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.

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.

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.

Predictive factors for successful sperm retrieval by microdissection testicular sperm extraction in men with nonobstructive azoospermia and a history of cryptorchidism

This study aims to explore the factors influencing the success rate of the microdissection testicular sperm extraction(Micro-TESE)in patients with nonobstructive azoospermia(NOA)and cryptorchidism.Clinical data of 162 patients with cryptorchidism who underwent Micro-TESE due to infertility from December 2015 to May 2020 in the First Affiliated Hospital of Nanjing Medical University were analyzed retrospectively.In the univariate analysis,significant differences in the age of patient at the time of orchidopexy(median[interquartile range,IQR]:7.0[4.0–11.0]years vs 11.5[9.0–14.5]years,P<0.001),interval between orchidopexy and Micro-TESE(mean±standard deviation:17.5±5.0 years vs 14.4±4.4 years,P<0.001),severity of cryptorchidism(unilateral[62.8%]vs bilateral[31.6%],P<0.001;location of cryptorchidism,intra-abdominal[27.3%]vs inguinal[44.8%]vs suprascrotal[66.7%],P<0.001),volume of the dominant testis(median[IQR]:17.00[15.00–19.00]ml vs 14.50[11.75–16.25]ml,P<0.001),and levels of follicle-stimulating hormone(FSH;P=0.004)and testosterone(P=0.006)were observed between the successful and failed sperm extraction groups.After conducting the multivariate analysis,four of these factors,including unilateral/bilateral cryptorchidism(P<0.001),location of cryptorchidism(P=0.032),age of orchidopexy(P<0.001),and dominant testicular volume,were adopted in the clinical prediction model to evaluate preoperatively the success rate of Micro-TESE for patients with NOA and cryptorchidism.The likelihood of successful sperm retrieval by Micro-TESE in men with NOA and cryptorchidism increased in patients with mild forms of cryptorchidism.

A preliminary study of sperm identification in microdissection testicular sperm extraction samples with deep convolutional neural networks

Sperm identification and selection is an essential task when processing human testicular samples for in vitro fertilization.Locating and identifying sperm cell(s)in human testicular biopsy samples is labor intensive and time consuming.We developed a new computer-aided sperm analysis(CASA)system,which utilizes deep learning for near human-level performance on testicular sperm extraction(TESE),trained on a custom dataset.The system automates the identification of sperm in testicular biopsy samples.A dataset of 702 de-identified images from testicular biopsy samples of 30 patients was collected.Each image was normalized and passed through glare filters and diffraction correction.The data were split 80%,10%,and 10%into training,validation,and test sets,respectively.Then,a deep object detection network,composed of a feature extraction network and object detection network,was trained on this dataset.The model was benchmarked against embryologists’performance on the detection task.Our deep learning CASA system achieved a mean average precision(mAP)of 0.741,with an average recall(AR)of 0.376 on our dataset.Our proposed method can work in real time;its speed is effectively limited only by the imaging speed of the microscope.Our results indicate that deep learning-based technologies can improve the efficiency of finding sperm in testicular biopsy samples.

No relationship between biopsy sites near the main testicular vessels or rete testis and successful sperm retrieval using conventional or microdissection biopsies in 220 non-obstructive azoospermic men

In 220 consecutive patients with non-obstructive azoospermia, sperm retrieval was attempted by a combination of conventional and microdissection testicular sperm extraction （TESE）. For sperm retrieval, 2-3 conventional biopsies were performed followed by a microdissection TESE in cases of negative conventional biopsies. During the surgery, the vasculature of the testis was assessed using the operative microscope, and the location of positive biopsies was registered in relation to the blood supply. The overall sperm retrieval rate was 58.2%. From the initial conventional biopsies, sperm could be retrieved in 46.8% of the patients. With microdissection TESE, sperm could be retrieved from an additional 11.4% of the patients. The further use of microdissection TESE improved the sperm retrieval rate significantly （P=0.017）. No significant accumulation of positive biopsies was found towards the rete testis or the main testicular vessels.

Testis sperm extraction

The last 20 years have produced developments in the treatment for patients with non-obstructive azoospermia(NOA)who were once considered to be infertile.The combination of intracytoplasmic sperm injection together with various testicular sperm retrieval techniques,including conventional testicular sperm extraction(TESE),microdissection TESE(micro-TESE)and fine needle aspiration(FNA),have revolutionized treatment for these men.In men with NOA,isolated regions of spermatogenesis within the testis are common.The goal for all types of sperm retrieval procedures is locating the focal region(s)of spermatogenesis,and harvesting the sperm for assisted reproduction.This review article explores the surgical management of men with NOA and describes all techniques that can be used for testicular sperm retrieval.A PubMed search was conducted using the key words:“sperm extraction”,“NOA”,“testicular FNA”,“testicular mapping”,“TESE”,and“testicular biopsy”.All articles were reviewed.Articles were included if they provided data on sperm retrieval rates.The methods for performing sperm retrieval rates and outcomes of the various techniques are outlined.Micro-TESE has a higher sperm retrieval rates with fewer postoperative complications and negative effects on testicular function compared with conventional TESE.

Laboratory and Clinical Outcomes of Single Sperm Cryopreservation in Patients Underwent Micro-TESE

For men with severe oligozoospermia, sperm cryopreservation can preserve surgically obtained sperm. How to cryopreserve single sperm in men is still a hot topic in assisted reproduction technology. Aim to analyze the laboratory and pregnancy outcomes of single sperm cryopreservation group, we retrospectively selected 38 cycles underwent single sperm cryopreservation and thawing as the study group and 618 cycles underwent conventional sperm cryopreservation and thawing as the control group, which were performed in the reproductive medicine center of the Sixth Affiliated Hospital, Sun Yatsen University, from April 2014 to October 2023. All the sperm came from microdissection testicular sperm extraction (micro-TESE), and performed intracytoplasmic sperm injection (ICSI) for fertilization. Zygotes were cultured to Day 3 embryo, which were freshly transferred to female uterus. Surplus embryos were cultured to blastosphere and cryopreserved. There was no statistical difference in female/male age, female BMI, infertility duration and female basal sex hormone (FSH, LH E2, AMH), No. of oocytes retrieved per cycle, No. of ICSI oocytes per cycle and No. of embryos transferred per cycle between the two groups (P > 0.05). No significant difference was found in two-pronuclear oocyte fertilization rate (59.23% VS 58.84%), Day 3 available embryo rate (61.81% VS 63.55%), Day 3 good-quality embryo rate (45.73% VS 50.27%), blastocyst formation rate (47.83% VS 49.46%), the implantation rate (47.37% VS 52.16%), clinical pregnancy rate (36.84% VS 47.18%), miscarriage rate (14.29% VS 12.68%) and live birth rate (85.71% VS 81.70%) between two groups (P > 0.05). In conclusion, single-sperm cryopreservation was the optimal method to preserve sperm after micro-TESE. It can increase the utilization of each sperm and lead to clinical pregnancy.

Machine learning-based prediction of pregnancy outcomes in couples with non-obstructive azoospermia using micro-TESE for ICSI: a retrospective cohort study

Objective:To develop a clinically applicable tool for predicting clinical pregnancy,providing individualized patient counseling,and helping couples with non-obstructive azoospermia(NOA)decide whether to use fresh or cryopreserved spermatozoa for oocyte insemination before microdissection testicular sperm extraction(mTESE).Methods:A total of 240 couples with NOA who underwent mTESE-ICSI were divided into two groups based on the type of spermatozoa used for intracytoplasmic sperm injection(ICSI):the fresh and cryopreserved groups.After evaluating several machine learning algorithms,logistic regression was selected.Using LASSO regression and 10-fold cross-validation,the factors associated with clinical pregnancy were analyzed.Results:The area under the curves(AUCs)for the fresh and cryopreserved groups in the Logistic Regression-based prediction model were 0.977 and 0.759,respectively.Compared with various modeling algorithms,Logistic Regression outperformed machine learning in both groups,with an AUC of 0.945 for the fresh group and 0.788 for the cryopreserved group.Conclusion:The model accurately predicted clinical pregnancies in NOA couples.

Sperm retrieval success and testicular histopathology in idiopathic nonobstructive azoospermia

Prior studies have investigated sperm retrieval rates in men with non obstructive azoospermia(NOA)secondary to specific etiologies,yet most cases of NOA are idiopathic.We compared sperm retrieval rates and testicular histopathology in idiopathic NOA(iNOA)and nonidiopathic NOA(niNOA).We performed a retrospective review of men with NOA who underwent microdissection testicular sperm extraction(microTESE)between 2000 and 2016.Men with no history of malignancy or cryptorchidism and negative genetic evaluation were considered idiopathic.Multivariable regression determined the association between idiopathic etiology and primary outcomes of sperm retrieval and active spermatogenesis on histopathology.Among 224 men,86(38.4%)were idiopathic,75(33.5%)were nonidiopathic,and 63(28.1%)did not undergo genetic testing.Median age and serum testosterone were higher among iNOA or no testing versus niNOA.Median follicle-stimulating hormone(FSH)was lower among iNOA or no testing versus niNOA.A higher proportion of iNOA or no testing versus niNOA had a clinical varicocele.Sperm retrieval rates were similar between iNOA,niNOA,and no testing(41.8%vs 48.0%vs 55.6%,respectively;P=0.255).Active spermatogenesis was seen in a higher proportion of iNOA or no testing versus niNOA(31.4%and 27.0%vs 16.0%,P=0.073).On multivariable analysis,iNOA was not associated with sperm retrieval or spermatogenesis(P=0.430 and P=0.078,respectively).Rates of sperm retrieval and spermatogenesis on testis pathology were similar in men with iNOA and niNOA.These data will be useful to clinicians in preoperative counseling for men with NOA and negative genetic evaluation.

PGT or ICSI?The impression of NGS-based PGT outcomes in nonmosaic Klinefelter syndrome

This retrospective study demonstrates the clinical outcomes of patients with nonmosaic Klinefelter's syndrome(KS)who underwent preimplantation genetic testing(PGT)with frozen-thawed testicular spermatozoa.Microdissection testicular sperm extraction(micro-TESE)was performed for sperm retrieval.Next-generation sequencing(NGS)was conducted for embryo analysis.A total of 18 couples aged≤35 years were included,and 22 oocyte retrieval cycles were completed.Euploidy was detected in 29 of 45(64.4%)embryos.Additionally,the numbers of aneuploid and mosaic embryos detected were 8(17.8%)and 8(17.8%),respectively,regardless of a lack of sex chromosome abnormalities.Finally,13 couples with euploid embryos completed 14 frozen embryo transfer(FET)cycles.Ten couples had clinical pregnancies,and 6 of them had already delivered 5 healthy babies and 1 monozygotic twin.There were also 4 ongoing pregnancies and 2 biochemical pregnancies,but no early pregnancy loss was reported.Based on our results,we speculate that for KS patients,when sperm can be obtained by micro-TESE,the cryopreservation strategy makes the ovarian stimulation procedure more favorable for female partners.The paternal genetic risk of sex chromosome abnormalities in their offspring is extremely low in men with KS.In addition to PGT,the intracytoplasmic sperm injection(ICSI)procedure is comparably effective but more economical for young nonmosaic KS couples.ICSI should be offered as an option for such couples,but monitoring by prenatal genetic diagnosis is recommended.