Development of a predictive model for increasing sperm retrieval sucpess by microdissection testicular sperm extraction in patients with nonobstructive azoospermia

Microdissection testicular sperm extraction(micro-TESE)is widely used to treat nonobstructive azoospermia.However,a good prediction model is required to anticipate a successful sperm retrieval rate before performing micro-TESE.This retrospective study analyzed the clinical records of 200 nonobstructive azoospermia patients between January 2021 and December 2021.The backward method was used to perform binary logistic regression analysis and identify factors that predicted a successful micro-TESE sperm retrieval.The prediction model was constructed using acquired regression coefficients,and its predictive performance was assessed using the receiver operating characteristic curve.In all,67 patients(sperm retrieval rate:33.5%)underwent successful micro-TESE.Follicle-stimulating hormone,anti-Miillerian hormone,and inhibin B levels varied significantly between patients who underwent successful and unsuccessful micro-TESE.Binary logistic regression analysis yielded the following six predictors:anti-Mullerian hormone(odds ratio[OR]=0.902,95%confidence interval[Cl]:0.821-0.990),inhibin B(OR=1.012,95%Cl:1.001-1.024),Klinefelter’s syndrome(OR=0.022,95%Cl:0.002-0.243),Y chromosome microdeletion(OR=0.050,95%Cl:0.005-0.504),cryptorchidism with orchiopexy(OR=0.085,95%Cl:0.008-0.929),and idiopathic nonobstructive azoospermia(OR=0.031,95%Cl:0.003-0.277).The prediction model had an area under the curve of 0.720(95%Cl:0.645-0.794),sensitivity of 65.7%,specificity of 72.2%,Youden index of 0.379,and cut-off value of 0.305 overall,indicating good predictive value and accuracy.This model can assist clinicians and nonobstructive azoospermia patients in decision-making and avoiding negative micro-TESE results.

Factors influencing the sperm retrieval rate of microdissection testicular sperm extraction in patients with nonmosaic Klinefelter syndrome

To investigate the factors affecting the sperm retrieval rate of microdissection testicular sperm extraction(micro-TESE)in patients with nonmosaic Klinefelter syndrome(KS),64 patients with nonmosaic KS who underwent micro-TESE in the Center for Reproductive Medicine of Peking University Third Hospital(Beijing,China)between January 2016 and December 2017 were included in the study.Data on medical history,physical examination and laboratory examination results,and micro-TESE outcomes were collected.Patients were divided into two groups according to micro-TESE outcomes.The following factors were compared between the two groups by the Mann‒Whitney U test or Student’s t-test based on the distribution(nonnormal or normal)of the factors:age,testicular size,follicle-stimulating hormone level,luteinizing hormone level,testosterone level,and anti-Müllerian hormone level.The overall success rate of sperm retrieval was 50.0%.Correlation analysis showed that testicular volume was positively correlated with testosterone level.Using a logistic regression model,age and anti-Müllerian hormone levels were found to be better predictors for the sperm retrieval rate than the other parameters.

Multiple factors affecting surgical outcomes and patency rates in use of single-armed two-suture microsurgical vasoepididymostomy： a single surgeon＇s experience with 81 patients

Vasoepididymostomy （VE）, as the most challenging procedure in microsurgeries, is often carried out with a double-armed two-suture technique. In this study, we evaluated the efficacy and safety of the single-armed two-suture VEs on humans and studied the factors that could possibly affect the patency rates. From July 2012 to July 2013, we reviewed 81 patients with consecutive primary epididymal obstruction who underwent single-armed two-suture longitudinal intussusception microsurgical VEs by a single surgeon, Kai Hong （KH）. At the same time, we analyzed seven factors that possibly related to the patency rates. With the single-armed technique, a total of 81 men underwent the microsurgical VEs. Data on 62 patients were completely recorded. 19 patients were lost to follow-up. Mean age was 31 years old. Mean follow-up time was 8.8 （2-17） months. The patency rate was 66.1% （41/62）. Natural pregnancy rate was 34.1% （14/41）. Overall pregnancy rate was 22.6% （14/62）. No severe surgical complications were noted. With logistic regression test analysis, there were two factors related to a higher patency rate： anastomosis sites （P = 0.035） and motile sperm found in the epididymal fluid （P = 0.006）. Motile sperm found in the epididymal fluid were associated with a higher patency rate （OR = 11.80, 95% CI = 1.79, 77.65）. The single-armed two-suture longitudinal VE technique is feasible for microsurgical practice. The patency and pregnancy rates are comparable to the doubled-armed technique. Anastomosis sites and motile sperm found in the epididymal fluid were the most two important factors related to higher patency.

Sperm retrieval rates and clinical outcomes for patients with different causes of azoospermia who undergo microdissection testicular sperm extraction-intracytoplasmic sperm injection

The aim of our study was to compare the sperm retrieval rates(SRRs)and clinical outcomes of patients with different causes of azoospermia who underwent microdissection testicular sperm extraction-intracytoplasmic sperm injection(micro-TESE-ICSI).We conducted a retrospective study at the Reproductive Medicine Center of Peking University Third Hospital in Beijing,China,from January 2014 to December 2017.This study examined 769 patients with nonobstructive azoospermia who underwent 347 cycles of micro-TESE-ICSI.Patients with azoospermia were classified into Group A(Klinefelter syndrome,n=284,125 cycles),Group B(azoospermia Y chromosome factor c[AZFc]microdeletion,n=91,64 cycles),Group C(cryptorchidism,n=52,39 cycles),Group D(previous mumps and bilateral orchitis,n=23,23 cycles),and Group E(idiopathic azoospermia,n=319,96 cycles).Clinical characteristics,SRR,embryonic development,and pregnancy outcomes of the patients were compared between all groups.Patients in Group D had the highest and most successful SRR.The average SRR for all patients was 46.0%.The rates of clinical pregnancy,implantation,and live birth in Group D were 78.3%,65.0%,and 74.0%,respectively,which were higher than those in all other groups(P<0.05).Group B patients had the lowest clinical pregnancy,implantation,and live birth rates of all groups(P<0.05).No differences were found in the miscarriage rate or birth defects among the groups(P>0.05).Patients with orchitis had the highest SRR and best clinical outcomes.Although AZFc microdeletion patients had a higher SRR,their clinical outcomes were worse.

Altered microRNA profiles of testicular biopsies from patients with nonobstructive azoospermia

Many studies have shown that microRNAs(miRNAs)play vital roles during the spermatogenesis.However,little is known about the altered miRNA profiles of testicular tissues in nonobstructive azoospermia(NOA).Using microarray technology,the miRNA expression profiles of testicular biopsies from patients with NOA and of normal testicular tissues were determined.Bioinformatics analyses were conducted to predict the enriched biological processes and functions of identified miRNAs.The microarray data were validated by quantitative reverse transcriptase polymerase chain reaction(qRT-PCR),the results of which were then validated with a larger sample size.Correlations between the miRNA expression levels and clinical characteristics were analyzed.Receiver operating characteristic(ROC)curve analysis was used to evaluate the diagnostic ability of miRNAs for azoospermia.Hierarchical clustering showed that 129 miRNAs were significantly differentially expressed between the NOA and control groups.Bioinformatics analysis indicated that the differentially expressed miRNAs were involved in spermatogenesis,cell cycle,and mitotic prometaphase.In the subsequent qRT-PCR assays,the selected miRNA expression levels were consistent with the microarray results,and similar validated results were obtained with a larger sample size.Some clinical characteristics were significantly associated with the expression of certain miRNAs.In particular,we identified a combination of two miRNAs(miR-10b-3p and miR-34b-5p)that could serve as a predictive biomarker of azoospermia.This study provides altered miRNA profiles of testicular biopsies from NOA patients and examines the roles of miRNAs in spermatogenesis.These profiles may be useful for predicting and diagnosing the presence of testicular sperm in individuals with azoospermia.

Clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection with fresh or cryopreserved sperm in patients with nonobstructive azoospermia

We performed this study to evaluate the clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection(micro-TESE-ICSI)treatment that used fresh or cryopreserved sperm in patients with nonobstructive azoospermia(NOA).A total of 338 NOA patients with 344 consecutive cycles received treatment in the reproductive medicine center of Peking University Third Hospital in Beijing,China,from January 2014 to December 2017.Fresh oocytes and fresh sperm were used in 222 patients with 234 cycles(Group A).Fresh oocytes and cryopreserved sperm were used in 116 patients with 110 cycles(Group B).We compared patient characteristics,embryonic development,and pregnancy outcomes between Groups A and B.There was no statistical difference in the patient characteristics,and no differences were observed with fertilization or quality embryo rates between Groups A and B.The rates of clinical pregnancy and live birth were both higher for Group A than those for Group B(both P<0.05).In conclusion,fresh testicular sperm appears to produce better ICSI outcomes than cryopreserved testicular sperm in patients with NOA.

RNAs in the testicular tissue of patients with non-obstructive azoospermia

Circular RNAs(circRNAs)are highly conserved and ubiquitously expressed noncoding RNAs that participate in multiple reproductionrelated diseases.However,the expression pattern and potential functions of circRNAs in the testes of patients with non-obstructive azoospermia(NOA)remain elusive.In this study,according to a circRNA array,a total of 37881 circRNAs were identified that were differentially expressed in the testes of NOA patients compared with normal controls,including 19874 upregulated circRNAs and 18007 downregulated circRNAs.Using quantitative real-time polymerase chain reaction(qRT-PCR)analysis,we confirmed that the change tendency of some specific circRNAs,including hsa_circ_0137890,hsa_circ_0136298,and hsa_circ_0007273,was consistent with the microarray data in another larger sample.The structures and characteristics of these circRNAs were confirmed by Sanger sequencing,and fluorescence in situ hybridization revealed that these circRNAs were primarily expressed in the cytoplasm.Bioinformatics analysis was used to construct the competing endogenous RNA(ceRNA)network,and numerous miRNAs that could be paired with circRNAs validated in this study were reported to be vital for spermatogenesis regulation.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated that genes involved in axoneme assembly,microtubule-based processes,and cell proliferation were significantly enriched.Our data suggest that there are aberrantly expressed circRNA profiles in patients with NOA and that these circRNAs may help identify key diagnostic and therapeutic molecular biomarkers forNoA patients.

Fertility achieved through in vitro fertilization in a male patient with 48,XXYY syndrome

The 48,XXYY syndrome is a rare sex chromosome aneuploidy with an incidence of 1：18 000-1：40 000 male births and is associated with hypergonadotropic hypogonadism as an endocrine disorder. Most men with this syndrome are never diagnosed in China. Due to sex chromosome aneuploidies and limited effective communication, these patients suffer from infertility.