Prenatal sonographic ultrasound predictors for the outcome in fetal gastroschisis: a retrospective analysis.

PURPOSE: To identify predictive ultrasound signs for unfavorable outcome in fetal gastroschisis (GS). METHODS: This is a retrospective cohort study among pregnant women with the prenatal diagnosis of GS between 1998 and 2011 at the University of Wuerzburg, Germany. Analysis included prenatal ultrasound scans, neonatal intensive care unit (NICU) records, and pediatric records. The collected variables included maternal and fetal demographics, as well as an analysis of predictors for unfavorable fetal outcome. Unfavorable outcome was defined by more than 2 postnatal surgical interventions, intestinal resections, and long time to oral feeding (≥4 weeks). RESULTS: 35 cases of fetal GS were diagnosed, whereby 23 cases met the inclusion criteria and were evaluated by prenatal ultrasound and postnatal outcome. Based on the postnatal situation, 15 patients were classified in a good prognosis group and 8 patients in a poor prognosis group. Fetuses with poor prognosis were presented later during pregnancy (21.1 ± 6 vs. 26.9 ± 5.3 weeks; p < 0.01) and delivered at earlier gestational age (35.6 ± 0.8 vs. 33.4 ± 1.4 weeks; p < 0.01) with lower birth weight (2074 ± 306.3 vs. 2559 ± 255.4 g; p < 0.01). There were no differences in prenatal findings like growth restriction, amniotic fluid index, or Doppler results between good and poor prognosis group. However, early detected and long-lasting bowel dilatation was associated with poor prognosis. CONCLUSION: Late presentation and early gestational age at delivery are associated with poor prognosis in neonates with GS. Furthermore, early onset as well as long duration of bowel dilatation is associated with poor fetal outcome, while other ultrasound characteristics are not able to predict poor prognosis of GS.

Co-Occurence of Reciprocal Translocation and COL2A1 Mutation in a Fetus with Severe Skeletal Dysplasia: Implications for Genetic Counseling.

Achondrogenesis type II is an autosomal-dominant disease leading to severe micromelic dwarfism. Here, we report on the postmortem identification of a de novo heterozygous mutation in the COL2A1 gene (c.1529G>A, p.Gly510Asp) in a fetus who presented with generalized hydrops fetalis and severe micromelia during prenatal sonographic examinations. Initially, a reciprocal translocation t(4;17)(q31;p13) was detected in this fetus by chorionic villus sampling. Subsequent chromosomal analysis of maternal and paternal blood showed that the patient's mother was carrier of the same reciprocal translocation. SNP array analysis of the fetus did not provide evidence for chromosomal imbalances or CNVs that could be associated with the fetal phenotype. The coexistence of a cytogenetic (reciprocal translocation) and a molecular genetic (COL2A1 mutation) abnormality in the fetus carries important implications for genetic counseling.

Amniotic fluid insulin and C-peptide as predictive markers for fetal macrosomia, birth injuries, and delivery complications?

BACKGROUND: Gestational diabetes mellitus (GDM) occurs in 3-5% of all pregnancies. GDM increases both maternal and fetal risks, causes fetal macrosomia, and hence increases the rates of caesarean sections and delivery complications such as shoulder dystocia. An early predictive marker and consequent early treatment could be beneficial, so amniotic fluid insulin and C-peptide have been examined in several studies. Increased amniotic fluid insulin in early amniocentesis between the 14th and 20th gestational week predicted a later GDM. A potential direct association with fetal macrosomia remains to be determined. MATERIAL AND METHODS: This retrospective study investigated amniotic fluid insulin/C-peptide from amniocenteses between 14 and 20 weeks of gestation in correlation with fetal birth weight, type of delivery, and complications. To focus on effects of fetal hyperinsulinism apart from therapeutic confounders, we included patients who did not participate in GDM screening. Insulin and C-peptide were measured in 144 samples of frozen amniotic fluid. Birth weight, type of delivery, complications, and birth injuries were noted. RESULTS: Birth weights ranged from 760 g to 4410 g with a mean weight of 3424 g at an average of 40 weeks gestation. The mean amniotic fluid insulin was 4.36 U/ml and the mean C-peptide concentration was 0.076 ng/ml. There was no correlation between amniotic fluid insulin or C peptide and birth weight, type of delivery, complications, and birth injuries. CONCLUSIONS: Amniotic fluid insulin and C-peptide are unsuitable as predictive marker for fetal macrosomia, type of delivery, complications, or birth injuries.

Probability of success of conservative treatment of infertility: exact timing as an important prognostic factor.

OBJECTIVE: To find out which forms of conservative infertility therapy led to the highest pregnancy rate and which factors influence the occurrence of a pregnancy. STUDY DESIGN: A total of 433 conservative treatment cycles were retrospectively evaluated. Ovarian stimulation was performed with clomiphene citrate (CC) or gonadotropins (follicle stimulating hormone [FSH] or human menopausal gonadotropin) with ovulation induction and luteal phase support in some cases. Patients then received intrauterine insemination (IUI) or had timed intercourse (TI). RESULTS: The pregnancy rates were 2.7% in CC/TI cycles, 8.2% in FSH/TI cycles, 10.3% in CC/IUI cycles, and 15.5% in FSH/IUI cycles. A cycle regulation by means of an ovulation induction and a luteal phase-supporting medication resulted in significantly higher pregnancy rates. When the TI and/or the IUI were carried out postovulatorily and in the case of already beginning endogenous ovulation (increase of the luteinizing hormone value shown in the last control), the success rate was significantly lower. CONCLUSION: Not only the choice of the optimal form of treatment but also a sufficient supportive medication in terms of an ovulation induction and a luteal phase support as well as exact timing are vital for the treatment success in conservative infertility treatment.

Perinatal risks after IVF and ICSI.

Pregnancies that occur after infertility treatment, particularly after assisted reproduction, constitute high-risk pregnancies. Occurrences of conditions such as high blood pressure, preeclampsia, growth retardations and bleeding are higher in comparison with the norm of spontaneously entered pregnancies. The rate of premature births and the frequency of intrauterine deaths are much higher than the average for all pregnancies. Furthermore, pregnancies resulting from in - vitro fertilisation (IVF) have significantly higher rates of requiring induced labour or caesarean section. However, it is to be assumed that these complications and unfortunate developments are not caused by extracorporeal fertilisation itself, but rather are due to the frequency of multiples and to the risk factors of the women involved. These women are, on average, older and there are often more problems with cycle irregularities, uterine anomalies and obesity than in the total collective of all pregnancies. The methods of modern reproductive medicine often bring a higher rate of multiple pregnancies. The clinical problem of multiple pregnancies is, above all, the raised rate of premature births and intrauterine growth retardations that contribute to the significantly higher rate of morbidity and mortality for these children. The slightly higher rate of congenital defects after IVF and intracytoplasmic sperm injection (ICSI) are also attributed more to the risk profile of the parents and less to the techniques themselves. The most important and easy-to-avoid complication is the multiple pregnancy, and it should be our goal to lower this rate even further.

Good fertilization results associated with high IL-1beta concentrations in follicular fluid of IVF patients.

OBJECTIVE: To determine the levels of interleukin-1 beta (IL-1beta) in follicular fluid and embryo culture fluid after controlled ovarian hyperstimulation and to assess the association of this cytokine with the outcome of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment and embryo transfer. STUDY DESIGN: A total of 256 couples undergoing the IVF/ICSI program were included in this prospective study. Zygote quality, embryo and blastocyst morphology were evaluated, and embryo transfer was performed 5 days after oocyte recovery. IL-1beta concentrations were measured in follicular fluid and embryo culture fluid of the third and fifth culture days. RESULTS: Embryo replacement was performed with a median of 2 embryos per cycle. In all, 44 clinical pregnancies were achieved in 256 assisted reproductive technology (ART) cycles (pregnancy rate: 19.8% per transfer). Follicular fluid concentrations of IL-1P were not significantly different in pregnant (2.1 pg/mL) and nonpregnant women (2.7 pg/mL). Follicular fluid of lVF, but not ICSI, patients with good fertilization rates (> 90%) contained significantly higher levels of IL-1beta (3.3 pg/ mL) than did follicular fluid of women with fertilization rates < or = 90% (2.0 pg/mL, p < 0.05). No correlation was found between intrafollicular IL-1beta and zygote morphology, day 3 and day 5 embryo morphology. There was no relationship between IL-1beta in culture fluid supernatants and embryonic development. CONCLUSION: In IVF patients high levels of intrafollicular IL-1beta were associated with good fertilization rates. There seems to be no correlation between IL-1beta concentrations in follicular fluid or embryo culture fluid and embryo morphology or pregnancy outcome of ART cycles.

3D-Endometrial volume and outcome of cryopreserved embryo replacement cycles.

PURPOSE: The success of artificial reproductive techniques not only depends on the quality of oocytes and spermatozoa but also on the receptivity of the endometrium. The aim of this study was to assess the value of measurement of endometrial volume by three-dimensional (3D) in comparison to 2D-ultrasound in the prediction of implantation in women having transfer of cryopreserved embryos. METHODS: One hundred and eight couples were included in this prospective study. All patients underwent the IVF or ICSI program and had transfer of cryopreserved embryos. Sixty-eight transfers were done in a spontaneous cycle and 40 in an artificial cycle. Endometrial thickness, pattern and three-dimensional volume were measured immediately before embryo transfer. RESULTS: Twenty clinical pregnancies were achieved (PR 18.5 % per transfer), the PR being similar in spontaneous (22.1 %) and artificial (12.5 %, ns) cycles. Three to five days after ovulation (spontaneous cycles) or after the endometrium reached a thickness of at least 8 mm (artificial cycles), a median of three embryos were replaced. In spontaneous cycles, there were no significant differences in endometrial thickness or volume between pregnant (11.9 mm, 2.9 ml) and non-pregnant women (10.7 mm, 3.4 ml). In artificial cycles, the endometrial volume (3.9 vs. 2.5 ml, p < 0.05), but not endometrial thickness (10.7 vs. 10.2 mm, ns) was significantly higher in pregnant than in non-pregnant women. CONCLUSIONS: In artificial cycles, a low endometrial volume is associated with a poor likelihood of implantation. Endometrial volume measured by 3D-ultrasound is an objective parameter to predict endometrial receptivity.

Metastasizing vulvar carcinosarcoma with squamous carcinomatous and leiomyosarcomatous differentiation: genetic evidence of clonal origin.

In this report, we present the first case of a vulvar carcinosarcoma with squamous carcinomatous and leiomyosarcomatous differentiation. Comparative genomic hybridization was used to analyze clonality of the two tumor components. A widely identical pattern of genetic imbalances in the comparative genomic hybridization analysis in both the carcinomatous and the sarcomatous tumor component strongly supported the concept of a bidirectionally differentiated neoplasm. In both tumor components and two lymph node metastases, an amplicon was detected on chromosome 11q12-q13, homing the cyclin D1 gene locus. In contrast, exclusively in the sarcomatoid component, a characteristic amplicon on 12q13-q14 was found. The cytogenetic profile of the lymph node metastases revealed an increase in imbalances compared with the primary tumor. In summary, we found strong indications for a clonal origin of the two tumor components in a vulvar carcinosarcoma and a good correlation of the histological morphology with the pattern of genetic imbalances.

Comparison of two media for sequential culture after IVF and ICSI shows no differences in pregnancy rates: a randomized trial.

BACKGROUND: Optimal culture conditions are crucial for embryonic development and blastocyst formation after in vitro fertilization (IVF) or Intracytoplasmic sperm injection (ICSI). A prospective randomized trial was carried out to compare the effects of two different sequential media (Vitrolife and MediCult) on embryo development and implantation. MATERIAL/METHODS: 176 couples were included in this prospective randomized study. All couples undergoing the IVF (n=84) or ICSI (n=92) program at the University of Würzburg were randomly assigned to either Vitrolife (n=87) or MediCult (n=89) sequential culture media. RESULTS: The overall median fertilization rate (FR) was 84.0% and was similar in the Vitrolife (FR=87.5%) and MediCult group (FR=80.0%). A mean of 2.7 embryos were replaced into the uterus, not significantly different between both groups. The pronuclear development was significantly enhanced in embryos cultured in Vitrolife than in those cultured in MediCult media (p=0.035). The embryonic development on day 3 was also superior in the Vitrolife group, but only in ICSI cycles (p<0.01). After 5 days of culturing, the blastocyst development was equivalent in both groups. The clinical pregnancy rate was 31.0% per transfer in the Vitrolife group and 28.1% in the MediCult group (not significant). CONCLUSIONS: The results demonstrate that implantation and clinical pregnancy rates with both media are comparable. Embryonic development until day three seemed to be enhanced when the embryos were cultured in Vitrolife media.

Pronuclear scoring. Time for international standardization.

Zygote scoring is an efficient tool for embryo selection not only in countries where embryo selection is not permitted. Several different scoring systems have been published so far, making comparisons of assessments between investigators and laboratories extremely difficult. Pronuclear evaluation should be standardized in a manner analogous to the standardization of cleavage stage embryo scoring or of semen evaluation by the World Health Organization. The ideal score should be clear and easily applicable. The items that have the greatest influence on embryonic development seem to be alignment and size of pronuclei, alignment and number of nucleoli, halo effect and appearance of vacuoles. These morphologic parameters can be observed in different features and can be summarized as a zygote score.

Umbilical endometriosis without previous pelvic surgery: a case report.

A 27-year-old woman with a periodically bleeding out of the umbilicus was found to have umbilical endometriosis. She was never pregnant before and had no pelvic surgery. The umbilical lesion was excised following a diagnostic laparoscopy revealing extragenital endometriosis. Umbilical endometriosis is a very rare disease, but should be considered in the differential diagnosis of umbilical lesions.