Adi Reches

The effect of CGG repeat number on ovarian response among fragile X premutation carriers undergoing preimplantation genetic diagnosis

OBJECTIVE To assess ovarian response among carriers of FMR1 premutation who undergo preimplantation genetic diagnosis (PGD). DESIGN Retrospective study. SETTING Academic IVF unit. PATIENT(S) Of 18 carriers of FMR1 premutation referred to PGD, eight had <100 CGG repeats and ten had >or=100 CGG repeats. INTERVENTION(S) Controlled ovarian stimulation (COH) and PGD. MAIN OUTCOME MEASURE(S) Correlation between the number of CGG repeats and the level of E2 at day of hCG administration, number of retrieved oocytes, number of two-pronuclear (2PN) zygotes, and dose of recombinant FSH. RESULT(S) There was a positive correlation between CGG repeats and the level of E2 at day of hCG administration, number of retrieved oocytes, and number of 2PN zygotes. There was a negative correlation between number of CGG repeats and the total dose of gonadotropins. The E2 level and the number of retrieved oocytes and 2PN zygotes were significantly higher and the dose of gonadotropins significantly lower for premutation patients with >or=100 CGG repeats compared with <100 CGG repeats. CONCLUSION(S) There is a positive correlation between E2 level, retrieved oocytes, 2PN zygotes, and number of CGG repeats. Premutation carriers with <100 CGG repeats suffer from impaired ovarian response and decreased fertilization rate.

Preimplantation genetic diagnosis for fragile X syndrome: is there increased transmission of abnormal FMR1 alleles among female heterozygotes?

Fragile X syndrome is caused by a CGG triplet‐repeat expansion mutation in the FMR1 gene. Previous studies have shown increased transmission of abnormal alleles in the 51–60 repeat range. This study was undertaken to evaluate the performance of preimplantation genetic diagnosis (PGD) for fragile X, and to assess the transmission rate of the abnormal FMR1 alleles in this setting.

Sustained Leukocyte Count during Rising Cortisol Level

Aims: To follow the trend of leukocyte counts relative to the serum cortisol levels in hospitalized patients. Methods: We retrospectively reviewed the charts of 59 hospitalized patients who had sequential blood profiles during a 2-week period. Results: The study cohort was divided into two subgroups according to the categorical cortisol levels: those within the normal range (<25 µg/dl; n = 31 patients) and those above the normal range (≧25 µg/dl; n = 28 patients). The baseline white blood cell counts (WBCCs) were similar in both groups. After 1 week, however, the WBCCs dropped significantly in the presence of normal cortisol levels and increased in the presence of elevated cortisol levels (p = 0.002). This pattern was not followed by the platelet counts. A significant correlation was observed between the cortisol levels and the 1 week concomitant WBCC (r = 0.33). Conclusion: Cortisol may be the mechanism with a positive effect on the maintenance of elevated leukocyte counts.

Spontaneous splenic rupture in pregnancy after heparin treatment

A 32-year-old woman presented in the 34th week of her fourth pregnancy with sudden diffuse abdominal pain. She had previously undergone a preterm delivery of twins at 24 weeks of gestation and an early miscarriage at seven weeks of gestation. After her first two pregnancies, she underwent evaluation for thrombophilia and was diagnosed as being homozygous for methyl-tetra-hydro-folatereductase (MTHFR) deficiency. During her third pregnancy, she had been treated with folic acid 5 mg daily and prophylactic subcutaneous low molecular weight heparin (enoxaparin) 40 mg daily. She carried that pregnancy to full-term (38 weeks) without complications. In the present pregnancy, she had received enoxaparin 40 mg and folic acid 5 mg daily until she presented with abdominal pain. She described the pain as sudden in onset, sharp and continuous. She denied any past or recent abdominal trauma. She had taken her last dose of enoxaparin at 19:00 and arrived at the hospital at 23:30 of the same evening. On admission, blood pressure was 100/70 mmHg and pulse 70 bpm. Physical examination revealed a diffusely tender and distended abdomen, with signs of peritoneal irritation. The uterine tone was normal, and there was no vaginal bleeding. Non-reactive stress testing and her biophysical profile were normal. She was transferred to our delivery room for further observation because of her unrelenting pain. A severe prolonged fetal bradycardia was identified 10 minutes later and an emergency caesarean was performed under the assumption of a placental abruption. The peritoneum was opened, revealing a large amount of fresh blood and blood clots in the abdominal cavity. A live baby was delivered. The amniotic fluid was clear and no evidence of abruption was seen on the placenta. After suturing the uterus, persistent bleeding was noted to appear from the upper abdominal cavity and a general surgeon was called in order to locate the source of bleeding. He performed a vertical abdominal incision and an exploratory laparotomy revealed a tear in the splenic hilum, whereupon he performed a splenectomy. There appeared to be no other source of bleeding. The patient received blood products during and after the operation. Her recovery was uneventful and she was discharged with a healthy baby 10 days after her admission. The pathology report confirmed a rupture of the splenic capsule.

Characteristics of microorganisms cultured from infected wounds post-hysterectomy

OBJECTIVE To characterize organisms causing wound infection following abdominal hysterectomy. STUDY DESIGN All patients who underwent an abdominal hysterectomy (December 2002-January 2006) and developed abdominal wall wound infection proven by a positive culture were included in the study. Patient information was collected from the computerized files. The isolated microorganisms were characterized for antibiotics susceptibility. RESULTS Sixty-eight (68/620, 10.96%) patients had positive wound cultures. Of 100 isolated microorganisms, 44 were resistant to cefonicid (prophylactic treatment) and 15 were resistant to combined ampicillin, gentamicin and metronidazole (empirical treatment). Major co-morbidities (including diabetes mellitus, hypertension, past malignancies, renal, cardiovascular and pulmonary diseases, hypothyroidism or anemia), were found to be significantly associated with pseudomonal infection (P<.008). CONCLUSION A significant portion of pathogens causing post-hysterectomy abdominal wall wound infection are resistant to the prophylactic treatment, and some are resistant to the empirical treatment. Further studies are necessary to evaluate the effectiveness of various prophylactic regimens with better coverage of Enterococcus fecalis, as well as the effectiveness of empirical treatment active against the resistant Enterobacteriaceae group.

Association of aberrant right subclavian artery with abnormal karyotype and microarray results

The objective of this study is to evaluate the incidence of chromosomal aberration (both microscopic and sub‐microscopic) in fetuses with an aberrant right subclavian artery (ARSA) detected by ultrasonographic anomaly scan.

Microarray analysis in pregnancies with isolated unilateral kidney agenesis

BackgroundThe objective of our study was to examine the risk for submicroscopic chromosomal aberrations among fetuses with apparently isolated solitary kidney.MethodsData acquisition was performed retrospectively by searching Israeli Ministry of Health-computerized database. All cases having chromosomal microarray analysis (CMA), referred because of an indication of isolated unilateral kidney agenesis between January 2013 and September 2016, were included. Rate of clinically significant CMA findings in these pregnancies was compared to pregnancies with normal ultrasound, based on a systematic review encompassing 9,792 cases and local data of 5,541 pregnancies undergoing CMA because of maternal request.ResultsOf the 81 pregnancies with isolated solitary kidney, 2 (2.47%) loss-of-copy number variants compatible with well-described deletion syndromes were reported (16p11.2–16p12.2 and 22q11.21 microdeletion syndromes). In addition, one variant of unknown significance was demonstrated. The relative risk for pathogenic CMA findings among pregnancies with isolated unilateral renal agenesis was not significantly different compared with the control population.ConclusionCMA analysis in pregnancies with unilateral renal agenesis might still be useful, to the same degree as it can be in the general population.

The genetic and clinical outcome of isolated fetal muscular ventricular septal defect (VSD)

Abstract Introduction: Our objective was to evaluate the incidence of chromosomal aberration (both microscopic and submicroscopic) and the clinical outcome of fetuses with isolated muscular ventricular septal defect (VSD). Material and methods: The study included 40 pregnant women whose fetuses were diagnosed with isolated muscular ventricular septal defect (mVSD). Of these, 30 patients underwent amniocentesis and 10 declined. All samples were tested by chromosomal microarray analysis (CMA). Of the 40 women in the study, 32 gave birth and the clinical outcome of the children was retrieved from the patients’ medical records. Results: Of the 30 patients who underwent amniocentesis, one was detected with mosaic Klinefelter syndrome and one was detected with a pathogenic copy number variant unrelated to the VSD. Clinical follow-up was performed on 26 children after birth. The first postnatal echocardiography did not detect a VSD in 13 (50%) of the followed-up children. Spontaneous closure occurred in another eight (30.8%) children during the postnatal follow-up period. In only five children (19.2%) VSD was still detected by echocardiography after the first year of life. Discussion: Isolated muscular VSD diagnosed prenatally does not appear to be a significant risk factor for chromosomal abnormalities and has a favorable clinical outcome.

OP08.06: Is aberrant right subclavian artery in fetuses a risk factor for microscopic and submicroscopic chromosomal aberrations?

Objectives: To investigate pregnancy outcome for fetuses with nuchal translucency (NT) ≥ 3.5 mm but normal karyotype and CMA. Methods: A retrospective population-based cohort study was performed. All patients referred to our institution for nuchal translucency ≥ 3.5 mm were included into the study. We proposed a fetal karyotype by invasive testing to all patients. We followed prenatally all patients until delivery; pregnancy outcome was also recorded and defined as adverse (termination of pregnancy [TOP], miscarriage [MC], or delivery of a child with structural defects or genetic disorders), or favourable (delivery of a child without any structural defects or genetic disorders diagnosed before discharge). Results: From October 2012 to November 2016, we identified 74 fetuses with NT ≥ 3.5 mm with normal karyotype and CMA. The mean maternal age was 33 years. An adverse perinatal outcome was observed in 27% of cases. In 3 cases (4%) a MC was observed and in one case a premature delivery at 25 WG with post-natal death was observed. The ultrasonographic follow-up showed 6 cases of major congenital heart diseases (CHD) and 4 cases of minor CHD. Further 4 cases of major anomalies were detected at ultrasonographic follow-up including diaphragmatic hernia, Dandy Walker malformation associated with skeletal dysplasia, hydronephrosis and discordance anomaly in monochorionic twins. Conclusions: Adverse pregnancy outcome increases with NT ≥ 3.5 mm, even with normal karyotype and CMA, as in one third of cases a congenital malformation or a MC was observed.

Improving preimplantation genetic diagnosis (PGD) reliability by selection of sperm donor with the most informative haplotype

BackgroundThe study is aimed to describe a novel strategy that increases the accuracy and reliability of PGD in patients using sperm donation by pre-selecting the donor whose haplotype does not overlap the carrier’s one.MethodsA panel of 4–9 informative polymorphic markers, flanking the mutation in carriers of autosomal dominant/X-linked disorders, was tested in DNA of sperm donors before PGD. Whenever the lengths of donors’ repeats overlapped those of the women, additional donors’ DNA samples were analyzed. The donor that demonstrated the minimal overlapping with the patient was selected for IVF.ResultsIn 8 out of 17 carriers the markers of the initially chosen donors overlapped the patients’ alleles and 2–8 additional sperm donors for each patient were haplotyped. The selection of additional sperm donors increased the number of informative markers and reduced misdiagnosis risk from 6.00% ± 7.48 to 0.48% ±0.68. The PGD results were confirmed and no misdiagnosis was detected.ConclusionsOur study demonstrates that pre-selecting a sperm donor whose haplotype has minimal overlapping with the female’s haplotype, is critical for reducing the misdiagnosis risk and ensuring a reliable PGD. This strategy may contribute to prevent the transmission of affected IVF-PGD embryos using a simple and economical procedure.Trial registrationAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. DNA testing of donors was approved by the institutional Helsinki committee (registration number 319-08TLV, 2008). The present study was approved by the institutional Helsinki committee (registration number 0385-13TLV, 2013).