Telomerase activity, telomere length, and the euploidy rate of human embryos.

BACKGROUND: Telomeres maintain chromosome stability, while telomerase counteracts their progressive shortening. Telomere length varies between cell types, with leukocyte telomere length (LTL) decreasing with age. Reduced telomerase activity has been linked to reproductive issues in females, such as low pregnancy rates and premature ovarian failure, with recent studies indicating correlations between telomere length in granulosa cells and IVF outcomes. OBJECTIVES: The study aims to explore the relationship between telomere length, telomerase activity, and euploid blastocyst rate in infertile women undergoing IVF/ICSI PGT-A cycles. METHODS: This prospective study involves 108 patients undergoing controlled ovarian stimulation and PGT-A. Telomere length and telomerase activity were measured in peripheral mononuclear cells and granulosa cells (GC), respectively. RESULTS: The telomere repeat copy number to single gene copy number ratio (T/S) results respectively 0.6 ± 0.8 in leukocytes and 0.7 ± 0.9 in GC. An inverse relationship was found between LTL and the patient's age (p < .01). A higher aneuploid rate was noticed in patients with short LTL, with no differences in ovarian reserve markers (p = .15), number of oocytes retrieved (p = .33), and number of MII (p = 0.42). No significant association was noticed between telomere length in GC and patients' age (p = 0.95), in ovarian reserve markers (p = 0.32), number of oocytes retrieved (p = .58), number of MII (p = .74) and aneuploidy rate (p = .65). CONCLUSION: LTL shows a significant inverse correlation with patient age and higher aneuploidy rates. Telomere length in GCs does not correlate with patient age or reproductive outcomes, indicating differential telomere dynamics between leukocytes and granulosa cells.

Totally intracorporeal colorectal anastomosis (TICA) versus classical mini-laparotomy for specimen extraction, after segmental bowel resection for deep endometriosis: a single-center experience.

PURPOSE: The surgical approach to bowel endometriosis is still unclear. The aim of the study is to compare TICA to conventional specimen extractions and extra-abdominal insertion of the anvil in terms of both complications and functional outcomes. METHODS: This is a single-center, observational, retrospective study conducted enrolling symptomatic women underwent laparoscopic excision of deep endometriosis with segmental bowel resection between September 2019 and June 2022. Women who underwent TICA were compared to classical technique (CT) in terms of intra- and postoperative complications, moreover, functional outcomes relating to the pelvic organs were assessed using validated questionnaires [Knowles-Eccersley-Scott-Symptom (KESS) questionnaire and Gastro-Intestinal Quality of Life Index (GIQLI)] for bowel function. Pain symptoms were assessed using Visual Analogue Scale (VAS) scores. RESULTS: The sample included 64 women. TICA was performed on 31.2% (n = 20) of the women, whereas CT was used on 68.8% (n = 44). None of the patients experienced rectovaginal, vesicovaginal, ureteral or vesical fistula, or ureteral stenosis and uroperitoneum, and in no cases was it necessary to reoperate. Regarding the two surgical approaches, no significant difference was observed in terms of complications. As concerns pain symptoms at 6-month follow-up evaluations on stratified data, except for dysuria, all VAS scales reported showed significant reductions between median values, for both surgery interventions. As well, significant improvements were further observed in KESS scores and overall GIQLI. Only the GIQLI evaluation was significantly smaller in the TICA group compared to CT after the 6-month follow-up. CONCLUSIONS: We did not find any significant differences in terms of intra- or post-operative complications compared TICA and CT, but only a slight improvement in the Gastro-Intestinal Quality of Life Index in patients who underwent the CT compared to the TICA technique.

PGT-M, a Useful Tool to Manage the Lynch Syndrome Transmission.

Lynch syndrome is one of the most common hereditary cancer sensitivity syndromes and is caused by autosomal-dominant germline mutations in DNA mismatch repair genes. In patients affected by this syndrome, pre-implantation genetic testing for monogenic disorders (PGT-M) could be the elective technique used to prevent the transmission of this hereditary syndrome to offspring. Notably, despite the severity of the condition, some authors have observed a markedly lower demand for PGT-M in these patients compared to those with other hereditary conditions. A 34-year-old woman with a medical history of Lynch syndrome associated with endometrial cancer came to the Villa Mafalda fertility center in Rome in order to conceive a healthy baby. In a pre-implantation genetic testing for aneuploidy (PGT-A) + PGT-M cycle, eight blastocysts were formed. Six out of eight blastocysts were affected by the same mother syndrome. One of the other two was aneuploid and the other one was a mosaic embryo, which resulted in a healthy pregnancy. The aim of this report is to emphasize the importance of a multidisciplinary approach to managing patients with this condition. In vitro fertilization (IVF), specifically PGT-M, is a tool that allow patients to conceive biological children with lower risk of inheriting the disease.

Mininvasive Cytoreduction Surgery plus HIPEC for Epithelial Ovarian Cancer: A Systematic Review.

Background and objectives: The Gold-Standard treatment for Advanced Epithelial Ovarian Cancer remains cytoreductive surgery followed by systemic chemotherapy. Surgery can be performed either by an open or minimally invasive approach (MIS), although the former remains the most widely used approach. Recently, Van Driel et al. proved that adding 100 mg/m2 of Cisplatin in Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at Interval Debulking Surgery (IDS) gives a disease-free survival (DFS) advantage. Similarly, Gueli-Alletti et al. demonstrated how the MIS approach is feasible and safe in IDS. Moreover, Petrillo et al. reported pharmacokinetic profiles with a higher chemotherapy concentration in patients undergoing HIPEC after MIS compared with the open approach. Therefore, the following review investigates the oncological and clinical safety consequences of the association between MIS and HIPEC. Methods: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the PubMed and Scopus databases in April 2022. Studies containing data about oncological and safety outcomes were included. We registered the Review to the PROSPERO site for meta-analysis with protocol number CRD42022329503. Results: Five studies fulfilled inclusion criteria. 42 patients were included in the review from three different Gynecological Oncological referral centers. The systematic review highlighted a Recurrence Rate ranging between 0 and 100%, with a 3-year Platinum-Free Survival between 10 and 70%. The most common HIPEC drug was Cisplatin, used at concentrations between 75 and 100 mg/m2 and at an average temperature of 42 °C, for 60 to 90 min. Only 1 Acute Kidney Insufficiency has been reported. Conclusions: The scarcity of clinical trials focusing on a direct comparison between MIS and the open approach followed by HIPEC in EOC treatment does not make it possible to identify an oncological advantage between these two techniques. However, the safety profiles shown are highly reassuring.

The number and rate of euploid blastocysts in women undergoing IVF/ICSI cycles are strongly dependent on ovarian reserve and female age.

STUDY QUESTION: Can the possibility of having at least one euploid blastocyst for embryo transfer and the total number of euploid blastocysts be predicted for couples before they enter the IVF programme? SUMMARY ANSWER: Ovarian reserve and female age are the most important predictors of having at least one euploid blastocyst and the total number of euploid blastocysts. WHAT IS KNOWN ALREADY: The blastocyst euploidy rate among women undergoing ART has already been shown to significantly decrease with increasing female age, and the total number of euploid embryos is dependent on the blastocyst cohort size. However, the vast majority of published studies are based on retrospective analysis of data. STUDY DESIGN, SIZE, DURATION: This prospective analysis included 847 consecutively enrolled couples approaching their first preimplantation genetic testing for aneuploidies (PGT-A) cycle between 2017 and 2020. Only couples for whom ejaculated sperm was available and women with a BMI of <35 kg/m2 were included in the study. Only the first cycle was included for each patient. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at an IVF centre where, for all patients, the planned treatment was to obtain embryos at the blastocyst stage for the PGT-A programme. The impact of the following covariates was investigated: a woman's serum AMH level, age, height, weight and BMI and a man's age, height, weight, BMI, sperm volume and sperm motility and morphology. The analysis was performed with a machine learning (ML) approach. Models were fit on the training set (677 patients) and their predictive performance was then evaluated on the test set (170 patients). MAIN RESULTS AND ROLE OF CHANCE: After ovarian stimulation and oocyte insemination, 40.1% of couples had at least one blastocyst available for the PGT-A. Of 1068 blastocysts analysed, 33.6% were euploid. Two distinct ML models were fit: one for the probability of having at least one euploid blastocyst and one for the number of euploid blastocysts obtained. In the training set of patients, the variable importance plots of both models indicated that AMH and the woman's age are by far the most important predictors. Specifically, a positive association between the outcome and AMH and a negative association between the outcome and female age appeared. Gradient-boosted modelling offers a greater predictive performance than generalized additive models (GAMs). LIMITATIONS, REASONS FOR CAUTION: The study was performed based on data from a single centre. While this provides a robust set of data with a constant ART process and laboratory practice, the model might be suitable only for the evaluated population, which may limit the generalization of the model to other populations. WIDER IMPLICATIONS OF THE FINDINGS: ML models indicate that for couples entering the IVF/PGT-A programme, ovarian reserve, which is known to vary with age, is the most important predictor of having at least one euploid embryo. According to the GAM, the probability of a 30-year-old woman having at least one euploid embryo is 28% or 47% if her AMH level is 1 or 3 ng/ml, respectively; if the woman is 40 years old, this probability is 18% with an AMH of 1 ng/ml and 30% with an AMH of 3 ng/ml. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by an unrestricted grant from Gedeon Richter. The authors declared no conflict of interests. TRIAL REGISTRATION NUMBER: N/A.

Which factors influence the success rate of egg donation programmes with imported vitrified oocytes?

RESEARCH QUESTION: Which factors influence the success rate of egg donation programmes with imported vitrified oocytes? DESIGN: Observational longitudinal cohort study of 431 oocyte donation cycles conducted between January 2015 and February 2019. A total of 398 couples underwent an IVF cycle with imported donated vitrified eggs. All consecutive oocyte donation cycles conducted at the Centre for Reproductive Medicine of the European Hospital in Rome, Italy, were included. RESULTS: A univariable analysis was conducted. Among the demographic characteristics studied, body mass index (BMI) was significantly able to influence outcome. In 49% of unsuccessful cycles, men were overweight, compared with 39.4% in cycles with a positive beta-HCG test (P = 0.03). The relationship between female or donor BMI and treatment outcome, however, was not statistically significant. The day on which the embryo is transferred affects the outcome of the cycle: transferring on day 2 versus day 5 reduces the probability of clinical pregnancy. The relationship between male BMI classes and semen parameters was studied: obese men have a significantly lower sperm concentration than normal-weight men (P = 0.006 after Bonferroni correction). No statistically significant differences were found in semen volume (P = 0.722), sperm morphology (P = 0.100) and motility (P = 0.179) in obese men compared with normal weight men. CONCLUSION: In addition to the number of oocytes available after warming, male BMI, semen characteristics and blastocyst transfer are critical parameters able to influence the reproductive outcomes of egg donation programmes with imported vitrified oocytes.

COVID-19 - compliant - IVF: reorganized clinical practice taking into account the pandemic.

PURPOSE: The need for protective measures during the COVID-19 pandemic forced assisted reproduction centers to adopt new protocols in order to reduce the risk of infection for patients and staff. A COVID-19 Compliant IVF (in vitro fertilization) program based on the use of follitropin delta to induce ovarian stimulation and fixed protocol with GnRH (Gonadotropin-Releasing Hormone) antagonists was applied to demonstrate the efficacy of this program in reducing the necessity of patients to be present within the clinic while maintaining the expected success rate. METHODS: The program was applied to 100 patients (women aged between 20 and 40 years, at their first IVF cycle): pretreatment assessment was carried out via video conference and clinical documentations were sent by email. Ovarian stimulation was based on doses of Follitropin delta selected on the basis of body weight and serum AMH (Anti-Müllerian Hormone). The study population was then compared with historical controls to assess the percentage of patients receiving fresh embryo transfer. Finally, a questionnaire was proposed to assess patient satisfaction. RESULTS: The ovarian stimulation protocol with a fixed dose of follitropin delta led to an optimal ovarian response (8-14 oocytes) in 54% of the women included in the study. The rate of hyper response was 15% and was significantly lower that what reported in the control group (26.8%, p < .05). The good control of ovarian response to stimulation is the reason for the large percentage of cycles associated with fresh embryo transfer (84%, n 84/100). The rate of fresh embryo transfer was significantly higher that what reported for the control population (68.5%, p < .05). In 40 out of 84 patients, blastocysts were available for the fresh embryo transfer procedure. Eighty-five percent (89/100) of survey responders reported being extremely satisfied with the simplified approach to the IVF cycle because of reduced number of visits, easy management of working hours and reduction in travel costs. CONCLUSIONS: The use of follitropin delta and fixed protocol with GnRH antagonist in COVID-19 - Compliant IVF program is associated to a low percentage of patients developing excessive ovarian response compared to conventional strategy and a very good level of patient satisfaction. Beyond the pandemic, the new approach to ovarian stimulation, modern technologies and telemedicine could play a key role in bridging the gap between different geographic areas and could offer advantages such as increased accessibility, cost saving and patient satisfaction.

Comparison of euploidy rates of blastocysts in women treated with progestins or GnRH antagonist to prevent the luteinizing hormone surge during ovarian stimulation.

STUDY QUESTION: Does the prevalence of euploid blastocysts differ between patients treated with progestin primed ovarian stimulation (PPOS) and those treated with conventional ovarian stimulation? SUMMARY ANSWER: The numbers of blastocysts and euploid blastocysts per patient and the number of euploid embryos per injected oocyte are similar for patients undergoing progestin-primed ovarian stimulation and for those undergoing conventional ovarian stimulation with GnRH antagonist. WHAT IS KNOWN ALREADY: New approaches to ovarian stimulation have been developed based on the use of drugs administrable by mouth instead of via injections. Attention has been dedicated to progestins to block the LH surge. Previous data regarding the number of oocytes retrieved and the number of good-quality embryos generated in PPOS have demonstrated similar outcomes when compared to conventional ovarian stimulation, even if some concerns regarding the quality of embryos have been advanced. STUDY DESIGN, SIZE, DURATION: This is a prospective non-inferiority age-matched case-control study. In a period of 6 months, a total of 785 blastocysts from 1867 injected oocytes obtained from 192 patients were available for analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile women undergoing IVF and preimplanation genetic testing (PGT) cycles were included. Forty-eight patients were treated with PPOS, and for each of them three age-matched historical controls (n = 144) treated with a GnRH antagonist protocol were selected. PGT was performed according to next-generation sequencing technology. MAIN RESULTS AND THE ROLE OF CHANCE: Basal characteristics were similar in the two groups; a substantial similarity of the main outcome measures in the two treatment groups has also been found. The rate of formation of euploid blastocysts per oocyte was 21% in both the two treatment groups. The percentage of patients with euploid embryos and the total number of euploid blastocysts per patient (median and interquartile range, IQR) in the PPOS group were 38.7 (25.5-52.9) and 2 (1.3-3.1), respectively. These figures were not significantly different in women treated with the GnRH antagonist protocol i.e. 42 (28-53.8) and 2.1 (1.3-2.9), respectively. LIMITATIONS, REASONS FOR CAUTION: This was a case-control study which may limit the reliability of the main findings. WIDER IMPLICATIONS OF THE FINDINGS: Our results encourage the use of PPOS, especially for oocyte donation, for fertility preservation and for patients in which total freezing of embryos is foreseen, for those expected to be high responders or candidates for preimplantation genetic testing. However, studies aiming to investigate the effect of PPOS on the live birth rate are warranted. STUDY FUNDING/COMPETING INTEREST(S): None.

How 1 h of abstinence improves sperm quality and increases embryo euploidy rate after PGT-A: a study on 106 sibling biopsied blastocysts.

PURPOSE: The aim of our study was to evaluate the influence of different ejaculatory abstinence time frames (several days versus 1 h) on semen parameters, blastocysts ploidy rate, and clinical results in assisted reproduction cycles on sibling oocytes. METHODS: This is a prospective study including 22 preimplantation genetic testing for aneuploidy (PGT-A) cycles performed between November 2015 and December 2018. Male partners with oligoastenoteratozoospermia produced two semen samples on the day of oocyte retrieval: the first one after several days of abstinence and the second, 1 h after the first one. Oocytes from each patient were divided into two groups: those in group 1 were injected with spermatozoa from the first ejaculate (N = 121) and oocytes in group 2 with spermatozoa from the second one (N = 144). Outcomes of aniline blue test, fertilization, blastocyst formation, ploidy rates, and clinical results were compared between the two groups. RESULTS: Semen volume resulted lower in the second sperm retrieval. Sperm concentration, motility, and morphology were similar in the two groups. A total of 106 blasotcysts were biospied. Higher blastocyst euploidy rates resulted in group 2 (43.6%) than in group 1 (27.5%). A higher percentage of mature chromatine was observed in group 2. CONCLUSION: Using spermatozoa from samples with a shorter abstinence could be a simple method to select higher quality spermatozoa, reducing aneuploidy rate in blastocysts. Prospective randomized controlled trials should be performed to confirm the potential advantage of using semen samples with short abstinence period to improve the outcome of assisted reproduction cycles.

The aging male: Relationship between male age, sperm quality and sperm DNA damage in an unselected population of 3124 men attending the fertility centre for the first time.

OBJECTIVE: the aim of our study was to put forward insights to treat any possible correlation among sperm quality, sperm DNA damage and male age as they may have fertility implications for men who choose to delay fatherhood. MATERIALS AND METHODS: Our study is a non-interventional retrospective analysis of 3124 semen samples from patients that were investigated for the conventional semen parameters. Tunel test assay was set up for the evaluation of the sperm DNA fragmentation index (DFI). We applied the Kappa index to compare both the 1999 and the 2010 World Health Organization (WHO) reference criteria to evaluate the competence of such semen parameters categorization during the standard routine of our laboratory. RESULTS: With regards to our findings, it is possible to underline a significant relationship between aging and semen volume (p = 0.001), motility (p = 0.009), semen viscosity (p < 0.003) and sperm DNA damage (p < 0.009). We found a trend when focusing on the semen concentration (p = 0.05). The analysis of sperm morphology did not show any influence with advancing age (p = 0.606). When comparing both the 1999 and the 2010 WHO scales we found no accordance in the appraisal of sperm morphology but a very good one in the evaluation of the other parameters. CONCLUSIONS: Conventional semen analysis represents the opportunity to draw up a proxy insight on the male fertility status even if semen quality can only indirectly assess the probability of pregnancy. Several studies have verified a decay in the male reproductive system, sperm quality and fertility with advancing age although the reported results are not yet conclusive. Our results substantially agree with those findings outlined in the literature. Moreover we find that the discrepancy between the two WHO reference scales would eventually lead to an improper diagnosis of infertility.

Influence of human sperm origin, testicular or ejaculated, on embryo morphokinetic development.

In this retrospective observational study (October 2014 - July 2016), the impact of sperm origin on embryo morphokinetics and on clinical outcomes after intracytoplasmic sperm injection was evaluated. The developmental kinetics of embryos obtained either with testicular sperm (40 cycles; testicular sperm group) or with thawed donor sperm (26 cycles; donor sperm group) was analysed up to day-3 of culture with a time-lapse incubation system. In the testicular sperm group, all patients were affected by nonobstructive azoospermia. The timing of second polar body extrusion (IIPB), and the time to reach the 4-cells (t4) and 9-cells (t9) stages, differed significantly between the two groups: the IIPB extrusion and t4 were anticipated, whereas t9 was retarded in the testicular sperm group. We hypothesise that a different sperm maturation grade may influence the timing of embryo development: an early paternal effect of testicular sperm could be manifested as an anticipation in the IIPB extrusion and in the time for reaching the 4-cells stage. Conversely, a later paternal effect could be visible as a retardation in the timing at which the embryo reaches the 9-cells stage. Interestingly, clinical outcomes did not differ between the two groups except the implantation rate which was significantly increased in the donor sperm group.

Analysis of MYO-Inositol effect on spermatozoa motility, in hyper viscous ejaculates and in patients with grades II and III varicocele.

The goal of this study is to evaluate MYOInositol effects on spermatozoa motility, in patients' ejaculates with severe varicocele or hyper viscosity. The study included normal viscosity ejaculate from 30 patients affected by varicocele and hyper viscosity ejaculate from 33 patients without any testicular pathologies. All selected samples showed sperm concentration > 2 million/ml and progressive motility < 32%. In both groups, the pellet obtained after centrifugation in buffered medium, was divided in two aliquots, both incubated for 15 minutes at 37°C: one with MYO-Inositol and the other one, as control, only in phosphate buffered saline (PBS). Afterwards, the sperm progressive motility was assessed using Computer Assisted Sperm Analysis (CASA system). Incubation with MYO-Inositol improved sperm progressive motility in high viscosity samples compared to control group (38.9% ± 3.0 vs 24.35% ± 2.41, respectively; p ≤ 0.0001). Conversely, no statistically significant difference was observed in total sperm progressive motility in varicocele samples compared with control group (22.7% ± 2.07 vs 26.7% ± 3.31, respectively; p = 0.085). The MYO-Inositol positive effect on spermatozoa motility may depend on the type of sperm damage: heavy structural and biochemical defects which typically affects patients with varicocele are not restored by Inositol. On the contrary, MYOInositol is able to improve sperm motility in semen samples with high viscosity, since those samples show no substantial structural sperm defects.

Anatomical-based classification of dorsolateral parametrectomy for deep endometriosis. Correlation with surgical complications and functional outcomes: A single- center prospective study.

OBJECTIVE: To evaluate complication rate and functional outcomes of nerve-sparing parametrectomy for deep endometriosis in relation to the extension of the surgical procedure, based on recognizable anatomical landmarks. METHODS: This was a prospective single-center study including all patients undergoing parametrectomy for deep endometriosis from September 2020 to June 2023 at our tertiary center. Dorsolateral parametrectomies were divided into parametrectomies medial to the presacral fascia and cranial to the medial rectal artery (superficial parametrectomy), and parametrectomies in which one of the two landmarks was overcome during the surgical procedure, leading to the excision of tissue lateral to the presacral fascia (deep parametrectomy type 1, or DP1) or caudal to the medial rectal artery (DP2). Finally, we used the hypogastric fascia as landmark to define type 3 deep parametrectomy (DP3), when the procedure was deeply lateral to the fascia. RESULTS: Bladder voiding deficit occurred in 9.7% of cases, with higher rates in DP2 (20.8%) and DP3 (30%) groups. Regarding postoperative gastrointestinal function, our data showed a significant improvement over time in all groups, with the exception of DP2; instead an improvement in postoperative bladder function was only shown in DP3. Parametrectomy was not associated with a simultaneous improvement in sexual function expressed with the female sexual function index, in any of the four groups. CONCLUSION: Our classification constitutes a concrete approach for comparing, in a standardized way, the complications and functional outcomes of parametrectomy, which, even if carried out by expert surgeons, demonstrates a non-negligible rate of bladder voiding deficit.

Vascular- and nerve-sparing bowel resection for deep endometriosis: A retrospective single-center study.

OBJECTIVE: Surgical management of bowel endometriosis is still controversial. Recently, many authors have pointed out the potential benefits of preserving the superior rectal artery, thus ensuring better perfusion of the anastomosis. The aim of this study was to evaluate the complication rate and functional outcomes of a bowel resection technique for deep endometriosis (DE) involving a nerve- and vascular-sparing approach. METHODS: A single-center retrospective study was conducted by enrolling patients who underwent segmental resection of the rectus sigmoid for DE in our department between September 2019 and April 2022. Intraoperative and postoperative complications were recorded for each woman, and functional outcomes relating to the pelvic organs were assessed using validated questionnaires (Knowles-Eccersley-Scott-Symptom [KESS] questionnaire and Gastro-Intestinal Quality of Life Index [GIQLI] for bowel function, Bristol Female Lower Urinary Tract Symptoms [BFLUTS] for urinary function, and Female Sexual Function Index [FSFI] for sexual function). These were evaluated preoperatively and postoperatively after 6 months from surgery. RESULTS: Sixty-one patients were enrolled. No patients had Clavien-Dindo grade 3 or 4 complications, there were no rectovaginal fistulas or ureteral lesions, and in no cases was it necessary to reoperate. Temporary bladder voiding deficits were reported in 8.2% of patients, which were treated with self-catheterizations, always resolving within 45 days of surgery. Gastrointestinal function evaluated by KESS and GIQLI improved significantly after surgery, whereas sexual function appeared to worsen, although without reaching the level of statistically significant validity. CONCLUSION: Our vascular- and nerve-sparing segmental bowel resection technique for DE had a low intraoperative and postoperative complication rate and produced an improvement in gastrointestinal function after surgery.

Preoperative diagnosis of ureteral medial deviations secondary to deep endometriosis using transvaginal ultrasound examinations: Can we predict the need for ureterolysis during laparoscopic surgery?

OBJECTIVE: To evaluate ureteral involvement using transvaginal sonography (TVS) regarding the distortion of the course of the ureters caused by deep endometriosis (DE), which can facilitate predicting the need for ureterolysis during surgery, even in the absence of ureteral stenosis or dilatation. METHODS: This is a single-center, observational, retrospective pilot study of 88 consecutive patients who later underwent surgery for DE that used ultrasound preoperative diagnosis of ureteral medial deviation of one or both ureters between January 2019 and January 2022. At TVS, the course of the ureter was considered medialized if, in longitudinal and transversal section, any distance was detectable between the ureter and the cervix at the point where the ureter crosses the uterine artery. The primary end point was to determine sensitivity, specificity, and positive and negative predictive values of "ureteral medial deviation" diagnosed using TVS, in order to predict the need for ureterolysis. RESULTS: Our series included 88 women with a median age of 39 (interquartile range 33-43) years. Ureteral medialization showed a relatively low false-positive rate (10.9%), with a specificity of 89.1% (95% confidence interval [CI] 81.4%-96.7%) and a sensitivity of 86.6% (95% CI 80.3%-92.9%), along with a high positive predictive value of 93.3% (95% CI 88.4%-98.1%), and a lower negative predictive value of 79.1% (95% CI 69.8%-88.5%), respectively. CONCLUSIONS: This study introduced a new ultrasound sign with a high degree of accuracy to predict ureterolysis and this may have positive implications in the management and surgical planning of patients with ureteral endometriosis.

Laparoscopic ureteroneocystostomy and round ligament bladder hitching for ureteral stenosis in parametrial deep endometriosis: Our tips for a tension-free anastomosis.

OBJECTIVE: To investigate the feasibility and the efficacy of laparoscopic ureteroneocystostomy with round ligament bladder hitching. METHODS: This is a monocentric retrospective study. Enrolled patients affected by deep endometriosis underwent laparoscopic nerve-sparing parametrectomy and monolateral ureteroneocystostomy with bladder suspension to the round ligament. Perioperative and postoperative outcomes were collected, as well as urinary and pain symptoms before and after surgery. RESULTS: Laparoscopic ureteroneocystostomy with round ligament bladder hitching was performed in nine women. The most frequent postoperative complication was post-voiding urinary retention (22.2%). No ureteral fistula or stenosis of the anastomosis was reported. CONCLUSION: In selected cases of ureteral resection and reimplantation, performing a round ligament bladder hitching allowed us to overcome the ureteral gap. This is a safe and feasible procedure to ensure stability of the anastomosis and avoid the possible disadvantages of the "standard" psoas hitch procedure.

Are ureterolysis for deep endometriosis really all the same? An anatomical classification proposal for ureterolysis: A single-center experience.

OBJECTIVE: Ureteral endometriosis has an incidence of 0.1% to 1%. The type of surgery required is either conservative (ureterolysis) or radical treatment, depending on the degree of ureter infiltration. The incidence of intraoperative and postoperative complications is heterogeneous. Thus, the aim of the current study was to propose a classification of ureterolysis based on the anatomical structure of the ureter and differing complication rates with procedures. METHODS: A total of 139 ureterolysis procedures were included in the study. Patients were divided into three groups according to the depth of ureterolysis required. Differences were recorded across the three types of ureterolysis in terms of intraoperative and postoperative complications. RESULTS: The incidence of ureteral fistula was reported in 0.7% of cases, with postoperative ureteral stenosis in 2% of type 2 ureterolysis. In the case of type 3 ureterolysis, after conservative procedures, 52.9% of patients required an ureteroneocystostomy to solve the ureteral stenosis. CONCLUSION: The risk of ureteral injury and ureteroneocystostomy after conservative procedures appears to be associated with type 3 ureterolysis, probably due to excessive devascularization, secondary to the incision of adventitia. Obviously, these data should be confirmed through a prospective study of a larger number, but our proposed classification can provide the basis for making data from future studies more comparable.

The complex relationship between female age and embryo euploidy.

BACKGROUND: Female age is the strongest predictor of embryo chromosomal abnormalities and has a nonlinear relationship with the blastocyst euploidy rate: with advancing age there is an acceleration in the reduction of blastocyst euploidy. Aneuploidy was found to significantly increase with maternal age from 30% in embryos from young women to 70% in women older than 40 years old. The association seems mainly due to chromosomal abnormalities occurring in the oocyte. We aimed to elaborate a model for the blastocyst euploid rate for patients undergoing in-vitro fertilization/intra cytoplasmic sperm injection (IVF/ICSI) cycles using advanced machine learning techniques. METHODS: This was a retrospective analysis of IVF/ICSI cycles performed from 2014 to 2016. In total, data of 3879 blastocysts were collected for the analysis. Patients underwent PGT-Aneuploidy analysis (PGT-A) at the Center for Reproductive Medicine of European Hospital (Rome, Italy) have been included in the analysis. The method involved whole-genome amplification followed by array comparative genome hybridization. To model the rate of euploid blastocysts, the data were split into a train set (used to fit and calibrate the models) and a test set (used to assess models' predictive performance). Three different models were calibrated: a classical linear regression; a gradient boosted tree (GBT) machine learning model; a model belonging to the generalized additive models (GAM). RESULTS: The present study confirms that female age, which is the strongest predictor of embryo chromosomal abnormalities, and blastocyst euploidy rate have a nonlinear relationship, well depicted by the GBT and the GAM models. According to this model, the rate of reduction in the percentage of euploid blastocysts increases with age: the yearly relative variation is -10% at the age of 37 and -30% at the age of 45. Other factors including male age, female and male Body Mass Index, fertilization rate and ovarian reserve may only marginally impact on embryo euploidy rate. CONCLUSIONS: Female age is the strongest predictor of embryo chromosomal abnormalities and has a non-linear relationship with the blastocyst euploidy rate. Other factors related to both the male and female subjects may only minimally affect this outcome.

The clinical use of time-lapse in human-assisted reproduction.

A major challenge in the assisted reproduction laboratory is to set up reproducible and efficient criteria to identify the embryo with the highest developmental potential. Over the years, several methods have been used worldwide with this purpose. Initially, standard morphology assessment was the only available strategy. It is now universally recognized that besides being a very subjective embryo selection strategy, morphology evaluation alone has a very poor prognostic value. More recently, the availability of time-lapse incubators allowed a continuous monitoring of human embryo development. This technology has spread quickly and many fertility clinics over the world produced a remarkable amount of data. To date, however, a general consensus on which variables, or combination of variables, should play a central role in embryo selection is still lacking. Many confounding factors, concerning both patient features and clinical and biological procedures, have been observed to influence embryo development. In addition, several studies have reported unexpected positive outcomes, even in the presence of abnormal developmental criteria. While it does not seem that time-lapse technology is ready to entirely replace the more invasive preimplantation genetic testing in identifying the embryo with the highest implantation potential, it is certainly true that its application is rapidly growing, becoming progressively more accurate. Studies involving artificial intelligence and deep-learning models as well as combining morphokinetic with other non-invasive markers of embryo development, are currently ongoing, raising hopes for its successful applicability for clinical purpose in the near future. The present review mainly focuses on data published starting from the first decade of 2000, when time-lapse technology was introduced as a routine clinical practice in the infertility centers.