Exploring the impact of pericentric inversion of chromosome 9 on fertility in sperm donors.

ABSTRACT: Pericentric inversion of chromosome 9 (inv[9]) is a common chromosomal structural variant, but its impact on clinical outcomes remains debated. The screening criteria of sperm banks are rarely mentioned to individuals with inv(9). In this study, we evaluated the fertility of sperm donors with inv(9) who met eligibility criteria for sperm banks (inv[9]-eligible donors). From March 2004 to May 2022, chromosomal analysis of 16 124 sperm donors at CITIC-Xiangya Human Sperm Bank in Hunan Province (Changsha, China) found that 251 (1.6%) had chromosome variations, with inv(9) being the most prevalent at 1.1%. All 169 inv(9)-eligible donors were contacted to collect fertility outcome data, along with 206 eligible donors without inv(9) as controls. In addition, semen samples from inv(9)-eligible donors and eligible donors underwent assessments of sperm fluorescence in situ hybridization (FISH), mitochondrial membrane potential, DNA fragmentation index, acrosome integrity, reactive oxygen species (ROS), and sperm morphology. Results showed that inv(9) did not significantly increase reproductive risks overall. Despite detecting ROS level differences, the clinical impact may be insignificant. This study provides new data on the inv(9) population that can serve as a valuable reference for decision-making by sperm banks as well as for genetic counseling and clinical guidance for individuals carrying inv(9) variant.

Comparison of Clinical Outcomes, Risks, and Costs for 20,910 Donor In Vitro Fertilization and 16,850 Donor Artificial Insemination Treatment Cycles: A Retrospective Analysis in China.

PURPOSE: To evaluate the effectiveness of donor in vitro fertilization (IVF-D) and donor artificial insemination (AI-D) in clinical outcomes, risks, and costs. METHODS: This study analyzed the cycle changes and clinical outcomes in 20,910 IVF-D and 16,850 AI-D cycles between 2013 and 2021 in the Reproductive and Genetic Hospital of CITIC-Xiangya. A cost-effectiveness analysis was performed to evaluate the costs per couple and per live birth cycle in the two treatment groups. RESULTS: IVF-D had higher pregnancy and live birth rates than AI-D (p < 0.001). The cumulative pregnancy and live birth rates for three AI-D cycles were 41.01% and 32.42%, respectively, higher than the rates for one or two AI-D cycles. The multiple birth and birth defect rate of AI-D was lower than that of IVF-D significantly. IVF-D mean cost per couple was higher than that of AI-D (CNY32,575 vs. CNY11,062, p < 0.001), with a mean cost difference of CNY21,513 (95% confidence interval, CNY20,517-22,508). The mean costs per live birth cycle for IVF-D and AI-D were CNY49,411 and CNY31,246, respectively. CONCLUSION: AI-D is more cost-effective and poses a lower risk for infertility couples than IVF-D, and patients should undergo three AI-D cycles to obtain the highest success rate.

Genetic testing of sperm donors at a human sperm bank in China.

Background: In China, numerous human sperm banks only perform three-generation family history evaluation to exclude genetic diseases with clinical symptoms; therefore, many inherited risks cannot be detected before donor qualification even when a thorough genetic family history evaluation has been performed. Hence, the risk of recessive disease inheritance persists with the current eligibility guidelines in China regarding the donor selection process. Methods: Retrospective study that reviewed the genetic test analyses and clinical outcomes of young adult men who were qualified sperm donors at the Hunan Province Human Sperm Bank of China from January 1, 2018, to May 1, 2021. We included a total of 3231 qualified sperm donors: all donors underwent primary screening for thalassemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Whereafter, 278 of donors underwent genetic testing for specific genes, and 43 donors underwent whole exome sequencing. Results: 2.4% of 3231 qualified sperm donors might have thalassemia and 1.4% might have G6PD deficiency. Sperm donors with thalassemia and G6PD deficiency would be eliminated. Specific gene testing identified 7 of the 278 donors (2.5%) as carriers of at least one pathogenic or likely pathogenic variant in a gene, including 1.9% of 154 donors (3/154) as carrier variants in α-Like or ß-Like globin genes, 17.6% of 17 donors (3/17) as carrier variants in GJB2, 12.5% of 8 donors (1/8) as carrier variants in SMN1. In addition, among the 43 sperm donors carrying the 111 pathogenic/likely pathogenic variants, eight (18.6%) were carriers of pathogenic variants of the GJB2 gene. The frequency, therefore, was approximately 1 in 5. Conclusions: The data suggest that used blood routine and RDT can make a preliminary screening of sperm donors, and special gene testing should be performed for sperm donors according to the regional incidence of specific genetic diseases. Meanwhile, whole exome sequencing can be used as a supplementary application in sperm donor genetic testing, and aid a successful and healthy pregnancy. However, industry guidelines must be modified to incorporate its use.

[Efficacy Analysis of Transcatheter Arterial Embolization in Acute Non-Variceal Upper Gastrointestinal Bleeding].

Objective: To evaluate the safety and effectiveness of transcatheter arterial embolization (TAE) in the treatment of acute non-variceal upper gastrointestinal bleeding (ANVUGIB), and to guide clinical practice and continue to optimize diagnosis and treatment strategies. Methods: This retrospective study included 266 patients who underwent angiography due to ANVUGIB between March 2016 and March 2021. Data on the positive rate of angiography, the technical success rate and clinical success rate of TAE, and the rebleeding rate and the all-cause mortality within 30 days after TAE treatment were collected, and the influencing factors relevant to the above events were analyzed accordingly. Results: All 266 patients completed angiography--the positive rate of angiography was 54.1% (144/266), the total technical success rate was 97.3% (217/223), the clinical success rate was 73.1% (155/212), and the rebleeding rate and all-cause mortality within 30 days were 26.9% (57/212) and 16.1% (35/217), respectively. This study found that shock index>1 ( OR=5.950; 95% CI: 1.481-23.895; P=0.012), computed tomography angiography (CTA) positive result ( OR=6.813; 95% CI: 1.643-28.252; P=0.008) and interval<24 h ( OR=10.530; 95% CI: 2.845-38.976; P<0.001) were independent predictors of positive angiography. Shock index>1 ( OR=2.544; 95% CI: 1.301-4.972; P=0.006) and INR>1.5 ( OR=3.207; 95% CI: 1.381-7.451; P=0.007) were independent risk factors for rebleeding. Patients with postoperative bleeding ( OR=3.174; 95% CI: 1.164-8.654; P=0.024) and patients with rebleeding after embolization ( OR=34.665; 95% CI: 11.471-104.758; P<0.001) had a higher risk of death within 30 days. Conclusion: TAE is safe and effective in the treatment of ANVUGIB. Patients with shock index>1 and positive CTA are more likely to be angiographic positive, and should undergo angiography as early as possible after bleeding. In addition, rebleeding after embolization deserves high attention.

Update on techniques for cryopreservation of human spermatozoa.

In the 1960s, sperm cryopreservation was developed as a method to preserve fertility. Currently, techniques for the cryopreservation of human spermatozoa have been widely used in assisted reproduction. However, although sperm cryobiology has made notable achievements, the optimal method for the recovery of viable spermatozoa after cryopreservation remains elusive. Postthawing sperm quality can be affected by cryoprotectants, ice formation, storage conditions, and osmotic stress during the freezing process. This review discusses recent advances in different cryopreservation techniques, cryoprotectants, and freezing and thawing methods during cryopreservation and new indications for the use of cryopreserved spermatozoa.

Micro-straw: An efficient cryopreservation carrier for rare human spermatozoa.

BACKGROUND: Many cryopreservation carriers have been introduced to freeze rare human spermatozoa, however, these carriers relative attributes and comparative effectivenesses have not yet been systematically studied. OBJECTIVES: Is the micro-straw cryopreservation carrier more effective for cryopreserving rare human spermatozoa compared with the Cryoplus and a new micro-straw (LSL straw) carriers? MATERIALS AND METHODS: This study involves 93 samples from healthy sperm donors and 40 samples from patients diagnosed with oligospermia, asthenospermia, oligoasthenospermia, or obstructive azoospermia. We determined the optimal freeze-thaw protocol for the Micro-straw carrier. The post-thaw survival rate, normal sperm morphology, acrosome integrity, and DNA fragmentation for Micro-straw, Cryoplus, and LSL carriers were then determined. Finally, we verified the effects of freezing using these carriers by comparing the qualities of post-thaw spermatozoa from patients. RESULTS: The highest total motility (TM) and progressive motility (PR) survival rates were obtained by placing the Micro-straw at 1 cm above the LN2 surface for 70 s during freezing and in a 42°C water bath for 40 s during thawing. No differences were observed in the PR survival rate, acrosome integrity, and DNA fragmentation of the post-thaw spermatozoa from the three carriers. However, the normal morphology rate of spermatozoa frozen using the Micro-straw carrier was higher than for the Cryoplus carrier (p < 0.05), and the TM survival rate of spermatozoa frozen with the Micro-straw was higher than that for the LSL carrier (p < 0.01). In verification tests, there were no significant differences in the quality of post-thaw spermatozoa cryopreserved using these carriers for both rare spermatozoa or epididymal sperm. DISCUSSION AND CONCLUSION: Micro-straw, Cryoplus, and LSL carriers are all efficient means of freezing rare human spermatozoa. However, the Micro-straw carrier is more economical, safe, and user-friendly.

MKK7-mediated phosphorylation of JNKs regulates the proliferation and apoptosis of human spermatogonial stem cells.

BACKGROUND: Human spermatogonial stem cells (SSCs) are the basis of spermatogenesis. However, little is known about the developmental regulatory mechanisms of SSC due to sample origin and species differences. AIM: To investigates the mechanisms involved in the proliferation of human SSC. METHODS: The expression of mitogen-activated protein kinase kinase 7 (MKK7) in human testis was identified using immunohistochemistry and western blotting (WB). MKK7 was knocked down using small interfering RNA, and cell proliferation and apoptosis were detected by WB, EdU, cell counting kit-8 and fluorescence-activated cell sorting. After bioinformatic analysis, the interaction of MKK7 with c-Jun N-terminal kinases ( JNKs ) was verified by protein co-immunoprecipitation and WB. The phosphorylation of JNKs was inhibited by SP600125, and the phenotypic changes were detected by WB, cell counting kit-8 and fluorescence-activated cell sorting. RESULTS: MKK7 is mainly expressed in human SSCs, and MKK7 knockdown inhibits SSC proliferation and promotes their apoptosis. MKK7 mediated the phosphorylation of JNKs, and after inhibiting the phosphorylation of JNKs, the phenotypic changes of the cells were similar to those after MKK7 downregulation. The expression of MKK7 was significantly downregulated in patients with abnormal spermatogenesis, suggesting that abnormal MKK7 may be associated with spermatogenesis impairment. CONCLUSION: MKK7 regulates the proliferation and apoptosis of human SSC by mediating the phosphorylation of JNKs.

[Advances in researches on cryopreservation of testicular spermatozoa].

Infertility affects approximately 20% of childbearing couples in the world, and azoospermia accounts for 10－15% of the causes of male infertility. The use of fresh or frozen-thawed testicular sperm for intracytoplasmic sperm injection (ICSI) has become a main method for azoospermia patients to realize their dream for reproduction. However, testicular spermatozoa are not further matured in the epididymis and therefore have an obviously lower anti-freezing ability than ejaculated sperm. The viability and retrieval rate of sperm are low after freeze-thaw with the conventional method of cryopreservation. Since the first live birth with frozen-thawed testicular spermatozoa, continuous improvement has been made in the methods of testicular sperm cryopreservation and increased the viability and retrieval rate of spermatozoa after freeze-thaw. This review focuses on the methods of testicular sperm cryopreservation in the past 20 years to provide a theoretical basis for the development of assisted reproductive technology.

Simultaneous embolization of a spontaneous porto-systemic shunt and intrahepatic arterioportal fistula: A case report.

BACKGROUND: Hepatic encephalopathy (HE) is a frequent and debilitating complication of chronic liver disease. Recurrent HE is strongly linked with spontaneous portosystemic shunts (SPSSs). Intrahepatic arterioportal fistulas (IAPFs) occur rarely but pose a major clinical challenge and may lead to or worsen portal hypertension. Herein, we present a rare case of recurrent HE secondary to a SPSS combined with an IAPF. CASE SUMMARY: A 63-year-old female with primary biliary cirrhosis presented with recurrent disturbance of consciousness for 4 mo. SPSS communicating the superior mesenteric vein with the inferior vena cava and IAPF linking the intrahepatic artery with the portal vein were found on contrast-enhanced abdominal computed tomography. The patient did not respond well to medical treatment. Therefore, simultaneous embolization of SPSS and IAPF was scheduled. After embolization, the symptoms of HE showed obvious resolution. CONCLUSION: The presence of liver vascular disorders should not be neglected in patients with chronic liver disease, and interventional therapy is a reasonable choice in such patients.

Sperm donor lifestyle survey: modifiable risk factors for potential sperm donors.

OBJECTIVES: To examine the association between modifiable lifestyle factors and the main semen parameter values, the number of qualified sperm donors, and to provide some sensible guidance for sperm donors. METHODS: Healthy men screened as potential sperm donors were recruited in the Hunan Province Human Sperm Bank of China from March 2019 to December 2019. Participants were invited to complete interviewer-assisted questionnaires on eleven items of information. Univariate and multivariate analyses were conducted to analyze which lifestyle factors collected by the questionnaire had an impact on the eligibility and main semen parameters of sperm donors. RESULTS: The eligibility of men as sperm donors was strongly influenced by the duration of abstinence (P = 0.002). The rate of eligibility sperm donors increased significantly with the number of days of abstinence. In addition, semen volume increased with abstinence time (P = 0.000). Exercise frequency (P = 0.025) and abstinence time (P = 0.000) were positively correlated with sperm concentration, and masturbation frequency was negatively correlated with sperm concentration (P = 0.013). Progressive sperm motility was significantly affected by abstinence time (P = 0.000) and bedtime (P = 0.047). CONCLUSIONS: Abstinence time was highly associated with semen parameters and donor qualification. Increase the abstinence time before donation may be meaningful in improving the proportion of eligible sperm donors.

[Efficacy of Transcatheter Embolization for Gastrointestinal Stromal Tumor with Gastrointestinal Hemorrhage in 17 Cases].

OBJECTIVE: To evaluate the clinical efficacy of transcatheter embolization for patients with gastrointestinal stromal tumor and gastrointestinal hemorrhage. METHODS: From June 2006 to June 2019, 17 patients with gastrointestinal stromal tumor and who were gastrointestinal bleeding treated with transcatheter embolization due to gastrointestinal hemorrhage in our hospital were included in this study. The technical and clinical success rates and clinical success rate were analyzed retrospectively. RESULTS: Among 17 patients who underwent angiography before embolotherapy, 5 patients (29.4%) showed tumor staining and contrast extravasation, 9 patients (52.9%) showed tumor staining but no significant contrast extravasation, and 3 patients (17.6%) were negative. 14 patients had with positive angiographic findings and then underwent transcatheter embolization. Technical success was achieved in 13 patients (76.5%). Of the 13 technically successful patients, 12 patients (70.6%) achieved clinical success, one patient (5.9%) suffered from repeated gastrointestinal bleeding, which was improved after conservative treatment. No embolization-related complication occurred. The 30-day mortality rate was 0%. CONCLUSION: Transcatheter embolization for gastrointestinal stromal tumor with gastrointestinal hemorrhage is a safe and effective minimally invasive technique.

[Role of Hemostatic Clips as Guidance during Transcatheter Arterial Embolization in Patients with Peptic Ulcer Bleeding after Endoscopic Treatment Failure].

OBJECTIVE: To investigate the feasibility and clinical efficacy of transcatheter arterial embolization using hemostatic clips as the guidance in the patients with peptic ulcer bleeding after endoscopic treatment failure. METHODS: From February 2009 to October 2018, 33 patients with peptic ulcer bleeding who were treated with transcatheter arterial embolization after endoscopic treatment failure were included in the study. Clinical success rate, 30-d mortality rate and complication rate were observed. RESULTS: According to Forrest grading of ulcer bleeding on endoscopy, 8 patients (24.2%) were defined as Ⅰa, 14 patients (42.5%) Ⅰb, 4 patients (12.1%) Ⅱa, and 7 patients (21.2%) Ⅱb. There were 8 patients not given endoscopic treatment due to poor vision. In 25 patients who received endoscopic treatment, 7 patients did not achieve primary endoscopic hemostasis and 18 patients had re-bleeding despite successful primary hemostasis. The mean interval time from endoscopic treatment failure to transcatheter arterial embolization was (35.42±67.54) h. All patients underwent arterial angiography, and 18 patients with positive angiographic findings were treated with embolization. Among the 15 patients with negative angiographic findings, hemostatic clip could be observed fluoroscopically in 8 patients and used as guidance for embolization. Prophylactic embolization was performed in 4 out of 7 patients without visualization of clip fluoroscopically. The clinical success rates in negative angiographic findings patients with and without clip guidance were 75.0% and 28.6% respectively. The clinical success rate with positive angiographic findings was 66.7%. The overall clinical success rate and 30-d mortality rate were 60.0% and 20.0% respectively. No complication related to embolization was observed. CONCLUSION: The preliminary clinical study demonstrates that transcatheter arterial embolization with the guidance of clips is effective and safe for patients with peptic ulcer bleeding after endoscopic treatment failure.

The transjugular approach is a safe and effective alternative for performing portal vein embolization.

To evaluate the safety and efficacy of the novel technique, transjugular portal vein embolization (TPVE).A single-center retrospective review of 18 patients (12 males and 6 females; mean age, 62 years) who underwent TPVE between January 2012 and January 2013 was conducted. The technical success rate, future liver remnant (FLR) volume, total liver volume (TLV) and FLR/TLV ratio after PVE were analyzed. Liver function, including total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and International Normalized Ratio (INR), was assessed before and after PVE. Any complications of TPVE and liver resection after TPVE were recorded.TPVE was performed on 18 patients before right hepatic resection for both primary and secondary hepatic malignancies (10 hepatocellular carcinomas, 4 cases of colorectal liver metastasis, and 4 cholangiocarcinomas). Technical success was achieved in 100% of patients (18 of 18). The mean FRL significantly increased to 580 ±â€Š155 mL (P < .001) after PVE. The mean FLR/TLV ratio (%) significantly increased to 34 ±â€Š4 (P < .001) after PVE. One patient suffered septicemia after TPVE. A small number patients experienced mild to moderate abdominal pain during TPVE. No other major complications occurred after TPVE in our study. The patient who developed septicemia died 3 days after the surgery as a result of this complication and subsequent multiple organ dysfunction syndrome (MODS).Transjugular portal vein embolization is a safe, efficacious, and promising novel technique to induce hypertrophy of the FLR.

Is Post-TIPS Anticoagulation Therapy Necessary in Patients with Cirrhosis and Portal Vein Thrombosis? A Randomized Controlled Trial.

Purpose To determine whether posttransjugular intrahepatic portosystemic shunt (TIPS) placement anticoagulation therapy could benefit patients with cirrhosis and portal vein thrombosis (PVT) from the perspective of a change in portal vein patency status and clinical outcomes. Materials and Methods The study was approved by the institutional review board, and informed consent was obtained from each patient. From October 2012 to February 2014, patients with cirrhosis and PVT who underwent TIPS placement were randomly assigned to the anticoagulation therapy or control group. All patients were followed at 1, 3, 6, and 12 months after the TIPS procedure. Outcome measures were a change of portal vein patency status and clinical measures including gastrointestinal rebleeding, shunt dysfunction, hepatic encephalopathy, and survival. Student t test, χ(2) test, Fisher exact test, Mann-Whitney U test, and logistical regression were applied where appropriate. Results A total of 64 patients were enrolled in the study, with 31 allocated to the anticoagulation group and 33 allocated to the control group. Overall, thrombi were improved in 61 patients (96.8%) after the procedure. PVT recanalization (ie, complete disappearance; reconstruction of cavernous transformation) was achieved in 26 patients (83.9%) in the anticoagulation therapy group and in 23 (71.8%) patients in tthe control group (P = .252). The presence of a superior mesenteric vein thrombus may help predict recanalization failure (unadjusted relative risk = 0.243; 95% confidence interval: 0.070, 0.843; P = .026). Clinical outcomes were also similar between the two groups. Conclusion Anticoagulation therapy may not be necessary in certain patients with PVT because TIPS placement alone can achieve a high persistent recanalization rate. (©) RSNA, 2015.

Ileal conduit stomal variceal bleeding managed by endovascular embolization.

Ileal conduit stomal varices are rare, and may result in bleeding. The standard treatment modality for management of this type of hemorrhage has not been established. We present the case of a 70-year-old woman with progressive ileal conduit stomal variceal bleeding which was successfully managed by endovascular embolization via the transjugular transhepatic approach. In conclusion, transjugular transhepatic endovascular embolization is a good choice in patients with ileal conduit stomal variceal bleeding who have failed conservative therapy.

Stent-grafts for the treatment of TIPS dysfunction: fluency stent vs Wallgraft stent.

AIM: To evaluate the clinical efficacy of an expanded polytetrafluoro-ethylene-covered Fluency stent compared with that of a polyethylene terephthalate-covered Wallgraft stent for the management of transjugular intrahepatic portosystemic shunt (TIPS) dysfunction. METHODS: A retrospective review of patients who underwent TIPS revision with stent-grafts between May 2007 and June 2011 was conducted. The patients were divided into two groups according to the stent-grafts implanted: the Fluency stent (Bard Incorporated, Karlsruhe, Germany) and the Wallgraft stent (Boston Scientific, Galway, Ireland). The primary patency rates were calculated and compared using the Kaplan-Meier method. RESULTS: A total of 73 patients were evaluated in this study: 33 with Fluency stents and 40 with Wallgraft stents. The primary patency rates at 12 and 24 mo were 91% and 85%, respectively, in the Fluency stent group and 78% and 63%, respectively, in the Wallgraft stent group. The primary shunt patency rates after TIPS revision were significantly better with the Fluency stent than with the Wallgraft stent (P = 0.033). CONCLUSION: TIPS revision with the Fluency stent has higher medium-term patency rates than that with the Wallgraft stent.

Gastrointestinal bleeding caused by extrahepatic arterioportal fistula associated with portal vein thrombosis.

An extrahepatic arterioportal fistula (APF) involving the gastroduodenal artery and superior mesenteric vein is rare and mostly results from iatrogenic injuries. The clinical symptoms associated with APFs may include abdominal pain, gastrointestinal bleeding, ascites, nausea, vomiting, diarrhea, or even congestive heart failure. We present the case of a 70-year-old man who presented with chronic abdominal pain and gastrointestinal bleeding secondary to APF and portal vein thrombosis. The endovascular embolization of APF was accomplished successfully, and symptoms of portal hypertension resolved immediately after intervention. Unfortunately, the patient did not respond well to anticoagulation therapy with warfarin. Therefore, the patient underwent implantation of a transjugular intrahepatic portosystemic shunt, and the complications of portal hypertension resolved. In conclusion, the embolization of APF is technically feasible and effective and can be considered the first-choice therapy in selected patients.

[Directed migration and morphological changes of cultured trophoblast cells in small electric fields].

OBJECTIVE: To study the effect of physiological direct current electric fields (dcEF) on the migration and morphology of trophoblast cells. METHODS: The trophoblast cells (HTR8) were exposed to dcEF at 100 mV/mm and 200 mV/mm for 5 and 24 hours. The cell images were recorded and analyzed by image analyzer. RESULTS: Trophoblast cells cultured in medium containing 20% calf serum showed significant galvanotropism, including directed migration and orientation in the electric fields with a field strength of 100 mV/mm and 200 mV/mm. The cells showed obvious anode migration and enhanced migration rates compared with the non-EF stimulated cells. The directed migration was serum dependent. No significant cell migration occurred in the serum free medium under dcEF stimulation. The trophoblast cells showed morphological changes such as elongation under dcEF stimulation. CONCLUSION: Physiological direct current electrical fields may induce directed migration of trophoblast cells and this response is serum dependent. The morphological change featured with elongation is evident under dcEF stimulation.