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Comparison of the largest published series of TESE procedures performed on patients with Klinefelter syndrome
Source publication
The aim of this study was to report the successful fertility treatment of men with Klinefelter syndrome using testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI).
A total of 42 men with Klinefelter syndrome who underwent 54 TESE procedures were identified. Before TESE, patients with serum testosterone levels less than 15....
Context in source publication
Context 1
... comparison of the sperm retrieval success rates reported in this study with those of prior series of attempted TESE procedures in patients with Klinefelter syndrome is pre- sented in Table 3 (10,11,15). Other groups operated on men with similar ages and slightly lower mean serum FSH levels, with 40 -48% success in retrieving testicular spermatozoa. ...
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Background
The safety of intracytoplasmic sperm injection (ICSI) with testicular sperm in azoospermic men has been a concern. We evaluated ICSI outcomes, including neonatal outcomes, in children born using testicular sperm or donor sperm.
Material/Methods
Ninety-nine males with nonobstructive azoospermia (NOA) who underwent microdissection testicu...
Citations
... In the past, it was widely believed that patients with KS were infertile and had no possibility of fatherhood. However, advances in assisted reproductive technology have made it possible for men with KS to have offspring through testicular sperm extraction technique (TESE) and ICSI in recent years [36]. Patients with KS are easily overlooked and missed due to their lack of obvious clinical symptoms before puberty. ...
The long arm of the Y chromosome (Yq) contains many amplified and palindromic sequences that are prone to self-reorganization during spermatogenesis, and tiny submicroscopic segmental deletions in the proximal Yq are called Y chromosome microdeletions (YCM). A retrospective study was conducted on male infertility patients of Zhuang ethnicity who presented at Reproductive Medical Center of Nanning between January 2015 and May 2023. Seminal fluid was collected for standard examination. YCM were detected by using a combination of multiplex PCR and agarose gel electrophoresis. Preparation of peripheral blood chromosomes and karyotyping of chromosomes was performed. 147 cases (9.22%) of YCM were detected in 1596 male infertility patients of Zhuang ethnicity. Significant difference was found in the detection rate of YCM between the azoospermia group and the oligospermia group ( P < 0.001). Of all types of YCM, the highest detection rate was AZFc ( n = 83), followed by AZFb + c ( n = 28). 264 cases (16.54%) of sex chromosomal aberrations were detected. The most prevalent karyotype was 47, XXY ( n = 202). The detection rate of sex chromosomal aberrations in azoospermia group was higher than that in severe oligospermia group and oligospermia group, and the differences were significant ( P < 0.001). 28 cases (1.57%) of autosomal aberrations and 105 cases (6.58%) of chromosomal polymorphism were identified. The current research has some limitations due to the lack of normal men as the control group but suggests that YCM and chromosomal aberrations represent key genetic factors influencing spermatogenesis in infertile males of Zhuang ethnicity in Guangxi.
... [19] Spermatozoa are found in around 69% of patients with Klinefelter syndrome after testicular sperm extraction procedures. [20] 5. Anabolic-androgenic steroids (AAS) can disturb the hypothalamus-pituitaryadrenal axis, leading to long-term impacts on male fertility. AAS has a negative feedback effect on the pituitary gland, reducing the release of folliclestimulating hormone (FSH) and luteinizing hormone (LH), which decreases intratesticular testosterone levels and inhibits sperm generation. ...
The lack of sperm in the ejaculate is the hallmark of azoospermia. 15% of male infertile individuals have azoospermia. Obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) are the two main types of azoospermia. Infertility is a widespread chronic condition that affects mostly people aged 25 to 44, accounting for around 15% of all couples worldwide. The specific causes of azoospermia are not often obvious, but when the pathophysiology is idiopathic, the sickness is primarily linked to difficulties with ciliary function and mucus quality. The lack of gonadotropin production or intrinsic testicular dysfunction might be the reason for the NOA analysis. Silber and Owen developed microsurgical procedures for treating obstructive azoospermia in 1977, which have since become the norm for reconstructive surgery in male reproductive tract disorders. Micro TESE, an innovative method based on microsurgical procedures, is successful for sperm retrieval in males with NOA having ICSI. Keywords: Azoospermia, Invitro fertilization (IVF), Spermatogenesis, Chromosome, Gonadotropin-releasing hormone.
... The gold-standard for treating NOA patients, is mTESE, with a high sperm retrieval rate of up to 64% in suitable patients operated on (Deruyver et al., 2014, Ramasamy et al., 2005, Schiff et al., 2005. Although these rates seem promising, the current manual examination process to find sperm within tissue recovered from mTESE surgeries is time-consuming and inefficient, typically taking anywhere between 1-6 h of laboratory time, and in some cases even up to 14 h (Mangum et al., 2020, Ramasamy et al., 2011. ...
Research question: Can artificial intelligence (AI) improve efficiency and efficacy of sperm searches in azoospermic samples?
Design: This two-phase proof-of-concept study beginning with a training phase using 8 azoospermic patients (>10000 sperm images) to provide a variety of surgically collected samples for sperm morphology and debris variation to train a convolutional neural network to identify sperm. Secondly, side-by-side testing on 2 cohorts, an embryologist versus the AI identifying all sperm in still images (cohort 1, N=4, 2660 sperm) and then a side-by-side test with deployment of the AI model on an ICSI microscope and the embryologist performing a search with and without the aid of the AI (cohort 2, N=4, >1300 sperm). Time taken, accuracy and precision of sperm identification was measured.
Results: In cohort 1, the AI model showed improvement in time-taken to identify all sperm per field of view (0.019+-0.30 x 10-5s versus 36.10+-1.18s, P<0.0001) and improved accuracy (91.95+-0.81% vs 86.52+-1.34%, P<0.001) compared to an embryologist. From a total of 688 sperm in all samples combined, 560 were found by an embryologist and 611 were found by the AI in <1000th of the time. In cohort 2, the AI-aided embryologist took significantly less time per droplet (98.90+-3.19s vs 168.7+-7.84s, P<0.0001) and found 1396 sperm, while 1274 were found without AI, although no significant difference was observed.
Conclusions: AI-powered image analysis has the potential for seamless integration into laboratory workflows, and to reduce time to identify and isolate sperm from surgical sperm samples from hours to minutes, thus increasing success rates from these treatments.
... If this H-P-T axis is working normally then FSH level is adequate and induction of spermatogenesis takes place normally but still there is absence of sperms on semen analysis then it will be termed posttesticular azoospermia. This is suggestive of exit block/outlet unit [9] mal-developement . ...
When newly married childless couples come to know that the male partner is without sperms (Azoospermia; 15% of infertile
men), it is an unexpected terrible shock for them. The treating clinician and couples both remain in confused state and cannot
decide the proper line of treatment. This unnecessary diagnostic delay further complicates the life of barren couples in many
ways. The present study focuses on identifying and classifying the type of azoospermia and planning an appropriate course of
management. A sample of 300 subjects was taken from Human Fertility Research Centre of RNT Medical College and Pacific
Medical College & Hospital, Udaipur. This is the first study from the Southern Rajasthan in non obstructive azoospermic males. It
was found that in the management of Category A, the Andrologist induces spermatogenesis with Gonadotrophins and in the
cases of Category B, the Embryologist can perform either sperm retrieval from testicles or epididymis with advent of
micromanipulation, and thus previously infertile men with azoospermia are given the chance to father their own children. It was
also concluded that FSH plays a major role in identifying, classifying, early decision taking and management of azoospermia.
Management procedures for pre-testicular and testicular azoospermia were stated. Implications and limitations of the study were drawn.
... Unfortunately, authors did not specify the testicular phenotype in relation to successful sperm retrieval [165]. Another report of 47 KS patients revealed 34 cases with SCs alone (71% SRR), 9 with LC hyperplasia alone (33% SRR), 1 with maturation arrest (without sperm retrieval), and 3 with focal spermatogenesis (67% SRR) [166]. In another study of 45 KS patients, 58% of total SRR was obtained, with 29 (64.4%) ...
... This was suggested to potentially improve spermatogenesis in KS cases with foci of spermatogenesis [172]. When applied to men with low T levels or low T:E2 ratios, a higher retrieval rate (66%) has been reported using pre-treatment with aromatase inhibitors to equilibrate the T:E2 ratio [162,166,177]. However, these success rates could also be attributed to the simultaneous use of microsurgical testicular sperm extraction (mTESE). ...
... The mTESE [207] is a very promising TESE procedure, presenting high rates of SSR (47-69%) in KS patients [166,167,[175][176][177]179,185,190,192,198,200,208,209], though none of these reports compared mTESE to cTESE. Although not in KS patients, both approaches were compared in the pioneering work of Schlegel [207,210], with authors obtaining an SRR of 63% by mTESE vs. an SRR of 41% by cTESE. ...
Klinefelter syndrome (KS), caused by the presence of an extra X chromosome, is the most prevalent chromosomal sexual anomaly, with an estimated incidence of 1:500/1000 per male live birth (karyotype 47,XXY). High stature, tiny testicles, small penis, gynecomastia, feminine body proportions and hair, visceral obesity, and testicular failure are all symptoms of KS. Endocrine (osteoporosis, obesity, diabetes), musculoskeletal, cardiovascular, autoimmune disorders, cancer, neurocognitive disabilities, and infertility are also outcomes of KS. Causal theories are discussed in addition to hormonal characteristics and testicular histology. The retrieval of spermatozoa from the testicles for subsequent use in assisted reproduction treatments is discussed in the final sections. Despite testicular atrophy, reproductive treatments allow excellent results, with rates of 40–60% of spermatozoa recovery, 60% of clinical pregnancy, and 50% of newborns. This is followed by a review on the predictive factors for successful sperm retrieval. The risks of passing on the genetic defect to children are also discussed. Although the risk is low (0.63%) when compared to the general population (0.5–1%), patients should be informed about embryo selection through pre-implantation genetic testing (avoids clinical termination of pregnancy). Finally, readers are directed to a number of reviews where they can enhance their understanding of comprehensive diagnosis, clinical care, and fertility preservation.
... In other studies, patients with a high FSH level and a tiny testicle (26 mIU/mL and 5 mL, respectively) had spermatozoa or mature spermatids extracted from them or described in testicular biopsies [23][24][25]. More recently, sperm retrieval rates for TESE attempts in 42 men with Klinefelter syndrome and mean FSH levels of 33.2 IU/L were 72% [26]. ...
A limited number of individuals with non-obstructive azoospermia (NOA) may recover spermatozoa through traditional testicular sperm extraction (TESE) techniques. There is an ongoing debate over the effectiveness of microdissection TESE compared to standard TESE methods. Microdissection TESE (micro-TESE) techniques enable the identification of spermatogenesis foci in non-obstructive forms of azoospermia. Only histological examination can provide an objective and definitive assessment of the testicular phenotype. This study aimed to evaluate the correlation between histopathological findings after microdissection TESE (micro-TESE) and the predictive role of various factors in determining the success of sperm retrieval. We evaluated 24 patients with azoospermia who underwent micro-TESE and considered the patient's hormonal profile, testis ultrasound, genetic evaluation, histology, and immunohistology (PLAP antibody) of collected testis biopsies. The preoperative blood FSH level, in conjunction with other parameters, may aid in the prediction of micro-TESE success. Sensitivity increases, and specificity decreases with higher FSH levels. Furthermore, testicular volume and FSH levels are typically normal in patients with maturation arrest. In conclusion, hormones, ultrasound evaluation of the testicles, testis volume, and available genetic tests have a predictive value in differentiating obstructive azoospermia (OA) from NOA with various sensitivity and specificity rates. Histological and immunohistochemical evaluation establishes the testicular phenotype accurately and guides patient management.
... The average success of sperm retrieval using mTESE is ~50%, with pregnancy rates of approximately 30% and a live birth rate of up to 25%. 1,[5][6][7] While advances in assisted reproductive technologies have dramatically changed the management of NOA, there is a knowledge gap in our understanding of the patient experience. A need exists for further research into patient perspectives, expectations, and satisfaction of treatment to frame both current and future potential therapies. ...
... Complications such as persistent pain, infection, swelling, hematoma, and hydrocele may occur after sperm retrieval. The incidence of complications has been reported to vary between 0-70% (21)(22)(23)(24). PESA complications generally have minimal morbidity compared to open surgery. ...
... It also causes minimal parenchymal damage by identifying tubules that are likely to produce sperm (22). Since androgen production is low in Klinefelter syndrome (KS) patients, a decrease in serum testosterone has been reported after micro-TESE (21). However, in most KS patients, testosterone levels return to preoperative values during the 1-year follow-up period. ...
İntrasitoplazmik sperm enjeksiyonu, birçok infertilite koşulu için in vitro fertilizasyon sağlamaktadır. Azospermik erkeklerde de fertilizasyon için önemli bir tedavi seçeneğidir. Azospermik erkek testislerinde sperm üretimi mümkündür. Bu hastalarda intrasitoplazmik sperm enjeksiyonundan önce epididim veya testisten sperm alınması gerekir. Epididim veya testislerden sperm elde etmek için çok sayıda sperm alma prosedürü geliştirilmiştir. Bu yöntemlerle elde edilen spermler, in vitro fertilizasyon için intrasitoplazmik sperm enjeksiyonunda kullanılmaktadır. Sperm alma yöntemini belirlerken en önemli faktör azosperminin obstrüktif veya non-obstrüktif olup olmadığıdır. Ayrıca işlemi yapan cerrahın tecrübesi de sperm alma tekniğinin belirlenmesinde etkilidir. Bu derlemede sperm elde etme yöntemleri anlatılmış ve ayrıca bu sperm elde etme yöntemleri ile ilgili güncel gelişmeler de ele alınmıştır. Hem obstrüktif hem de non-obstrüktif azospermik hastalarda cerrahi sperm elde etme yöntemlerinin endikasyonları, her bir yöntemin teknik yönleri, olası komplikasyonları, bu yöntemlerin avantaj ve dezavantajları anlatılmış ve birbirlerine göre üstünlükleri de tartışılmıştır. Ayrıca, bu yöntemlerle elde edilmiş olan sperm kullanılan intrasitoplazmik sperm enjeksiyonu sonrası fertilizasyon oranları ve gebeliğin devamına ilişkin kanıtlar karşılaştırmalı bir şekilde sunulmuş ve eleştirel bir şekilde tartışılmıştır.
... This lack of a deleterious effect of a previous testosterone treatment was also found in five out of six other studies (Mehta et al., 2013;Plotton et al., 2015;Rohayem et al., 2015;Garolla et al., 2018;Boeri et al., 2020). Schiff et al., (2005) reported a deleterious effect, but they included only five patients with previous testosterone therapy. Since testosterone treatment could have decreased AMH secretion, we checked that AMH plasma levels did not differ according to prior testosterone therapy. ...
... Since testosterone treatment could have decreased AMH secretion, we checked that AMH plasma levels did not differ according to prior testosterone therapy. Treatments designed to increase testosterone secretion were reported in six out of 28 studies (Schiff et al., 2005;Ramasamy et al., 2009;Rohayem et al., 2015;Majzoub et al., 2016;Ozer et al., 2018;Guo et al., 2020), without consistent results for SRR. Only patients with low testosterone levels were treated, which introduces a selection bias that prevents a comparison of SRR between treated and non-treated patients. ...
... References with m-TESE only m-TESE n m-TESE1 n (SRR) (Vernaeve et al., 2004) 50 24 (48%) (Schiff et al., 2005) 29 29 (69%) (Kyono et al., 2007) 17 6 (53.3%) (Bakircioglu et al., 2006) Authors' roles H.L. and I.P. designed the study. I.P. was responsible for the logistical aspects of the study. ...
Study question:
Should testicular sperm extraction (TESE) in non-mosaic 47,XXY Klinefelter syndrome (KS) patients be performed soon after puberty or could it be delayed until adulthood?
Summary answer:
The difference in sperm retrieval rate (SRR) in TESE was not significant between the 'Young' (15-22 years old) cohort and the 'Adult' (23-43 years old) cohort of non-mosaic KS patients recruited prospectively in parallel.
What is known already:
Several studies have tried to define predictive factors for TESE outcome in non-mosaic KS patients, with very heterogeneous results. Some authors have found that age was a pejorative factor and recommended performing TESE soon after puberty. To date, no predictive factors have been unanimously recognized to guide clinicians in deciding to perform TESE in azoospermic KS patients.
Study design, size, duration:
Two cohorts (Young: 15-22 years old; Adult: 23-43 years old) were included prospectively in parallel. A total of 157 non-mosaic 47,XXY KS patients were included between 2010 and 2020 in the reproductive medicine department of the University Hospital of Lyon, France. However 31 patients gave up before TESE, four had cryptozoospermia and three did not have a valid hormone assessment; these were excluded from this study.
Participants/materials, setting, methods:
Data for 119 patients (61 Young and 58 Adult) were analyzed. All of these patients had clinical, hormonal and seminal evaluation before conventional TESE (c-TESE).
Main results and the role of chance:
The global SRR was 45.4%. SRRs were not significantly different between the two age groups: Young SRR=49.2%, Adult SRR = 41.4%; P = 0.393. Anti-Müllerian hormone (AMH) and inhibin B were significantly higher in the Young group (AMH: P = 0.001, Inhibin B: P < 0.001), and also higher in patients with a positive TESE than in those with a negative TESE (AMH: P = 0.001, Inhibin B: P = 0.036). The other factors did not differ between age groups or according to TESE outcome. AMH had a better predictive value than inhibin B. SRRs were significantly higher in the upper quartile of AMH plasma levels than in the lower quartile (or in cases with AMH plasma level below the quantification limit): 67.7% versus 28.9% in the whole population (P = 0.001), 60% versus 20% in the Young group (P = 0.025) and 71.4% versus 33.3% in the Adult group (P = 0.018).
Limitations, reasons for caution:
c-TESE was performed in the whole study; we cannot rule out the possibility of different results if microsurgical TESE had been performed. Because of the limited sensitivity of inhibin B and AMH assays, a large number of patients had values lower than the quantification limits, preventing the definition a threshold below which negative TESE can be predicted.
Wider implications of the findings:
In contrast to some studies, age did not appear as a pejorative factor when comparing patients 15-22 and 23-44 years of age. Improved accuracy of inhibin B and AMH assays in the future might still allow discrimination of patients with persistent foci of spermatogenesis and guide clinician decision-making and patient information.
Study funding/competing interest(s):
The study was supported by a grant from the French Ministry of Health D50621 (Programme Hospitalier de Recherche Clinical Régional 2008). The authors have no conflicts of interest to disclose.
Trial registration number:
NCT01918280.
... Postoperative complication rates vary according to the SR technique applied, with an incidence ranging from 0 to 70%, including persistent pain, edema, infection, hydrocele, hematoma, androgen deficiency to atrophy and testicular failure (41)(42)(43)(44). Intratesticular hematoma has been reported in most patients undergoing c-TESE with single or multiple incisions, based on ultrasound assessment performed after the procedure. ...
... However, most cases resolve spontaneously, without significantly compromising testicular function (43). However, some authors have reported that excision of a large volume of testicular parenchyma by c-TESE is associated with a high risk of transient or permanent reduction in testosterone levels due to testicular devascularization (17,42). ...
Men presenting with non-obstructive azoospermia are the most challenging clinical scenario for an infertile couple. Intracytoplasmic Sperm Injection (ICSI) with testicular sperm retrieval gave a chance for biological fatherhood once sperm can be found, but unfortunately sperm recovery rate (SSR) is something near 50%, leading to a discussion about what surgical retrieval technique is the best. Historically sperm have been retrieved using conventional Testicular Sperm Extraction (c-TESE), Testicular Sperm Aspiration (TESA), a combination of Testicular Fine Needle Aspiration (TfNA)/c-TESE, Testicular Microdissection (TM) and Open Testicular Mapping (OTEM). c-TESE published in 1995 by Devroey and cols. consists of testis delivery, a large unique albuginea incision and extraction of a portion from the majority of testicular tubules. TESA published in 1996 by Lewin and cols. is done percutaneously using a 21–23 gauge needle and a syringe to aspire testicular tubules. TfNA was published in 1965 by Obrant and Persson as an aspiration biopsy and cytological exam to verify sperm production. In 1999 Turek and cols. published the use of TfNA combined with c-TESE for sperm retrieval. In 1999, Peter Schlegel published a technique using a microsurgical approach to identify more probable sperm production areas inside the testicle that could be excised with better precision and less tissue. OTEM is a multiple biopsy approach, published in 2020 by Vieira and cols., based on TfNA principles but done at the same time without albuginea opening or surgical microscope need. Since Testicular Microdissection publication, the method became the gold standard for sperm retrieval, allowing superior SSR with minimal tissue removal, but the amount of testicular dissection to find more probable spermatogenesis areas, difficulties in comparative design studies, diversity TM results among doctors and other methods that can achieve very similar results we question TM superiority. The objective is review existing literature and discuss advantages and disadvantages of all the methods for sperm retrieval in non-obstructive azoospermia.
