Basal FSH values are positively associated with aneuploidy incidence in pre-advanced maternal age (AMA) but not in AMA patients.

PURPOSE: To assess the impact of maternal age on the association between maternal basal FSH and aneuploidy. METHODS: A retrospective study including data from 1749 blastocysts diagnosed as euploid or aneuploid by PGT-A (preimplantation genetic testing for aneuploidy). Aneuploidy incidence was compared between embryos from mothers with high vs. low basal FSH levels (above and below the group median, respectively) in total, pre-AMA (advanced maternal age; < 35 years, 198 embryos) and AMA (≥ 35 years, 1551 embryos) patient groups, separately. To control for the interference of potentially confounding variables, the association between aneuploidy and high basal FSH levels was assessed by multivariate logistic analysis in overall, pre-AMA and AMA patient groups. RESULTS: Overall, aneuploidy rate was 9% higher (p = 0.02) in embryos from patients with high basal FSH (63.7%) compared to those with low basal FSH (58.4%). In the pre-AMA subgroup, aneuploidy incidence was 35% higher (p = 0.04) in embryos from patients with high basal FSH (53.5%) compared to those with low basal FSH (39.4%). Differently, aneuploidy occurrence did not vary between embryos from AMA patients with low (61.0%) and high (64.8%) basal FSH (p = 0.12). The multivariate analysis revealed that, in pre-AMA embryos, the association between aneuploidy occurrence and high basal FSH is independent of potential confounding variables (p = 0.04). CONCLUSION: Maternal basal FSH values are associated with embryo aneuploidy in pre-AMA but not in AMA patients. The present findings suggest that basal FSH is a useful parameter to assess aneuploidy risk in pre-AMA patients and reinforce the hypothesis that excessive FSH signalling can predispose to oocyte meiotic errors.

Association between Physical Activity and Menstrual Cycle Disorders in Young Athletes.

Our study aims to evaluate clinical predictors of menstrual cycle disorders in female athletes who compete in running disciplines. This is a prospective observational study. Women were recruited between January and May 2022. Fifty-three patients were enrolled and completed a questionnaire about menstrual cycle, physical activity, and food habit characteristics. Of the women in our population, 39.6% had menstrual irregularities and reported a significantly higher number of kilometers run per week (67 vs. 35, p:0.02). The number of kilometers run per week was associated with menstrual irregularities (for 10 km, OR 1.35; IC95% 1.05-1.73; p: 0.02) after adjusting for BMI, age, level of sport and caloric intake. The variable of "km run per week" appeared as a diagnostic indicator of irregular menstrual cycle with statistical significance (AUC ROC curve 0.71, IC95% 0.54-0.86, p-value=0.01) and the cut-off of 65 km run per week is a good indicator of the presence of irregular menstrual cycle (sensitivity (SE) and specificity (SP) of 55% and 81.48%). Menstrual cycle disorders are very frequent in female athletes, and the variable of km run per week may play a role in screening endurance athletes at high risk for these disorders.

Survival after sentinel node biopsy alone in early-stage cervical cancer: a systematic review.

OBJECTIVE: To assess the oncologic outcomes of sentinel lymph node biopsy alone as part of surgical management in patients with early-stage cervical cancer. METHODS: A systematic search of the literature was performed following the PRISMA checklist. MEDLINE (through PubMed), EMBASE, and Scopus databases were searched from June 1991 to May 2023. Studies of women with early-stage cervical cancer International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA-IIA, of any age or histology, and articles only in English language were included. After the removal of duplicates, only articles including sentinel node mapping alone compared with full pelvic lymphadenectomy were retained. RESULTS: Four studies with a total of 2226 patients were included. Among these, 354 (15.9%) underwent sentinel lymph node biopsy alone. A total of 2210 (99.2%) patients had FIGO 2009 stage I disease and 1514 (68%) patients had squamous cell carcinoma. Median body mass index was 25.5 kg/m2 (range 23.5-27). Lymph vascular space invasion was present in 633 patients (34%) who underwent full lymphadenectomy and in 78 patients (22%) who underwent sentinel node biopsy alone. The results of the survival analysis showed that there was no significant difference in the 3-year progression-free survival rates of patients who underwent either sentinel biopsy alone or lymphadenectomy. Three-year recurrence-free survival was 93.1% (95% CI 28.3% to 64.7%) for patients who underwent sentinel node biopsy alone and 92.5% (95% CI 39.0% to 53.4%) for patients who underwent sentinel node biopsy and lymphadenectomy (p=0.773). CONCLUSIONS: In patients with early-stage cervical cancer, performing sentinel lymph node biopsy alone compared with pelvic lymphadenectomy does not appear to independently confer a higher risk or recurrence.

The impact of oocyte central granularity on ICSI practice: developmental competence of dysmorphic and morphologically normal companion oocytes.

PURPOSE: To assess the effects of oocyte central granularity and its underlying endocrine environment on developmental competence of dysmorphic and morphologically normal oocytes. METHODS: Retrospective cohort study including 1,082 patients undergoing autologous ICSI cycles. Of these, 211 patients provided 602 oocytes with central granularity (CG) and 427 morphologically normal cycle companion oocytes (NCG). The remaining 871 patients provided only morphologically normal oocytes in cycles not yielding dysmorphic oocytes (N). Patient profile associated with CG was characterized, and fertilization rates, early morphokinetics and live birth rates were compared between N, CG and NCG groups. Patient characteristics associated with implantation and delivery performance of CG-derived embryos were assessed. RESULTS: CG was associated with higher maternal age, basal FSH concentrations and total FSH dose, but with lower circulating AMH (p ≤ 0.035). Fertilization rates were reduced and early morphokinetic parameters were delayed in CG (p < 0.025) and NCG (p < 0.05) groups as compared to the N group. Embryos derived from CG oocytes achieved a markedly lower live birth rate (14.9%) as compared to those derived from NCG (36.8%; p = 0.03) and N oocytes (29.8%; p = 0.002). The negative relationship between CG and live birth was confirmed by a multivariate analysis controlling for potential confounders (OR:2.59, IC:1.27-5.31; P = 0.009). Implantation and delivery rates following transfers of CG-derived embryos were inversely associated with maternal age. CONCLUSION: CG oocytes, but not their morphologically normal cycle companions, have severely compromised developmental competence. Maternal age should be a key parameter in deciding whether or not to utilize CG oocytes in ICSI cycles.

Association between treatment-related lymphopenia and survival in glioblastoma patients following postoperative chemoradiotherapy.

PURPOSE: Our study investigated the association between treatment-related lymphopenia and overall survival (OS) in a series of glioblastoma (GBM) patients. We also explored clinical and dosimetric predictors of lymphocytes depletion. METHODS: Between 2015 and 2019, 64 patients were treated at the same institution with postoperative chemoradiotherapy. Peripheral lymphocyte count (PLC) data and dose-volume histogram parameters were collected. Radiotherapy (RT) schedule consisted in standard total dose of 60 Gy in 30 daily fractions, with concomitant and adjuvant temozolomide (TMZ). Posttreatment acute absolute lymphopenia (nadir AAL) was calculated as a PLC lower than 1.0â€¯× 103/mm3. Acute relative lymphopenia (ARL) was expressed by the nadir-PLC/baseline-PLC ratio < 0.5. Nadir-PLC was the lowest PLC registered between the end of RT and the first month of follow-up. Survival rates were estimated with Kaplan-Meier curves. Clinical and dosimetric variables related to AAL/ARL and OS were identified by univariate and multivariate analyses. RESULTS: A total of 57 patients were eligible and included in the analyses. The median PLC was significantly decreased following chemoradiotherapy (2180/mm3 vs 900/mm3). Median OS was 16 months (range 5-55 months), with no significant difference between patients who developed nadir AAL and those who did not (16 months vs 16.5 months; p = 0.304). When considering ARL vs non-ARL, median OS was 14 months vs 26 months (p = 0.013), respectively. In multivariate Cox regression only age, sex, extent of surgery, access to adjuvant chemotherapy and brain D98% were independently associated with OS. CONCLUSION: Although iatrogenic immunosuppression could be associated with inferior clinical outcomes, our data show that treatment-related lymphopenia does not adversely affect GBM survival. Prospective studies are required to confirm these findings.

Tubal histopathological abnormalities in BRCA1/2 mutation carriers undergoing prophylactic salpingo-oophorectomy: a case-control study.

OBJECTIVE: To describe tubal histopathological abnormalities in women with germline BRCA1/2 mutations and in controls. METHODS: Consecutive women with BRCA1/2 mutations undergoing bilateral salpingo-oophorectomy between 2010 and 2020 in two centers (San Gerardo Hospital, Monza and San Matteo Hospital, Pavia) were considered in this analysis and compared with controls who had the same surgical procedure for benign conditions. Frequency of p53 signature, serous tubal intraepithelial carcinoma, and high-grade serous ovarian cancer were compared between the two groups. RESULTS: A total of 194 women with pathogenic BRCA1/2 mutations underwent prophylactic salpingo-oophorectomy. Of these, 138 women (71%) had a completely negative histological examination, while in 56 (29%) patients an ovarian or tubal alteration was reported. Among controls, 84% of patients had a p53wt signature, while 16% had a p53 signature. There was no difference in the frequency of a p53 signature between cases and controls; however, women with BRCA1/2 mutations were more likely to have pre-malignant or invasive alterations of tubal or ovarian epithelium (p=0.015). Among mutation carriers, older age both at genetic testing and at surgery was associated with an increased risk of having malignancies (OR=1.07, p=0.006 and OR=1.08, p=0.004, respectively). The risk of malignancy seems to be increased in patients with a familial history of high-grade serous ovarian cancer. Previous therapy with tamoxifen was significantly more frequent in patients with malignant lesions (40.0% vs 21.3%, p=0.006). CONCLUSION: We found that a p53 signature is a frequent finding both in BRCA1/2 mutation carriers and in controls, while pre-invasive and invasive lesions are more frequent in BRCA1/2 mutation carriers. Genetic and clinical characteristics are likely to affect the progression to malignancy.

Maternal age affects the relationship of basal FSH and anti-Müllerian hormone concentrations with post-ICSI/IVF live birth.

RESEARCH QUESTION: Does the association of basal FSH and anti-Müllerian hormone (AMH) concentrations with post-IVF/intracytoplasmic sperm injection (ICSI) live birth change with maternal age? DESIGN: A total of 2003 IVF/ICSI patients were stratified according to basal FSH/AMH in concordant favourable (CF; AMH >1 ng/ml and FSH ≤10 IU/l), concordant unfavourable (CU; AMH ≤1 ng/ml and FSH >10 IU/l), discordant with favourable AMH (DFA) and discordant with favourable FSH (DFF) groups, as well as according to age in pre-advanced maternal age (pre-AMA; <35), AMA-1 (≥35, ≤37), AMA-2 (>37, ≤40) and AMA-3 (>40). IVF/ICSI outcomes were compared among CF, CU, DFA and DFF groups, and the association of basal FSH and AMH concentrations with live birth was tested by univariate and multivariate analysis in total, pre-AMA and AMA groups, separately. RESULTS: Different outcome patterns were observed in discordant AMH/FSH groups from different age categories; favourable basal FSH concentrations were associated with higher delivery rates in pre-AMA patients, but with lower delivery rates in AMA groups. Within pre-AMA patients, DFF patients presented higher delivery rates but lower oocyte yield compared with DFA patients. In the univariate analysis, favourable AMH (P < 0.02) and oocyte yield (P < 0.002) were positively associated with live birth in all AMA groups. The multivariate analysis revealed that favourable basal FSH, but not AMH or oocyte yield, is associated with live birth in pre-AMA patients independently of other variables (P = 0.012). CONCLUSIONS: The relationship of basal FSH and AMH with IVF/ICSI success changes with maternal age; basal FSH better reflects clinical outcomes probably determined by oocyte quality in pre-AMA patients, while AMH better suits AMA patients.

Circummaxillary Sutures in Patients With Apert, Crouzon, and Pfeiffer Syndromes Compared to Nonsyndromic Children: Growth, Orthodontic, and Surgical Implications.

OBJECTIVE: To evaluate patency of circummaxillary sutures in children with Apert, Crouzon, and Pfeiffer Syndromes and to compare it to a nonsyndromic matched control group. DESIGN: Case-control study. SETTING: Tertiary care public hospital. MATERIALS AND METHODS: Thirty-eight computed tomography (CT) scans of patients affected by syndromic craniofacial synostosis (13 patients with Apert syndrome, 20 patients with Crouzon syndrome, and 5 patients with Pfeiffer syndrome), average age 5 ± 2.8 years, range 1.9 to 12 years, were compared to age- and sex-matched control CTs of 38 nonsyndromic children. Computed tomography scans of the study group had to be performed prior to any midfacial surgery. MAIN OUTCOME MEASURES: Midpalatal suture, zygomaticomaxillary sutures, and pterigomaxillary sutures were evaluated and scored. RESULTS: The syndromic group showed a significant earlier ossification of all sutures compared to the nonsyndromic group. Significant differences were already present in early childhood and continued through adolescence. CONCLUSIONS: Based on the differences in terms of maxillary sutural ossification identified, midfacial hypoplasia does not seem to be only secondary to premature cranial base ossification, but also to primary synostosis of facial sutures, thus providing new insights into the pathogenesis of midface deficiency in children with craniofacial-synostosis. Care should be taken when planning any maxillary orthopedics, such as expansion or maxillary protraction, given the high frequency of early fusion of circummaxillary sutures.

Long-term follow-up of late maxillary orthopedic advancement with the Liou-Alternate rapid maxillary expansion-constriction technique in patients with skeletal Class III malocclusion.

INTRODUCTION: The objective of this study was to evaluate short and long-term results of the application of the alternate rapid maxillary expansion/constriction (Alt-RAMEC) technique in patients with skeletal Class III malocclusion. METHODS: Forty-two white patients were consecutively treated with the Alt-RAMEC technique. The average age of the patients was 12.7 ± 1.6 years (range, 9.4-15.9 years) before protraction. The average age at long-term follow-up was 19.4 ± 2.8 years (range, 17.2-26.9 years). A sample of nontreated patients with Class III malocclusion from the archives of orthognatic surgery in our hospital was used as a control group. The initial records were matched for sex, the severity of Class III malocclusion, and age (mean, 12.1 ± 1.4 years; range, 9.7-14.1 years) with the old records available in the archive. The control sample had records presurgery (mean, 19.8 ± 2.2 years; range, 16.6-21.6 years). RESULTS: The sagittal advancement of A-point, after the application of the technique, was 5.43 ± 2.71 mm. Some mandibular dentoalveolar adaptation was noted. The position of the maxilla was stable in the long term. In contrast, the control group showed limited growth at the maxillary level during the long-term follow-up period. CONCLUSIONS: Our results showed that the Alt-RAMEC technique, performed at the correct time, with a double-hinged expander, followed by Class III spring or elastic traction, 24 h/d, allows for satisfactory maxillary protraction, with stable long-term results. The comparison with a sample of matched nontreated patients with Class III malocclusion allowed to suggest the positive effect of the treatment on the maxillary position vs the natural evolution of the Class III skeletal discrepancy.

Italian electronic personal assessment questionnaire-pelvic floor (I.ePAQ-PF): Psychometric validation of the urinary section.

AIM: Tools for remote clinical assessment have become increasingly important. Patient-reported outcome questionnaires are increasingly being considered as the keystones of pelvic floor disorder assessment. An innovative English language multidisciplinary electronic Personal Assessment Questionnaire (ePAQ-PF) was psychometrically validated in 2006. A certified Italian version (I.ePAQ-PF) has been recently made available by the Italian Society of Urodynamics. In this study, we aimed to test the psychometric properties to validate the urinary dimension of the I.ePAQ-PF. METHODS: Women complaining of lower urinary tract symptoms were enrolled. After providing informed consent, women filled in the I.ePAQ-PF via a dedicated touch-screen display (T0), together with concurrent questionnaires: International Consultation on Incontinence Questionnaire-Short form, Urgency Severity Scale, Urogenital Distress Inventory, and Patient Global Impression of Improvement. Cronbach's α and Spearman's correlation coefficients were adopted (validity). A test-retest was performed in 47 cases (reliability), and the intraclass correlation coefficient (ICC) was analyzed. I.ePAQ-PF was also administered after treatment (T1) and compared with baseline data via a Wilcoxon's test and Cohen's effect-size tests (responsiveness). RESULTS: Ninety-three women were included. Internal consistency was confirmed (Cronbach's α >.7). A Spearman's correlation test showed a good correlation (>0.6) between I.ePAQ-PF and conceptually similar questionnaires. I.ePAQ-PF seems to be highly reproducible in all domains (ICC >0.86). The questionnaire scored significantly differently (Wilcoxon test P < .003) in all domains after the treatment. Responsiveness was further confirmed by Cohen's effect size of more than 30%. CONCLUSIONS: The Italian ePAQ-PF (urinary domain) fully satisfies the psychometric properties of validity, reliability, and responsiveness and is ready for clinical application in Italian clinical settings.

Two ultrastaging protocols for the detection of lymph node metastases in early-stage cervical and endometrial cancers.

OBJECTIVE: To date, there is no universal consensus on which is the optimal ultrastaging protocol for sentinel lymph node (SLN) evaluation in gynecologic malignancies. To estimate the impact of different ultrastaging methods of SLNs on the detection of patients with nodal metastases in early-stage cervical and endometrial cancers and to describe the incidence of low-volume metastases between two ultrastaging protocols. METHODS: We retrospectively compared two ultrastaging protocols (ultrastaging-A vs ultrastaging-B) in patients with clinical stage I endometrial cancer or FIGO stage IA-IB1 cervical cancer who underwent primary surgery including SLN biopsy from October 2010 to December 2017 in our institution. The histologic subtypes and grades of the tumors were evaluated according to WHO criteria. Only SLNs underwent ultrastaging, while other lymph nodes were sectioned and examined by routine hematoxylin and eosin (H&E). RESULTS: Overall 224 patients were reviewed (159 endometrial cancer and 65 cervical cancer). Lymph node involvement was noted in 15% of patients with endometrial cancer (24/159): 24% of patients (9/38) with the ultrastaging protocol A and 12% (15/121) with the ultrastaging protocol B (p=0.08); while for cervical cancer, SLN metastasis was detected in 14% of patients (9/65): 22% (4/18) in ultrastaging-A and 11% (5/47) in ultrastaging-B (p=0.20). Overall, macrometastasis and low-volume metastases were 50% and 50% for endometrial cancer and 78% and 22% for cervical cancer. Median size of nodal metastasis was 2 (range 0.9-8.5) mm for the ultrastaging-A and 1.2 (range 0.4-2.6) mm for the ultrastaging-B protocol in endometrial cancer (p=0.25); 4 (range 2.5-9.8) mm for ultrastaging-A and 4.4 (range 0.3-7.8) mm for ultrastaging-B protocol in cervical cancer (p=0.64). CONCLUSION: In endometrial or cervical cancer patients, the incidence of SLN metastasis was not different between the two different types of ultrastaging protocol.

Standard ultra-staging compared to one-step nucleic acid amplification for the detection of sentinel lymph node metastasis in endometrial cancer patients: a retrospective cohort comparison.

INTRODUCTION: The objective of this study was to compared standard ultra-staging (SU) with one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis in women with apparent uterine-confined endometrial cancer. METHODS: All women underwent SLN identification with complete surgical staging. All SLNs were cut perpendicular to the long axis and two adjacent 5 µm sections were cut at each of two levels 50 µm apart. At each level, one slide was stained with hematoxylin and eosin and the other with immunohistochemistry using the AE1/AE3 anti-cytokeratin antibody, as well as one negative control slide for a total of five slides per block. For OSNA analysis, the 2 mm sections of the lymph nodes were homogenized to form a lysate. The lysate was then centrifuged and inserted into the RD 100i instrument where the isothermal amplification of CK19 mRNA was executed. RESULTS: Of the 396 patients included in the retrospective analysis, 214 were in the SU group, and 182 in the OSNA group. Overall 869 SLNs were identified (490 SU, 379 OSNA). Sixty patients exhibited SLN metastasis (34 SU, 26 OSNA). Macrometastasis, micrometastases, and isolated tumor cells (ITC) were 5.1%, 4.1%, and 0.2%, respectively, in the US group, and 2.4%, 6.3%, and 0.1%, respectively, in the OSNA group (p=0.022). CONCLUSIONS: The OSNA assay detected a higher rate of micrometastasis and a lower rate of macrometastasis and ITC when compared with SU. The clinical and prognostic impact of ITC is debatable and controversial. Further studies are needed to clarify the respective roles of the OSNA and SU methods, and the possible role of ITC in the prognosis of patients with apparent early-stage endometrial cancer.

Added diagnostic value of respiratory-gated 4D 18F-FDG PET/CT in the detection of liver lesions: a multicenter study.

PURPOSE: The aim of the present study was to evaluate the added diagnostic value of respiratory-gated 4D18F-FDG PET/CT in liver lesion detection and characterization in a European multicenter retrospective study. METHODS: Fifty-six oncological patients (29 males and 27 females, mean age, 61.2 ± 11.2 years) from five European centers, submitted to standard 3D-PET/CT and liver 4D-PET/CT were retrospectively evaluated. Based on visual analysis, liver PET/CT findings were scored as positive, negative, or equivocal both in 3D and 4D PET/CT. The impact of 4D-PET/CT on the confidence in classifying liver lesions was assessed. PET/CT findings were compared to histology and clinical follow-up as standard reference and diagnostic accuracy was calculated for both techniques. At semi-quantitative analysis, SUVmax was calculated for each detected lesion in 3D and 4D-PET/CT. RESULTS: Overall, 72 liver lesions were considered for the analysis. Based on visual analysis in 3D-PET/CT, 32/72 (44.4%) lesions were considered positive, 21/72 (29.2%) negative, and 19/72 (26.4%) equivocal, while in 4D-PET/CT 48/72 (66.7%) lesions were defined positive, 23/72 (31.9%) negative, and 1/72 (1.4%) equivocal. 4D-PET/CT findings increased the confidence in lesion definition in 37/72 lesions (51.4%). Considering 3D equivocal lesions as positive, sensitivity, specificity, and accuracy were 88.9, 70.0, and 83.1%, respectively, while the same figures were 67.7, 90.0, and 73.8% if 3D equivocal findings were included as negative. 4D-PET/CT sensitivity, specificity, and accuracy were 97.8, 90.0, and 95.4%, respectively, considering equivocal lesions as positive and 95.6, 90.0, and 93.8% considering equivocal lesions as negative. The SUVmax of the liver lesions in 4D-PET (mean ± SD, 6.9 ± 3.2) was significantly higher (p < 0.001) than SUVmax in 3D-PET (mean ± SD, 5.2 ± 2.3). CONCLUSIONS: Respiratory-gated PET/CT technique is a valuable clinical tool in diagnosing liver lesions, reducing 3D undetermined findings, improving diagnostic accuracy, and confidence in reporting. 4D-PET/CT also improved the quantification of SUVmax of liver lesions.

Lymph node evaluation in high-risk early stage endometrial cancer: A multi-institutional retrospective analysis comparing the sentinel lymph node (SLN) algorithm and SLN with selective lymphadenectomy.

OBJECTIVE: The aim of this study was to determine the impact of the sentinel lymph node mapping algorithm (SLN-A) on the staging in high-risk endometrial cancer (EC) compared to SLN plus selective lymphadenectomy (S-LND). METHODS: We retrospectively analyzed the database from a multicenter collaboration that included women with high risk features who underwent primary surgical staging. RESULTS: One-hundred and seventy-one women were identified (171), 66 in the SLN-A and 105 in the S-LND group, respectively. Pelvic LD was performed on 115 patients (67.2%) and aortic dissection was performed in 54/105 of the women in the S-LND group (51%). The 5-year comparison did not show a significant difference in the strategy adopted for nodal staging, regarding disease-free survival (DFS) [HR: 0.82; 95% CI 0.53-1.28; p = 0.390]. CONCLUSIONS: In this study focusing on women with EC in the HR groups, we did not find a difference in the 5-year DFS when comparing the SLN-A strategy with S-LND. The SLN strategy did not seem to compromise the prognosis of patients with a higher risk of recurrence.

Laparoscopic Sentinel Node Mapping in Cervical and Endometrial Malignancies: A Case-Control Study Comparing Two Near-Infrared Fluorescence Systems.

STUDY OBJECTIVE: The goal of this study was to evaluate the intraoperative and perioperative surgical outcomes of 2 different florescence systems commonly used for sentinel lymph node (SLN) mapping in women with early-stage cervical cancer or endometrial cancer. DESIGN: Case-control study (Canadian Task Force classification II-2). SETTING: The Gynecology Oncology Surgical Unit of the San Gerardo Hospital, Italy. PATIENTS: Thirty-four consecutive women with early stage-cervical cancer (stage IA-1B1) or apparent confined stage I endometrial cancer were included in the study. INTERVENTIONS: Between October 2016 and May 2017, 34 patients underwent laparoscopic surgery with SLN mapping using indocyanine green dye: 22 women were mapped with the Storz 1S system (Karl Storz Endoscopy, Tuttlingen, Germany; Group A), whereas 12 women underwent planned surgery with the Novadaq PinPoint system (Novadaq, Mississauga, Ontario, Canada; Group B). MEASUREMENT AND MAIN RESULTS: We compared the surgical and perioperative outcomes of Group A and Group B. Patients in Group B had a shorter duration of the SLN mapping time than those in Group A (p = .0003). The median number of SLNs removed was 2 (range, 0-5) in Group A and 2 (range, 1-3) in Group B (p = .501). Bilateral mapping was 77.3% in Group A and 83.3% in Group B (p = .334), respectively. No differences were recorded in terms of body mass index, length of hospital stay, type of tumor, bilateral mapping, or number of lymph nodes removed. Body mass index was found to have no impact on the duration of the mapping (p = .353). CONCLUSION: From our preliminary experience we can conclude that both fluorescence systems are valid and applicable for SLN detection in the case of early-stage cervical or endometrial cancer. The PinPoint system seems to allow surgeons easier and faster identification of the SLNs, particularly in endometrial cancer patients.

Real-Time Fluorescent Sentinel Lymph Node Mapping with Indocyanine Green in Women with Previous Conization Undergoing Laparoscopic Surgery for Early Invasive Cervical Cancer: Comparison with Radiotracer ± Blue Dye.

STUDY OBJECTIVE: To evaluate the added value of the fluorescence dye indocyanine green (ICG) for sentinel lymph node (SLN) mapping in women with cervical cancer who had undergone previous conization (stage 1A-1B1) by comparing ICG versus Tc99m radiotracer + blue dye (BD). DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: Two European academic medical centers, San Gerardo Hospital, Italy and University of Berne, Switzerland. PATIENTS: Sixty-five women with early stage (IA-IB1) cervical cancer who had undergone previous conization and who underwent SLN mapping with Tc99m ± BD (n = 23) or ICG (n = 42) followed by pelvic lymphadenectomy and fertility-sparing surgery or hysterectomy were included in this analysis. INTERVENTION: Overall detection rate and bilateral SLN mapping rates of ICG were compared with those obtained using the standard Tc99m radiocolloid and BD. MEASUREMENT AND MAIN RESULTS: Overall, 220 SLNs were detected. The median number of SLNs per patient in the Tc99m ± BD group was 2 (range, 1-5) and in the ICG group, 3 (range, 2-15). The detection rate of SLNs was 95.7% in Tc99m ± BD group and 100% in the ICG group (p = .354). The women injected with ICG had a higher rate of bilateral mapping of the SLNs as compared with the Tc99m ± BD group (95.2% vs 69.6%, p = .016%). Only 12% of the patients (8/65) presented metastatic nodes, 2 in the Tc99m ± BD group and 6 in the ICG group. CONCLUSION: In early-stage cervical cancer patients conization had no significant impact on the SLN detection rate using both techniques (ICG and radiotracer ± BD). In this scenario a higher bilateral mapping rate was confirmed using the fluorescent dye ICG rather than the standard techniques.

Dysmorphic patterns are associated with cytoskeletal alterations in human oocytes.

Study question: Are specific morphological anomalies in human mature oocytes, as revealed by transmitted light microscopy, associated with intrinsic damage to the meiotic spindle and actin cytoskeleton? Summary answer: Aggregates of smooth endoplasmic reticulum (SER) and domains of centrally localized granular cytoplasm (GC) reflect intrinsic damage to the oocyte cytoskeleton, namely alterations in spindle size, chromosome misalignment and cortical actin disorganization. What is known already: In preparation for ICSI, oocytes are often selected for use in treatment by morphological criteria, but the rationale and implications of this practice are controversial. Very little information is available on the relationship between oocyte morphology and intrinsic cellular characteristics, such as the actin cytoskeleton, meiotic spindle and chromosome alignment. Study design, size, duration: A total of 170 metaphase II (MII) oocytes were donated by consenting IVF patients and analysed; 62 were classified as morphologically normal (control), 54 had SER clusters and 54 had centrally localized GC. Participants/materials, setting, methods: Supernumerary oocytes were fixed within 3 h from recovery and stained for tubulin, chromatin and actin. Spindles were analysed for 1D and 2D characteristics by high-performance confocal microscopy. Chromosomes were classified as scattered or aligned and the conformation and intensity of cortical actin was evaluated. Main results and the role of chance: In comparison with control oocytes, both SER and GC oocytes showed greater spindle length (P = 0.033 and 0.003, respectively) and GC oocytes also showed greater spindle width (P= 0.049) and area (P= 0.036). Control and SER oocytes had statistically comparable rates of chromosome displacement from the metaphase plate, unlike GC oocytes where chromosome displacement occurred at higher rate (P = 0.013). In situations where a complete Z-stack was reconstructed from a polar angle, chromosome disposition was classified as being normal when two sets of concentric arrays were visible. Based on these parameters, the proportions of oocytes with normal chromosomal arrangement or partial/total disarrangement was not statistically different between control and SER oocytes. Conversely, in GC oocytes, chromosome disarrangement was higher (P = 0.002). All control oocytes displayed a continuous meshwork of suboolemmal actin, which appeared as an uninterrupted ring in thin optical sections. In contrast, in SER and  GC groups, integrity of suboolemmal actin was observed in only 66.7 and 42.9% of oocytes, respectively (P = 0.0001). Large scale data: N/A. Limitations reason for caution: Only two of several known oocyte dysmorphisms were investigated, while oocyte quality was assessed only by cytoskeletal criteria. Wider implications of the findings: This study represents a significant step toward a more objective assessment of oocyte morphology, offering information that can assist embryologists to make a more aware and rationally founded decision on whether, and with what possible implications, oocytes with certain dysmorphic characters should be used for treatment or discarded. More generally, it also demonstrates that morphometric parameters of the cytoskeleton and chromosome organization can be used as biomarkers of oocyte quality. Study funding and competing interest(s): This study was funded by Biogenesi Reproductive Medicine Centre (Monza, Italy). All authors declare no conflict of interests.

The impact on survival of two different staging strategies in apparent early stage endometrial cancer comparing sentinel lymph nodes mapping algorithm and selective lymphadenectomy: An Italian retrospective analysis of two reference centers.

OBJECTIVE: The role of lymphadenectomy in endometrial cancer is still uncertain. We aimed to evaluate the survival outcomes of two different strategies in apparent uterine confined disease by comparing sentinel lymph node (SLN) mapping and selective lymphadenectomy (LD). METHODS: We retrospectively reviewed women with preoperative stage I endometrial cancer underwent surgical staging with either SLN mapping, or LD in two Italian centers. RESULTS: Eight hundred and two women underwent surgical staging for preoperative stage I endometrial cancer were revised (145 Monza; 657 Rome). All patients underwent peritoneal washing, simple hysterectomy with bilateral salpingo-oophorectomy and nodal staging including SLN mapping, or LD. Overall 8229 lymph nodes were removed (1595 in Monza, 6634 in Rome). Pelvic lymphadenectomy was performed in 33.1% and 52.4% in Monza and Rome, respectively (p<0.001). Patients with positive pelvic LN were 16.7% and 7.3%, in SLN and LD groups, respectively (p=0.002). Disease-free survival (DFS) curves did not showed a statistically significant difference between centers and strategies adopted (SLN mapping, LD, SLN+LD) with a HR of 0.87 (95% CI 0.63-2.16; p=0.475). CONCLUSIONS: Survival outcomes were similar for both strategies. The SLN strategy allowed to identify a higher rate of stage IIIC1 disease even with a lower median number of lymph node removed in SLN group. Applying a SLN algorithm does not impair the prognosis of endometrial cancer patients. The clinical impact and management of low volume metastasis in high-risk patients should be further clarify.

Indocyanine Green versus Radiotracer with or without Blue Dye for Sentinel Lymph Node Mapping in Stage >IB1 Cervical Cancer (>2 cm).

STUDY OBJECTIVE: To compare sentinel lymph node (SLN) mapping in women with cervical cancer stage >IB1 (tumor size >2 cm) using indocyanine green (ICG) versus the standard technique using radioisotope technetium 99m radiocolloid (Tc99m) radiotracer with or without blue dye. DESIGN: European multicenter, retrospective observational study (Canadian Task Force classification II-2). SETTING: Four academic medical centers. PATIENTS: Ninety-five women with stage IB1 cervical cancer (>2 cm) who underwent SLN mapping with Tc99m with or without blue dye or ICG and radical hysterectomy. INTERVENTION: The detection rate and bilateral mapping rate were compared between ICG and standard Tc99m radiotracer with or without blue dye. Lymphadenectomy was performed, and the false-negative rate was assessed. MEASUREMENTS AND MAIN RESULTS: Forty-seven patients underwent SLN mapping with Tc99m with or without blue dye, and 48 did so with ICG. All patients underwent radical hysterectomy with or without bilateral salpingo-oophorectomy between 2008 and 2016. The overall detection rate of SLN mapping was 91.5% for Tc99m with or without blue dye and 100% for ICG. A 91.7% rate of bilateral migration was achieved for ICG, significantly higher than the 66% obtained with Tc99m with or without blue dye (p = .025). Nine of the 23 SLN-positive patients (39.1%) were diagnosed exclusively as a result of the ultrastaging used to identify micrometastases or isolated tumor cells only. CONCLUSIONS: In advanced cervical cancer (stage IB1 >2 cm), the detection rate and bilateral migration rate on real-time fluorescent SLN mapping were higher with ICG than with Tc99m radiotracer with or without blue dye. SLN mapping and ultrastaging can provide additional information for nodal staging in advanced cervical cancer. In this setting, ICG is a promising tool for mapping, appearing less affected by higher disease stage compared with traditional methods.

Retrospective analysis of treatments with recombinant FSH and recombinant LH versus human menopausal gonadotropin in women with reduced ovarian reserve.

PURPOSES: The aim of this study is to determine whether a clinical advantage is gained with use of LH in combination with FSH or as a component of human menopausal gonadotropin (hMG) to achieve optimal ovarian stimulation. METHODS: In this study, we compared retrospectively two regimens, r-FSH/r-LH and hMG, for the treatment of women with reduced ovarian reserve, identified as subjects with antral follicle count (AFC) < 11 and AMH ≤ 1.1 ng/ml. RESULTS: Overall, the clinical pregnancy per started cycle was higher in the r-FSH/r-LH group (12.5 vs. 8.1%, P < 0.02), while implantation (11.1 vs. 9.5%) and miscarriage rates (29.9 vs. 35.9%) were comparable. Data were further analysed performing separate comparisons in subpopulations with different ranges of AFC, i.e. < 4, 4-6 and 7-10. Major differences between the two regimens were observed in women with AFC < 4. In this subpopulation, not only was the clinical pregnancies per started cycle higher in the r-FSH/r-LH group (10.2 vs. 1.5%, P < 0.01), but also implantation was significantly higher (13.0 vs. 2.8%, P < 0.02). CONCLUSIONS: A r-FSH/r-LH regimen appears to be beneficial for the treatment of women with extremely poor ovarian reserve. It should be considered however that, being retrospective, this study is affected by obvious limitations, such as post-treatment patient selection criteria and absence of randomisation.