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11 pages, 526 KiB  
Article
Preliminary Results of Microsurgical Sperm Retrieval in Azoospermic Patients: A Randomized Controlled Trial Comparing Operating Microscope vs. Surgical Loupes
by Mirko Preto, Luca Boeri, Lorenzo Cirigliano, Marco Falcone, Valentina Parolin, Federica Peretti, Ilaria Ferro, Natalia Plamadeala, Martina Scavone, Emanuele Zupo and Paolo Gontero
J. Clin. Med. 2025, 14(3), 970; https://doi.org/10.3390/jcm14030970 - 3 Feb 2025
Viewed by 523
Abstract
Objectives: To compare surgical outcomes and sperm retrieval rates (SRRs) between conventional microsurgical-assisted testicular sperm extraction (m-TeSE—Group A) and testicular sperm extraction performed with surgical loupes (l-TeSE—Group B) in adult males with non-obstructive azoospermia (NOA). Methods: A multicentric prospective randomized trial (ethics committee [...] Read more.
Objectives: To compare surgical outcomes and sperm retrieval rates (SRRs) between conventional microsurgical-assisted testicular sperm extraction (m-TeSE—Group A) and testicular sperm extraction performed with surgical loupes (l-TeSE—Group B) in adult males with non-obstructive azoospermia (NOA). Methods: A multicentric prospective randomized trial (ethics committee no. 202/2022) in accordance with the CONSORT guidelines was conducted from March 2022 to April 2024. Adult males with NOA without genetic alterations who signed the informed consent were enrolled. SRRs, intra- and postoperative complications (according to the Clavien–Dindo classification), and hormonal profile changes were considered as outcomes during the follow-up period. Results: A total of 42 NOA patients were enrolled. The median age was 35 years (IQR: 33–49). The preoperative median FSH was 16.5 mIU/mL (IQR: 11.6–22.5) and the total testosterone was 4.6 (3.5–5.6). Overall, the SRR was 22.6%, with sperm retrieved from 19 testes. Histopathological findings reported Sertoli cell-only syndrome (SCOS) in 46.4% (39 cases), hypospermatogenesis in 26.2%, and germ cell arrest in 26.2% of the patients. No intraoperative complications were recorded. The postoperative complications were minimal (Clavien–Dindo grade I), but no significant differences were recorded in-between the two surgical approaches. Considering the operative time of the testicular exploration alone, Group B seemed to be faster than the m-TeSE, with a median time saving of 8 min (p < 0.01). Conclusion: The use of surgical loupes was safe and comparable with m-TeSE in terms of the SRRs and complication rates. L-TeSE offered a reduction in the operative time compared with m-TeSE. Full article
(This article belongs to the Section Reproductive Medicine & Andrology)
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<p>Through the operative microscope, the surgeon searched for the more dilated, more opaque, and whiter seminiferous tubules, possibly located near the blood vessels.</p>
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14 pages, 273 KiB  
Article
Multivitamin Supplementation and Fertility Outcome: A Retrospective Single-Center Cohort Study and the Clinical and Medicolegal Value of Nutritional Counseling
by Giuseppe Gullo, Simona Zaami, Adriana Vita Streva, Sofia Burgio, Valentina Billone, Yulia Kotlik, Elena Chitoran, Silvia Ganduscio, Giovanni Baglio, Antonio Perino and Gaspare Cucinella
Life 2025, 15(1), 48; https://doi.org/10.3390/life15010048 - 2 Jan 2025
Viewed by 1053
Abstract
Resveratrol can beneficially affect growth and follicle development and lead to improved sperm function parameters in pre-clinical studies, while information from clinical studies is still inconclusive. This study aims to evaluate the biological and clinical impact of a resveratrol-based multivitamin supplement on level [...] Read more.
Resveratrol can beneficially affect growth and follicle development and lead to improved sperm function parameters in pre-clinical studies, while information from clinical studies is still inconclusive. This study aims to evaluate the biological and clinical impact of a resveratrol-based multivitamin supplement on level II assisted reproduction cycles (IVF and intracytoplasmic sperm injection [ICSI]). A retrospective, case-control study, involving 70 infertile couples undergoing IVF/ICSI cycles, was conducted at the Assisted Reproductive Center, Obstetrics and Gynecology Unit-Villa Sofia-Cervello Hospital in Palermo. The study group underwent pre-treatment with a daily nutraceutical based on resveratrol, whereas the control group received 400 mcg/day of folic acid. Primary endpoints to be evaluated were the number of mature follicles developed (>16 mm), total oocytes and Metaphase II (MII) oocytes retrieved, fertilization rate, number of embryos/blastocysts obtained, and semen quality. Secondary objectives in our evaluation were the duration and dosage of gonadotropins, the starting dose, the number of blastocysts to be transferred and frozen, implantation rate, and, ultimately, biochemical and clinical pregnancy rates. In the study group, a significantly higher number of mature follicles, oocytes, and MII oocytes were collected compared to the control group. In the study group, a higher fertilization rate as well as higher numbers of cleavage embryos per patient, blastocysts per patient, and frozen blastocysts were obtained. In the study group, a shorter administration time and lower dosages of gonadotropins required to reach follicle maturity were also observed compared to controls, with fewer dose adjustments during stimulation compared to the starting dose. No significant differences were found in biochemical or clinical pregnancy rates. A 12-month period of dietary supplementation with a resveratrol-based multivitamin nutraceutical leads to better biological effects on ICSI cycles. Full article
(This article belongs to the Special Issue Biological and Clinical Research of Germ Cells)
16 pages, 1604 KiB  
Article
Predictive Value of Varicocele Grade and Histopathology in Simultaneous Varicocelectomy and Sperm Retrieval in Non-Obstructive Azoospermia: A Retrospective Cohort Study
by Aris Kaltsas, Fotios Dimitriadis, Michael Chrisofos, Nikolaos Sofikitis and Athanasios Zachariou
Medicina 2024, 60(12), 2056; https://doi.org/10.3390/medicina60122056 - 13 Dec 2024
Viewed by 995
Abstract
Background and Objectives: Varicocele repair in men with non-obstructive azoospermia (NOA) remains a subject of debate due to inconsistent outcomes. This study aimed to evaluate the impact of microsurgical varicocelectomy on sperm recovery rates in men with NOA and to assess the role [...] Read more.
Background and Objectives: Varicocele repair in men with non-obstructive azoospermia (NOA) remains a subject of debate due to inconsistent outcomes. This study aimed to evaluate the impact of microsurgical varicocelectomy on sperm recovery rates in men with NOA and to assess the role of varicocele grade and testicular histopathology in predicting postoperative outcomes. Materials and Methods: A retrospective cohort study was conducted of 78 men diagnosed with NOA and clinical varicocele who underwent microsurgical subinguinal varicocelectomy with simultaneous diagnostic and therapeutic testicular biopsy at the Department of Urology of the University of Ioannina between September 2013 and December 2021. Varicoceles were graded I to III based on physical examination and Doppler ultrasound. Histopathological patterns were classified as hypospermatogenesis (HYPO), early maturation arrest (EMA), late maturation arrest (LMA), or Sertoli cell-only syndrome (SCOS). Patients were followed postoperatively at 3, 6, 9, and 12 months, with semen analyses performed according to World Health Organization guidelines to assess sperm presence. Results: At the 12-month follow-up, spermatozoa were detected in the ejaculate of 26 out of 78 patients, resulting in an overall sperm return to ejaculate rate of 33.3%. Varicocele grade significantly influenced outcomes: patients with Grade II varicoceles had the highest sperm return to ejaculate rate (45.2%, 14/31), followed by Grade III (39.1%, 9/23) and Grade I (12.5%, 3/24) (p-value < 0.05). The sperm retrieval rate (SRR) from testicular biopsies also varied with varicocele grade: Grade II had the highest SRR (54.8%, 17/31), followed by Grade III (47.8%, 11/23) and Grade I (33.3%, 8/24). Histopathological findings were significant predictors of sperm retrieval: patients with HYPO had an SRR of 84.8% (28/33) and a sperm return to ejaculate rate of 66.7% (22/33); those with LMA had an SRR of 47.1% (8/17) and a sperm return rate of 23.5% (4/17). No sperm retrieval was observed in patients with EMA (0%, 0/4) or SCOS (0%, 0/24) (p-value < 0.01). Multivariate logistic regression identified varicocele grade and histopathology as independent predictors of sperm retrieval, with higher grades and favorable histopathology associated with increased likelihood of success. Conclusions: Microsurgical varicocelectomy can induce spermatogenesis in a significant proportion of men with NOA, particularly those with higher-grade varicoceles and favorable histopathological patterns such as HYPO or LMA. Varicocele grade and histopathological findings are important predictors of postoperative outcomes and should inform patient selection and counseling. These findings provide valuable insights for optimizing fertility treatments in men with NOA undergoing varicocele repair. Full article
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<p>Histopathological patterns of testicular biopsies.</p>
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<p>Sperm return to ejaculate and testicular sperm retrieval rates by varicocele grade.</p>
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<p>Kaplan–Meier curves illustrating the time to sperm recovery after microsurgical varicocelectomy in patients with non-obstructive azoospermia, stratified by varicocele grade.</p>
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17 pages, 634 KiB  
Review
Predictors of Successful Testicular Sperm Extraction: A New Era for Men with Non-Obstructive Azoospermia
by Aris Kaltsas, Sofoklis Stavros, Zisis Kratiras, Athanasios Zikopoulos, Nikolaos Machairiotis, Anastasios Potiris, Fotios Dimitriadis, Nikolaos Sofikitis, Michael Chrisofos and Athanasios Zachariou
Biomedicines 2024, 12(12), 2679; https://doi.org/10.3390/biomedicines12122679 - 25 Nov 2024
Cited by 1 | Viewed by 1644
Abstract
Background/Objectives: Non-obstructive azoospermia (NOA) is a severe form of male infertility characterized by the absence of sperm in the ejaculate due to impaired spermatogenesis. Testicular sperm extraction (TESE) combined with intracytoplasmic sperm injection is the primary treatment, but success rates are unpredictable, [...] Read more.
Background/Objectives: Non-obstructive azoospermia (NOA) is a severe form of male infertility characterized by the absence of sperm in the ejaculate due to impaired spermatogenesis. Testicular sperm extraction (TESE) combined with intracytoplasmic sperm injection is the primary treatment, but success rates are unpredictable, causing significant emotional and financial burdens. Traditional clinical and hormonal predictors have shown inconsistent reliability. This review aims to evaluate current and emerging non-invasive preoperative predictors of successful sperm retrieval in men with NOA, highlighting promising biomarkers and their potential clinical applications. Methods: A comprehensive literature review was conducted, examining studies on clinical and hormonal factors, imaging techniques, molecular biology biomarkers, and genetic testing related to TESE outcomes in NOA patients. The potential role of artificial intelligence and machine learning in enhancing predictive models was also explored. Results: Traditional predictors such as patient age, body mass index, infertility duration, testicular volume, and serum hormone levels (follicle-stimulating hormone, luteinizing hormone, inhibin B) have limited predictive value for TESE success. Emerging non-invasive biomarkers—including anti-Müllerian hormone levels, inhibin B to anti-Müllerian hormone ratio, specific microRNAs, long non-coding RNAs, circular RNAs, and germ-cell-specific proteins like TEX101—show promise in predicting successful sperm retrieval. Advanced imaging techniques like high-frequency ultrasound and functional magnetic resonance imaging offer potential but require further validation. Integrating molecular biomarkers with artificial intelligence and machine learning algorithms may enhance predictive accuracy. Conclusions: Predicting TESE outcomes in men with NOA remains challenging using conventional clinical and hormonal parameters. Emerging non-invasive biomarkers offer significant potential to improve predictive models but require validation through large-scale studies. Incorporating artificial intelligence and machine learning could further refine predictive accuracy, aiding clinical decision-making and improving patient counseling and treatment strategies in NOA. Full article
(This article belongs to the Section Molecular Genetics and Genetic Diseases)
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<p>Flowchart of TESE success prediction in NOA patients using clinical data, molecular biomarkers, imaging techniques, and AI.</p>
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9 pages, 3846 KiB  
Article
Short-Term Metformin Therapy in Clomiphene Citrate Resistant PCOS Patients Improves Fertility Outcome by Regulating Follicular Fluid Redox Balance: A Case-Controlled Study
by Mustafa Tas
Diagnostics 2024, 14(19), 2215; https://doi.org/10.3390/diagnostics14192215 - 4 Oct 2024
Viewed by 941
Abstract
Objectives: To determine the effect of short-term metformin administration on follicular fluid (FF) total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and nuclear factor kappa B (NF-kB) in women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Methods: Fifty-eight patients [...] Read more.
Objectives: To determine the effect of short-term metformin administration on follicular fluid (FF) total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and nuclear factor kappa B (NF-kB) in women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Methods: Fifty-eight patients aged 23–34 who were planned to have intracytoplasmic sperm injection due to clomiphene citrate-resistant PCOS were included in the study. Participants were divided into two groups according to whether they used metformin or not. While 30 of 58 PCOS patients were using short-term metformin in combination with controlled ovarian stimulation, 28 PCOS patients were not using metformin. Metformin was started in the mid-luteal period and continued until the day before oocyte retrieval at 850 mg twice daily. To determine FF-NF-kB, TAS, TOS and OSI values, a dominant follicle ≥17–18 mm in diameter was selected for aspiration. Results: The number of mature follicles and fertilization rates of the metformin group were significantly higher than those not taking metformin. FF-TOS and OSI of the metformin group were significantly lower than those of the group not receiving metformin. Patients receiving metformin had higher FF-TAS than the group not receiving metformin. FF-NF-kB levels of the metformin group were significantly lower than the group not receiving metformin. Insulin resistance, FF-NF-kB and FF-TOS were negatively correlated with the number of mature oocytes. FF-TAS was positively correlated with the number of oocytes. Conclusions: Short-term metformin treatment in clomiphene-resistant PCOS improves the number of mature follicles and fertilization rates by regulating the intra-follicle redox balance. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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<p>Graphical representation of follicular fluid NF-kB (<b>A</b>), TOS (<b>B</b>), TAS (<b>C</b>) and OSI (<b>D</b>) levels in groups that received and did not receive short-term metformin treatment. Note that inflammatory markers (NF-KB) and oxidant markers (TOS, OSI) decreased in the metformin group, while antioxidant TAS increased.</p>
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<p>Graphical representation of correlation matrix of variables. Blue colors indicate positive correlations, and red colors indicate negative correlations.</p>
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11 pages, 1062 KiB  
Article
Successful Sperm Retrieval and Clinical Pregnancies Following Micro-TESE and ICSI Treatments in Patients with Nonobstructive Azoospermia Due to Various Etiologies
by Guangmin Liu, Zenghui Huang, Wenbing Zhu, Huan Zhang, Liqing Fan and Chuan Huang
Cells 2024, 13(18), 1582; https://doi.org/10.3390/cells13181582 - 20 Sep 2024
Viewed by 1548
Abstract
(1) Background: Nonobstructive azoospermia (NOA) etiologies affect the sperm retrieval rate (SRR) by microdissection testicular sperm extraction (micro-TESE) and the clinical outcomes following intracytoplasmic sperm injection (ICSI); (2) Methods: We investigated seven NOA etiologies. The SRR and clinical outcomes of 627 patients were [...] Read more.
(1) Background: Nonobstructive azoospermia (NOA) etiologies affect the sperm retrieval rate (SRR) by microdissection testicular sperm extraction (micro-TESE) and the clinical outcomes following intracytoplasmic sperm injection (ICSI); (2) Methods: We investigated seven NOA etiologies. The SRR and clinical outcomes of 627 patients were analyzed between November 2017 and July 2022 in the Reproductive and Genetic Hospital of China International Trust and Investment Corporation-Xiangya (CITIC-Xiangya); (3) Results: The overall SRR was 39.4% (247/627). The SRR according to NOA etiologies were: Y chromosome azoospermia factor c microdeletions (26/46, 56.5%), Klinefelter syndrome (KS), 36/85, 42.4%), idiopathic (110/398, 27.6%), cryptorchidism (20/29, 69.0%), chromosome anomalies (7/13, 53.9%), orchitis (45/50, 90.0%), and cancer (3/6, 50.0%). The SRR were different for spermatogonia arrest (26/96, 27.1%), maturation arrest (76/177, 42.9%), and SCOS (30/80, 37.5%) according to histological examinations. The clinical pregnancy rate was similar among the NOA etiologies. The high-quality embryo rate differed between successful (54.7%) and unsuccessful (40.9%) pregnancies. Moreover, the successfully pregnant women (28.99 years) were younger than the unsuccessfully pregnant ones (30.92 years); (4) Conclusions: The SRR from patients with NOA was associated with the etiology and histological categories, while the clinical outcome was associated with the high-quality embryo rate and the female partner’s age. Full article
(This article belongs to the Special Issue Sperm Biology and Reproductive Health)
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<p>Schematic overview of this study. Abbreviations: NOA, non-obstructive azoospermia; Micro-TESE, microdissection testicular sperm extraction; OA, obstructive azoospermia; AZFc, Y chromosome azoospermia factor c; KS, Klinefelter syndrome; ICSI, intracytoplasmic sperm injection.</p>
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<p>The sperm retrieval percentage by histopathological type. All patients were divided into 3 histopathological types present on pathology report at time of micro-TESE. (<b>A</b>) The sperm retrieval percentage by histopathological type in patients with NOA. (<b>B</b>) The proportion of each histopathological type in the successful sperm retrieval and unsuccessful sperm retrieval groups, respectively. SCOS, Sertoli cell-only syndrome. Yes, successful sperm retrieval. No, unsuccessful sperm retrieval.</p>
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49 pages, 2032 KiB  
Review
Non-Obstructive Azoospermia and Intracytoplasmic Sperm Injection: Unveiling the Chances of Success and Possible Consequences for Offspring
by Ahmad Majzoub, Marina C. Viana, Arnold P. P. Achermann, Isadora T. Ferreira, Rita J. Laursen, Peter Humaidan and Sandro C. Esteves
J. Clin. Med. 2024, 13(16), 4939; https://doi.org/10.3390/jcm13164939 - 21 Aug 2024
Cited by 2 | Viewed by 2466
Abstract
Non-obstructive azoospermia (NOA) is found in up to 15% of infertile men. While several causes for NOA have been identified, the exact etiology remains unknown in many patients. Advances in assisted reproductive technology, including intracytoplasmic sperm injection (ICSI) and testicular sperm retrieval, have [...] Read more.
Non-obstructive azoospermia (NOA) is found in up to 15% of infertile men. While several causes for NOA have been identified, the exact etiology remains unknown in many patients. Advances in assisted reproductive technology, including intracytoplasmic sperm injection (ICSI) and testicular sperm retrieval, have provided hope for these patients. This review summarizes the chances of success with ICSI for NOA patients and examines preoperative factors and laboratory techniques associated with positive outcomes. Furthermore, we reviewed possible consequences for offspring by the use of ICSI with testicular sperm retrieved from NOA patients and the interventions that could potentially mitigate risks. Testicular sperm retrieved from NOA patients may exhibit increased chromosomal abnormalities, and although lower fertilization and pregnancy rates are reported in NOA patients compared to other forms of infertility, the available evidence does not suggest a significant increase in miscarriage rate, congenital malformation, or developmental delay in their offspring compared to the offspring of patients with less severe forms of infertility or the offspring of fertile men. However, due to limited data, NOA patients should receive specialized reproductive care and personalized management. Counseling of NOA patients is essential before initiating any fertility enhancement treatment not only to mitigate health risks associated with NOA but also to enhance the chances of successful outcomes and minimize possible risks to the offspring. Full article
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<p>Etiology of non-obstructive azoospermia.</p>
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<p>(<b>A</b>) Intracytoplasmic sperm injection; (<b>B</b>) trophectoderm biopsy for preimplantation genetic testing.</p>
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<p>Testicular sperm retrieval techniques.</p>
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<p>Outcomes of intracytoplasmic sperm injection on the health of offspring from patients with non-obstructive azoospermia.</p>
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20 pages, 1922 KiB  
Review
Micro/Nanorobotics in In Vitro Fertilization: A Paradigm Shift in Assisted Reproductive Technologies
by Prateek Benhal
Micromachines 2024, 15(4), 510; https://doi.org/10.3390/mi15040510 - 10 Apr 2024
Viewed by 3297
Abstract
In vitro fertilization (IVF) has transformed the sector of assisted reproductive technology (ART) by presenting hope to couples facing infertility challenges. However, conventional IVF strategies include their own set of problems such as success rates, invasive procedures, and ethical issues. The integration of [...] Read more.
In vitro fertilization (IVF) has transformed the sector of assisted reproductive technology (ART) by presenting hope to couples facing infertility challenges. However, conventional IVF strategies include their own set of problems such as success rates, invasive procedures, and ethical issues. The integration of micro/nanorobotics into IVF provides a prospect to address these challenging issues. This article provides an outline of the use of micro/nanorobotics in IVF specializing in advancing sperm manipulation, egg retrieval, embryo culture, and capacity future improvements in this swiftly evolving discipline. The article additionally explores the challenges and obstacles associated with the integration of micro/nanorobotics into IVF, in addition to the ethical concerns and regulatory elements related to the usage of advanced technologies in ART. A comprehensive discussion of the risk and safety considerations related to using micro/nanorobotics in IVF techniques is likewise presented. Through this exploration, we delve into the core principles, benefits, challenges, and potential impact of micro/nanorobotics in revolutionizing IVF procedures and enhancing affected person outcomes. Full article
(This article belongs to the Special Issue Micro/Nano Robotics Technologies in Applied Science and Engineering)
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<p>In vitro fertilization technique: (<b>a</b>) conventional IVF procedure where sperm is injected inside the egg cell or oocyte (<b>b</b>) micro/nanorobotic-based manipulation of the egg cell and sperm. Later, the fused cell with sperm is injected inside the uterine cavity; (<b>c</b>) and the embryo development cycle after it is injected inside the uterine cavity. Figure created with <a href="http://BioRender.com" target="_blank">BioRender.com</a> (accessed on 10 February 2024).</p>
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<p>Gamete and embryo manipulation strategies. (<b>a</b>) Electromagnetic field manipulation of cells, (<b>b</b>) positive dielectrophoresis (pDEP), (<b>c</b>) negative dielectrophoresis (nDEP), and (<b>d</b>) electrorotation (ER).</p>
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<p>A microrobot with a form like that of a sperm is created using the process of electrospinning. This microrobot comprises a microbead and an ultra-fine fiber that closely match the physical structure of a sperm cell. The microbead is composed of iron oxide nanoparticles (45-00-252 Micromod Partikeltechnologie GmbH, Rostock, Germany) and possesses a magnetic dipole moment (m). On the other hand, the fiber generates propulsive force when subjected to oscillating magnetic fields. The fields are produced by arranging electromagnetic coils in an orthogonal configuration (as shown in the bottom-right inset) [<a href="#B43-micromachines-15-00510" class="html-bibr">43</a>]. <a href="#micromachines-15-00510-f003" class="html-fig">Figure 3</a> Reprinted with permission from Ref. [<a href="#B43-micromachines-15-00510" class="html-bibr">43</a>]. Copyright 2016, IEEE.</p>
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<p>(<b>A</b>) A schematic representation of a micromotor resembling a spiral, which functions to capture, transport, and discharge an oocyte or embryo within the endometrium and fallopian tube. An overview of embryo transfer strategies: (<b>B</b>) tethered methodology incorporating a microcatheter; (<b>C</b>) untethered methodology utilizing microcarriers; and (<b>D</b>) a combined methodology in which untethered carriers are introduced via a catheter. © Reprinted/adapted with permission from Ref [<a href="#B7-micromachines-15-00510" class="html-bibr">7</a>]. 9 February 2023, Springer Nature) with an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium.</p>
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<p>Micro-pipette techniques have been widely used to study the mechanical characteristics of oocytes and embryos, utilizing several methods for assessment. These approaches can be classified into three main types. (<b>a</b>) Two studies, Liu et al. (2012) [<a href="#B54-micromachines-15-00510" class="html-bibr">54</a>] (top left) and Sun et al. (2003) [<a href="#B55-micromachines-15-00510" class="html-bibr">55</a>], (top right) provide information on indentation-based techniques where an oocyte is either pushed against flexible supports or deformed by a force-sensing microneedle. Green (1987) [<a href="#B56-micromachines-15-00510" class="html-bibr">56</a>] (bottom left) illustrates an oocyte being crushed by a quartz-fiber ‘poker’, while Murayama et al. (2004) [<a href="#B57-micromachines-15-00510" class="html-bibr">57</a>] (bottom right) show an oocyte being probed by a material testing system (MTS) from the left side. The value ‘2’ on figure indicates the second figure [<a href="#B57-micromachines-15-00510" class="html-bibr">57</a>] where in a Hamster egg zona was subjected to a compression force of 130 nN. (<b>b</b>) Compression-based methods: Abadie et al. (2014) [<a href="#B58-micromachines-15-00510" class="html-bibr">58</a>] depict an oocyte about to be compressed between a micropipette and a floating platform, whereas Wacogne et al. (2008) [<a href="#B59-micromachines-15-00510" class="html-bibr">59</a>] show an oocyte being compressed between a micropipette and a flexible post from a side angle. ‘Target image” refers to the algorithm used to monitor the movement of the pipette. (<b>c</b>) Aspiration-based methods: Yanez et al. (2016) [<a href="#B60-micromachines-15-00510" class="html-bibr">60</a>] display a picture of an embryo being partially drawn into a micropipette, with the depth of aspiration marked between arrows. Khalilian et al. (2010b) [<a href="#B61-micromachines-15-00510" class="html-bibr">61</a>] illustrate a portion of the zona pellucida (ZP) being drawn into a micropipette. <a href="#micromachines-15-00510-f003" class="html-fig">Figure 3</a> Reprinted/adapted with permission from Ref. [<a href="#B53-micromachines-15-00510" class="html-bibr">53</a>], Copyright 2016, Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.</p>
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<p>Analysis of the challenges and ethical considerations associated with the integration of advanced technologies into ART. The analysis data of the number of scientific publications indicate that there are still technical challenges to overcome. Some of the keywords used during a search in Web of Science and Scopus include: “advanced technologies during IVF and ART, Technical Issues in IVF, advanced technology in ARTs, Robotics in IVF and ART, Advanced technology ethical and regulatory issues in IVF, Affordability of use of advanced technologies in IVF”.</p>
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13 pages, 393 KiB  
Review
Investigating the Association of Assisted Reproduction Techniques and Adverse Perinatal Outcomes
by Anastasios Potiris, Paraskevas Perros, Eirini Drakaki, Despoina Mavrogianni, Nikolaos Machairiotis, Antonios Sfakianakis, Theodoros Karampitsakos, Dionysios Vrachnis, Nikolaos Antonakopoulos, Periklis Panagopoulos, Peter Drakakis and Sofoklis Stavros
J. Clin. Med. 2024, 13(2), 328; https://doi.org/10.3390/jcm13020328 - 6 Jan 2024
Cited by 11 | Viewed by 2777
Abstract
Background: Infertility affects about 80 million individuals worldwide and 10–15% of couples at reproductive age will seek medical assistance. There is increasing evidence that pregnancies after Assisted Reproduction Techniques (ART) are associated with pre-term birth, low birthweight, congenital defects, and increased mortality rates. [...] Read more.
Background: Infertility affects about 80 million individuals worldwide and 10–15% of couples at reproductive age will seek medical assistance. There is increasing evidence that pregnancies after Assisted Reproduction Techniques (ART) are associated with pre-term birth, low birthweight, congenital defects, and increased mortality rates. The aim of this review is to assess all the published literature and provide an updated review on the effect of assisted conception and perinatal and neonatal outcomes. Methods: Comprehensive research on Pubmed/Medline, Scopus, and Google scholar electronic databases was conducted from July 2023 up to September 2023, using the terms assisted reproductive techniques, ART, in vitro fertilization, IVF, intracytoplasmic sperm injection, ICSI, preterm birth, PTB, low birth weight, LBW, chromosomal defects, congenital defects, and hypospadias. In total, 87 full text articles were retrieved and after a careful evaluation, 31 studies were selected for data extraction. Results: Our review demonstrated a higher risk of congenital and chromosomal defects, and a higher incidence of male genital tract defects and heart defects in ART pregnancies. Regarding pre-term birth, our results were contradictory. Conclusions: Although assisted reproduction techniques are associated with increased risks, they are safe regarding perinatal outcomes and couples should not be discouraged from utilizing them. Our results aim to alert clinicians to these specific outcomes and offer more personalized care and counseling to infertile couples and their children. Full article
(This article belongs to the Special Issue Gynecologic and Obstetric Pathologies: From Birth to Menopause)
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<p>Flowchart of the selection process.</p>
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12 pages, 664 KiB  
Article
A Prior History of Cryptozoospermia Is Associated with a Significantly Higher Chance of a Successful Microdissection Testicular Sperm Extraction Compared to Non-Obstructive Azoospermia
by James Wren, Matthew Hudnall, Minh Pham, Anne L. Darves-Bornoz, Joshua A. Halpern, Nelson E. Bennett, Robert E. Brannigan and Matthias D. Hofer
J. Clin. Med. 2023, 12(23), 7255; https://doi.org/10.3390/jcm12237255 - 23 Nov 2023
Cited by 1 | Viewed by 1820
Abstract
Background: Our study sought to evaluate the rates of successful sperm retrieval following microdissection testicular sperm extraction (mTESE) in patients with a prior history of cryptozoospermia, compared to patients with non-obstructive azoospermia (NOA). Methods: A retrospective chart analysis evaluating all mTESE procedures was [...] Read more.
Background: Our study sought to evaluate the rates of successful sperm retrieval following microdissection testicular sperm extraction (mTESE) in patients with a prior history of cryptozoospermia, compared to patients with non-obstructive azoospermia (NOA). Methods: A retrospective chart analysis evaluating all mTESE procedures was performed from January 2004 to August 2018. Inclusion criteria involved all males >18 years of age with a diagnosis of cryptozoospermia and/or NOA that underwent a mTESE. The patient’s genetic profile, hormonal profile, semen analysis, testicular volumes, pathology and comorbidities were analyzed. Results: We identified 40 patients with cryptozoospermia and 221 patients with NOA. Successful mTESE occurred in 34/40 (85%) cryptozoospermic males compared to 104/221 (48%) NOA males (p < 0.001). In univariate and multivariate analyses, patients with cryptozoospermia were more likely to undergo a successful mTESE than patients with NOA (OR 5.56 [1.79–17.29], p = 0.003; OR 5.41 [1.94–15.08], p = 0.0013), respectively. Factors that were associated with a statistically significant lower chance of successful mTESE included Sertoli-cell only pathology, pre-operative testosterone < 300 ng/dL and FSH > 7.6 mIU/mL. Conclusion: Despite patients with a history of cryptozoospermia having a significantly higher chance of a successful sperm retrieval than patients with NOA, couples should be counselled on the possibility of an unsuccessful sperm extraction, in order to optimize the pre-operative IVF planning and to manage operative expectations. Full article
(This article belongs to the Section Nephrology & Urology)
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<p>A bar graph demonstrating the rates of successful micro-testicular sperm extraction (mTESE) between males with azoospermia compared to cryptozoospermia.</p>
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<p>Flow diagram of the chance of successful sperm retrieval (SSR) following mTESE.</p>
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10 pages, 1736 KiB  
Article
Noninvasive Prediction of Sperm Retrieval Using Diffusion Tensor Imaging in Patients with Nonobstructive Azoospermia
by Sikang Gao, Jun Yang, Dong Chen, Xiangde Min, Chanyuan Fan, Peipei Zhang, Qiuxia Wang, Zhen Li and Wei Cai
J. Imaging 2023, 9(9), 182; https://doi.org/10.3390/jimaging9090182 - 8 Sep 2023
Cited by 3 | Viewed by 1879
Abstract
Microdissection testicular sperm extraction (mTESE) is the first-line treatment plan for nonobstructive azoospermia (NOA). However, studies reported that the overall sperm retrieval rate (SRR) was 43% to 63% among men with NOA, implying that nearly half of the patients fail sperm retrieval. This [...] Read more.
Microdissection testicular sperm extraction (mTESE) is the first-line treatment plan for nonobstructive azoospermia (NOA). However, studies reported that the overall sperm retrieval rate (SRR) was 43% to 63% among men with NOA, implying that nearly half of the patients fail sperm retrieval. This study aimed to evaluate the diagnostic performance of parameters derived from diffusion tensor imaging (DTI) in predicting SRR in patients with NOA. Seventy patients diagnosed with NOA were enrolled and classified into two groups based on the outcome of sperm retrieval during mTESE: success (29 patients) and failure (41 patients). Scrotal magnetic resonance imaging was performed, and the DTI parameters, including mean diffusivity and fractional anisotropy, were analyzed between groups. The results showed that there was a significant difference in mean diffusivity values between the two groups, and the area under the curve for mean diffusivity was calculated as 0.865, with a sensitivity of 72.2% and a specificity of 97.5%. No statistically significant difference was observed in fractional anisotropy values and sex hormone levels between the two groups. This study demonstrated that the mean diffusivity value might serve as a useful noninvasive imaging marker for predicting the SRR of NOA patients undergoing mTESE. Full article
(This article belongs to the Section Medical Imaging)
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<p>Histopathological examination. The mTESE shows that a milky white and thicker seminiferous tubule is selected (arrowhead) under an 18× microscope (<b>A</b>). After the selected milky white and thicker seminiferous tubule is cut up, mature sperm are found (arrowhead) under a 200× microscope (<b>B</b>). The Histopathology slide shows the seminiferous tubules of a NOA patient with sperm retrieval; few spermatozoa are distributed in the seminiferous tubule (arrowhead) (H&amp;E, 200) (<b>C</b>). Histopathology slide shows the seminiferous tubules of a NOA patient without sperm retrieval; no mature sperm is found in the seminiferous tubule (H&amp;E, 200) (<b>D</b>).</p>
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<p>Boxplots show FA and MD distribution between the two groups. The mean FA value is not significantly different between the two groups (<span class="html-italic">p</span> &gt; 0.05) (<b>A</b>). The mean MD value is significantly higher among the patients in Group A than among those in Group B (<span class="html-italic">p</span> &lt; 0.001) (<b>B</b>). FA: fractional anisotropy, MD: mean diffusivity, ****: <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>DTI parameter maps of a 34-year-old NOA patient with sperm retrieval. ROIs are outlined at the maximum level of the testes at b value = 0 s/mm<sup>2</sup> along the outer border of the testes (right and left) (<b>A</b>). ROIs are automatically replicated to the MD (<b>B</b>) and FA (<b>C</b>) parameter maps. The MD values are 1974.7 × 10<sup>−6</sup> mm<sup>2</sup>/s (left testis) and 1831.5 × 10<sup>−6</sup> mm<sup>2</sup>/s (right testis). The FA values are 83.8 × 10<sup>−3</sup> (left testis) and 68.1 × 10<sup>−3</sup> (right testis).</p>
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<p>DTI parameter maps of a 30-year-old NOA patient without sperm retrieval. ROIs are outlined at the maximum level of the testes at b value = 0 s/mm<sup>2</sup> along the outer border of the testes (right and left) (<b>A</b>). ROIs are automatically replicated to the MD (<b>B</b>) and FA (<b>C</b>) parameter maps. The MD values are 1355.6 × 10<sup>−6</sup> mm<sup>2</sup>/s (left testis) and 1417 × 10<sup>−6</sup> mm<sup>2</sup>/s (right testis). The FA values are 90.4 × 10<sup>−3</sup> (left testis) and 125.9 × 10<sup>−3</sup> (right testis).</p>
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<p>The ROC curves show the diagnostic accuracy of MD value in successful sperm retrieval of NOA patients.</p>
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11 pages, 637 KiB  
Article
Comparison of Cumulative Live Birth Rates between Flexible and Conventional Progestin-Primed Ovarian Stimulation Protocol in Poor Ovarian Response Patients According to POSEIDON Criteria: A Cohort Study
by Ying Chen, Yifan Chu, Wen Yao, Luyao Wang, Wanjiang Zeng and Jing Yue
J. Clin. Med. 2023, 12(18), 5775; https://doi.org/10.3390/jcm12185775 - 5 Sep 2023
Cited by 4 | Viewed by 1812
Abstract
Research Question: To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle of a conventional progestin-primed ovarian stimulation (cPPOS) regimen with a flexible progestin-primed ovarian stimulation (fPPOS) regimen in poor ovarian response patients, according to POSEIDON criteria. Design: Poor ovarian response [...] Read more.
Research Question: To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle of a conventional progestin-primed ovarian stimulation (cPPOS) regimen with a flexible progestin-primed ovarian stimulation (fPPOS) regimen in poor ovarian response patients, according to POSEIDON criteria. Design: Poor ovarian response women, according to POSEIDON criteria, who underwent the first PPOS protocol for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) between January 2018 and December 2020 were included. The fPPOS group involved 113 participants, and the cPPOS group included 1119 participants. In the cPPOS group, medroxyprogesterone acetate (MPA) (10 mg/d) was administrated on the gonadotropin injection the same day as gonadotropin injections in the cPPOS group, while MPA was started either on the day when the leading follicle with mean diameter > 12mm was present and/or serum E2 was >300 pg/mL in the fPPOS protocol group. The primary outcome was CLBR. Results: The fPPOS protocol had higher CLBR per oocyte retrieval cycle compared to the cPPOS group, even without a statistically significant difference (29.6% vs. 24.9%, p = 0.365). The fPPOS group had fewer numbers of retrieved oocytes (2.87 ± 2.03 vs. 3.76 ± 2.32, p < 0.001) but a higher MII oocyte rate (89.8% vs. 84.7%, p = 0.016). In addition, the number of available embryos in the two groups was comparable (1.37 ± 1.24 vs. 1.63 ± 1.38, p = 0.095). There were five women in the fPPOS group, and 86 women in the cPPOS group had a premature LH surge (4.2% vs. 6.8%, p = 0.261). In the fPPOS group, there was one instance of premature ovulation, while in the cPPOS group, there were six occurrences of premature ovulation (0.8 vs. 0.5%, p = 1.000). Conclusion(s): The novel fPPOS protocol appears to achieve higher CLBR even without significant differences and with MPA consumption compared with cPPOS protocol in low-prognosis patients. Full article
(This article belongs to the Special Issue New Advances in Clinical Reproductive Medicine)
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<p>Flow chart of the selection of patients for inclusion in this study. IVF, in vitro fertilization. ICSI, intracytoplasmic sperm injection. POSEIDON criteria, The Patient-Oriented Strategies Encompassing Individualized Oocyte Number criteria. fPPOS, flexible progestin-primed ovarian stimulation protocol. cPPOS, conventional progestin-primed ovarian stimulation protocol. PSM, propensity score matching.</p>
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13 pages, 348 KiB  
Article
Onco-TESE (Testicular Sperm Extraction): Insights from a Tertiary Center and Comprehensive Literature Analysis
by Lorenzo Cirigliano, Marco Falcone, Murat Gül, Mirko Preto, Carlo Ceruti, Natalia Plamadeala, Federica Peretti, Ilaria Ferro, Martina Scavone and Paolo Gontero
Medicina 2023, 59(7), 1226; https://doi.org/10.3390/medicina59071226 - 29 Jun 2023
Cited by 5 | Viewed by 2584
Abstract
Background and Objectives: The peak of incidence of testicular cancer (TC) occurs among individuals in their reproductive age, emphasizing the importance of fertility preservation as an integral aspect of disease management. Sperm cryopreservation performed before orchiectomy is ineffective in azoospermic men, necessitating [...] Read more.
Background and Objectives: The peak of incidence of testicular cancer (TC) occurs among individuals in their reproductive age, emphasizing the importance of fertility preservation as an integral aspect of disease management. Sperm cryopreservation performed before orchiectomy is ineffective in azoospermic men, necessitating alternative approaches such as microdissection testicular sperm extraction (mTESE) at the time of orchiectomy (onco-mTESE) to obtain viable sperm. This study presents the findings from our institution’s experience with onco-mTESE and critically discusses our results in light of the existing body of literature. Materials and Methods: This is a tertiary center retrospective analysis of onco-mTESE procedures performed at a single center between December 2011 and July 2022. The included patients were post-puberal men with testicular tumors requiring orchiectomy, along with concomitant severe oligozoospermia or azoospermia. Bilateral mTESE was performed in all cases. Surgical outcomes, sperm retrieval rates, the usage of preserved viable sperm, assistive reproductive techniques’ results, and post-operative serum testosterone were recorded. Results: A total of nine patients were included, with a median age of 34 (IQR 29–36) years. All patients had germ cell tumors (GCTs), with seminomatous and non-seminomatous GCTs accounting for 44.4% (n = 4) and 55.6% (n = 5) of patients, respectively. Sperm retrieval occurred in three (33%) patients: one patient in the ipsilateral testis, one in the contralateral testis, and one in both testes. No complications were reported during the procedure, and no post-operative hypogonadism was observed. Among the three patients with successful sperm retrieval, an intracytoplasmic sperm injection (ICSI) was performed in two patients, resulting in two pregnancies, leading to one healthy live birth and one miscarriage. Conclusions: In the context of TC, it is essential to conduct a thorough evaluation of testicular function, including a semen analysis and cryopreservation. Onco-mTESE has proven its safety in preserving fertility in azoospermic cases while ensuring the efficacy of oncological treatment. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Testicular Cancer)
26 pages, 678 KiB  
Review
The Klinefelter Syndrome and Testicular Sperm Retrieval Outcomes
by Rosália Sá, Luís Ferraz, Alberto Barros and Mário Sousa
Genes 2023, 14(3), 647; https://doi.org/10.3390/genes14030647 - 4 Mar 2023
Cited by 13 | Viewed by 9207
Abstract
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, [...] Read more.
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. Full article
(This article belongs to the Special Issue Genetic Causes of Human Infertility)
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<p>Outpatient conventional TESE employing local anesthesia using the three-finger technique and spermatic cord block. <b>Left</b>. Exposure of the tunica albuginea after entering the tunica vaginalis space. <b>Right</b>. Exposure of the seminiferous tubules.</p>
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Article
Cycle Characteristics and Pregnancy Outcomes of Early Rescue Intracytoplasmic Sperm Injection Cycles in Normal and Hyper-Ovarian Response Women: A Six-Year Retrospective Study
by Liang Chen, Hanjing Zhou, Xueli Liu, Jing Zhao, Qianrong Qi and Qingzhen Xie
J. Clin. Med. 2023, 12(5), 1993; https://doi.org/10.3390/jcm12051993 - 2 Mar 2023
Cited by 3 | Viewed by 2220
Abstract
This study aims to analyze the cycle characteristics, pregnancy, and neonatal outcomes in early rescue intracytoplasmic sperm injection (r-ICSI) cycles in normal and hyper-ovarian response women in their first IVF/ICSI attempts. Data from short-term in vitro fertilization (IVF, N = 7148), early r-ICSI [...] Read more.
This study aims to analyze the cycle characteristics, pregnancy, and neonatal outcomes in early rescue intracytoplasmic sperm injection (r-ICSI) cycles in normal and hyper-ovarian response women in their first IVF/ICSI attempts. Data from short-term in vitro fertilization (IVF, N = 7148), early r-ICSI (N = 618), and ICSI (N = 1744) cycles were retrospectively analyzed from normal and hyper-ovarian women who underwent their first IVF/ICSI cycles at our center from October 2015 to October 2021. The r-ICSI group was subdivided into partial r-ICSI (N = 451) and total r-ICSI (N = 167) based on the number of fertilized oocytes in the IVF part. Cyclic characteristics, pregnancy, delivery and neonatal outcomes in the fresh cycle were compared among the four groups; pregnancy, delivery and neonatal outcomes in frozen-thawed cycles were compared regarding cleavage and blastocyst transfers derived from r-ICSI cycles. Partial r-ICSI cycles showed different cyclic characteristics compared to total r-ICSI cycles, presenting as elevated AMH and estradiol levels on trigger day and an increased number of oocytes retrieved. Early r-ICSI delayed blastocyst development as seen by the increase in the number of day 6 blastocysts. There was no significant difference among the groups in clinical pregnancy, pregnancy loss, and live birth in fresh cleavage-stage embryo transfer cycles. However, early r-ICSI groups showed a reduction in clinical pregnancy and live birth rates in fresh blastocyst transfer cycles but not in the frozen-thawed cycles. For pregnant women, early r-ICSI did not show a negative effect on the risk of preterm birth, Cesarean section, neonatal birth weight, and sex ratio. In conclusion, early r-ICSI had comparable pregnancy, delivery, and neonatal outcomes when compared with short-term IVF and ICSI groups in fresh cleavage-stage embryo transfer cycles, but early r-ICSI did result in reduced pregnancy outcomes in fresh blastocyst embryo cycles, possibly due to delayed blastocyst development and asynchronization with the endometrium. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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<p>Cycles included in this study. IVF, in vitro fertilization; ICSI, intracytoplasmic sperm injection; TESA, testicular sperm aspiration; PGT, preimplantation genetic testing; ET, embryo transfer; FET, frozen-thawed embryo transfer; BL, blastocyst; TFF, total fertilization failure.</p>
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<p>(<b>A</b>) Comparison of live birth rates per fresh embryo transfers from cleavage-stage and blastocyst transfers among the four groups. (<b>B</b>) Comparison of live birth rates per frozen embryo transfers from r-ICSI derived cleavage-stage and blastocyst transfers. Bars with different letters differ significantly among groups (<span class="html-italic">p</span> &lt; 0.05).</p>
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