A survey study evaluating donor gamete utilization rates, patient satisfaction and fertility treatment outcomes according to desired race and ethnicity.

OBJECTIVE: To evaluate donor gamete utilization, patient satisfaction, and fertility treatment outcomes of patients pursuing treatment with donor gametes stratified by the desired race and ethnicity of the gamete donor. DESIGN: Survey study SUBJECTS: Patients planning to undergo treatment using donor sperm and/or donor oocytes at a single academic fertility clinic in the Southeastern United States between 2015 and 2020. INTERVENTION OR EXPOSURE: None MAIN OUTCOME MEASURES: Utilization rates of donor gametes, satisfaction with donor gamete selection and fertility treatment outcomes stratified by race and ethnicity of patient, as well as that of their gamete donor. RESULTS: Four hundred fifty patients were eligible for inclusion and 170 (38%) responded to the survey. Amongst the respondents, 59% desired a non-Hispanic White gamete donor and 20% desired a non-Hispanic Black gamete donor. Patients seeking a non-Hispanic Black gamete donor had lower odds of utilizing donor gametes (OR = 0.13, 95% CI 0.04 - 0.40) compared to individuals seeking a non-Hispanic White gamete donor. When evaluating satisfaction with donor gamete selection, patients seeking a non-Hispanic Black gamete donor reported lower satisfaction compared to individuals seeking a non-Hispanic White gamete donor (OR 0.19, 95% CI [0.09-0.43]). When evaluating fertility outcomes, Non-Hispanic Black patients and those utilizing non-Hispaninc Black gamete donors were found to have a lower odds of successful conception compared to non-Hispanic White patients (OR=0.18, 95% CI 0.07-0.46) and individuals seeking non-Hispanic White gamete donors (OR=0.26, 95% CI 0.09-0.75), respectively. CONCLUSION: Patients seeking non-Hispanic Black donor gametes have lower utilization rates, less satisfaction with gamete donor selection, and lower odds of conception when compared to those seeking non-Hispanic White gamete donors. These findings highlight the need for more racial diversity within donor gamete banks, as well as within the donor pools available through agencies and fertility clinics.

Optimal antimüllerian hormone levels in oocyte donors: a national database analysis.

OBJECTIVE: To study the relationship between high antimüllerian hormone (AMH) levels in oocyte donors and embryo development and pregnancy outcomes among donor oocyte recipients. DESIGN: Retrospective cohort study. SETTING: Donor Egg Bank Database. PATIENTS: Patients undergoing in vitro fertilization using vitrified donor oocytes from 35 in vitro fertilization centers in the United States between 2013 and 2021. For each recipient, the first oocyte lot that was received with a planned insemination and embryo transfer (ET) was included. INTERVENTION: Oocyte donor-recipient cycles. MAIN OUTCOME MEASURES: Ongoing pregnancy rate (OPR) per ET. RESULTS: A total of 3,871 donor oocyte-recipient thaw cycles were analyzed. On the basis of donor AMH serum concentration, cycles were stratified into the high AMH group (AMH ≥5 ng/mL; n = 1,821) and the referent group (AMH <5 ng/mL; n = 2,050). Generalized estimating equation models were used to account for donors that contributed more than one lot of oocytes. The number of usable embryos per lot (median [interquartile range]) was significantly increased in the high AMH group (2 [2-4]) compared with the referent group (2 [1-3]) (relative risk [RR] 1.06; confidence interval [CI] 1.01-1.12). Among recipients with a planned ET, there was no difference in OPR between the high AMH group (45.4%) and the referent group (43.5%) (RR 1.04; 95% CI 0.94-1.15). Among preimplantation genetic testing for aneuploidy cycles, the embryo euploidy rate per biopsy was similar at 66.7% (50%-100%) in both groups (RR 1.04; CI 0.92-1.17). The OPR per euploid ET among patients who used preimplantation genetic testing for aneuploidy was also comparable, at 52% in the high AMH group and 54.1% in the referent group (RR 0.95; CI 0.74-1.23). CONCLUSION: This large national database study observed that there was no association between a high level of AMH (≥5 ng/mL) in oocyte donors and an OPR in the recipient after the first ET. On the basis of these findings, recipients and physicians can be reassured that oocyte donors with a high AMH level can be expected to produce outcomes that are at least as good as donors with an AMH level (<5 ng/mL).

A Geospatial Analysis of Disparities in Access to Oncofertility Services.

Importance: Fertility preservation (FP), including oocyte and embryo cryopreservation prior to gonadotoxic therapy, is an urgent and essential component of comprehensive cancer care. Geographic proximity to a center offering FP is a critical component of ensuring equitable access for people with cancer desiring future fertility. Objective: To characterize the distribution of centers offering FP services in the US, quantify the number of self-identified reproductive-age female individuals living outside of geographically accessible areas, and investigate the association between geographic access and state FP mandates. Design, Setting, and Participants: This cross-sectional analysis calculated 2-hour travel time isochrone maps for each center based on latitude and longitude coordinates. Population-based geospatial analysis in the US was used in this study. Fertility clinics identified through the 2018 Centers for Disease Control and Prevention Fertility Clinic Success Rates Report were defined as oncofertility centers by meeting 4 criteria: (1) offered oocyte and embryo cryopreservation, (2) performed at least 1 FP cycle in 2018, (3) served people without partners, and (4) had an accredited laboratory. County-level data were obtained from the 2020 US Census, with the primary at-risk population identified as reproductive-age female individuals aged 15 years to 44 years. The analysis was performed from 2021 to 2022. Exposures: Location outside of 2-hour travel time isochrone of an oncofertility center. Main Outcomes and Measures: Oncofertility centers were compared with centers not meeting criteria and were classified by US region, state FP mandate status, number of assisted reproductive technology cycles performed, and number of FP cycles performed. The number and percentage of at-risk patients, defined as those living outside of accessible service areas by state, were identified. Results: Among 456 Centers for Disease Control and Prevention-reporting fertility clinics, 86 (18.9%) did not meet the criteria as an oncofertility center. A total of 3.63 million (5.70%) reproductive-age female individuals lack geographic access to an oncofertility center. States with FP mandates have the highest rates of eligible female patients with geographic access (98.54%), while states without active or pending legislation have the lowest rates (79.57%). The greatest disparities in geographic access to care are most concentrated in the Mountain West and West North Central regions. Conclusions and Relevance: Patients face numerous barriers to comprehensive cancer care, including a lack of geographic access to centers capable of offering FP services. This cross-sectional study identified disparities in geographic access and potential opportunities for strategic expansion.

Medical Student Duty Hours and Shelf Performance: Is There a Correlation?

OBJECTIVE: To date, there is limited information about medical student duty hours, shelf scores, and overall clerkship performance in obstetrics and gynecology (OB/GYN). As a result, we were curious to know whether spending more time in the clinical environment translated to an improved learning experience or, in contrast, translated to decreased study time and worse overall clerkship performance. STUDY DESIGN: A retrospective cohort analysis was performed at a single academic medical center of all medical students on the OB/GYN clerkship from August 2018 to June 2019. Recorded student duty hours were tabulated per day and per week, by student. National Board of Medical Examiners (NBME) Subject Exam (Shelf) equated percentile scores for the quarter of year were used. RESULTS: Our statistical analysis showed that working long hours did not translate to higher or lower shelf score, or higher overall clerkship grade. However, working longer hours in the last 2 weeks of the clerkship was associated with high shelf score. CONCLUSION: Longer medical student duty hours did not correlate to higher shelf scores or overall clerkship grades. Future multicenter studies are necessary to evaluate the importance of medical student duty hours and continue optimizing the educational experience of the OB/GYN clerkship. KEY POINTS: · Clinical hours were not associated with shelf examination scores.. · Clinical hours were not associated with overall clerkship grade.. · Longer clinical hours at the end of clerkship are correlated with higher examination scores..

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.

Direct-to-consumer fertility testing: utilization and perceived utility among fertility patients and reproductive endocrinologists.

RESEARCH QUESTION: What is the utilization of direct-to-consumer fertility tests (DTCFT) among fertility patients? How does the perceived utility of DTCFT differ between patients and reproductive endocrinologists (REI)? DESIGN: Infertility patients visiting the Duke Fertility Center between December 2020 and December 2021 were sent an electronic invitation to participate in a patient survey. Members of the Society of Reproductive Endocrinology and Infertility were also sent e-mail invitations to participate in the REI survey. DTCFT were defined as tests not ordered by a physician or performed at a physician's office, including calendar methods of ovulation prediction, urinary ovulation prediction kits, basal body temperature (BBT) monitoring, hormone analysis, ovarian reserve testing and semen analysis. Patients and REI were asked how likely they were to recommend a given DTCFT, on a 0-10 Likert scale. RESULTS: In total, 425 patients (response rate 50.5%) and 178 REI (response rate 21.4%) completed the surveys. Patients reported the utilization of calendar methods of ovulation prediction (83.8%), urinary ovulation prediction (78.8%), BBT monitoring (30.8%), hormone analysis (15.3%), semen analysis (10.1%) and ovarian reserve testing (9.2%). REI rated the utility of all DTCFT significantly lower than patients did (average discordance -4.2, P < 0.001), except for urinary ovulation prediction, which REI gave a significantly higher score (discordance +1.0, P < 0.001). Prior pregnancy was significantly associated with home ovulation prediction utilization among patients (adjusted odds ratio 3.21, 95% confidence interval 1.2-9.83). CONCLUSIONS: Methods of ovulation prediction are commonly used by fertility patients. Significant discordance exists in the perceived utility of DTCFT between patients and REI. Patient education and guidelines are needed to better inform individuals considering DTCFT.

Markers of ovarian reserve as predictors of future fertility.

OBJECTIVE: To determine the association between ovarian reserve biomarkers and future fertility among late reproductive-age women. DESIGN: Cohort study of participants enrolled in Time to Conceive (TTC), a time-to-pregnancy cohort study of the ovarian reserve biomarkers. SETTING: Community. PATIENT(S): Women aged 30-44 years without a history of infertility who provided a blood sample at enrollment in TTC and who agreed to future follow-up. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): The primary outcomes were probability of achieving a live birth >3 years after enrollment in TTC, diagnosis of infertility at any time, and time-to-pregnancy in future pregnancy attempts. RESULT(S): Women with diminished ovarian reserve, defined as those with an antimüllerian hormone (AMH) level <0.7 ng/mL or follicle-stimulating hormone (FSH) level ≥10 mIU/mL, did not have low risk of future live birth (relative risk [RR], 1.32; 95% confidence interval [CI], 0.95-1.83 and RR, 1.28; 95% CI, 0.97-1.70, respectively) compared with women with normal ovarian reserve after adjusting for age at blood draw, race, obesity, use of hormonal contraception, and year of enrollment in original study. Among women in the cohort that attempted to conceive, there was not a significant association between diminished ovarian reserve, as measured by AMH or FSH, and risk of future infertility (RR, 0.65; 95% CI, 0.21-2.07 and RR,1.69; 95% CI, 0.86-3.31, respectively). Similarly, there was no association between AMH and FSH levels and future fecundability (fecundability ratio, 0.97; 95% CI, 0.59, 1.60; and fecundability ration, 0.86; 95% CI, 0.55-1.36, respectively). CONCLUSION: Diminished ovarian reserve is not associated with reduced future reproductive capacity. Given the lack of association, women should be cautioned regarding use biomarkers of ovarian reserve as predictors of their future reproductive capacity.

Systemic inflammation and menstrual cycle length in a prospective cohort study.

BACKGROUND: Local inflammation plays an important role in normal folliculogenesis and ovulation, and conditions of chronic systemic inflammation, such as obesity and polycystic ovarian syndrome, can disrupt normal follicular dynamics. OBJECTIVE: This study aimed to determine the association between systemic inflammation, as measured by C-reactive protein levels, and menstrual cycle length. STUDY DESIGN: This study was a secondary analysis using data from Time to Conceive, a prospective time-to-pregnancy cohort study. The association between cycle length and C-reactive protein was analyzed using multivariable linear mixed and marginal models adjusted for age, race, education, body mass index, time since oral contraceptive use, alcohol, smoking, caffeine consumption, and exercise. Time to Conceive enrolled women aged 30 to 44 years with no history of infertility who were attempting to conceive for <3 months. Serum C-reactive protein levels were measured on cycle day 2, 3, or 4. Participants recorded daily menstrual cycle data for ≤4 months. RESULTS: Main outcome measures included menstrual cycle length and follicular and luteal phase lengths. Multivariable analysis included 1409 cycles from 414 women. There was no linear association between C-reactive protein levels and menstrual cycle length. However, compared with <1 mg/L, a C-reactive protein level >10 mg/L was associated with >3 times the odds (adjusted odds ratio, 3.7; 95% confidence interval, 1.67-8.11) of long cycles (defined as ≥35 days). When evaluating follicular phase length, a C-reactive protein level of >10 mg/L was associated both with follicular phases that were 1.7 (95% confidence interval, 0.23-3.09) days longer and with >2 times the odds of a long follicular phase (adjusted odds ratio, 2.2; 95% confidence interval, 1.05-4.74). CONCLUSION: There is a potential pathophysiological association between systemic inflammation and menstrual cycle changes. Further studies are needed to determine if systemic inflammation alters the menstrual cycle or if long menstrual cycles are a marker for elevated systemic inflammation.

Reproductive Functions of the Mitochondrial Progesterone Receptor (PR-M).

Classic transcriptional regulation by progesterone via the nuclear progesterone receptors A and B (PR-A, PR-B) has been recognized for decades. Less attention has been given to a mitochondrial progesterone receptor (PR-M) responsible for non-nuclear activities. PR-M is derived from the progesterone receptor (PR) gene from an alternate promoter with the cDNA encoding a unique 5' membrane binding domain followed by the same hinge and hormone-binding domain of the nPR. The protein binds to the mitochondrial outer membrane and functions to increase cellular respiration via increased beta-oxidation and oxidative phosphorylation with resulting adenosine triphosphate (ATP) production. Physiologic activities of PR-M have been studied in cardiac function, spermatozoa activation, and myometrial growth, all known to respond to progesterone. Progesterone via PR-M increases cardiomyocyte cellular respiration to meet the metabolic demands of pregnancy with increased contractility. Consequential gene changes associated with PR-M activation include production of proteins for sarcomere development and for fatty acid oxidation. Regarding spermatozoa function, progesterone via PR-M increases cellular energy production necessary for progesterone-dependent hyperactivation. A role of progesterone in myometrial and leiomyomata growth may also be explained by the increase in necessary cellular energy for proliferation. Lastly, the multi-organ increase in cellular respiration may contribute to the progesterone-dependent increase in metabolic rate reflected by an increase in body temperature through compensatory non-shivering thermogenesis. An evolutionary comparison shows PR-M expressed in humans, apes, and Old World monkeys, but the necessary gene sequence is absent in New World monkeys and lower species. The evolutionary advantage to PR-M remains to be defined, but its presence may enhance catabolism to support the extended gestation and brain development found in these primates.

Impact of increasing antimüllerian hormone level on in vitro fertilization fresh transfer and live birth rate.

Objective: The objective of our study was to assess the association between AMH and live birth among women with elevated AMH undergoing first fresh IVF. Serum antimüllerian hormone (AMH) correlates with oocyte yield during in vitro fertilization (IVF). However, there are limited data regarding IVF outcomes in women with elevated AMH levels. Design: Retrospective cohort study using the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System database from 2012-2014. Setting: Fertility clinics reporting to Society for Assisted Reproductive Technology. Patients: First, fresh, autologous IVF cycles with elevated AMH levels (≥5.0 ng/mL). Subanalyses were performed to examine patients with or without polycystic ovary syndrome (PCOS). Interventions: None. Main Outcome Measures: Odds of live birth. Results: Our cohort included 10,615 patients with elevated an AMH level, including 2,707 patients with PCOS only. The adjusted odds of live birth per initiated cycle were significantly lower per each unit increase in the AMH level (odds ratio, 0.97; 95% confidence interval, 0.96-0.98). Increasing AMH level was associated with increased cancellation of fresh transfer (odds ratio, 1.12; 95% confidence interval, 1.10-1.15) up to an AMH level of 12 ng/mL. The decrease in the live birth rate appears to be caused by the increasing incidence of cancellation of fresh transfer because the live birth rate per completed transfer was maintained. Similar trends were observed in the PCOS and non-PCOS subanalyses. Conclusions: Among patients with AMH levels of ≥5 ng/mL undergoing fresh, autologous IVF, each unit increase in AMH level is associated with a 3% decrease in odds of live birth because of the increased incidence of fresh embryo transfer cancellation.

Fibroids and Fertility: A Comparison of Myomectomy and Uterine Artery Embolization on Fertility and Reproductive Outcomes.

Importance: Leiomyomata, or fibroids, are a common gynecological problem affecting many women of reproductive age. Historically, myomectomy is offered to women with symptomatic fibroids who desire to preserve fertility. More recently, uterine artery embolization (UAE) has been explored as another fertility-sparing option. Objective: This review aims to provide an in-depth summary of the effects on fertility and reproductive outcomes following myomectomy and UAE for the treatment of symptomatic fibroids. Evidence Acquisition: Articles were obtained from PubMed using search terms myomectomy, uterine artery embolization, and fertility, as well as American Society of Reproductive Medicine practice committee reports. References from identified sources were searched to allow for thorough review. Results: While myomectomy and UAE are both fertility-sparing options for women with fibroids, reproductive outcomes following myomectomy are superior to UAE with higher rates of clinical pregnancy and live births and lower rates of spontaneous abortion, abnormal placentation, preterm labor, and malpresentation. Conclusions: Myomectomy should be offered to women with symptomatic submucosal or cavity-distorting fibroids who have a strong desire for a future pregnancy. For women who are not appropriate surgical candidates, UAE can be offered, although detrimental effects on future fertility should be disclosed. Relevance: A thorough understanding of the efficacy of both myomectomy and UAE, as well as their impact on future fertility, allows for improved counseling when deciding the optimal intervention for women with fibroids who desire future fertility.

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.

Understanding Patient Evaluation of Abnormal Uterine Bleeding (AUB): A Standardized Patient Case on AUB for OB/GYN Clerkship Students.

INTRODUCTION: The differential diagnosis for abnormal uterine bleeding (AUB) among reproductive-age women is broad and includes common and life-threatening conditions. Recognition and accurate diagnosis of AUB are important but can be challenging for medical students. We developed a standardized patient (SP) encounter for medical students during their OB/GYN clerkship. METHODS: We implemented two SP encounters, on AUB and dyspareunia, that included a postencounter note and SP evaluations. Here, we describe the implementation of the SP encounter on AUB. Students received formative feedback on their interpersonal and history-taking skills, differential diagnosis, and management plan from the SP as well as OB/GYN residents and faculty. Student cumulative feedback was obtained mid-clerkship and following the clerkship. Summary statistics and qualitative data for students' experiences are reported. RESULTS: SP cases were implemented at the Duke University School of Medicine with 101 second-year medical students who completed the encounter from September 2018 to July 2019. Regarding the AUB case, SPs identified students as adequate history takers, with a mean evaluation score of 3.45 (SD = 0.15) out of 5. Most students (94%) correctly identified at least one diagnosis and provided evidence. Endometrial cancer/hyperplasia (63%) and uterine leiomyoma (60%) were most likely to be identified. Regarding both SP encounters, of the 82 students (81%) completing the end-of-clerkship survey, 57% indicated that the experience enhanced their overall learning at least adequately well or better. DISCUSSION: The AUB case provided students with the opportunity to exercise their diagnostic and management skills.