Char Syndrome a novel mutation and new insights: A clinical report.

Transcription Factor AP-2 Beta (TFAP2B) functions in the differentiation of neural crest cell derivatives and contributes to the embryogenesis of the ductus arteriosus. Mutations of TFAP2B produces Char syndrome. Char syndrome is an autosomal dominant disorder comprising facial dysmorphism, hand anomalies, and patent ductus arteriosus (PDA). In this report, we describe a proband with a de novo TFAP2B frameshift mutation c.650delG p.(Gly217Alafs*32) in the basic domain. The proband presented mainly with musculoskeletal features of Char syndrome. No PDA was identified at presentation suggesting that this syndrome may prove to be phenotypically heterogeneous. This report will help illustrate the genotype/phenotype correlation of TAFB2 mutations and better delineate the clinical features in Char syndrome.

Non-invasive pre-implantation genetic testing of human embryos: an emerging concept.

The accurate genetic screening of pre-implantation embryos currently entails the use of technically challenging and biologically invasive biopsies of the human embryos. Investigating a more conservative sampling approach has emerged as a timely and desired alternative. Circulating cell-free embryonic DNA is present in the blastocoel fluid and spent culture media of blastocysts, and this has lately been sought as an attractive source of genetic information. The genetic analysis of cell-free embryonic DNA has been reported, to be useful in evaluating the genetic constitution of embryos; thus, providing a potential alternative to conventional biopsy-derived pre-implantation genetic testing (PGT). In this review, we have summarized these non-invasive alternative applications of PGT and discussed their current limitations and future clinical implications.

Inadequacy of initiating rosuvastatin then metformin on biochemical profile of polycystic ovarian syndrome patients.

BACKGROUND: Polycystic ovary syndrome (PCOS) afflicts at least 5% of women. Both metformin and statin have been used as methods to ameliorate symptoms and improve prognosis. AIM: To test the efficacy of concomitant usage of metformin and statins in PCOS patients. MATERIALS AND METHODS: This is a prospective, randomized, double-blinded, placebo controlled study. 37 patients received rosuvastatin (10 mg/day) for a period of 3 months, then the patients were randomly allocated to one of two groups: the first group (or intervention group) received rosuvastatin (10 mg/day) plus metformin (850 mg twice daily after meals), and the second group (referred to as control group hereafter) received rosuvastatin (10 mg/day) plus placebo for a period of 3 months. Biochemical and clinical data were collected at each time point. RESULTS: There were no significant differences between the intervention and control groups for baseline lipid profile (LDL, HDL, triglycerides, total cholesterol), CRP, homocysteine, DHEAS, testosterone and insulin (p > 0.05 for all variables). There were no significant differences in lipid profile, CRP, homocysteine, DHEAS, testosterone and insulin between the intervention and placebo groups at 3 and 6 months after treatment (p > 0.05 for all). Significant differences in the outcome variables of LDL, total cholesterol and FBS emerged within the intervention group, with significantly higher levels at 6 months compared to 3 months. We also did not find any significant group differences in unit change of the outcome variables between baseline and 3 months. CONCLUSIONS: We found that the combination of statin and metformin has no advantage in PCOS management. In fact, the increase of LDL, total cholesterol and FBS within the intervention group warrants reassessment of current regimens to avoid any patient harm.

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis.

BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB). OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA). SEARCH STRATEGY: We searched international scientific databases, trial registration websites, and references of identified articles. SELECTION CRITERIA: Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB. MAIN RESULTS: Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75). AUTHOR'S CONCLUSIONS: In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.

A randomised controlled double-blind clinical trial of 17-hydroxyprogesterone caproate for the prevention of preterm birth in twin gestation (PROGESTWIN): evidence for reduced neonatal morbidity.

OBJECTIVE: To determine whether 17 alpha-hydroxyprogesterone caproate (17OHPC) prolongs gestation beyond 37 weeks of gestation (primary outcome) and reduces neonatal morbidity (secondary outcome) in twin pregnancy. DESIGN: Randomised controlled double-blind clinical trial. SETTING: Tertiary-care university medical centre. POPULATION: Unselected women with twin pregnancies. METHODS: Participants received weekly injections of 250 mg 17OHPC (n = 194) or placebo (n = 94), from 16-20 to 36 weeks of gestation. Randomisation was performed using the permuted-block randomisation method. Data were analysed on an intention-to-treat basis. MAIN OUTCOME MEASURE: Preterm birth (PTB) rate before 37 weeks of gestation. RESULTS: There were no significant differences in the average gestational age at delivery, or in the rates of PTB before 37, 32, and 28 weeks of gestation, between the two groups. The proportion of very-low-birthweight neonates (<1500 g) was significantly lower in the 17OHPC group (7.6%) compared with placebo (14.3%) (relative risk, RR 0.5; 95% confidence interval, 95% CI 0.3-0.9; P = 0.01). Progestogen-treated neonates had a significantly lower composite neonatal morbidity (19.1%) compared with placebo (30.9%) (odds ratio, OR 0.53; 95% CI 0.31-0.90; P = 0.02), with significantly lower odds for respiratory distress syndrome (14.4 versus 23.4%; OR 0.55; 95% CI 0.31-0.98; P = 0.04), retinopathy of prematurity (1.1 versus 4.6%; OR 0.21; 95% CI 0.05-0.96; P = 0.04), and culture-confirmed sepsis (3.4 versus 12.8%; OR 0.24; 95% CI 0.10-0.57; P = 0.00). CONCLUSIONS: Intramuscular 17OHPC therapy did not reduce PTB before 37 weeks of gestation in unselected twin pregnancies. Nonetheless, 17OHPC significantly reduced neonatal morbidity parameters and increased birthweight.

The utilization of pre-implantation genetic testing in the absence of governance: a real-time experience.

To create a diagnostic document describing the utilization of pre-implantation genetic testing (PGT) in the absence of monitoring and regulation. Retrospective cohort study of couples undergoing PGT between 2004 and 2007 in Lebanon. The clinical indications for 192 PGT cycles performed during the study period were gender selection (96.3%), chromosomal aneuploidy (3.1%), and balanced translocation (0.5%). When gender selection was sought, the selection of a son was desired in 94.1% of cases. Of couples undergoing PGT for sex selection, 16.2% were childless, 8.6% had one child of the opposite gender, 28.1% had two same-gender children, 29.7% had three same-gender children, and 11.9% had four or more. Our findings demonstrate the morally questionable consequences of self-regulated systems in which physicians are the sole gatekeepers of norms and ethics.

Idiopathic premature ovarian failure: what is the most suitable ovarian stimulation protocol?

OBJECTIVE: To evaluate the ovarian response to ovarian stimulation in women with idiopathic premature ovarian failure (POF) in a prospective, controlled, and sequential crossover pilot study. MATERIALS AND METHODS: Ten women with idiopathic premature ovarian failure and normal karyotype were included in the study. Phase I was comprised of three consecutive control cycles consisting each of estrogen progestin sequential therapy. Phase II was comprised of three consecutive treatment cycles combining the use of gonadotropin-releasing hormone agonist (GnRHa) in the background of estrogen priming, followed by gonadotropin ovarian stimulation and corticosteroid immunosuppression. RESULTS: Ovulation rates in the treatment cycles (0/10; 0%) did not differ from control cycles (0/10; 0%). CONCLUSIONS: The findings of this pilot study showed that the combination of estrogen priming, corticosteroid immune-suppression, GnRHa pituitary desensitization, and followed by gonadotropin ovarian stimulation is ineffective in restoring ovarian function in women with idiopathic POF.

The effect of maternal fasting during Ramadan on preterm delivery: a prospective cohort study.

OBJECTIVE: To determine the effect of fasting during the month of Ramadan on the rate of preterm delivery (PTD). DESIGN: A prospective cohort study of women with singleton pregnancies who elected to fast and matched controls. SETTING: Four medical centres in Beirut, Lebanon. POPULATION: Women presenting for prenatal care (20-34 weeks of gestation) during the month of Ramadan, September 2008. METHODS: Data were collected prospectively. The frequency of PTD was evaluated in relation to the duration of fasting and the stage of gestation at the time of fasting. MAIN OUTCOME MEASURES: The primary endpoint was the percentage of pregnant women who had PTD, defined as delivery before 37 completed weeks of gestation. RESULTS: A total of 468 women were approached, of whom 402 were included in the study. There were no differences in smoking history and employment. There was no difference in the proportion of women who had PTD at <37 weeks (10.4% versus 10.4%) or PTD at <32 weeks (1.5% versus 0.5%) in the Ramadan-fasted group and the controls, respectively. The PTD rate was also similar in those who fasted before or during the third trimester. The mean birthweight was lower (3094 ± 467 g versus 3202 ± 473 g, P = 0.024) and the rate of ketosis and ketonuria was higher in the Ramadan-fasted women. On multivariate stepwise logistic regression analysis, fasting was not associated with an increased risk of PTD (odds ratio 0.72; 95% confidence interval 0.34-1.54; P = 0.397). The only factor that had a significant effect on the PTD rate was body mass index (odds ratio 0.43; 95% confidence interval 0.20-0.93; P = 0.033). CONCLUSIONS: Fasting during the month of Ramadan does not seem to increase the baseline risk of preterm delivery in pregnant women regardless of the gestational age during which this practice is observed.

Genetics of autoimmune thyroid disease in the Lebanese population.

This study aims to investigate the association of human leukocyte antigen (HLA) class II genes and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) with autoimmune thyroid diseases in the Lebanese population. A total of 128 patients with autoimmune thyroid disease (55 with Graves' disease (GD) and 73 with Hashimoto's thyroiditis (HT)) were typed for HLA DQA1 (0301 and 0501) and DQB1 (0201, 0302, and 0303) and for 49A/G CTLA-4 using PCR-based sequence-specific priming methods. A total of 186 matched controls were typed for the same alleles and compared to the diseased population. Results showed no significant differences in HLA DQB1*0201 or DQB1*0301 allelic frequencies or CTLA-4 polymorphisms between patients and controls. For GD, there was a weak association with HLA DQB1*0302 [34.6% (19 of 55) vs. 21.5% (40 of 186), P = 0.048, odds ratio (OR) = 1.926, confidence interval (CI) = 0.999-3.715] and HLA DQB1*0302-DQA1*0501 haplotype [56.36% (31 of 55) vs. 40.8% (76 of 186), P = 0.042, OR = 1.870, CI = 1.018-3.433]. For HT, the frequencies of DQB1*0302-DQA1*0501 haplotype [28.8% (21of 73) vs. 14.5% (27 of 186), P = 0.008, OR = 2.378, CI = 1.241-4.558] and DQB1*0302-DQA1*0301 haplotype [60.2% (44 of 73) vs. 38.7% (72 of 186), P = 0.002, OR = 2.402, CI = 1.381-4.180] were significantly higher in patients. On the other hand, weak association was found between HT and DQA1*0301 allele [32.9% (24 of 73) vs. 20.9% (39 of 186), P = 0.044, OR = 1.846, CI = 1.011-3.373]. Findings show that DQB1*0302-DQA1*0501 and DQB1*0302-DQA1*0301 haplotypes may play a role in the pathogenesis of HT in the Lebanese population. For the 49A/G CTLA-4 polymorphism, no significant difference was found between patients and controls.

Induction of final follicle maturation with a gonadotropin-releasing hormone agonist in women at risk of ovarian hyperstimulation syndrome undergoing gonadotropin stimulation and intrauterine insemination: proof-of-concept study.

OBJECTIVE: To evaluate the reproductive performance and safety of gonadotropin-stimulated intrauterine insemination (IUI) cycles in women at risk for ovarian hyperstimulation syndrome (OHSS) when final follicle maturation was induced using a gonadotropin-releasing hormone (GnRH) agonist. MATERIALS AND METHODS: Thirty-three women presenting with a history of cancelled ovarian stimulation for fear of OHSS, underwent repeat gonadotropin ovarian stimulation for IUI. They were all found to be at high-risk for OHSS once more, and were counseled to receive a GnRH agonist to trigger final follicle maturation before insemination. GnRH agonist trigger of ovulation (triptorelin) was given subcutaneously every 12 hours in three repeated doses: 0.3, 0.2, 0.2 mg, respectively. RESULTS: Induction with the agonist was associated with a 30.3% take-home pregnancy rate and 20% miscarriage rate. Multiple pregnancy rates were 26.7%. There were no reported cases of clinically significant moderate/severe ovarian hyperstimulation syndrome. CONCLUSIONS: The use of a GnRH agonist to trigger final follicle maturation in stimulated cycles of hyper responders was associated with a favorable reproductive outcome and no incidence of OHSS. The rate of multiple pregnancies nevertheless was found to be uncontrollably elevated, raising serious concerns regarding the safety of this protocol in standard clinical practice in the context of IUI.

A randomised comparison of patient satisfaction with vaginal and sublingual misoprostol for induction of labour at term.

OBJECTIVE: To compare patient satisfaction with two routes of misoprostol for term labour induction. DESIGN: Prospective randomised trial. SETTING: Tertiary care hospital. POPULATION: A total of 170 women admitted at > or = 37 weeks of gestation for induction of labour. METHODS: Women were randomised to receive 50 micrograms of either sublingual or vaginal misoprostol. MAIN OUTCOME MEASURES: Patient satisfaction with the route of administration. RESULTS: Despite a similar proportion reporting the labour induction as more painful than expected in both groups, a significantly lower proportion mentioned that the pelvic examinations were very painful in the sublingual group (19.7 versus 36.1%, relative risk [RR] 0.5, 95% CI 0.3-0.9). Request for analgesia was similar in both groups. More women in the sublingual group thought that the labour experience was better than expected (RR 2.0, 95% CI 1.2-3.3), had a positive attitude towards induction in subsequent pregnancies (RR 1.6, 95% CI 1.1-2.3) and preferred the same route in subsequent pregnancies (RR 3.1, 95% CI 2.2-4.5). Mean number of misoprostol doses, oxytocin augmentation, tachysystole and hyperstimulation, induction to vaginal delivery interval, vaginal delivery after a single dose, vaginal birth within 12 and 24 hours, and caesarean delivery rates were similar in both groups. CONCLUSION: Sublingual misoprostol (50 micrograms) is associated with a significantly higher patient satisfaction rate compared with a similar dose of vaginal misoprostol. Sublingual administration offers additional choice to women, in particular those wishing to avoid vaginal administration.

Complex translocation (8;12;21): a new variant of t(8;21) in acute myeloid leukemia.

Variants of the t(8;21)(q22;q22) involving chromosomes 8, 21, and other chromosomes account for approximately 3% of all t(8;21)(q22;q22) in acute myeloid leukemia (AML) patients. In this paper, we report a case of AML-M2 with a t(8;12;21)(q22;p12 approximately p13;q22) associated with chromosomal abnormalities, including loss of the Y chromosome and trisomy 8q22 approximately qter. Using a dual-color fluorescence in situ hybridization (FISH) analysis with ETO and AML1 probes, we demonstrated an ETO/AML1 fusion signal on the derivative chromosome 8. Using whole painting probes for chromosomes 8 and 12, we demonstrated a three-way translocation, t(8;12;21)(q22;p12 approximately p13;q22). Reverse transcription polymerase chain reaction (RT-PCR) analysis showed the presence of AML1/ETO fusion transcript. The present case highlights the importance of the combination of approaches, i.e., standard karyotyping, FISH, and RT-PCR, for the detection of variants of t(8;21)(q22;q22), shedding light on region 8q22 approximately qter which could harbor potential genes responsible for leukemogenesis.

Homologous telomere association of 19q in a female with premature ovarian failure.

Premature ovarian failure (POF) may be due to a variety of genetic mechanisms. We report here, for the first time, telomere association of the long arms of chromosome 19, identified at low frequency (1%) in the peripheral blood cultures of a 30-year-old female with POF. Repeat cultures identified, in addition, the presence of 16q and 22q associations at a lower frequency (0.5%). These consistent observations are suggestive of a non-random event. Their association with POF may just be coincidental or may hypothetically explain it by an abnormal mechanism of chromosome separation, a constitutional telomere anomaly or an unidentified chromosome instability disorder.

A unilateral twin extrauterine pregnancy occurring in a solitary fallopian tube: therapeutic choices.

A unilateral twin tubal pregnancy occurring in a solitary fallopian tube is presented. The gynecological history was notable for a previous extrauterine pregnancy in the contralateral fallopian tube and reconstructive surgery to the ipsilateral one. Radical total salpingectomy was performed. The rationale for this management is discussed and different therapeutic alternatives presented.

Tamoxifen and ovarian cysts: a prospective study.

PURPOSE: To prospectively follow a group of women with breast cancer on tamoxifen for the development of ovarian cysts. METHODS: 72 women were followed every 6 months with pelvic examination and vaginal ultrasound. Chi square and Student's t-test were used for statistical analysis. RESULTS: The duration of treatment was 31.5+/-20 months. The mean age was 51.2+/-9.8 years. 55.6% were post-menopausal. Out of 72 women, 18 (25%) developed ovarian cysts. The mean age of women who developed ovarian cysts was significantly lower than in those who did not (47.0+/-7.0 and 52.5+/-10.2 years, respectively, P=0.03), however, the mean duration of treatment was not significantly different (33.3+/-17.4 and 29.3+/-20 months, respectively, P=0.45). Out of 32, 14 (43.8%) pre-menopausal and out of 40, 4 (10%) post-menopausal women developed ovarian cysts (P=0.003). They developed the cysts after an average duration of 33.3+/-18 and 50.7+/-6.2 months, respectively (P=0.7). The average diameter of the cysts was 2.8+/-1.2 cm. All cysts were simple except for one pre-menopausal women. All the cysts in post-menopausal women resolved spontaneously. One pre-menopausal patient had a multi-loculated cyst, was operated and had a serious cystadenoma. In nine patients, the cysts resolved spontaneously and in three after discontinuation of tamoxifen, and one patient was lost to follow-up. All cysts were asymptomatic. CONCLUSION: Ovarian cysts frequently develop in women with breast cancer on tamoxifen. The majority of the cysts resolve spontaneously, therefore an expectant management with follow-up ultrasonography is recommended.

Teflonoma presenting as a cystourethrocele.

We report an unusual case of teflonoma which appeared three years after teflon injection and presented as cystourethrocele. The pathology confirmed the presence of a giant cell reaction compatible with a teflonoma.

The conventional doses of human chorionic gonadotropins may not always be sufficient to induce ovulation in all women: a reappraisal.

BACKGROUND: Failure of ovulation has occasionally been reported following the administration of conventionally recommended doses of exogenous human chorionic gonadotropins. CASE: A 25-year-old nulliparous woman with polycystic ovary syndrome underwent ovulation induction for primary infertility. Following successful ovarian stimulation, she failed to ovulate during two consecutive cycles in response to human chorionic gonadotropin doses of 5,000 and 10,000 IU. When challenged with a higher than conventional dose (15,000 IU) on the third cycle, she ovulated and conceived. CONCLUSION: Conventional doses of exogenous human chorionic gonadotropins occasionally fail to complete the ovulatory process in some women. Women with polycystic ovary syndrome appear to be particularly susceptible. Routine documentation of ovulation and individualization of the dose of exogenous human chorionic gonadotropins could therefore prove to be useful in some of these women in order to achieve the best treatment outcome.