Ursula Zollner

Umbilical endometriosis without previous pelvic surgery: a case report

Abstract. 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.

Perinatal risks after IVF and ICSI

Abstract 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.

Assessment of endocrine status in patients undergoing in-vitro fertilization treatment

Abstract Endocrine evaluation as a prerequisite for every patient undergoing routine in-vitro fertilization (IVF) and embryo transfer for tubal or male factor infertility is still a matter of debate. The aim of this study was to determine if a full endocrine work-up, including the measurement of androgens, gonadotropins, prolactin and TSH, is conclusive for the subsequent success in IVF/ET. 71 infertile women without known endocrinopathies (e.g., polycystic ovarian disease), who were scheduled to enter the IVF/ET program were studied under strictly standardized conditions during the follicular phase of a natural cycle. Fasting serum concentrations of follicle stimulating hormone, luteinizing hormone, oestradiol, progesterone, prolactin, testosterone (T), dehydroepiandrosterone, 17-OH-progesterone, androstenedione and thyroid stimulating hormone (TSH) were measured using commercially available radioimmunoassays. Ovarian stimulation was performed by a long gonadotrophin-releasing hormone agonist/human menopausal gonadotrophin protocol. The overall clinical pregnancy rate was 15.5% in the first started IVF cycle. While patients who conceived in the first treatment cycle had significantly lower T levels (368±49 pg/ml) than those who did not (518±27 pg/ml, p=0.042, Kruskal & Wallis H-test), but the percentage of women with elevated T concentrations was not different. Similarly, TSH concentrations were significantly higher in women with a clinical pregnancy (1.9±0.2 mU/ml) than in non-pregnant women (1.4±0.3 mU/ml, p=0.046), but levels were still within the normal range. There were no further significant differences in hormone levels between pregnant and non-pregnant patients. These results do not suggest the measurement of a full hormonal profile in all infertile women before IVF/ET in non-endocrine infertility, taking into account the low likelihood to identify endocrinological disturbances, the considerable cost of endocrine testing and the paucity of therapeutic consequences

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/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 μU/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.

Evaluation of a cut‐off value for sperm motility after different hours of incubation to select the suitable reproductive technology (IVF or ICSI)

BACKGROUND The aim of this study was to enhance the predictability of conventional semen parameters for in-vitro fertilization outcome. The utility of late sperm motility in presence of a cumulus-oocyte complex after different hours of incubation was investigated to predict the outcome of IVF in borderline and normal ejaculates (at least 5 x 10(6) motile sperm). METHODS The study was done on 52 infertile couples undergoing conventional in-vitro fertilization and embryo transfer. Sperm were prepared by the Percoll cushion centrifugation with swim-down. Cocultures were established by inseminating the cumulus-oocyte complexes with 100000 motile spermatozoa and incubating them for 48 hours. Another 100000 spermatozoa were incubated in culture medium for 48 hours. Sperm motility (WHO a+b) was determined at 0, 4, 24 and 48 hours of incubation. RESULTS The fertilization rate was 65.5% (42.9-88.1). The conventional semen parameters did not correlate with the fertilization rate. Sperm motility measured after different hours of incubation was found to be significantly positively correlated with the fertilizing ability of sperm in vitro in Spearmans rank correlation test: motility after 0 h (p<0.02), after 4 h (p=0.0025). after 24 h (n.s.) and after 48 h (p=0.0071). Cut-off values for late sperm motility were determined and differences in fertilization rates were calculated for these cut-off values after different hours of incubation. A cut-off value of 20% progressive motile spermatozoa after 48 hours gave the best statistical power (fertilization rate 71.7 vs. 50.2%, p<0.001). Significant differences in the fertilization rates were also observed for a cut-off value of 35% after 24 hours of incubation (70.1 vs. 46.2%, p=0.001) and for a cut-off point of 60% after 4 hours (72.4 vs. 51.5%, p=0.001). CONCLUSIONS The predictive power of sperm motility after 48 h for fertilization outcome provides support in the decision-making process within the assisted reproduction setting. If less than 20% of sperm are motile after 48 h micromanipulatory techniques should be considered.

LIF and TNF alpha concentrations in embryo culture media are predictive for embryo implantation in IVF

Abstract Objective There is strong evidence that the cytokines leucemia inhibitory factor (LIF) and tumor necrosis factor (TNF) alpha are related to embryo development and implantation. The aim of this study was to determine the levels of LIF and TNF alpha in embryo culture media and to assess its relationship to the outcome of in-vitro fertilization and embryo transfer. Methods A total of 99 patients were included in this prospective trial and underwent either IVF or ICSI procedure. A total of 865 oocytes were collected. Embryos were cultured in sequential media until day 5. A standardized morphology evaluation of all embryos, including a detailed pronuclear scoring, was performed daily during this period followed by the replacement of one or two selected embryos. Collected embryo culture fluids of days 3 and 5 were analysed for LIF and TNF alpha on days 3 and 5. Results Mean TNF alpha concentration in culture media on day 3 was 0.54 and 0.37 pg/mL on day 5 and was significantly lower in women conceiving than in not conceiving (0.43 pg/mL versus 0.59 pg/mL on day 3). Mean LIF concentration on day 3 was 31.5 pg/mL and 35.5 pg/mL on day 5 and was significantly higher in women conceiving (56.2 pg/mL versus 22.2 pg/mL on day 3). Conclusions The results indicate that LIF could have a function in early embryogenesis and as a factor required for embryo implantation. High TNF alpha concentrations seem to be predictive of implantation failure.

Umbilical cord entanglement in monoamniotic twins.

Monoamniotic twins are very rare, occurring with a frequency of 0.004% of all live births1. When a human embryo, at blastocyst stage, divides as late as the 8th day following fertilization, the result is monochorionic monoamniotic twins, which constitute approximately only 1% of all monozygotic twins2. Due to the numerous possible complications associated with monoamniocity, early delivery at 32 weeks’ gestation by primary Cesarean section is recommended1. The perinatal mortality rate is 28–60%. We report clinical and imaging findings in a 27year-old primigravida, who came to our clinic for the first time at 22 + 4 weeks of pregnancy. In the first trimester, the referring gynecologist had diagnosed monoamniotic twin pregnancy. There were no other pregnancy-associated complications. Weekly ultrasound follow-up examinations showed appropriate growth of both fetuses and absence of signs of twin-totwin transfusion syndrome. No fetal anomalies were diagnosed. Umbilical artery and fetal middle cerebral artery blood flow measurements were normal in both cases. The umbilical cord had a ball-of-wool-like configuration (Figure 1a). On color Doppler sonography there were no signs of a knot or constriction (Figure 1). To optimize monitoring, the patient was admitted at the 30th week of gestation. Cardiotocography was performed daily and showed no abnormal results. In order to avoid possible complications associated with cord entanglement, a primary Cesarean section was performed at 32 + 5 weeks. Delivery of the first twin showed it to be normally developed and the umbilical cord was cut without complication (Apgar scores, 7, 8 and 9 at 1, 5 and 10 min, respectively; arterial pH, 7.36; weight, 1920 g). The second twin (Apgar scores, 8, 9 and 9; arterial pH, 7.36, weight, 1470 g) had multiple coils of umbilical cord wrapped around the neck (Figure 2a). The umbilical cord convolution involved the cords of both twins (Figure 2b). The neonatal period and pediatric follow-up were problem-free. Due to the lack of prospective randomized studies, there is no consensus regarding the monitoring of Figure 1 Umbilical cord entanglement on two-dimensional (a) and three-dimensional (b) color Doppler imaging in monoamniotic twins at 28 weeks’ gestation.

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 patients 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.

Uterine artery blood flow in the periimplantation period in embryo transfer cycles

Abstract Objective To assess the role of the uterine artery blood flow in the prediction of implantation in women undergoing embryo transfer during the periimplantation period. Methods A total of 233 couples were included in this prospective study. All patients had embryo transfer, 125 were performed in in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and 108 in cryo cycles. Ultrasound measurements were performed immediately before transfer. The pulsatility index (PI), Resistance index (RI) and the peak systolic velocity (PSV) were measured in both uterine arteries using endovaginal ultrasound. Results In IVF/ICSI cycles the doppler parameters PI (2.48 vs. 2.15), RI (0.78 vs. 1.30) and PSV (60 vs. 63) did not differ significantly between the pregnant and non-pregnant group. The pregnancy rate per transfer was similar in women showing an unilateral (24%), bilateral (33%) or no (27%) notch in the uterine blood flow. In cryo cycles the uterine artery blood flow parameters PI (3.2 vs. 3.0), RI (0.9 vs. 0.9) and PSV (53.2 vs. 51.2) did not differ either between pregnant and not pregnant patients. Conclusions Previous studies were aiming at the measurement of arterial doppler parameters during the follicular phase which may not be adequate for the prediction of implantation. However, our results show that doppler studies during the early luteal phase of assisted reproductive technology cycles are not indicative for the likelihood of pregnancy, too.

Correspondence (letter to the editor):Inconsistent terminology.

We noticed some inconsistencies in the terminology used in the review article by Dudenhausen et al, which we wish to clarify. In twin pregnancies, a distinction is made—depending on placentation and zygosity—between dichorionic (two placentas) and monochorionic (one placenta) pregnancies and dizygous (non-identical/biovular) and monozygous (identical) twins. We make a plea for using the terms zygosity and chorionicity correctly. To monitor the pregnancy and antenatal care, determining zygosity is irrelevant and sonographically impossible (in dichorionic placentation); it is exclusively chorionicity that is important. A monochorionic twin pregnancy can develop only from monozygous twins, whereas a dichorionic pregnancy can, as Dudenhausen and Maier mentioned, develop from two different fertilized ova (dizygous) or a single ovum (monozygous) that has divided at a very early stage. The statement “monozygous twins have a thin membrane, dizygous twins have a thick membrane” is therefore incorrect. Monochorionic twins have a thin membrane, and dichorionic twins (which may be monozygous or dizygous) have a thick membrane. Diagnostic evaluation by ultrasonography can determine the zygosity with any degree of certainty therefore only in monochorionic twins, not in dichorionic twins (exception: if the twins are not the same sex). Further, we wish to point out that fetofetal transfusion syndrome (FFTS) with a stuck twin is not mild FFTS (Figure 2), but according to the criteria set out by Quintero et al. (1), it is severe FFTS.