Comparing the efficacy and pregnancy outcome of intrauterine balloon and intrauterine contraceptive device in the prevention of adhesion reformation after hysteroscopic adhesiolysis in infertile women: a prospective, randomized, controlled trial study.

STUDY OBJECTIVE: To evaluate the efficacy and pregnancy outcomes of intrauterine balloon and intrauterine contraceptive devices in the prevention of adhesion reformation following hysteroscopic adhesiolysis in infertile women with moderate to severe intrauterine adhesion. DESIGN: A prospective, randomized, controlled trial study. SETTING: A tertiary university hospital. PATIENTS: A total of 130 patients with moderate (American Fertility Society [AFS] score of 5-8) and severe (AFS score of 9-12) intrauterine adhesions were recruited. INTERVENTIONS: 86 patients were evenly allocated to group treated with an IUD for 1 month and group treated with an IUD for 2 months. 44 patients were allocated to group treated with a Foley catheter balloon.(IUD: Yuangong IUD). MEASUREMENTS AND MAIN RESULTS: The primary outcome measures were the AFS score, endometrial thickness, and pregnancy outcome. After hysteroscopy, the AFS score was significantly decreased(P<0.05), whereas endometrial thickness was significantly increased across the three groups(P<0.001). Notably, the decline in the AFS score in the balloon group was greater than that in the IUD-1-month group and IUD-2-month group(P<0.01), with no significant difference between the IUD groups(P = 0.298). Lastly, In addition, the extent of the increase in endometrial thickness(P = 0.502) and the pregnancy outcomes(P = 0.803) in the three groups were not significantly different. CONCLUSION: Inserting a balloon or placing an IUD for one or two months can effectively lower the risk of adhesion recurrence and restore the shape of the uterine cavity. While the therapeutic effect of the balloon was superior to that of the IUD, no significant differences were observed in the one-month and two-month IUD groups. TRIAL REGISTRATION: This research was registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/enIndex.aspx ); Clinical trial registry identification number: ChiCTR-IOR-17,011,943 ( http://www.chictr.org.cn/showprojen.aspx?proj=17979 ). Date of trial registration: July 11, 2017.

Fertility Intention Among Chinese Reproductive Couples During the COVID-19 Outbreak: A Cross-Sectional Study.

A decline in the fertility rate has been observed worldwide, which hampers social development severely. Given the impacts of COVID-19 on individuals and society, it is of great significance to investigate the fertility intention of reproductive couples under COVID-19. The convenience sampling method was used to obtain our study sample. The self-administered questionnaire included the following components: sociodemographic characteristics (age, residence, education, occupation, characteristics of the couples, and annual household income), reproductive history (parity, number of children, child gender, and duration of preparing pregnancy), and attitudes toward COVID-19, was distributed online via an applet of WeChat. The results showed that among 4,133 valid questionnaires, 1,091 had fertility intention before COVID-19, whereas 3,042 did not, indicating a fertility intention rate of 26.4% among participating couples. Of the 1,091 couples who had fertility intention before COVID-19, 520 (47.7%) were affected by the outbreak, whereas 571 (52.3%) were not. By multivariable logistic regression analysis, we further found that couples living in Hubei Province, the epicenter in China (OR 2.20, 95% CI 1.35-3.60), and couples who prepared for pregnancy longer before COVID-19 (OR 1.19, 95% CI 1.06-1.33) were more likely to change their fertility intention under the pandemic. In addition, most of the participants reported their fertility intention was affected by the inconvenience of seeking medical service under COVID-19. Therefore, more forms of medical services to provide convenience for patients might be effective ways to reverse the declined fertility intention rate in facing COVID-19.

Karyotype of the Blastocoel Fluid Derived by Laser-Assisted Hatching Demonstrates a Low Agreement With the Trophectoderm.

Objective: The aim of this study is to compare the amplification efficiency and the genomic profiles of blastocoel fluid (BF) derived by laser-assisted hatching and trophectoderm (TE) cells derived from the same blastocyst. Methods: Fifty-four fresh blastocysts underwent shrinkage by laser-assisted hatching, and each BF sample was collected individually. BF and TE cells were retrieved from each blastocyst for chromosome analysis through multiple annealing and looping-based amplification cycles (MALBAC) and next-generation sequencing (NGS). Results: Fifty-four BF samples and 32 TE samples were retrieved for this study. Out of the 54 BF samples, only 35 provided reliable NGS data for comprehensive chromosome analysis (64.8%), while all 32 TE samples did (100%). Finally, there were 23 pairs of BF and TE samples from the same blastocyst. Only 17.4% of the BF-DNA karyotypes were completely agreeable with the TE samples (4/23). Conclusion: Blastocoel fluid derived by laser-assisted hatching is easy to operate, and BF-DNA can be successfully amplified and subjected to NGS. Due to the low amplification efficiency and increased discordance with TE, BF does not adequately represent the status of the rest of the blastocyst. The use of BF as a single source of DNA for preimplantation genetic screening (PGS) is not yet advised.

Effect of new biological patch in repairing intrauterine adhesion and improving clinical pregnancy outcome in infertile women: study protocol for a randomized controlled trial.

BACKGROUND: Endometrial fibrosis caused by intrauterine adhesion (IUA) can lead to hypomenorrhea, amenorrhea, and even infertility and abortion. The postoperative recurrence rate of severe IUA remains high, giving rise to low pregnancy rates. An extracellular matrix (ECM) scaffold, a new biological material that can promote cell proliferation and differentiation at lesions, has been widely used in general surgery and neurosurgery. The present study applied ECM scaffolds in obstetrics and gynecology for the first time to improve endometrial fibrosis, repair severe IUA, and improve pregnancy outcomes for infertile patients. METHODS: This paper presents a prospective randomized single-blind controlled superiority study of infertile women aged ≤40 years with IUA. According to the scoring criteria for IUA established by the American Fertility Society, patients with moderate or severe IUA were randomized into two groups at a ratio of 1:1; patients in the experimental group were treated with an ECM scaffold (small intestinal submucosa [SIS]) + intrauterine balloon, while patients in the control group were treated with an intrauterine balloon only. A hysteroscopic examination of adhesion repair was performed again after 2 months of postoperative hormone replacement therapy. Endometrial tissue was sampled during the two operations, and immunohistochemistry was used to observe endometrial and microvascular proliferation. After thawing and resuscitation, a postoperative frozen embryo transfer was performed on the participants in both groups, and their endometrial thickness, intrauterine volume, endometrial vascularization flow index, endometrial flow index, and uterine artery blood flow resistance were evaluated by 3D ultrasonography. The rates of embryo implantation, clinical pregnancy, and early spontaneous abortion were observed. DISCUSSION: The ECM scaffold (SIS) + intrauterine balloon method was able to repair endometrial fibrosis and improve IUA. This new technique represents a novel treatment method for improving the pregnancy outcome of infertile patients with moderate/severe IUA. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR2100052027 . Registered on October 14, 2021.

Analysis of the effect of phloroglucinol on pregnancy outcomes involving frozen embryo transfers in patients with endometriosis: A retrospective case-control study.

Objective: Abnormal contraction of uterus and vascular smooth muscle lead to the formation of hypoxia environment in uterus. Abnormal contraction may be the basis of dysmenorrhea, endometriosis, infertility and other diseases. Phloroglucinol is a non-atropine and non-papaverine smooth muscle spasmolytic agent, which can reduce the abnormal contraction of uterine smooth muscle. This study investigated the effect of phloroglucinol on frozen embryo transfer in patients with endometriosis. Methods: The data of patients with endometriosis who underwent a frozen embryo transfer in Shanghai Changzheng Hospital from August 2018 to August 2021, comprising a total of 453 cycles, were retrospectively analyzed. The patients for whom phloroglucinol was included over 217 cycles were administered intramuscully 40 mg phloroglucinol starting on the day of progesterone administration, then once daily up to day 7 after the embryo transfer. Those for whom phloroglucinol was not administered over 236 cycles were used as the control group. The age of 35 years was used as a boundary in this study to observe the pregnancy outcomes of patients in the two different age groups. Results: The biochemical pregnancy rate (63.13% vs. 51.27%), embryo implantation rate (44.64% vs. 33.60%), clinical pregnancy rate (59.64% vs. 48.30%), and live birth rate (52.99% vs. 36.86%) after the administration of phloroglucinol were higher than for patients in the control group, and the early abortion rate (7.75% vs. 20.18%) was also lower. The differences were statistically significant (P < 0.05). In particular, in the age group <35 years old, the embryo implantation rate (51.81% vs. 39.38%), clinical pregnancy rate (69.34% vs. 57.55%), and the live birth rate (63.50% vs. 44.60%) after phloroglucinol intervention rose significantly, and the abortion rate dropped (6.32% vs. 17.5%), indicating a statistically significant difference (P < 0.05). However, pregnancy outcomes showed no difference in the age group ≥35 years old (P > 0.05). Conclusion: Continuous low-dose phloroglucinol pretreatment before and after frozen embryo transfer can improve both the clinical pregnancy and live birth rates and reduce the risk of abortion in younger infertile patients with endometriosis.

Novel LAT Pathogenic Variants in a POI Family and Its Role in the Ovary.

Premature ovarian insufficiency (POI) affects about 1% of women under 40 years and leads most often to definitive infertility with adverse health outcomes. Genetic factor has been reported to play an important role in POI. However, the genetic etiology remains unknown in the majority of the POI patients. Whole-exome sequencing and variant analysis were carried out in a POI pedigree. In vitro studies of the wild-type and mutant proteins were conducted in primary granulosa cells (GCs) and granulosa cell line. The result showed that the patients carried compound heterozygous nonsynonymous mutations (c.245C > T and c.181C > G) in LAT gene, which were identified to be transmitted from their parents. The two variants were assessed to affect residues that were conserved across different species examined, and were predicted to be deleterious by software predictions. Protein structure predicting result indicated that the two variants could alter their interactions with surrounding residues, which may change the internal structure of the LAT protein. Moreover, LAT protein expression in GCs was demonstrated for the first time, and further functional assays suggested that this mutation could reduce LAT expression and influence GC survival, which may contribute to the etiology of POI. In summary, we detect novel LAT pathogenic variants in a POI pedigree and report for the first time that LAT is present and functional in the GCs of the ovary. Our findings not only shed new light on the role of LAT in GCs, but also broaden the spectrum of genetic causes of POI.

Comprehensive Characterization of Microbial Community in the Female Genital Tract of Reproductive-Aged Women in China.

The microbiota in the human body play critical roles in many physiological and pathological processes. However, the diversity and dynamics of the female genital tract (FGT) microbiota have not been fully unveiled. In this study, we characterized the microbiome variations in reproductive-aged Chinese women, and we revealed that the cervicovaginal microbiota were dominated by Lactobacillus. Overall, the composition of microbiota in the uterine cavity was more diverse than that in the vagina and cervix. A positive correlation between Lactobacillus iners and Lactobacillus crispatus was observed in both the vagina and the cervix, suggesting that these two species might have a symbiotic relationship in the cervicovaginal microbiota. Moreover, we, for the first time, stratified the reproductive-aged Chinese women into subgroups, based on their microbiome profiles. Furthermore, we identified the bacteria whose abundance changed in the uterine cavity of infertile patients when compared with healthy controls, such as L. iners and L. crispatus. Functionally, the metabolism-related pathways, neurotrophin signaling pathway, and adipocytokine signaling pathway were predominantly dysregulated in the uterine cavity of infertile patients. In conclusion, we characterized a comprehensive microbial landscape in FGT, as well as their functional roles in female infertility of the Chinese population.

H3K4me3-Mediated Upregulation of LncRNA-HEIPP in Preeclampsia Placenta Affects Invasion of Trophoblast Cells.

Preeclampsia (PE) is a pregnancy-related disease defined as onset of hypertension and proteinuria after the 20th week of pregnancy, which causes most maternal and perinatal morbidity and mortality. Although placental dysfunction is considered as the main cause of PE, the exact pathogenesis of PE is not yet fully understood. Long non-coding RNAs (lncRNAs) are implicated in a broad range of physiological and pathological processes, including the occurrence of PE. In this study, we investigated the expression and functions of HIF-1α pathway-related lncRNA-HEIPP (high expression in PE placenta) in the pathogenesis of PE. The expression of lncRNA-HEIPP in the placenta from women who underwent PE was screened by lncRNA microarray and then verified using real-time polymerase chain reaction. Then, the methylation profile of the lncRNA-HEIPP promoter and the enrichment of H3K4me3 binding were assessed by bisulfite pyrosequencing and chromatin immunoprecipitation (ChIP)-quantitative polymerase chain reaction (qPCR) assay, respectively. It was found that the level of lncRNA-HEIPP in the PE placenta was significantly higher than that in normal placenta and was increased in HTR-8/SVneo human trophoblast cells upon hypoxia treatment. Moreover, we reported that H3K4me3 manifested significantly higher promoter occupancy on lncRNA-HEIPP promoter in HTR-8/SVneo cells upon hypoxia treatment and found that the downregulation of lncRNA-HEIPP promoted trophoblast invasion. Our findings suggested that the hypoxia-induced expression of lncRNA-HEIPP mediated by H3K4me3 modification in trophoblast may contribute to the pathogenesis of PE.

Outcomes of poor responders following growth hormone co-treatment with IVF/ICSI mild stimulation protocol: a retrospective cohort study.

PURPOSE: No research has studied the effect of GH co-treatment in mild stimulation protocol for poor responders. We therefore conducted this retrospective analysis to assess the outcome of IVF/ICSI cycles after the adjunct GH use to the mild stimulation protocol in poor responders. METHODS: 132 poor responders who received mild stimulation protocol at Reproductive Medicine Center of Changzheng Hospital from January 2014 to December 2016 were included in this study. Good-quality embryo rate, clinical pregnancy rate, and live birth rate were compared between the GH group (n = 61) and control group (n = 71). RESULTS: IVF good-quality embryo rate (68.1 versus 51.5%; P = 0.008*) and ICSI good-quality embryo rate (53.9 versus 36.7%; P = 0.045*) was significantly higher in the GH group. Though the clinical outcomes did not reach a statistically significant difference between the two groups due to the limited sample size, there was a trend of higher rate in GH group in the aspect of clinical pregnancy rate (52.4 versus 47.1%; P = 0.609) and live birth rate (35.7 versus 27.5%; P = 0.392). CONCLUSION: The results suggested that the adjuvant GH treatment in mild stimulation protocol for poor responders could significantly improve good-quality embryo rate, and might therefore improve the clinical outcomes.

A systematic review and meta-analysis of nonpharmacological adjuvant interventions for patients undergoing assisted reproductive technology treatment.

BACKGROUND: Assisted reproductive technology (ART) is not always successful, yet places a high psychological burden on individuals. OBJECTIVES: To assess whether nonpharmacological adjuvant interventions could improve outcomes among patients receiving ART. SEARCH STRATEGY: Electronic databases were searched from inception to March 2017, using keywords such as "fertility treatment," "emotional distress," and "clinical pregnancy." SELECTION CRITERIA: Reports of randomized controlled trials investigating the impact of nonpharmacological interventions on emotional disorders and the pregnancy rate in patients receiving ART published in any language were included. DATA COLLECTION AND ANALYSIS: Data were extracted into a predesigned form. Psychological ratings were pooled using standardized mean differences (SMDs). Heterogeneity was assessed. The primary outcome measures were psychological ratings at baseline and after intervention. MAIN RESULTS: Overall, 34 randomized controlled trials, with a total of 7213 patients, met the inclusion criteria. Nonpharmacological interventions reduced anxiety when compared with control interventions (SMD 0.25, 95% confidence interval 0.08-0.42; I2 =85%), but they had no significant effects on depression and infertility distress. CONCLUSIONS: Nonpharmacological interventions could improve the psychological outcomes of patients undergoing ART treatment.

Changes in human umbilical vein endothelial cells induced by endothelial nitric oxide synthase traffic inducer.

This study investigated the changes in human umbilical vein endothelial cells (HUVECs) induced by overexpression of endothelial nitric oxide synthase traffic inducer (NOSTRIN) and its role in cellular injury. Recombinant NOSTRIN-expressing and empty vectors were transfected into cultured HUVECs, and factor VIII-related antigen was examined by using immunohistochemical analysis. Growth curves were generated for both transfected and untransfected cells and these indicated that the proliferative ability of cells overexpressing NOSTRIN was significantly decreased. The expression of NOSTRIN and eNOS proteins was detected by using Western blot analysis, endothelial NOS (eNOS) activity was assayed by using spectrophotometry, and NO2 (-)/NO3 (-) levels were measured using nitrate reductase. Immunohistochemical analysis demonstrated that all groups expressed NOSTRIN in the plasma membrane and cytoplasm, and Western blot analysis confirmed that NOSTRIN levels were significantly higher in cells transfected with the NOSTRIN plasmid (P<0.01). The activity of eNOS and the levels of NO2 (-)/NO3 (-) were significantly decreased in NOSTRIN overexpressing cells as compared with empty vector and untransfected cells (P<0.01 and P<0.01, respectively). Morphological and ultrastructural changes were observed under light and electron microscopy, and it was found that NOSTRIN-overexpressing cells were elongated with deformities of the karyotheca, injury to the plasma membrane, increased lipids in the cytoplasm, and shortened microvilli. This study showed that overexpression of NOSTRIN had a significant effect on eNOS activity in HUVECs and resulted in significant cellular damage.

CR16 forms a complex with N-WASP in human testes.

The expression of corticosteroids and regional expression 16 (CR16) and neural Wiscott-Aldrich syndrome protein (N-WASP) was studied in the testes of men with idiopathic azoospermia by (1) immunohistochemistry and Western blot to detect the expression of CR16 and N-WASP protein, (2) reverse transcription with the polymerase chain reaction (RT-PCR) to determine the amounts of CR16 and N-WASP mRNA, and (3) double-staining immunofluorescence and laser scanning confocal microscopy (LSCM) to demonstrate the co-localization of CR16 and N-WASP proteins. Immunohistochemistry revealed CR16 and N-WASP proteins in the Sertoli cells, specifically in the Sertoli cell-spermatogenic cell junctions (SspJs) in the epithelium of the seminiferous tubules. RT-PCR indicated that the relative amounts of CR16 and N-WASP mRNA were significantly decreased in men with idiopathic azoospermia, although the ratio of CR16 and N-WASP mRNA was approximately 1:1 in both groups of men. Western blot showed the presence of the CR16 monomer and N-WASP in all tissues examined, but the relevant bands were paler in men with idiopathic azoospermia than those in healthy men. The distribution of CR16 and N-WASP was similar in the epithelium of seminiferous tubules based on double-staining immunofluorescence and LSCM, thereby suggesting that CR16 and N-WASP were co-localized in the SspJs as a CR16/N-WASP complex. The decreased levels of CR16 and N-WASP in the testes of men with idiopathic azoospermia compared with healthy men and the co-localization at the SspJs as a CR16/N-WASP complex in the epithelium of seminiferous tubules suggest that CR16 and N-WASP play a role in the pathogenesis of azoospermia.

[Expression of CR16 in the testis of patients with idiopathic azoospermia].

OBJECTIVE: To investigate the expression of corticosteroids and regional expression 16 (CR16) in the testis of patients with idiopathic azoospermia and the role of CR16 in spermatogenesis. METHODS: Immunohistochemistry and RT-PCR were used to detect the expression levels of the CR16 protein and mRNA in the testes of 48 patients with idiopathic azoospermia and 10 healthy men. RESULTS: Immunohistochemistry showed that the CR16 protein expressed in the Sertoli cells and spermatids-binding region in the epithelium of seminiferous tubules. The level of the CR16 protein was markedly lower in the idiopathic azoospermia patients than in the healthy men, and RT-PCR also showed a significantly decreased level of CR16 mRNA in the testis of the patients. CONCLUSION: The expressions of the CR16 protein and mRNA decrease markedly in the testis of patients with idiopathic azoospermia, indicating a correlation with the pathogenesis of azoospermia.