The novel incorporation of aromatase inhibitor in hormonal replacement therapy cycles: a randomized controlled trial.

RESEARCH QUESTION: Does the incorporation of the aromatase inhibitor, letrozole, in hormone replacement therapy (HRT) improve the pregnancy outcome in vitrified-warmed blastocyst transfer cycles? DESIGN: A randomized controlled trial; HRT was used in all cycles. Exogenous oestradiol, 6 mg daily started on day 2 or day 3 of the cycle. Tri-laminar endometrium 9 mm or thicker was the targeted cut-off. Thereafter, participants were randomized into two groups. Group A (HRT plus letrozole): 2.5 mg oral letrozole was given twice daily for 5 days only with continuation of daily oestradiol. Then, daily intramuscular progesterone was started with continuation of oestradiol. Group B (HRT only): daily intramuscular progesterone was administered in addition to daily oestradiol. In both groups, good-quality day-5 blastocyst transfer was planned on the sixth progesterone day with continuation of oestradiol and progesterone. Ongoing pregnancy rate was the primary outcome. RESULTS: A total of 112 patients were randomized, 56 in each group. Three participants did not have good-quality blastocyst after warming (one in group A and two in group B) and were excluded from the study. Group A and B included 55 and 54 participants, respectively. Ongoing pregnancy rate was significantly higher in group A than group B (RR 1.39, 95% CI 1.04 to 1.86, P = 0.023). Additionally, clinical pregnancy rate was significantly higher in group A (RR 1.31, 95% CI 1.02 to 1.68, P = 0.030). CONCLUSIONS: A new protocol of incorporating letrozole in HRT cycles seems to significantly increase probability of pregnancy, compared with HRT alone.

Enhanced recovery after surgery (ERAS) following radical cystectomy: is it worth implementing for all patients?

PURPOSE: To report the overall effect of ERAS protocol implementation in patients undergoing radical cystectomy and its impact on the length of hospital stay (LOS) and surgical outcomes considering their comorbid conditions. METHODS: Retrospective cohort study including 296 patients (146 non-ERAS patients vs. 150 ERAS patients) undergoing radical cystectomy and urinary diversion from 2010 to 2018. Age-adjusted Charlson Comorbidity Index (ACCI) score eight was set as cut off value between low-risk and high-risk patients. The primary outcome was LOS. Secondary outcomes were time to bowel movements, tolerance of regular diet, the incidence of postoperative ileus, postoperative complications, and 30- and 90-day readmission rates. RESULTS: A higher comorbidity burden was identified in the ERAS group compared to non-ERAS patients (p = 0.04). Median (IQR) LOS for non-ERAS was group 8(4) and 8(5) for ERAS group (p = 0.07). ERAS group demonstrated shorter time to resume bowel movements as well as time to tolerance of regular diet (p = 0.007, p = 0.023, respectively). Low-risk patients managed by the ERAS protocol demonstrated a significantly shortened gastrointestinal (GIT) recovery time (p = 0.001) as well as a reduction of LOS (p = 0.04). No significant reduction of LOS was identified for patients with higher comorbidity when placed on the ERAS protocol (p = 0.65). There were no significant differences in postoperative complications or readmission rates between groups. CONCLUSION: ERAS protocol implementation following radical cystectomy showed significant improvements in GIT recovery, nevertheless, it did not result in a decrease in LOS or readmission rates. Low-risk patients appeared to derive more benefit from ERAS protocol implementation than high-risk patients.

Cricotracheal separation: do not get fooled by what you see.

INTRODUCTION: Laryngeal involvement in neck trauma is quite considerable. The presence of a cricotracheal separation type of injury can be easily missed and overlooked, especially if the neck does not show any external signs. Blunt trauma to the neck affects many anatomical structures inside the intact-looking neck that threatens the victim's life. At exploration, the surgeon must be aware of the full impact of the injury on different neck structures. AIM OF WORK: Raise the attention on the proper management of laryngeal trauma victims. PATIENTS AND METHOD: This is a retrospective study carried out on 23 patients who suffered from cricotracheal separation as a result of laryngeal trauma. RESULTS: Cricotracheal separation is a frequent finding in an innocent-looking neck. The mechanism of the trauma itself is an excellent clue to suspect its presence. CONCLUSION: This type of laryngeal injury must be kept in mind and must be suspected. Some recommendations and guidelines are presented on the proper handling of such patients.

Philtrum length and intercommissural distance measurements at mixed dentition period.

Anthropometric measurements of the lip and mouth are of great importance in clinical dysmorphology as well as reconstructive plastic surgery. In this study, the philtrum length (PhL) and intercommissural distance (ICmD) nomograms for Egyptian children in the mixed dentition period were established. A group of 1,338 Egyptian students in primary schools (735 boys and 603 girls) were included in the study. The students were at mixed dentition period and their ages ranged from 7 to 12 years. Anthropometric norms of PhL and ICmD were developed with significant sex difference in certain groups. A ratio between PhL and ICmD was developed. These data will help facilitate both objective and subjective evaluation of the lip and mouth for proper diagnosis of orofacial anomalies and variations as well as for ideal treatment plans.

Effect of metformin on maternal and neonatal outcomes in pregnant obese non-diabetic women: A meta-analysis.

BACKGROUND: Metformin reduces maternal and neonatal weight gain in gestational diabetes mellitus; however, this effect is poorly investigated in non-diabetic women. OBJECTIVE: We performed this meta-analysis to investigate the effect of metformin intake during pregnancy on maternal and neonatal outcomes in obese non-diabetic women. MATERIALS AND METHODS: We searched Medline, EMBASE, and Cochrane CENTRAL for eligible randomized controlled trials addressing the efficacy of metformin in pregnant obese non-diabetic women. Data were extracted and analyzed using RevMan software (Version 5.3). Neonatal birth weight was the key outcome. Secondary outcomes included maternal weight gain, the incidence of preeclampsia, and neonatal adverse effects (miscarriage, stillbirth and congenital anomalies). RESULTS: Pooled data from two RCTs (n=843) showed that metformin caused a significant reduction in maternal gestational weight gain (MD-1.35, 95% CI: [2.08, -0.630]), compared to placebo. The summary effect-estimate did not favor either of the two groups in terms of reduction of neonatal birth weight Z score (MD-0.09, 95% CI: [0.23, 0.06]). Metformin was associated with 41% reduction in the risk of preeclampsia; however, this reduction was not statistically significant [RR 0.59, 95% CI: [0.03, 11.46]). None of the neonatal adverse events including stillbirth [RR 1.14, 95% CI: 0.42, 3.10]) and congenital anomalies (RR= 1.36, 95% CI: [0.58, 3.21]) differed significantly between the two groups. CONCLUSION: For obese pregnant women, metformin could decrease gestational weight gain with no significant reduction in neonatal birth weight. In light of the current evidence, metformin should not be used to prevent poor pregnancy outcomes in obese non-diabetic women.

ACE Gene in Egyptian Ischemic Stroke Patients.

BACKGROUND: Angiotensin-1-converting enzyme (ACE) is a crucial player in vascular homeostasis and in the pathogenesis of atherosclerosis and hypertension. The present study was conducted to determine whether there is an association between the ACE insertion/deletion (I/D) polymorphism and ischemic stroke in Egyptian population. Also, we analyzed the ACE gene I/D polymorphism as a risk factor for small-vessel (SV) versus large-vessel (LV) disease. METHODS: Sixty patients with ischemic stroke were included: 30 with SV disease and 30 with LV disease. In addition, a control group of 30 apparent healthy subjects were studied. Clinical assessment, computed tomography, magnetic resonance imaging brain, and genetic study using the polymerase chain reaction of ACE gene were done for all subjects. RESULTS: We found that the distribution of ACE gene polymorphism frequency was significantly different between the 3 groups. The DD genotype was far more common in stroke patients compared to controls. It was also significantly more common in each of the patient groups compared to controls but rather similar in the 2 patient groups with SV and LV diseases. CONCLUSION: We found that the ACE gene deletion/deletion genotype is common in Egyptian patients with non-cardioembolic ischemic stroke but does not appear to be specific neither to SV nor to LV disease.

Protecting Ovaries During Chemotherapy Through Gonad Suppression: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate whether gonadotropin-releasing hormone (GnRH) analog administration during chemotherapy can protect against development of ovarian toxicity. DATA SOURCES: MEDLINE (1966 to present), EMBASE (1980 to present), Cochrane Central Register of Controlled Trials (CENTRAL), World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched through March 2015 using the phrases: "gonadotropin-releasing hormone," "chemotherapy," and "premature ovarian failure." Hand-search on conference abstracts, SCOPUS, and ISI Web of Science were also searched. METHODS OF STUDY SELECTION: Published English-language randomized controlled trials comparing resumption of ovarian function between GnRH analogs plus chemotherapy with chemotherapy without GnRH analogs were included. Studies including women with pelvic metastases or recent history of receiving chemotherapy were excluded. Accordingly, 10 eligible trials (907 women) were analyzed. TABULATION, INTEGRATION, AND RESULTS: Our primary outcome was the proportion of women with resumed ovarian function (defined as resumption of menstruation, prevention of chemotherapy-induced ovarian failure, or both) at the longest follow-up after the end of chemotherapy. Secondary outcomes were evaluating ovarian reserve parameters and pregnancy. Risk ratio was used to integrate qualitative results and mean difference was used for quantitative data. Gonadotropin-releasing hormone analog cotreatment did not significantly increase ovarian function resumption (320/468 [68.4%] in GnRH analog arm and 263/439 [59.9%] in the chemotherapy alone arm; risk ratio 1.12, 95% confidence interval [CI] 0.99-1.27). No protective effect existed after subgroup analyses (type of malignancy [P=.31], age [P=.14], and GnRH analog type [P=.44]). Gonadotropin-releasing hormone analogs did not protect any of ovarian reserve parameters, whether follicle-stimulating hormone (mean difference -2.63, 95% CI -7.33 to 2.07), antral follicle count (mean difference 1.66, 95% CI -0.69 to 4.01), or anti-Müllerian hormone (mean difference 0.31, 95% CI -0.41 to 1.03). Spontaneous pregnancy was also comparable (risk ratio 1.63, 95% CI 0.94-2.82). CONCLUSION: Gonadotropin-releasing hormone analog administration during chemotherapy does not appear to protect the ovaries from gonadal toxicity. It is not a reliable method for fertility preservation.

Functional G1199A ABCB1 polymorphism may have an effect on cyclosporine blood concentration in renal transplanted patients.

Cyclosporine A (CsA) shows significant inter-individual variability in its pharmacokinetics, which may be due to polymorphisms in ABCB-1 genes coding for P-glycoprotein. The aim of this study was to explore the role of genetic polymorphisms of ABCB-1 in affecting the CsA blood concentrations in renal transplanted patients over the first 3 months after transplantation. Renal transplanted patients receiving CsA (n = 40) were genotyped for ABCB -1 C3435T (I1145I) and G1199A (S400N) polymorphisms. CsA blood concentrations were measured on Day 7, 30, and 90 after transplantation. G1199A variant showed higher CsA blood concentrations in stable patients, that was significant for trough levels (198 vs. 136 ng/mL on Day 7, P = .004, 196 vs. 125 ng/mL on Day 30, P = .007, 194 vs. 121 ng/mL on Day 90, P = .005 for stable vs. unstable groups). Polymorphisms of ABCB-1 have only a minor effect on CsA blood concentrations. The functional G1199A polymorphism can affect the drug levels more than non-functional C3435T. This polymorphism might be of a potential prognostic value in renal transplanted patients.

Blastocyst-stage versus cleavage-stage embryo transfer in women with high oestradiol concentrations: randomized controlled trial.

This prospective, randomized, controlled trial tested the hypothesis that delaying embryo transfer to the blastocyst stage can increase the probability of clinical pregnancy and live birth in women with high oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) undergoing intracytoplasmic sperm injection using the long protocol. A total of 200 women with oestradiol >3000 pg/ml on the HCG day with four or more good-quality, day-3 embryos were randomized in a 1:1 ratio to undergo day-3 or day-5 embryo transfer. Clinical pregnancy rates (CPR; 41% versus 59%; relative risk 0.70, 95% CI 0.52­0.93) and ongoing pregnancy/live-birth rates (35% versus 52%; relative risk 0.67, 95% CI 0.46­0.93) were lower in women undergoing cleavage-stage than blastocyst-stage embryo transfer. Using receiver operating characteristic curves, among women undergoing cleavage-stage embryo transfer, a detrimental cut-off value for not achieving pregnancy for oestradiol was 4200 pg/ml, with lower CPR and ongoing pregnancy/live-birth rates (P = 0.006 and 0.02, respectively). No detrimental cut-off value for oestradiol was identified among women undergoing blastocyst-stage embryo transfer. Delaying embryo transfer to the blastocyst stage can increase the probability of pregnancy in women with high oestradiol on the HCG day

N-acetyl cysteine: could it be an effective adjuvant therapy in ICSI cycles? A preliminary study.

This randomized controlled trial tested the hypothesis that addition of N-acetyl cysteine (NAC) can increase the probability of pregnancy in intracytoplasmic sperm injection (ICSI) cycles using the long agonist protocol. Women undergoing ICSI cycles due to male factor were randomly assigned to receive either long protocol (group A, 38 women) or long protocol plus NAC (group B, 38 women). Clinical pregnancy was the primary outcome. Granulosa cell apoptosis, fertilization rate, number of grade-one embryos and ongoing pregnancy were the secondary outcomes. Clinical pregnancy rate was insignificantly higher in NAC group (52.6%) than control (47.4%). Early and late apoptosis were also insignificantly lower in group B than in group A. Irrespective of the used protocol, there was significant negative correlation between both early and late apoptosis and fertilization rate (both P<0.001) and the number of good-quality embryos (P=0.007 and P<0.001, respectively). Pregnant patients had significantly lower early and late apoptosis than those who didn't achieve pregnancy (P<0.001). In conclusion, NAC supplementation did not significantly increase the probability of pregnancy in ICSI cycles using long agonist protocol. It appears that granulosa cell apoptosis may be an important prognosticator for ICSI cycle outcome.

Does luteal estradiol supplementation have a role in long agonist cycles?

OBJECTIVE: To test the hypothesis that the addition of 6 mg estradiol (E2) valerate either orally or vaginally to progesterone (P) for luteal support, can increase the probability of pregnancy in intracytoplasmic sperm injection (ICSI) cycles using the long agonist protocol. DESIGN: Prospective open-labeled randomized controlled trial. SETTING: Private and university fertility centers. PARTICIPANT(S): Women undergoing ICSI cycles, with controlled ovarian hyperstimulation using long agonist protocol. INTERVENTION(S): On embryo transfer day, participants were randomized to receive, only P (group A, n = 90), P along with 6 mg E(2) valerate either orally (group B, n = 90), or vaginally (group C, n = 90) for luteal support. MAIN OUTCOME MEASURE(S): Clinical pregnancy was the main outcome. luteal serum E(2) and P profiles were the secondary outcomes. RESULT(S): Highest pregnancy rate was achieved in group C (45.56%), it was significantly higher than A (relative risk 1.52, 95% CI: 1.03 to 2.24). Day 0 (hCG day) E2 levels were similar in the three groups. Group A had lower E2 levels on days 7, 10, and 13 and a higher magnitude of E2 decline on days 7 and 10. Similar levels of luteal E2 were documented in groups B and C. P levels were similar in the three groups. CONCLUSIONS(S): Addition of 6 mg E(2) valerate to P support may encumber the sharp decline in luteal E(2) level. It may enhance the probability of pregnancy if administered vaginally.

The correlation between basal serum follicle-stimulating hormone levels before embryo cryopreservation and the clinical outcome of frozen embryo transfers.

OBJECTIVE: To evaluate the correlation between basal serum FSH level before the fresh IVF/intracytoplasmic sperm injection (ICSI) cycle and the clinical outcome of the subsequent frozen embryo replacement cycles. DESIGN: Retrospective observational study. SETTING: University tertiary referral center, London, United Kingdom. PATIENT(S): Five hundred four consecutive frozen embryo transfer (FET) cycles where serum FSH levels were obtained, on days 1-4 of the cycle before the fresh IVF +/- ICSI cycles. INTERVENTION(S): Frozen-thawed embryo transfer. MAIN OUTCOME MEASURE(S): Clinical pregnancy (CP) and live birth (LB). RESULT(S): Basal serum FSH in 127 women (25.2%) who had a CP was significantly lower compared with that in women who did not have a CP. Multivariate regression analysis showed significant correlation between basal serum FSH levels and clinical pregnancy and a low significance to LB, but there was no statistical significant differences between women who had a CP and those who did not with regard to age, treatment protocol (natural or hormone treatment cycle), or the freeze-thaw interval. The LB rate was higher in natural cycles (n = 71; 21.2%) than in hormone treatment cycles (n = 28; 16.7%). Conceiving in the fresh cycle had a positive influence on the FET outcome. CONCLUSION(S): Basal serum FSH level before fresh IVF/ICSI cycle is inversely correlated to a CP outcome in FET cycles. A trend was present between FSH levels and LB, but this failed to reach statistical significance.