Retrospective evaluation of established cut-off values for the sFlt-1/PlGF ratio for predicting imminent delivery in preeclampsia patients.

OBJECTIVE: The outcome of preeclampsia is difficult to predict. Laboratory markers such as soluble fms-like tyrosine kinase (sFlt-1) and placental growth factor (PlGF) are thought to be predictive factors. A 2012 study by Verlohren et al. evaluated cut-off values for assessing time to delivery in patients with elevated sFlt-1/PlGF ratios. The present study aimed to evaluate findings in patients with elevated sFlt-1/PlGF ratios who gave birth at Kepler University Hospital in Linz, Austria. The hypothesis was tested, that our patients show longer pregnancy duration despite elevated sFlt-1/PlGF ratios. STUDY DESIGN: This retrospective data analysis included all patients with sFlt-1/PlGF ratios above the established cut-off values between January 2014 and October 2017. Two groups were analyzed relative to gestational age and were matched with healthy controls: 24 + 0 to 33 + 6 gestational weeks, sFlt-1/PlGF ratio >655.2; and 34 + 0 to 36 + 6 gestational weeks, sFlt-1/PlGF ratio >201. MAIN OUTCOME MEASURES: sFlt-1/PlGF ratio and time to delivery correlation. RESULTS: In the <34-week group, 43.2% of the patients delivered beyond 48 h, with a mean sFlt-1/PlGF ratio of 885.06, showing a significantly lower sFlt-1/PlGF ratio than patients who delivered within 2 days (P = 0.04). In the >34-week group, 66.7% were still pregnant after 48 h, with a mean sFlt-1/PlGF ratio of 273.7. CONCLUSION: The sFlt-1/PlGF ratio appears to be a powerful tool for diagnosing and predicting preeclampsia. However, the data do not confirm the cut-off values described earlier, with longer pregnancy durations in this group of patients.

Postpartum Galactostasis of the Vulva in a Case of Bilateral Lactating Ectopic Breast Tissue.

BACKGROUND: In the general population, the incidence of accessory breast tissue, a congenital malformation, is 1-5%. The most common site is the lower axilla. Detecting such tissue may be problematic, and accessory breasts below the umbilicus are extremely rare. CASE: This report describes the case of a 5-day postpartum 29-year-old woman, G2P2, with painful vulvar swelling 6 cm in diameter. The patient was diagnosed with polymastia in the vulva, without polythelia, with galactostasis due to suturing of a birth laceration covering an excretory duct. The sutures were removed, and the pain decreased. Breastfeeding was continued. CONCLUSION: Ectopic breast tissue is rare but should be taken into consideration in the differential diagnosis of a vulvar mass, especially postpartum in lactating women.

Good-quality blastocysts derived from vacuolized morulas show reduced viability.

OBJECTIVE: To study whether late spontaneous vacuolization on day 4 is an artefact or an alternate means of blastocele formation and to analyze its impact on pregnancy outcome and live birth. DESIGN: Prospective observational study. SETTING: University teaching hospital. PATIENT(S): A total of 424 patients who fulfilled inclusion criteria were subgrouped according to the spontaneous vacuolization on day 4: Group 1 had all morulas affected, group 2 showed no signs of vacuoles, and group 3 was mixed (some day 4 embryos had vacuoles and others did not). INTERVENTION(S): Screening for the presence of vacuoles on day 4 and fresh single-blastocyst transfer. MAIN OUTCOME MEASURE(S): Morula and blastocyst scoring, utilization rate, pregnancy and live birth rates. RESULT(S): Patients of group 1 had a reduced blastocyst formation rate on day 5 (P<.01) and significantly fewer good-quality blastocysts for usage (P<.05). In addition, pregnancy (P<.001) and live birth (P<.01) rate were significantly worse in group 1 compared with groups 2 and 3. CONCLUSION(S): Late onset of vacuolization around compaction stage is a negative predictor of blastocyst formation and outcome.

Time-lapse imaging provides further evidence that planar arrangement of blastomeres is highly abnormal.

PURPOSE: Recently, guidelines on the annotation of dynamic human embryo monitoring recommended screening for the presence of planar blastomere arrangement at the 4-cell stage. This observational study was set up in order to analyze whether developmental kinetics of planar human embryos are different from tetrahedral ones. METHODS: Therefore, embryos of 115 consecutive ICSI patients (showing 32 planar and 554 tetrahedral embryos) were cultured in a new time-lapse system (Miri TL) and their embryos were annotated for morphokinetic development and screened for irregular cleavages and morphological dysmorphisms. RESULTS: Significantly less planar embryos reached blastocyst stage and showed worse quality as compared to regular tetrahedral embryos. The rate of bi- and/or multinucleation was also significantly higher in the affected group. Irregular cleavages, particularly embryo rolling, were more often seen in planar embryos. Morphokinetics between planar and tetrahedral were distinguishable up to 4-cell stage (t2-t4), thereafter the observed delay in planar embryos (t8) was more likely the result of a higher rate of arrested embryos in the planar group. CONCLUSIONS: Planar embryos are associated with both a significant increase in irregular cleavage as well as a delay in preimplantation development. This indicates that planar embryos are rather abnormal and should only be considered for transfer if no other embryos are available.

Oocyte competence in in vitro fertilization and intracytoplasmic sperm injection patients suffering from endometriosis and its possible association with subsequent treatment outcome: a matched case-control study.

INTRODUCTION: Endometriosis affects up to 15% of women of reproductive age. There is an obvious lack of studies dealing with morphological parameters of oocyte morphology in endometriosis patients in assisted reproduction. One aim of the study is to describe oocyte morphology in patients undergoing intracytoplasmic sperm injection suffering from endometriosis. In addition, the impact of endometriosis on in vitro fertilization results is analyzed. Both in vitro fertilization and intracytoplasmic sperm injection patients are then matched with an endometriosis-free control group for highlighting the possible association of endometriosis with pregnancy outcome. MATERIAL AND METHODS: Oocyte morphology of endometriosis patients was assessed in two groups. Both study group and control group consisted of 129 in vitro fertilization/intracytoplasmic sperm injection cycles each. Patients were matched according to anti-Müllerian hormone, female age, previous treatment cycles, and method of fertilization. Endometriosis was graded according to the revised American Society for Reproductive Medicine guidelines of 1997. RESULTS: Patients with endometriosis had a significantly lower rate of mature oocytes (p < 0.03) and morphologically normal oocytes (p < 0.001). In particular, brownish oocytes (p < 0.009; stage I-IV) and the presence of refractile bodies (p < 0.001; stage IV) were found to be increased. Endometriosis stage IV was associated with significantly worse-quality oocytes than stages I-III (p < 0.01). Fertilization was significantly reduced in conventional in vitro fertilization but not in intracytoplasmic sperm injection (p < 0.03). This was due to lower fertilization rates in stage III-IV endometriosis compared with stage I-II (p < 0.04). No difference was observed with respect to rates of implantation, clinical pregnancy, miscarriage, live birth, and malformation. CONCLUSIONS: Endometriosis patients, in particular those with severe endometriosis, present lower-quality oocytes. Once fertilized, no impairment of further preimplantation embryo development and pregnancy outcome right up to healthy live birth rate has to be expected.

Quantitative and qualitative trophectoderm grading allows for prediction of live birth and gender.

PURPOSE: Prolonged in vitro culture is thought to affect pre- and postnatal development of the embryo. This prospective study was set up to determine whether quality/size of inner cell mass (ICM) (from which the fetus ultimately develops) and trophectoderm (TE) (from which the placenta ultimately develops) is reflected in birth and placental weight, healthy live-birth rate, and gender after fresh and frozen single blastocyst transfer. METHODS: In 225 patients, qualitative scoring of blastocysts was done according to the criteria expansion, ICM, and TE appearance. In parallel, all three parameters were quantified semi-automatically. RESULTS: TE quality and cell number were the only parameters that predicted treatment outcome. In detail, pregnancies that continued on to a live birth could be distinguished from those pregnancies that aborted on the basis of TE grade and cell number. Male blastocysts had a 2.53 higher chance of showing TE of quality A compared to female ones. There was no correlation between the appearance of both cell lineages and birth or placental weight, respectively. CONCLUSIONS: The presented correlation of TE with outcome indicates that TE scoring could replace ICM scoring in terms of priority. This would automatically require a rethinking process in terms of blastocyst selection and cryopreservation strategy.

Viability of cumulus cells is associated with basal AMH levels in assisted reproduction.

OBJECTIVE(S): An interesting non-invasive approach to select embryos for transfer is analyzing the health state of somatic granulosa cells surrounding the oocyte addressing their mutual dependence. This prospective study was set up to analyse whether the DNA integrity of cumulus cells correlates with preimplantation development and basal AMH levels. STUDY DESIGN: Therefore, 56 patients who gave written consent were enrolled. Sequential denudation of the cumulus-oocyte-complexes was performed in order to separate corona radiata from outer cumulus cells. DNA integrity of both cell types was analysed using a modified chromatin dispersion test. RESULTS: The percentage of viable corona radiata cells per patient showed a linear correlation to blastulation (P<0.05). These innermost cells showed significantly lower rates of strand breaks (P<0.01) as compared to outer cumulus cells. Age-corrected AMH was significantly associated with the DNA integrity of outer cumulus cells (P<0.05). CONCLUSION(S): For the first time it could be shown that in fact clinical embryologists deal with two different entities of cumulus cells, inner and outer ones. It seems that any protective mechanism of the female gamete follows an outward gradient, so that negative effects, e.g. apoptosis, may impair outer cumulus cells first. Age-corrected AMH reflects quality of these outer cumulus cells. KEYWORDS: AMH; Corona radiata cells; DNA fragmentation; Outer cumulus cells; SCD test.

Ectopic pregnancies with unusual location and an angular pregnancy: Report of eight cases.

OBJECTIVE: The increased use of assisted reproduction techniques has been accompanied by an increase in ectopic pregnancies with unusual location being associated with significant maternal morbidity and mortality. This article reports on seven cases of ectopic pregnancies with unusual location and an angular pregnancy. Diagnostic and therapeutic strategies are discussed and a brief review of literature is presented. STUDY DESIGN: Case series of seven cases with ectopic pregnancy in unusual location, following assisted reproductive technique or conceived spontaneously (cesarean scar pregnancy and early abdominal pregnancy in mesoappendix) and an angular pregnancy, having presented at our hospital during the last eight years. Retrospective analyses. RESULTS: Interstitial pregnancy, cornual pregnancy, cesarean scar pregnancy, early abdominal pregnancy in omentum majus, heterotopic (cervical) pregnancy, early abdominal pregnancy in mesoappendix, angular pregnancy. All patients were surgically treated. CONCLUSION: Diagnosis of ectopic pregnancy with unusual location may be difficult, and differentiation of intact intrauterine or extrauterine pregnancy with adequate consideration of the area of uterine ostium of the fallopian tube may be delicate. Moreover, varying treatment strategies and high rates of complications aggravate the situation.

Pharmacological stimulation of sperm motility in frozen and thawed testicular sperm using the dimethylxanthine theophylline.

OBJECTIVE: To evaluate whether the use of theophylline improves sperm motility and treatment outcome in frozen-thawed testicular sperm extraction (TESE). DESIGN: Artificial sperm activation was offered to azoospermic patients between January and October 2010 in two different centers (identical lab conditions). SETTING: IVF units of public hospitals. PATIENT(S): Sixty-five patients participated and gave informed consent. INTERVENTION(S): Sibling oocytes were split into a study (intracytoplasmic sperm injection [ICSI] with thawed testicular sperm treated with theophylline) and a control group (ICSI with thawed untreated sperm). MAIN OUTCOME MEASURE(S): Sperm motility, time for sperm selection, rates of fertilization, implantation, clinical pregnancy, and live birth. RESULT(S): All patients but one (98.5%) showed a significant improvement in testicular sperm motility when theophylline was used. In addition, sperm selection took significantly less time in the study as compared with in the untreated control group. Corresponding rates of fertilization (79.9% vs. 63.3%) and blastulation (63.9% vs. 46.8%) were significantly increased. Significantly more patients achieved clinical pregnancy if embryos/blastocysts derived from oocytes that had been injected with pharmacologically stimulated testicular spermatozoa were transferred (53.9% vs. 23.8%). This also holds true for the implantation rate. CONCLUSION(S): Theophylline turned out to be a reliable tool in stimulating testicular spermatozoa after thawing. Its immediate effect allows for faster and more accurate selection of viable sperm, which in turn improved fertilization and pregnancy outcome in this prospective study.

Age-related distribution of basal serum AMH level in women of reproductive age and a presumably healthy cohort.

In this study, day 1 to 4 serum anti-Müllerian hormone (AMH) level was analyzed in 2,741 patients attending our department for reproductive medicine or reproductive surgery, including a subgroup of 1,105 women who attended an assisted reproductive technology program because of a male factor as a presumably healthy subgroup. Day 1 to 4 serum AMH levels showed an age-dependent distribution and there is a wide range of AMH in each year of age analyzed, showing that even young women are at a risk of reduced ovarian reserve.