Walking the tightrope: Fertility preservation among hereditary breast and ovarian Cancer syndrome Previvors.

INTRODUCTION: Fertility-related concerns cause significant anxiety among patients with Hereditary Breast and Ovarian Cancer Syndrome (HBOC). The Society of Gynecologic Oncology and the American Society for Reproductive Medicine recommend patients diagnosed with HBOC receive early referral to a reproductive endocrinologist. However, evidence about fertility trends in this patient population are limited and guidelines are scarce. The aim of this study is to compare fertility preservation among patients with HBOC to control patients undergoing fertility treatment without a diagnosis of infertility. METHODS: This retrospective study included patients who presented to a single academic institution for fertility preservation in the setting of diagnosis of HBOC. In this study, HBOC patients are referred to as those who had tested positive for pathogenic mutations in BRCA1, BRCA2 or were at high-risk for HBOC based on a strong family history (defined as >3 family members diagnosed with HBOC) without a genetic mutation. HBOC patients were matched in a 1:1 fashion to a control group undergoing fertility preservation without a diagnosis of infertility or HBOC. All analysis was done using SPSS version 9.4 (SAS Institute, Cary, NC). RESULTS: Between August 1st, 2016 and August 1st, 2022, 81 patients presented to the study center for consultation in the setting of HBOC. Of those who presented, 48 (59.2%) ultimately underwent oocyte cryopreservation and 33 (40.7%) underwent embryo cryopreservation. Patients who underwent oocyte cryopreservation due to BRCA1 status were more likely to present for fertility consultation at a younger age compared to control patients (32.6 vs. 34.7 years, p = 0.03) and were more likely to undergo oocyte cryopreservation at a younger age (32.1 vs. 34.6 years, p = 0.007). There was no difference in age at initial consultation or age at procedure for patients with BRCA2 or patients with a strong family history compared to control patients (p > 0.05). There was no difference in the mean age of patients with HBOC at presentation for consultation for embryo cryopreservation or the mean age the patient with HBOC underwent embryo cryopreservation compared to control patients (p > 0.05). Patients with BRCA1 or BRCA2 did not have expedited time from consultation to first cycle start (p > 0.05). After adjusting for factors including anti-Müllerian hormone (AMH) level and age, patients considered in the HBOC group due to family history had less time between consultation and oocyte cryopreservation cycle compared to control patients. (179 vs. 317 days, p = 0.045). There was no difference in time from consultation to starting cycle for embryo cryopreservation for patients with HBOC compared to controls (p > 0.05). CONCLUSION: Patients with HBOC did not undergo expedited fertility treatment compared to control patients undergoing oocyte and embryo cryopreservation for non-infertility reasons. Patients diagnosed with BRCA1 had more oocytes retrieved compared to the control population which is possibly due to earlier age of presentation in the setting of recommended age of risk reducing surgery being age 35-40. When age matched, cycle outcomes did not differ between HBOC and control patients. Given the known cancer prevention benefit and recommendations for risk-reducing surgery, future studies should focus on guidelines for fertility preservation for patients with HBOC.

Obstetric outcomes of nulliparous women with pelvic pain undergoing fertility treatment.

RESEARCH QUESTION: Is there any association between pelvic pain and primary caesarean delivery for patients undergoing assisted reproductive technology (ART) treatment? DESIGN: Retrospective cohort study of nulliparous patients with singleton pregnancies who underwent ART treatment and achieved a live birth between 2012 and 2020. Cases included patients diagnosed with pelvic pain. A 3:1 ratio propensity-score-matched population of patients without a history of pelvic pain was included as the control group. Comparative statistics were performed using chi-squared test and Student's t-test. A multivariate regression analysis was conducted to evaluate the association between pelvic pain and mode of delivery. RESULTS: One hundred and seventy-four patients with pelvic pain were compared with 575 controls. Patients with pelvic pain reported a significantly longer duration of infertility compared with controls (18.98 ± 20.2 months versus 14.06 ± 14.06 months; P = 0.003). Patients with pelvic pain had a significantly higher rate of anxiety disorders (115 ± 21.9 versus 55 ± 31.6; P = 0.009) and use of anxiolytics at embryo transfer (17 ± 3.2 versus 12 ± 6.9; P = 0.03) compared with controls. In addition, patients with pelvic pain had a higher rate of primary caesarean delivery compared with controls (59.8% versus 49.0%; P = 0.01). After adjusting for multiple variables, a significant association was found between pelvic pain and increased odds of primary caesarean delivery (adjusted OR 1.48, 95% CI 1.02-2.1). CONCLUSION: Patients with pelvic pain have significantly higher odds of primary caesarean delivery compared with patients without a history of pelvic pain. The infertility outpatient setting may be uniquely positioned to identify patients at risk for undergoing primary caesarean delivery, and could facilitate earlier intervention for pelvic floor physical therapy during the preconception and antepartum periods.

Single Euploid Embryo Transfer Outcomes After Uterine Septum Resection.

STUDY OBJECTIVE: To study pregnancy outcomes after single euploid embryo transfer (SEET) in patients who underwent prior uterine septum resection to those with uteri of normal contour, without Müllerian anomalies or uterine abnormalities including polyps or fibroids, and without a history of prior uterine surgeries. DESIGN: Retrospective cohort study. SETTING: Single academic affiliated center. PATIENTS: 60 cycles of patients with prior hysteroscopic uterine septum resection who underwent an autologous SEET between 2012 and 2020 were used as the investigational cohort. A 3:1 ratio propensity score matched control cohort of 180 single euploid embryo transfer cycles from patients without a history of uterine septa were used as the control group. INTERVENTIONS: No interventions administered. MEASUREMENTS AND MAIN RESULTS: Pregnancy, clinical pregnancy loss, ongoing clinical pregnancy, and live birth rates in patients with a history of uterine septum resection compared with matched patients without Müllerian anomalies or uterine surgeries. Patients with a prior uterine septum had significantly lower rates of chemical pregnancy (58.33% vs 77.2%, p = .004), implantation (41.67% vs 65.6%, p = .001), and live birth (33.33% vs 57.8%, p = .001) per transfer. No statistical difference in clinical pregnancy loss rates was found when comparing septum patients with controls (8.33% vs 7.8%, p = .89). CONCLUSION: Patients with a history of hysteroscopic resection who undergo in vitro fertilization are more susceptible to suboptimal clinical outcomes compared with patients with normal uteri. Early pregnancy loss rates in patients with a uterine septum are higher than in those without; however, after resection, the rates are comparable. Patients born with septate uteri require assessment of surgical intervention prior to SEET, and to optimize their reproductive outcomes.

Rescue in vitro maturation using ovarian support cells of human oocytes from conventional stimulation cycles yields oocytes with improved nuclear maturation and transcriptomic resemblance to in vivo matured oocytes.

PURPOSE: Determine if the gene expression profiles of ovarian support cells (OSCs) and cumulus-free oocytes are bidirectionally influenced by co-culture during in vitro maturation (IVM). METHODS: Fertility patients aged 25 to 45 years old undergoing conventional ovarian stimulation donated denuded immature oocytes for research. Oocytes were randomly allocated to either OSC-IVM culture (intervention) or Media-IVM culture (control) for 24-28 h. The OSC-IVM culture condition was composed of 100,000 OSCs in suspension culture with human chorionic gonadotropin (hCG), recombinant follicle stimulating hormone (rFSH), androstenedione, and doxycycline supplementation. The Media-IVM control lacked OSCs and contained the same supplementation. A limited set of in vivo matured MII oocytes were donated for comparative evaluation. Endpoints consisted of MII formation rate, morphological and spindle quality assessment, and gene expression analysis compared to in vitro and in vivo controls. RESULTS: OSC-IVM resulted in a statistically significant improvement in MII formation rate compared to the Media-IVM control, with no apparent effect on morphology or spindle assembly. OSC-IVM MII oocytes displayed a closer transcriptomic maturity signature to IVF-MII controls than Media-IVM control MII oocytes. The gene expression profile of OSCs was modulated in the presence of oocytes, displaying culture- and time-dependent differential gene expression during IVM. CONCLUSION: The OSC-IVM platform is a novel tool for rescue maturation of human oocytes, yielding oocytes with improved nuclear maturation and a closer transcriptomic resemblance to in vivo matured oocytes, indicating a potential enhancement in oocyte cytoplasmic maturation. These improvements on oocyte quality after OSC-IVM are possibly occurring through bidirectional crosstalk of cumulus-free oocytes and ovarian support cells.

The Association of Twin Chorionicity with Maternal Outcomes.

OBJECTIVE: Our objective was to investigate the association between maternal outcomes and twin chorionicity in a large, contemporary obstetric population. STUDY DESIGN: Retrospective cohort study was conducted at a single, large tertiary care center. Prenatal and inpatient records for all individuals with twin gestations were reviewed from 2000 to 2016. Patients with monoamniotic twins, higher-order multiples reduced to twins, multiple sets of twins in the study period, or undetermined chorionicity were excluded. Patients with monochorionic twins were compared with those with dichorionic twins. The co-primary outcomes were gestational diabetes mellitus and hypertensive disorders of pregnancy. Secondary outcomes included cesarean delivery, preterm delivery, postpartum hemorrhage, and other maternal outcomes. Bivariate and multivariate analyses were performed to assess associations of chorionicity with maternal outcomes. RESULTS: Of the 2,979 patients eligible for inclusion, 2,627 (88.2%) had dichorionic twin gestations and 352 (11.8%) had monochorionic twin gestations. Patients with monochorionic twins were less likely to self-identify as non-Hispanic White and to have conceived via assisted reproductive technology but were more likely to be publicly insured, multiparous and have prenatal care with a maternal-fetal medicine provider. Neither gestational diabetes mellitus (6.8% monochorionic vs. 6.2% dichorionic, p = 0.74; adjusted odds ratio [OR] 1.06, 95% confidence interval (CI) 0.60-1.86) nor hypertensive disorders of pregnancy (21.9% monochorionic vs. 26.3% dichorionic, p = 0.09; adjusted OR 0.99, 95% CI, 0.71-1.38) differed by chorionicity. Of the secondary maternal outcomes, patients with monochorionic twins experienced a lower frequency of cesarean delivery (46.0 vs. 61.8%, p < 0.001), which persisted after multivariate analyses (adjusted OR 0.60, 95% CI 0.46-0.80). There were no differences in preterm delivery, preterm premature rupture of membranes, hemorrhage, hysterectomy, or intrahepatic cholestasis of pregnancy. CONCLUSION: The odds of gestational diabetes mellitus and hypertensive disorders of pregnancy do not appear to differ by twin chorionicity. KEY POINTS: · Hypertensive disorders of pregnancy do not differ by twin chorionicity.. · Gestational diabetes mellitus does not differ by twin chorionicity.. · Maternal outcomes are similar for individuals with monochorionic and dichorionic twin gestations..

Oncofertility program implementation increases access to fertility preservation options and assisted reproductive procedures for breast cancer patients.

BACKGROUND AND OBJECTIVES: Breast cancer treatment can cause premature ovarian failure, yet the majority of young cancer patients do not receive adequate education about treatment effects before initiating chemotherapy. We studied the impact of an oncofertility program on access to fertility preservation. METHODS: An oncofertility program was initiated to foster collaboration between oncologists and reproductive endocrinologists, and to help increase access to fertility preservation. Documented conversations about fertility concerns, specialist referrals, appointments, and fertility preservation procedures were compared between breast cancer patients from 2004 to 2006, before oncofertility program initiation, and 2007-2012, after program initiation. The study included women <45, stages 0-III, diagnosed before (n = 278) and after (n = 515) program initiation. RESULTS: Demographics for the cohorts were similar. Fertility discussions (P < 0.0001), patients interested in maintaining fertility at diagnosis (P = 0.0041), referrals to reproductive endocrinologists (P < 0.0001), appointments (P < 0.0001), and fertility preservation procedures (P < 0.0183) increased significantly after programmatic implementation. CONCLUSIONS: An oncofertility program increased discussions about fertility preservation and access to assisted reproductive procedures. This program positively impacted compliance with national guidelines advising reproductive-age cancer patients to be offered fertility preservation counseling as an initial component of the multidisciplinary care plan. J. Surg. Oncol. 2017;115:116-121. © 2016 Wiley Periodicals, Inc.

Fertility treatment outcomes in transgender men with a history of testosterone therapy.

Objective: To evaluate fertility treatment outcomes among transgender (TG) men with a history of gender-affirming hormone therapy with exogenous testosterone. Design: Descriptive, retrospective cohort study. Patients: Transgender men with a history of gender-affirming hormone therapy with exogenous testosterone underwent fertility treatments, including embryo cryopreservation, in vitro fertilization (IVF), co-IVF, oocyte cryopreservation, and intrauterine insemination (IUI), between 2013 and 2021. Intervention: Gender-affirming hormone therapy with testosterone. Main Outcome Measures: Live births (LBs), number of frozen embryos, and number of frozen oocytes. Other outcome measures included total gonadotropin used, peak estradiol levels, oocytes retrieved, oocyte maturity rate, fertilization rate, and embryo grade. Results: A total of 77 TG men self-presented or were referred to care at a single academic fertility center, of which 46 (59.7%) TG men underwent fertility preservation and/or family-building counseling, with 16 (20.8%) patients proceeding to fertility treatment. Of those patients who underwent treatment, 11 (68.8%) had a history of gender-affirming hormone therapy with exogenous testosterone use. Cohort 1 included IVF (n = 1), co-IVF (n = 1), embryo cryopreservation (n = 2), cohort 2 included oocyte cryopreservation (n = 4), and cohort 3 included IUI (n = 3). In cohort 1, both the patients who underwent IVF and the patients who underwent co-IVF achieved LBs. All embryo cryopreservation cycles froze three or more embryos. In cohort 2, the average number of frozen mature oocytes was 19.3 ± 16.2 (range 6-43). All patients who underwent IUI cycles achieved LB. Conclusion: In this study, no correlation existed between patient age, time on or off gender-affirming hormone therapy with exogenous testosterone, total gonadotropin used, and number of oocytes retrieved. All patients who completed IVF or embryo cryopreservation produced high-quality blastocytes, and this is the first study to show successful IUI cycles in patients with a history of gender-affirming hormone therapy with exogenous testosterone. This study demonstrates that TG men who have used gender-affirming hormone therapy previously can successfully undergo fertility treatments to attain oocyte and embryo cryopreservation, pregnancy, and LBs.

Are Obstetrics and Gynecology Residents Equipped to Care for Transgender and Gender Nonconforming Patients? A National Survey Study.

Purpose: Our study aims to assess three self-reported outcomes: (1) comfort of, (2) competency in, and (3) curricular satisfaction of OB-GYN residents in caring for transgender and gender nonconforming (TGNC) patients. Methods: This was a cross-sectional survey of a convenience sample of OB-GYN residents consisting of 28 questions on a 4-point Likert scale. The survey was distributed to OB-GYN residents via residency program directors and coordinators. Descriptive statistics and multivariate linear regression modeling were performed to identify demographic and training characteristics associated with differences in comfort, competency, and curricular satisfaction. Results: One-hundred twenty-six surveys were completed by OB-GYN residents (response rate=12.6%). Composite mean scores were calculated in the three self-reported outcome domains: comfort (2.8±0.67), competency (2.7±0.61), and satisfaction (2.2±0.82) which correlate to being "somewhat not" and "somewhat" comfortable, competent, and satisfied. Trainees who identified as lesbian, gay, bisexual, or queer were found to have higher comfort scores. Older age and male gender identity were associated with higher competency scores. No significant differences in comfort, competency, and satisfaction scores between residency training level were observed. The majority (78.1%, N=89) of trainees "strongly agreed" that it was important for them to obtain training in TGNC care topics. Conclusion: OB-GYN residents strongly agreed that learning about care for TGNC patients was important. Residents reported being more competent and comfortable than satisfied, which suggests that further curricular and clinical exposure is necessary to address the unique health care needs of this underserved patient population and to meet the educational needs of OB-GYN residents.

Impact of Fertility Concerns on Tamoxifen Initiation and Persistence.

BACKGROUND: Adjuvant tamoxifen reduces breast cancer recurrence risk and mortality; however, initiation and treatment persistence are poor for younger patients. We hypothesized that a unique set of factors, including fertility concerns, would contribute to the poor tamoxifen use among premenopausal patients. METHODS: From 2007 to 2012, 515 premenopausal patients younger than age 45 years, with stage 0 to III hormone receptor-positive breast cancer, for whom tamoxifen was recommended, were identified. Clinical and pathologic tumor characteristics, treatment regimens, and fertility concerns were recorded. Clinical factors associated with tamoxifen noninitiation and discontinuation were identified using univariate and multivariable analysis. After the recommendation for tamoxifen, patient reasons for tamoxifen noninitiation or discontinuation were also documented. All statistical tests were two-sided. RESULTS: Based on multivariable analysis, fertility concerns were statistically associated with both noninitiation (odds ratio = 5.04, 95% confidence interval (CI) = 2.29 to 11.07) and early discontinuation (hazard ratio = 1.78, 95% CI = 1.09 to 3.38) of tamoxifen. Other independent predictors of noninitiation included a diagnosis of ductal carcinoma in situ, declining radiation, and not receiving chemotherapy (stage I-III). Additionally, smoking and not receiving radiation therapy were statistically significant predictors of early withdrawal from therapy. Primary patient reasons for noninitiation and early discontinuation included concerns about side effects and fertility. CONCLUSION: This study provided insight into factors associated with tamoxifen use for reproductive-aged breast cancer survivors, with a new focus on fertility. Fertility concerns negatively impacted tamoxifen initiation and continuation among premenopausal patients. Interventions to optimize treatment initiation and persistence for young cancer patients should include access to fertility preservation options.