The Full-Term Delivery of a Normal Female Infant by a Woman with a Levonorgestrel Intrauterine System in Situ and Identified as Having Uterine Adenomyosis: A Case Report

Abstract This study reports an IVF patient who had adenomyosis underwent 2 in vitro fertilization (IVF) cycles and 3 frozen embryo transfer (FET) cycles but all failed. Then a Levonorgestrel-releasing intrauterine system (LNG-IUS) was inserted into her uterine. When her next menstrual period did not occur, the patient performed a urinary pregnancy test and it was positive. The pregnancy progressed normally and the delivery was uncomplicated. An elective Caesarean delivery was performed at 39 weeks gestation. The IUD was found in the placenta and the postpartum recovery was uneventful. This is the first report of a woman, who having been identified with uterine adenomyosis, delivered a normal female infant with an LNG-IUS in situ. This case report indicated that LNG-IUS may play some roles in changing the uterine environment of adenomyosis

Sex ratio shift after frozen single blastocyst transfer in relation to blastocyst morphology parameters

Abstract The sex ratio shift was observed in peoples who underwent ART treatment. Moreover, there is limited evidence on differences in sex ratio between single frozen-thawed blastocyst morphology, insemination type and transfer days. So further research is needed in this area with regard to factors possibly affecting the sex ratio. Retrospective study based on multicenter including two large assisted reproduction centers in Shanghai and Wuhan in China. A total of 6361 singleton delivery offspring after frozen-thawed blastocyst transfer. Propensity score weighting and logistic regression models were used to estimate the associations between blastocyst morphology grading and child sex ratio. The main outcome measures is singleton sex ratio. In our study, the primary outcome measure was sex ratio which was calculated as the proportion of male newborns among all live births. Higher quality blastocysts resulted in a higher sex ratio than single poor-quality frozen-thawed blastocyst transfer. Among the three blastocyst morphological parameters of trophectoderm (TE), Grade A and B were significantly associated with a higher sex ratio than Grade C. The similar trend was observed in both IVF and ICSI treated subgroups. As compared with expansion (4 + 3), expansion degree 6 achieved a higher sex ratio in overall populations and IVF treated subgroup. Transferring blastocysts of day 6 had the highest sex ratio both in IVF group and ICSI group. A 6.95% higher sex ratio in transferring blastocysts of day 5 in IVF group than those in ICSI group. No significant association between inner cell mass degree and sex ratio was observed. However, as compared with IVF treatment, all morphology parameters achieved the similar or the biased sex ratio favoring female in ICSI treated subgroup. Quality of blastocysts was positively associated with sex ratio. TE score and expansion degree rather than ICM were significantly associated with sex ratio at birth. ICSI treatment promotes the biased sex ratio favoring female

Effects of the histone deacetylase inhibitor ‘Scriptaid’ on the developmental competence of mouse embryos generated through round spermatid injection

Study questionCan the histone deacetylase inhibitor Scriptaid improve the efficiency of the development of round spermatid injection (ROSI)-fertilized embryos in a mouse model?Summary answerTreatment of ROSI mouse zygotes with Scriptaid increased the expression levels of several development-related genes at the blastocyst stage, resulting in more efficient in vitro development of the blastocyst and an increased birth rate of ROSI-derived embryos.What is known alreadyThe full-term development of embryos derived through ROSI is significantly lower than that following ICSI in humans and other species.Study design, size, durationOocytes, spermatozoa and round spermatids were collected from BDF1 (C57BL/6 × DBA/2) mice. For in vitro development experiments, mouse ROSI-derived zygotes were treated with Scriptaid at different concentrations (0, 125, 250, 500 and 1000 nM) and for different exposure times (0, 6, 10, 16 or 24 h). Next, blastocysts of the optimal Scriptaid-treated group and the non-treated ROSI group were separately transferred into surrogate ICR mice to compare in vivo development with the ICSI group (control). Each experiment was repeated at least three times.Participants/materials, setting, methodsMetaphase II (MII) oocytes, spermatozoa and round spermatids were obtained from sexually mature BDF1 female or male mice. The developmental potential of embryos among the three groups (the ICSI, ROSI and optimal Scriptaid-treated ROSI groups) was assessed based on the rates of obtaining zygotes, two-cell stage embryos, four-cell stage embryos, blastocysts and full-term offspring. In addition, the expression levels of development-related genes (Oct4, Nanog, Klf4 and Sox2) were analysed using real-time PCR, and the methylation states of imprinted genes (H19 and Snrpn) in these three groups were detected using methylation-specific PCR (MS-PCR) sequencing following bisulfite treatment.Main results and the role of chanceThe in vitro experiments revealed that treating ROSI-derived zygotes with 250 nM Scriptaid for 10 h significantly improved the blastocyst formation rate (59%) compared with the non-treated group (38%) and further increased the birth rates of ROSI-derived embryos from 21% to 40% in vivo. Moreover, in ROSI-derived embryos, the expression of the Oct4, Nanog and Sox2 genes at the blastocyst stage was decreased, but the optimal Scriptaid treatment restored expression to a level similar to their ICSI counterparts. In addition, Scriptaid treatment moderately repaired the abnormal DNA methylation pattern in the imprinting control regions (ICRs) of H19 and Snrpn.Large scale dataN/A LIMITATIONS, REASONS FOR CAUTION: Because of the ethics regarding the use of human gametes for ROSI studies, the mouse model was used as an approach to explore the effects of Scriptaid on the developmental potential of ROSI-derived embryos. However, to determine whether these findings can be applied to humans, further investigation will be required.Wider implications of the findingsScriptaid treatment provides a new means of improving the efficiency and safety of clinical human ROSI.Study funding/competing interestsThe study was financially supported through grants from the National Key Research Program of China (No. 2016YFC1304800); the National Natural Science Foundation of China (Nos: 81170756, 81571486); the Natural Science Foundation of Shanghai (Nos: 15140901700, 15ZR1424900) and the Programme for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning. There are no conflicts of interest to declare

Construction and in vitro characterization of dual-modality single-photon emission computed tomography-MRI nanoprobes targeting HAb18G/CD147 in breast tumors

Objective: To prepare dual-modality single-photon emission computed tomography (SPECT)-MRI molecular nanoprobes targeting HAb18G/CD147 expressed on breast cancer cell membranes and investigate the physicochemical and biological properties in vitro. Methods: Superparamagnetic iron oxide nanoparticles (SPIOs) were prepared by one-pot reaction method as described. The single-chain antibody fragments HAbF18(ab')2 were conjugated to SPIOs via chemical method and then labeled with 125I using Iodogen method. The final 125I-SPIO-HAbF18(ab')2 nanoprobes were purified. SPIOs or 125I-HAbF18(ab')2 were used as control. We carried preliminary evaluation on their physicochemical properties and biological characteristics in vitro: transmission electron microscope (TEM) and dynamic light scattering (DLS) were used to measure these nanoparticle sizes and the hydrodynamic diameters. The MRI T2 transverse relaxation efficiency of these nanoprobes at different Fe2+ concentrations were measured with 1.5 T clinical MR scanner. The 125I-SPIO-HAbF18(ab')2 and 125I-HAbF18(ab')2 radiochemical purity were measured by thin layer chromatography and the radio chemical yield was calculated. We also conducted stability tests in vitro and octanol/water partition coefficient experiments. Two breast tumor cell lines, MDA-MB-231 (HAb18G-overexpressing cells,experimental group) and MDA-MB-468 (control), were used for assessment of cells viability at different Fe2+ concentrations (1, 5, 10, 20, 40 μg/ml) by methyl thiazolyl tetrazolium assay. Specific binding experiments in vitro included two parts:magnetic resonance imaging and radionuclide tests, the above-mentioned breast cancer cell lines were incubated with 125I-SPIO-HAbF18(ab')2 nanoprobes respectively and took MDA-MB-231 cells which were not treated as blank group. First comparing the MR signal intensity differences among experimental group, the control group and blank group, then calculated the rate of MRI signal changes; Two breast tumor cell lines, MDA-MB-231 and MDA-MB-468 were incubated with 125I-SPIO-HAbF18(ab')2 nanoprobes too, then measured radioactivity counting by γ counter at different time and calculated the cell binding rates, and did statistical analysis by using one-way ANOVA. Results: The SPIOs were fairly homogeneous with an average core size of (10.32±1.30) nm;the SPIO and 125I-SPIO-HAbF18(ab')2 hydrodynamic diameter of 44.80 and 52.64 nm, and MRI scanning showed that the transverse relaxation efficiency of SPIO and 125I-SPIO-HAbF18(ab')2 were 38.79 and 106.73 mM-1 · s-1, respectively. The radio chemical yield of 125I-SPIO-HAbF18(ab')2 and 125I-HAbF18(ab')2 were 41.90% and 85.50%, respectively. The radio chemical yield of the two groups were >95%, suggesting well stability in vitro. The lipo-hydro partition coefficient values were -0.99 ± 0.03 and-1.49 ± 0.08, respectively, which demonstrated that they were both water-soluble substances. Different Fe2+ concentrations (1,5,10,20,40μg/ml) of 125I-SPIO-HAbF18(ab')2 on breast cancer cell lines MDA-MB-231 and MDA-MB-468 showed no significant inhibition of cell proliferation (F values were 0.78, 0.66; P values were 0.58, 0.66). The cell-specific binding experiment showed: MRI signal intensity values on experimental group, the control group and the blank group were (1 670 ± 5), (1 930 ± 8), (2 349 ± 14), respectively, significant differences existed among these groups (F=4 408.48, P=0.000), the rate of signal intensity change of experimental group and the control group were 28.87%, 17.78%. SPECT:MDA-MB-231 could uptake 125I-SPIO-HAbF18(ab')2, the cell binding rates were (6.52 ± 0.60)% and (10.52 ± 2.04)% in 20 min and 4 h, respectively. Conclusions: Our results suggested that the dual-modality SPECT-MRI nanoprobes 125I-SPIO-HAbF18(ab')2 were prepared successfully with good physicochemical properties and biological characteristics in vitro. These dual-modality molecular imaging nano-probes may have potential to improvearly detection and diagnosis of HAb18G/CD147-expressing cancers and to facilitate the development of HAb18G/CD147-directed interventions