Association between oocyte donors' or recipients' body mass index and clinical outcomes after first single blastocyst transfers-the uterus is the most affected.

OBJECTIVE: To assess whether high body mass index (BMI) in either oocyte donors or recipients is associated with poorer outcomes after the first single blastocyst transfer. DESIGN: Retrospective study including 1,394 first blastocyst single embryo transfers (SETs) conducted by 1,394 recipients during oocyte donation cycles with the gametes retrieved from 1,394 women (January 2019-July 2021). Four BMI clusters were defined for both donors and recipients (underweight: <18.5 kg; normal weight: 18.5-24.9 kg; overweight: 25-29.9 kg; and obese: ≥30 kg). SETTING: Network of private IVF centers. PATIENTS: A total of 1,394 recipients aged 42.4 ± 4.0 and with a BMI of 23.2 ± 3.8 kg/m2, and 1,394 donors aged 26.1 ± 4.2 and with a BMI of 21.9 ± 2.5 kg/m2. INTERVENTION: All oocytes were vitrified at 2 egg banks and warmed at 8 in vitro fertilization clinics that were part of the same network. Intracytoplasmic sperm injection, blastocyst culture, and either fresh or vitrified-warmed SETs were conducted. Putative confounders were investigated, and the data were adjusted through regression analyses. MAIN OUTCOME MEASURES: The primary outcome was the live birth rate (LBR) per SET according to donors' and/or recipients' BMI. The main secondary outcome was the miscarriage rate (<22 gestational weeks) per clinical pregnancy. RESULTS: The LBR per blastocyst SET showed no significant association with donors' BMI. Regarding recipients' BMI, instead, the multivariate odds ratio was significant in obese vs. normal-weight recipients (0.58, 95% confidence interval, 0.37-0.91). The miscarriage rate per clinical pregnancy was also significantly associated with recipients' obesity, with a multivariate odds ratio of 2.31 (95% confidence interval, 1.18-4.51) vs. normal-weight patients. A generalized additive model method was used to represent the relationship between predicted LBR or miscarriage rates and donors' or recipients' BMI; it pictured a scenario where the former outcome moderately but continuously decreases with increasing recipients' BMI to then sharply decline in the BMI range of 25-35 kg/m2. The miscarriage rate, instead, increases almost linearly with respect to both donors' and recipients' increasing BMI. CONCLUSION: Obesity mostly affects the uterus, especially because of higher miscarriage rates. Yet, poorer outcomes can be appreciated already with a BMI of 25 kg/m2 in both oocyte donors and recipients. Finer markers of nutritional homeostasis are therefore desirable; recipients should be counseled about poorer expected outcomes in cases of overweight and obesity; and oocyte banks should avoid assigning oocytes from overweight donors to overweight and obese recipients.

Cryostorage management of reproductive cells and tissues in ART: status, needs, opportunities and potential new challenges.

Among the wide range of procedures performed by clinical embryologists, the cryopreservation of reproductive cells and tissues represents a fundamental task in the daily routine. Indeed, cryopreservation procedures can be considered a subspecialty of medically assisted reproductive technology (ART), having the same relevance as sperm injection or embryo biopsy for preimplantation genetic testing. However, although a great deal of care has been devoted to optimizing cryopreservation protocols, the same energy has only recently been spent on developing and implementing strategies for the safe and reliable storage and transport of reproductive specimens. Herein, we have summarized the content of the available guidelines, the risks, the needs and the future perspectives regarding the management of cryopreservation biorepositories used in ART.

Effect of rLH Supplementation during Controlled Ovarian Stimulation for IVF: Evidence from a Retrospective Analysis of 1470 Poor/Suboptimal/Normal Responders Receiving Either rFSH plus rLH or rFSH Alone.

We retrospectively studied a real-life population of 1470 women undergoing IVF, with poor/suboptimal/normal ovarian responsiveness to controlled ovarian stimulation (COS), comparing the cumulative live birth rate (cLBR) when COS was performed using rFSH alone or rFSH + rLH in a 2:1 ratio. Overall, we observed significantly higher cLBR in the rFSH alone group than in the rFSH + rLH group (29.3% vs. 22.2%, p < 0.01). However, considering only suboptimal/poor responders (n = 309), we observed comparable cLBR (15.6% vs. 15.2%, p = 0.95) despite the fact that patients receiving rFSH + rLH had significantly higher ages and worse ovarian reserve markers. The equivalent effectiveness of rFSH + rLH and rFSH alone was further confirmed after stratification according to the number of oocytes retrieved: despite basal characteristics were still in favor of rFSH alone group, the cLBR always resulted comparable. Even subdividing patients according to the POSEIDON classification, irrespective of differences in the baseline clinical characteristics in favor of FSH alone group, the cLBR resulted comparable in all subgroups. Despite the retrospective, real-life analysis, our data suggest that rLH supplementation in COS may represent a reasonable option for patients with predictable or unexpected poor/suboptimal ovarian responsiveness to FSH, those matching the Bologna criteria for poor responsiveness, and those included in the POSEIDON classification.

Are commercial warming kits interchangeable for vitrified human blastocysts? Further evidence for the adoption of a Universal Warming protocol.

PURPOSE: To study whether a new combination of different warming kits is clinically effective for vitrified human blastocysts. METHODS: This is a longitudinal cohort study analysing two hundred fifty-five blastocysts warming cycles performed between January and October 2018. Embryos were vitrified using only one brand of ready-to-use kits (Kitazato), whereas the warming procedure was performed with three of the most widely used vitrification/warming kits (Kitazato, Sage and Irvine) after patient stratification for oocyte source. The primary endpoint was survival rate, while the secondary endpoints were clinical pregnancy, live birth and miscarriage rates. RESULTS: We observed a comparable survival rate across all groups of 100% (47/47) in KK, 97.6% (49/50) in KS, 97.6% (41/42) in KI, 100% (38/38) in dKK, 100% (35/35) in dKS and 100% (43/43) in dKI. Clinical pregnancy rates were also comparable: 38.3% (18/47) in KK, 49% (24/49) in KS, 56.1% (23/ 41) in KI, 47.4% (18/38) in dKK, 31.4% (11/35) in dKS and 48.8% (21/ 43) in dKI. Finally, live birth rates were 29.8% (14/47) in KK, 36.7% (18/49) in KS, 46.3% (19/41) in KI, 36.8% (14/38) in dKK, 25.7% (9/35) in dKS and 41.9% (18/43) in dKI, showing no significant differences. CONCLUSION: This study confirmed the efficacy of applying a single warming protocol, despite what the "industry" has led us to believe, supporting the idea that it is time to proceed in the cryopreservation field and encouraging embryologists worldwide to come out and reveal that such a procedure is possible and safe.

Erratum: Positive PET in a Patient With Esophageal Leiomyoma.

This corrects the article DOI: 10.1038/ajg.2016.205.

Circulating Tumor DNA Reflects Tumor Metabolism Rather Than Tumor Burden in Chemotherapy-Naive Patients with Advanced Non-Small Cell Lung Cancer: 18F-FDG PET/CT Study.

We aimed to evaluate the relationships between circulating tumor cells (CTCs) or plasma cell-free DNA (cfDNA) on one side and a comprehensive range of 18F-FDG PET/CT-derived parameters on the other side in chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC). Methods: From a group of 79 patients included in a trial evaluating the role of pretreatment circulating tumor markers as predictors of prognosis in chemotherapy-naive patients with advanced NSCLC, we recruited all those who underwent 18F-FDG PET/CT for clinical reasons at our institution before inclusion in the trial (and thus just before chemotherapy). For each patient, a peripheral blood sample was collected at baseline for the evaluation of CTCs and cfDNA. CTCs were isolated by size using a filtration-based device and then morphologically identified and enumerated; cfDNA was isolated from plasma and quantified by a quantitative polymerase chain reaction using human telomerase reverse transcriptase. The following 18F-FDG PET/CT-derived parameters were computed: maximum diameter of the primary lesion (T), of the largest lymph node (N), and of the largest metastatic lesion (M); SUVmax; SUVmean; size-incorporated SUVmax; metabolic tumor volume; and total lesion glycolysis. All parameters were independently measured for T, N, and M. The associations among CTCs, cfDNA, and 18F-FDG PET/CT-derived parameters were evaluated by multivariate-analysis. Patients were divided into 2 groups according to the presence of either limited metastatic involvement (M1a or M1b due to extrathoracic lymph nodes only) or disseminated metastatic disease. The presence or absence of metabolically active bone lesions was also recorded for each patient, and patient subgroups were compared. Results: Thirty-seven patients recruited in the trial matched our PET-based criteria (24 men; age, 64.5 ± 8.1 y). SUVmax for the largest metastatic lesion was the only variable independently associated with baseline cfDNA levels (P = 0.016). Higher levels of cfDNA were detected in the subgroup of patients with metabolically active bone lesions (P = 0.02), but no difference was highlighted when patients with more limited metastatic disease were compared with patients with disseminated metastatic disease. Conclusion: The correlation of cfDNA levels with tumor metabolism, but not with metabolic tumor volume at regional or distant levels, suggests that cfDNA may better reflect tumor biologic behavior or aggressiveness rather than tumor burden in metastatic NSCLC.

Progressive Disintegration of Brain Networking from Normal Aging to Alzheimer Disease: Analysis of Independent Components of 18F-FDG PET Data.

Brain connectivity has been assessed in several neurodegenerative disorders investigating the mutual correlations between predetermined regions or nodes. Selective breakdown of brain networks during progression from normal aging to Alzheimer disease dementia (AD) has also been observed. Methods: We implemented independent-component analysis of 18F-FDG PET data in 5 groups of subjects with cognitive states ranging from normal aging to AD-including mild cognitive impairment (MCI) not converting or converting to AD-to disclose the spatial distribution of the independent components in each cognitive state and their accuracy in discriminating the groups. Results: We could identify spatially distinct independent components in each group, with generation of local circuits increasing proportionally to the severity of the disease. AD-specific independent components first appeared in the late-MCI stage and could discriminate converting MCI and AD from nonconverting MCI with an accuracy of 83.5%. Progressive disintegration of the intrinsic networks from normal aging to MCI to AD was inversely proportional to the conversion time. Conclusion: Independent-component analysis of 18F-FDG PET data showed a gradual disruption of functional brain connectivity with progression of cognitive decline in AD. This information might be useful as a prognostic aid for individual patients and as a surrogate biomarker in intervention trials.

Comparisons between glucose analogue 2-deoxy-2-((18)F)fluoro-D-glucose and (18)F-sodium fluoride positron emission tomography/computed tomography in breast cancer patients with bone lesions.

AIM: To compare 2-deoxy-2-((18)F)fluoro-D-glucose((18)F-FDG) and (18)F-sodium ((18)F-NaF) positron emission tomography/computed tomography (PET/CT) accuracy in breast cancer patients with clinically/radiologically suspected or known bone metastases. METHODS: A total of 45 consecutive patients with breast cancer and the presence or clinical/biochemical or radiological suspicion of bone metastatic disease underwent (18)F-FDG and (18)F-fluoride PET/CT. Imaging results were compared with histopathology when available, or clinical and radiological follow-up of at least 1 year. For each technique we calculated: Sensitivity (Se), specificity (Sp), overall accuracy, positive and negative predictive values, error rate, and Youden's index. McNemar's χ(2) test was used to test the difference in sensitivity and specificity between the two diagnostic methods. All analyses were computed on a patient basis, and then on a lesion basis, with consideration ofthe density of independent lesions on the co-registered CT (sclerotic, lytic, mixed, no-lesions) and the divergent site of disease (skull, spine, ribs, extremities, pelvis). The impact of adding (18)F-NaF PET/CT to the work-up of patients was also measured in terms of change in their management due to (18)F-NaF PET/CT findings. RESULTS: The two imaging methods of (18)F-FDG and (18)F-fluoride PET/CT were significantly different at the patient-based analysis: Accuracy was 86.7% and 84.4%, respectively (McNemar's χ(2) = 6.23, df = 1, P = 0.01). Overall, 244 bone lesions were detected in our analysis. The overall accuracy of the two methods was significantly different at lesion-based analysis (McNemar's χ(2) = 93.4, df = 1, P < 0.0001). In the lesion density-based and site-based analysis, (18)F-FDG PET/CT provided more accurate results in the detection of CT-negative metastasis (P < 0.002) and vertebral localizations (P < 0.002); (18)F-NaF PET/CT was more accurate in detecting sclerotic (P < 0.005) and rib lesions (P < 0.04). (18)F-NaF PET/CT led to a change of management in 3 of the 45 patients (6.6%) by revealing findings that were not detected at (18)F-FDG PET/CT. CONCLUSION: (18)F-FDG PET/CT is a reliable imaging tool in the detection of bone metastasis in most cases, with a diagnostic accuracy that is slightly, but significantly, superior to that of (18)F-NaF PET/CT in the general population of breast cancer patients. However, the extremely high sensitivity of (18)F-fluoride PET/CT can exploit its diagnostic potential in specific clinical settings (i.e., small CT-evident sclerotic lesions, high clinical suspicious of relapse, and negative (18)F-FDG PET and conventional imaging).

Divergent targets of glycolysis and oxidative phosphorylation result in additive effects of metformin and starvation in colon and breast cancer.

Emerging evidence demonstrates that targeting energy metabolism is a promising strategy to fight cancer. Here we show that combining metformin and short-term starvation markedly impairs metabolism and growth of colon and breast cancer. The impairment in glycolytic flux caused by starvation is enhanced by metformin through its interference with hexokinase II activity, as documented by measurement of 18F-fluorodeoxyglycose uptake. Oxidative phosphorylation is additively compromised by combined treatment: metformin virtually abolishes Complex I function; starvation determines an uncoupled status of OXPHOS and amplifies the activity of respiratory Complexes II and IV thus combining a massive ATP depletion with a significant increase in reactive oxygen species. More importantly, the combined treatment profoundly impairs cancer glucose metabolism and virtually abolishes lesion growth in experimental models of breast and colon carcinoma. Our results strongly suggest that energy metabolism is a promising target to reduce cancer progression.

Baseline and ongoing PET-derived factors predict detrimental effect or potential utility of 18F-FDG PET/CT (FDG-PET/CT) performed for surveillance in asymptomatic lymphoma patients in first remission.

PURPOSE: To identify both clinical and FDG PET/CT-derived factors predicting the occurrence of relapse, or conversely, the likelihood of false positive findings in surveillance FDG-PET/CT studies (PETsv). METHODS: The study included 149 asymptomatic patients with Hodgkin's lymphoma (HL) (n = 55) or diffuse large B cell lymphoma (DLBCL) (n = 94) in first remission. PETSv studies were performed 12, 18, 24 and 36 months thereafter. Logistic regression analysis was performed to identify clinical and imaging-derived predictors of either PET-detected relapse or false-positive (FP) results. Tested clinical variables were: 1) age, 2) HL vs. DLBCL, 3) stage of disease, 4) bulky disease, 5) previous radiotherapy. PET/CT-derived variables were: 1) maximum standardized uptake value at baseline, 2) size-incorporated maximum standardized uptake value (SIMaxSUV) at baseline, 3) positive interim PET(PET-2), 4) presence of hot spots likely to be unrelated to the disease in final PET, 5) residual non-FDG avid mass. RESULTS: Accuracy was 88 % for PETsv1, 95 % for PETsv2, 95 % for PETsv3 and 91 % for PETsv4. However, PPV was relatively low in all PETsv. Best predictors of relapse were result of interim PET, HL versus NHL type, SIMaxSUV, age ≥ 60. Best predictors of FP were previous radiotherapy and hot spots unrelated to the disease in final PET. CONCLUSIONS: The present study confirms the need of restricting the use of surveillance PET/CT to patients at high risk of relapse. Information derived from PET/CT performed at baseline (metabolic disease burden), in the course (PET2) and at the end of therapy (unrelated hot spots) can help to select high-risk patients and also to identify patients more likely to present equivocal findings at PETsv.

Allogeneic cell transplant expands bone marrow distribution by colonizing previously abandoned areas: an FDG PET/CT analysis.

Mechanisms of hematopoietic reconstitution after bone marrow (BM) transplantation remain largely unknown. We applied a computational quantification software application to hybrid 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) images to assess activity and distribution of the hematopoietic system throughout the whole skeleton of recently transplanted patients. Thirty-four patients underwent PET/CT 30 days after either adult stem cell transplantation (allogeneic cell transplantation [ACT]; n = 18) or cord blood transplantation (CBT; n = 16). Our software automatically recognized compact bone volume and trabecular bone volume (IBV) in CT slices. Within IBV, coregistered PET data were extracted to identify the active BM (ABM) from the inactive tissue. Patients were compared with 34 matched controls chosen among a published normalcy database. Whole body ABM increased in ACT and CBT when compared with controls (12.4 ± 3 and 12.8 ± 6.8 vs 8.1 ± 2.6 mL/kg of ideal body weight [IBW], P < .001). In long bones, ABM increased three- and sixfold in CBT and ACT, respectively, compared with controls (0.9 ± 0.9 and 1.7 ± 2.5 vs 0.3 ± 0.3 mL/kg IBW, P < .01). These data document an unexpected distribution of transplanted BM into previously abandoned BM sites.

Adult advanced chronic lymphocytic leukemia: computational analysis of whole-body CT documents a bone structure alteration.

PURPOSE: To assess the presence of alteration of bone structure and bone marrow metabolism in adult patients who were suspected of having advanced chronic lymphocytic leukemia (ACLL) by using a computational prognostic model that was based on computational analysis of positron emission tomography (PET)/computed tomography (CT) images. MATERIALS AND METHODS: In this retrospective study, all patients signed written informed consent as a requisite to undergo PET/CT examination. However, due to its observational nature, approval from the ethical committee was not deemed necessary. Twenty-two previously untreated chronic lymphocytic leukemia patients underwent PET/CT for disease progression. PET/CT images were analyzed by using dedicated software, capable of recognizing an external 2-pixel bone ring whose Hounsfield coefficient served as cutoff to recognize trabecular and compact bone. PET/CT data from 22 age- and sex-matched control subjects were used as comparison. All data are reported as means ± standard deviations. The Student t test, log-rank, or Cox proportional hazards model were used as appropriate, considering a difference with a P value of less than .05 as significant. RESULTS: Trabecular bone was expanded in ACLL patients and occupied a larger fraction of the skeleton with respect to control subjects (mean, 39% ± 5 [standard deviation] vs 31% ± 7; ie, 32 of 81 mL/kg of ideal body weight vs 27 of 86 mL/kg of ideal body weight, respectively; P < .001). After stratification according to median value, patients with a ratio of trabecular to skeletal bone volume of more than 37.3% showed an actuarial 2-year survival of 18%, compared with 82% for those with a ratio of less than 37.3% (P < .001), independent from age, sex, biological markers, and disease duration. CONCLUSION: These data suggest that computational assessment of skeletal alterations might represent a new window for prediction of the clinical course of the disease.

Sperm macrocephaly syndrome in a patient without AURKC mutations and with a history of recurrent miscarriage.

This paper reports a case of recurrent miscarriage in a patient affected by a variant phenotype of sperm macrocephaly syndrome (SMS). SMS is usually related to specific sperm characteristics (large head, multiple tail) and homozygous mutations in the aurora kinase C gene (AURKC). However, the present case observed large-headed spermatozoa with no flagellar abnormalities and no mutations detectable by AURKC sequencing. Furthermore, the patient had repeatedly conceived by intracytoplasmic sperm injection, but pregnancy always aborted. This study performed morphological analysis (Papanicolau staining), annexin V/propidium iodide staining, sperm chromatin structure assay (SCSA), fluorescence in-situ hybridization (FISH) and transmission electron microscopy. This study observed large-headed, mono-tailed, mono-centriolar spermatozoa characterized by abnormal chromatin and swollen mitochondria. SCSA revealed a high ratio of late apoptotic cells with fairly intact amount of DNA. The FISH analysis showed 100% disomy rate. As far as is known, this is the first study to include gene sequencing, TEM, cytogenetic analysis and sperm DNA fragmentation in a case of SMS and also to report recurrent miscarriage related to this specific condition. SMS may be associated with important abnormalities of the sperm subcellular structure and with disomy even in the absence of mutations in the AURKC coding sequence. Sperm macrocephaly syndrome (SMS) is a rare condition that affects spermatozoa and is related to infertility. It is characterized by a specific phenotype of large-headed, multi-tailed spermatozoa with an abnormal chromosomal status. A very few pregnancies have been obtained so far in SMS patients by means of IVF procedures. We present a case of SMS that differs from the classical syndrome as we observed large-headed spermatozoa without tail abnormalities. The affected patient had achieved three pregnancies following IVF, but all aborted. We carried out a detailed examination of the patient's spermatozoa - morphological, cytogenetic, DNA fragmentation and ultrastructural analysis - and we observed that his spermatozoa are characterized by a large head whose texture appears apoptotic, a single tail and a midpiece whose mitochondria appear swollen. The DNA content within the spermatozoa was altered, as well as the chromosomal status, suggesting that some error must have occurred during spermatogenesis. Interestingly, the genetic sequencing of the specific gene usually related to SMS syndrome (AURKC) revealed no mutations in our patient, suggesting that other genes may be involved in determining this syndrome. As far as is known, this is the first study in which spermatozoa of a SMS patient have been observed using morphological analysis, ultrastructural analysis, cytogenetic analysis and sperm DNA fragmentation analysis together. Moreover, it is believed that this is first report of recurrent miscarriage due to this specific syndrome.

Outcome of in vitro fertilization in patients with proven poor ovarian responsiveness after early vs. mid-follicular LH exposure: a prospective, randomized, controlled study.

OBJECTIVE: To compare early vs. mid-follicular exposure to LH in patients with poor ovarian responsiveness undergoing in vitro fertilization (IVF). DESIGN: Prospective, randomized, controlled trial. SETTING: University Hospital, University-affiliated private Clinic. PATIENTS: Five hundred-thirty women with poor ovarian responsiveness during the first IVF cycle, undergoing their second IVF attempt. INTERVENTIONS: In a GnRH-analogue long protocol, ovarian stimulation with recombinant FSH (300 IU/day) plus randomly assigned addition of recombinant LH (150 IU/day) from day 1 (early LH exposure; n = 264) or from day 7 (late LH exposure; n = 266). MAIN OUTCOME MEASURE(S): Primary outcome was the number of oocytes retrieved. Secondary outcomes were: cancellation rate, total gonadotropin dose, duration of ovarian stimulation, number of embryos available for transfer, pregnancy rate per started cycle, per OPU and per embryo transfer, implantation rate, delivered/ongoing pregnancy rate. RESULTS: Apart from the totally administered LH dose, that was significantly higher in the group receiving it from day 1, all parameters related to IVF outcome were non significantly different in the two groups. CONCLUSIONS: Adding LH to FSH from day 1 or from day 7 of ovarian stimulation in a GnRH-agonist long protocol exerts comparable effects on IVF outcome in poor responders.

Ovarian endometriomas and IVF: a retrospective case-control study.

We performed this retrospective case-control study analyzing 428 first-attempt in vitro fertilization (IVF) cycles, among which 254 involved women with a previous or present diagnosis of ovarian endometriosis. First, the results of these 254 cycles were compared with 174 cycles involving patients with proven non-endometriotic tubal infertility having similar age and body mass index. Women with ovarian endometriosis had a significantly higher cancellation rate, but similar pregnancy, implantation and delivery rates as patients with tubal infertility. Second, among the women with ovarian endometriosis, the women with a history of laparoscopic surgery for ovarian endometriomas prior to IVF and no visual endometriosis at ovum pick-up (n = 112) were compared with the non-operated women and visual endometriomas at ovum pick-up (n = 142). Patients who underwent ovarian surgery before IVF had significantly shorter period, lower antral follicle count and required higher gonadotropin doses than patients with non-operated endometriomas. The two groups of women with a previous or present ovarian endometriosis did, however, have similar pregnancy, implantation and live birth rates. In conclusion, ovarian endometriosis does not reduce IVF outcome compared with tubal factor. Furthermore, laparoscopic removal of endometriomas does not improve IVF results, but may cause a decrease of ovarian responsiveness to gonadotropins.

Diagnosis of pelvic endometriosis with use of macroscopic versus histologic findings.

OBJECTIVE: To obtain histologic confirmation of lesions suspected of endometriosis at laparoscopy. DESIGN: Prospective clinical study. SETTING: Patients in an academic hospital. PATIENT(S): Women of reproductive age who complained of chronic pelvic pain. INTERVENTION(S): A total of 122 biopsies were obtained from 54 patients undergoing laparoscopy, after exclusion of other potential causes of pelvic pain. MAIN OUTCOME MEASURE(S): Lack of consistency between laparoscopic and histologic diagnosis of endometriosis, in particular for minimal/mild stages. RESULTS: Endometriosis was confirmed by histology in 54% of the excised lesions. Diagnosis was more often confirmed among classic lesions than for all atypical lesions considered together. The histologic diagnosis of fibrosis was the most common among those biopsies, which lacked the presence of endometriosis. The revised American Fertility Association (AFS) scores before and after histologic confirmation differed significantly. In particular, 20 patients in either revised AFS class I or II were down-graded to stage 0. No single anatomical site turned out to be particularly prone to misdiagnosis at laparoscopy, in comparison to the other sites. CONCLUSION(S): These results confirm the need of histologic confirmation to obtain a diagnosis of endometriosis. However, the clinical impact of such findings remains a matter of debate.