Use of spinal cord stimulation in treatment of intractable headache diseases.

Headache diseases remain one of the leading causes of disability in the world. With the development of neuromodulation strategies, high cervical spinal cord stimulation (hcSCS) targeting the trigeminocervical complex has been deployed to treat refractory headache diseases. In this article, we review the proposed mechanism behind hcSCS stimulation, and the various studies that have been described for the successful use of this treatment strategy in patients with chronic migraine, cluster headache, and other trigeminal autonomic cephalalgias.

Development of a Model to Estimate the Optimal Number of Oocytes to Attempt to Fertilize During Assisted Reproductive Technology Treatment.

Importance: Surplus cryopreserved embryos pose a challenge for in vitro fertilization patients and clinics; with Roe v. Wade overturned, some states may deem the discarding of surplus embryos illegal, radically changing in vitro fertilization practice. An evidence-based tool would help limit surplus embryo creation. Objective: To develop a prediction tool for determining how many oocytes should be exposed to sperm to create embryos to conserve the chance of live birth while minimizing surplus embryos. Design, Setting, and Participants: This diagnostic study used data from member clinics of the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System between 2014 to 2019. A total of 410 719 oocyte retrievals and 460 577 embryo transfer cycles from 311 237 patients aged 18 to 45 years old who initiated their first oocyte stimulation cycle between January 1, 2014, and December 31, 2019, were included. Data were analyzed from February to June 2022. Exposures: Female patient age, anti-mullerian hormone level, diminished ovarian reserve diagnosis, number of oocytes retrieved, and the state where the clinic is located were included in the final models. Main Outcomes and Measures: The algorithm was based on 3 models with outcomes: (1) day of transfer; (2) proportion of retrieved oocytes that become usable blastocysts; and (3) number of blastocysts needed for transfer for 1 live birth to occur. Results: The median (IQR) age at stimulation cycle start was 35 (29-32) years and the median (IQR) number of oocytes retrieved was 10 (6-17). The likelihood of recommending that all oocytes be exposed to sperm increased with age; less than 20.0% of retrievals among patients younger than 32 years and more than 99.0% of retrievals among patients older than 42 years received recommendations that all oocytes be exposed to sperm. Among cycles recommended to expose fewer than all oocytes, the median (IQR) numbers recommended for 1 live birth were 7 oocytes (7-8) for patients aged less than 32 years, 8 (7-8) for patients aged 32 to 34 years, and 9 (9-11) for patients aged 35 to 37 years. Conclusions and Relevance: In this diagnostic study of in vitro fertilization cycles, a prediction tool was developed to aid clinicians in determining the optimal number of oocytes to expose to sperm, reducing the number of unused embryos created and immediately addressing current patient and clinician concerns.

Evaluation of BCL6 and SIRT1 as Non-Invasive Diagnostic Markers of Endometriosis.

(1) Background: Endometriosis is characterized by the presence of endometrial glands and stroma outside of the uterus and is often associated with severe pelvic pain and infertility. Our study explored the utilization of B-Cell Lymphoma 6 (BCL6) and Sirtuin 1 (SIRT1) as potential biomarkers in serum, plasma, urine, and cervical mucus for a non-invasive diagnostic test for endometriosis. BCL6 was chosen based on its previously reported elevated expression in endometrial biopsies, and SIRT1 is co-expressed and upregulated in the endometrium of women with endometriosis. (2) Methods: BCL6 and SIRT1 levels were measured using enzyme-linked immunoassay (ELISA) in samples from 20 women with endometriosis (ten with stages I/II and ten with stages III/IV) and ten women without endometriosis. (3) Results: Levels of SIRT1 in sera showed a statistically significant elevation in advanced stages III/IV compared to controls and stages I/II. No significant differences were found in other bodily fluids for SIRT1 or any bodily fluids tested for BCL6. (4) Conclusions: These results suggest some potential of SIRT1 expression within serum as a predictor of advanced asymptomatic stages of endometriosis. Using immunohistochemistry (IHC) staining and H-SCORE values for the elevated BCL6 (and potentially SIRT1) levels in endometrial biopsy samples seems to have higher diagnostic potential based on the previously published studies.

Older Neighbors and The Neighborhood Context of Child Well-Being: Pathways to Enhancing Social Capital for Children.

Drawing on Coleman's concept of social capital, researchers have investigated how the quality of neighborhood social networks influences child development and well-being. The role of non-kin older neighbors in advancing child well-being through the enhancement of social capital, however, has been under-studied. Our objective was to delineate specific pathways through which non-kin older neighbors contribute to neighborhood quality for children and families and potentially advance child well-being. We examined open-ended interview data from 400 parents who cared for at least one child under 18 years of age and resided in 20 neighborhoods in Cleveland, Ohio. A subsample of 113 parents connected older neighbors to neighborhood quality for families and children in their narratives. Our analysis identified three primary pathways through which parents positively linked older neighbors to neighborhood quality: older neighbors support parents and children, promote neighborhood safety, and contribute to neighborhood residential stability. These contributions are evidence of intergenerational closure, reciprocated exchange, and informal social control working together to create social capital in neighborhoods for children. It is by enhancing social capital that older neighbors potentially improve child well-being. We discuss the implications of our findings for neighborhood research and practice.

The influence of neighborhood violent crime on child-rearing: Integrating neighborhood ecologies and stratified reproduction approaches.

While relationships between neighborhood violent crime and adverse child outcomes are well-established, less is known about how neighborhood violent crime influences child-rearing strategies. To address this gap, we blend neighborhood ecologies and stratified reproduction frameworks and examine interview data collected in 2014-2015 from 107 adult caregivers residing in three low and three elevated violent crime neighborhoods in Cleveland, Ohio. Our objective is to examine how perceptions of neighborhood violent crime and its relationship to self-reported child-rearing practices vary by level of neighborhood violence. We find that, although caregivers in low and elevated violent crime neighborhoods shared the perception of neighborhood violent crime as a concern, their narratives of child-rearing practices differed. Caregivers in elevated violent crime neighborhoods were more likely than their low violent crime counterparts to describe in experience-near terms how violent crime threatened their children's well-being. To protect children, caregivers in elevated violent crime neighborhoods reported engaging in severely constrained child-rearing strategies. These constraints have unintended consequences. While they may protect children in the short-term, they may also reproduce inequities by reducing family quality of life in other ways. These findings advance understanding of how neighborhood violent crime differentially affects child-rearing. We integrate neighborhood ecologies and stratified reproduction frameworks to capture how social inequities interact in neighborhood settings to constrain child-rearing and perpetuate inequities over time.

Role of Human Galectins in Inflammation and Cancers Associated with Endometriosis.

Galectins are a family of ß-galactoside-binding proteins that contribute to multiple cellular functions, including immune surveillance and apoptosis. Human galectins are also important regulators of inflammation, making them a research target for various inflammatory diseases and tumorigenesis associated with pro-inflammatory conditions. This review focuses on the involvement of human galectins in modulation of inflammation and in the pathophysiology of endometriosis and endometriosis-associated neoplasms. Endometriosis is a chronic inflammatory disease with unknown etiology. Galectins -1, -3 and -9 were found to be overexpressed in ectopic and eutopic endometrium of females with endometriosis compared to those without endometriosis. These findings suggest galectins' role in the progression on endometriotic lesions and their potential use as diagnostic biomarkers and/or targets for therapeutic approaches. Galectins -1, -3, and -9 have also been implicated in the development of endometriosis-associated neoplasms. Furthermore, galectin-3 has been shown to interact with KRAS protein and contribute to cellular growth, proliferation, inflammation, and the uptake of nutrients in endometriotic lesions and may be involved in the maintenance and propagation of endometriosis. These galectins have been shown to be upregulated in certain forms of cervical, ovarian, endometrial, and colon cancer associated with endometriosis and have become a potential target for anti-cancer therapies.

Differences in Balance Ability and Motor Control between Dancers and Non-Dancers with Varying Foot Positions.

The purpose of this study was to investigate balance and motor control in dancers and non-dancers with different foot positions. Physically active female dancers (n = 11) and non-dancers (n = 9) randomly completed two balance tests in a single visit: 1) Y-balance test (YBT), and 2) motor control test (MCT). Each test was completed with two different foot positions: 1) first ballet position in which heels were touching and feet were externally rotated to 140 degrees, and 2) sixth ballet position in which heels were spaced 10 cm apart and forward parallel. For the YBT, participants completed three attempts at anterior, posteromedial, and posterolateral reaches, which were averaged and standardized to limb length for a composite score. For the MCT, participants completed a multi-directional target test on a Biosway balance system, and accuracy and time to completion were analyzed. Findings revealed no differences in YBT score (p = 0.255), MCT score (p = 0.383), or MCT time (p = 0.306) between groups in the sixth position. However, dancers displayed better YBT scores (p = 0.036), MCT scores (p = 0.020), and faster MCT times (p = 0.009) in the first position. Results suggest that superior balance and motor control in dancers may be limited to less innate dance-specific foot positions.

Interaction between TRPV1-expressing neurons in the hypothalamus.

Transient receptor potential vanilloid type 1 (TRPV1) is a ligand-gated ion channel expressed in the peripheral and central nervous systems. TRPV1-dependent mechanisms take part in a wide range of physiological and pathophysiological pathways including the regulation of homeostatic functions. TRPV1 expression in the hypothalamus has been described as well as evidence that TRPV1-dependent excitatory inputs to hypothalamic preautonomic neurons are diminished in diabetic conditions. Here we aimed to determine the functional expression of TRPV1 in two hypothalamic nuclei known to be involved in the central control of metabolism and to test the hypothesis that TRPV1-expressing neurons receive TRPV1-expressing inputs. A mouse model (TRPV1Cre/tdTom) was generated to identify TRPV1-expressing cells and determine the cellular properties of TRPV1-expressing neurons in adult mice. Our study demonstrated the functional expression of TRPV1 in the dorsomedial hypothalamic nucleus and paraventricular nucleus in adult mice. Our findings revealed that a subset of TRPV1Cre/tdTom neurons receive TRPV1-expressing excitatory inputs, indicating direct interaction between TRPV1-expressing neurons. In addition, astrocytes likely play a role in the modulation of TRPV1-expressing neurons. In summary, this study identified specific hypothalamic regions where TRPV1 is expressed and functional in adult mice and the existence of direct connections between TRPV1Cre/tdTom neurons. NEW & NOTEWORTHY Transient receptor potential vanilloid type 1 (TRPV1) is expressed in the hypothalamus, and TRPV1-dependent regulation of preautonomic neurons is decreased in hyperglycemic conditions. Our study demonstrated functional expression of TRPV1 in two hypothalamic nuclei involved in the control of energy homeostasis. Our results also revealed that a subset of TRPV1-expressing neurons receive TRPV1-expressing excitatory inputs. These findings suggest direct interaction between TRPV1-expressing neurons.

The Feasibility of Using the BrightHearts Biofeedback-Assisted Relaxation Application for the Management of Pediatric Procedural Pain: A Pilot Study.

OBJECTIVE: The objective of this pilot study was to assess the acceptability and feasibility of using BrightHearts, a biofeedback-assisted relaxation application (app), in children undergoing painful procedures. METHODS: Thirty children 7 to 18 years of age undergoing a medical procedure (peripheral blood collection, botulinum toxin injection, or intravenous cannula insertion) participated. Participants used BrightHearts, a heart rate-controlled biofeedback-assisted relaxation training app delivered via an iPad with heart rate measured through a pulse oximeter worn on the ear or thumb. Feasibility was assessed through observations and patient, parent/carer, and healthcare professional feedback. Patient, parent/carer, and healthcare professional satisfaction with BrightHearts was rated using investigator-developed surveys. RESULTS: Eighty-three percent of child participants reported that they found BrightHearts helpful during the procedure and that they would use BrightHearts again. All parents and 96% of healthcare professionals indicated they would use BrightHearts again. Sixty-four percent of healthcare providers perceived that BrightHearts assisted with the ease of performing the procedure. Qualitative analyses found 2 themes: (1) BrightHearts calms through providing distraction and biofeedback and (2) the impact of BrightHearts on the procedure. CONCLUSIONS: This pilot study demonstrates the feasibility of using biofeedback-assisted relaxation delivered via the BrightHearts app in children undergoing peripheral blood collection and cannulation. Future studies are required to evaluate BrightHearts' efficacy in reducing pain and anxiety during painful procedures and distinguish the effects of a biofeedback-mediated app from distraction.

Caregivers' Perceptions and Attitudes Toward Child Maltreatment: A Pilot Case Study in Tel Aviv, Israel, and Cleveland, USA.

The purpose of this pilot cross-national study was to uncover similarities and differences in three areas that might affect the development of community-based programs targeting child maltreatment: behaviors considered to be maltreatment, perceived contributors to maltreatment, and whether the government or neighbors can do anything about maltreatment. Data were obtained from two neighborhood-based, cross-sectional surveys of adult caregivers of minors: one in Cleveland, USA, the other in Tel Aviv, Israel. The sample consisted of a total of 120 caregivers, in each city 20 residing in a low-SES neighborhood, 20 in a medium-SES neighborhood, and 20 in an elevated-SES neighborhood. Participants were asked (a) to provide three examples of behaviors they considered to be child abuse, (b) to rate the degree to which each of 13 factors contribute to child maltreatment, and (c) to rate the degree to which they agreed with a range of attitudes about maltreatment. The same coding scheme was used in both sites. Logistic regression analyses assessed city differences in dichotomous outcomes, while linear regression analyses assessed city differences in ratings of continuous outcomes. Analyses adjusted for individual and neighborhood characteristics, and accounted for residential clustering in neighborhoods. Primary results indicated that residence in Tel Aviv was associated with greater odds of citing emotional/psychological abuse compared to Cleveland residents. Also compared to Cleveland residents, Tel Aviv residents (a) viewed family structure, family values, religion, child-raising knowledge, and personal history of maltreatment as contributing less to maltreatment, (b) were less likely to agree that anyone could abuse a child or that spanking is necessary, and (c) had substantially greater odds of endorsing the government's ability to address child maltreatment. Concerning study implications, this investigation demonstrated the importance of context in shaping constructions of child maltreatment and the need for caution in replicating interventions without due consideration of potential differences in context, policy, and public opinion.

Discrepancies between clinical assessments of sensory function and electrical perceptual thresholds after incomplete chronic cervical spinal cord injury.

STUDY DESIGN: Prospective experimental. OBJECTIVES: To compare sensory function as revealed by light touch and pin prick tests of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) and the electrical perceptual threshold (EPT) exams in individuals with chronic incomplete cervical spinal cord injury (SCI). SETTING: Pittsburgh, United States. METHODS: EPT was tested using cutaneous electrical stimulation (0.5 ms pulse width, 3 Hz) in 32 healthy controls and in 17 participants with SCI over key points on dermatomes C2 to T4 on each side of the body. Light touch and pin prick ISNCSCI scores were tested at the same key dermatomes in SCI participants. RESULTS: In controls, EPT values were higher in older males (1.26±0.2 mA, mean±s.d.) compared with younger males (1.0±0.2 mA) and older females (0.9±0.2 mA), regardless of the dermatome and side tested. Fifteen out of the seventeen SCI participants showed that the level of sensory impairment detected by the EPT was below the level detected by the ISNCSCI (mean=4.5±2.4, range 1-9). The frequency distribution of EPTs was similar to older male controls in dermatomes above but not below the ISNCSCI sensory level. The difference between EPT and ISNCSCI sensory level was negatively correlated with the time post injury. CONCLUSIONS: The results show that, in the chronic stage of cervical SCI, the EPT reveals spared sensory function at lower (~5) spinal segments compared with the ISNCSCI sensory exam. It is hence found that the EPT is a sensitive tool to assess recovery of sensory function after chronic SCI.

Lifestyle and in vitro fertilization: what do patients believe?

BACKGROUND: Patients have many beliefs regarding lifestyle factors and IVF outcomes. METHODS: Observational study of 208 IVF patients at an academic infertility center. Main outcome measures were perceived influence of various lifestyle factors assessed by multivariable logistic regression and p-value tests for linear trend (Pt). RESULTS: A majority of participants believed that there were many women's lifestyle choices that were influential, compared to fewer male factors (cessation of tobacco (72 %), alcohol (69 %), caffeine (62 %), and use of vitamins (88 %)). Compared to participants with less education, participants with a higher education level were less likely to believe vitamins were helpful and some alcohol use was not harmful. As income decreased, participants were less likely to consider dietary factors contributory to IVF success, such as women (p-trend, p = 0.02) and men (p-trend, p = 0.009) consuming a full-fat dairy diet. Participants' beliefs were most commonly influenced by physicians (84 %) and the internet (71 %). CONCLUSIONS: Patients believed many lifestyle factors are associated with IVF success. Understanding patients' assumptions regarding the effect of lifestyle factors on IVF success may better allow physicians to counsel patients about IVF outcomes.

The impact of lifestyle modifications, diet, and vitamin supplementation on natural fertility.

BACKGROUND: Infertility is a relatively common condition. When patients are confronted with this diagnosis, there are medical, psychological, and financial sequelae. Patients often wonder if there is anything they can do to optimize their natural fertility or increase the effectiveness of infertility treatments. FINDINGS: If there is a clear impact on fertility, such as with smoking and alcohol, cessation should be advised. Similarly, weight loss should be recommended if the BMI is in the overweight and obese category, and weight gain should be recommended for an underweight BMI. The evidence surrounding other lifestyle modifications is less clear. There are conflicting data regarding an optimal fertility diet and consumption of vitamins and supplements. Antioxidants seem to improve semen parameters in men, but the effect on female fertility is less clear. If conflicting evidence exists, such as with caffeine consumption or exercise, moderation should be emphasized. Finally, the diagnosis of infertility and subsequent fertility treatments are stressful for both partners. The psychological aspects should not be ignored and methods such as yoga and cognitive behavioral therapy may be beneficial. CONCLUSION: Continued research will determine the optimal lifestyle modifications to achieve pregnancy.

Why do patients choose to attend a private emergency department?

OBJECTIVE: Understanding the reasons patients decide to attend a particular acute care service, and their expectations of that service, is important in providing optimal patient care. The present study aimed to determine factors influencing patient decisions to attend a private Australian ED, an issue that has not been previously addressed in the literature. METHODS: Semi-structured face-to-face interviews with ED patients, purposively sampled to broadly reflect the departmental caseload and casemix. The two primary questions asked were: 'Why did you choose to come to this emergency department?' and 'What are your general expectations of this emergency department visit?'. Interviews were audio recorded, transcribed verbatim, and then analysed using manifest and then latent content analysis techniques. RESULTS: All patients approached (n = 30) agreed to interview. Four key themes were identified: prior experience of the hospital, convenient location of the hospital, anticipated high-quality care and anticipated short wait times. CONCLUSIONS: Patients chose to use the private ED because of prior experience, proximity, and an expectation they would be seen promptly and be provided with competent care.

Reducing barriers to timely MR imaging scheduling.

Scheduling a magnetic resonance (MR) imaging study at the authors' large health system in 2011 required considerable preparation before an appointment time was given to a patient. Difficulties in promptly scheduling appointments resulted from the varying time required for examinations, depending on the requested protocol, availability of appropriate MR imaging equipment, examination timing, prior insurance authorization verification, and proper patient screening. These factors contributed to a backlog of patients to schedule that regularly exceeded 300. A multidisciplinary process-improvement team was assembled to improve the turnaround time for scheduling an outpatient MR imaging examination (the interval between the time when the order was received and the time when the patient was informed about the MR imaging appointment). Process improvements targeted by the team included protocol turnaround time, schedule standardization, schedule intervals, examination timing, service standards, and scheduling redesign. Using lean methods and multiple plan-do-check-act cycles, the time to schedule an outpatient MR imaging examination improved from 117 hours to 33 hours, a 72% reduction, during the 9-month study period in 2011-2012. The number of patients in the scheduling queue was reduced by 90%. Overall MR imaging examinations within the specific patient population studied increased from 773 patient studies during the first month of intervention to 1444 studies the following month and averaged over 1279 patient studies per month throughout the study.

Perceptions among infertile couples of lifestyle behaviors and in vitro fertilization (IVF) success.

PURPOSE: To assess how patients perceive various lifestyle behaviors impact IVF success. METHODS: Cross-sectional study of heterosexual, English-speaking couples (n = 138) who completed web-based surveys during IVF treatment cycle. Perceived impact of lifestyle choices assessed by multivariable logistic regression and p-value tests for linear trend (Pt). RESULT(S): During the IVF cycle, most patients consider it helpful for women to exercise (76 %), avoid stress (87 %) and limit activity after embryo transfer (92 %). The majority of patients (62 %) consider rigorous exercise (4+ h/week) helpful and nearly one-third (32 %) perceive benefit to complete bed rest after transfer. Overall, couples with a sex-specific infertility diagnosis are more likely to consider partner's lifestyle choices impactful: male-factor couples are more likely to consider it helpful for men to limit cellular phone use (OR:2.73,CI:1.06-7.04) and diminished ovarian reserve couples are more likely to consider it helpful for women to limit exposure to plastics (OR:2.38,CI:1.03-5.51). Patients at higher levels of education (Pt < 0.01) and income (P(t) < 0.01) are less likely to consider lifestyle impactful. CONCLUSION(S): Patient perceptions of the impact of lifestyle factors on IVF success vary by sex, infertility diagnosis and socioeconomic factors. Despite counseling to the contrary, many patients perceive benefit to rigorous exercise during the IVF cycle and complete bedrest following transfer. Results provide insight into patient beliefs and highlight opportunities to improve patient education, alleviate patient anxieties and potentially improve IVF outcomes.

Modifiable Risk Factors and Infertility: What are the Connections?

Infertility is a relatively common condition, greatly affecting couples medically and psychologically. Although infertility treatment is safe, it can be time-intensive, expensive and increase the risk of multiple gestations. Thus, to reduce costs and risks, couples may initially consider lifestyle change to increase their fertility and chances of pregnancy. For many of the diet factors studied (for example: caffeine, soy, protein, iron), there are conflicting data. However, there are some items men and women consume that are detrimental to fertility, such as alcohol and tobacco. The data on exercise are varied but may have an effect on ovulation and fertility - positive or negative. Body mass index appears to impact fertility also, with obesity in both men and women negatively affecting pregnancy rates. In addition, there remains concern and a growing body of research on environmental toxin exposures and reproductive health. Finally, supporting patients through infertility diagnosis and treatment is critical, as psychological stress may impact conception. It is imperative that the relationship between lifestyle factors and fertility continue to be explored as to lessen the morbidity associated with infertility.

In vitro fertilization outcomes and alcohol consumption in at-risk drinkers: the effects of a randomized intervention.

BACKGROUND AND OBJECTIVES: Women's use of alcohol in pregnancy is associated with an increased risk of fetal loss and birth defects. Also, alcohol use in women decreases the success of infertility treatment, such as in vitro fertilization (IVF). Our goal was to determine if there were differences in IVF outcomes and alcohol use parameters among at-risk drinkers randomized to a brief intervention (BI) versus assessment only (AO). METHODS: We conducted a randomized controlled trial to determine the effect of BI or AO among at-risk drinkers on IVF. We studied 37 women (AO = 21; BI = 16). RESULTS: While the BI group had a significantly greater decrease in the number of drinks/drinking day compared to the AO group (p = .04), there were no differences in the likelihood of implantation failure, chemical pregnancy, spontaneous abortion, preterm birth, or live birth. CONCLUSIONS: BI and AO contributed to a decrease in alcohol use and did not demonstrate differences in IVF outcomes. A larger study may confirm these preliminary findings. SCIENTIFIC SIGNIFICANCE: Our results will assist care providers in treating alcohol use in pregnancy in an effective way, such that IVF cycles and the chance of pregnancy are optimized.

Ovarian reserve in women treated for acute lymphocytic leukemia or acute myeloid leukemia with chemotherapy, but not stem cell transplantation.

Purpose. It is well known that chemotherapy regimens may have a negative effect on ovarian reserve, leading to amenorrhea or premature ovarian failure. There are little data regarding the effects of leukemia chemotherapy on ovarian reserve, specifically in women who received the chemotherapy as adults and are having regular menstrual periods. Our primary objective was to determine if premenopausal women with a history of chemotherapy for leukemia, without subsequent stem cell transplantation, have decreased ovarian reserve. Materials and Methods. We measured ovarian reserve in five women who had been treated for acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) and compared them to age-matched control women without a history of chemotherapy. Results. There appeared to be a trend towards lower antimullerian hormone and antral follicle counts and higher follicle-stimulating hormone levels in the leukemia group. Conclusion. Our results indicate that chemotherapy for AML or ALL without stem cell transplantation may compromise ovarian reserve. Although our results should be confirmed by a larger study, oncologists, infertility specialists, and patients should be aware of the potential risks to ovarian function and should be counseled on options for fertility preservation.