Mosaic embryo transfer versus additional IVF with PGT-A Cycle: a decision model comparing live birth rate and cost.

PURPOSE: To evaluate the relative live birth rate and net cost difference between mosaic embryo transfer and an additional cycle of IVF with PGT-A for patients whose only remaining embryos are non-euploid. METHODS: A decision analytic model was designed with model parameters varying based on discrete age cutoffs (<35, 35-37, 38-39, 40-42, 43-44, >44). Model inputs included probabilities of successful IVF, clinical pregnancy, and live birth as well as costs of IVF with PGT-A, embryo transfer, live birth, amniocentesis, and dilation and curettage. All costs were modeled from the healthcare system perspective and adjusted for inflation to 2023 $USD. Model outcomes were sub-stratified by degree and type of mosaicism. RESULTS: For patients younger than 43, an additional cycle of IVF with PGT-A resulted in a higher relative live birth rate (<35, +20%; 35-37, +15%; 38-39, +17%; 40-42, +6%; average, +14.5%) compared to mosaic embryo transfer with an average additional cost of $16,633. For patients older than 42, mosaic embryo transfer resulted in a higher live birth rate (43-44, +5%; >44, +3%; average, +4%) while on average costing $9572 less than an additional cycle of IVF with PGT-A. CONCLUSION: Mosaic embryo transfers are a superior alternative to an additional cycle of IVF with PGT-A for patients older than 42 whose only remaining embryos are non-euploid. Mosaic embryo transfers also should be considered for patients younger than 42 who are unable to pursue additional autologous IVF cycles. Counseling and care should be personalized to individual patients and embryos.

Fertility issues in hypopituitarism.

Women with hypopituitarism have lower fertility rates and worse pregnancy outcomes than women with normal pituitary function. These disparities exist despite the use of assisted reproductive technologies and hormone replacement. In women with hypogonadotropic hypogonadism, administration of exogenous gonadotropins can be used to successfully induce ovulation. Growth hormone replacement in the setting of growth hormone deficiency has been suggested to potentiate reproductive function, but its routine use in hypopituitary women remains unclear and warrants further study. In this review, we will discuss the clinical approach to fertility in a woman with hypopituitarism.

Oncofertility research pitfall? Recall bias in young adult cancer survivors.

Objective: To assess recall bias by evaluating how well female cancer survivors remember details regarding their cancer diagnosis, treatment, and fertility preservation (FP) counseling.Oncofertility literature cites recall bias as a pitfall of retrospective surveys, but limited data exist to quantify this bias. Design: Retrospective secondary analysis of cross-sectional survey data. Setting: Single academic medical center. Patients: Female oncology patients of reproductive age, 18-44 years old, at least 6 months past their last chemotherapy treatment. Interventions: Not applicable. Main Outcome Measures: Recall of details surrounding cancer diagnosis and chemotherapy regimens, recall of FP counseling and ovarian reserve testing, and rates of chart-documented FP counseling. Results: In total, 117 patients completed the survey, with 112 verified via chart review. When asked to report the chemotherapy regimen, 57% (64 of the 112) marked "I don't know/prefer not to say." Regarding FP, 80% (90 of the 112) denied being offered counseling. Of the 37 (33%) who had documented FP conversations, 13 (35%) did not recall mention of fertility. Only 2 of 8 patients with ovarian reserve testing recalled this being performed at their initial visit. Multivariable logistic regression revealed older age was significantly associated with not being offered FP (odds ratio [OR] 0.87). Conclusions: Our results confirm that the accuracy of oncology patients' reporting is limited by a poor recall, particularly regarding their specific chemotherapy regimen. More than 1 in 3 patients documented to have been offered FP counseling do not recall this discussion. Importantly, only one-third of cancer survivors had chart-documented FP counseling. Increased efforts are needed to ensure adequate follow-up beyond the initial visit.

Evaluation of at-home serum anti-Müllerian hormone testing: a head-to-head comparison study.

BACKGROUND: For optimal fertility testing, serum anti-Müllerian hormone levels are used in combination with other testing to provide reliable ovarian reserve evaluations. The use of the ADx 100 card is widely commercially available for at-home reproductive hormone testing, but data demonstrating that its results are reproducible outside of a clinical setting are limited, as well as comparisons of its performance with other newer blood collection techniques. This study aimed to evaluate the concordance of serum AMH levels found via standard venipuncture and self-administered blood collection using the TAP II device (TAP) and ADx card in women of reproductive age. METHODS: This was a prospective, head-to-head-to-head within-person crossover comparison trial that included 41 women of reproductive age (20-39 years). It was hypothesized that the TAP device would be superior to the ADx card both in terms of agreement with venipuncture reference standard and patient experience. Each subject had their blood drawn using the three modalities (TAP, ADx, and venipuncture). We evaluated the concordance of AMH assays from samples obtained via the TAP device and ADx card with the gold standard being venipuncture. Two-sided 95% CIs were generated for each method to compare relative performance across all three modes. Patient preference for the TAP device versus the ADx card was based on self-reported pain and Net Promoter Score (NPS). RESULTS: The TAP device was superior to the ADx card on all outcome measures. TAP R-squared with venipuncture was 0.99 (95% CI 0.99, > 0.99), significantly higher than the ADx card, which had an R-squared of 0.87 (95% CI 0.80, 0.94) under most favorable treatment. TAP sensitivity and specificity were both 100% (no clinical disagreement with venipuncture), versus 100 and 88%, respectively, for the ADx card. Average pain reported by users of the TAP device was significantly lower than the ADx card (0.75 versus 2.73, p < 0.01) and the NPS was significantly higher than the ADx card (+ 72 versus - 48, p < 0.01). CONCLUSIONS: The TAP was non-inferior to venipuncture and superior to the ADx card with respect to correlation and false positives. Moreover, the TAP was superior to both alternatives on patient experience. TRIAL REGISTRATION: NCT04784325 (Mar 5, 2021).

Impact of comprehensive state insurance mandates on in vitro fertilization utilization, embryo transfer practices, and outcomes in the United States.

BACKGROUND: Previous studies have demonstrated that state mandated coverage of in vitro fertilization may be associated with increased utilization, fewer embryos per transfer, and lower multiple birth rates, but also lower overall live birth rates. Given new legislation and the delay between enactment and effect, a revisit of this analysis is warranted. OBJECTIVE: This study aimed to characterize the current impact of comprehensive state in vitro fertilization insurance mandates on in vitro fertilization utilization, live birth rates, multiple birth rates, and embryo transfer practices. STUDY DESIGN: We conducted a retrospective cohort study of in vitro fertilization cycles reported by the 2018 Centers for Disease Control and Prevention Assisted Reproductive Technology Fertility Clinic Success Rates Report in the United States. In vitro fertilization cycles were stratified according to state mandate as follows: comprehensive (providing coverage for in vitro fertilization with minimal restrictions) and noncomprehensive. The United States census estimates for 2018 were used to calculate the number of reproductive-aged women in each state. Outcomes of interest (stratified by state mandate status) included utilization rate of in vitro fertilization per 1000 women aged 25 to 44 years, live birth rate, multiple birth rate, number of embryo transfer procedures (overall and subdivided by fresh vs frozen cycles), and percentage of transfers performed with frozen embryos. Additional subanalyzes were performed with stratification of outcomes by patient age group. RESULTS: In 2018, 134,997 in vitro fertilization cycles from 456 clinics were reported. Six states had comprehensive mandates; 32,029 and 102,968 cycles were performed in states with and without comprehensive in vitro fertilization mandates, respectively. In vitro fertilization utilization in states with comprehensive mandates was 132% higher than in noncomprehensive states after age adjustment; increased utilization was observed regardless of age stratification. Live birth rate per cycle was significantly higher in states with comprehensive mandates (35.4% vs 33.4%; P<.001), especially among older age groups. Multiple birth rate as a percentage of all births was significantly lower in states with comprehensive mandates (10.2% vs 13.8%; P<.001), especially among younger patients. Mean number of embryos per transfer was significantly lower in states with comprehensive mandates (1.30 vs 1.36; P<.001). Significantly fewer frozen transfers were performed as a percentage of all embryo transfers in states with comprehensive mandates (66.1% vs 76.3%; P<.001). Among fresh embryo transfers, significantly fewer embryos were transferred in comprehensive states among all patients (1.55 vs 1.67; P<.001). CONCLUSION: Comprehensive state mandated insurance coverage for in vitro fertilization services is associated with greater utilization of these services, fewer embryos per transfer, fewer frozen embryo transfers, lower multiple birth rates, and higher live birth rates. These findings have important public health implications for reproductive-aged individuals in the United States and present notable opportunities for research on access to fertility care.

Virtual Compared With In-Clinic Transvaginal Ultrasonography for Ovarian Reserve Assessment.

OBJECTIVE: To evaluate noninferiority of virtual transvaginal ultrasonography compared with in-clinic ultrasonography for ovarian reserve assessment. METHODS: We conducted a single-site, head-to-head crossover trial. Participants performed self-administered virtual transvaginal ultrasonography at home, guided by a remote-certified ultrasound technologist, then underwent transvaginal ultrasonography in-clinic with another ultrasound technologist. Participants were women in the greater Boston area interested in evaluating ovarian reserve and recruited through social media, health care referrals, and professional networks. The uterus and ovaries were captured in sagittal and transverse views. These randomized recordings were reviewed by two or three independent, blinded reproductive endocrinologists. The primary outcome was noninferiority of the rate of clinical quality imaging produced at home compared with in clinic. Sample size was selected for greater than 90% power, given the 18% noninferiority margin. Secondary outcomes included antral follicle count equivalency and net promoter score superiority. RESULTS: Fifty-six women were enrolled from December 2020 to May 2021. Participants varied in age (19-35 years), BMI (19.5-33.9), and occupation. Ninety-six percent of virtual and 98% of in-clinic images met "clinical quality." The difference of -2.4% (97.5% CI lower bound -5.5%) was within the noninferiority margin (18%). Antral follicle counts were equivalent across settings, with a difference in follicles (0.23, 95% CI -0.36 to 0.82) within the equivalence margin (2.65). Virtual examinations had superior net promoter scores (58.1 points, 97.5% CI of difference 37.3-79.0, P<.01), indicating greater satisfaction with the virtual experience. CONCLUSION: Virtual transvaginal ultrasonography remotely guided by an ultrasonography technologist is noninferior to in-clinic transvaginal ultrasonography for producing clinical quality images and is equivalent for estimating antral follicle count. Virtual transvaginal ultrasonography had superior patient satisfaction and has potential to significantly expand patient access to fertility care. FUNDING SOURCE: This study was sponsored by Turtle Health. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04687189.

Racial and ethnic disparities among donor oocyte banks in the United States.

OBJECTIVE: To determine whether racial and ethnic distributions of oocyte donors contributing to US oocyte banks differ from the demographics of US women and donor oocyte recipients. DESIGN: Cross-sectional study. SETTING: United States donor oocyte banks, US census, and fertility clinics reporting to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. PATIENTS: Oocyte donors from 12 banks, women aged 18-44 years based on the 2019 census, and US recipients of cryopreserved donor oocytes from 2012 to 2015. INTERVENTION: None. MAIN OUTCOME MEASURE: Proportions of donors identifying as each racial and ethnic group. RESULTS: Of the 1,574 oocyte donors, 678 (43.1%) identified as white compared with 54.8% of US women and 69.1% of donor oocyte recipients. Proportions of donors identifying as Hispanic or two or more races were larger than those of US women and donor oocyte recipients (Hispanic: 24.1% vs. 20.8%, and 24.1% vs. 8.8%, respectively; two or more races: 16.1% vs. 2.3%, and 16.1% vs. 0.5%, respectively). African American donors were underrepresented compared with US women (8.9% vs. 14.0%) and oocyte recipients (8.9% vs. 10.8%). Although the proportion of Asian donors was similar to that of US women (7.7% vs. 7.1%), Asian donors were underrepresented compared with donor oocyte recipients (7.7% vs. 10.6%). CONCLUSION: Racial and ethnic distribution of oocyte donors differs significantly from the demographics of US women and cryopreserved donor oocyte recipients. These data suggest a need for targeted recruitment of African American and Asian oocyte donors.

Development of a fertility risk calculator to predict individualized chance of ovarian failure after chemotherapy.

PURPOSE: To develop an innovative machine learning (ML) model that predicts personalized risk of primary ovarian insufficiency (POI) after chemotherapy for reproductive-aged women. Currently, individualized prediction of a patient's risk of POI is challenging. METHODS: Authors of published studies examining POI after gonadotoxic therapy were contacted, and six authors shared their de-identified data (N = 435). A composite outcome for POI was determined for each patient and validated by 3 authors. The primary dataset was partitioned into training and test sets; random forest binary classifiers were trained, and mean prediction scores were computed. Institutional data collected from a cross-sectional survey of cancer survivors (N = 117) was used as another independent validation set. RESULTS: Our model predicted individualized risk of POI with an accuracy of 88% (area under the ROC 0.87, 95% CI: 0.77-0.96; p < 0.001). Mean prediction scores for patients who developed POI and who did not were 0.60 and 0.38 (t-test p < 0.001), respectively. Highly weighted variables included age, chemotherapy dose, prior treatment, smoking, and baseline diminished ovarian reserve. CONCLUSION: We developed an ML-based model to estimate personalized risk of POI after chemotherapy. Our web-based calculator will be a user-friendly decision aid for individualizing risk prediction in oncofertility consultations.

Oocyte cryopreservation versus ovarian tissue cryopreservation for adult female oncofertility patients: a cost-effectiveness study.

PURPOSE: In December 2019, the American Society for Reproductive Medicine designated ovarian tissue cryopreservation (OTC) as no longer experimental and an alternative to oocyte cryopreservation (OC) for women receiving gonadotoxic therapy. Anticipating increased use of OTC, we compare the cost-effectiveness of OC versus OTC for fertility preservation in oncofertility patients. METHODS: A cost-effectiveness model to compare OC versus OTC was built from a payer perspective. Costs and probabilities were derived from the literature. The primary outcome for effectiveness was the percentage of patients who achieved live birth. Strategies were compared using incremental cost-effectiveness ratios (ICER). All inputs were varied widely in sensitivity analyses. RESULTS: In the base case, the estimated cost for OC was $16,588 and for OTC $10,032, with 1.56% achieving live birth after OC, and 1.0% after OTC. OC was more costly but more effective than OTC, with an ICER of $1,163,954 per live birth. In sensitivity analyses, OC was less expensive than OTC if utilization was greater than 63%, cost of OC prior to chemotherapy was less than $8100, cost of laparoscopy was greater than $13,700, or standardized discounted costs were used. CONCLUSIONS: With current published prices and utilization, OC is more costly but more effective than OTC. OC becomes cost-saving with increased utilization, when cost of OC prior to chemotherapy is markedly low, cost of laparoscopy is high, or standardized discounted oncofertility pricing is assumed. We identify the critical thresholds of OC and OTC that should be met to deliver more cost-effective care for oncofertility patients.

The Risk of Congenital Anomalies by Fertility Treatment Modality.

IMPORTANCE: Up to 4% of all births in developed nations involve assisted reproductive technology (ART), along with other fertility treatment modalities. Thus, ART pregnancies constitute an important epidemiologic population with a known increased risk of congenital anomalies. In this review, we summarize current fertility treatment modalities and their associated risk of congenital anomalies. OBJECTIVE: To review the risk of birth defects among pregnancies conceived with ART and other fertility treatments. EVIDENCE ACQUISITION: Articles were obtained from PubMed and the American College of Obstetricians and Gynecologists and American Society of Reproductive Medicine committee opinions. RESULTS: In vitro fertilization has been associated with a 25% to 50% increased risk of birth defects, including abnormalities of these organ systems: cardiovascular (25%-40% of anomalies), genitourinary (10%-60%), gastrointestinal (10%-20%), and musculoskeletal (10%-35%). Although the data are mixed, intracytoplasmic sperm injection has also been found to be associated with an increased risk of defects, particularly hypospadias, when compared with conventional in vitro fertilization. The risk among fresh versus frozen cycles and cleavage stage versus blastocyst transfers remains uncertain. There appears to be no significant added risk with preimplantation genetic testing, although more studies are needed. Ovulation induction with oral agents appears safe and not associated with an increased risk of anomalies. Oocyte cryopreservation also appears safe, but the data are still limited, requiring future investigation. CONCLUSIONS AND RELEVANCE: While the relative risk of birth defects among ART pregnancies is increased when compared with spontaneous conceptions, the absolute risk remains low. There are no standard screening recommendations for ART pregnancies. Per the American College of Obstetricians and Gynecologists, patients who have undergone ART should be counseled regarding the risk of birth defects and available antenatal evaluation, including fetal echocardiogram and detailed ultrasound evaluation.

The Implementation of Communication Didactics for OB/GYN Residents on the Disclosure of Adverse Perioperative Events.

OBJECTIVE: Communication skills are key components of the patient-physician relationship, yet are not routinely taught during residency. Institutional data demonstrates 75% of residents regularly encounter difficult communication scenarios. This study's objective is to develop and pilot a communications didactic/skills training program for Obstetrics & Gynecology (OB/GYN) residents focused on the disclosure of adverse perioperative events. DESIGN: This was an observational, prospective cohort pilot study. OB/GYN residents completed a 4-hour interactive curriculum using VitalTalk methodology, certified facilitators, and simulated patients in 2019. Participants completed self-assessments of their skill levels at 3 time points: prior to training, immediately post-training, 3-month post-training. Wilcoxon signed rank tests were used to evaluate change in skill levels. SETTING: University-based program in North Carolina. PARTICIPANTS: Participants included all OB/GYN residents from postgraduate years 1-4. Out of 31 residents, 27 participated in the training, 24 completed the immediately post-training survey, and 23 completed the 3-month post-training survey. RESULTS: At baseline, most residents rated their global skill level in communication as novice (37.0%) or advanced beginner (33.3%). Immediately following the intervention, 41.7% of residents ranked their global skill as "competent" and 20.8% as "proficient." These changes were statistically significant (p < 0.001). Notable improvements were seen across multiple variables, including the handling of emotional reactions (p = 0.046). No significant changes were noted between the immediately post-training and 3-month time points, suggesting skill retention. Majority of trainees (78.3%) felt that refresher courses would be useful for skill maintenance. CONCLUSION: A simulation-based formalized communication curriculum is effective for improving OB/GYN resident competence and skill levels in the disclosure of adverse perioperative events. Specific to adverse surgical complications, this curriculum appears feasible for implementation by other training programs. Further work is needed to identify the most beneficial timing and modality of these workshops.

Combined Oocyte Retrieval and Robot-assisted Hysterectomy in a Super Morbidly Obese Patient with Endometrial Carcinoma.

AIM: To report on the unique, innovative management of a super morbidly obese patient presenting for fertility preservation in the setting of Grade 2 endometrioid endometrial adenocarcinoma. CASE REPORT: A back-to-back oocyte retrieval and robot-assisted total laparoscopic hysterectomy (RA-TLH) with bilateral salpingo-oophorectomy (BSO) was performed in a 37-year-old nulligravid woman with super morbid obesity (BMI 63 kg/m2) with endometrial cancer. MAIN OUTCOME MEASURE: the successful retrieval of oocytes for fertility preservation and oncologic intervention via RA-TLH with BSO in the same operative and anesthetic episode. RESULTS: This combined procedure strategy was successful in our case and is a feasible option for similar high-risk patients in the future. CONCLUSION: Identifying safe and effective approaches for oocyte retrieval in morbidly obese patients represents a pressing need as obesity rates rise among reproductive-aged women. Back-to-back oocyte retrieval and RA-TLH with BSO are not only feasible, but could also decrease significant anesthetic risks for morbidly obese patients.

Measuring and improving student engagement in clinical training.

PURPOSE: Volunteer service learning activities, including Student Run Clinics (SRCs), are becoming an increasingly popular extracurricular component of medical education. While there are reports that student clinicians generally enjoy their educational experiences at SRCs, it is not understood how to optimize and measure student engagement in them. To identify key drivers of student engagement a tool was created to measure volunteer experience at the Crimson Care Collaborative (CCC), a primary care SRC. METHODS: CCC volunteers were asked to complete an online engagement survey. Cross-sectional survey data were collected for 149 CCC volunteers (53% response rate). RESULTS: Multivariate linear regression showed that overall 'likelihood to recommend CCC to a friend' was significantly associated with students' perception of the clarity of their role within the clinic, frequency of interprofessional interactions, and overall quality of medical education. Students who volunteer more frequently and for longer periods of time had higher engagement scores. CONCLUSIONS: Measuring engagement is feasible in volunteer settings. Engagement appears to be dependent on both structural and experiential components. Easily modifiable components of job design (role definition, expected frequency of volunteering), are key drivers of volunteer engagement.

Association between shunt-responsive idiopathic normal pressure hydrocephalus and alcohol.

OBJECTIVE Idiopathic normal pressure hydrocephalus (iNPH) is characterized by ventriculomegaly, gait difficulty, incontinence, and dementia. The symptoms can be ameliorated by CSF drainage. The object of this study was to identify factors associated with shunt-responsive iNPH. METHODS The authors reviewed the medical records of 529 patients who underwent shunt placement for iNPH at their institution between July 2001 and March 2015. Variables associated with shunt-responsive iNPH were identified using bivariate and multivariate analyses. Detailed alcohol consumption information was obtained for 328 patients and was used to examine the relationship between alcohol and shunt-responsive iNPH. A computerized patient registry from 2 academic medical centers was queried to determine the prevalence of alcohol abuse among 1665 iNPH patients. RESULTS Bivariate analysis identified associations between shunt-responsive iNPH and gait difficulty (OR 4.59, 95% CI 2.32-9.09; p < 0.0001), dementia (OR 1.79, 95% CI 1.14-2.80; p = 0.01), incontinence (OR 1.77, 95% CI 1.13-2.76; p = 0.01), and alcohol use (OR 1.98, 95% CI 1.23-3.16; p = 0.03). Borderline significance was observed for hyperlipidemia (OR 1.56, 95% CI 0.99-2.45; p = 0.054), a family history of hyperlipidemia (OR 3.09, 95% CI 0.93-10.26, p = 0.054), and diabetes (OR 1.83, 95% CI 0.96-3.51; p = 0.064). Multivariate analysis identified associations with gait difficulty (OR 3.98, 95% CI 1.81-8.77; p = 0.0006) and alcohol (OR 1.94, 95% CI 1.10-3.39; p = 0.04). Increased alcohol intake correlated with greater improvement after CSF drainage. Alcohol abuse was 2.5 times more prevalent among iNPH patients than matched controls. CONCLUSIONS Alcohol consumption is associated with the development of shunt-responsive iNPH.