Endometrium is vital to the establishment of pregnancy through its cyclical regeneration, which, when disrupted, can lead to endometrial thinning and Asherman's syndrome (AS). AS is characterized by infertility, pelvic pain, menstrual irregularities, and placental complications. Currently, treatments such as hysteroscopic adhesiolysis and hormone replacement therapy have demonstrated variable efficacy with limited clinical evidence. Recent developments in cell therapy have introduced menstrual blood-derived mesenchymal stem cells (MenSCs) as a promising alternative therapeutic strategy. Menstrual blood offers a noninvasive, periodically available source of mesenchymal stem cells, MenSCs for endometrial regeneration. This review comprehensively examines the endometrial regenerative process, pathophysiology of AS, and therapeutic prospects of MenSCs, underscoring the need for continued research to optimize treatment strategies.
Aiming to promote the safe and appropriate provision of regenerative medicine (RM) in Japan, the Japanese government implemented the Act on the Safety of Regenerative Medicine (RM Act) on November 25, 2014. A supplemental rule of the RM Act stipulated that its legal framework be reviewed 5 years after implementation assessing scientific progress and environmental change, and based on the review that amendments to the legal framework be considered. The review of the RM Act started in July 2019, and an act to partially amend the RM Act and the Clinical Trials Act (the Amendment Act) was promulgated on June 14, 2024. The Amendment Act added gene therapy and its related technologies to the scope of the RM Act, and on-site inspections and grounds for disqualification of Certified Committees for RM were established. In the present review, which is based on publicly available material, we summarize the flow of the discussions concerning the regulatory changes to the RM Act as well as other pertinent matters. In addition, in line with the scope of the special issue “Future of Regenerative Medicine Viewed by Young Scientists”, based on our experience as young investigators with the perspective of officers under this unique legal framework, we offer insights that RM research investigators, including international and experienced professional investigators, who will contribute to Japan's continued status as a world leader in RM, should consider in their RM research for in light of the recent amendment of the RM Act.
In Japan, there is a registry for fertility treatment (the JSOG registry), which is a system that only registers select clinical data related to assisted reproductive technology (ART). This system does not include patient-derived data, so innovative tools that can complement the shortcomings of the existing registry may be useful. In this study we explored the potential of using a smartphone application platform to collect clinical data from patients directly. We recruited participants using the smartphone application “Luna Luna” and requested information that is typically gathered during a medical checkup, including basic physical characteristics, medical history, and results of fertility examinations such as hormone levels and semen analysis. We also asked the participants about the most recent fertility treatment they received and the details of the treatment. We recruited more than 13,000 participants within Japan nationwide in one month, and successfully collected information that is necessary in clinical practice for fertility treatment. Furthermore, through the participants, we were able to obtain information concerning their partners. We gained an expanded understanding of the circumstances surrounding fertility tests performed in Japan and details of fertility treatment such as ovarian stimulation and pregnancy outcomes by each fertility treatment method. This smartphone application has the potential as a promising tool for doctors and couples for information management during fertility treatment.
Ferric carboxymaltose (FCM) is widely used to correct anemia and replenish iron stores rapidly, particularly in Western populations. However, lower doses of FCM are typically used in East Asia, with limited research on their effectiveness, especially in postpartum women. This randomized controlled trial aimed to assess the efficacy of low-dose FCM compared with oral ferrous sulfate in increasing postpartum hemoglobin (Hb) levels and replenishing iron stores in East Asian women. Sixty postpartum women with Hb levels < 10 g/dL and serum ferritin ≤ 30 ng/mL were randomized to receive either intravenous FCM (500 mg at baseline and 2 weeks) or oral ferrous sulfate (210 mg daily for 4 weeks). The primary outcome was the increase in Hb levels at 2 weeks post-enrollment. Secondary outcomes included serum ferritin, transferrin saturation, the Edinburgh Postnatal Depression Scale (EPDS) score, and adverse events at 4 weeks. The FCM group demonstrated a significantly greater increase in Hb levels at 2 weeks (mean difference 0.42 g/dL; 95% CI: 0.12–0.72; P = 0.006), with markedly higher ferritin (adjusted mean difference 356.0 ng/mL; 95% CI: 321.0–403.0; P < 0.001) and transferrin saturation (adjusted mean difference 10.76%; 95% CI: 4.20–17.31; P = 0.002) at 4 weeks. Although there was no significant difference in final Hb levels at 4 weeks (mean difference 0.36 g/dL; 95% CI: -0.01–0.72; P = 0.055), the FCM group had a lower median EPDS score (median difference -3.0; 95% CI: -5.0 to -1.0; P = 0.002) and fewer gastrointestinal side effects, including constipation and nausea. Hypophosphatemia occurred asymptomatically in three patients in the FCM group. These findings suggest that low-dose FCM infusion is highly effective in increasing Hb levels at 2 weeks post-enrollment, with fewer gastrointestinal side effects and higher ferritin levels observed at 4 weeks post-enrollment compared with oral ferrous sulfate. This study was registered at the UMIN Clinical Trials Registry, which meets the requirements of the ICMJE, on December 1, 2021 (ID: UMIN000046049).
Introduction While the provision of unapproved regenerative medicine has been problematic worldwide, few studies have examined the implementation status of regenerative medicine (RM) in the specific field. This study aimed to determine the current status of therapy and clinical research in the obstetrics and gynecology (OBGYN) in Japan under the Act on the Safety of Regenerative Medicine (RM Act). Methods Detailed data were extracted from publicly available websites provided by the Ministry of Health, Labour, and Welfare. We extracted descriptive details, including risk classification of the RM Act, modality, target disease, locality, institution, and administration route. For therapy, the price for each modality was evaluated. Results The total number of therapeutic provision plans in OBGYN (1.9% of RM in Japan) are classified as Class II (moderate) risk. Most were administered in clinics in urban areas for treating endometrial or ovarian infertility by locally administering platelet-rich plasma (PRP) or autologous mesenchymal stem cells (MSCs). The price using MSCs is approximately eight times more expensive that of those involving PRP (1832.1 ± 1139.8 vs 240.8 ± 106.5 thousand yen, p < 0.0001). Regarding research, four plans (2.2%) were submitted to target implantation failure and advanced gynecological cancer using autologous lymphocytes, dendritic cells, or MSCs. Conclusion The RM Act permits knowledge of the current status of regenerative medicine even for unapproved uses in a specific clinical field. The study findings shall prompt a worldwide discussion regarding the required regulations for therapy and clinical research of RM.
Repeated implantation failure is a major cause of infertility among healthy women. Uterine β-catenin (CTNNB1) plays a critical role in implantation. However, the role of embryonic CTNNB1 during implantation remains unclear. We addressed this topic by analyzing mice carrying Ctnnb1-deficient (Ctnnb1Δ/Δ) embryos. Ctnnb1Δ/Δ embryos were produced by intercrossing mice bearing Ctnnb1-deficient eggs and sperms. We found that Ctnnb1Δ/Δ embryos developed to the blastocyst stage; thereafter, they were resorbed, leaving empty decidual capsules. Moreover, leukemia inhibitory factor, a uterine factor essential for implantation, was undetectable in Ctnnb1Δ/Δ blastocysts. Furthermore, CDX2, a transcription factor that determines the fate of trophectoderm cells, was not observed in Ctnnb1Δ/Δ blastocysts. Intrauterine injection with uterine fluids (from control mice) and recombinant mouse leukemia inhibitory factor proteins rescued the uterine response to Ctnnb1Δ/Δ blastocysts. These results suggest that embryonic CTNNB1 is required for the secretion of blastocyst-derived factor(s) that open the implantation window, indicating that the uterine response to implantation can be induced using supplemental materials. Therefore, our results may contribute to the discovery of a similar mechanism in humans, leading to a better understanding of the pathogenesis of repeated implantation failure.
There are many previous reports on the effects of ethanol on physiological function, including reports of elevated blood estrogen levels in women who drank alcohol. However, the mechanism of ethanol's effects on ovarian functions, such as follicle development and hormone secretion, hasn't been fully clarified. Therefore, in this study, we investigated the impacts of ethanol on these phenomena and their mechanisms using a primary culture system of rat ovarian granulosa cells. In the present experiment, groups were created in which FSH or ethanol was added alone or FSH and ethanol were co-added, and mRNA and protein expression in each group was measured for LH receptor (LHR) and sex steroid hormone synthase, as well as for estradiol production, cAMP accumulation, FSH receptor (FSHR) internalization rate. The addition of FSH induced mRNA expression of LHR and aromatase, which led to membrane LHR expression and estradiol production. The coexistence of ethanol enhanced all these responses. The action of FSH is exerted via cAMP, and the co-addition of ethanol enhanced this cAMP production. Ethanol alone didn't induce cAMP production. The enhancing effect of ethanol was also observed for cAMP induced by cholera toxin. Ethanol had no significant effect on the internalization rate of FSHR. In conclusion, ethanol increased FSH-stimulated cAMP production by increasing the activity of adenylyl cyclase, which enhanced FSH actions in rat granulosa cells. Alcohol is an exacerbating factor in several female hormone-related diseases, and the mechanism of ethanol-induced increase in estrogen secretion may be involved in the pathogenesis of these diseases.
There are many previous reports on the effects of ethanol on physiological function, including reports of elevated blood estrogen levels in women who drank alcohol. However, the mechanism of ethanol's effects on ovarian functions, such as follicle development and hormone secretion, has not been fully clarified. Therefore, in this study, we investigated the impacts of ethanol on these phenomena and their mechanisms using a primary culture system of rat ovarian granulosa cells (GCs). In the present experiment, groups were created in which follicle-stimulating hormone (FSH) or ethanol was added alone or FSH and ethanol were co-added, and mRNA and protein expression in each group was measured for luteinizing hormone receptor (LHR) and sex steroid hormone synthase, as well as for estradiol (E 2 ) production, cAMP production, and FSH receptor (FSHR) internalization rate. The addition of FSH induced mRNA expression of LHR and aromatase, which led to membrane LHR expression and E 2 production. The coexistence of ethanol enhanced all these responses. The action of FSH is exerted via cAMP, and the co-addition of ethanol enhanced this cAMP production. Ethanol alone did not induce cAMP production. The enhancing effect of ethanol was also observed for cAMP induced by cholera toxin. Ethanol had no significant effect on the internalization rate of FSHR. In conclusion, ethanol increased FSH-stimulated cAMP production by increasing the activity of adenylyl cyclase, which enhanced FSH actions in rat GCs. Alcohol is an exacerbating factor in several female hormone-related diseases, and the mechanism of ethanol-induced increase in estrogen secretion revealed in this study may be involved in the pathogenesis of these diseases.
Pregnant patients have an increased risk of torsion compared to that seen in nonpregnant patients, and those with larger cysts undergo torsion more frequently, which can cause obstructions during labor. The risks associated with emergent surgery are higher than those with elective surgery. Laparoscopic surgery can be safely performed during pregnancy. Single-port laparoscopic surgery is reported to be a minimally invasive laparoscopic technique. We report three cases of ovarian dermoid cysts, which were successfully removed during pregnancy through elective single-port laparoscopic surgery. In all cases, imaging showed a dermoid cyst and the cyst size was greater than 6 cm. All patients requested the surgery. The ovarian cysts were successfully removed by single-port laparoscopy without additional ports and without intra- or postoperative complications. All pregnancies progressed well and delivered vaginally at full term. The single-port laparoscopic approach is useful for removing ovarian cysts during pregnancy.
OBJECTIVE: To quantitatively evaluate the effect of a booster vaccination dose against coronavirus disease 2019 (COVID-19) on menstrual cycle in a large-scale retrospective cohort study using a menstrual cycle tracking smartphone application (app). METHODS: Prospectively or retrospectively recorded data, including the start and finish dates of menstrual cycles, were collected with the app. Detailed data on vaccinations, side effects, and participants' characteristics were retrospectively collected from a questionnaire on the app. For each COVID-19 vaccination shot (first, second, and third), within-individual changes in menstrual cycle length up to the fourth postvaccination cycle were evaluated. RESULTS: Among the 7,376 and 6,873 participants who had the first and second COVID-19 vaccine doses in different menstrual cycles, respectively, menstrual cycles immediately after the vaccination (first postvaccination cycles) were an average of 0.22 days (95% CI, 0.06–0.39) and 0.37 days (95% CI, 0.20–0.54) longer than the prevaccination cycle. In contrast, among the 1,672 participants who received the first and second doses in the same cycle, the first postvaccination cycle was an average of 4.21 days (95% CI, 3.69–4.72) longer. The second to fourth postvaccination cycles returned to the level of the prevaccination cycle. However, among the 4,768 participants who had the third COVID-19 vaccine dose, the menstrual cycle immediately after the vaccination was an average of 1.20 days (95% CI, 1.00–1.40) longer, with prolongation of cycles of 0.27 days (95% CI, 0.10–0.44) to 0.41 days (95% CI, 0.22–0.59) persisting from the second to the fourth postvaccination cycle. CONCLUSION: The booster shot against COVID-19 may have a greater and longer-lasting effect on menstrual cycles than the primary-series shots. Although the effect size was small, evidence on the side effects of immunization on menstruation should be accumulated.
Background Melanocytes are an essential part of the epidermis, and their regeneration has received much attention because propagation of human adult melanocytes in vitro is too slow for clinical use. Differentiation from human pluripotent stem cells to melanocytes has been reported, but the protocols to produce them require multiple and complex differentiation steps. Method We differentiated human embryonic stem cells (hESCs) that transiently express JMJD3 to pigmented cells. We investigated whether the pigmented cells have melanocytic characteristics and functions by qRT-PCR, immunocytochemical analysis and flow cytometry. We also investigated their biocompatibility by injecting the cells into immunodeficient mice for clinical use. Result We successfully differentiated and established a pure culture of melanocytes. The melanocytes maintained their growth rate for a long time, approximately 200 days, and were functional. They exhibited melanogenesis and transfer of melanin to peripheral keratinocytes. Moreover, melanocytes simulated the developmental processes from melanoblasts to melanocytes. The melanocytes had high engraftability and biocompatibility in the immunodeficient mice. Conclusion The robust generation of functional and long-lived melanocytes are key to developing clinical applications for the treatment of pigmentary skin disorders.
BACKGROUND:Menstrual blood-derived cells show regenerative potential as a mesenchymal stem cell and may therefore be a novel stem cell source of treatment for refractory infertility with injured endometrium. However, there have been few pre-clinical studies using cells from infertile patients, which need to be addressed before establishing an autologous transplantation. Herein, we aimed to investigate the therapeutic capacity of menstrual blood-derived cells from infertile patients on endometrial infertility.METHODS:We collected menstrual blood-derived cells from volunteers and infertile patients and confirmed their mesenchymal stem cell phenotype by flow cytometry and induction of tri-lineage differentiation. We compared the proliferative and paracrine capacities of these cells. Furthermore, we also investigated the regenerative potential and safety concerns of the intrauterine transplantation of infertile patient-derived cells using a mouse model with mechanically injured endometrium.RESULTS:Menstrual blood-derived cells from both infertile patients and volunteers showed phenotypic characteristics of mesenchymal stem cells. In vitro proliferative and paracrine capacities for wound healing and angiogenesis were equal for both samples. Furthermore, the transplantation of infertile patient-derived cells into uterine horns of the mouse model ameliorated endometrial thickness, prevented fibrosis, and improved fertility outcomes without any apparent complications.CONCLUSIONS:In our pre-clinical study, intrauterine transplantation of menstrual blood-derived cells may be a novel and attractive stem cell source for the curative and prophylactic therapy for injured endometrium. Further studies will be warranted for future clinical application.
Ovarian clear cell carcinoma (OCCC), one of the histopathological types of ovarian cancer, has a poor prognosis when it recurs; however, it is difficult to precisely predict the risk of recurrence. Here, we analyzed pathological images of OCCC to elucidate the relationship between pathological findings and recurrence, and using machine learning, we established a classifier to predict the recurrence and several other prognosis indicators of this disease. In total, 110 patients with OCCC treated with primary surgery at a single institution were enrolled in this study. We used the deep-learning neural networks to process the whole slide images of OCCC obtained by digitally scanning the original hematoxylin and eosin-stained glass slides. The images were preprocessed and used as input to the machine learning pipeline. We fine-tuned its parameters to predict the recurrence, progression-free survival, and the overall survival days of all patients. We predicted the recurrence of OCCC with an overall accuracy of 93%, area under the receiver operating characteristic curve of 0.98, and sensitivity/specificity above 0.92 using Resnet 34. Furthermore, we predicted progression-free survival/overall survival of the patients with ~90% accuracy. In conclusion, our study demonstrates the feasibility of using a machine learning system to predict different features of OCCC samples using histopathological images as input. This novel application provides accurate prognosis information and aids in the development of personalized treatment strategies.
Abstract Background It is worthwhile to identify women at risk of developing postpartum depression during pregnancy. This study aimed to determine the optimal time and cutoff score for antenatal screening for prediction of postpartum depressive symptoms (PDS) using the Edinburgh Postnatal Depression Scale (EPDS) and to identify risk factors for PDS. Methods The target population was healthy pregnant women receiving antenatal care at a university hospital in Tokyo, Japan. During the first, second, and third trimesters, 3–4 days postpartum, and one month postpartum, they were asked to take the Japanese version of the EPDS questionnaire. The primary outcome of the study was PDS, defined as an EPDS score ≥ 9 at one month postpartum. The area under the receiver operating characteristics curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of EPDS scores at each antenatal screening time were calculated. Results From 139 pregnant women, 129 were successfully followed up throughout the study. The number of women with an EPDS score ≥ 9 during the first, second, and third trimesters, 3–4 days postpartum, and one month postpartum were 6/126 (4.8%), 9/124 (7.3%), 5/117 (4.3%), 17/123 (13.8%), and 15/123 (12.2%), respectively. Screening during the second trimester had the highest AUC to predict PDS (0.89) among antenatal screenings. The optimal EPDS cutoff score during the second trimester was 4/5 (sensitivity: 85.7%; specificity: 77.1%; PPV: 33.3%; NPV: 97.6%). An EPDS score ≥ 5 during the second trimester (adjusted odds ratio [aOR]: 15.9; 95% confidence interval [95%CI]: 3.2–78.1) and a family history of mental illness (aOR: 4.5; 95%CI: 1.2–17.5) were significantly associated with PDS. Conclusions Our study suggests that the EPDS score at the second trimester with the cutoff value of 4/5 may be adequate for initial screening for prediction of PDS. Women with an EPDS score ≥ 5 at the second trimester require more elaborate follow-up.
Ovarian pregnancy is a rare disease, accounting for 0.5%–3% of ectopic pregnancies. Ovarian pregnancy risk factors and preoperative diagnosis have been extensively reported. However, its histopathology and surgical findings have been poorly studied. To examine appropriate surgical procedures, we investigated the clinical features, surgical findings, and histopathological examinations of four ovarian pregnancy cases treated in our hospital. In histopathological examination, most specimens did not contain ovarian tissues; in some cases, villous tissues were buried in a clot. Therefore, evaluating the appropriateness of surgical resection range from histopathological images was difficult. However, the postoperative course was favorable; no cases manifested complications. Considering all these facts, we regarded the surgical procedures of the four cases in this study as appropriate. For the treatment of ovarian pregnancies, especially for the outward development type, a sufficient therapeutic effect may be achieved even without extensive excision of the ovarian tissues by laparoscopic surgery.
People of reproductive age have unmet needs related to deficiencies in fertility literacy. Here, we aimed to investigate whether providing fertility-related information via a smartphone application could improve fertility treatment-related literacy in participants. We performed a randomized control-group pretest posttest study and recruited participants between June 18 and 25, 2020. Participants' fertility treatment-related literacy was assessed with a pretest that comprised of 28 questions and participants were allocated with stratified randomization to either intervention group or control group. The intervention comprised a one-week smartphone application-based provision of information on fertility-related information and the control group received general information about women's healthcare. Effectiveness of intervention was assessed using a posttest. A total of 4137 participants were administered the questionnaire and pretest, among which 3765 participants (91.0 %) responded and were randomly allocated into either the intervention group (N = 1883) or the control group (N = 1882). A significantly higher posttest mean score was observed for the intervention group compared to the control group (P = 0.0017). We also observed that posttest scores were significantly improved compared to pretest scores in both the intervention and control group (P < 0.001). When examining by specific test question, the proportion answering correctly increased at posttest compared to pretest for both intervention and control groups (P < 0.001). Furthermore, the intervention group showed a greater mean difference between posttest and pretest scores than the control group (P < 0.001). In conclusion, educational intervention using a smartphone application contributed to enhancing fertility treatment-related literacy.
Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer (EOC) that is associated with elevated interleukin-6 (IL-6) expression, resistance to chemotherapy, and increased mortality. Although bevacizumab (Bev) is a widely used anti-angiogenic agent for EOC, the efficacy of Bev and the role of IL-6 in modulating angiogenesis in OCCC are unknown. We performed tube formation assays using human umbilical vein endothelial cells (HUVEC) cultured in OCCC cell-conditioned medium and using cells directly co-cultured with OCCC cells. We observed that IL-6 inhibition significantly mitigated the ability of Bev to impede tube formation in both cases. Furthermore, IL-6 blockade disrupted the anti-angiogenic efficacy of Bev and its concomitant anti-tumor activity. In addition, IL-6 inhibition resulted in a significant increase in angiopoietin-1 (Ang1) secretion and decreased vascular endothelial growth factor (VEGF) expression. Clinical specimens also exhibited this reciprocal relationship between IL-6 and Ang1 expression. Finally, depletion of Ang1 abrogated the effects of IL-6 inhibition on Bev activity, demonstrating that IL-6 supports the anti-angiogenic activity of Bev by suppressing Ang1 expression and promoting dependence on VEGF for angiogenesis. Altogether, our data suggest that OCCC tumors with high IL-6 levels are candidates for Bev therapy.
Background: The clinical value of personalized embryo transfer (pET) guided by the endometrial receptivity analysis (ERA) tests for recurrent implantation failure (RIF) cases is still unclear. The aim of this study is to clarify the efficacy of ERA leading to personalization of the day of embryo transfer (ET) in RIF patients. Methods: A retrospective study was performed for 94 patients with RIF who underwent ERA between July 2015 and December 2019. Pregnancy outcomes in a previous vitrified-warmed blastocyst transfer (previous VBT) and a personalized vitrified-warmed blastocyst transfer (pVBT) in identical patients were compared. The details of each pVBT were further analyzed between patients in a non-displaced group, which indicated “receptive” cases in ERA results and those who were in the displaced group, which indicated “non-receptive” cases. Results: When the pregnancy rate, both per patient and per transfer cycle, of previous VBT and pVBT were compared, a significant increase in pVBT was observed between the two methods (5.3% vs. 62.8%, 4.4% vs. 47.9%, respectively). The pregnancy rates, implantation rates, and clinical pregnancy rates of the first pVBT were significantly higher in the displaced group than the non-displaced group. The cumulative ongoing pregnancy rate of the displaced group tended to be higher compared to that of the non-displaced group in the first pVBT, although the difference was not statistically significant (51.0% vs. 31.1%, [Formula: see text] = 0.06). Conclusions: Our study demonstrates that pVBT guided by ERA tests may improve pregnancy outcomes in RIF patients whose window of implantation (WOI) is displaced, and its effect may be more pronounced at the first pVBT. The displacement of WOI may be considered to be one of the causes of RIF, and its adjustment may contribute to the improvement of pregnancy outcomes in RIF patients.
AIM:This study aimed to validate a simplified method of quantifying chemotherapy-induced peripheral neuropathy using the PainVision PS-2100® (PV) electrical perception system.METHODS:We assessed patients diagnosed with epithelial ovarian cancer, fallopian tube cancer, or peritoneal cancer and were about to undergo first-time paclitaxel and carboplatin chemotherapy. Peripheral neuropathy was assessed before and after chemotherapy administration in all patients according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE4.0), using a conventional assessment in combination with the PV system. The PV device comprises electrodes attached to the ulnar side of the forearm and the first joint of index fingers on both the left and right sides to measure the electrical perceptual threshold. The average of three threshold measurements was recorded for each patient.RESULTS:Thirty female patients (age 51.6 ± 12.2 [mean ± SD]) were included, and median number of chemotherapy drug treatments was 5 (first quartile: 4, second quartile: 5, and third quartile: 5). Twenty-seven patients (90%) reported posttreatment numbness; NCI-CTCAE4.0 perceptual anomaly grades were as follows: G1, 57 (40%); G2, 19 (13%); and G3, 7 (5%). A positive correlation was identified between right medial side PV threshold score and perceptual anomaly grade on measurements of the inner right-hand side only.CONCLUSION:Our preliminary results suggest that peripheral neuropathy may be quantified using PV. As CIPN often lowers QOL, it needs to be appropriately evaluated. Future studies with a larger patient cohort and methodological refinements to improve accuracy are warranted.