Article

Single incision laparoscopic surgery (SILS) for ovarian tissue cryopreservation

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Abstract

Study objective: To present single-incision laparoscopic surgery (SILS) as an alternative to standard multi-port laparoscopic surgery (MPLS) for ovarian tissue cryopreservation (OTC). Design: Retrospective cohort study (Canadian Task Force classification II-2). Setting: Tertiary medical center. Patients: Two hundred thirty-one patients referred for oncological fertility preservation. Intervention: Non-inferiority comparison of SILS to MPLS for ovarian cryopreservation for future transplantation. Measurements and main results: Duration of the procedure, intra and post-operative complications, hospital stay and time (days) from surgery to chemotherapy. We additionally compared number of ampules (each ampule contains 10 slivers of ovarian cortex tissue) preserved and number of oocytes retrieved during the preparation process. Adjustments for age, previous chemotherapy and partial vs. complete oophorectomy ratio were performed. MPLS was performed in 163 (71.2%) patients and SILS was performed in 66 (28.8%) patients. Ten patients (15.2%) in the SILS group and 32 (19.8%) in the MPLS group were pre-pubertal. Malignant conditions distribution was similar. Procedure duration and overall complication rates were similar. Number of ampules extracted from the preserved tissue was somewhat higher in the SILS group as compared to MPLS (14.7 vs. 10.6, respectively; p<0.01). Conclusion: Our findings suggest that SILS is an interesting alternative to MPLS. Future prospective trials may prove some benefit in ovarian tissue volume or time until chemotherapy initiation.

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... In US, the Oncofertility consortium consensus statement recommends the procedure for patients aged up to 42 years who could or did not want to cryopreserve oocytes or embryos (Backhus, et al., 2007). OTC has been performed in patients aged up to 40 or even 49 years by others (Jadoul, et al., 2017, Karavani, et al., 2018. However, pregnancies have been rarely observed when OTC is performed in women older than 35 years and none have been reported after 38 years (Gellert, et al., 2018). ...
... Several centres perform ovarian biopsy (1/3 to 2/3 of one ovary), while others routinely perform unilateral oophorectomy . Oophorectomy by single-incision laparoscopic surgery was shown not to be inferior to standard 2-or 3-port laparoscopy in terms of complication rate, duration of the procedure, hospital stay and delay to start chemotherapy (Karavani, et al., 2018). ...
... Although reduced-port laparoscopy is feasible and less invasive, it requires a learning curve and should not be offered in case of pelvic diseases such as endometrioma or fibroma (Karavani, et al., 2018, Kikuchi, et al., 2013. As such, this technique can be offered by trained surgeons in the absence of pelvic disease. ...
Article
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The guideline is aimed at healthcare professionals who are involved in information provision and decision making with women scheduled to undergo gonadotoxic treatments or women and transmen considering fertility preservation for other reasons. This includes, but is not limited to, reproductive medicine specialists, endocrinologists, oncologists and oncological surgeons and gynaecologists, paramedical and reproductive biologists (including embryologists), and geneticists. For the benefit of patient education and shared decision-making, a patient version of this guideline will be developed.
... Unilateral oophorectomy or ovarian cortex biopsy are both tolerable, and in terms of surgical approach, laparoendoscopic single-site and multi-port laparoscopic access with or without robotic assistance are both reported to be feasible, and minilaparotomy is also being utilized (52)(53)(54)(55). The surgical approach did not influence the hospitalization period or chemotherapy delay (56). Although the impact of gonadotoxic treatment with and without unilateral oophorectomy has not yet been fully reported, the FetriPROTKET network group recommended that only 50% of one ovary to be removed and cryopreserved in adult women and that unilateral oophorectomy to be performed in prepubertal girls with small ovarian volumes (10). ...
Article
Fertility preservation (FP) in pediatric and adolescent oncology patients presents a complex interplay between cancer treatment imperatives and reproductive aspirations, demanding a multi-disciplinary approach. Essential guidelines emphasize the importance of early referrals to FP specialists, ensuring timely counseling on oocyte and ovarian tissue cryopreservation options. Proper patient selection and risk assessment, considering intrinsic and extrinsic factors, is crucial for judicious resource utilization and optimal outcomes. Gonadotoxic effects of cancer treatments pose significant threats to reproductive capabilities. Oocyte cryopreservation (OC) is preferred in post-pubertal adolescents without partners. Cultural and religious concerns, especially regarding hymenal integrity, influence FP decisions, necessitating culturally sensitive consent processes. Ovarian tissue cryopreservation (OTC) offers an alternative for those unfit for OC. Despite its experimental label in some societies, emerging data support the efficacy of OTC, with ovarian tissue transplantation (OTT) showing promise in restoring ovarian function. However, the reintroduction of potentially malignant cells during transplantation remains a concern. Overall, while FP offers hope for future parenthood, the intricacies of decision-making and the potential medical, ethical, and cultural challenges underscore the importance of a personalized, multi-disciplinary approach. In this review, guidelines from various societies have been comprehensively reviewed and analyzed to provide insight into the clinical practice of oncofertility.
... Conventional 3-port laparoscopy has classically been the approach of choice; however, the authors' experience suggested a SILS approach may be superior for reasons that include shorter operative time and better cosmesis. Karayani et al. also published that the ease of specimen delivery using this technique has been shown to lead to better preservation of ovarian tissue and result in a better-quality specimen for cryopreservation [5]. ...
Article
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Objective We aim to compare conventional 3-port with single-incision laparoscopic surgery (SILS) for oophorectomy in patients undergoing ovarian cryopreservation. Background Demand for cryopreservation of ovarian tissue prior to the initiation of gonadotoxic treatment has risen significantly since its introduction in England in 2013. Traditionally, laparoscopic oophorectomy is performed using a 3-port technique with an umbilical port and 2 smaller 5-mm working ports. Energy devices can be used to allow haemostatic dissection of the ovary and this is delivered through the umbilical port site. In an attempt to improve efficiency, post-operative outcomes, and enhance cosmesis; our department initiated the use of the Applied Medical GelPoint Mini Advanced Access Platform single port technique using a vertical trans-umbilical approach for ovarian cryopreservation. Methods All patients undergoing laparoscopic oophorectomy for cryopreservation between September 2013 and August 2017 were included. The patients were consented for SILS, 3-port and open oophorectomies. All patients received maximum local anaesthetic wound infiltration intra-operatively. Case notes and theatre electronic data were reviewed and data was collected on additional procedure, conversion rate, operative time, post-operative analgesia requirement, complications and length of hospital stay. Results A total of 106 patients underwent laparoscopic oophorectomy during the study period. Of these, 40 underwent conventional 3-port, 65 had SILS and 1 patient had open. No cases were converted from the intended method. There was a statistically significant difference in the mean operative time; with SILS being faster than the conventional 3-port method (SILS: 40.4 min; 3-port: 51.7 min; p = 0.017). There was no difference in length of stay or perioperative analgesics, and complication rates in both groups were low. Informal qualitative feedback included surgeons stating that the ovary was much easier to deliver using the SILS technique. Patients were also happy with a single cosmetically appeasing scar hidden within the umbilicus. Conclusion SILS is an acceptable technique in ovarian cryopreservation allowing a quicker operative time, easier delivery of the ovary, and better cosmesis. A learning curve is recognised due to the ergonomics of single port laparoscopy; however, the technique can be established easily in departments with existing laparoscopic capabilities. This is the first paper which establishes this within a Paediatric Surgical setting, and adult literature suggests that further prospective trials may prove some benefit in ovarian tissue volume or time to initiation of treatment due to enhanced recovery.
... The age of the enrolled patients seems to be crucial. In various recommendations, we find the upper age limit from 35 years [6] to even 49 years [7][8][9]. However, pregnancy was rarely achieved in women over 35 years of age, and none over 38 years of age was found [10]. ...
Article
Update of the recommendations of the Fertility Preservation Working Group in Oncological, Hematological and Other Patients Treated with Gonadotoxic Therapies "ONCOFERTILITY" (GROF) of the Polish Society of Oncological Gynecology regarding cryopreservation and autologous ovarian tissue transplantation. The Fertility Preservation Working Group in Oncological, Hematological and Other Patients Treated with Gonadotoxic Therapies "ONCOFERTILITY" (GROF) of the Polish Society of Oncological Gynecology has developed current clinical guidelines and recommendations to improve the quality of healthcare provision in the area of reproductive health in patients undergoing therapy that may impair their reproductive potential. The guidelines are based on current scientific evidence available at the time of writing this document. In the absence of scientific evidence on some aspects, a consensus was reached among GROF stakeholders. The purpose of the guidelines is to assist healthcare professionals in making decisions in specific clinical situations regarding the selection of an appropriate and effective diagnostic and therapeutic process. The document provides practical guidelines for the management of cryopreservation and autologous ovarian tissue transplantation.
... One of the most important advantages of laparoscopic surgery is that patients recover very quickly, enabling them to promptly start chemotherapy [97]. In particular, a single-port laparoscopy is widely used in surgical gynecology and is associated with a low rate of complications following OT extraction [102]. ...
Article
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Although advances in cancer treatment and early diagnosis have significantly improved cancer survival rates, cancer therapies can cause serious side effects, including ovarian failure and infertility, in women of reproductive age. Infertility following cancer treatment can have significant adverse effects on the quality of life. However, established methods for fertility preservation, including embryo or oocyte cryopreservation, are not always suitable for female cancer patients because of complicated individual conditions and treatment methods. Ovarian tissue cryopreservation and transplantation is a promising option for fertility preservation in pre-pubertal girls and adult patients with cancer who require immediate treatment, or who are not eligible to undergo ovarian stimulation. This review introduces various methods and strategies to improve ovarian tissue cryopreservation and transplantation outcomes, to help patients and clinicians choose the best option when considering the potential complexity of a patient’s situation. Effective multidisciplinary oncofertility strategies, involving the inclusion of a highly skilled and experienced oncofertility team that considers cryopreservation methods, thawing processes and devices, surgical procedures for transplantation, and advances in technologies, are necessary to provide high-quality care to a cancer patient.
... Popularity of single-incision laparoscopic surgery increased in recent years and is utilized in many different surgical areas [23][24][25][26][27][28][29][30]. Difficulties in single-port surgery are mostly caused by impeded handling through straight and therefore crossing instruments. ...
Article
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Background Minimally invasive single-port surgery is always associated with large incisions up to 2–3 cm, complicated handling due to the lack of triangulation, and instrument crossing. The aim of this prospective study was to report how medical students without any laparoscopic experience perform several laparoscopic tasks (rope pass, paper cut, peg transfer, recapping, and needle threading) with the new SymphonX single-port platform and to examine the learning curves in comparison to the laparoscopic multi-port technique. Methods A set of 5 laparoscopic skill tests (Rope Pass, Paper cut, Peg Transfer, Recapping, Needle Thread) were performed with 3 repetitions. Medical students performed all tests with both standard laparoscopic instruments and the new platform. Time and errors were recorded. Results A total of 114 medical students (61 females) with a median age of 23 years completed the study. All subjects were able to perform the skill tests with both standard laparoscopic multi-port and the single-port laparoscopic system and were able to significantly improve their performance over the three trials for all five tasks—rope pass (p < 0.001), paper cut (p < 0.001), peg transfer (p < 0.001), needle threading (p < 0.001), and recapping (p < 0.001). In 3 out of 5 tasks, medical students performed the tasks faster using the standard multi-port system—rope pass (p < 0.001), paper cut (p < 0.001), and peg transfer (p < 0.001). In the task recapping, medical students performed the task faster using the new single-port system (p = 0.003). In the task needle threading, there was no significant difference between the standard multi-port system and the new single-port system (p > 0.05). Conclusion This is the first study analyzing learning curves of the commercially available SymphonX platform for abdominal laparoscopic surgery when used by novices. The learning curve and the error rate are promising.
... This is the first human case series using the commercially available surgical platform symphonX that eliminates instrument crossing and large incisions. Single-incision laparoscopic surgery (SILS) became increasingly popular in recent years and is used in many surgical fields [10][11][12][13][14][15]. Major issues such as higher rates of herniation due to single-incision sizes from 20 to 30 mm and increased risk of common bile duct injuries are reported in the context of SILS and cholecystectomy. ...
Article
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Background Minimally invasive single-port surgery is often associated with large incisions up to 2–3 cm, complicated handling due to the lack of triangulation, and instrument crossing. Aim of this prospective study was to perform true single-port surgery (cholecystectomy) without the use of assisting trocars using a new surgical platform that allows for triangulation incorporating robotic features, and to measure the perioperative outcome and cosmetic results. Methods As the first European site after FDA and CE-mark approval, the new device has been introduced to our academic center. In patients with cholecystitis and cholecystolithiasis, the operation was performed through only one 15-mm trocar. For patients safety, intraoperative cholangiography using intravenous ICG and a standard Stryker 1588 system was routinely performed. Results Symphonx was used in n = 12 patients for abdominal surgery (6 females, mean age 42.5 [30–77], mean BMI 26.2 [19.3–38.9]. A total of 8 patients underwent surgery using no additional ports besides the 15-mm trocar; in the remaining patients, one assisting instrument (3–5 mm) was used. Mean OR time was 107 [72–221] minutes. The postoperative course was uneventful in 11 patients; in one patient, a seroma at the surgical site required interventional drainage 1 month postoperatively. No intraoperative complications occurred. Conclusion This is the first human case series using the commercially available symphonX platform for abdominal laparoscopic surgery and the first series using the system without assisting instruments. Laparoscopic cholecystectomy in patients with cholecystitis and cholecystolithiasis using the symphonX platform through only one 15-mm trocar is feasible, safe, and more cost-efficient compared to robotic platforms.
Article
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Purpose To evaluate the evolution of fertility preservation surgery in children and young adults at high risk of infertility from a single centre to a networked ‘Hub and Spoke’ service. Methods A case note review of patients referred for ovarian or testicular cryopreservation between Jan 2013 and Dec 2023. Demographic data, procurement numbers, and site of procurement were collected. Specialist feedback was obtained to identify the challenges faced. Results Over time, the number of referrals increased from 4 to 349 patients per year with the number of Spoke centres rising to 36 ovarian and 16 testicular. In 2013–2014; 100% of procurement was ovarian as compared to 2023; 51% ovarian, 49% testicular. Of the 395 referrals in 2021, 81% (n = 319) went on to have procurement and storage of tissue. Between 2013 and 2016, 96% of cases were performed at the Hub. In 2023, 53/349 (15%) cases were performed at the Hub with the remaining 296 (85%) procured at Spoke sites. Surgical issues such as access to theatre, variation and availability of surgical equipment, thermal injury to ovarian tissue and variation in the size of the testicular specimen were identified. Conclusion The Hub and Spoke model successfully delivers treatment to patients close to home as safely possible within their local treatment centre.
Preprint
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Cryopreservation of human ovarian tissue is a technology for protection of reproductive potential in patients undergoing aggressive anticancer treatments. This technology includes the following stages: saturation by permeable cryoprotectants, freezing, thawing, removal of cryoprotectants, and tissues in vitro or in situ culture. The aim of our investigations was the evaluation of genetic risks and molecular alterations in human ovarian tissue during in vitro culture. Ovarian tissue was frozen in 6% ethylene glycol and 6% dimethyl sulfoxide with speed of cooling 0.3°C/min and thawed at 100°C. After removal of cryoprotectants tissue fragments were in vitro cultured with the soluble extract of basement membrane protein (Matrigel) 3-D culture system for 7 days. Morphological and functional assessments were conducted using microscopic observation and RNA-Seq. Comparative analysis of tissue morphology before and after culture was performed with bioinformatics for gene expression and variant analysis, including functional annotation and study of protein-protein interaction. DNA and RNA analyses after cultivation indicated a rise in gene fusion and alternative splicing events, potentially affecting gene expression and cellular functions. It was concluded that long-time in vitro culture of human ovarian tissue results in substantial changes in its morphology and genetic alteration.
Article
Study question: Does a chemically defined maturation medium supplemented with FGF2, LIF, and IGF1 (FLI) improve in vitro maturation (IVM) of cumulus-oocyte complexes (COCs) obtained from children, adolescents, and young adults undergoing ovarian tissue cryopreservation (OTC)? Summary answer: Although FLI supplementation did not increase the incidence of oocyte meiotic maturation during human IVM, it significantly improved quality outcomes, including increased cumulus cell expansion and mitogen-activated protein kinase (MAPK) expression as well as enhanced transzonal projection retraction. What is known already: During OTC, COCs, and denuded oocytes from small antral follicles are released into the processing media. Recovery and IVM of these COCs is emerging as a complementary technique to maximize the fertility preservation potential of the tissue. However, the success of IVM is low, especially in the pediatric population. Supplementation of IVM medium with FLI quadruples the efficiency of pig production through improved oocyte maturation, but whether a similar benefit occurs in humans has not been investigated. Study design, size, duration: This study enrolled 75 participants between January 2018 and December 2021 undergoing clinical fertility preservation through the Fertility & Hormone Preservation & Restoration Program at the Ann & Robert H. Lurie Children's Hospital of Chicago. Participants donated OTC media, accumulated during tissue processing, for research. Participants/materials, setting, methods: Participants who underwent OTC and include a pediatric population that encompassed children, adolescents, and young adults ≤22 years old. All participant COCs and denuded oocytes were recovered from media following ovarian tissue processing. IVM was then performed in either a standard medium (oocyte maturation medium) or one supplemented with FLI (FGF2; 40 ng/ml, LIF; 20 ng/ml, and IGF1; 20 ng/ml). IVM outcomes included meiotic progression, cumulus cell expansion, transzonal projection retraction, and detection of MAPK protein expression. Main results and the role of chance: The median age of participants was 6.3 years, with 65% of them classified as prepubertal by Tanner staging. Approximately 60% of participants had been exposed to chemotherapy and/or radiation prior to OTC. On average 4.7 ± 1 COCs and/or denuded oocytes per participant were recovered from the OTC media. COCs (N = 41) and denuded oocytes (N = 29) were used for IVM (42 h) in a standard or FLI-supplemented maturation medium. The incidence of meiotic maturation was similar between cohorts (COCs: 25.0% vs 28.6% metaphase II arrested eggs in Control vs FLI; denuded oocytes: 0% vs 5.3% in Control vs FLI). However, cumulus cell expansion was 1.9-fold greater in COCs matured in FLI-containing medium relative to Controls and transzonal projection retraction was more pronounced (2.45 ± 0.50 vs 1.16 ± 0.78 projections in Control vs FLIat 16 h). Additionally, MAPK expression was significantly higher in cumulus cells obtained from COCs matured in FLI medium for 16-18 h (chemiluminescence corrected area 621,678 vs 2,019,575 a.u., P = 0.03). Limitations, reasons for caution: Our samples are from human participants who exhibited heterogeneity with respect to age, diagnosis, and previous treatment history. Future studies with larger sample sizes, including adult participants, are warranted to determine the mechanism by which FLI induces MAPK expression and activation. Moreover, studies that evaluate the developmental competence of eggs derived from FLI treatment, including assessment of embryos as outcome measures, will be required prior to clinical translation. Wider implications of the findings: FLI supplementation may have a conserved beneficial effect on IVM for children, adolescents, and young adults spanning the agricultural setting to clinical fertility preservation. Study funding/competing interest(s): This work was supported by Department of Obstetrics and Gynecology startup funds (F.E.D.), Department of Surgery Faculty Practice Plan Grant and the Fertility & Hormone Preservation & Restoration Program at the Ann & Robert H. Lurie Children's Hospital of Chicago (M.M.L. and E.E.R.). M.M.L. is a Gesualdo Foundation Research Scholar. Y.Y.'s research is supported by the internal research funds provided by Colorado Center of Reproductive Medicine. Y.Y., L.D.S., R.M.R., and R.S.P. have a patent pending for FLI. The remaining authors have no conflict of interest. Trial registration number: N/A.
Chapter
This chapter reviews the best practices to establish an ovarian tissue cryopreservation program in your center. We share with you the worldwide regulatory experience in ovarian tissue cryopreservation and transplantation and point out to the areas of improvement. The laboratory efficacy of ovarian tissue cryopreservation (OTC) has been demonstrated through extensive preclinical research. The method has also proved to be clinically useful and it has also been exhaustively evaluated in clinical studies worldwide, becoming an innovative clinical option for fertility preservation. The success rates for regaining fertility after ovarian tissue transplantation has been reported in several cohorts and a metaanalysis, however, it is evident that there is still room for improvement to increase the efficacy of transplantation procedures and the final functionality of the grafted tissues. There is thus a need for continuous research on this topic. Programs for fertility preservation have been established within centers that perform other assisted reproductive technologies, which are already under regulatory conditions for the handling of human gamete cells and reproductive tissues. The centers offering OTC and ovarian tissue transplantation must have a rigorous quality control system. Legislations and regulations can vary among countries but the quality of these services must be under regulatory surveillance worldwide.
Article
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Ovarian tissue cryopreservation (OTC) is the only pre-treatment option currently available to preserve fertility for prepubescent girls and patients who cannot undergo ovarian stimulation. Currently, there is no standardized method of processing ovarian tissue for cryopreservation, despite evidence that fragmentation of ovaries may trigger primordial follicle activation. Because fragmentation may influence ovarian transplant function, the purpose of this systematic review was (1) to identify the processing sizes and dimensions of ovarian tissue within sites around the world, and (2) to examine the reported outcomes of ovarian tissue transplantation including, reported duration of hormone restoration, pregnancy, and live birth. A total of 2,252 abstracts were screened against the inclusion criteria. In this systematic review, 103 studies were included for analysis of tissue processing size and 21 studies were included for analysis of ovarian transplantation outcomes. Only studies where ovarian tissue was cryopreserved (via slow freezing or vitrification) and transplanted orthotopically were included in the review. The size of cryopreserved ovarian tissue was categorized based on dimensions into strips, squares, and fragments. Of the 103 studies, 58 fertility preservation sites were identified that processed ovarian tissue into strips (62%), squares (25.8%), or fragments (31%). Ovarian tissue transplantation was performed in 92 participants that had ovarian tissue cryopreserved into strips (n = 51), squares (n = 37), and fragments (n = 4). All participants had ovarian tissue cryopreserved by slow freezing. The pregnancy rate was 81.3%, 45.5%, 66.7% in the strips, squares, fragment groups, respectively. The live birth rate was 56.3%, 18.2%, 66.7% in the strips, squares, fragment groups, respectively. The mean time from ovarian tissue transplantation to ovarian hormone restoration was 3.88 months, 3.56 months, and 3 months in the strips, squares, and fragments groups, respectively. There was no significant difference between the time of ovarian function’ restoration and the size of ovarian tissue. Transplantation of ovarian tissue, regardless of its processing dimensions, restores ovarian hormone activity in the participants that were reported in the literature. More detailed information about the tissue processing size and outcomes post-transplant are required to identify a preferred or more successful processing method. Systematic Review Registration [https://www.crd.york.ac.uk], identifier [CRD42020189120].
Article
The use of a rigid tube endoscope (RTE) through a laparoendoscopic single site surgery device for intracavitary visualization during endoscopic uniportal surgery (EUS) is directly related to the fulcrum effect and physical competition (externally between surgeons and on instrumentation through the single port). These facts may have precluded a wider spread of EUS. In an attempt to separate the imaging system from the laparoendoscopic single site surgery device, a tiered project (3 models) that can help overcome these drawbacks is detailed. ZEUS1, a new non-RTE imaging system device for EUS was successfully tested in EUS surgery in a pig model. Still under investigation, ZEUS2 becomes a wired structure that serves as the basis for an endoscopic microcamera with intracavitary pan-tilt-zoom functions. ZEUS3 uses the inner ring of the surgical wound protector as a microchamber crown. Further studies are needed to materialize the ZEUS2 and ZEUS3 models and confirm their efficacy and safety.
Article
Resumen El uso de un endoscopio de tubo rígido (RTE) a través de un dispositivo de cirugía laparoendoscópica de puerto único durante la cirugía endoscópica uniportal (EUS) está directamente relacionado con el efecto fulcro y la competencia física (entre cirujanos y a través del puerto). En un intento de separar el sistema de imagen del dispositivo cirugía laparoendoscópica de puerto único, se describe un proyecto escalonado (3 modelos) para ayudar a superar estos inconvenientes. ZEUS1, un nuevo dispositivo de sistema de imagen sin RTE para EUS, fue probado con éxito en cirugía EUS en un modelo porcino. Aún en investigación, ZEUS2 se convierte en una estructura cableada que sirve de base a una microcámara endoscópica intracavitaria con funciones de giro, inclinación y zoom. ZEUS3 contempla el aro interno del protector de herida quirúrgica como una corona de microcámaras. Son necesarios nuevos estudios para materializar los modelos ZEUS2 y ZEUS3 y confirmar su eficacia y seguridad.
Article
Background/purpose: The purpose of this systematic review by the American Pediatric Surgical Cancer Committee was to summarize evidence from the current medical literature regarding fertility restoration and hormone replacement for female children and adolescents treated with gonadotoxic treatments. Methods: Using PRISMA guidelines, questions were addressed by searching Medline, Cochrane, Embase Central and National clearing house databases using relevant search terms. Eligible studies included those that addressed ovarian tissue cryopreservation (OTC), oocyte harvest, ovarian transposition, and ovarian tissue auto-transplantation for females under the age of 20. Four reviewers independently screened studies for eligibility, extracted data and assessed the risk of bias. Study outcomes were summarized in a narrative synthesis. Results: Two thousand two hundred seventy-six studies were identified by database search and manual review and 2185 were eliminated based on defined exclusion criteria. Ninety-one studies served as the basis for the systematic review. There were 1019 patients who underwent OTC with ages ranging from 0.4 to 20.4 years old, with 298 under the age of 13. Twenty patients aged 13-20 years old underwent successful oocyte harvest. Thirty-seven children underwent ovarian transposition as a means of fertility preservation. Eighteen patients underwent auto-transplantation of thawed ovarian cortical tissue that was harvested before the age of 21 years resulting in 10 live births. Conclusions: Clinically accepted and experimental fertility preservation options such as OTC, oocyte cryopreservation, and ovarian transposition are available to females aged 20 years and younger who are at risk for premature ovarian insufficiency and infertility due to gonadotoxic treatments. There is a large cohort of pediatric-aged patients, with a wide variety of diagnoses and treatments, who have undergone fertility preservation. Currently, fertility and hormone restoration experience for patients who were 20- years of age or younger at the time of fertility preservation remains limited. Level of evidence: IV.
Article
Study question: How effective is ovarian tissue cryopreservation (OTC)? Summary answer: In our cohort of patients who underwent OTC, premature ovarian failure (POF) rates, return rates and pregnancy rates after autotransplantation were 31.5, 4.4 and 33%, respectively. What is known already: OTC for fertility purposes has been performed for >20 years now. With over 86 live births reported worldwide and success rates of ~30% after autotransplantation of frozen-thawed ovarian cortex, the procedure should no longer be considered experimental. However, very few publications report the efficacy of this procedure. Study design, size, duration: Cases of ovarian tissue cryobanking for fertility preservation performed between 1997 and 2013 in a single institution were reviewed by analysis of the cryobank database and a prospective questionnaire sent out in March 2015. Participants/materials, setting, methods: There were 545 patients who underwent OTC during this period. The analysis included indications for OTC, survival rates, ovarian function and spontaneous pregnancies after OTC, come-back rates for ovarian tissue transplantation, pregnancy rates after transplantation, and complication and satisfaction rates. Main results and the role of chance: OTC was performed in this cohort at a mean age of 22.3 ± 8.8 years for oncological indications (79%), benign gynecological pathologies (17.5%) and genetic risks of POF (3.5%). Of the 545 patients, 29% were under 18 years of age at the time of OTC and 15% were prepubertal. While 10% of patients died from their disease, 21 patients (3.9%) underwent autotransplantation, 7 of whom delivered a healthy baby, yielding a post-transplantation live birth rate of 33%. Of 451 patients who were sent the questionnaire, 143 agreed to respond (32%). Nevertheless, ovarian function could not be evaluated in 36% of those who answered. Of 92 evaluable patients, 31.5% were menopausal and 68.5% showed persistent ovarian function. Of 52 women who attempted to conceive naturally, 37 were successful (71%). Among 140 patients who answered the questionnaire, 96% were satisfied with the procedure and only 1 major complication (intra-abdominal hemorrhage) was encountered. Among all the patients, 12% have donated their ovarian cortex for research purposes or have had it destroyed. Limitations, reasons for caution: The questionnaire participation rate (32%), limited follow-up (mean 7.6 ± 3.5 years) and use of only clinical criteria for evaluation of ovarian function made it difficult to accurately assess the risk of POF and efficiency of OTC. Wider implications of the findings: Our findings confirm a 30% pregnancy rate after ovarian cortex autotransplantation but also stress the difficulties of evaluating the real efficacy of OTC. Study funding/competing interest(s): No funding was sought for this study and none of the authors have any conflict of interest. Trial registration number: ClinicalTrials.gov Registration ID: CRYOFONOV01.