Robotic-assisted uterine transposition followed by anatomic pelvic repositioning for a patient with intramural fibroids and rectal cancer.

OBJECTIVE: To report the first described case of robotic-assisted utero-ovarian transposition followed by anatomic repositioning in the pelvis and cervicovaginal anastomosis in a woman with uterine fibroids, which was performed for fertility preservation in the context of pelvic radiation for rectal cancer. DESIGN: Description of technique and live-action narrated surgical footage showing uterine transposition and repositioning. SETTING: University hospital. PATIENTS: A 36-year-old woman with a new diagnosis of cT3N2M0 rectal adenocarcinoma planned for neoadjuvant chemotherapy and pelvic radiation and desired fertility preservation permissive of future pregnancy. A transvaginal ultrasound revealed a 5-cm posterior leiomyoma and a normal endometrial cavity. The patient elected for utero-ovarian transposition before chemoradiation. The patient included in this video gave consent for publication and posting of the video online, including on social media, the journal website, scientific literature websites, and other applicable sites. Per institutional guidelines, an Institutional Review Board review was not required. INTERVENTIONS: Robotic-assisted utero-ovarian transposition was performed in an inpatient setting 2 weeks after ovarian stimulation and oocyte retrieval. She was given a gonadotropin-releasing hormone agonist for menstrual suppression after oocyte retrieval. The uterus and adnexa were transposed en bloc to the upper abdomen, with perfusion via retroflected infundibulopelvic ligaments. Intravenous indocyanine green was administered intraoperatively to visualize uterine perfusion. Three weeks postoperatively, the patient underwent surgical management of small bowel obstruction, which was successfully managed with laparoscopic adhesiolysis. The patient subsequently completed chemoradiation and had a complete response to the rectal tumor. She therefore elected for surveillance. Seven months after transposition and 2 months after completion of treatment, the patient underwent uncomplicated robotic-assisted utero-ovarian anatomic repositioning in the pelvis with cervicovaginal anastomosis. Chromopertubation confirmed tubal patency. MAIN OUTCOME MEASURES: Restoration of normal pelvic anatomy and resumption of reproductive physiology. RESULTS: At her 4-month postoperative visit, the cervix and vagina were normal in appearance. The patient reported the return of spontaneous menses and sexual activity without complications. CONCLUSION: This case is unique because of the presence of bulky intramural uterine fibroids. The described technique may be useful for selected cancer patients who desire to carry a pregnancy after pelvic radiation for cancer treatment, and demonstrates that patients considering utero-ovarian transposition need not be excluded solely on the basis of the presence of uterine fibroids.

Knowledge of fertility and perception of fertility treatment among adults with sickle cell disease (KNOW FERTILITY).

Introduction: This study assessed fertility knowledge in adults with sickle cell disease using the Cardiff Fertility Knowledge Scale and Fertility Treatment Perception Survey and compared knowledge scores in respondents with sickle cell disease to previously reported unaffected cohorts. Methods: This cross-sectional study surveyed adults over age 18 with sickle cell disease at an adult sickle cell disease center using a 35-question survey addressing infertility risk factor knowledge and perceptions of fertility treatment. Analyses included summary statistics for continuous and categorical variables, univariate linear regression, and Mann-Whitney U tests for group comparisons of Fertility Knowledge Scale scores. Fertility Treatment Perception Survey scores were measured by medians of the two positive statements and four negative statements to generate separate positive and negative treatment belief scores. Statistical significance was set at p < 0.05 for all analyses. Results: Ninety-two respondents (71 female, 21 male) with median age of 32 years (IQR: 25.0, 42.5) completed the survey between October 2020-May 2021. Sixty-five percent of respondents reported taking sickle cell disease treatment and 18% reported refusing at least one sickle cell disease treatment due to fertility concerns. The mean Fertility Knowledge Score was 49% (SD: 5.2), lower than reported in an international cohort (57% vs. 49%, p = 0.001), and higher than in a cohort of reproductive-aged Black women in the USA (49% vs. 38%, p = 0.001). Less than 50% of respondents correctly identified common infertility risk factors including sexually transmitted infections, advanced age, and obesity. Mean positive fertility perception score was 3 (IQR 3, 4), and negative fertility perception score was 3.5 (IQR 3, 4). Factors associated with agreement with negative fertility perception statements included: trying to conceive, refusing sickle cell disease treatment, and undergoing fertility treatment. Discussion: Opportunities exist to improve knowledge of infertility risk factors among adults with sickle cell disease. This study raises the possibility that nearly one in five adults with sickle cell disease refuse SCD treatment or cure due to infertility concerns. Education about common infertility risks factors needs to be addressed alongside disease- and treatment- associated fertility risks.

Expecting more: the case for incorporating fertility services into comprehensive sickle cell disease care.

Assisted reproductive technologies (ART) are not yet systematically available to people with sickle cell disease or their parents. Fertility care for these groups requires addressing sickle cell disease-associated infertility risks, fertility preservation options, pregnancy possibilities and outcomes, and, when needed, infertility treatment. People with a chance of having a child with sickle cell disease can use in-vitro fertilisation with preimplantation genetic testing to conceive a child unaffected by sickle cell disease. Also, parents of children with sickle cell disease can use this technology to identify embryos to become potential future matched sibling donors for stem cell transplant. In the USA, disparities in fertility care for the sickle cell disease community are especially stark. Universal screening of newborn babies' identifies sickle cell disease and sickle cell trait, guidelines direct preconception genetic carrier screening, and standard-of-care fertility preserving options exist. However, potentially transformative treatments and cures for patients with sickle cell disease are not used due to iatrogenic infertility concerns. In diversely resourced care settings, obstacles to providing fertility care to people affected by sickle cell disease persist. In this Viewpoint, we contend that fertility care should be incorporated into the comprehensive care model for sickle cell disease, supporting alignment of treatment goals with reproductive life plans and delivering on the promise of individualised high-quality care for people with sickle cell disease and their families. We consider the obligation to provide fertility care in light of medical evidence, with acknowledgment of formidable obstacles to optimising care, and powerful historical and ethical considerations.

A multidisciplinary pediatric oncofertility team improves fertility preservation and counseling across 7 years.

BACKGROUND: Oncofertility is a developing field of increasing importance, particularly in pediatric oncology, where most patients are likely to survive long-term and have not yet had the opportunity to have children. AIMS: We performed a quality improvement initiative to increase our rates of fertility preservation counseling and referral through the implementation of a pediatric oncofertility team, and we report outcomes 7 years following implementation of our initiative. METHODS AND RESULTS: We compare our baseline oncofertility survey to 44 post-intervention survey respondents and electronic medical record documentation for 149 patients treated in 2019. Ninety-five percent of post-intervention survey respondents recalled fertility counseling (baseline 70%, p = .004) and 89.3% were appropriately referred for fertility preservation (baseline 50%, p = .017). Counseling was documented in 60.4% of charts; 81% of patients analyzed by chart review were appropriately referred for fertility preservation. Fertility preservation outcomes differed by sex assigned at birth. CONCLUSION: Creation of an oncofertility team produced improvements in fertility counseling and fertility preservation referral across an extended period of time.

Fertility preservation for pediatric patients with hemoglobinopathies: Multidisciplinary counseling needed to optimize outcomes.

Hemoglobinopathies are autosomal recessive disorders that occur when genetic mutations negatively impact the function of hemoglobin. Common hemoglobinopathies that are clinically significant include sickle cell disease, alpha thalassemia, and beta thalassemia. Advancements in disease-modifying and curative treatments for the common hemoglobinopathies over the past thirty years have led to improvements in patient quality of life and longevity for those who are affected. However, the diseases, their treatments and cures pose infertility risks, making fertility preservation counseling and treatment an important part of the contemporary comprehensive patient care. Sickle cell disease negatively impacts both male and female infertility, primarily by testicular failure and decreased ovarian reserve, respectively. Fertility in both males and females with beta thalassemia major are negatively impacted by iron deposition due to chronic blood transfusions. Hematopoietic stem cell transplant (HSCT) is currently the only curative treatment for SCD and transfusion dependent beta thalassemia. Many of the conditioning regimens for HSCT contain chemotherapeutic agents with known gonadotoxicity and whole-body radiation. Although most clinical studies on toxicity and impact of HSCT on long-term health do not evaluate fertility, gonadal failure is common. Male fertility preservation modalities that exist prior to gonadotoxic treatment include sperm banking for pubertal males and testicular cryopreservation for pre-pubertal boys. For female patients, fertility preservation options include oocyte cryopreservation and ovarian tissue cryopreservation. Oocyte cryopreservation requires controlled ovarian hyperstimulation (COH) with ten to fourteen days of intensive monitoring and medication administration. This is feasible once the patient has undergone menarche. Follicular growth is monitored via transvaginal or transabdominal ultrasound, and hormone levels are monitored through frequent blood work. Oocytes are then harvested via a minimally invasive approach under anesthesia. Complications of COH are more common in patients with hemoglobinopathies. Ovarian hyperstimulation syndrome creates a greater risk to patients with underlying vascular, pulmonary, and renal injury, as they may be less able to tolerate fluids shifts. Thus, it is critical to monitor patients undergoing COH closely with close collaboration between the hematology team and the reproductive endocrinology team. Counseling patients and families about future fertility must take into consideration the patient's disease, treatment history, and planned treatment, acknowledging current knowledge gaps.

Preconception ovarian reserve and placenta-mediated pregnancy complications among infertile women.

RESEARCH QUESTION: Are preconception ovarian reserve markers, such as Anti-Mullerian hormone and antral follicle count, associated with preeclampsia and placenta mediated pregnancy complications among women with unexplained infertility who conceive with superovulation? DESIGN: This is a secondary analysis of women with unexplained infertility who had a singleton live birth after enrollment in the Analysis of Multiple Intrauterine Gestations after Ovarian Stimulation (AMIGOS) trial that randomized couples to superovulation with letrozole, clomiphene, or gonadotropins with insemination for up to 4 cycles. RESULTS: Compared to controls (N = 156), women who developed preeclampsia (N = 17) had lower Anti-Mullerian hormone levels (2.24 ± 1.20 vs. 2.89 ± 2.32, p = 0.07) and lower antral follicle count (18 ± 7.67 vs. 21 ± 11.43, p = 0.16); though these differences were not statistically significant. There was no relationship between Anti-Mullerian hormone (OR: 1.00, 95% CI: 0.76-1.25) or antral follicle count (OR: 0.98, 95% CI 0.93-1.04) with preeclampsia and between Anti-Mullerian hormone (OR: 1.00, 95% CI: 0.83-1.17) and antral follicle count (OR: 1.00, 95% CI: 0.97-1.04) with placenta medicated pregnancy complications after adjusting for age, BMI and race. CONCLUSIONS: Preconception ovarian reserve markers are not associated with preeclampsia and placenta mediated pregnancy complications among women with unexplained infertility who conceive with superovulation with insemination.

Trainee-Led Quality Improvement Project to Improve Fertility Preservation Counseling for Patients With Cancer.

PURPOSE: Oncofertility counseling regarding the reproductive risks associated with cancer therapy is essential for quality cancer care. We aimed to increase the rate of oncofertility counseling for patients of reproductive age (18-40 years) with cancer who were initiating systemic therapy at the Johns Hopkins Cancer Center from a baseline rate of 37% (25 of 68, June 2019-January 2020) to 70% by February 2021. METHODS: We formed an interprofessional, multidisciplinary team as part of the ASCO Quality Training Program. We obtained data from the electronic medical record and verified data with patients by phone. We surveyed patients, oncologists, and fertility specialists to identify barriers. After considering a prioritization matrix, we implemented Plan-Do-Study-Act (PDSA) cycles. RESULTS: We identified the following improvement opportunities: (1) oncologist self-reported lack of knowledge about counseling and local fertility preservation options and (2) lack of a standardized referral mechanism to fertility services. During the first PDSA cycle (February 2020-August 2020, disrupted by COVID-19), we introduced the initiative to increase oncofertility counseling at faculty meetings. From September 2020 to November 2020, we implemented a second PDSA cycle: (1) educating and presenting the initiative at Oncology Grand Rounds, (2) distributing informative pamphlets to oncologists and patients, and (3) implementing an electronic medical record order set. In the third PDSA cycle (December 2020-February 2021), we redesigned the order set to add information (eg, contact information for fertility coordinator) to the patient after-visit summary. Postimplementation (September 2020-February 2021), counseling rates increased from 37% to 81% (38 of 47). CONCLUSION: We demonstrate how a trainee-led, patient-centered initiative improved oncofertility care. Ongoing work focuses on ensuring sustainability and assessing the quality of counseling.

Teaming in the contemporary fertility clinic: creating a culture to optimize patient care.

When a diverse group of individuals is working together in the contemporary fertility clinic to provide time-sensitive and complex care for patients, a high degree of coordination and collaboration must take place. When performed dynamically, this process is referred to as teaming. Although the positive impact of teamwork in health care settings has been well established in the literature, the concept of teaming has limited foundation in the clinic. This review will provide an overview of how teaming can be used to improve patient care in today's fertility clinics. Approaches to integrating teaming into the clinic that will be discussed include framing, the creation of a psychologically safe environment for staff input, and facilitating collaborative constructs to support teaming. Best practices to implement teaming and how to address challenges to teaming in today's clinical environment will also be addressed.

Acceptable, hopeful, and useful: development and mixed-method evaluation of an educational tool about reproductive options for people with sickle cell disease or trait.

PURPOSE: People with sickle cell disease (SCD) or trait have many reproductive options, some of which decrease the chance of passing SCD to children, including in vitro fertilization with preimplantation genetic testing (IVF + PGT). Few are aware of these options, and educational materials are needed. This study aimed to develop an accessible, non-directive patient education material about reproductive options for those with SCD or trait via a process that incorporated stakeholders from the SCD community. METHODS: Multidisciplinary stakeholders guided development and revision of a novel pamphlet. Researchers applied health literacy scales to measure pamphlet understandability. We interviewed nine patients with SCD and six multidisciplinary clinicians to evaluate the pamphlet. Interviews were recorded, transcribed, and coded by a five-member team who developed a codebook and proposed themes that were revised by all research team members. Feedback was incorporated into a revised pamphlet. RESULTS: A two-page pamphlet describing reproductive options for people with SCD including IVF + PGT was acceptable to key stakeholders, including people with SCD. Material about this complex topic met health literacy standards, including being written at a 5th grade level. Patients reported feeling hopeful after reviewing the pamphlet, and participants considered the pamphlet useful, clear, and appropriate for distribution in clinics and online. CONCLUSIONS: Though awareness of reproductive options for those with SCD or trait is low, patients and providers find a novel pamphlet about this topic acceptable and useful. Educational materials about complex topics including IVF + PGT can be written at a level understandable to the average American.

Natural vs. programmed cycles for frozen embryo transfer: study protocol for an investigator-initiated, randomized, controlled, multicenter clinical trial.

BACKGROUND: Randomized trials of assisted reproductive technology (ART) have been designed for outcomes of clinical pregnancy or live birth and have not been powered for obstetric outcomes such as preeclampsia, critical for maternal and fetal health. ART increasingly involves frozen embryo transfer (FET). Although there are advantages of FET, multiple studies have shown that risk of preeclampsia is increased with FET compared with fresh embryo transfer, and the reason for this difference is not clear. NatPro will compare the proportion of preeclampsia between two commonly used protocols for FET,modified natural and programmed cycle. METHODS: In this two-arm, parallel-group, multi-center randomized trial, NatPro will randomize 788 women to either modified natural or programmed FET and follow them for up to three FET cycles. Primary outcome will be the proportion of preeclampsia in women with a viable pregnancy assigned to a modified natural cycle FET (corpus luteum present) protocol compared to the proportion of preeclampsia in pregnant women assigned to a programmed FET (corpus luteum absent) protocol. Secondary outcomes will compare the proportion of live births and the proportion of preeclampsia with severe features between the protocols. CONCLUSION: This study has a potential significant impact on millions of women who pursue ART to build their families. NatPro is designed to provide clinically relevant guidance to inform patients and clinicians regarding maternal risk with programmed and modified natural cycle FET protocols. This study will also provide accurate point estimates regarding the likelihood of live birth with programmed and modified natural cycle FET. TRIAL REGISTRATION: ClinicalTrials.gov NCT04551807 . Registered on September 16, 2020.

Predictive factors for fertility preservation in pediatric and adolescent girls with planned gonadotoxic treatment.

PURPOSE: To characterize female pediatric and adolescent patients seen for fertility preservation consultation at an academic medical center and to describe the association between demographic or clinical factors and the use of fertility preservation treatment (FPT). METHODS: This is a retrospective chart analysis of female pediatric and adolescent patients seen for fertility preservation consultation at an academic fertility center over a 14-year period from 2005 to 2019. RESULTS: One hundred six females aged 3-21 years were seen for fertility preservation consultation with a mean age of 16.6 years. Diagnoses included hematologic malignancies (41.5%), gynecologic malignancies (9.4%), other malignancies (31.1%), non-malignant hematologic disease (14.2%), and non-malignant conditions (3.8%). Overall, 64.2% of subjects pursued fertility preservation, including oocyte cryopreservation (35.8%) and ovarian tissue cryopreservation (23.6%). Overall, age, minority race, diagnosis, time since diagnosis, and median household income were not significantly associated with odds of completing an FPT procedure. Among all patients, those who underwent gonadotoxic therapy prior to consultation had a lower odds of receiving FPT (OR= 0.24, 95% CI 0.10-0.55). Among patients without chemotherapy exposure, no factors were associated with FPT. CONCLUSIONS: Among pediatric and adolescent patients at an academic center undergoing a fertility preservation consultation, there were no socioeconomic or clinical barriers to FPT use in those who had not yet undergone gonadotoxic therapy. The only factor that was negatively associated with odds of pursuing FPT was prior chemotherapy exposure.

Cost-effectiveness of preimplantation genetic testing for aneuploidy for fresh donor oocyte cycles.

OBJECTIVE: To determine whether in vitro fertilization (IVF) with preimplantation genetic testing for aneuploidy (PGT-A) is cost effective to achieve a live birth compared with IVF alone in fresh donor oocyte cycles. DESIGN: Theoretical cost-effectiveness study. SETTING: Not applicable. PATIENTS: None. INTERVENTIONS: Comparison between the cost of IVF with PGT-A vs. IVF alone to achieve a live birth. The model analyzed a hypothetical single fresh oocyte donor IVF cycle with PGT-A vs. IVF alone and followed the progression of a single embryo through the different decision nodes. Cost estimates assigned to each clinical event were based on data obtained from the literature and institutional costs. MAIN OUTCOME MEASURES: Cost per live birth. RESULTS: In the base-case analysis, IVF with PGT-A was not cost effective in fresh donor oocyte cycles when compared with IVF alone to achieve a live birth. The cycles using PGT-A cost an additional $6,018.66. The incremental cost-effectiveness ratio was found to be $119,606.59 per additional live birth achieved with IVF with PGT-A. Monte Carlo simulations demonstrated that IVF with PGT-A was not cost effective in nearly all iterations. CONCLUSIONS: PGT-A in fresh donor oocyte IVF cycles is not cost effective compared with IVF alone over a wide range of probabilities and costs.

Ovarian tissue cryopreservation in young females with cancer and its impact on ovarian follicle density.

BACKGROUND: Cancer therapy in young females results in irreversible damage to their ovaries potentially leading to premature ovarian failure (POF) and infertility. Ovarian follicle density (FD) serves as a key predictor of reproductive potential for a woman. FD is significantly reduced after cryopreservation in adult women with cancer. FD in young females with cancer has not been investigated. The specific aim of this study was to assess the efficacy of ovarian tissue cyropreservation (OTC) in young females with cancer by evaluating its impact on FD. METHODS: An IRB approved prospective human and animal trial enrolled girls (ages 6-18 years) with cancer at high risk for POF from July 1, 2012 through June 30, 2018. All participants underwent pre-operative ultrasounds evaluating their ovaries.  Following a normal ultrasound, each patient underwent a left ovarian tissue harvest prior to cancer therapy. The ovarian tissue was sectioned for use in pathologic analysis, fertility preservation and xenotransplantation before and after cryopreservation. Comparative statistical analyses of the means of FD before and after cryopreservation were implemented using mixed regression modeling that accounted for the correlation among samples from the same patient and differences in age. RESULTS: Six girls were enrolled (mean, 12 years; median, 13 years, range, 6-17 years). Pathologic analysis was carried out in all viable grafts and ovarian follicle densities were determined. Mean ovarian follicle density (+/- SEM) before cryopreservation was 50.5 +/- 4.26 follicles/mm2 and after cryopreservation was 44.1 +/- 4.25 follicles/mm2, p < 0.001. Following cryopreservation, on average the ovarian tissue retained 89.0.% of the FD of paired fresh samples (95% CI 82.8%, 95.2%). CONCLUSIONS: FD in young females with cancer is significantly reduced following OTC. However, the degree of reduction may be less than that reported in adult women. This is the first study in adolescent girls to provide histologic evidence of preservation of ovarian follicle density and potential efficacy of the ovarian tissue cryopreservation strategy.  By providing this evidence base, the potential benefit to young females with cancer and their family may be prognostically and clinically significant.