Analysis of risk characteristics for metachronous metastasis in different period of nasopharyngeal carcinoma.

OBJECTIVE: To identify the main risk factors for metachronous metastatic nasopharyngeal carcinoma (NPC) in different periods after radiotherapy and estimate the weight of various factors in the early or late metachronous metastasis (EMM/LMM) groups. METHODS: This retrospective registry consists of 4434 patients with newly diagnosed NPC. Cox regression analysis was used to assess the independent significance of various risk factors. The Interactive Risk Attributable Program (IRAP) was used to calculate the attributable risks (ARs) for metastatic patients during different periods. RESULTS: Among 514 metastatic patients, 346 (67.32%) patients diagnosed with metastasis within 2 years after treatment were classified into the EMM group, while other 168 patients were classified into the LMM group. The ARs of T-stage, N-stage, pre-Epstein-Barr virus (EBV) DNA, post-EBV DNA, age, sex, pre-neutrophil-to-lymphocyte ratio, pre-platelet-to-lymphocyte ratio, pre-hemoglobin (HB), and post-HB were 20.19, 67.25, 2.81, 14.28, 18.50, - 11.17%, 14.54, 9.60, 3.74% and - 9.79%, respectively, in the EMM group. In the LMM group, the corresponding ARs were 3.68, 49.11, - 18.04%, 2.19, 6.11, 0.36, 4.62, 19.77, 9.57 and 7.76%, respectively. After multivariable adjustment, the total AR for tumor-related factors was 78.19%, and that for patient-related factors was 26.07% in the EMM group. In the LMM group, the total AR of tumor-related factors was 43.85%, while the weights of patient-related factors was 39.97%. In addition, except for these identified tumor- and patient-related factors, other unevaluated factors played a more important role in patients with late metastasis, with the weight increasing by 15.77%, from 17.76% in the EMM group to 33.53% in the LMM group. CONCLUSION: Most metachronous metastatic NPC cases occurred in the first 2 years after treatment. Early metastasis was mainly affected by tumor-related factors, which accounted for a declining percentage in the LMM group.

Reflecting on the utility of standardized uptake values on 18F-FDG PET in nasopharyngeal carcinoma.

BACKGROUND: To rethink the clinical significance of standardized uptake values (SUVs) of nasopharyngeal carcinoma (NPC) on 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET). METHODS: We retrospectively reviewed 369 NPC patients who underwent pretreatment 18F-FDG PET. The predictive value of the SUVmax of the primary tumor (SUVmax-t) and regional lymph nodes (SUVmax-n) was evaluated using probability density functions. Receiver operating characteristic curves were used to determine optimal cutoffs for the SUVmax-n/SUVmax-t ratio (NTR). Kaplan-Meier and Cox regression analyses were used to assess survival. RESULTS: The optimal SUVmax-t and SUVmax-n cutoffs were 7.5 and 6.9, respectively. High SUVmax-t and SUVmax-n were related to local and regional recurrence, respectively. Patients with low SUVmax had better 3-year overall survival (OS). To avoid cross-sensitization of cutoff points, we stratified patients with high SUVmax into the low and high NTR groups. The 3-year distant metastasis-free survival (DMFS; 92.3 vs. 80.6%, P = 0.009), progression-free survival (PFS; 84.0 vs. 67.7%, P = 0.011), and OS (95.9 vs. 89.2%, P = 0.002) significantly differed between the high vs. low NTR groups for patients with high SUVmax. Multivariable analysis showed that NTR was an independent prognostic factor for DMFS (hazard ratio [HR]: 2.037, 95% CI: 1.039-3.992, P = 0.038), PFS (HR: 1.636, 95% CI: 1.021-2.621, P = 0.041), and OS (HR: 2.543, 95% CI: 1.214-5.325, P = 0.013). CONCLUSION: High SUVmax was associated with NPC recurrence. NTR is a potential prognosticator for DMFS, suggesting that heterogeneity in the pretreatment 18F-FDG uptake between the primary tumor and lymph nodes is associated with high invasion and metastatic potential.

Prognosis viewing for nasopharyngeal carcinoma treated with intensity-modulated radiation therapy: application of nomogram and decision curve analysis.

OBJECTIVE: To view and evaluate the prognosis factors in patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiation therapy using nomogram and decision curve analysis (DCA). METHODS: Based on a primary cohort comprising consecutive patients with newly confirmed NPC (n = 1140) treated between January 2014 and December 2015, we identified independent prognostic factors of overall survival (OS) to establish a nomogram. The model was assessed by bootstrap internal validation and external validation in an independent validation cohort of 460 patients treated between January 2013 and December 2013. The predictive accuracy and discriminative ability were measured by calibration curve, concordance index (C-index) and risk-group stratification. The clinical usefulness was assessed by DCA. RESULTS: The nomogram incorporated T-stage, N-stage, age, concurrent chemotherapy and primary tumour volume (PTV). The calibration curve presented good agreement for between the nomogram-predicted OS and the actual measured survival probability in both the primary and validation cohorts. The model showed good discrimination with a C-index of 0.741 in the primary cohort and 0.762 in the validation cohort. The survival curves of different risk-groups were separated clearly. Decision curve analysis demonstrated that the nomogram provided a higher net benefit (NB) across a wider reasonable range of threshold probabilities for predicting OS. CONCLUSION: This study presents a predictive nomogram model with accurate prediction and independent discrimination ability compared with combination of T-stage and N-stage. The results of DCA supported the point that PTV can help improve the prognostic ability of T-stage and should be added to the TNM staging system.

Individualized radiology screening for newly diagnosed nasopharyngeal carcinoma.

OBJECTIVES: Current guidelines recommend universal PET/CT screening for metastases staging in newly diagnosed nasopharyngeal carcinoma (NPC) despite the low rate of synchronous distant metastasis (SDM). The study aims to achieve individualized screening recommendations of NPC based on the risk of SDM. METHODS AND MATERIALS: 18 pre-treatment peripheral blood indicators was retrospectively collected from 2271 primary NPC patients. A peripheral blood risk score (PBRS) was constructed by indicators associated with SDM on least absolute shrinkage and selection operator (LASSO) regression. The PBRS-based distant metastases (PBDM) model was developed from features selected by logistic regression analyses in the training cohort and then validated in the validation cohort. Receiver operator characteristic curve analysis, calibration curves, and decision curve analysis were applied to evaluate PBDM model performance. RESULTS: Pre-treatment Epstein-Barr viral DNA copy number, percentage of total lymphocytes, serum lactate dehydrogenase level, and monocyte-to-lymphocyte ratio were most strongly associated with SDM in NPC and used to construct the PBRS. Sex (male), T stage (T3-4), N stage (N2-3), and PBRS (≥1.076) were identified as independent risk factors for SDM and applied in the PBDM model, which showed good performance. Through the model, patients in the training cohort were stratified into low-, medium-, and high-risk groups. Individualized screening recommendations were then developed for patients with differing risk levels. CONCLUSION: The PBDM model offers individualized recommendations for applying PET/CT for metastases staging in NPC, allowing more targeted screening of patients with greater risk of SDM compared with current recommendations.

Recommendation for imaging follow-up strategy based on time-specific disease failure for nasopharyngeal carcinoma.

BACKGROUND: To develop a common follow-up strategy for appropriate imaging examination at an appropriate time for nasopharyngeal carcinoma (NPC). METHODS: Independent prognostic factors were identified by Cox regression analysis, and a nomogram model was developed. Random survival forest (RSF) model was constructed to depict probability of disease failure during a 5-year follow-up and establish a reasonable risk-based follow-up strategy. RESULTS: The nomogram model finally categorized the patients into three risk groups. RSF model demonstrated distribution trends for local and regional recurrences, bone metastasis, liver metastasis, and lung metastasis of NPC. Adequate imaging at follow-up should be considered between 10 and 21 months for patients at moderate-risk of recurrence or metastasis and 7-36 months for those at high-risk. CONCLUSIONS: The temporal distribution of incidence rates of recurrence or metastasis varied among different risk groups. We recommend implementing a focused and targeted imaging surveillance intervention at appropriate times to improve its efficiency and reduce costs.

PET/CT standardized uptake value and EGFR expression predicts treatment failure in nasopharyngeal carcinoma.

OBJECTIVE: This study inventively combines epidermal growth factor receptor (EGFR) expression of the primary lesion and standardized uptake value (SUV) of positron emission tomography and computed tomography (PET/CT) to predict the prognosis of nasopharyngeal carcinoma (NPC). This study aimed to evaluate the predictive efficacy of maximum standard uptake value (SUVmax) and EGFR for treatment failure in patients with NPC. METHODS: This retrospective study reviewed the results of EGFR expression and pretreatment 18F-FDG PET/CT of 313 patients with NPC. Time-dependent receiver operator characteristics was used for analyzing results and selecting the optimal cutoff values. Cox regression was used to screen out multiple risk factors. Cumulative survival rate was calculated by Kaplan-Meier. RESULTS: The selected cutoff value of SUVmax-T was 8.5. The patients were categorized into four groups according to EGFR expression and SUVmax-T. There were significant differences in the 3-year local recurrence-free survival (LRFS) (p = 0.0083), locoregional relapse-free survival (LRRFS) (p = 0.0077), distant metastasis-free survival (DMFS) (p = 0.013), and progression-free survival (PFS) (p = 0.0018) among the four groups. Patients in the EGFR-positive and SUVmax-T > 8.5 group had the worst survival, while patients in the EGFR-negative and SUVmax-T ≤ 8.5 group had the best prognosis. Subsequently, patients with only positive EGFR expression or high SUVmax-T were classified as the middle-risk group. There were also a significant difference in 3-year overall survival among the three risk groups (p = 0.034). SUVmax-T was associated with regional recurrence-free survival and LRRFS in multivariate analysis, whereas EGFR was an independent prognostic factor for LRRFS, DMFS, and PFS. CONCLUSION: The combination of SUVmax-T and EGFR expression can refine prognosis and indicate clinical therapy.

Biological target volume based on fluorine-18-fluorode-oxyglucose positron emission tomography/computed tomography imaging: a spurious proposition?

PURPOSE: To assess whether the high metabolic region of fluorine-18-fluorode-oxyglucose (18F-FDG) in the primary lesion is the crux for recurrence in patients with nasopharyngeal carcinoma (NPC), to assess the feasibility and rationale for use of biological target volume (BTV) based on 18F-FDG positron emission tomography/computed tomography (18F-FDG-PET/CT). METHODS: The retrospective study included 33 patients with NPC who underwent 18F-FDG-PET/CT at the time of initial diagnosis as well as the time of diagnosis of local recurrence. Paired 18F-FDG-PET/CT images for primary and recurrent lesion were matched by deformation coregistration method to determine the cross-failure rate between two lesions. RESULTS: The median volume of the Vpri (primary tumor volume using the SUV thresholds of 2.5), the Vhigh (the volume of high FDG uptake using the SUV50%max isocontour), and the Vrecur (the recurrent tumor volume using the SUV thresholds of 2.5) were 22.85, 5.57, and 9.98 cm3, respectively. The cross-failure rate of Vrecur∩high showed that 82.82% (27/33) of local recurrent lesions had < 50% overlap volume with the region of high FDG uptake. The cross-failure rate of Vrecur∩pri showed that 96.97% (32/33) of local recurrent lesions had > 20% overlap volume with the primary tumor lesions and the median cross rate was up to 71.74%. CONCLUSION: 18F-FDG-PET/CT may be a powerful tool for automatic target volume delineation, but it may not be the optimal imaging modality for dose escalation radiotherapy based on applicable isocontour. The combination of other functional imaging could delineate the BTV more accurately.

Do all patients at the initial stage of nasopharyngeal carcinoma need bone metastasis screening? A retrospective study.

BACKGROUND: To identify patients at low risk of synchronous bone metastasis who should not receive bone scans when initially diagnosed with nasopharyngeal carcinoma (NPC). METHODS: In total, 6652 patients were enrolled in the training cohort and 1919 patients in the multicenter external validation cohort. Logistic regression analyses were performed to assess independent predictors of synchronous bone metastasis for the nomogram model. RESULTS: After risk stratification, 46.3% (3081/6652) patients were separated into the low-risk group with an incidence of 0.71% for synchronous bone metastasis. The odds ratio of the intermediate and high-risk groups was 5.61 and 23.82 times that of the low-risk group, respectively. For patients with high EBV DNA, we recommend routine screening for N2-3 female patients, but that all male subgroups are screened. CONCLUSIONS: Bone scans should not be routine. Patients in the low-risk group should not be screened, which would avoid excessive radiation and economize iatrical resource.

[FISH analysis of meiotic segregation results of the spermatozoa from male pericentric inversion carriers].

OBJECTIVE: To analyze the meiotic segregation results of the spermatozoa from male pericentric inversion carriers by fluorescence in-situ hybridization (FISH). METHODS: Using chemical depolymerization and multicolor FISH, we analyzed the meiotic segregation results of the spermatozoa from 4 male pericentric inversion carriers. RESULTS: Of the 4 males studied, 46,XY,inv(9) (p11q12) was found in 2, 46,XY,inv(9) (p11q13) in 1 and 46,XY,inv(6) (p22q24) in the other; the lengths of the inverted segments represented 16.0, 16.0, 21.0 and 76.0% of the size of the whole chromosome involved; and the frequencies of recombinant sperm were 0.2, 0.4, 0.3 and 43.9%, del(p)/dup(q) accounting for 22.4% and del(q)/dup(p) 21.5%, respectively. CONCLUSION: Males with pericentric inversion may produce spermatozoa with recombinant chromosomes and the rate of recombination varies principally according to the size proportion to the whole chromosome involved. The results of FISH analysis of chromosomal unbalanced spermatozoa can provide accurate personalized information on the genetic risk of fertility.

Prognostic value of neutrophils for patients with nasopharyngeal carcinoma.

OBJECTIVE: To investigate the relationship between absolute neutrophils count (ANC) in different periods of treatment and the outcomes of patients and assess effect of longitudinal neutrophils variation during radiotherapy (RT) on prognosis in patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 1753 patients with newly diagnosed NPC were retrospectively analyzed. Complete blood counts of patients were obtained before treatment, before, during, and end of RT. The survival rate was calculated by Kaplan-Meier method and the result was compared by the log-rank test. The univariate and multivariate COX regression analyses were performed to investigate the association between the variation of ANC and survival for patients in different periods. RESULTS: Higher ANC pretreatment (>4 × 109/L) and pre-RT (>7 × 109/L) were correlated with poor OS (89.7% vs 85.6%, P = .009; 88.3% vs 77.3%, P = .002, respectively). An increase >5 × 109/L of ANC during RT was associated with adverse OS (87.9% vs 73.6%, P = .042). The multivariate Cox regression analysis showed that high ANC of pre-RT (>7 × 109/L) and a high increase (>5 × 109/L) of ANC during RT were independent prognostic factors of patients with NPC (P = .002, .044, respectively). CONCLUSION: Our results demonstrated that ANC was an independent prognostic factor for survival in patients with NPC who received RT. Neutrophils may promote tumor resistance to radiotherapy in NPC. LEVEL OF EVIDENCE: 2a.

Significance of boost dose for T4 nasopharyngeal carcinoma with residual primary lesion after intensity-modulated radiotherapy.

BACKGROUND: Previous studies showed poorer survival in T4 disease with residual lesion. To evaluate the efficacy and toxicity of a boost dose for T4 nasopharyngeal carcinoma (NPC), patients with a residual primary lesion after intensity-modulated radiotherapy (IMRT). METHODS: 398 T4 NPC patients with residual primary lesions after radical IMRT were retrospectively reviewed. An IMRT boost dose of 4-6.75 Gy was delivered to the residual lesions in 2-3 fractions. Propensity score matching (PSM) was applied to balance potential confounders between groups (ratio, 1:2). The presence of Epstein-Barr virus (EBV) DNA in plasma after IMRT was used for risk stratification. RESULTS: Patients who received boost radiation had significantly improved overall survival (OS) and local recurrence-free survival (LRFS) compared with those who did not (all P < 0.05). In the matched cohort, 3-year OS was 86.6% in the boost radiation group and 72.7% in the non-boost group (P = 0.022). Three-year LRFS was 93.4% in the boost radiation group and 83.5% in the non-boost group (P = 0.022). In the subgroup analysis, boost dose was shown to significantly improve 3-year OS (88.0% vs. 74.1%, P = 0.021) in the low-risk group (with undetectable plasma EBV DNA after IMRT). The administration of a boost dose also improved 3-year OS in the high-risk group (with detectable plasma EBV DNA after IMRT) (66.7% vs. 60.0%, P = 0.375). Multivariate analysis demonstrated that boost dose was the only protective prognostic factor. CONCLUSION: The addition of a boost dose for T4 NPC patients with residual primary lesion after radical IMRT provides satisfactory tumor control and clinical benefit. Additional timely and effective strengthening treatments are recommended for patients with detectable levels of plasma EBV DNA after radiotherapy.

Selectively recommend 18F-FDG PET/CT for patients with de novo nasopharyngeal carcinoma in endemic areas.

INTRODUCTION: To identify the subset of patients with de novo nasopharyngeal carcinoma (NPC) for whom [18F] fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET/CT) should be recommended, and to determine whether PET/CT is a cost-effective decision for precise M staging in endemic areas. MATERIALS AND METHODS: Retrospective analysis of data of 4469 patients diagnosed with de novo NPC between January 2014 and December 2019. The detection rate of distant metastasis was compared between different groups. Univariate and multiple logistic regression analysis was applied to identify the risk factors for distant metastasis. The cost-effectiveness of the diagnostic strategies was assessed. RESULTS: The detection rate of distant metastasis in the whole cohort was 5.46%. In multivariate analysis, male sex, T3-4 stage, N2-3 stage, and high plasma Epstein-Barr virus (EBV) DNA (≥ 14,650 copies/mL) were risk factors for distant metastases. NPC patients with T3-4 stage combined with N2-3 stage, high EBV DNA combined with male sex, or N2-3 stage combined with high EBV DNA were defined as recommended group with relatively higher tendency for metastasis. Distant metastasis incidence in recommended group and unrecommended group were 10.25% and 1.75%, respectively (P < 0.001). In the recommended group, PET/CT significantly improved the detection rate of distant metastasis (13.25% vs 9.02%, P = 0.005). Cost-effectiveness analysis revealed that additional cost for every one percent increase in distant metastasis detection rate was $22,785.58 in the recommended group (< Willingness-to-pay (WTP) threshold of $32,700.00) and $310,912.90 in the unrecommended group. CONCLUSIONS: In patients with de novo NPC, the tendency for metastasis can be predicted based on clinical parameters. 18F-FDG PET/CT should be selectively recommended for the subset of patients with a relatively higher tendency for metastasis.

Effect of relevant factors on radiation-induced nasopharyngeal ulcer in patients with primary nasopharyngeal carcinoma treated with intensity-modulated radiation therapy.

OBJECTIVE: To analyze the correlation between relevant factors and radiation-induced nasopharyngeal ulcer (RINU) in primary nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). METHODS: Clinical data were collected for 599 patients with newly diagnosed NPC who had completed IMRT. The entire cohort was randomly divided into two subgroups. The relationship between RINU and IMRT dose-volume were statistically analyzed with ROC curves and the Chi-square test. Nutritional status during and after treatment was compared between patients with vs without RINU. RESULTS: The results obtained showed that dose-volume had no effect on the incidence of RINU (P > .05). Nutrition-related parameters differed significantly between patients with vs without RINU (P < .05). CONCLUSION: The results obtained show that the incidence of RINU is not related to IMRT dose-volume in the treatment of primary NPC. The incidence of RINU was found to be related to nutritional status during and after radiation therapy. LEVEL OF EVIDENCE: 2a.

Effectiveness and cost-effectiveness analysis of nimotuzumab for the radiotherapy of locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: This study aimed to assess the effectiveness and cost-effectiveness of nimotuzumab in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: LA-NPC patients treated between October 2013 and December 2016 were retrospectively reviewed. A well-balanced cohort of patients who received nimotuzumab in addition to standard treatment (n = 50) and patients who did not receive nimotuzumab (n = 100) was selected using propensity score-matching method (1:2 ratio) for the cost-effectiveness analysis. RESULTS: Compared with concurrent chemoradiotherapy (CCRT) alone, addition of nimotuzumab to CCRT significantly improved the 3-year overall survival (OS) (98.00% vs. 91.00%, P = 0.032). On multivariate analysis, nimotuzumab (hazard ratio = 0.124, 95% confidence interval: 0.017-0.902, P = 0.039) showed prognostic significance for OS. No serious treatment-related adverse events were observed in the nimotuzumab group (P > 0.05). Cost-effectiveness analysis revealed that addition of nimotuzumab increased the average treatment costs by $14,364.63. The additional cost for every one percent increase in OS rate was $ 2,052.09. CONCLUSION: Addition of nimotuzumab to CCRT for LA-NPC confers significant survival benefits; however, it is not cost-effective.

Selection of a high-level physician may help improve outcomes of nasopharyngeal carcinoma.

BACKGROUND: To assess the relationship between the level of clinical radiation oncologist and the prognosis of patients with nasopharyngeal carcinoma (NPC). To our knowledge, no previous study has explicitly assessed the relationship with cancer prognosis and clinical radiation oncologists level. The effect of physicians on the prognosis has been entirely ignored. METHODS: Clinical data were collected for 1140 patients with newly diagnosed NPC. Based on the 3-year overall survival, the treating physicians were classified into 3 grades: high-level group, medium-level group, and low-level group. Cox proportional hazards regression analysis was used to assess the independent significance of different prognostic factors. Propensity score matching (PSM) was used to minimize the influence of confounders so that difference in outcomes provides an unbiased estimate of the influence of physician. Interactive Risk Attributable Program (IRAP) was used to calculate the attribution risk of individual risk factors or a combination of multiple factors. RESULTS: The 3-year OS in the high-level, medium-level, and low-level groups was 92.9%, 87.7%, and 83.5%, respectively (p = 0.003). After propensity score matching, the 3-year OS was 92.4%, 87.4%, and 82.9%, respectively (p = 0.004). IRAP was used to calculate the attribution risk of mortality risk. After multivariable adjustment, patient-related factors including tumor accounted for 90.02% [95% confidence interval (CI), 73.43-96.84%) and physician factors accounted for 17.66% (95% CI, 5.39-44.65%) of the mortalityrisk. All related factors, including patient-related factors and physician factors accounted for 92.02% (95% CI, 77.83-97.43%). CONCLUSION: Our study demonstrated obvious differences in the prognosis of patients treated by various clinical radiation oncologists. The largest share of prognosis risk was found to be at the patient level, while variation in prognosis was, in part, attributable to differences among physicians.

Metabolic tumor volume and conformal radiotherapy based on prognostic PET/CT for treatment of nasopharyngeal carcinoma.

For patients with nasopharyngeal carcinoma (NPC), prognostic indicators to customize subsequent biologically conformal radiation therapy may be obtained via 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (F-FDG) positron emission tomography/computed tomography (PET/CT). This retrospective study assessed the prognostic significance and feasibility of conformal radiotherapy for NPC, based on F-FDG PET/CT. Eighty-two patients with NPC underwent F-FDG PET/CT prior to intensity-modulated radiation therapy (IMRT). The maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of the primary tumor were measured, with MTVx based on absolute SUVx values ≥ specific threshold x on each axial image. The cut-off SUVmax and MTV values for predicting 3-year progression-free survival (PFS) were calculated according to a receiver operating characteristic curve. Assessed were correlations between SUVmax and MTV and between threshold x and MTVx, and the MTV percentage of the primary tumor volume at threshold x. The SUVmax and MTV were positively associated, as were MTV and primary tumor volume. Primary tumor volume, SUVmax, and MTV were significant predictors of survival. The 3-year PFS rates for SUVmax ≤8.20 and >8.20 were 91.1% and 73.0%, respectively (P = .027). With furthermore analysis, patients having tumor with smaller MTV had higher 3-year PFS than patients having tumor with larger MTV. The 3-year PFS rate was inversely related to MTV. SUVmax and MTV, derived by PET/CT, are important for assessing prognosis and planning radiotherapy for patients with NPC. Small MTV indicated better 3-year PFS compared with large MTV. For the best therapeutic effect, MTV4.0 was the best subvolume to determine radiotherapy boost.

Effect of sperm DNA fragmentation on clinical outcome of frozen-thawed embryo transfer and on blastocyst formation.

During the last decades, many studies have shown the possible influence of sperm DNA fragmentation on assisted reproductive technique outcomes. However, little is known about the impact of sperm DNA fragmentation on the clinical outcome of frozen-thawed embryo transfer (FET) from cycles of conventional in vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI). In the present study, the relationship between sperm DNA fragmentation (SDF) and FET clinical outcomes in IVF and ICSI cycles was analyzed. A total of 1082 FET cycles with cleavage stage embryos (C-FET) (855 from IVF and 227 from ICSI) and 653 frozen-thawed blastocyst transfer cycles (B-FET) (525 from IVF and 128 from ICSI) were included. There was no significant change in clinical pregnancy, biochemical pregnancy and miscarriage rates in the group with a SDF >30% compared with the group with a SDF ≤30% in IVF and ICSI cycles with C-FET or B-FET. Also, there was no significant impact on the FET clinic outcome in IVF and ICSI when different values of SDF (such as 10%, 20%, 25%, 35%, and 40%) were taken as proposed threshold levels. However, the blastulation rates were significantly higher in the SDF ≤30% group in ICSI cycle. Taken together, our data show that sperm DNA fragmentation measured by Sperm Chromatin Dispersion (SCD) test is not associated with clinical outcome of FET in IVF and ICSI. Nonetheless, SDF is related to the blastocyst formation in ICSI cycles.