One size does not fit all: the personal nature of completed embryo donation.

PURPOSE: To assess factors associated with embryo donation among individuals interested in donation in the United States. METHODS: An invitation to complete the 123-item survey was emailed from June to September 2022 to patients at a private practice fertility clinic with interest in donation at the time of IVF. Survey questions included disposition decision, attitudes about embryo status and genetic relatedness, donation disclosure, ideal donation arrangement, and decision satisfaction. RESULTS: Three hundred thirty-seven completed the survey. Two hundred thirty donated to another person(s), 75 discarded embryos, 25 remained undecided, and disposition was unknown for 7 respondents. There were no demographic differences between groups based on final disposition or use of donor gametes. Few gamete recipients were interested in donation due to biological attachment to embryos. Final embryo disposition was associated with religious factors, not wanting to waste embryos, and storage fee concerns. Final disposition was also significantly associated with concern about donor-conceived children's (DCP) welfare, being denied the ability to complete donation, personal IVF outcomes, financial or legal issues, future contact with DCP, cognitive appraisal of disposition, beliefs about embryos, someone else raising their genetic child, anonymity, and beliefs about DCP not knowing genetic relationships (p < .001). Donation to others was associated with less regret and greater satisfaction with the emotional/medical aspects of donation and counseling compared to those who discarded embryos (p < .001). CONCLUSION: The decision to donate embryos to another person(s) is complex. Counseling that considers individual circumstances, values, and evolving dynamics may facilitate informed decision-making for those navigating infertility treatment, family building, and embryo disposition.

Analgesia Using Transcutaneous Electric Nerve Stimulation in Office Bladder Chemodenervation, a Randomized Controlled Trial.

IMPORTANCE: Office bladder chemodenervation, performed via cystoscopy with intradetrusor onabotulinumtoxinA (BOTOX) injections, is a common treatment for overactive bladder/urge urinary incontinence. Transcutaneous electric nerve stimulation (TENS) has shown to provide analgesia during office hysteroscopy. Adjuvant analgesia using TENS during bladder chemodenervation has not been studied. OBJECTIVE: The primary outcome is a clinically significant (10-mm) difference in pain visual analog scale (VAS) measurements during injections for chemodenervation using active TENS compared with placebo TENS. We hypothesize that active TENS use will significantly change pain VAS scores. Secondary outcomes include 5-point pain Likert scale, satisfaction 10-point scale, and adverse events. STUDY DESIGN: This was a double-blind randomized control trial of men and women with urinary urge incontinence undergoing office chemodenervation performed in an academic and private setting. Participants were randomized into 2 groups: chemodenervation with active TENS or placebo TENS. Power calculation determined 100 patients would be required detect a difference of 10 mm on pain VAS. RESULTS: One hundred one (85 female and 16 male) participants were recruited. No differences were noted in the demographics. Participants in the active TENS group reported a difference of greater than 10 mm in pain VAS scores (48 ± 23 vs 31 ± 23, P = 0.01). Satisfaction index scores were high but no difference was noted between groups (8.6 vs 8.7, P = 0.68). CONCLUSIONS: Most participants were eligible to use TENS units. Transcutaneous electric nerve stimulation is a safe and noninvasive adjuvant analgesia option for patients undergoing this procedure. Lower pain levels and high satisfaction rates suggest that this is an additional analgesic option during outpatient chemodenervation.

Examining reasons that patients discard cryopreserved oocytes.

PURPOSE: Assess the rate, rationale, and characteristics of patients who cryopreserved and subsequently discarded their oocytes, and compare their characteristics to patients with continued cryopreservation of oocytes. METHODS: All patients who disposed of cryopreserved oocytes between 2009 and 2022 reported their reason for discarding their oocytes. This was a retrospective cohort study. RESULTS: Of 5,010 patients who underwent oocyte cryopreservation (OC) cycles, 201 (4%) patients elected to discard their oocytes and 751 (15%) thawed oocytes for clinical use. The average ages of OC and disposal were 35 and 39 years old, respectively. Of the 201 patients who discarded their oocytes, 71 patients (35%) requested disposal after having a child. Twenty-six (13%) discarded oocytes because of worsening cancer and three (1.4%) discarded because of death. 16 (8%) discarded oocytes due to cost of cryopreservation and eight (4%) due to low oocyte yield. Ten (5%) patients underwent new IVF cycles and discarded previously stored oocytes. Sixty-seven patients (33%) discarded oocytes for unspecified reasons. When comparing patients who discarded oocytes with those who did not, the former had lower AMH (2.7 vs 3.5 ng/ml, p < 0.001) but otherwise comparable age and number of cryopreserved oocytes. The mean age for those with continued cryopreservation was 35.4 years at time of OC and 40 years at time of data collection in June 2023. CONCLUSION: Childbirth was the most common reason to dispose of oocytes followed by unspecified reasons. Larger studies of oocyte disposal may better define clinical characteristics of patients most likely to use, maintain or discard their oocytes.

Preimplantation genetic testing for sickle cell disease: a cost-effectiveness analysis.

Objective: To evaluate the cost-effectiveness of in vitro fertilization with preimplantation genetic testing for monogenic disease (IVF + PGT-M) in the conception of a nonsickle cell disease (non-SCD) individual compared with standard of care treatment for a naturally conceived, sickle cell disease (SCD)-affected individual. Design: A Markov simulation model was constructed to evaluate a one-time IVF + PGT-M treatment compared with the lifetime standard of care costs of treatment for an individual potentially born with SCD. Using an annual discount rate of 3% for cost and outcome measures, quality-adjusted life years were constructed from utility weights and life expectancy values and then used as the effectiveness measurement. An incremental cost-effectiveness ratio was calculated for both treatment arms, and a willingness-to-pay threshold of $50,000 per quality-adjusted life year was assumed. Setting: Tertiary care or university medical center. Patients: A hypothetical cohort of 10,000 patients was analzyed over a lifetime horizon using yearly cycles. Interventions: In vitro fertilization with preimplantation genetic testing for monogenic disease use in conception of a non-SCD individual. Main Outcome Measures: The primary outcomes of interest were the incremental cost and effectiveness of an IVF+PGT-M conception compared with the SOC treatment of an SCD-affected individual. Results: In vitro fertilization with preimplantation genetic testing for monogenic disease was the optimal strategy in 93.17% of the iterations. An incremental savings of $137,594 was demonstrated with a gain of 1.96 QALYs and 3.69 life years over a lifetime. Sensitivity analysis demonstrated that SOC treatment never met equivalent cost-effectiveness. Conclusions: Our model demonstrates that IVF + PGT-M for selection against SCD, compared with lifetime SOC treatment for those affected, is the most cost-effective strategy within the United States healthcare sector.

Reproductive genetics laboratory may impact euploid blastocyst and live birth rates: a comparison of 4 national laboratories' PGT-A results from vitrified donor oocytes.

OBJECTIVE: To evaluate potential variation in the euploid blastocyst rate and live birth rate (LBR) per single frozen euploid blastocyst transfer, among 4 unique United States reproductive genetics laboratories. Analyses were limited to blastocysts derived from vitrified donor oocytes, to minimize variation in oocyte quality. DESIGN: Retrospective cohort study from 2016 to 2020. SETTING: Donor Egg Bank Database. PATIENT(S): Patients undergoing in vitro fertilization with donor oocytes. We excluded patients with uterine factor, male factor, or surgically extracted sperm. Only healthy women <34 years old were accepted as oocyte donors. INTERVENTION(S): Next generation sequencing platforms for chromosomal analysis MAIN OUTCOME MEASURE(S): Euploid blastocyst rate and LBR per euploid transfer. Secondary outcomes included the rate of aneuploidy, mosaic calls, biochemical pregnancy loss, and miscarriage rate. RESULT(S): A total of 2,633 embryos were included. Four laboratories had >200 embryos tested. Euploid blastocyst rate was significantly higher in laboratory A (73.6%) vs. B (63.3%), C (60.9%), and D (52.3%). Mosaic rate was significantly lower for Laboratories B (2.8%) and C (5.5%) vs. Laboratories A (9.9%) and D (11.5). The LBR was significantly higher in laboratory A (58.73%) vs. laboratory D (47.3%). There were no significant differences in the implantation or miscarriage rate among laboratories. CONCLUSION(S): In this large study, controlling for oocyte quality, some preimplantation genetic testing for aneuploidy (PGT-A) laboratories report a significantly higher euploid blastocyst rate with concurrent higher LBR. This type of comparison is important as it provides insight into the role of the PGT-A process in outcomes. Further research is needed to evaluate the differences in laboratory techniques and bioinformatic algorithms accounting for variable outcomes across PGT-A laboratories.

The impact of the COVID-19 pandemic on gestational carriers.

Reproductive medicine has been significantly impacted by the coronavirus (COVID-19) pandemic, and this includes the gestational carrier (GC) process. The objectives of this commentary are to evaluate the impact of COVID-19 on the GC process, as well to communicate Shady Grove Fertility's considerations of and response to COVID-19 on the GC process to the larger assisted reproductive technology (ART) community. We also gathered conclusions drawn from available data on the impact of COVID-19 infection on maternal and neonatal morbidity and mortality as well as on counseling patients on vaccination. We compiled proposals to mitigate risk and to maximize safe evaluation and treatment for GCs during the ongoing pandemic. Over 2 years after the onset of the pandemic, the multiple resurgences of cases in the USA have necessitated nimble strategies to provide ongoing and safe reproductive care and have posed unique challenges to the GC process. With the prospect of the virus continuing to spread globally well into the future, as healthcare professionals of the ART community, we will need to ensure effective collaboration and communication as we provide care during the ongoing pandemic.

Live birth after transfer of a single euploid vitrified-warmed blastocyst according to standard timing vs. timing as recommended by endometrial receptivity analysis.

OBJECTIVE: To determine whether endometrial receptivity analysis (ERA) improves live births in patients with and without a history of unsuccessful frozen embryo transfers (FETs). DESIGN: Retrospective cohort study. SETTING: Large reproductive center. PATIENT(S): Patients with and without ERA before euploid single FET were included in the analysis. INTERVENTION(S): Subjects in the exposed group underwent ERA and ERA-timed FETs. Subjects in the unexposed group followed a standard protocol FET without ERA. Outcomes were compared between nonreceptive and receptive subjects undergoing an ERA-timed FET and between ERA-timed vs. standard protocol FETs. MAIN OUTCOME MEASURE(S): The primary outcome was a live birth; secondary outcomes were biochemical and clinical pregnancy rates. RESULT(S): A total of 307 ERA-timed FETs and 2,284 standard protocol FETs were analyzed. One hundred twenty-five patients (40.7%) were ERA receptive, and 182 (59.3%) were ERA nonreceptive. After adjusting for the number of the previously failed FETs, there was no difference in the proportion of receptive and nonreceptive ERA results. There were no statistically significant differences in live births in patients with ERA-receptive vs. ERA-nonreceptive results (48.8% and 41.7%, respectively; adjusted odds ratio 1.17; 95% CI, 0.97-1.40). There were no statistically significant differences in live births in patients with or without ERA testing results before FET (44.6% and 51.3%, respectively; adjusted odds ratio 0.87; 95% CI, 0.73-1.04). CONCLUSION(S): Patients with an increasing number of previous failed euploid FET cycles are not at an increased risk of a displaced window of implantation. Patients categorized as receptive vs. nonreceptive and those without ERA testing results have comparable FET success rates.

Gestational carrier pregnancy outcomes from frozen embryo transfer depending on the number of embryos transferred and preimplantation genetic testing: a retrospective analysis.

OBJECTIVE: To compare gestational age, birth weight (BW), and live birth rates in gestational carriers (GC) after the transfer of 1 or 2 frozen embryo(s) with or without preimplantation genetic testing for aneuploidy (PGT-A), with the understanding that several social and economic factors may motivate intended parents to request the transfer of 2 embryos and/or PGT-A when using a GC. DESIGN: Retrospective cohort study SETTING: An assisted reproductive technology practice. PATIENT(S): All frozen blastocyst transfers with GCs from 2009-2018. INTERVENTION(S): One or 2 embryo frozen embryo transfers with and without PGT-A. MAIN OUTCOME MEASURE(S): Live birth, preterm birth, and low BW. RESULTS: A total of 583 frozen embryo transfer cycles with vitrified high-grade blastocysts (grade BB or higher) to GCs were analyzed. Although the live birth rate was significantly greater in frozen embryo transfers with 2 embryos, after single embryo transfer (SET), the mean gestational age and BW of live births were statistically significantly greater than those of double embryo transfer (DET). The rate of multiple births was 1.9% for SET compared to 20.0% for DET per transfer. Only 3.8% of live births from SET experienced low BW and 0.6% had very low or extremely low BW. By comparison, 12.5% of DET live births were low BW and 5% were very low BW. After SET, 13.4% of live births were preterm, compared with 40% in DET. The analysis also included a total of 194 transfers with PGT-A compared to 389 cycles without. Overall, live births per transfer were not significantly different between these latter 2 subgroups. CONCLUSION: Frozen embryo transfer cycles in GCs with DET were associated with more preterm births and lower birth weights compared with those of SET. Intended parents and GCs should be counseled that DET is associated with greater risks of adverse pregnancy and perinatal outcomes, which mitigates higher live birth rates. The use of PGT-A did not appear to improve the live birth rate.

Clarifying the relationship between total motile sperm counts and intrauterine insemination pregnancy rates.

OBJECTIVE: To study the relationship between postwash total motile sperm count (TMSC) and intrauterine insemination (IUI) outcomes. DESIGN: Retrospective review SETTING: Large fertility clinic PATIENT(S): A total of 92,471 insemination cycles from 37,553 patients were included in this study. INTERVENTION(S): All stimulated clomiphene citrate, letrozole, and/or injectable gonadotropin IUI cycles performed at a single institution from 2002 through 2018 were reviewed. Generalized estimating equations (GEE) analysis was used to account for multiple cycles by individual patients and to adjust for female partner age, body mass index, and stimulation protocol. MAIN OUTCOME MEASURE(S): Successful clinical pregnancy was defined as ultrasound confirmation of an intrauterine gestational sac with fetal cardiac activity. RESULT(S): A total of 92,471 insemination cycles were available to evaluate the relationship between postwash TMSC and clinical pregnancy. Pregnancy rates were highest with TMSC of ≥9 × 106 and declined gradually as TMSC decreased. Complete data for the adjusted GEE analysis were available for 62,758 cycles. Adjusted GEE analysis among cycles with TMSC of ≥9 × 106 (n = 46,557) confirmed that TMSC in this range was unrelated to pregnancy. Conversely, TMSC was highly predictive of pregnancy (Wald χ2 = 39.85) in adjusted GEE analysis among cycles with TMSC of <9 × 106 (n = 16,201), with a statistically significant decline. CONCLUSIONS: IUI pregnancy is optimized with TMSC of ≥9 × 106, below which the rates gradually decline. Although rare, pregnancies were achieved with TMSC of <0.25 × 106. Since the decline in pregnancy is gradual and continuous, there is no specific threshold above which IUI should be recommended. Rather, these more specific quantitative predictions can be used to provide personalized counseling and guide clinical decision making.

Views of parents of children with sickle cell disease on pre-implantation genetic diagnosis.

Pre-implantation genetic diagnosis (PGD) is an option for parents who have a child with sickle cell disease (SCD) to have another child without SCD. We conducted a survey of 19 parents with at least one child with SCD to investigate views on PGD. Before education, 44% of parents were aware of PGD. All parents rated PGD education as important. All parents considering another child also reported interest in using PGD if insurance covered its costs. Parents who have a child with SCD appear to be interested in PGD and educational tools informing this group about PGD should be developed.

Cautery artifact understages urothelial cancer at initial transurethral resection of large bladder tumours.

INTRODUCTION: We sought to determine how frequently cautery (thermal) artifact precludes an accurate determination of stage at initial transurethral resection of bladder tumour (TURBT) of large bladder tumours. METHODS: We queried our institution's billing data to identify patients who underwent TURBT for large bladder tumours >5cm (CPT 52240) by two urologists at an academic centre from January 2009 through April 2013. Only patients who underwent initial-staging TURBT for urothelial cancer were included. Pathological reports were reviewed for stage, number of separate pathological specimens per TURBT, and presence of cautery artifact. Operative reports were reviewed for whether additional cold cup biopsies were taken of other suspicious areas of the bladder, resident involvement, and type of electrocautery. RESULTS: We identified 119 patients who underwent initial staging TURBT for large tumours. Cautery artifact interfered with accurate staging in 7/119 (6%) of cases. Of these, six patients underwent restaging TURBT, with 50% percent experiencing upstaging to T2 disease. Tumour size, tumour grade, whether additional cold cup biopsies were taken, number of separate pathological specimens sent, and resident involvement were not associated with cautery artifact (all p>0.05). Bipolar resection had a higher rate of cautery artifact 5/42 (12%), compared to monopolar resection 2/77 (2.6%) approaching significance (p=0.095). CONCLUSIONS: Cautery artifact may delay accurate staging at initial TURBT for large tumours by understaging up to 6% of patients.

Suppression of ERß signaling via ERß knockout or antagonist protects against bladder cancer development.

Epidemiological studies showed that women have a lower bladder cancer (BCa) incidence, yet higher muscle-invasive rates than men, suggesting that estrogen and the estrogen receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERß), may play critical roles in BCa progression. Using in vitro cell lines and an in vivo carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced mouse BCa model, we found that ERß plays a positive role in promoting BCa progression. Knockdown of ERß with ERß-shRNA in ERß-positive human BCa J82, 647v and T24 cell lines led to suppressed cell growth and invasion. Mice lacking ERß have less cancer incidence with reduced expression of the proliferation marker Ki67 in BBN-induced BCa. Consistently, our results show that non-malignant urothelial cells with ERß knockdown are more resistant to carcinogen-induced malignant transformation. Mechanism dissection found that targeting ERß suppressed the expression of minichromosome maintenance complex component 5 (MCM5), a DNA replication licensing factor that is involved in tumor cell growth. Restoring MCM5 expression can partially reverse ERß knockdown-mediated growth reduction. Supportively, treating cells with the ERß-specific antagonist, 4-[2-Phenyl-5,7-bis(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP), reduced BCa cell growth and invasion, as well as MCM5 expression. Furthermore, we provide the first evidence that BCa burden and mortality can be controlled by PHTPP treatment in the carcinogen-induced BCa model. Together, these results demonstrate that ERß could play positive roles in promoting BCa progression via MCM5 regulation. Targeting ERß through ERß-shRNA, PHTPP or via downstream targets, such as MCM5, could serve as potential therapeutic approaches to battle BCa.

Redefining abnormal follicle-stimulating hormone in the male infertility population.

UNLABELLED: Study Type - Diagnostic (validating cohort). Level of Evidence 2a. What's known on the subject? and What does the study add? FSH is a hormone released by the anterior pituitary gland via stimulation from gonadotrophin-releasing hormone and potentially other factors. FSH reflects the status of spermatogenesis (i.e. the ability to produce sperm) as a result of the feedback between the testis and hypothalamus/pituitary glands. An elevated FSH level is indicative of abnormal spermatogenesis and may indicate primary testicular failure. The range for 'normal' FSH varies somewhat between institutions but has been defined by the Strong Memorial Hospital (Rochester, NY, USA) clinical laboratory as 1.4-18.1 IU/L based on the ADVIA Centaur (Siemens Medical Solutions, Tarrytown, NY, USA) FSH assay. The findings obtained in the present study could be helpful for predicting male factor infertility in patients with a borderline high FSH level (≈4.5 IU/L) and a low testosterone level compared to someone with a borderline high FSH level and a normal testosterone level. Although the 'normal' range for FSH is qualified as a value in the range 1.4-18.1 IU/L, the present study shows that an FSH level >4.5 IU/L was associated with abnormal semen analysis in terms of morphology and sperm concentration in the present patient population. Therefore, these findings suggest that FSH values lower than those currently considered normal may be associated with abnormal semen analysis, and that the 'normal' range for FSH used in clinical settings may need to be reconsidered. OBJECTIVE: • To examine the correlation between follicle-stimulating hormone (FSH) and testosterone/FSH levels with semen analysis parameters to evaluate whether the range for judging normal FSH levels should be reconsidered. PATIENTS AND METHODS: • The present study included 610 male infertility patients from a single urology infertility clinic between 2004 and 2008. • Patients (n=153) were excluded for obstructive azoospermia, hypogonadotrophic hypogonadism, steroid use or failure to complete testing. • Abnormal semen analysis values were based on the WHO 1999 criteria. • We performed t-tests, anova, chi-squared tests and logistic regression to statistically examine the association between the FSH (or testosterone/FSH ratio) level and semen parameters. RESULTS: • The FSH level showed statistically significant associations, as well as evidence of a dose response, with abnormal sperm concentration and morphology but not with semen volume. • In men with FSH levels >7.5 IU/L, the risk of abnormal semen quality was five- to thirteen-fold higher than that of men with FSH levels <2.8 IU/L depending on the specific semen parameter. • Similarly, semen parameters were had a greater probability of being abnormal with decreasing testosterone/FSH ratios. CONCLUSION: • A significantly increased risk of abnormal semen analyses among men with FSH levels >4.5 IU/L and decreasing testosterone/FSH ratios suggests that redefining normal FSH in infertile men would be valuable.

(Almost) painless surgery: a historical review of the evolution of intraurethral anesthesia in urology.

OBJECTIVE: The discovery of local anesthesia revolutionized urologic surgery. We investigate the evolution of intraurethral anesthesia in urologic surgery beginning in 1884. METHODS: A review of the literature was performed, reviewing the history of local anesthesia for urologic surgery, with a specific emphasis on intraurethral anesthesia. Using the University of Rochester libraries catalog "Voyager," a search was performed reviewing the primary literature published on intraurethral anesthesia beginning from 1884 through 2009. We also reviewed published literature in Ovid Med and PubMed for articles relevant to the topic of intraurethral anesthesia. The search terms were intraurethral, cocaine, lidocaine, and anesthesia. RESULTS: In the 1840s, it was demonstrated that ether, nitrous oxide, and chloroform could prevent the pain of surgery, resulting in a dramatic increase in surgery. At Massachusetts General Hospital between 1845 and 1847, surgeries increased 2.5-fold. Four decades later, it was demonstrated that cocaine allowed for adequate analgesia without the side effects of general anesthesia, resulting in a dramatic increase in urologic surgery. Cocaine was gradually replaced as an intraurethral anesthetic as safer local anesthetics, such as lidocaine, became introduced. Modern studies show conflicting results over the efficacy and ideal administration of intraurethral anesthetics. CONCLUSIONS: Local anesthesia was rapidly accepted by urologists around the world and used in a wide variety of urologic surgeries, contributing to the acceptance of anesthesia and a revolution of the practice of surgery. To this day, intraurethral anesthesia continues to be a widely used and effective technique in urology, although the ideal method of use is largely left up to individual preference.

Wine and treatment of genitourinary disease: from antiquity to modern times.

OBJECTIVE: Wine is one of the oldest documented medicinal remedies, dating back thousands of years. We explore the medicinal uses of wine, with a focus on the treatment of genitourinary disease, beginning in ancient Egypt, India, and Israel, and then moving forward to include Greek, Roman, and Arabic medicine. Our review continues into the Middle Ages and renaissance, and finally evaluates the medicinal properties of wine as we understand them in our current scientific paradigm and its specific application to urology. METHODS: A review of the literature was completed, reviewing the medical theories and medicinal uses of wine from ancient civilization to the present. RESULTS: Wine has been used in the treatment of genitourinary disease for thousands of years. This agent has been employed by physicians in nearly all cultures and in all eras of medical history. Medical uses include, but are not limited to, appetite stimulant, anesthetic, tonic, antiseptic, vasodilator, diuretic, antibacterial agent, and diaphoretic. The physiologic properties and value of this ancient medicine continue to be studied today. CONCLUSIONS: The medicinal use of wine has common applications over thousands of years and multiple civilizations. The pharmacologic and physiologic properties of this agent continue to be studied and applied in the modern era and continue to be relevant in the field of urology.