Donor side effects experienced under minimal controlled ovarian stimulation (COS) with in vitro maturation (IVM) versus conventional COS for in vitro fertilization (IVF) treatment.

OBJECTIVE: To evaluate oocyte retrieval experiences and side effects under minimal controlled ovarian stimulation (COS) for in vitro maturation (IVM) compared to conventional COS. DESIGN: Retrospective Survey Study SETTING: Clinical in vitro fertilization (IVF) treatment center in Spain. SUBJECTS: Data were collected from subjects undergoing minimal COS (n=110; 600-800 IU FSH) for IVM and conventional COS for egg donation (n=48; 1800-2600 IU FSH) from April 2022 to November 2023. INTERVENTION/EXPOSURE: Minimal and conventional controlled ovarian stimulation. MAIN OUTCOME MEASURES: The most common side effects suffered during ovarian stimulation and after OPU, satisfaction level, and the likelihood of recommending or repeating minimal or conventional COS. Statistical analysis included Mann Whitney and Chi-square tests, with a significance level set at p<0.05. RESULTS: During minimal COS, most subjects did not experience breast swelling (86%), pelvic or abdominal pain (76%), nausea or vomiting (96%), and bleeding (96%). After oocyte pick-up, the majority (75%) reported no pelvic or abdominal pain. The most common side effect was abdominal swelling (52%). Compared to conventional COS cycles, minimal COS subjects reported significantly less post-retrieval pain, with 33% experiencing no pain (vs. 6%; p=0.0011) and with a reduced severe level of pain (5% vs.19%; p=0.0097), leading to fewer subjects requiring pain medication (25% vs. 54%; p=0.0003). Additionally, 85% of women were very satisfied with minimal stimulation and would recommend or repeat the treatment. CONCLUSION: Reducing the hormonal dose for ovarian stimulation has a beneficial effect on subjects, suggesting the combination of minimal COS with IVM techniques is a well-tolerated alternative for women who cannot or do not wish to undergo conventional controlled ovarian hyperstimulation.

Development of laparoscopic skills in skills-naïve trainees using self-directed learning with take-home laparoscopic trainer boxes.

Background: To determine if take home laparoscopic trainer boxes with only self-directed learning can develop laparoscopic skills in surgically naive learners. Methods: 74 starting PGY1 OB/Gyn residents and OB/Gyn clerkship medical students volunteered for the study. Learners performed a laparoscopic peg transfer task with only task instructions and no additional training. Initial tasks were recorded and scored. The participants took home a laparoscopic trainer box for 3 weeks to practice without guidance and returned to perform the same task for a second/final score. Initial and final scores were compared for improvement. This improvement was compared to practice and variables such as demographics, surgical interest, comfort with laparoscopy, and past experiences. Results: Mean peg transfer task scores improved from 287 (SD = 136) seconds to 193 (SD = 79) seconds (p < 0.001). Score improvement showed a positive correlation with number of home practice sessions with a linear regression R2 of 0.134 (p = 0.001). More practice resulted in larger increases in comfort levels, and higher comfort levels correlated with better final task scores with a linear regression R2 of 0.152 (p < 0.001). Interest in a surgical specialty had no impact on final scores or improvement. Playing a musical instrument and having two or more dexterity-based hobbies was associated with a better baseline score (p = 0.032 and p = 0.033 respectively), but no difference in the final scores or score improvement. No other past experiences impacted scores. Conclusions: Our study demonstrates that the use of home laparoscopic box trainers can develop laparoscopic skills in surgical novices even without formal guidance or curriculum.

Human-induced pluripotent stem cell-derived ovarian support cell co-culture improves oocyte maturation in vitro after abbreviated gonadotropin stimulation.

STUDY QUESTION: Can in vitro maturation (IVM) and developmental competence of human oocytes be improved by co-culture with ovarian support cells (OSCs) derived from human-induced pluripotent stem cells (hiPSCs)? SUMMARY ANSWER: OSC-IVM significantly improves the rates of metaphase II (MII) formation and euploid Day 5 or 6 blastocyst formation, when compared to a commercially available IVM system. WHAT IS KNOWN ALREADY: IVM has historically shown highly variable performance in maturing oocytes and generating oocytes with strong developmental capacity, while limited studies have shown a positive benefit of primary granulosa cell co-culture for IVM. We recently reported the development of OSCs generated from hiPSCs that recapitulate dynamic ovarian function in vitro. STUDY DESIGN, SIZE, DURATION: The study was designed as a basic science study, using randomized sibling oocyte specimen allocation. Using pilot study data, a prospective sample size of 20 donors or at least 65 oocytes per condition were used for subsequent experiments. A total of 67 oocyte donors were recruited to undergo abbreviated gonadotropin stimulation with or without hCG triggers and retrieved cumulus-oocyte complexes (COCs) were allocated between the OSC-IVM or control conditions (fetal-like OSC (FOSC)-IVM or media-only IVM) in three independent experimental design formats. The total study duration was 1 April 2022 to 1 July 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Oocyte donors between the ages of 19 and 37 years were recruited for retrieval after informed consent, with assessment of anti-Mullerian hormone, antral follicle count, age, BMI and ovarian pathology used for inclusion and exclusion criteria. In experiment 1, 27 oocyte donors were recruited, in experiment 2, 23 oocyte donors were recruited, and in experiment 3, 17 oocyte donors and 3 sperm donors were recruited. The OSC-IVM culture condition was composed of 100 000 OSCs in suspension culture with hCG, recombinant FSH, androstenedione, and doxycycline supplementation. IVM controls lacked OSCs and contained either the same supplementation, FSH and hCG only (a commercial IVM control), or FOSCs with the same supplementation (Media control). Experiment 1 compared OSC-IVM, FOSC-IVM, and a Media control, while experiments 2 and 3 compared OSC-IVM and a commercial IVM control. Primary endpoints in the first two experiments were the MII formation (i.e. maturation) rate and morphological quality assessment. In the third experiment, the fertilization and embryo formation rates were assessed with genetic testing for aneuploidy and epigenetic quality in blastocysts. MAIN RESULTS AND THE ROLE OF CHANCE: We observed a statistically significant improvement (∼1.5×) in maturation outcomes for oocytes that underwent IVM with OSCs compared to control Media-IVM and FOSC-IVM in experiment 1. More specifically, the OSC-IVM group yielded a MII formation rate of 68% ± 6.83% SEM versus 46% ± 8.51% SEM in the Media control (P = 0.02592, unpaired t-test). FOSC-IVM yielded a 51% ± 9.23% SEM MII formation rate which did not significantly differ from the media control (P = 0.77 unpaired t-test). Additionally, OSC-IVM yielded a statistically significant ∼1.6× higher average MII formation rate at 68% ± 6.74% when compared to 43% ± 7.90% in the commercially available IVM control condition (P = 0.0349, paired t-test) in experiment 2. Oocyte morphological quality between OSC-IVM and the controls did not significantly differ. In experiment 3, OSC-IVM oocytes demonstrated a statistically significant improvement in Day 5 or 6 euploid blastocyst formation per COC compared to the commercial IVM control (25% ± 7.47% vs 11% ± 3.82%, P = 0.0349 logistic regression). Also in experiment 3, the OSC-treated oocytes generated blastocysts with similar global and germline differentially methylated region epigenetic profiles compared commercial IVM controls or blastocysts after either conventional ovarian stimulation. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: While the findings of this study are compelling, the cohort size remains limited and was powered on preliminary pilot studies, and the basic research nature of the study limits generalizability compared to randomized control trials. Additionally, use of hCG-triggered cycles results in a heterogenous oocyte cohort, and potential differences in the underlying maturation state of oocytes pre-IVM may limit or bias findings. Further research is needed to clarify and characterize the precise mechanism of action of the OSC-IVM system. Further research is also needed to establish whether these embryos are capable of implantation and further development, a key indication of their clinical utility. WIDER IMPLICATIONS OF THE FINDINGS: Together, these findings demonstrate a novel approach to IVM with broad applicability to modern ART practice. The controls used in this study are in line with and have produced similar to findings to those in the literature, and the outcome of this study supports findings from previous co-culture studies that found benefits of primary granulosa cells on IVM outcomes. The OSC-IVM system shows promise as a highly flexible IVM approach that can complement a broad range of stimulation styles and patient populations. Particularly for patients who cannot or prefer not to undergo conventional gonadotropin stimulation, OSC-IVM may present a viable path for obtaining developmentally competent, mature oocytes. STUDY FUNDING/COMPETING INTEREST(S): A.D.N., A.B.F., A.G., B.P., C.A., C.C.K., F.B., G.R., K.S.P., K.W., M.M., P.C., S.P., and M.-J.F.-G. are shareholders in the for-profit biotechnology company Gameto Inc. P.R.J.F. declares paid consultancy for Gameto Inc. P.C. also declares paid consultancy for the Scientific Advisory Board for Gameto Inc. D.H.M. has received consulting services from Granata Bio, Sanford Fertility and Reproductive Medicine, Gameto, and Buffalo IVF, and travel support from the Upper Egypt Assisted Reproduction Society. C.C.K., S.P., M.M., A.G., B.P., K.S.P., G.R., and A.D.N. are listed on a patent covering the use of OSCs for IVM: U.S. Provisional Patent Application No. 63/492,210. Additionally, C.C.K. and K.W. are listed on three patents covering the use of OSCs for IVM: U.S. Patent Application No. 17/846,725, U.S Patent Application No. 17/846,845, and International Patent Application No.: PCT/US2023/026012. C.C.K., M.P.S., and P.C. additionally are listed on three patents for the transcription factor-directed production of granulosa-like cells from stem cells: International Patent Application No.: PCT/US2023/065140, U.S. Provisional Application No. 63/326,640, and U.S. Provisional Application No. 63/444,108. The remaining authors have no conflicts of interest to declare.

The voice of infertility: a review of fertility podcasts.

Over the past several years, there has been a significant increase in the popularity of podcast use. The purpose of this study was to review the availability, content, and authorship of podcasts on the topic of fertility and to compare those hosted by physicians vs patients. A search for podcasts relating to the term 'fertility' was performed using 10 podcast platforms. Information relating to each podcast was recorded. Chi-square was used for comparison of proportions and the Mann-Whitney test for continuous variables. Of the 133 podcasts that met inclusion criteria, the most common subject was patient education (62%), followed by fertility awareness (30%), and Third Party Reproduction (13%). A majority of podcasts were hosted by patients (40%), holistic health professionals (28%), and physicians (16%). When comparing podcasts hosted by physicians vs. patients, there was no difference in overall content (p = 0.07), frequency of episodes (p = 0.77), number of episodes (p = 0.63) and number of listener ratings (p = 0.47). We conclude that many fertility podcasts exist with most hosted by patients describing their fertility experiences. Understanding the landscape of fertility podcasts will allow physicians to identify areas of interest and create content which educates and enhances connection with patients.

Socioeconomic disparities in fertility treatments and associated likelihood of livebirth following in vitro fertilization.

OBJECTIVE: To determine whether neighborhood-level socioeconomic characteristics are associated with the likelihood of livebirth (LB) following in vitro fertilization (IVF). Specifically, we evaluated neighborhood-level household income, unemployment rate, and educational attainment. DESIGN: A retrospective cross-sectional study was conducted for patients undergoing autologous IVF cycles. SETTING: Large academic health system. INTERVENTIONS: For each patient, ZIP code of residence was used as a proxy for neighborhood. Neighborhood characteristics were compared between patients with and without LB. Generalized estimating model was used to adjust the association between SES factors and likelihood of a live birth with respect to relevant clinical factors. RESULTS: A total of 4942 autologous IVF cycles from 2768 patients were included: 1717 (62.0%) had at least one associated LB. Patients who achieved LB from IVF were younger, had higher anti-Mullerian hormone (AMH) levels, lower body mass index (BMI), and differed by ethnic background, primary language, and neighborhood socioeconomic characteristics. In a multivariable model, language, age, AMH, and BMI were associated with a live birth from IVF. None of the neighborhood-level socioeconomic variables were associated with the total number of IVF cycles or cycles required to achieve first LB. CONCLUSION: Patients living in neighborhoods with lower annual household income have lower odds of livebirth after IVF compared to those living in more affluent areas, despite undergoing the same number of IVF stimulation cycles.

Histopathologic evaluation of dichorionic twin placentas in unassisted and in vitro fertilized pregnancies affected by preeclampsia.

OBJECTIVE: Pregnancies achieved with assisted reproductive technology have an increased risk of multiple gestations, preeclampsia, and placental morphologic abnormalities. Inflammatory processes affect dichorionic twin pregnancies disproportionately more than singleton gestations and have been associated with adverse pregnancy outcomes, such as fetal growth restriction and preeclampsia. Our objective is to investigate the placental morphology of dichorionic twin pregnancies complicated by preeclampsia conceived with in vitro fertilization (IVF) versus unassisted. METHODS: This is a retrospective analysis of placentas from dichorionic twin pregnancies affected by preeclampsia conceived with IVF versus without assistance from 2010 to 2016 at a tertiary care university hospital. Placental pathology findings were analyzed both independently and in aggregate stratified into composite outcome scores using a modified placental synoptic framework. Individual placental abnormalities were grouped into composite categories based on the site of origin: anatomic placental abnormalities; maternal vascular malperfusion; placental villous maldevelopment; fetal vascular malperfusion; chronic utero-placental separation; maternal-fetal interface disturbance; inflammation of infectious etiology; and inflammation of idiopathic etiology. Placental histopathological statistical analysis was performed using Fisher's exact test. Demographic variables and pregnancy outcomes were compared between groups using the Student's t test or Mann-Whitney U test, where appropriate. p < .05 defined statistical significance. RESULTS: Of 117 dichorionic twin pregnancies, 60 resulted from IVF (Group A) and 57 were conceived without assistance (Group B). Patients in Group A were older (36 [29-37] vs. 33 [32-38] respectively; p = .042) and less parous (18.3% vs. 38.6% percent parous in Group A and Group B, respectively p = .009) than Group B, respectively. No differences were found between groups regarding mode of delivery, gestational age at delivery, placental weight/birthweight, fetal growth restriction, and discordance of fetal growth. There were significantly more inflammatory changes of unknown etiology and composite inflammatory abnormalities in Group A versus Group B (26.7% vs. 10.5%, p = .02). The cumulative number of inflammatory abnormalities per patient had a significantly different distribution among groups (p = .005), and Composite Chronic Inflammation and Infection were found to be significantly more abundant in Group A versus Group B (p = .02). The distribution of placental composite anatomic placental abnormalities, maternal vascular malperfusion, placental villous maldevelopment, fetal vascular malperfusion, chronic utero-placental separation, or maternal-fetal interface disturbance was not statistically different between groups. The distribution of placental abnormalities was not different between groups for any individually analyzed pathological condition. Due to the relatively small sample size, adjustment for potential confounders was not performed. CONCLUSION: Dichorionic twin pregnancies affected by preeclampsia are associated with more placental inflammatory abnormalities if conceived with IVF versus unassisted. Further research is needed to ascertain the underlying mechanisms of these observed differences.

Employer-based insurance coverage increases utilization of planned oocyte cryopreservation.

PURPOSE: To determine the utilization of planned oocyte cryopreservation (OC) in the year immediately prior to, and the year of, insurance coverage commencement for employees at our institution. METHODS: Patient demographics and cycle outcomes were retrospectively compared between the first OC cycles occurring in 2017 vs. 2018 according to insurance coverage and type, age, and the number of oocytes retrieved and cryopreserved. Continuous demographic variables including age, BMI, day 3 FSH and E2, AMH, gravidity, and parity were compared using student T-tests. Cycle outcomes, including the number of oocytes retrieved and cryopreserved were compared using linear regression models, adjusting for potential confounders including age, BMI, and ovarian reserve parameters. RESULTS: Between January 2017 and December 2018, 123 patients underwent planned OC at our institution. Patient age ranged from 23 to 44 years and did not significantly differ from 2017 to 2018 (mean 34.9 vs. 35.2). There was a 12% increase in planned OC utilization from 2017 (N = 58) to 2018 (N = 65). Significantly, more patients had any insurance coverage in 2018 vs. 2017 (71.9% vs. 40.4%, p = 0.001), a 78% increase. From 2017 to 2018, the number of patients with hospital-based insurance coverage undergoing planned OC increased by a factor of 8 (5 to 41.5%, p < 0.001), while the number of self-pay patients significantly decreased (p = 0.001). No differences were found regarding cycle outcomes. CONCLUSION: A greater proportion of women at our institution had insurance coverage for planned OC in 2018 vs. 2017. Employer-based insurance coverage for planned OC was associated with a significant increase in utilization by hospital employees.

A content and quality evaluation of ACGME-accredited reproductive endocrinology and infertility fellowship program webpages.

PURPOSE: To analyze the content of websites of ACGME-accredited REI fellowship programs in the USA and to determine whether there are differences in content across geographic regions. METHODS: All ACGME-accredited REI fellowship websites active as of September 2020 were evaluated and reviewed using 20 criteria in the following nine domains: program overview, contact information, application information, curriculum, current fellows, research, alumni, faculty, and fellowship benefits. Website content was compared across geographic regions (Northeast, Midwest, South, and West) of the USA. Analyses were completed using chi-squared univariate tests with p < 0.05 considered statistically significant. RESULTS: Out of the 49 accredited REI fellowship programs, 45 (92%) had a dedicated website. The most commonly available information included a program description (88%), clinical sites (84%), and application requirements (78%). Programs less commonly shared information regarding research requirements and didactics (65% for each). Current fellows were featured in 55% of websites with their pictures displayed in 41% and ongoing research in 20%. Salary and alumni information were included in only 14% and 12% of sites, respectively. When comparing content by geographic region, programs in the South had less information regarding application requirements (p < 0.001), interview dates (p = 0.03), and clinical sites (p = 0.04) compared to all other regions. CONCLUSIONS: REI fellowship websites have significant variability in content available to applicants, and many are lacking information about core fellowship requirements. An informative and well-constructed website has the potential to improve perception of a graduate program.

Perception of Breast Cancer Risk in Over 11,000 Patients During Routine Mammography Exam.

To assess women's knowledge of personal breast cancer risk. Additionally, we aimed to determine how often physicians are discussing individualized risk assessments of breast cancer with their patients, and if those discussion affected risk perception. Surveys were distributed in radiology centers in New York and made available to patients presenting for routine mammography. As exact number of patients who viewed the survey is unknown, response rate could not be assessed. Data from the survey was used to calculate each patient's personal breast cancer risk using the National Cancer Institute Breast Cancer Risk Assessment Tool. Each patient's actual breast cancer risk was compared to her perceived risk. 15,006 subjects submitted the survey and 11,365 were included in the final analysis. Fourteen percent of women were accurate in their 5-year estimation as compared to calculated risk, and only 7% of respondents were accurate in their estimation of risk by 90 years of age. There was no association between time since discussion of breast cancer risk and accuracy of estimating personal breast cancer risk (p = 0.17). There was no difference in risk estimation accuracy between women who had ever or had never discussed risk with her physician (p = 0.1064). Patients' perceived personal risk of developing breast cancer does not match the Gail model calculated risk. These findings hold true whether or not her physician had discussed personal breast cancer risk with her in the past. Further studies should determine effective strategies to educate patients about their breast cancer risk.

A Case of Babesiosis in a Pregnant Patient Treated with Red Blood Cell Exchange Transfusion.

Babesiosis, caused predominantly by Babesia microti, is an emerging health risk in the Northeastern and Midwestern United States. We present a case of a pregnant woman with history of splenectomy diagnosed with babesiosis at 23 5/7 weeks of gestational age refractory to antimicrobial therapy. She underwent the first reported red blood cell exchange transfusion for babesiosis in pregnancy, at 24 4/7 weeks of gestational age, which resulted in resolution of parasitemia. She had a full term, uncomplicated cesarean delivery. Exchange transfusion is potentially a safe treatment option for severe babesiosis infection in pregnancy and should be considered when other methods are poorly tolerated or ineffective.