Success Rate and Predicting Factors for Repeated High-Dose Intradetrusor Dysport Injections in Children With Neurogenic Bladder: A Retrospective Study.

OBJECTIVES: Evaluating the effectiveness and safety of repeated high-dose intradetrusor abobotulinumtoxin A (Dysport®) injections for the treatment of pediatric neurogenic bladders refractory to medications. DESIGN: Retrospective interventional study. PARTICIPANTS: The cohort included 37 children (22 boys and 15 girls) of median age 9.2 years. Inclusion criteria were diagnosis of neurogenic bladder and failure to respond to medical treatment. Exclusion criteria were augmented bladder, insufficient data, and interval of > 11 months between video-urodynamic study and Dysport injection. INTERVENTIONS: All participants were treated with an intra-detrusor injection of Dysport 30 IU/kg (up to 1000 IU) under general anesthesia. Repeated (second and third) injections were scheduled (6-12 months) in patients who demonstrated an improvement in cystometric parameters. All participants underwent video urodynamic testing before onset of treatment and 4-5 months after subsequent injection. MAIN OUTCOME MEASURES: Success of treatment was defined as a decrease in end filling pressure (EFP) to < 40 cm H2O and/or a 20% increase in maximal cystometric capacity (MCC). These parameters along with initial bladder features were evaluated for ability to predict treatment success. RESULTS: No side effects of Dysport were observed or reported. The overall success rate was 62%. MCC increased by a median of 30% (IQR 200-300, p < 0.001), 37% (IQR 197-310, p = 0.001) and 45% (IQR 245-300, p = 0.025) after the first, second and third injections, respectively. Median EFP decreased from 45 cm H2O to 34 cm H2O (IQR 20-45, p = 0.029), 23 cm H2O (IQR 20-37, p = 0.004), and 20 cm H2O (IQR 12-32, p = 0.049) after the first, second, and third injections, respectively. No predicting factor of success of treatment were found; However, three of five cases of "end stage" bladder showed improvement. CONCLUSIONS: High-dose Dysport injection is safe and effective for the treatment of neurogenic bladder. Studies with larger cohort and a control group would further elucidate which bladders would benefit most. At present, we recommend treating also bladders with "end stage" features with botulinum toxin before considering augmentation.

Fluoroscopic-guided hysteroscopic tubal cannulation results in high technical success and pregnancy rates comparable with the more traditional laparoscopically guided hysteroscopic tubal cannulation.

Objective: To compare women with proximal tubal obstruction (PTO) undergoing hysteroscopic tubal cannulation with fluoroscopic guidance vs. laparoscopic guidance. Design: Retrospective cohort study. Setting: All fluoroscopically-guided hysteroscopic tubal cannulations were performed in an ambulatory suite. All laparoscopically-guided hysteroscopic tubal cannulations were performed in a hospital operating room. Patients: Infertile women with unilateral or bilateral PTO on hysterosalpingography who failed selective salpingography in the radiology suite and had a planned laparoscopy or hysteroscopy in the operating room for defects seen on sonohysterography were studied. Intervention: All women had a Novy catheter system positioned hysteroscopically to cannulate the occluded fallopian tube(s). Women undergoing fluoroscopically guided hysteroscopic tubal cannulation (FHTC), which used contrast and C-arm pelvic imaging at an ambulatory center, were compared with those undergoing hospital-based laparoscopically guided hysteroscopic tubal cannulation (LHTC) with laparoscopic visualization. Main Outcome Measurements: Tubal cannulation success; bilateral cannulation success; tubal perforations; post-FHTC non-in vitro fertilization (non-IVF) intrauterine pregnancies; days from procedure to pregnancy for non-IVF intrauterine pregnancies; and time to non-IVF pregnancy hazards ratio. Results: A total of 76 infertile women undergoing either FHTC (34 women) or LHTC (42 women) between 2015 and 2019 were included. Demographic variables were similar among the 2 groups. A total of 31 (92%) of 34 of patients undergoing FHTC and 36 (86%) of 42 of patients undergoing LHTC had at least one tube successfully cannulated. In total, 30 (78%) of 34 of patients undergoing FHTC and 32 (79%) of 42 patients undergoing LHTC had all occluded tubes successfully cannulated. Tubal perforation occurred in 1 (3%) of 34 FHTC cases and 3 (7%) of 42 LHTC cases. A similar percentage of non-IVF treatment-induced intrauterine pregnancies were achieved in the FHTC and LHTC groups (10/34 [29%] vs. 12/42 [29%]). Among patients who conceived without IVF, time from procedure to pregnancy was lower in the FHTC group (101 ± 124.6 days) compared with the LHTC group (228 ± 216 days). There was a significant difference in time to pregnancy when only those who conceived were considered (hazard ratio, 9.39; 95% confidence interval, 2.42-36.51); however, there was no significant difference when all subjects regardless of pregnancy outcome were analyzed (hazard ratio, 1.48; 95% confidence interval, 0.64-3.446). Conclusion: Fluoroscopically guided hysteroscopic tubal cannulation is a safe, effective, incision free procedure that results in comparable rates of tubal patency and intrauterine pregnancies as LHTC. This technique should be considered in women undergoing treatment of PTO when operative laparoscopy is not otherwise indicated.

Racial Disparities in Fertility Care: A Narrative Review of Challenges in the Utilization of Fertility Preservation and ART in Minority Populations.

Significant ethnic and racial disparities exist in the utilization and outcomes of assisted reproductive technology (ART) in the United States. The popularity of fertility preservation (FP) procedures, a specific application of ART for those desiring to delay childbearing, has increased; however, many minority populations have seen a less rapid uptake of these services. Minority patients pursuing ART are more likely to have poorer in vitro fertilization (IVF) and pregnancy outcomes. These outcomes are used to predict success after FP and may lessen the appeal of such procedures in these populations. Suboptimal outcomes are further compounded by challenges with receiving referrals to, accessing, and paying for FP services. Resolving these disparities in minority populations will require culturally appropriate education surrounding the benefits of ART and FP, the demonstration of favorable outcomes in ART and FP through continued research engaging minority participants, and continued advocacy for expanded access to care for patients.

The Status of Fertility Preservation (FP) Insurance Mandates and Their Impact on Utilization and Access to Care.

Fertility preservation (FP) is the use of a specific medical intervention to protect the fertility of individuals whose disease or disease treatment may lead to infertility. These medical interventions include the cryopreservation of oocytes, embryos, ovarian tissue, sperm, and testicular tissue; oocyte and embryo cryopreservation are the most widely used interventions in the United States. Although guidelines recommend FP prior to undergoing gonadotoxic treatments, cost barriers are high. For example, the average cost of an oocyte cryopreservation cycle in the United States exceeds $10,000. High cost and lack of insurance coverage are two of the most cited reasons explaining the low Reproductive Endocrinology and Infertility (REI) referral rates and limited FP utilization. Broadening insurance mandates for FP prior to gonadotoxic treatments could improve utilization and provide cancer survivors with improved quality of life post treatment.

Extensive Hydrocelectomy Using the Harmonic Scalpel Supersedes Classic Techniques.

OBJECTIVE: To present our technique using the harmonic scalpel for scrotal, extensive hydrocelectomy in adolescents and its advantages, compared with the historical techniques. Scrotal hydrocelectomy is an old-timer procedure in-which the Lord plication, the Jaboulay and the bottleneck techniques are the standard of care, up to date. A cumbersome, unpleasant scrotal dressing is commonly used to try to mitigate postoperative edema and hematoma.1 The harmonic scalpel denaturates proteins by ultrasonic vibrations, and provides advantages over conventional electrocautery with respect to bleeding, drain volume, postoperative pain, and the return to normal activity.2-5 MATERIALS: Adolescents with a large hydrocele, and no inguinal hernia were selected for this operation. All tissue layers except the skin were divided by harmonic scalpel Focus (Eticon). RESULTS: Between 2017 and 2023, 43 adolescents at a median age of 14.3years (range 12-18years), were operated with this technique, using the harmonic scalpel, by a single surgeon. Median operative time was 23 minutes (range 18-35 minutes). No scrotal dressing was used. One patient had a postoperative seroma that was drained spontaneously. CONCLUSION: The described technique is simple and time-saving, with no postoperative major edema nor hematoma in this series. The only disadvantage is the higher cost of the harmonic scalpel, that may be offset by a short time of recovery. Following our experience, we no longer use other techniques for this surgery.

Survey of young women with breast cancer to identify rates of fertility preservation (FP) discussion and barriers to FP care.

PURPOSE: To identify the proportion of reproductive age women with breast cancer that engaged in a fertility preservation discussion and reproductive endocrinology and infertility (REI) consultation. METHODS: This cross-sectional survey recruited women 18-42 years who were diagnosed with breast cancer from 2006 to 2016 by phone or email and asked them to complete an online survey. Demographic characteristics, barriers to FP, utilization of FP consultation, and FP procedures (oocyte and embryo cryopreservation) were analyzed. RESULTS: A majority of women (64%) did not have FP discussed by any provider. Older women and those who were parents at the time of diagnosis were less likely to engage in a FP discussion. However, there were no significant differences in partner status or cancer stage between women with or without FP discussions. Of the women who desired future children prior to the cancer diagnosis, 93% received chemotherapy; however, only 34% of these women had a consultation with an REI. The most common reasons for declining FP consultation were already having their desired number of children (41%), financial barriers (14%), and concern about delaying cancer treatment and cancer recurrence (12%). Forty percent of women who desired future children and met with an REI pursued FP procedures. CONCLUSION: Younger women were more likely to receive FP counseling. FP consultations and procedures were low even in women who desired future fertility, with the predominant barriers being cost, fears concerning a delay in cancer treatment, and future cancer recurrence.

The accuracy of cystography under general anesthesia in children with vesicoureteral reflux.

PURPOSE: To examine the accuracy of cystography under general anesthesia in children with vesicoureteral reflux (VUR). MATERIALS AND METHODS: A prospective study of children who had VUR on cystography without general anesthesia (i.e., the gold-standard), and who are candidates for endoscopic VUR repair surgery. All children subsequently underwent a cystography under general anesthesia before injection using standardized method, which was compared to the gold-standard cystography. χ2 and Mann-Whitney U tests were used to compare proportions and medians between groups. RESULTS: Between 2017 and 2021, 126 renal units in 13 boys and 50 girls were included. Median age was 3.4 years (interquartile range [IQR] 1.5-6.5). Median time from cystography without to cystography with general anesthesia was 3.8 months (IQR 2.7-6). Of the 126 renal units, 96 had VUR on cystography without general anesthesia. On dichotomous analysis (no VUR vs. any VUR) sensitivity, specificity, negative and positive predictive values of cystography under general anesthesia were 47% (45/96), 87% (26/30), 34% (26/77) and 92% (45/49), respectively. Accuracy was 56.3%; Cohen's Kappa coefficient was 0.22, indicating poor agreement. In subgroup analysis, the sensitivity of cystography under general anesthesia was significantly lower in primary VUR (20% vs. 55% in secondary VUR, p = 0.01) and active VUR (14% vs. 52% in passive VUR, p = 0.008). CONCLUSION: Cystography under general anesthesia was poorly correlated to cystography performed while the child was awake or lightly sedated. Clinical decision relying on this cystography is questionable.

Fluoroscopically-Guided Hysteroscopic Tubal Cannulation: A Procedure for Proximal Tubal Obstruction.

Objectives: To evaluate the cannulation success rate, cumulative pregnancy, and time to intrauterine pregnancy rate following fluoroscopically-guided hysteroscopic tubal cannulation (FHTC) for infertile subjects with proximal tubal obstruction. Methods: This retrospective study evaluated subjects with unilateral or bilateral proximal tubal obstruction on hysterosalpingography, who failed concomitant selective salpingography and subsequently underwent FHTC at the time of a hysteroscopy performed for findings seen on sonohysterography. FHTC employed a Novy Catheter (CooperSurgical, Inc, Trumbull, CT.) with or without the 3 French inner catheter and guidewire, to cannulate the occluded fallopian tube(s), followed by the injection of HypaqueTM (Amersham Health, Inc, Princeton, NJ.) contrast under C-arm imaging. Technical success rates, complications, post-procedure pregnancies, and average time from surgery to pregnancy were evaluated. Results: Thirty-two women between January 1, 2017 and December 31, 2019 met the entry criteria and underwent FHTC. Of those women with bilateral obstruction, 6/6 (100%) of subjects achieved at least unilateral patency, while patency was achieved in 23/26 (88.5%) subjects with unilateral obstruction. Twenty-nine of 32 (90.6%) subjects had at least one tube successfully cannulated with 34/38 (89.5%) of proximally obstructed tubes opened. Asymptomatic tubal perforation occurred in 1/38 tubes (2.6%). Ten subjects (34.5%) achieved intrauterine pregnancies without in vitro fertilization in an average of 64.9 days from the procedure. There were no multiple pregnancies and one ectopic pregnancy. Conclusions: FHTC is a safe, effective, incision free procedure that results in 90% of tubes successfully cannulated, and an observed short time to intrauterine pregnancy.

Positron charge sensing using a double-gated graphene field effect transistor.

We utilize a high-mobility double-gated graphene field-effect transistor to measure the accumulated charge created by positron annihilation in its back-gate. The device consists of an exfoliated graphene flake stacked between two hexagonal boron nitride flakes placed on a 1 cm2 substrate of 500 µm thick conducting p-doped Si capped by 285 nm-thick SiO2. The device is placed in close proximity to a 780 kBq 22Na positron source emitting a constant flux of positrons. During the measurement, positrons annihilate within the back-gate, kept floating using a low-capacitance relay. The accumulated positive charge capacitively couples to the graphene device and builds a positive voltage, detectable through a shift in the top-gate dependent graphene resistance characteristic. The shift in the position of the top-gate Dirac peak is then used for extracting the exact voltage buildup and quantitative evaluation of the accumulated charge. Reaching a positron current sensitivity of ∼1.2 fA/Hz, detected over 20 min, our results demonstrate the utility of two-dimensional layered materials as probes for charging dynamics of positrons in solids.

Fertility Treatments and Breast Cancer: A Significant Risk for Our Patients?

Fertility medications have been postulated to increase the risk of breast cancer because of the transient but substantial elevation in hormones occurring with their use. Multiple studies exploring the relationship between fertility medications and risk of breast cancer are limited by the wide variety of fertility treatment regimens and confounded by infertility as an independent risk factor for breast cancer. The Practice Committee Guidelines of the American Society of Reproductive Medicine acknowledge that although this relationship is complex, no additional risk of breast cancer has been consistently linked to infertility medications. This article reviews the major studies both supporting and refuting this statement and makes recommendations regarding risk counseling and breast cancer screening in patients with a history of fertility treatments and infertility.

Society for Assisted Reproductive Technology advertising guidelines: How likely are member clinics to maintain compliance after resolving their violations?

OBJECTIVE: To evaluate the Society for Assisted Reproductive Technology (SART) member in vitro fertilization centers' compliance with SART's advertising guidelines after delayed correction of previous violations. DESIGN: Retrospective cohort study. SETTING: Internet. PATIENTS: None. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Clinics that were cited for noncompliance with SART advertising guidelines in 2019 and exceeded the two-week grace period in correcting their violations were studied. These clinics were rereviewed in 2020, at least 6 months after their initial citation, for violations of SART advertising guidelines in all six categories: supplemental data noncompliance, link to SART Clinical Summary Report and disclaimer statement missing, unsubstantiated claims, statements denigrating other clinics, and claims of superiority. RESULTS: In 2019, 44 (27%) of 161 of clinics reviewed by the SART advertising committee had at least one violation that was eventually resolved but not within the two-week grace period. On rereview in 2020, one clinic had not renewed its SART membership and 10 (23%) of the remaining 43 clinics were noted to have violations at the subsequent review. Improper presentation of supplemental data was the most common violation category in both the initial review, 32 (73%) of 44 clinics, and on rereview, 7 (70%) of 10 clinics cited a second time for violations. CONCLUSIONS: Of the in vitro fertilization clinics with previous violations with delayed correction in 2019, 77% were subsequently compliant when reevaluated in 2020, indicating that advertising committee disciplinary and educational measures were largely effective. The most common citation for both years was maintaining consistent and transparent supplemental data on their websites.

Do endometrial natural killer and regulatory T cells differ in infertile and clinical pregnancy patients? An analysis in patients undergoing frozen embryo transfer cycles.

PROBLEM: Clinical significance of endometrial and peripheral blood natural killer (NK) and regulatory T cells (Tregs) during frozen embryo transfer (FET) cycles has not been well characterized. DESIGN: Retrospective cohort study. METHOD OF STUDY: Endometrial tissue was collected from infertility patients prior to a frozen embryo transfer cycle as part of an endometrial receptivity analysis (ERA® ) biopsy or endometrial scratch test. Uterine NK (uNK) and Treg cell density was compared based on pregnancy status in the subsequent frozen embryo transfer cycle. Peripheral blood was also collected from a separate cohort of patients undergoing frozen embryo transfer. Treg cell density was compared by the presence or the absence of a clinical pregnancy in each phase of the cycle. RESULTS: In the 33 luteal phase biopsies there were more endometrial Tregs, similar uNK and a trend toward lower CD16+ uNK cells in women with a future ongoing clinical pregnancy compared to non-pregnant women. There were no differences in uNK and Treg density in natural scratch cycles vs programmed cycles or in non-receptive vs receptive endometrium (ERA® cycles). In the peripheral blood analysis, the pregnant group had higher peripheral blood Tregs on the day of serum ß-hCG time point when compared to the non-pregnant group. CONCLUSION: Higher levels of endometrial Tregs and lower levels of CD16+ uNK cells are positive prognostic factors for infertile women prior to frozen embryo transfer. Our work on phenotypic and proportional analyses of endometrial immune cells may complement the ERA® in predicting improved pregnancy rates in patients with implantation failure.

Novel predictive and therapeutic options for better pregnancy outcome in frozen embryo transfer cycles.

Since 1978, in the first decades of in vitro fertilization (IVF), the use of ovarian hyperstimulation allowed for the development and transfer of multiple embryos. As IVF technology improved, the number of multiple pregnancies increased, which led to gradual reduction in the number of embryos that were transferred. Embryo freezing (vitrification) was recommended to allow subsequent transfer if the fresh cycle was unsuccessful. However, experimentation has continued to improve pregnancy outcomes. We discuss here the significance of frozen embryo transfer cycle and the impact of uterine and peripheral immunity dominated by NK cells and regulatory T cells and human chorionic gonadotropin on pregnancy outcome in this innovative mode of IVF therapy.

Society for Assisted Reproductive Technology advertising guidelines: How are member clinics doing?

OBJECTIVE: To examine whether Society for Assisted Reproductive Technology (SART) member in vitro fertilization (IVF) centers adhere to the Society's new advertising policy, updated in January 2018, and evaluate other services advertised by region, insurance mandate and university affiliation status. Historically, a large percentage of IVF clinics have not adhered to SART guidelines for IVF clinic website advertising and have had variability in how financial incentives and other noncore fertility services are advertised. DESIGN: Cross-sectional study. SETTING: Not applicable. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Adherence of SART participating websites to objective criteria from the 2018 SART advertising guidelines. RESULT(S): All 361 SART participating clinic websites were evaluated. Approximately one third of clinics reported success rate statistics directly on their websites, but only 52.6% of those clinics reported current statistics. Similarly, only 67.5% of SART member clinics included the required disclaimer statement regarding their outcome statistics. Only 10.5% of websites were wholly compliant with SART guidelines regarding presentation of supplemental data. There were no significant differences between academic and nonacademic centers, programs in mandated versus nonmandated states, or East versus West Coast clinics in any of these areas. CONCLUSION(S): Many of the SART member websites failed to adhere to core guidelines surrounding reporting IVF clinic success rates. Consideration for additional education and streamlining as well as simplifying success rate advertising guidelines is recommended.

Human chorionic gonadotropin-mediated modulation of pregnancy-compatible peripheral blood natural killer cells in frozen embryo transfer cycles.

PROBLEM: To evaluate pregnancy-compatible phenotypic and functional changes in peripheral blood natural killer (pNK) cells during frozen embryo transfer (FET) cycles. METHOD OF STUDY: Peripheral blood was collected from patients undergoing frozen embryo transfer cycles at three separate time points in the cycle. pNK cell phenotype was analyzed by flow cytometry. Impact of pregnancy status on pNK cell cytotoxicity was characterized by two methods: (1) a three-dimensional endovascular tube formation approach and (2) a NK cell-specific K562 cell kill assay. RESULTS: A total of 35 patients were enrolled, 15 with clinical pregnancies and 20 with negative serum ß-hCG levels. Overall percentage of CD45+ CD3- CD56+ pNK cell did not change during the FET cycle. Pregnancy resulted in an increase in CD45+ CD3- CD56+ pNK cell population on the day of serum ß-hCG. pNK cells from non-pregnant patients caused significant tube disruption when compared to pregnant patients. Addition of serum from pregnant women reduced the tube disruption by pNK cells from non-pregnant patients. pNK cells from pregnant patients showed significantly lower cytotoxicity toward K562 cells in serum-free conditions. The addition of pregnancy serum decreased non-pregnant pNK cell cytotoxicity. Pregnancy status had no impact on VEGF-A and VEGF-C serum levels. Recombinant hCG added to non-pregnant serum resulted in a significant reduction in non-pregnant pNK cell-mediated K562 cell kill. CONCLUSION: There was no difference in pNK cell populations based on timing of the FET cycle. However, pregnancy increased the percentage of CD45+ CD3- CD56+ pNK cells. Additionally, pNK cells from pregnant women have reduced cytotoxicity and this is possibly mediated by hCG.

Is intracytoplasmic sperm (ICSI) better than traditional in vitro fertilization (IVF): confirmation of higher blastocyst rates per oocyte using a split insemination design.

PURPOSE: To explore the effects of traditional vs. intracytoplasmic sperm injection (ICSI) insemination method on the outcome of high-quality blastocyst development in a split sibling oocyte cohort. METHODS: In this retrospective cohort study, we analyzed 62 ICSI/IVF split cycles. Sibling oocytes were randomly assigned to ICSI or IVF insemination. Two hundred thirty-four ICSI-only cycles and 152 IVF-only cycles were also analyzed for comparison. Blastocysts were graded by Gardner's embryo grading and were considered a high-quality blastocyst if 3BB or better (Gardner 1999). RESULTS: In the ICSI/IVF split group, (1) ICSI oocytes had a higher fertilization rate per oocyte allocated (73% vs 62%, p < 0.001), (2) more high-quality day 2 embryos (69% vs 55%, p < 0.005), (3) ICSI oocytes had a lower blastulation rate per 2PN (46% vs 54%, p < 0.05), but a higher blastulation rate when calculated per oocyte allocated (40% vs 32%, p < 0.05). The ICSI-only group had a lower fertilization rate (65% vs 70%, p < 0.001) but more high-quality day 2 embryos in comparison to the IVF-only group (68% vs 64%, p < .05). The total high-quality blastulation rate was higher for the IVF-only group per 2PN (49% vs 43%, p < 0.05) and per oocyte retrieved (34% vs 28%, p < 0.05). CONCLUSIONS: This distinctive IVF/ICSI sibling oocyte split design demonstrated a higher-quality blastulation rate in the IVF group compared to the ICSI group when calculated per 2PN, but not per oocyte allocated to each insemination procedure.