Blastocyst development after sperm selection at high magnification is associated with size and number of nuclear vacuoles

Spermatozoa selection at high magnification before intracytoplasmic sperm injection seems to be positively associated with pregnancy rates after day 3 embryo transfers. The aim was to demonstrate an association between the presence of vacuoles in sperm nuclei and the competence of embryos to develop to day 5. Grading of spermatozoa at x 6000-x 12,500 magnification: grade I, no vacuoles; grade II, or=1 large vacuole; grade IV, large vacuoles with other abnormalities. The outcome of embryo development in a group of 25 patients after sibling oocyte injection with the four different grades of spermatozoa showed no significant difference in embryo quality up to day 3. However, the occurrence of blastocyst formation was 56.3 and 61.4% with grade I and II spermatozoa respectively, compared with 5.1% with grade III and 0% with grade IV respectively (P < 0.001). Spermatozoa selection at high magnification using Nomarski interference contrast is useful to identify more precisely the size and the number of nuclear vacuoles that greatly exert a negative effect on embryo development to the blastocyst stage. These observations confirm previous studies pointing to possible 'early and late paternal effects', both of which may have an impact on early embryonic development.     

Temporal changes in key maternal and fetal factors affecting birth outcomes: A 32-year population-based study in an industrial city

Background

In Australia and internationally, there is concern about the growing proportion of women giving birth by caesarean section. There is evidence of increased risk of placenta accreta and percreta in subsequent pregnancies as well as decreased fertility; and significant resource implications. Randomised controlled trials (RCTs) of continuity of midwifery care have reported reduced caesareans and other interventions in labour, as well as increased maternal satisfaction, with no statistically significant differences in perinatal morbidity or mortality. RCTs conducted in the UK and in Australia have largely measured the effect of teams of care providers (commonly 6–12 midwives) with very few testing caseload (one-to-one) midwifery care. This study aims to determine whether caseload (one-to-one) midwifery care for women at low risk of medical complications decreases the proportion of women delivering by caesarean section compared with women receiving 'standard' care. This paper presents the trial protocol in detail.

Methods/design

A two-arm RCT design will be used. Women who are identified at low medical risk will be recruited from the antenatal booking clinics of a tertiary women's hospital in Melbourne, Australia. Baseline data will be collected, then women randomised to caseload midwifery or standard low risk care. Women allocated to the caseload intervention will receive antenatal, intrapartum and postpartum care from a designated primary midwife with one or two antenatal visits conducted by a 'back-up' midwife. The midwives will collaborate with obstetricians and other health professionals as necessary. If the woman has an extended labour, or if the primary midwife is unavailable, care will be provided by the back-up midwife. For women allocated to standard care, options include midwifery-led care with varying levels of continuity, junior obstetric care and community based general medical practitioner care. Data will be collected at recruitment (self administered survey) and at 2 and 6 months postpartum by postal survey. Medical/obstetric outcomes will be abstracted from the medical record. The sample size of 2008 was calculated to identify a decrease in caesarean birth from 19 to 14% and detect a range of other significant clinical differences. Comprehensive process and economic evaluations will be conducted.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN012607000073404.     

Twin-twin transfusion syndrome: mathematical modelling

Twin-twin transfusion syndrome (TTTS) represents a pregnancy complication with a high risk for perinatal mortality and postnatal morbidity. Mathematical models have been utilized to examine the mechanisms of disease and potential treatment modalities. We developed four consecutive models based on pathophysiology mechanisms. Conceptually, these models remained simple, but with increased complexity in details. We present our models tutorially with the necessary equations expressed in words. The aetiology of TTTS was related to AV anastomoses from donor to recipient and their growth commensurate with placental growth. We assessed that natural growth of placenta and foetuses causes the diameter and length of the AV, as well as the AV's pressure gradient, to increase proportional to gestational age. The AV transfusion then increases faster than natural foetal growth. A progressively increasing discordance subsequently develops, not compensated for by foetal growth. A simulation is performed to show how this discordance in blood volumetric development causes successive discordances in other functions, particularly renal, circulatory, and cardio-vascular, resulting in disease progression to the various stages of TTTS. In conclusion, mathematical modelling of TTTS has provided an understanding of the sequence of events that leads to the various presentations of TTTS stages as well as the efficacy of therapies.     

Hypophosphatasia: molecular testing of 19 prenatal cases and discussion about genetic counseling

OBJECTIVE: We studied hypophosphatasia (HP) mutations in 19 cases prenatally detected by ultrasonography without familial history of HP. We correlated the mutations with the reported ultrasound signs, and discussed genetic counseling with regard to the particular dominantly inherited prenatal benign form of HP. METHOD: The coding sequence of the tissue nonspecific alkaline phosphatase (TNSALP) gene was analyzed by DNA sequencing, and 3D modeling was used to locate the mutated amino acids with regard to the functional domains of TNSALP. RESULTS: Although reported ultrasound signs were heterogeneous, two mutated alleles were found in 18 of the 19 cases studied, indicating recessive transmission of the disease. Functional domains of TNSALP were affected by 74% of missense mutations. In all the cases, including one with only a heterozygous mutation, molecular, biological, and familial data do not corroborate the hypothesis of prenatal benign HP. The mutation c.1133A>T observed in the prenatal benign form of HP and common in USA was not found in this series. CONCLUSION: The results point out the prenatally detectable allelic heterogeneity of HP. The nature of the detected mutations and the evidence of recessive inheritance do not support these cases being affected with prenatal benign HP.     

Fetal heart rate monitoring patterns in women with amniotic fluid proteomic profiles indicative of inflammation

We hypothesized that abnormal fetal heart rate monitoring patterns (FHR-MPs) occur more often in pregnancies complicated by intra-amniotic inflammation. Therefore, our objective was to examine the relationships among FHR-MP abnormalities, intra-amniotic inflammation and/or infection, acute histological chorioamnionitis, and early-onset neonatal sepsis (EONS) in pregnancies complicated by preterm birth. Additionally, the ability of various FHR-MPs to predict EONS was investigated. FHR-MPs from 87 singleton premature neonates delivered within 48 hours from amniocentesis (gestational age, mean +/- SD: 28.9 +/- 3.3 weeks) were analyzed blindly using strict National Institute of Child Health and Human Development criteria. Strips were evaluated at three time points: at admission, at amniocentesis, and prior to delivery. Intra-amniotic inflammation was established based on a previously validated proteomic fingerprint (mass-restricted score). Diagnoses of histological chorioamnionitis and EONS were based on well-recognized pathological, clinical, and laboratory criteria. We determined that fetuses of women with severe intra-amniotic inflammation had a higher FHR baseline throughout the entire monitoring period and an increased frequency of a nonreactive FHR-MP at admission. Of all FHR-MPs, a nonreassuring test at admission had 32% sensitivity, 95% specificity, 73% positive predictive value, 77% negative predictive value, and 76% accuracy in predicting EONS. Although a nonreassuring FHR-MP at admission was significantly associated with EONS after correcting for gestational age (odds ratio, 5.6; 95% confidence interval, 1.2 to 26.2; P = 0.030), the majority of the neonates that developed EONS had an overall reassuring FHR-MP. Nonreassuring FHR-MPs at either amniocentesis or delivery had no association with EONS. We conclude that in cases complicated by preterm birth, a nonreassuring FHR-MP at the initial evaluation is a specific but not a sensitive predictor of EONS. An abnormal FHR-MP can thus raise the level of awareness that a fetus with EONS may be born, but it is not a useful clinical indicator of the need for antibiotic treatment of the neonate.     

High-intensity focused ultrasound for the targeted destruction of uterine tissues: experiences from a pilot study using a mobile HIFU unit

Background High intensity focused ultrasound (HIFU) is a novel method which offers the non-invasive ablation of tissues without harming overlying organs or skin. It has been introduced successfully in urology for the ablation of prostatic hyperplasia and seems to be promising in the treatment of uterine fibroids. In this study we aimed to examine the feasibility and possible side effects of HIFU treatment of uterine tissues using an experimental mobile HIFU unit with ultrasound guidance. Methods For these experiments, a 1.07 MHz ultrasound source was used which allows treatment depths between 0 and 10 cm. In 12 patients scheduled to have abdominal hysterectomy, 5–60 impulses of HIFU were applied through the intact skin upon uterine tissues directly prior to the surgical procedure. Tissue intensities lay between 3,200 and 6,300 W/cm2 and a fixed pulse length of 4 s was used. Results No side effects were encountered other than one first-degree skin burn and the treatment was well tolerated. Histology showed clearly demarcated coagulative necrosis in the targeted tissues. Treatment was concluded in less than 45 min for each patient. Conclusion Focused ultrasound is an effective method to selectively destroy tissue within the uterus and the transabdominal access route is very feasible. This study shows that a mobile ultrasound source can be used safely and effectively to destroy uterine tissues, such as fibroids, without major side effects.     

Recurrence of ischemic placental disease

OBJECTIVE: To test the hypothesis that the presence of preeclampsia, small for gestational age (SGA)-birth, and placental abruption in the first pregnancy confers increased risk in the second pregnancy. METHODS: A retrospective cohort study entailing a case-crossover analysis was performed based on women who had two consecutive singleton live births (n=154,810) between 1989 and 1997 in Missouri. Small for gestational age was defined as infants with birth weight below the 10th centile for gestational age. Risk and recurrence of ischemic placental disease was assessed from fitting logistic regression models after adjusting for several confounders. RESULTS: Preeclampsia in the first pregnancy was associated with significantly increased risk of preeclampsia (odds ratio 7.03, 95% confidence interval 6.51, 7.59), SGA (odds ratio 1.16, 95% confidence interval 1.06, 1.27), and placental abruption (odds ratio 1.90, 95% confidence interval 1.51, 2.38) in the second pregnancy. Similarly, women with SGA and abruption in the first pregnancy were associated with increased risks of all other conditions in the second pregnancy. CONCLUSION: Women with preeclampsia, SGA, and placental abruption in their first pregnancy--conditions that constitute ischemic placental disease--are at substantially increased risk of recurrence of any or all these conditions in their second pregnancy. Although causes of these conditions remain largely speculative, these entities may manifest through a common pathway of ischemic placental disease with significant risk of recurrence.     

Hyperthermic intraperitoneal chemotherapy in conjunction with surgery for the treatment of recurrent ovarian carcinoma

OBJECTIVES: To review experience of secondary surgical cytoreduction (SSC) with hyperthermic intraperitoneal chemotherapy (IPHC). METHODS: Eligible patients with ovarian cancer in whom pre-operative evaluation indicated that there was a good possibility that disease could be resected to < or = 5 mm underwent surgery followed by intraperitoneal perfusion of cisplatin (100 mg/m2) or mitomycin C (30-40 mg total dose) heated to 41-43 degrees C (105.8-109.4 degrees F) for 90 min. Data for analysis were extracted from retrospective chart review. RESULTS: Eighteen patients underwent surgery and IPHC between 9/02 and 3/05. Characteristics were median age 64 (37-77) years, mean prior laparotomies 1.4 (0-3), mean chemotherapy regimens 3.2 (0-7), mean time from initial therapy to IPHC 30.6 (1-88) months. Original histology: papillary serous 12, poorly differentiated adenocarcinoma 1, serous low malignant potential 2, mucinous 1 and mixed subtypes 2. 13 had recurrent disease and 5 had persistent disease following front-line therapy. 15 received cisplatin and 3 mitomycin C. The mean duration of surgery was 9.8 (5-16) h. The maximum dimension of residual lesions at the end of surgery prior to IPHC was nil (n=11), < or = 2 mm (n=4), < or = 5 mm (n=2) and < or = 10 mm (n=1). Mean time to return of bowel function was 7 (5-20) days and mean time to hospital discharge 11.5 (5-49) days. All patients developed CTEP grade 1 or 2 metabolic or hematologic toxicities. CTEP grade 3 or 4 metabolic toxicity occurred in 72% and a hematologic toxicity in 28%.There was one peri-operative death due to pulmonary embolus. Median progression-free interval was 10 months and median overall survival was 31 months. Improved outcome was significantly related to the size of residual disease prior to IPHC and postoperative chemotherapy. CONCLUSIONS: IPHC is a relatively well-tolerated procedure with the majority of the morbidity being related to associated surgery. When combined with SSC it has the potential to extend quality life in some patients with recurrent ovarian cancer and warrants continued research. Randomized studies are needed earlier in the course of the disease.