Impact of pre-treatment in GnRH-antagonist cycles triggered with GnRH agonist on reproductive outcomes.

OBJECTIVE: Pre-treatment (PT) therapies in IVF are known to be used as pre-stimulation modality to improve cycle outcomes. This study aims to assess whether PT in GnRH antagonist cycles triggered with GnRH-agonist impact oocyte maturation response. METHODS: Data were retrospectively collected for patients who underwent GnRH antagonist cycle with agonist triggering with and without PT. The patients were allocated to groups according to their PT status. The primary outcome evaluated was suboptimal maturation response. Suboptimal maturation to trigger was defined as no oocyte upon retrieval when adequate response was expected. RESULTS: The study population included 196 patients who underwent GnRH antagonist cycle with agonist triggering. The study group included 69 patients who received PT. The control group included 127 patients with no PT. In univariate analysis, the PT group significantly displayed suboptimal response compared to the controls (p = 0.008). All the patients in the study group with suboptimal response (with or without hCG re-triggering) were treated with GnRH-agonist as PT. Basal and pre-trigger LH values were significantly lower in the study group compared to controls (p < 0.001). Multivariate regression analysis revealed that PT with GnRH agonist was a significant predictor for suboptimal response. CONCLUSIONS: Pre-treatment, and particularly the use of GnRH-agonist as PT in antagonist cycles triggered with agonist, increases the risk of suboptimal response to GnRH-agonist trigger. This might be explained by prolonged pituitary suppression, which lasts beyond the PT cessation.

Toward clinical and molecular dissection of frontonasal dysplasia with facial skin polyps: From Pai syndrome to differential diagnosis through a series of 27 patients.

Unique or multiple congenital facial skin polyps are features of several rare syndromes, from the most well-known Pai syndrome (PS), to the less recognized oculoauriculofrontonasal syndrome (OAFNS), encephalocraniocutaneous lipomatosis (ECCL), or Sakoda complex (SC). We set up a research project aiming to identify the molecular bases of PS. We reviewed 27 individuals presenting with a syndromic frontonasal polyp and initially referred for PS. Based on strict clinical classification criteria, we could confirm only nine (33%) typical and two (7%) atypical PS individuals. The remaining ones were either OAFNS (11/27-41%) or presenting with an overlapping syndrome (5/27-19%). Because of the phenotypic overlap between these entities, OAFNS, ECCL, and SC can be either considered as differential diagnosis of PS or part of the same spectrum. Exome and/or genome sequencing from blood DNA in 12 patients and from affected tissue in one patient failed to identify any replication in candidate genes. Taken together, our data suggest that conventional approaches routinely utilized for the identification of molecular etiologies responsible for Mendelian disorders are inconclusive. Future studies on affected tissues and multiomics studies will thus be required in order to address either the contribution of mosaic or noncoding variation in these diseases.

Using adhesive glue to repair first degree perineal tears: a prospective randomized controlled trial.

Our objective was to evaluate the effectiveness of adhesive glue in repairing first degree perineal tears. We conducted a noninferiority prospective, randomized, controlled trial comparing adhesive glue with traditional suturing. Each case was evaluated immediately after birth and after the puerperium. The two-sample t-test and the Mann-Whitney nonparametric test were applied to compare quantitative variables between the treatment groups. The chi-squared test and Fisher's exact test were used to assess the association between qualitative variables. A total of 102 women participated, 28 in the suture arm and 74 in the adhesive glue arm. While cosmetic and functional results of adhesive glue use were not inferior to suturing, the use of adhesive glue was associated with a shorter procedure, less need for local anesthetic, less pain, and greater satisfaction. Our results suggest a novel approach for the repair of common postpartum first degree lacerations. The use of adhesive glue achieves cosmetic and functional results equal to traditional suturing and offers some immediate advantages for the patient. While further clinical trials are needed to validate our results, it is important to inform obstetrician of the possible use of adhesive glue in these very common clinical scenarios. This trial is registered with NCT00746707.

Zygote serine decreased uptake from the fertilization medium is associated with implantation and pregnancy.

PURPOSE: To identify an association between amino acids (AAs) metabolism and reproductive outcome. METHODS: Prospective collection, observational study, in patients undergoing fresh, double embryo transfer (ET), in a tertiary hospital referral IVF unit. Spent day 1 and day 3 media were collected. Concentrations of taurine, aspartic acid, proline, and serine in the medium were determined using a liquid-chromatography mass-spectrometer (LCMS/MS). Data was analyzed according to excretion versus uptake, and a cut-off value was calculated based on a receiver operating curve (ROC). Pregnancy rates were also calculated after stratification into subgroups in accordance with AA metabolism. RESULTS: Seven out of 19 patients conceived (36.8 %). The ORs for pregnancy when the zygotes secreted aspartic acid, serine and proline above the cut-off value were 2.9, 5.67 and 5.21 (p < 0.05). When both transferred embryos were above the cut-off value of serine the PR's were 62.5 %, 12.5 % when both were below, and 33.3 % when one was above and the other below (p = 0.04). Similar results were obtained for proline; PR's were 66.7, 18.7 and 28.6 % respectively, but with a borderline statistical significance (p = 0.08). The same trend was observed in the case of aspartic acid but not near statistical significance. No differences in PRs were found in association with taurine turnover during fertilization or any of the studied AAs during the cleavage stage. There was no correlation between zygote or embryo AAs metabolism and embryo morphology. CONCLUSIONS: Serine and possibly proline decreased uptake from the fertilization medium is associated with pregnancy and might be useful for embryo selection.

The value of human chorionic gonadotropin stimulation test in predicting ovarian response during in-vitro fertilization.

PURPOSE: To assess the predictive value of human Chorionic Gonadotropin (hCG) theca-stimulation test for ovarian reserve in women undergoing in-vitro fertilization (IVF) treatments. METHODS: 39 women were included in the study. All participants received a single hCG 10000 IU injection on cycle day 2-3. Serum levels of estradiol, testosterone, androstenedione and 17-OH progesterone were measured prior to the injection and on days 1, 3 and 7 following the injection. hCG-induced hormone levels were compared with ovarian response during the subsequent IVF cycle. RESULTS: There were 11 good responders (>10 oocytes) and 22 low responders (<3 oocytes). Before hCG stimulation serum E2 levels were higher in low responders compared to good responders (370.3 ± 443 vs. 138.3 ± 54 pmol/ml). Following hCG stimulation, day 3 androstendione levels showed an increase in good responders compared to low responders. The ratio between day 3 androstendione and day 0 estradiol was significantly different between the two groups (p = 0.03). ROC analysis of this test revealed area = 0.837 (good prediction), which was much better than day 3 FSH (area = 0.635, poor prediction). CONCLUSIONS: These preliminary results demonstrate the potential use of the hCG theca stimulation test in differentiating between good and poor responders. Larger series are needed for further verification of the test in routine clinical application.

Ovarian hyperstimulation syndrome: definition, incidence, and classification.

Ovarian hyperstimulation syndrome (OHSS) is a iatrogenic complication of controlled ovarian stimulation. Although considered uncommon, the severe form is potentially fatal. Different clinical classifications have been developed through the years. No matter whether it is termed "grade C" or "critical" OHSS, life-threatening events may develop. Hence it is prudent to recognize the population at risk. Several risk factors for OHSS have been identified; some are considered major risk factors such as polycystic ovary syndrome; others are less well defined. Preventive measures could be taken before and during the treatment cycle while taking into consideration the patient's characteristics and the various treatment options and approaches that currently exist.

[Chronic pelvic pain and Allen-Masters syndrome].

Allen-Masters syndrome, first described at 1955, is considered an uncommon etiology for chronic pelvic pain. The syndrome associates traumatic delivery to lacerations found on the posterior leaf of the broad Ligament. The authors report the clinical and laparoscopic findings of a female patient who was admitted to their department for evaluation due to chronic pelvic pain. The patient had a history of normal delivery six months before her admission. In the laparoscopy the authors reported finding bilateral Lacerations in the posterior leaf of the broad Ligament. Coagulation of both lacerations was performed and the patient reported significant improvement in her complaints. The relevant literature was reviewed and the article discusses the process of diagnosis and treatment.

[Fallopian tube torsion--a rare complication in the reproductive age].

Isolated fallopian tube torsion (ITT) is a rare condition defined as a total or partial rotation of the fallopian tube around its vascular axis. The torsion initiaLLy interferes with the venous and lymphatic circulation. If unrelieved in time, rapid progression occurs, occluding the arterial circulation and Leading to gangrene and hemorrhagic necrosis. The cLinicaL appearance usually includes sharp lower abdominal pain, with or without peritoneal signs. Urinary and gastrointestinal signs might also occur. isolated fallopian tube is a rare condition; the incidence s estimated to be 1:500,000 mostly in reproductive age women. ITT is most common in the right side, although several reports claim that there is no difference between the sides. The etiology is not completely understood, but tubal anomalies (anatomic or physiologic) as well as trauma or pelvic inflammation are predisposing factors. The clinical appearance and the imaging in these cases are not pathognomonic, and many cases are delayed by means of diagnosis and treatment. The treatment is surgical. Detorsion or salpingectomy is usually performed by laparoscopy. Three cases that were treated lately at the Department of Obstetrics and Gynecology at the Hadassah Medical Center are presented together with a review of the literature.

Drug-eluting stents versus coronary artery bypass grafting in patients with diabetes mellitus.

BACKGROUND: Reduction of restenosis and reinterventions was recently reported with percutaneous interventions (PCI) with drug-eluting stents (Cypher). This study compares results of Cypher (Cordis, Miami Lakes, FL) stenting and surgical revascularization in diabetic patients. METHODS: From January 2002 to January 2005, 518 consecutive diabetic patients underwent myocardial revascularization; 176 by PCI incorporating Cyphers and 342 treated surgically. Single-vessel patients in the surgical group were treated with the left internal thoracic artery (ITA) and most multivessel patients were treated with two ITAs. After matching for age, sex, right system revascularization, and extent of coronary disease, two groups (86 patients each) were used to compare the two revascularization modalities. RESULTS: Both groups were similar; however, left main, poor ejection fraction, total occlusion, and bifurcation lesions were more prevalent in the surgical group, and in-stent restenosis in the PCI group. The mean number of coronary vessels treated was higher in the surgical group (2.05 vs 1.6, p < 0.001). Mean follow-up was 18 months. Overall mortality (early and late) was 2.3% and 3.5% in the Cypher and surgical groups, respectively (p = 0.65). Angina returned in 39.5% of the Cypher group and 15.1% of the surgical group, p < 0.001. There were 25 reinterventions in the Cypher group compared with five in the surgical group (p = 0.010). The Cox proportional hazard model revealed assignment to the Cypher group to be the only independent predictor of reangina (odds ratio [OR] 3.26, 95% confidence interval [CI] 1.63 to 6.53) and reintervention (OR 4.17, 95% CI 1.92 to 20.83). CONCLUSIONS: Despite improved results of PCI with Cyphers, midterm clinical outcome of diabetic patients treated surgically is better.

Comparison between multivessel stenting with drug eluting to the LAD and bilateral internal thoracic artery grafting.

BACKGROUND: Reduction of restenosis and reinterventions was reported with drug-eluting stents (Cypher). This study compares results of multivessel Cypher stenting with bilateral internal thoracic artery (BITA) grafting. METHODS: From January 2002 to June 2004, 725 consecutive patients underwent multivessel myocardial revascularization, 95 by 2 or more Cypher stents and 630 by BITA. After matching for age, sex, and extent of coronary artery disease, 2 groups (87 patients each) were used to compare the 2 revascularization modalities. RESULTS: The 2 groups were similar; however, left main and the use of an intra-aortic balloon pump were more prevalent in the BITA group. The number of coronary vessels treated per patient was higher in the BITA group (2.71 versus 2.24 for BITA and Cypher, respectively; P = .001). Mean follow-up was 12 months. Thirty-day mortality was 0 in both groups. There were no late deaths in the BITA group and 2 (2.3%) in the Cypher group (P value was not significant). Angina returned in 29.9% of the Cypher group and 12.6% of the BITA group (P = .005). Multivariable Cox analysis revealed percutaneous intervention (PCI) (Cypher group) to be the only independent predictor of angina recurrence (Odds Ratio 2.62, 95% Confidence Interval 1.11-6.17). There were 10 reinterventions (PCI) in the Cypher group compared to 5 in the BITA group. One-year reintervention-free survival (Kaplan-Meier) of the BITA group was 96% compared to 88% in the Cypher group (P = .015). CONCLUSIONS: Midterm clinical outcome of surgically treated patients is still better. However, the reintervention gap between surgery and percutaneous interventions was reduced by treating 2 or more coronary vessels with Cypher stents.

Drug-eluting stents versus bilateral internal thoracic grafting for multivessel coronary disease.

BACKGROUND: Reduction of restenosis and reinterventions was recently reported with percutaneous interventions (PCI), including drug-eluting stents (Cypher; Cordis, Miami Lakes, FL). This study compares results of multivessel Cypher stenting with those of bilateral internal thoracic artery (BITA) grafting. METHODS: From January 2002 to June 2004, 768 consecutive patients underwent multivessel myocardial revascularization; 138 by PCI including Cyphers and 630 by BITA. After matching for age, sex, ejection fraction, extent of coronary disease, and congestive heart failure, two groups (113 patients each) were used to compare the two revascularization modalities. RESULTS: Both groups were similar; however, left main and intraaortic balloon were more prevalent in the BITA group. The number of coronary vessels treated per patient was higher in the BITA group (2.87 vs 2.22, p < 0.001). Follow-up ranged between 6 and 34 months. Thirty-day mortality was 0.9% in the BITA and zero in the PCI group (p = 0.32). There were no late deaths in the BITA and three (2.7%) in the Cypher group (p = 0.08). Angina returned in 28.3% of the Cypher and 12.4% of the BITA group, p = 0.003. A Cox proportional hazard model revealed assignment to the Cypher group to be the only predictor of angina recurrence (odds ratio 2.78, 95% confidence interval 1.46-2.56). There were 16 (14.2%) reinterventions in the Cypher group compared with six (5.3%) in the BITA group. One-year reintervention-free survival (Kaplan-Meier) of the BITA was 96% compared with 86.6% in the Cypher group (p = 0.005, log-rank test). CONCLUSIONS: Despite improved results of PCI with Cyphers, midterm clinical outcome of multivessel patients treated with BITA is still better.

Revascularization of left anterior descending coronary artery in patients with single and multivessel disease: comparison between off-pump internal thoracic artery and drug-eluting stent.

STUDY OBJECTIVES: The left anterior descending artery (LADA), particularly when the proximal segment of the vessel is involved, is a challenging area for percutaneous coronary interventions (PCIs); therefore, coronary artery bypass grafting is often considered and sometimes performed even in patients with single-vessel disease involving the LADA. This study compares mid-term results of LADA revascularization with a drug-eluting stent (DES), with off-pump coronary artery bypass grafting (OPCAB) in patients with single-vessel or multivessel coronary artery disease (CAD). DESIGN: Matched-groups, retrospective cohort comparison between the DES and OPCAB. PATIENTS: From June 2002 to December 2003, 354 patients underwent myocardial revascularization of the LADA by OPCAB, and 168 by DES. After matching for age, sex, and extent of CAD, two groups (116 patients each) were used to compare the two revascularization modalities. The groups were similar; however, an ejection fraction of <30%, old myocardial infarction, and use of an intraaortic balloon pump were more prevalent in the OPCAB group. RESULTS: The average number of coronary vessels treated per patient in the two groups was similar (OPCAB, 1.97; DES, 1.6; p = 0.581). The 30-day mortality rate was 0.9% in the OPCAB group and 0% in the DES group (p = 0.329). The mean duration of follow-up was 12 months. There was one late death in each group. Angina returned in 31% of patients in the DES group and in 11.2% of the patients in the OPCAB group (p = 0.001). There were 12 reinterventions in the DES group compared to three reinterventions in the surgical group (p = 0.020). The only independent predictor (Cox proportional hazards regression model) of the return of angina (risk ratio [RR], 3.36; 95% confidence interval [CI], 1.57 to 7.14) and reintervention (RR, 3.9; 95% CI, 1.34 to 11.24) was assignment to the DES group. CONCLUSIONS: The mid-term clinical outcome of OPCAB in patients with CAD, including multivessel disease, was better than that for PCIs with only one DES used in patients with similar extents of CAD.