Time lapse microscopy is useful for elective single-embryo transfer.

The aim of our study was to evaluate time lapse microscopy (TLM) as a selection tool for single-embryo transfer (SET) on day 5, blastocyst stage. An observational cohort study was conducted. Patients who had SET were compared to patients who had double embryo transfer (DET). A total of 108 patients were included in analysis, 83 had SET, and 25 underwent DET. Embryos were incubated and evaluated using TLM. The pregnancy rates were similar between the groups (42.2% in SET and 48.0% in DET). However, the multiple pregnancy rate was significantly higher in the DET group compared to the SET group (41.7% versus 2.9%, respectively; p < 0.001). This study concludes that SET with TLM do not decrease pregnancy rates compared to DET. However, transfers of two embryos increase the rate of multiple pregnancies.

Extracorporeal membrane oxygenation in pediatric patients: our experience in the last ten years.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) in children after cardiac surgery is well established. ECMO support is becoming an integral tool for cardiopulmonary resuscitation in specified centers. OBJECTIVES: To review our use of ECMO over a 10 year period. METHODS: All children supported with ECMO from 2000 to 2010 were reviewed. Most of these children suffered from cardiac anomalies. The patients were analyzed by age, weight, procedure, RACHS-1 when appropriate, length of support, and outcome. RESULTS: Sixty-two children were supported with ECMO; their median age was 3 months (range 0-216 months) and median weight 4.3 kg (range 1.9-51 kg). Thirty-four patients (52.3%) needed additional hemofiltration or dialysis due to renal failure. The children requiring ECMO support represented a wide spectrum of cardiac lesions; the most common procedure was arterial switch operation (27.4%, n=17). ECMO was required mainly for failure to separate from the heart-lung machine (n=55). The median duration of ECMO support was 4 days (range 1-14 days); 29 (46.7%) patients were weaned successfully from ECMO during this time period, and 5 of them died during hospitalization, yielding an overall hospital survival rate of 38.7%. CONCLUSIONS: ECMO support has significant survival benefit for patients with post-cardiotomy heart failure. Its early deployment should be considered in cardiopulmonary resuscitation.

Aromatase inhibitors and the endometrium.

OBJECTIVE: To investigate the potential impact of aromatase inhibitors, given after stopping tamoxifen treatment, on the endometrium of postmenopausal breast cancer patients. METHODS: Review of all available literature of studies on aromatase inhibitor therapy in postmenopausal breast cancer patients previously treated with tamoxifen. RESULTS: (1) Endometrial thickness was found to be significantly lower in patients switched from tamoxifen treatment to aromatase inhibitor therapy, compared to those who continued tamoxifen treatment. This significant difference between the 2 groups was maintained throughout the entire treatment. (2) Vaginal bleeding was significantly more common in patients who continued tamoxifen therapy as compared to those who switched to aromatase inhibitors. (3) Replacement of tamoxifen treatment by aromatase inhibitors in postmenopausal breast cancer patients resulted in the appearance of only few, benign endometrial pathologies. The different endometrial pathologies were more common in patients who continued tamoxifen therapy, compared to patients who switched to aromatase inhibitors. (4) Endometrial cancer was recovered in significantly more patients who continued tamoxifen therapy as compared to those switched to aromatase inhibitors. However, some studies showed no significant statistical differences in the frequency of endometrial cancer diagnosed in the tamoxifen group as compared to the aromatase inhibitor group. CONCLUSION: These findings may hint on the possibility that aromatase inhibitors may provide a potential protective effect on the endometrium in patients previously treated with tamoxifen.

Long-term follow-up of postmenopausal breast cancer patients following discontinuation of tamoxifen therapy.

BACKGROUND: There is a need to evaluate the extent of endometrial pathologies that might develop in postmenopausal breast cancer patients following discontinuation of tamoxifen (TAM) therapy. METHODS: The medical records of 153 postmenopausal breast cancer patients who remained untreated following discontinuation of tamoxifen therapy were evaluated for various clinical features, for endometrial thickness measurements, as detected by transvaginal ultrasonography, and for various endometrial pathologies detected. The last endometrial thickness measurement performed before discontinuation of tamoxifen was compared with endometrial thickness measured following discontinuation of tamoxifen. RESULTS: Patients were followed for 37.5+/-31.3 months. There was a gradual and significant decrement of endometrial thickness measured at the last ultrasonographic study performed before cessation of tamoxifen, compared to that observed in all four ultrasonographic studies performed following discontinuation of tamoxifen (P=0.001). Endometrial thickness gradually and significantly decreased in correlation with the time intervals of the four ultrasonographic studies performed following discontinuation of tamoxifen (P=0.001). Overall, 40 hysteroscopies were performed in 38 (24.8%) patients. No tissue was obtained in 18 (11.8%) patients. Overall endometrial pathologies were diagnosed in 22 (14.4%) patients. Benign endometrial polyps were the most frequent endometrial pathology recovered: 17 (11.1%) patients. No endometrial malignancy was diagnosed. The rate of endometrial pathologies considerably decreased with the extension of time following discontinuation of tamoxifen therapy. CONCLUSIONS: Long-term follow-up of postmenopausal breast cancer patients who remained untreated following discontinuation of TAM therapy did not reveal any malignant endometrial pathology. Only few benign endometrial pathologies were diagnosed, which became fewer in time.

Fertility preservation options for women with malignancies.

UNLABELLED: Cancer is not rare in younger women. There has been a remarkable improvement in the survival rates due to progress in cancer treatment. The necessary treatment for most of the common cancer types occurring in younger women implies either removal of the reproductive organs or cytotoxic treatment that could partially or definitively affect reproductive function. Early loss of ovarian function not only puts the patients at risk for menopause-related complications at a very young age, but is also associated with loss of fertility. Further, women in the western hemisphere have been delaying initiation of childbearing to later in life. The results of these changes have led to an increase in patients facing the risk of premature ovarian failure, and therefore seeking help in preserving their fertility. This increase in demand has resulted in a proliferation of techniques to preserve fertility. Indeed, the number of options is increasing; some are more established procedures, such as embryo cryopreservation, and some are still experimental, such as ovarian cryopreservation. Because of the variations in type and dose of chemotherapy, the type of cancer, the time available before onset of treatment, the patient's age and the partner status, each case is unique and requires a different strategy of fertility preservation. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall the potential early loss of ovarian function secondary to radiotherapy and/or chemotherapy for cancer at a young age; explain the increasing demands for fertility preservation; and summarize the limited number of proven, safe, and efficacious methods.

Mode of ventilation during cardiopulmonary bypass does not affect immediate postbypass oxygenation in pediatric cardiac patients.

STUDY OBJECTIVE: To investigate the impact of different modes of ventilation during cardiopulmonary bypass (CPB) on immediate postbypass oxygenation in pediatric cardiac surgery. DESIGN: Prospective, randomized clinical trial. SETTING: University hospital. PATIENTS: 50 pediatric patients (18 girls, 32 boys), aged 4 months to 15 years, undergoing elective repair of congenital heart disease. INTERVENTIONS: Patients were randomized to receive one of 5 modes of ventilation during bypass. Groups 1 and 2 received high-frequency/low-volume ventilation with 100% (group 1) or 21% oxygen (group 2). Groups 3 and 4 received continuous positive airway pressure of 5 cm H(2)O with 100% (group 3) or 21% oxygen (group 4); and in group 5, each patient's airway was disconnected from the ventilator (passive deflation). MEASUREMENTS: Blood gas analysis and spirometry data were recorded 5 minutes before chest opening, 5 minutes before inducing bypass, 5 minutes after weaning from bypass, and 5 minutes after chest closure. MAIN RESULTS: There were no differences in Pao(2) values among the 5 groups studied and at the different time points. Lung compliance was higher 5 minutes before bypass in group 1 versus group 5 (34 +/- 13 mL/cm H(2)O vs 20 +/- 9 mL/cm H(2)O; P = 0.048). CONCLUSIONS: Mode of ventilation during CPB did not affect immediate postbypass oxygenation.

What we learned from extended culture of 'rejected' day-3 cleavage stage embryos: a prospective cohort study.

BACKGROUND: To test whether poor quality day-3 embryos can undergo successful blastulation and implantation. METHODS: A prospective cohort study was conducted. Whether or not a good quality embryo was transferred on day-3, poor quality (rejected) embryos were further cultured and followed. The clinical outcome of each embryo was assessed. RESULTS: A total of 694 rejected embryos (from 205 patients) were included, with a blastulation rate of 21.2% (147 embryos) compared to 64.2% general blastulation rate reported by our laboratory (P < 0.01). In a multivariate logistic regression model, only their grade on day-3 significantly affected blastulation (P = 0.01). A total of 97 embryos attained eligibility for fresh transfer or cryopreservation, only 6 of which resulted from a day-3 embryo scored < 2. Of these, 52 were transferred, resulting in 21 pregnancies (16 clinical and 5 chemical). In summary, 694 cultured embryos yielded 16 clinical pregnancies; a 2.3% clinical pregnancy rate. CONCLUSIONS: Low score day-3 embryos can result in successful blastulation and clinical pregnancies. However, the normal blastulation rate is poor.

Noninvasive test for the diagnosis of ovarian hormone-secreting-neoplasm in postmenopausal women.

CONTEXT: The diagnosis of ovarian hormone-secreting neoplasm in postmenopausal women is currently based on imaging modalities and selective venography. However, these diagnostic tests are not always accurate. In order to improve and simplify the diagnosis, we propose a noninvasive hormonal test. OBJECTIVE: To report our experience using noninvasive hormonal test for the diagnosis of ovarian hormone producing tumor in two postmenopausal women. DESIGN AND INTERVENTION: Evaluation of androgen and estradiol serum levels following 1. Adrenal hormonal depression, 2. ovarian hormonal depression and 3. ovarian hormonal stimulation. SETTING: Tertiary care medical center. MAIN OUTCOME MEASURES: Changes in androgen and estradiol levels. RESULTS: In the first case, total testosterone, free androgen index and estradiol serum levels decreased following ovarian depression by GnRH-antagonist (6.9 nmol/L, 67 nmol/L and < 70 pmol/L, respectively) and subsequently increased after ovarian stimulation with LH (11.5 nmol/L, 117 nmol/L and 176 pmol/L, respectively). Histological evaluation revealed steroid cell tumor in one ovary. In the second case, estradiol serum levels decreased following ovarian depression by GnRH-antagonist (73 pmol/L) and subsequently increased following ovarian stimulation with FSH (118 pmol/L). Histological evaluation revealed granulosa cell tumor in one ovary. CONCLUSIONS: To our knowledge, these are the first cases of ovarian hormone-producing tumors in postmenopausal women diagnosed by noninvasive hormonal test. The proposed test can be considered in postmenopausal women suspected of having androgen and/or estrogen producing tumors.

Colchicine inhibits heterotopic ossification: experimental study in rabbits.

BACKGROUND: Heterotopic ossification is a common complication of hip surgery and musculoskeletal or brain trauma. OBJECTIVES: To confirm by in vivo study that colchicine inhibits osteoblast cell proliferation with marked decrease in tissue mineralization. METHODS: Heterotopic ossification was induced in three groups of New Zealand white rabbits (females, 6 months old, weight 3-3.5 kg) by injecting 2 ml bone marrow drawn from the iliac crest into their right thigh muscle. To prevent heterotopic ossification, colchicine (0.25 mg/ day) was administered orally for 4 weeks to two groups of adult rabbits: group A (preload group)--1 week preceding bone marrow injection; group B--on day of injection; and group C--control group. RESULTS: After 4 weeks the rabbits were evaluated by radiographs and ultrasound for evidence of heterotopic ossification. At the end of the study histologic samples were taken from all the thighs. Imaging and histologic studies showed, with statistical significance, almost complete prevention of heterotopic ossification formation in group A (preload) and a marked decrease in group B, when compared with the controls where large new bone had formed at the injection site. These results indicated the inhibitory effects of colchicine on a bone-forming process in soft tissue such as heterotopic ossification. CONCLUSIONS: The role of colchicine in preventing heterotopic ossification in other bone-forming conditions, such as hip arthroplasty or pelvic trauma, and after brain trauma, remains to be evaluated in a clinical setting.

Use of a novel joint-simulating culture system to grow organized ex-vivo three-dimensional cartilage-like constructs from embryonic epiphyseal cells.

A method for growth and maintenance of vital cartilaginous tissue is necessary for cartilage repair by in-vitro produced biologic implants. A previously tested perfusion system simulating joint activity was used. Whole epiphyses collected from thirty 11-day-old chick embryos were divided into two groups. One group was grown in a tissue culture dish for 10 days. The other group was placed in a perfusion system termed a joint-simulating device (JSD). After a period of 10 days, histology and immunohistochemistry were performed on five epiphyses from each group. Histologically, epiphyses grown in the device coalesced into a homogenous three-dimensional mass. The bridging tissue between individual epiphyses was highly cellular (PCNA staining positive) and was composed of mesenchymal stem cells as shown by expression of FGF receptor 3. No such tissue formed between epiphyses in the tissue culture dish and the epiphyseal cores were shown to be necrotic. The rest of the epiphyses were evaluated for radioactive sulfate incorporation into glycosaminoglycans (GAGs). A tenfold increase in sulfate incorporation occurred in epiphyses grown within the JSD as compared to the traditional culture method. In conclusion, embryonic epiphyses could be a suitable source for the ex-vivo growth of tissue-engineered cartilage constructs that might later be used as an in-vivo cartilage implant. The joint simulating device effectively maintains cartilage viability and bioactivity for as long as 10 days.

GnRH-antagonist programming versus GnRH agonist protocol: a randomized trial.

OBJECTIVE: Testing the ability to program IVF GnRH-antagonist cycles to avoid weekend oocyte retrieval. STUDY DESIGN: Preliminary randomized clinical trial. Patients presenting an indication for IVF or IVF-ICSI were assigned into either the Treatment Group - GnRH antagonist protocol, programmed to start stimulatory agents on a Friday, with oral 2mg estradiol valerate twice a day from the 2nd day of cycle until the first Friday to follow, or to the Control Group - long luteal GnRH agonist protocol. RESULTS: The performance of 27 Treatment Group patients and 24 Control Group patients was analyzed. Cycle dynamics were not clinically or statistically different except for a significant difference in the number of follicles measuring ≥18 mm on hCG administration day. There were no differences in the number of aspirated ova, fertilization rates, embryo quality or number of embryos to be transferred. Pregnancy rate was 41.7% in the Treatment Group and 50% in the Control Group (P>0.5). Only one patient assigned to the Treatment Group had a weekend retrieval. CONCLUSIONS: Preliminary results demonstrate no compromise related to follicular estrogen programming in a GnRH antagonist protocol and provide reassurance regarding the ability to achieve programming goals.

Tamoxifen enhances apoptotic effect of cisplatin on primary endometrial cell cultures.

BACKGROUND: Cisplatin (CDDP) dose-limited by its side-effects is, in some instances, synergistically amplified when combined with tamoxifen (TAM). TAM has been shown to modulate apoptotic pathways of normal endometrial cells, whereas CDDP induces apoptosis in malignant endometrial cells. Their combined effect on normal or malignant endometrium is as yet unknown. This study aimed to evaluate the combined CDDP and TAM's apoptotic effect on normal endometrial tissue in the context of hormonal milieu. MATERIALS AND METHODS: Primary endometrial cell cultures were established and maintained both in the presence and absence of steroidal hormones. The cultures were treated for 24 hours with 20 microM TAM and 50 microM CDDP as single drugs and in combination. Apoptosis was determined by evaluation of pre G1 cell populations in the cell cycle analysis with flow cytometer. RESULTS AND CONCLUSION: CDDP induced apoptosis in all cultures regardless of hormonal environment, while TAM significantly enhanced CDDP-induced apoptosis in steroidal deficient media in an additive manner. These are novel findings depicting CDDP's effect on normal endometrium, singularly and combined with TAM.

The acquired midtarsus deformity classification system--interobserver reliability and intraobserver reproducibility.

A radiographic classification (Schon's) divides Charcot midtarsus deformities into four types identified by Roman numerals (I to IV), according to the anatomical location of the pathological process,11 and an objective method of severity staging using radiographic criteria is introduced and tested. A beta stage is assigned if one of the following criteria is met: 1. a dislocation is present; 2. the lateral talar-first metatarsal angle is > or = 30 degrees; 3. the lateral calcaneal-fifth metatarsal angle > or = 0; or 4. the AP talar-first metatarsal angle is > or = 35 degrees. An alpha stage can be assigned when all four features are absent. Clinical features useful in assessing and managing these deformities have been associated with the various types and stages. To determine whether the classification system is valid, a study was performed. Two examination booklets and an instructional booklet designed to teach the method were distributed to 75 orthopaedic surgeons at the AOFAS summer meeting to test for intraobserver reproducibility and interobserver reliability. Information about the participants was recorded, and the tests were scored. The highest scores for correct responses were achieved by foot and ankle fellows, followed by orthopaedic residents. Attending orthopaedic surgeons achieved the lowest scores. The most common error was a type I deformity misidentified as a type II. The interobserver reliability for correctly classifying the deformities was 81%, and the intraobserver reproducibility was 97%. We concluded that this classification system, intended to clarify the patterns of acquired midfoot collapse, permits assignment of both anatomic type (I to IV) and degree of severity (alpha-beta) with high reliability and reproducibility. It can therefore be used as a tool for diagnosis, planning treatment, and assessing the prognosis.

Massive pulmonary emboli in children: does fiber-optic-guided embolectomy have a role? Review of the literature and report of two cases.

Massive pulmonary emboli is a rare disease in children, with only 39 reported cases in the last 50 years. Almost 50% of the patients died suddenly without receiving medical treatment. Most of the patients who were managed medically (70% of the treated patients) underwent surgical pulmonary embolectomy with 80% survival. Surgical pulmonary embolectomy is a blind procedure that can be improved by using intraoperative angioscopy. This technique was reported in adults with good results. In this article, we describe two pediatric patients who underwent fiber-optic-guided surgical pulmonary embolectomy. To our knowledge, this technique has never been reported in the pediatric population.

Right ventricular outflow tract strategies for repair of tetralogy of Fallot: effect of monocusp valve reconstruction.

OBJECTIVES: The absence of a pulmonary valve (PV) after tetralogy of Fallot (TOF) repair has been shown to impact postoperative right ventricular (RV) function. The purposes of this study were to (i) compare early outcomes after PV-sparing vs transannular patching (TAP) with monocusp valve reconstruction or TAP alone and (b) assess the mid-term results after polytetrafluoroethylene (PTFE) membrane monocusp reconstruction. METHODS: From 2003 to 2009, 163 patients underwent TOF repair. Sixty-nine patients (42.3%) underwent a PV-sparing procedure (Group A), 74 (45.4%) underwent PTFE membrane monocusp valve reconstruction (Group B) and 20 (12.3%) underwent TAP only (Group C). Early outcomes were evaluated by the right-to-left ventricular pressure ratio, RV outflow tract gradient, tricuspid and PV function, intensive care unit (ICU) parameters and need for reintervention. Group B patients were also evaluated at intermediate term for clinical and echocardiographic parameters, including tricuspid and monocusp valve function and mobility. RESULTS: The median age, weight and PV Z-value of Group B patients were significantly lower; 20.5 months, 9.3 kg and -4, respectively. Postoperatively, the right-to-left ventricular pressure ratio was <0.5 in all groups. Mechanical ventilation time, fluid drainage duration and total ICU stay showed no significant difference between Groups A and B, while Group C was significantly longer (P < 0.01). There were five (3%) early deaths: three from Group A and two from Group B. The incidences of moderate or severe pulmonary insufficiency (PI) on discharge were 8.2% in Group A, 9% in Group B and 50% in Group C (P < 0.001). Among Group B patients, 85% of the evaluated patients had less than moderate PI in the intermediate-term follow-up, QRS duration <140 ms in 83.3% and right-to-left ventricular diameter ratio of 0.6 ± 0.2. Two (2.6%) patients underwent reoperation for monocusp replacement. There were two (2.7%) mid-term deaths. CONCLUSIONS: The use of a PTFE membrane monocusp valve and a valve-sparing strategy prevents immediate PI and improves short-term clinical outcomes. PTFE membrane monocusp appears advantageous in preventing severe intermediate-term PI and facilitates the preservation of RV function.

Embryo quality and implantation rates are not influenced by total motile count values in an ICSI programme: a novel point of view.

Total motile count (TMC) is a useful tool for sperm evaluation, comprising both quantitative and motility parameters. Although frequently used, TMC has not yet been evaluated as a contributory variable for intracytoplasmic sperm injection (ICSI) cycles. In this study we evaluate the possible role of TMC as a prognostic parameter in cycles designated for ICSI. We also test the existence of a possible TMC-threshold value that might be predictive for ICSI cycle outcome in the everyday practice. This is a retrospective cohort study in which the research question is addressed by a locally weighted regression (LOESS) analysis. Primary outcome measures are fertilization rate, good quality embryos rate and implantation rate. A total of 666 patients were included, contributing 1456 cycles. The effect of TMC over the fertilization rate was significant, depicting an inverted U-shaped curve: with up to approximately 10 million motile sperm, fertilization rates increased as TMC increased, but from this point on decreased. A slight increment in the rate of good embryo formation with increasing value of TMC was noted, but this did not reach a statistical significance. TMC values demonstrated no effect in the case of implantation rates. ICSI may offer an advantage related to fertilization rates for the sub-fertile male population, with a motile sperm count up to 10 million.

Efficacy of laser in situ keratomileusis in correcting anterior and non-anterior corneal astigmatism: comparative study.

PURPOSE: To compare the efficacy of conventional laser in situ keratomileusis (LASIK) in treating corneal astigmatism and in treating noncorneal ocular residual astigmatism. SETTING: Private practice, Nashville, Tennessee, USA. DESIGN: Retrospective case series. METHODS: The records of dominant eyes of consecutive patients who had LASIK were retrospectively analyzed to compare the efficacy of LASIK in eyes with predominantly anterior corneal astigmatism with the efficacy in eyes with predominantly ocular residual astigmatism (ORA). The ORA was determined by vector analysis using refractive cylinder and topographic astigmatism. Preoperatively, the ratio of ORA to preoperative refractive cylinder (R) was used to divide the patients into 2 groups; that is, eyes with predominantly anterior corneal astigmatism (ORA/R ratio <1.0) and eyes with predominantly ORA (ORA/R ratio ≥1.0). Efficacy was determined by examining the magnitude of the remaining uncorrected astigmatism and comparing the index of success (proportion of preoperative refractive astigmatism that remained uncorrected by LASIK) between the 2 groups. RESULTS: The study evaluated 61 eyes of 61 patients. Conventional LASIK was twice as efficacious in the low-ORA group as in the high-ORA group. The index of success was 0.24 and 0.50, respectively, and the difference between groups was statistically significant (P = .036). CONCLUSION: The efficacy of astigmatic correction by LASIK was significantly higher in eyes in which the preoperative refractive astigmatism was located mainly on the anterior corneal surface than in eyes in which it was mainly located posterior to the anterior corneal surface.