Controlled ovarian stimulation for endometriosis patients with ultra-long GnRH-agonist or GnRH-antagonist protocols: A retrospective study by propensity score matching.

OBJECTIVES: Although in vitro fertilization with embryo transfer is the most effective treatment for infertile patients with endometriosis, ovarian stimulation protocols are controversial. STUDY DESIGN: We recruited 639 patients with endometriosis from January 2016 to June 2020; 111 and 528 patients were treated with the gonadotropin-releasing hormone (GnRH) antagonist and ultra-long GnRH agonist protocols, respectively. Potential baseline differences between the regimens were adjusted by propensity score matching. Clinical and laboratory data, including the cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLBR), were compared. RESULTS: Ovulation induction required significantly longer use of gonadotropins in the GnRH agonist group. However, the GnRH agonist group had a lower starting dose of gonadotropin (all p < 0.05). Furthermore, significantly lower clinical pregnancy, implantation, and live birth rates were observed in the GnRH antagonist group receiving fresh assisted reproductive technology cycles (all p < 0.05); however, pregnancy outcomes using the subsequent freeze-thaw cycles for the same oocyte retrieval were not significantly different. CCPR and CLBR for the oocyte retrieval cycles of the antagonist and ultra-long agonist protocols were similar. The ultra-long agonist protocol resulted in more favorable implantation of fresh embryos and improved clinical outcomes of the fresh cycle. CONCLUSIONS: This novel strategy could be appropriate for endometriosis patients who are temporarily unsuitable for fresh embryo transfer. The GnRH antagonist protocol can be combined with the whole embryo freezing strategy to achieve CCPR and CLBR similar to the ultra-long agonist regimen, thus simultaneously avoiding the long pre-treatment duration of GnRH agonists during the ultra-long agonist protocol.

The vitrification system may affect preterm and cesarean delivery rates after single vitrified blastocyst transfer.

The purpose of this study was to investigate the possible effects of different vitrification systems on single vitrified blastocyst transfer cycles. The clinical and birth outcomes of 412 patients who underwent single vitrified blastocyst transfer between January 2018 and June 2020 were retrospectively analyzed and compared between patients who underwent blastocyst vitrification with kit A (group A, 196 patients) and those who underwent blastocyst vitrification with kit B (group B, 216 patients). Clinical outcomes, including the clinical pregnancy rate, ongoing pregnancy rate, early miscarriage rate, late miscarriage rate, ectopic pregnancy rate, twin pregnancy rate, and induced labor rate due to fetal malformation, were not significantly different between the two groups (P > 0.05). The preterm delivery rate among singleton newborns (11.57% vs. 3.23%, P < 0.05) and the cesarean delivery rate were significantly higher in group B than in group A (70.25% vs. 57.26%, P < 0.05). Birth outcomes, including the male-to-female ratio, low-birth-weight rate, macrosomia rate, birth defect rate, newborn gestational age, neonatal body weight, and singleton neonatal body length, were not significantly different (P > 0.05). Our findings suggest that different vitrification systems might differentially affect birth outcomes. Such disparity could reflect differences in kit composition and/or protocol.ABBREVIATIONS: DMSO: dimethyl sulfoxide; ES: equilibration solution; VS: vitrification solution; BMI: body mass index; ICSI: intracytoplasmic sperm injection; OR: odds ratio; CI: confidence interval.

Identification of Three Potential circRNA Biomarkers of Polycystic Ovary Syndrome by Bioinformatics Analysis and Validation.

OBJECTIVE: It is well known that circRNAs are closely involved in the progression of various diseases. However, their functions and potential regulatory mechanisms in polycystic ovary syndrome (PCOS) remain largely unknown. In the present study, our aim was to investigate the potential diagnostic value of circRNAs in PCOS. METHODS: The circRNA dataset GSE145296, mRNA dataset GSE155489 and miRNA GSE138572 were downloaded from Gene Expression Omnibus (GEO) database. Then, differentially expressed genes (DEGs) were identified. Based on the potential interactions, a network of cirRNA-related competing endogenous RNAs (ceRNAs) was constructed. Biological functions were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. For further validation, qRT-PCR method was used to detect the expression level of the candidate circRNAs. Then, receiver operating characteristics (ROC) were constructed to evaluate the diagnostic value of the three differentially expressed circRNA (DE-circRNA). RESULTS: We constructed a network of cirRNA-related ceRNA network. Hsa_circ_0075691, hsa_circ_0075692 and hsa_circ_0085997 were validate to be dysregulated in PCOS. CONCLUSION: Hsa_circ_0075691, hsa_circ_0075692 and hsa_circ_0085997 may be potential diagnostic biomarkers of PCOS, but their specific regulatory mechanisms still need to be further studied.

Explore the potential molecular mechanism of polycystic ovarian syndrome by protein-protein interaction network analysis.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders prevailing in reproductive age women, present in 3-15% population of women worldwide. Although there are many studies on PCOS, its underlying mechanism remains to be determined. The present study was to construct protein-protein interaction networks based on the potential disease-causing genes for PCOS and characterize the underlying molecular mechanisms of PCOS using the networks. PCOS-associated genes were extracted from DisGeNet and the protein-protein interaction networks (PPIN) of PCOS were constructed using the String Database. Then we utilized MCODE algorithm to analyse the hub-gene modules from the PPIN. Finally, the major biological functions and signaling pathways involved in the hub modules were explored by functional enrichment analysis. A total of 522 candidate genes associated to PCOS were extracted from DisGeNET database. The PPIN constructed using the genes we have collected above included 488 genes and 2767 interaction relationships. Moreover, seven major gene modules were obtained after analyzing the PPIN with the use of MCODE plug-in. The major modules generated were enriched in certain biological functions such as cancer and cell proliferation and apoptosis, regulation of lipid and glucose metabolism, cell cycle and so on. The integrated analysis performed in the current study revealed that these hub modules and their related genes are closely associated to the pathogenesis of PCOS, which may probably provide novel insights for the treatment of PCOS and the study of its latent pathogenic mechanism. The relationship between several of the key genes including ALB, TOP2A, PTGER3, NPB and BRD2 in the modules and PCOS has not been investigated previously and it remains to be verified by further research of large sample, multi-center and multi-ethnic.

Mitochondrial DNA Copy Number in Human Blastocyst: A Novel Biomarker for the Prediction of Implantation Potential.

The relationship between mitochondrial DNA (mtDNA) copy number and the outcome of embryo transfer is under debate. Our aim was to explore the relationship between mtDNA copy number in human blastocysts and embryonic development to determine whether mtDNA represents a novel biomarker for the prediction of implantation potential. A total of 246 blastocysts were analyzed by next-generation sequencing. There was no correlation between mtDNA copy number and maternal age in all blastocyst groups and euploid blastocyst groups. Additionally, the mtDNA copy number was not significantly higher in aneuploid blastocysts. Subsequently, no relationship was observed between mtDNA copy number and blastocyst quality. The assessment of clinical pregnancy outcome after the transfer of euploid blastocysts to the uterus indicated that the mtDNA copy number was significantly lower in the clinical pregnancy group than in those who failed implantation. The cut-off value of mtDNA copy number was 320.5, which was a highly predictive value. Blastocysts with an increased mtDNA copy number had lower implantation potential, and mtDNA copy number was largely equal in terms of maternal age, chromosome ploidy, and quality of blastocysts.