Segmentation of In vitro Fertilization with High-intensity Focused Ultrasound in Repeated Implantation Failure with Adenomyosis.

Adenomyosis is a complex issue in reproductive-age women not only on worsening of quality of life due to severe dysmenorrhea or heavy menstrual bleeding but also on the impact of infertility. A 39-year-old female, gravida 0 para 0, with a history of bilateral ovarian endometrioma post laparoscopic surgery presented to our hospital due to suspected deep infiltrative endometriosis (DIE), adenomyosis, and repeated implantation failure. Initially, gonadotropin-releasing hormone analog treatment for DIE with progestin-primed ovarian stimulation protocol was arranged. Four D5 blastocysts were obtained and freezed. Two frozen embryo transfer were performed after ultrasound-guided high-intensity focused ultrasound (USgHIFU) treatment of adenomyosis. She later had a dichorionic diamniotic twin pregnancy, and two healthy newborns were delivered by Cesarean section at gestational age of 35 weeks due to antepartum hemorrhage with placenta previa and preeclampsia. In conclusion, USgHIFU can be a potential treatment option in segmented in vitro fertilization in future.

Novel mutation of MAP3K1 gene in 46,XY DSD with complete gonadal dysgenesis.

OBJECTIVE: Swyer syndrome, or 46, XY complete gonadal dysgenesis, is a disorder of human sexual development which present with female external genitalia, lack of female reproductive organs, and a 46, XY karyotype. Many genes that participate in human sexual development have been implicated in the pathogenesis of 46, XY gonadal dysgenesis. CASE REPORT: A 18-year-old phenotypically female was presented with primary amenorrhea. Surveillance revealed hypergonadotropic hypogonadism, a normal male 46, XY karyotype and absent of functional gonad, which was confirmed by pathological examination of the streak gonad. Whole exome sequencing showed germline mutations of a novel missense variant, c.570G > C, p.Lys190Asn, in exon 2 of MAP3K1 gene. CONCLUSION: Given evolutionary conservation of lysine residue at position 190, the amino acid substitution may interfere with interaction between MAP3K1 and RHOA, and contributes to complete gonadal dysgenesis in the context of 46,XY.

The pro-inflammatory and anti-inflammatory role of hyaluronic acid in endometriosis.

OBJECTIVE: Endometriosis is a bothersome disease affected women worldwide, the mechanism of disease development is still under investigation. Several inflammatory responses after clinical hyaluronic acid (HA) use were reported. Cyclooxygenase (COX)-2 mediated inflammation pathway is involved in the pathogenesis of endometriosis. Thus, we tried to investigate the inflammatory role of hyaluronic acid in endometriosis. MATERIALS AND METHODS: Peritoneal fluid was collected in endometriosis and disease-free patients for the measurement of HA. Endometriotic stromal cells were treated with IL-1ß and HA and expression of COX-2 was evaluated. Mice model of endometriosis was established and treated with fluid or gel form of HA. Endometriotic lesion size and weight were recorded and level of COX-2 was evaluated by immunohistochemistry staining. RESULTS: The level of HA in the peritoneal fluid had no statistically significant difference between normal, early and advanced stage endometriosis patients. The overexpression of COX-2 protein was detected when treating endometriotic stromal cell with HA in the presence of IL-1ß (P < 0.001). The endometriotic lesion size was reduced in mice model when treated with higher concentration gel form HA. It further showed less proportion of strong COX-2 expression compare of gel form HA to fluid form treatment in COX-2 expression score of endometriosis lesion. CONCLUSION: Both proinflammatory evidence, elevated COX-2 expression, and anti-inflammatory result, reduced endometriosis lesion size and COX-2 expression score, were noted in our study after treating HA in in vivo and in vitro models. We hypothesized it is possible that HA may induce an acute proinflammatory response followed by chronic anti-inflammatory reaction in the formation of endometriosis.

Variants in Maternal Effect Genes and Relaxed Imprinting Control in a Special Placental Mesenchymal Dysplasia Case with Mild Trophoblast Hyperplasia.

Placental mesenchymal dysplasia (PMD) and partial hydatidiform mole (PHM) placentas share similar characteristics, such as placental overgrowth and grape-like placental tissues. Distinguishing PMD from PHM is critical because the former can result in normal birth, while the latter diagnosis will lead to artificial abortion. Aneuploidy and altered dosage of imprinted gene expression are implicated in the pathogenesis of PHM and also some of the PMD cases. Diandric triploidy is the main cause of PHM, whereas mosaic diploid androgenetic cells in the placental tissue have been associated with the formation of PMD. Here, we report a very special PMD case also presenting with trophoblast hyperplasia phenotype, which is a hallmark of PHM. This PMD placenta has a normal biparental diploid karyotype and is functionally sufficient to support normal fetal growth. We took advantage of this unique case to further dissected the potential common etiology between these two diseases. We show that the differentially methylated region (DMR) at NESP55, a secondary DMR residing in the GNAS locus, is significantly hypermethylated in the PMD placenta. Furthermore, we found heterozygous mutations in NLRP2 and homozygous variants in NLRP7 in the mother's genome. NLRP2 and NLRP7 are known maternal effect genes, and their mutation in pregnant females affects fetal development. The variants/mutations in both genes have been associated with imprinting defects in mole formation and potentially contributed to the mild abnormal imprinting observed in this case. Finally, we identified heterozygous mutations in the X-linked ATRX gene, a known maternal-zygotic imprinting regulator in the patient. Overall, our study demonstrates that PMD and PHM may share overlapping etiologies with the defective/relaxed dosage control of imprinted genes, representing two extreme ends of a spectrum.

NLRP7 contributes to in vitro decidualization of endometrial stromal cells.

BACKGROUND: Nucleotide-binding oligomerization domain (NACHT), leucine rich repeat (LRR) and pyrin domain (PYD) 7 containing protein, NLRP7, is a member of the NLR family which serves as innate immune sensors. Mutations and genetic variants of NLRP7 have been found in women with infertility associated conditions, such as recurrent hydatidiform mole, recurrent miscarriage, and preeclampsia. Decidualization of endometrial stromal cells is a hallmark of tissue remodeling to support embryo implantation and proper placental development. Given defective decidualization has been implicated in miscarriage as well as preeclampsia, we aimed to explore the link between the NLRP7 gene and decidualization. METHODS: Endometrial samples obtained from pregnant women in the first trimester and non-pregnant women were used to study NLRP7 expression pattern. The human telomerase reverse transcriptase (hTERT)-immortalized human endometrial stromal cells (T-HESCs) were used to study the effect of NLRP7 on decidualization. Decidualization of T-HESCs was induced with 1 µM medroxyprogesterone acetate (MPA) and 0.5 mM 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP). siRNA was used to knock down NLRP7 while lentiviral vectors were used to overexpress NLRP7 in cells. NLRP7 expression was detected by immunofluorescence, qRT-PCR, and Western blotting. Decidualization markers, Insulin-like growth factor-binding protein 1 (IGFBP-1) and prolactin (PRL), were detected by qRT-PCR and ELISA. Nuclear translocation of NLRP7 was detected by the subcellular fractionation and confocal microscopy. The effect of NLRP7 on progesterone receptor (PR) activity was evaluated by a reporter system. RESULTS: NLRP7 was up-regulated in the decidual stromal cells of human first-trimester endometrium. After in vitro decidualization, T-HESCs presented with the swollen phenotype and increased expressions of IGFBP-1 and PRL. Knockdown or over-expression of NLRP7 reduced or enhanced the decidualization, respectively, according to the expression level of IGFBP-1. NLRP7 was found to translocate in the nucleus of decidualized T-HESCs and able to promote PR activity. CONCLUSIONS: NLRP7 was upregulated and translocated to the nucleus of the endometrial stromal cells in an in vitro decidualization model. Overexpressed NLRP7 promoted the IGFBP-1 expression and PR reporter activation. IGFBP-1 expression decreased with the knockdown of NLRP7. Therefore, we suggest that NLRP7 contributes to in vitro decidualization of endometrial stromal cells.