percentage of oocytes transferred were found in the long protocol. The clinical pregnancy rate per embryo transfer was 39.3% in the long protocol and 19.2% in the short protocol (p=0.001).

EGF and IGF-I as predictors of ICSI outcome in human preimplantation embryo cultures.

PURPOSE OF INVESTIGATION: Detection of EGF and IGF-I in human embryo cultures and their effect on ICSI outcome. METHODS: Collection of culture medium from embryos of 50 women under ICSI program. EGF and IGF-I were measured via enzyme immunoassay. RESULTS: ICSI outcome was independent of age, infertility years, FSH, LH, prolactine and E2. EGF detection was higher in 48- (32%), than in 72-hour embryos (14%) (p < 0.001). EGF negative embryos are likely to be arrested at the morula stage (p < 0.001) and are associated with poor pregnancy rates (p < 0.05). IGF-I was undetected in 48-hour embryos. CONCLUSIONS: For the first time human embryos were surveyed from fertilization until embryo transfer, regarding EGF and IGF-I production. IGF-I is not a predictor of ICSI outcome. EGF is present in one-third of human embryo cultures at 48 hours, but this ratio wanes at the morula stage. EGF negative embryos are associated with lower pregnancy rates.

Tissue evaluation of immune markers in endometrial and cervical carcinomas.

Major histocompatibility complex (HLA system) class II molecules including HLA-DR antigens, associate with peptides, which are derived from antigens, for presentation to T4 lymphocytes. Functional and adhesion assays have shown that CD4 molecule interacts with HLA class II molecules, leading to enhanced responses of T4 cells. In the present study, we examined the tissue expression of HLA-DR antigens and the quantitative variance of T4 lymphocytes in a series of 50 "endometrioid" adenocarcinomas of the endometrium and 35 cervical squamous-cell carcinomas. A three-step avidin-biotin immunoperoxidase staining method was applied. As primary antibodies, we used the TAL.1BS monoclonal antihuman HLA-DR alpha (alpha) chain antibody and the OPD4 mouse antihuman antibody; the latter mainly identifies benign T4 lymphocytes. Twenty-four percent (24%) of women with endometrial cancer were high immune responders, while the relative percentage in women with cervical cancer was 40%; the respective tumours were of early clinical and surgical stages. HLA-DR determinants were predominantly expressed in membranes of stromal cells, mainly histiocytes, usually around HLA-DR+ lymphoid cells, as well as on endothelial cells. Greater numbers of OPD4+ aggregated lymphocytes were observed when the tumour stroma was rich in HLA-DR+ cells. Epithelial elements, either cancerous or benign, were seldom HLA-DR+. In those samples, positive immunolabelling was often confined in the intercellular space and did not seem to activate an effective host immune response against neoplastic cells. High expression of HLA-DR molecules in professional antigen presenting stromal cells may be used as a lymphocyte activation marker in endometrial and cervical carcinomas. This activation appears to be an early event in the evolution of invasive endometrial and cervical carcinomas.

Angiogenic properties of carcinoma in situ and microinvasive carcinoma of the uterine cervix.

Neovascularization is a critical step in the growth, progression and metastasis of tumors. The degree of angiogenesis may correlate with disease stage and provide prognostic information in various neoplasms. Microvessel density was studied in 24 patients with severe cervical intraepithelial neoplasias, 15 patients with microinvasive carcinomas (International Federation of Gynecology and Obstetrics IA1) and 15 healthy controls who had undergone hysterectomy for benign conditions. The microvessel density (MVD) in microinvasive squamous cell carcinomas was 40 +/- 2.42 (mean +/- SD) and in squamous carcinomas in situ (CIS) 20.41 +/- 2.29 (p < 0.05). Among patients with CIS and controls (13.33 +/- 1.59) there was also a significant difference in the number of vessels (p < 0.05). No significant correlation was found in relation to depth of invasion and histological grade of the microinvasive carcinomas. It is concluded that microinvasive squamous cell cervical carcinoma is an angiogenetic disorder and it seems that the onset of angiogenesis is an early event, usually in a preinvasive stage.

The prognostic significance of the immunohistochemical expression of p53, bcl-2, c-erb B-2 and cathepsin-D in ovarian cancer patients receiving platinum with cyclophosphamide or paclitaxel chemotherapy.

PURPOSE: To evaluate the prognostic significance of the immunohistochemical expression of p53, bcl-2, c-erbB-2 and cathepsin-D in epithelial ovarian cancer (EOC). METHODS: We analyzed 100 patients with ovarian carcinoma, FIGO Stage IC-IV who underwent primary cytoreductive surgery and received adjuvant chemotherapy with cyclophosphamide and a platinum analogue (CP) (n = 46) or paclitaxel and a platinum analogue (TP) (n = 54). Immunohistochemical expression was studied on paraffin-embedded tissue from the primary tumor. RESULTS: After a median follow-up of 55 months median progression-free survival (PFS) and overall survival (OS) were 16 and 41 months, respectively. Positive bcl-2 staining and absence of cathepsin-D expression were associated with an increased complete response rate in the CP group (p = 0.011 and p = 0.003) but not in the TP group. PFS and OS were not associated with the expression of any of the markers studied. FIGO stage (p = 0.006) and histology (p = 0.047) were the only independent prognostic factors for survival. CONCLUSION: Bcl-2 and cathepsin D expression are associated with response to CP but not TP chemotherapy. P53, bcl-2, c-erb B-2 and cathepsin D expression was not correlated with PFS and OS in our study.

A double embryo transfer on days 2 and 4 or 5 improves pregnancy outcome in patients with good embryos but repeated failures in IVF or ICSI.

The purpose of this paper was to evaluate the outcome of a double embryo transfer during the same cycle for patients who had had three or more implantation failures in IVF-ET or ICSI-ET programs after the transfer of good quality embryos in all attempts. Forty-five women who had had previous unsuccessful attempts in IVF-ET or ICSI-ET programs after transfer of good quality embryos (Group A) were included in the study. Group A was divided into two subgroups, Group A1 consisted of 34 patients who underwent embryo transfer on day 2 and day 4 after pick-up and Group A2 consisted of ten patients who underwent embryo transfer on day 2 and day 5 after pick-up. Forty-two other women with a similar unsuccessful history in IVF-ET (Group B) were studied as controls. The patients in this group had a day 4 or 5 only transfer without having an additional day 2 transfer. The outcome of the procedure was compared in the two groups. Double embryo transfer had beneficial effects on patients with good embryos but with previous failure attempts. These patients had a 38.2% clinical pregnancy rate and a 50% total pregnancy rate if the additional embryo transfer was done on day 4 and a 60% clinical and 60% total pregnancy rate if the additional embryo transfer was done on day 5. Our data showed that excellent pregnancy rates can be obtained with a commercially available medium and double embryo transfers on days 2 and 4 or 5 after pick-up for patients with good quality embryos that have had previous failure attempts in an IVF-ET program. Due to the fact that endometrial maturation varies considerably in each patient, an adequate endometrial maturation and improved uterine receptivity seem to be the reason for improved pregnancy rates with double embryo transfers. It was also shown that morullae have high viability and high potential for implantation and pregnancy.

Results of controlled ovarian stimulation for ART in poor responders according to the short protocol using different gonadotrophins combinations.

INTRODUCTION: Improving pregnancy rates in intricate cases of ovarian stimulation remains a challenge during IVF and intracytoplasmic sperm injection (ICSI). Different protocols of ovulation induction have been proposed. METHODS: The short protocol of ovarian stimulation using recombinant follicle-stimulating hormone (rFSH) with or without the use of luteinizing hormone (LH) in IVF or ICSI outcome in patients with many failed attempts and maternity age > or = 37 years was investigated. The prognostic significance of high but normal values of day 3 serum FSH concentrations was also evaluated. RESULTS: Results show that FSH levels of >9 mIU/ml are associated with poor results even with the use of human menopausal gonadotrophin (HMG). Results were generally comparable when rFSH was used alone or in combination with HMG, except for the quality and the number of embryos transferred, the later being better in the rFSH + HMG group. CONCLUSION: In conclusion intricate cases have good chances for achieving a pregnancy using the short protocol and the outcome is further improved when LH is added from the beginning of ovarian stimulation. A slight elevation of day 3 FSH seems to be a strong prognostic factor for a poor outcome.

Endometriosis and reproductive disorders.

The classic concept of endometriosis as a cause of infertility is challenged. Traditionally, both surgical and medical therapy have focused on alleviation of symptoms, prevention of disease progression, and promotion of fertility. In spite of significant developments in medical and surgical approaches, the optimal therapy for treating endometriosis-associated infertility has yet to be established. The relationship between prevalence of fecundity and stage of the disease was studied according to the type of management. Of 151 women who were consecutively proved by laparoscopy to have endometriosis stage I and II, operative laparoscopy was performed in 49, medical treatment in 59, and expectant management in 43 cases. During a 24-month period, the cumulative pregnancy rates were 36.7%, 30.5%, and 20.9%, respectively. Survival analysis over the 20 weeks of pregnancy showed that the probability of carrying the pregnancy beyond this week was 30.6%, 25.4%, and 16.2%, respectively. Of 64 patients with advanced disease, 34 (53%) became pregnant during the 2-year follow-up period. A significantly increased pregnancy rate was found for the first year as compared to the second (76% vs. 24%). The existence of adhesions affected adversely the outcome of the treatment when early achievement of pregnancy is considered. Diagnosis and treatment of endometriosis was beneficial for the infertile women. Laparoscopic surgery seems to be the best treatment in these cases, as it increases the fecundity and involves minimal risk.

Group B streptococcus colonization of Greek pregnant women and neonates: prevalence, risk factors and serotypes.

OBJECTIVE: To evaluate the prevalence and risk factors of group B streptococcus (GBS) colonization among pregnant women and their neonates in Greece, and to examine the serotype distribution of the GBS strains isolated and their susceptibility to antibiotics. METHODS: A vaginal and a rectal swab were obtained from 1014 pregnant or parturient women followed at public and private hospitals in Athens and in a city of northern Greece. Cultures were also taken 24 h after birth from 428 neonates born to these women. RESULTS: The overall maternal and neonatal colonization rates were 6.6% and 2.4%, respectively. The vertical transmission rate was 22.5%. By logistic regression analysis, multiparity (>/=III) was associated with a lower colonization rate (odds ratio 4.4, 95% confidence interval 1.08-18.63). In contrast with other studies, middle-class women followed privately were more frequently colonized (10%) than those followed at the public hospital (3.9%) (odds ratio 3.1, 95% confidence interval 1.83-5.42). A higher number of prenatal visits was also associated with a higher colonization rate (change in true odds ratio when visits increased by one, 1.3; 95% confidence interval 1.14-1.60). No association was found between colonization and maternal age, previous obstetric history, marital status, nationality, prematurity, Caesarean section, or infant birth weight. The most common serotypes were II (26.9%), III (22.4%), Ia (19%), Ib (12%), and V (9%). A considerable proportion of the isolated strains was resistant to erythromycin (4.5%), clindamycin (6%), or both (6%). CONCLUSION: The rate and risk factors of maternal and neonatal GBS colonization may vary in different communities. These rates, as well as the incidence of neonatal disease, need to be thoroughly evaluated in each country to allow the most appropriate preventive strategy to be selected.

Fetal blood sampling in twin pregnancies.

OBJECTIVE: To evaluate the role of fetal blood sampling for prenatal diagnosis in twin pregnancies. METHODS: This was a retrospective study of 84 twin pregnancies that had undergone fetal blood sampling between the years 1977 and 2000. These results were compared with those from a similar study on amniocentesis and chorionic villus sampling. RESULTS: Miscarriage occurred in 3.6% of cases after fetal blood sampling. The total fetal loss rate was 13.6% and the fetal loss that could be attributed to the procedure was 8.2%. The procedure-related fetal loss rate was dependent on the indication for fetal blood sampling. The rates of preterm delivery at 28 weeks and neonatal mortality were 16.9%, 28.3%, 10.9%, 3.1% and 7.7%, respectively. CONCLUSION: Fetal blood sampling in twin pregnancies carries higher risks for the fetus than do amniocentesis and chorionic villus sampling. However, it remains useful in evaluating the fetal condition in special circumstances such as hydrops and infection.

Knowledge, attitude, and behavior of female students concerning contraception in Athens, Greece.

The aims of this study were to investigate the knowledge, attitudes and behavior of female high school and university students concerning contraception. The study was performed at the Alexandra University Hospital in Athens. A total of 297 female students participated in the study. A questionnaire was used to evaluate the depth of knowledge and attitude of respondents concerning contraception. Our findings suggest students have a defective knowledge of contraception. Their main source of information were friends but the majority would prefer to receive information from doctors. The most popular contraceptive method was the male condom. The attitude and behavior of young women in our study were consequently defective. In conclusion, there is a need to provide students with correct, detailed and broad-based information on conception and contraception as part of the school curriculum to help them acquire adequate knowledge and develop appropriate attitudes on contraception and sexual health.

Vulvar intraepithelial neoplasia (VIN)--diagnostic and therapeutic challenges.

PURPOSE: Vulvar intraepithelial neoplasia (VIN) represents a current diagnostic and therapeutic challenge. The present retrospective study is an institutional experience on the diagnosis and management of VIN. METHODS: One hundred and thirteen women with VIN were reviewed and analyzed. Diagnosis was established by colposcopically directed biopsies whereas treatment was performed by either a surgical or a laser CO2 approach. RESULTS: The mean age of all VIN patients was 47.4 years. The most common symptom was pruritus (60.1%). The majority of the lesions were multifocal (N = 64, 56.6%) and located in the non-hairy part of the vulva (87.6%). VIN management consisted of laser CO2 treatment in 51 patients (45.1%), surgical treatment in 37 (32.7%) whereas 25 VIN, cases were managed by conventional medical treatment. The risk of disease relapse was not associated with VIN grade (p = 0.35) nor with the treatment modality used (p = 0.42). The risk of disease relapse was significantly higher for multifocal lesions (p < 0.001). Long-term follow-up of our patients showed that four patients (3.5%) developed an invasive vulvar carcinoma. CONCLUSION: Our study confirms other reports concerning the diagnostic and treatment difficulties of the management of VIN. Although the benefits of treatment are obvious there seems to be no guarantee that invasion will not occur.

Does pre-treatment with micronized progesterone affect the ovarian response to a gonadotropin releasing hormone agonist flare-up protocol?

The purpose of this study was to investigate the ovarian response and the receptivity of the endometrium in women pre-treated with micronized progesterone. Eighty-two normogonodotropic women undergoing in vitro fertilization were studied. Thirty received micronized progesterone 1500 mg/day from day 21 of the cycle for a minimum of 2 weeks, and 52 did not receive micronized progesterone (control group). A gonadotropin releasing hormone agonist (GnRH-a) was administered to all the patients in the follicular phase (flare-up). Twenty-five cycles were cancelled for fertilization failure due to male factor, 12 (40%) in the progesterone group and 13 (25%) in the control group (p = 0.271). There was no difference in the number of oocytes retrieved (7.3 +/- 5 vs. 8.2 +/- 4), fertilization rate (50.8% vs. 65%), clinical pregnancy rate (16.6% vs. 25%) or implantation rate (8% vs. 14%). In the progesterone group cases without fertilization, we performed two biopsies to evaluate the receptivity of the endometrium. Pinopode expression was noted 7 days after oocyte retrieval. It seems that the administration of micronized progesterone in the previous cycle does not affect the ovarian response to the combination of follicular phase GnRH-a and gonadotropins, nor the receptivity of the endometrium.

Intravenous leiomyomatosis.

INTRODUCTION: Intravenous leiomyomatosis (IVL) is rare and it is characterized by intravascular nodular masses of histologically benign smooth muscle that may extend variable distances. Although histologically benign, IVL might be malignant in its mode of behavior. CASE REPORT AND DISCUSSION: A case of IVL is reported with emphasis on immunohistochemical analysis and recent literature.

Septic lithiasis of the pelvis.

Laparoscopic cholecystectomy has become a standard technique for the treatment of symptomatic cholelithiasis. Despite a significant reduction in the complication rate with increasing experience, bile duct injury and gallstone spillage still occur more frequently with this approach than with the open procedure. Unretrieved gallstones, in particular, have been associated with late infection and the formation of abscesses in virtually every area of the abdominal cavity. We present a rare case of an isolated pelvic abscess that developed in a postmenopausal woman 5 months after laparoscopic cholecystectomy for recurrent cholecystitis. The preoperative differential diagnosis of this case is also discussed.

Second-trimester amniocentesis vs. chorionic villus sampling for prenatal diagnosis in multiple gestations.

OBJECTIVE: To study the impact of invasive procedures for prenatal diagnosis on multiple pregnancies and compare first-trimester chorionic villus sampling with second-trimester amniocentesis. DESIGN: Retrospective study of 347 second-trimester amniocenteses and 69 chorionic villus sampling procedures. RESULTS: Miscarriage occurred in 4.18% of women after amniocentesis and 4.54% of women after chorionic villus sampling. In the amniocentesis group the risk of miscarriage was higher in the cases with transplacental entry (4.54%) than in those with transamniotic entry (2.08%). The rates of preterm delivery < or = 32 weeks and preterm delivery < or = 35 weeks in the amniocentesis group were 11.8% and 32.4% and in the chorionic villus sampling group 16.66% and 23.8%, respectively. Total fetal loss rate was similar in the amniocentesis group (8.8%) and the chorionic villus sampling group (10.22%). In the 21 cases where selective feticide was carried out the total fetal loss rate was lower in the chorionic villus sampling group (8.3%) than in the amniocentesis group (11.1%), although the difference did not reach statistical significance. CONCLUSION: Chorionic villus sampling appears to be a safe alternative to amniocentesis and should be considered as the method of choice particularly when there is a high risk of an affected fetus necessitating selective feticide.

Fecundity of infertile women with minimal or mild endometriosis. A clinical study.

Despite significant developments in medical and surgical approaches for treating endometriosis, the optimal therapy has yet to be established. The relationship between prevalence of fecundity and stage of endometriosis according to their management was studied. Of 151 consecutive women with laparoscopy-proved endometriosis stage-1 and 2, operative laparoscopy was performed in 49, medical treatment in 59 and expectant management in 43 cases. During a 24-month period the cumulative pregnancy rates were found to be 36.7%, 30.5% and 20.9% respectively. Survival analysis showed that the probability of carrying the pregnancy beyond 20 weeks were 30.6%, 25.4% and 16.2% respectively. Diagnosis and treatment of early endometriosis is beneficial for the infertile women. Laparoscopic surgery seems to be the milestone of treatment in these cases, increasing the fecundity and involving minimal risk.

Vaginal intraepithelial neoplasia: report of 102 cases.

BACKGROUND: Vaginal intraepithelian neoplasia (VAIN) is a rare asymptomatic disorder. The aims of the current study were to profile patients with VAIN and to evaluate the response to treatment. MATERIAL AND METHODS: We reviewed the records of 102 patients with VAIN diagnosed from 1990 to 2000. RESULTS: Patients with VAIN, VAIN2 and VAIN3 had the following mean ages 44.5, 47.8 and 61.8 years, respectively (p < 0.001). All patients with VAIN were found to have abnormal Papanicolaou smears. Localization of the lesions to the upper third of the vagina was observed in 80% of the cases. Recurrences following laser ablation and partial vaginectomy reached 21%. Patients with minimal VAIN lesions from whom punch biopsies were obtained had the lowest recurrence rate. Multifocality significantly affected the risk of recurrence (p = 0.03). CONCLUSION: VAIN most often involves the upper third of the vagina and is often multifocal. Patient selection and operator skill have a significant influence on the treatment outcome.