Dimitrios Hassiakos

The diagnostic value of laparoscopy in 2365 patients with acute and chronic pelvic pain

Objective: To discriminate the etiology in 2365 patients with acute and chronic pelvic pain (APP, CPP). Methods: Diagnostic laparoscopy was carried out in 736 patients (31.1%) with APP and in 1629 (68.9%) with CPP. In 315 patients (13.3%) the diagnostic procedure was extended to operative laparoscopy. Results: The most frequent laparoscopic findings in patients with APP were acute salpingitis and pelvic adhesions (22.8%) and ectopic pregnancy (19%), while in patients with CPP the most frequent findings were pelvic adhesions (35.4%) and endometriosis (24.6%). In 7.5% of patients with APP and 24% with CPP, laparoscopy did not reveal any pathological finding in the pelvis. Among the 315 patients in whom operative laparoscopy was carried out, 40% suffered from APP and 60% from CPP. In the 446 patients (18.9%) without laparoscopic findings no treatment was given, while of the remaining 905 patients 40% were subjected to laparotomy and 60% received conservative treatment. The total incidence of side effects reached 4.7% and serious side effects resulting from emergency laparotomy occurred in 0.15% of patients with pelvic pain. Conclusion: Our results in a large group of patients with pelvic pain show that there are discrepancies in the incidence of laparoscopic findings between patients with APP and CPP. Discrepancies between the two groups of patients were also found during operative laparoscopy, the treatment administered after laparoscopic diagnosis and the complications encountered.

Concentrations of angiogenic factors in follicular fluid and oocyte-cumulus complex culture medium from women undergoing in vitro fertilization: association with oocyte maturity and fertilization

OBJECTIVE To determine the concentration of angiogenic factors (vascular endothelial growth factor [VEGF], basic fibroblast growth factor [bFGF], and angiogenin) in the follicular fluid (FF) and oocyte-cumulus complex culture medium (CM) of women undergoing IVF and to investigate the association of the concentrations with the maturity and fertilization of the oocyte. DESIGN Prospective study. SETTING Academic tertiary-care institution. PATIENT(S) IVF patients with unexplained or tubal factor infertility. INTERVENTION(S) Analysis of VEGF, bFGF, and angiogenin FF and CM concentrations. MAIN OUTCOME MEASURE(S) Oocyte maturity and fertilization and FF and CM angiogenic factor concentrations. RESULT(S) VEGF, bFGF, and angiogenin were determined in FF and CM. FF angiogenin concentrations were significantly higher when the oocyte was mature versus immature. CM VEGF concentrations were significantly higher when the oocyte was nonfertilized versus fertilized. Positive correlations were observed between angiogenic factors in CM. CONCLUSION(S) VEGF, bFGF, and angiogenin (determined for the first time) are secreted in the FF and CM. Elevated CM VEGF concentrations, probably implying oocyte-cumulus complex hypoxia, are negatively associated with oocyte fertilization. Elevated FF angiogenin concentrations are positively associated with oocyte maturity, possibly indicating angiogenins biological role beyond neovascularization.

Hysteroscopy in Women with Implantation Failures after In Vitro Fertilization: Findings and Effect on Subsequent Pregnancy Rates

OBJECTIVE To evaluate hysteroscopic findings and estimate the effect of hysteroscopy on achieving a pregnancy in women with a history of 2 implantation failures after in vitro fertilization (IVF). DESIGN Prospective observational and matched case control study. DESIGN CLASSIFICATION II-2. SETTING Private assisted reproduction units. PATIENTS A total of 1475 patients with a history of 2 consecutive implantation failures after IVF who had a hysteroscopy were studied; there were 414 matched pairs of women with a similar history who either had or did not have a hysteroscopy. INTERVENTIONS Hysteroscopy (diagnostic or operative), IVF/intracytoplasmic sperm injection cycle. MEASUREMENTS AND MAIN RESULTS Hysteroscopic findings, clinical pregnancy rate (CPR), and ongoing pregnancy rate (OPR) were measured. In all, 36.6% of the study population had abnormal hysteroscopic findings and 22.2% had unsuspected findings; women with abnormal hysteroscopic findings showed significantly increased CPR and increased OPR in a new IVF cycle compared with those with a normal hysteroscopy result. Women who had a hysteroscopy showed significantly increased CPR and OPR compared with matched control subjects who did not have the procedure. Hysteroscopy and appropriate therapy significantly increased the chances of achieving a subsequent clinical and ongoing pregnancy. CONCLUSION Women with 2 implantation failures after IVF had a remarkably high possibility for unsuspected abnormalities seen at hysteroscopy. Hysteroscopy could serve as a positive prognostic factor for achieving a subsequent pregnancy.

Possible Early Prediction of Preterm Birth by Determination of Novel Proinflammatory Factors in Midtrimester Amniotic Fluid

Abstract:  Interferon‐γ‐inducible T cell‐α chemoattractant (ITAC) is a chemokine, directing activated T lymphocytes toward sites of inflammation. ADAM‐8 (A disintegrin and metalloprotease‐8) is a glycoprotein expressed in cells promoting inflammation. Elastase, a protease targeting at the degradation of intra‐ or extracellular proteins, is inhibited by secretory leukocyte proteinase inhibitor (SLPI), which protects against microbial invasion. Adhesion molecules (soluble intercellular adhesion molecule—sICAM‐1 and soluble vascular cell adhesion molecule—sVCAM‐1) serve as markers of inflammation or tissue damage. We hypothesized that elevated midtrimester amniotic fluid concentrations of above substances, and decreased levels of SLPI could possibly be useful predictors of asymptomatic intra‐amniotic inflammation and/or infection, eventually resulting in preterm labor and delivery. The study involved 312 women undergoing midtrimester amniocentesis. Thirteen cases, progressing to preterm delivery (<37 weeks), were matched with 21 controls (delivering >37 weeks) for age, parity, and gestational age at amniocentesis. Amniotic fluid levels of the above substances were measured by enzyme‐linked immunosorbent assay (ELISA). Only amniotic fluid ITAC and ADAM‐8 levels were significantly higher (P= 0.005 and P < 0.02, respectively) in women delivering at <37 weeks than at >37 weeks. SLPI concentrations significantly increased in women going into labor without ruptured membranes irrespective of pre‐ or term delivery (P < 0.007, P < 0.001, respectively) and correlated with elastase (r= 0.508, P < 0.002). In conclusion, elevated midtrimester amniotic fluid levels of ITAC and ADAM‐8 could predict occult infections/inflammations, possibly resulting in preterm birth.

Vascular Endothelial Growth Factor and Placenta Growth Factor in Intrauterine Growth-Restricted Fetuses and Neonates

The angiogenic factors vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) are respectively up- and downregulated by hypoxia. We aimed to study circulating levels of the above factors in intrauterine growth restriction (IUGR) and to correlate their levels with the customized centiles of the infants. The study included 25 IUGR and 25 appropriate for gestational age (AGA) full-term, singleton infants and their mothers. Maternal (MS), fetal (UC), and neonatal day 1 (N1) and 4 (N4) blood was examined. MS and N1 PlGF, as well as UC VEGF levels correlated with the customized centiles of the infants (r= 0.39, P=.007, r=0.34, P=.01, and r= -0.41, P=.004, resp). Furthermore, UC, N1, and N4 VEGF levels were higher in girls (r=0.36, P=.01, r=0.33, P=.02, and r=0.41, P=.005 resp). In conclusion, positive and negative correlations of examined factors with the customized centiles of the infant could rely on placental function and intrauterine oxygen concentrations-both being usually lower in IUGR cases-while higher VEGF levels in girls should possibly be attributed to the stimulating action of estrogens.

Changes in hormonal profile and seminal parameters with use of aromatase inhibitors in management of infertile men with low testosterone to estradiol ratios

OBJECTIVE To compare the effects of 2.5 mg letrozole with those of 1 mg anastrazole daily on the hormonal and semen profiles of a subset of infertile men with low T/E(2) ratios. DESIGN Prospective, nonrandomized study. SETTING Reproductive medicine clinic. PATIENT(S) The study group consisted of 29 infertile men with a low serum T/E(2) ratio (<10). INTERVENTION(S) Patients were divided into two groups. Group A included 15 patients treated with 2.5 mg letrozole orally once daily for 6 months, and Group B consisted of 14 patients treated with 1 mg anastrazole orally every day for 6 months. MAIN OUTCOME MEASURE(S) Hormonal evaluation included measurement of serum FSH, LH, PRL, T, and E(2). In all sperm analyses pretreatment and posttreatment total motile sperm counts (ejaculate volume × concentration × motile fraction) were evaluated. RESULT(S) The use of aromatase inhibitors (either letrozole or anastrazole) in cases of infertile men with low T/E(2) ratios improved both hormonal and semen parameters. CONCLUSION(S) This study suggests that some men with severe oligospermia, low T levels, and normal gonadotropin concentration may have a treatable endocrinopathy.

Placental growth factor and soluble fms-like tyrosine kinase-1 are useful markers for the prediction of preeclampsia but not for small for gestational age neonates: a longitudinal study

OBJECTIVE To determine maternal serum concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) longitudinally in normal pregnancies, pregnancies that developed preeclampsia and pregnancies that deliver a small for gestational age (SGA) infant, in order to evaluate them as markers for the prediction of preeclampsia. STUDY DESIGN In this case-control study we included 12 singleton pregnancies that developed preeclampsia and 104 randomly selected singleton normal pregnancies. Fourteen of the normal pregnancies gave birth to an SGA infant. Blood samples and ultrasonographic data were collected during the 1st, 2nd and 3rd trimesters of pregnancy. RESULTS In preeclamptic pregnancies, PlGF (pg/mL) (median; inter-quartile range) was significantly lower in the 2nd (208; 84-339) (p=0.035) and in the 3rd trimester (202; 109-284) (p=0.002) while sFlt-1 was significantly higher only in the 3rd trimester (2521; 2101-3041) (p=0.011) compared to normal pregnancies (PlGF 2nd: 311; 243-440, PlGF 3rd: 780; 472-1037, sFlt-1 3rd: 1616; 1186-2220). In pregnancies with SGA infants, PlGF and sFlt-1 did not differ significantly from normal pregnancies in any trimester. The sFlt-1 to PlGF ratio was significantly higher in preeclamptic pregnancies than in normal pregnancies, in both the 2nd and 3rd trimesters. The relative difference and the slope of PlGF concentration between 1st and 2nd trimester were significantly reduced in preeclampsia compared to normal pregnancies. A logistic regression model with predictors BMI, 2nd trimester Doppler PI and relative difference of PlGF from the 1st to the 2nd trimester gave 46% sensitivity and 99% specificity for the prediction of preeclampsia, with a very high negative predictive value of 98.3%. CONCLUSIONS Our study confirms that maternal serum PlGF concentration is significantly lower, at least after 20th week, while sFlt-1 concentration is significantly higher in 3rd trimester, in pregnancies destined to develop preeclampsia. Pregnancies that gave birth to SGA infants do not have altered angiogenic factor concentrations throughout pregnancy. The relative difference of PlGF from the 1st to the 2nd trimester, uterine artery Doppler PI in the 2nd trimester and BMI are the most powerful markers for the prediction of preeclampsia.

Hysteroscopic resection of uterine septum and reproductive outcome in women with unexplained infertility.

Background/Aims: To investigate the reproductive outcome after hysteroscopic resection of uterine septum in women with septate uterus and otherwise idiopathic primary infertility. Methods: Sixty-eight patients with septate uterus and idiopathic primary infertility were included in this prospective observational study. All patients underwent hysteroscopic metroplasty with scissors under general anesthesia. Main outcome measures were clinical pregnancy rate, live birth and abortion rate at 12 months’ follow-up and at mean follow-up time. Results: At 12 months’ follow-up, the clinical pregnancy rate, the live birth rate and the abortion rate were 44% (30/68), 36.8% (25/68) and 16.6% (5/30), respectively. At total follow-up time, the overall pregnancy rate, the live birth rate and the abortion rate were 53.8% (35/65), 41.5% and 14.2% (7/35), respectively, while the stillbirth rate was 2.8% (1/35). Conclusion: Hysteroscopic metroplasty in women with septate uterus and unexplained infertility could improve clinical pregnancy rate and live birth rate in patients with otherwise unexplained infertility. If such a patient is looking for a spontaneous pregnancy, this is more likely to occur during the first 15 months following the procedure.

Changes in the quantity of collagen type I in women with genuine stress incontinence

Abstract The aim of this study, was to examine changes in the quantity of collagen type I in the pubocervical fascia of women with genuine stress incontinence (GSI), with and without pelvic relaxation . Seventy-eight patients participated in the study and they were divided into three groups that were comparable with respect to their age and parity. All the patients underwent filling cystometry and patients with detrusor instability were excluded from the study. Biopsies were obtained from the pubocervical fascia. The presence of collagen type I was determined with an immunohistochemical technique. The X-test was used for statistical analysis and a P < 0.05 was considered statistically significant. Collagen type I was significantly reduced in patients with GSI irrespective of the presence or absence of genital prolapse. Thus we found that women with GSI had a significant reduction of collagen type I in the pubocervical fascia which consequently affects the tensile strength of the pubocervical fascia and the support provided to the bladder neck.

Cervical pregnancy treated with transvaginal ultrasound-guided intra-amniotic instillation of methotrexate

AimAim of the study was to investigate the efficacy of single transvaginal ultrasound-guided intraamniotic installation of methotrexate in the management of cervical pregnancy with concurrent review of the literature.Materials and methodsSix patients with cervical pregnancy are included in the study. All patients were treated with single transvaginal ultrasound-guided intraamniotic installation of 70 mg of methotrexate plus folic acid p.o. The main presenting symptoms were mild to moderate vaginal bleeding and lower abdominal cramp-like pain, resembling the clinical presentation of a threatened abortion. The typical ultrasound findings were the absence of intrauterine gestational sac and the detection of a gestational sac within the cervical canal, invading the anterior or the posterior wall of the cervix and normal appearance of the adnexa, bilaterally. The hourglass-shaped cervix was not characteristic at 5 weeks of gestation but it was at 8 weeks of gestation.DiscussionUltrasound-guided intraamniotic installation of methotrexate in the management of cervical pregnancy appears to be an effective and safe method but the choice of the method should be depended on the gestational age of cervical pregnancy, the presence of active bleeding or not and its severity, the desire for preservation of future fertility, the presence of coexisting valuable intrauterine pregnancy and the experience of the physician in charge.