The zona pellucida (ZP) is a glycoprotein matrix surrounding mammalian oocytes. Upon fertilization, ZP hardening prevents sperm from binding to and penetrating the ZP. Here, we report that targeted gene deletion of the liver-derived plasma protein fetuin-B causes premature ZP hardening and, consequently, female infertility. Transplanting fetuin-B-deficient ovaries into wild-type recipients restores fertility, indicating that plasma fetuin-B is necessary and sufficient for fertilization. In vitro fertilization of oocytes from fetuin-B-deficient mice only worked after rendering the ZP penetrable by laser perforation. Mechanistically, fetuin-B sustains fertility by inhibiting ovastacin, a cortical granula protease known to trigger ZP hardening. Thus, plasma fetuin-B is necessary to restrain protease activity and thereby maintain ZP permeability until after gamete fusion. These results also show that premature ZP hardening can cause infertility in mice.
A retrospective study recently showed that oocytes presenting with a high birefringence of the inner zona layer were more often associated with conception cycles. To further investigate these findings, a prospective study was conducted between September 2005 and September 2006 including intracytoplasmic sperm injection (ICSI) cycles presenting with at least two embryos for transfer. Using a polarization imaging system, oocytes were classified prior to ICSI treatment as having either a high zona birefringence (HZB) or a low zona birefringence (LZB) of the zona pellucida. Using zona birefringence as the only selection criterion, two fertilized oocytes, preferably derived from HZB oocytes, were selected for further culture and transfer. The required criteria were met by 135 ICSI cycles (124 patients; 34.9 +/- 4.1 years of age). Embryos for transfer were used in 20 cycles derived from HZB/HZB oocytes, in 50 cycles from HZB/LZB oocytes and in 65 from LZB/LZB oocytes. The corresponding implantation (P < 0.025), pregnancy (P < 0.005) and live birth (P < 0.025) rates were significantly different between HZB/HZB and HZB/LZB versus LZB/LZB group. Embryo development was superior in embryos derived from HZB oocytes. This study concludes that oocyte zona birefringence is a good selection criterion and a good predictive criterion for embryo implantation potential.
The research was supported by a grant from Deutsche Forschungsgemeinschaft and by the START program of the Medical Faculty of RWTH Aachen University. J.F., E.D., J.N., B.R. and W.J.-D. declare that they are named inventors on the RWTH Aachen University patent application EP 13157317.2, 'Use of fetuin-B for culture of oocytes', applied for by RWTH Aachen University.
Here we report two cases of first-trimester parvovirus B19 CASE REPORTS Case 1A 32-year-old primigravida was referred to our unit after routine ultrasound examination revealed increased fetal nuchal translucency (NT) at 13 + 1 weeks' gestation. A detailed sonographic evaluation demonstrated an NT of 4.4 mm, biventricular myocardial hypertrophy, moderate skin edema, mild ascites and bilateral pleural effusion. The ductus venosus (DV) blood flow was normal (positive awave, pulsatility index for veins (PIV): 1.56) 1 . However, the measurement of the fetal middle cerebral artery peak systolic velocity (MCA-PSV) showed an increased velocity of 37 cm/s, suggestive of fetal anemia (Figure 1). Maternal parvovirus (PV) infection was diagnosed by determining PV-specific immunoglobulin-G (IgG) and IgM as well as PV-B19 DNA by polymerase chain reaction (PCR). Fetal karyotype was normal. Subsequently, fetal therapy by cordocentesis was offered. The placenta was located laterally. Because of the softness of the 25-G spinal needle and an inability to correct the intrauterine position, three attempts were needed to place the needle next to the umbilical cord insertion site. No paralyzing agent was used. The umbilical vein was then punctured in one attempt and 3 mL of packed red cells were transfused. The initial hemoglobin count was 0.8 g/dL. No bradycardia was observed during the procedure, which took about 2 minutes.After 2 days, decline of the MCA-PSV and complete resolution of the fetal hydrops were observed. Ultrasound and Doppler examinations were continued for a period of 10 weeks at 3-week intervals. Measurements of MCA-PSV continued to show velocities in the upper percentile range, but no additional signs of fetal anemia were detected. However, at 24 + 5 weeks' gestation the fetus presented again with severe hydrops fetalis and cardiomegaly. The measurement of MCA-PSV showed an increased velocity of 85 cm/s. Cordocentesis and intrauterine blood transfusion were performed. The initial hemoglobin count was 1.4 g/dL (reticulocytes 13.2%, thrombocytes 22/nL). PCR for PV-B19 DNA was positive in maternal blood as well as in fetal ascites and blood. Two further intrauterine blood transfusions followed (at 25 + 3 and 26 + 2 weeks' gestation) (Table 1) and finally
Objective: To assess predictors for survival and complications among a relatively large cohort of fetuses with hydrothorax treated by thoracoamniotic shunting. Methods: All cases with hydrothorax treated by thoracoamniotic shunting in a 10-year period (2002-2011) in two centers were retrospectively reviewed. Results: A total of 78 fetuses with hydrothorax treated with thoracoamniotic shunting were included in the study. Mean gestational age at diagnosis was 25.6 weeks (12-34 weeks). Initial thoracoamniotic shunting was performed at a mean gestational age of 26.5 weeks (16-33 weeks). A mean of 2.53 shunts (1-7) were inserted per fetus. Of the 78 fetuses, 9 (11.5%) died in utero, 69 (88.5%) were born alive and 46 (59%) survived. Prognostic markers significantly associated with nonsurvival were polyhydramnios, hydrops placentae and mediastinal shift at initial scan, onset of hydrops after first shunt placement, rupture of membranes, a shunt-birth interval <4 weeks and low gestational age at birth. In our cohort, fetuses with trisomy 21 had a significantly better survival than euploid fetuses. Conclusions: Although associated with a significant rate of repeated interventions, thoracoamniotic shunting in fetuses with severe hydrothorax results in an overall survival rate of 59%. Fetuses with hydrothorax and trisomy 21 have a better survival when compared to euploid fetuses.
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