Assisted reproductive technology use and outcomes in childhood cancer survivors.

BACKGROUND: Treatment exposures for childhood cancer reduce ovarian reserve. However, the success of assisted reproductive technology (ART) among female survivors is not well established. METHODS: Five-year survivors of childhood cancer in the Childhood Cancer Survivor Study were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, which captures national ART outcomes. The authors assessed the live birth rate, the relative risk (RR) with 95% confidence intervals (95% CIs), and associations with treatment exposure using generalized estimating equations to account for multiple ovarian stimulations per individual. Siblings from a random sample of survivors were recruited to serve as a comparison group. RESULTS: Among 9885 female survivors, 137 (1.4%; median age at diagnosis, 10 years [range, 0-20 years]; median years of follow-up after age 18 years, 11 years [range, 2-11 years]) underwent 224 ovarian stimulations using autologous or donor eggs and/or gestational carriers (157 autologous ovarian stimulation cycles, 67 donor ovarian stimulation cycles). In siblings, 33 (1.4%) underwent 51 autologous or donor ovarian stimulations. Of those who used embryos from autologous eggs without using gestational carriers, 97 survivors underwent 155 stimulations, resulting in 49 live births, for a 31.6% chance of live birth per ovarian stimulation (vs. 38.3% for siblings; p = .39) and a 43.9% chance of live birth per transfer (vs. 50.0%; p = .33). Prior treatment with cranial radiation therapy (RR, 0.44; 95% CI, 0.20-0.97) and pelvic radiation therapy (RR, 0.33; 95% CI, 0.15-0.73) resulted in a reduced chance of live birth compared with siblings. The likelihood of live birth after ART treatment in survivors was not affected by alkylator exposure (cyclophosphamide-equivalent dose, ≥8000 mg/m2 vs. none; RR, 1.04; 95% CI, 0.52-2.05). CONCLUSIONS: Childhood cancer survivors are as likely to undergo treatment using ART as sibling controls. The success of ART treatment was not reduced after alkylator exposure. The results from the current study provide needed guidance on the use of ART in this population.

Utility of Office Hysteroscopy in Diagnosing Retained Products of Conception Following Early Pregnancy Loss After In Vitro Fertilization.

OBJECTIVE: To evaluate the utility of office hysteroscopy in diagnosing and treating retained products of conception in patients with infertility who experience early pregnancy loss (EPL) after in vitro fertilization (IVF). METHODS: We evaluated a retrospective cohort of 597 pregnancies that ended in EPL in patients aged 18-45 years who conceived through fresh or frozen embryo transfer at an academic fertility practice between January 2016 and December 2021. All patients underwent office hysteroscopy after expectant, medical, or surgical management of the EPL. The primary outcome was presence of retained products of conception at the time of office hysteroscopy. Secondary outcomes included incidence of vaginal bleeding, presence of intrauterine adhesions, treatment for retained products of conception, and duration of time from EPL diagnosis to resolution. Log-binomial regression and Poisson regression were performed, adjusting for potential confounders including oocyte age, patient age, body mass index, prior EPL count, number of prior dilation and curettage procedures, leiomyomas, uterine anomalies, and vaginal bleeding. RESULTS: Of the 597 EPLs included, 129 patients (21.6%) had retained products of conception diagnosed at the time of office hysteroscopy. The majority of individuals with EPL were managed surgically (n=427, 71.5%), in lieu of expectant management (n=140, 23.5%) or medical management (n=30, 5.0%). The presence of retained products of conception was significantly associated with vaginal bleeding (relative risk [RR] 1.72, 95% CI 1.34-2.21). Of the 41 patients with normal pelvic ultrasonogram results before office hysteroscopy, 10 (24.4%) had retained products of conception detected at the time of office hysteroscopy. When stratified by EPL management method, retained products of conception were significantly more likely to be present in individuals with EPL who were managed medically (adjusted RR 2.66, 95% CI 1.90-3.73) when compared with those managed surgically. Intrauterine adhesions were significantly less likely to be detected in individuals with EPL who underwent expectant management when compared with those managed surgically (RR 0.14, 95% CI 0.04-0.44). Of the 127 individuals with EPL who were diagnosed with retained products of conception at the time of office hysteroscopy, 30 (23.6%) had retained products of conception dislodged during the office hysteroscopy, 34 (26.8%) chose expectant or medical management, and 63 (49.6%) chose surgical management. The mean number of days from EPL diagnosis to resolution of pregnancy was significantly higher in patients who elected for expectant management (31 days; RR 1.18, 95% CI 1.02-1.37) or medical management (41 days; RR 1.54, 95% CI 1.25-1.90) when compared with surgical management (27 days). CONCLUSION: In patients with EPL after IVF, office hysteroscopy detected retained products of conception in 24.4% of those with normal pelvic ultrasonogram results. Due to the efficacy of office hysteroscopy in diagnosing and treating retained products of conception, these data support considering office hysteroscopy as an adjunct to ultrasonography in patients with infertility who experience EPL after IVF.

Fertility restoration in mice with chemotherapy induced ovarian failure using differentiated iPSCs.

BACKGROUND: Treatment options for premature ovarian insufficiency (POI) are limited to hormone replacement and donor oocytes. A novel induced pluripotent stem cell (iPSC) transplant paradigm in a mouse model has potential translational applications for management of POI. METHODS: Mouse ovarian granulosa cell derived-iPSCS were labelled with green fluorescent protein (GFP) reporter and differentiated in vitro into oocytes. Differentiated cells were assayed for estradiol and progesterone secretion by enzyme-linked immunosorbent assays. After Fluorescence-Activated Cell Sorting (FACS) for the cell surface marker anti-Mullerian hormone receptor (AMHR2), enriched populations of differentiated cells were surgically transplanted into ovaries of mice that had POI secondary to gonadotoxic pre-treatment with alkylating agents. A total of 100 mice were used in these studies in five separate experiments with 56 animals receiving orthotopic ovarian injections of either FACS sorted or unsorted differentiated iPSCSs and the remaining animals receiving sham injections of PBS diluent. Following transplantation surgery, mice were stimulated with gonadotropins inducing oocyte development and underwent oocyte retrieval. Nine transplanted mice were cross bred with wild-type mice to assess fertility. Lineage tracing of resultant oocytes, F1 (30 pups), and F2 (42 pups) litters was interrogated by GFP expression and validation by short tandem repeat (STR) lineage tracing. FINDINGS: [1] iPSCs differentiate into functional oocytes and steroidogenic ovarian cells which [2] express an ovarian (GJA1) and germ cell (ZP1) markers. [3] Endocrine function and fertility were restored in mice pretreated with gonadotoxic alkylating agents via orthotopic transplantation of differentiated iPSCS, thus generating viable, fertile mouse pups. INTERPRETATION: iPSC-derived ovarian tissue can reverse endocrine and reproductive sequelae of POI. FUNDING: Center for Infertility and Reproductive Surgery Research Award, Siezen Foundation award (RMA). Reproductive Scientist Development Program, Marriott Foundation, Saltonstall Foundation, Brigham Ovarian Cancer Research Fund (K.E).

Ultra-low-dose and very-low-dose Lupron downregulation protocols for poor responders based on POSEIDON group 3 and 4 classifications.

PURPOSE: The objective of this study was to assess if very-low-dose Lupron (VLDL) and ultra-low-dose Lupron (ULDL) protocols can have comparable cycle outcomes when compared to other "poor responder" stimulation protocols based on POSEIDON classification groups 3 (PG3) and 4 (PG4). METHODS: A retrospective cohort study at a single, large academic center was performed. Women in PG3 (age < 35, AMH < 1.2 ng/mL) or PG4 (age ≥ 35, AMH < 1.2 ng/mL) undergoing in vitro fertilization using an ULDL (Lupron 0.1 to 0.05 mg daily), VLDL (Lupron 0.2 to 0.1 mg daily), microflare (Lupron 0.05 mg twice a day), estradiol priming/antagonist, antagonist, or minimal stimulation protocols from 2012 to 2021 were included. The primary outcome was the number of mature oocytes (MII) obtained. The secondary outcome was live birth rate (LBR). RESULTS: The cohort included 3601 cycles. The mean age was 38.1 ± 3.8 years. In the PG3 group, ULDL and VLDL protocols produced a comparable number of MIIs (5.8 ± 4.3 and 5.9 ± 5.4, respectively) and live births (33.3% and 33.3%, respectively) when compared to other protocols. In the PG4 group, ULDL and VLDL protocols resulted in a higher percentage of MIIs when compared to microflare or minimal stimulation (Microflare/ULDL: adjusted relative risk (aRR) 0.78 (95% CI 0.65, 0.95); min stim/ULDL: aRR 0.47 (95% CI 0.38, 0.58); microflare/VLDL: aRR 0.77 (95% CI 0.63, 0.95); min stim/VLDL: aRR 0.47 (95% CI 0.38, 0.95)). There were no significant differences in LBR. CONCLUSION: Dilute Lupron downregulation protocols have comparable outcomes to other poor responder protocols and are reasonable to use.

Fertility Preferences and Practices Among Young Women With Breast Cancer: Germline Genetic Carriers Versus Noncarriers.

BACKGROUND: Young women with breast cancer who carry germline genetic pathogenic variants may face distinct fertility concerns, yet limited data exist comparing fertility preferences and practices between carriers and noncarriers. PATIENTS AND METHODS: Participants in the Young Women's Breast Cancer Study (NCT01468246), a prospective cohort of women diagnosed with breast cancer at ≤40 years, who completed a modified Fertility Issues Survey were included in this analysis. RESULTS: Of 1052 eligible participants, 118 (11%) tested positive for a pathogenic variant. Similar proportions (P = .23) of carriers (46%, [54/118]) and noncarriers (37%, [346/934]) desired more biologic children prediagnosis, and desire decreased similarly postdiagnosis (carriers, 30% [35/118] vs. noncarriers, 26% [244/934], P = .35). Among those desiring children postdiagnosis (n = 279), concern about cancer risk heritability was more common among carriers (74% [26/35] vs. noncarriers, 36% [88/244], P < .01). Carriers were more likely to report that concern about cancer risk heritability contributed to a lack of certainty or interest in future pregnancies (20% [16/81] vs. noncarriers, 7% [49/674], P = .001). Similar proportions (P = .65) of carriers (36% [43/118]) and noncarriers (38% [351/934]) were somewhat or very concerned about infertility post-treatment; utilization of fertility preservation strategies was also similar (carriers, 14% [17/118] vs. noncarriers, 12% [113/934], P = .78). CONCLUSION: Carriers were similarly concerned about future fertility and as likely to pursue fertility preservation as noncarriers. Concern about cancer risk heritability was more frequent among carriers and impacted decisions not to pursue future pregnancies for some, underscoring the importance of counseling regarding strategies to prevent transmission to offspring, including preimplantation genetic testing.

The impact of fertility preservation on the timing of breast cancer treatment, recurrence, and survival.

BACKGROUND: Many young women with breast cancer undergo fertility preservation (FP) before cancer treatment. This study examined the impact of FP on breast cancer outcomes. METHODS: The authors performed a retrospective cohort study of 272 women aged 20 to 45 years with newly diagnosed stage 0 to III breast cancer who underwent an FP consultation between 2005 and 2017. Among these women, 123 (45.2%) underwent FP (fertility preservation-positive [FP+]). The remaining 149 women did not undergo FP (fertility preservation-negative [FP-]). RESULTS: The characteristics at enrollment were similar with the exception of ethnicity (FP+, 87.8% White; FP-, 67.8% White; P = .002) and BRCA status (FP+, 27.7% BRCA+; FP-, 15.5% BRCA+; P = .021). The median follow-up was approximately 4 years. Women who underwent FP had longer times to first treatment (FP+, 37 days; FP-, 31 days; adjusted hazard ratio [aHR], 0.74; confidence interval [CI], 0.56-0.99) and neoadjuvant chemotherapy (FP+, 36 days; FP-, 26 days; aHR, 0.41; CI, 0.24-0.68) and from surgery to adjuvant chemotherapy (FP+, 41 days; FP-, 33 days; aHR, 0.58; CI, 0.38-0.90). Adjusted 3- and 5-year invasive disease-free survival (IDFS) rates were comparable between the 2 groups (3-year IDFS: FP+, 85.4%; FP-, 79.4%; P = .411; 5-year IDFS: FP+, 73.7%; FP-, 67.1%; P = .288). Similarly, no difference in overall survival (OS) was observed between the 2 groups (3-year OS: FP+, 95.5%; FP-, 93.5%; P = .854; 5-year OS: FP+, 84.2%; FP-, 81.4%; P = .700). CONCLUSIONS: FP after a breast cancer diagnosis delays the time to treatment by a small amount, but this delay does not lead to inferior IDFS or OS.

Safety of Surgical Fertility Preservation Procedures in Children Prior to Hematopoietic Stem Cell Transplant.

Long-term survival following hematopoietic stem cell transplant (HSCT) in childhood continues to improve, and patients are thus increasingly faced with the late effects of treatment. Infertility is very common for both males and females following HSCT and is one of the most distressing sequelae. Adoption and surrogate egg or sperm donation are possibilities for some patients, but post-HSCT reversal of gonadal failure is not possible. We have recently initiated an oncofertility program with a dedicated practitioner with specific expertise in this area. Our practice is for her to meet with all families and age-appropriate patients during the pre-HSCT evaluation period. This allows patients and families to be accurately informed about the expected treatment-related infertility risk and the available options for fertility preservation. Sperm banking and egg or embryo cryopreservation are established approaches but are not achievable for many children and adolescents. Recently, the harvesting and cryopreservation of ovarian and testicular tissue represents a novel surgical option that allows for the possibility of fertility preservation to be extended to children of all ages. The purpose of this investigation is to evaluate the safety of these procedures proximal to conditioning therapy and HSCT. This is a retrospective report on a consecutive cohort of all patients aged 0 to 25 years who, after discussion with our oncofertility specialist, chose to undergo surgical fertility preservation (laparoscopic unilateral oophorectomy or testicular biopsy) at our institution between March 2018 and April 2020. These procedures occurred under general anesthesia at the time of central line placement prior to the initiation of HSCT conditioning. We assess the safety of the procedures in terms of postoperative complications and impact on HSCT course. Twenty-two patients underwent fertility preservation surgical procedures. Thirteen patients (59%) were female, median age 13 years (1 to 22 years), and 9 (41%) were male, median age 8 years (5 to 12 years). Fourteen (63%) were prepubertal and 8 (36%) pubertal. HSCT indications were hematologic malignancies/solid tumor (40%) and nonmalignant diseases (60%). Most received an allogenic graft (68%) and 81% had myeloablative conditioning. All patients became neutropenic at a median of 10 days (0 to 51 days) from the surgical procedure; 1 was neutropenic at the time of testicular tissue cryopreservation (TTC). The mean duration for the procedures performed, including ovarian tissue cryopreservation (OTC) or TTC, was 98 minutes (49 to 260 minutes) and 97 minutes (56 to 178 minutes), respectively. Estimated blood loss was minimal and no postoperative site infections occurred. One postprocedure, blood culture-negative fever was reported without an identifiable source; the patient completed 48 hours of antibiotics with resolution of fever. Sixty-two percent of females and 56% of males started conditioning within 24 hours of OTC/TTC (15 hours to 113 days; median, 1 day). The median time to engraftment was 22 days (9 to 33 days) in females and 17 days (11 to 67 days) in males, consistent with our institutional benchmarks. One patient with aplastic anemia had primary graft failure, attributed to low cell dose. This patient engrafted after a second transplant from an alternative donor but ultimately died of multiorgan failure. He was neutropenic for over 60 days and never experienced surgical site infection. There were no procedure-related delays to start of conditioning or to discharge. Children of all ages can now be offered the possibility of fertility preservation following HSCT for benign and malignant conditions. Our review suggests that these procedure for both females and males can be performed close to the start of conditioning, which allows for coupling with central access placement. These procedures appear to be safe and do not add to transplant-related morbidity.

Quality of embryos on day 7 after medium refreshment on day 6: a prospective trial.

STUDY QUESTION: Are embryos that fail to meet biopsy or freezing criteria on day 6 (D6) more likely to meet these criteria on day 7 (D7) if cultured in fresh medium from D6 to D7? SUMMARY ANSWER: Refreshment of medium on D6 did not increase the proportion of usable embryos on D7, with an adverse effect for women ≥40 years old. WHAT IS KNOWN ALREADY: Embryo development in continuous single-step medium, from fertilization to the blastocyst stage, is equivalent to that using a sequential media protocol. However, there remains a theoretical benefit of refreshing the culture environment by transitioning slowly developing D6 embryos to a fresh medium droplet of the same composition, with a renewed source of nutrients and a milieu free of metabolic toxins. STUDY DESIGN, SIZE, DURATION: This was a prospective trial of culture media exposure in which embryos were randomized on D6 to remain in the same culture medium from D3 to D7 (continuous, n = 620) or be moved to fresh medium (fresh, n = 603) on D6, with re-evaluation on D7. Data were collected from IVF cycles, with or without ICSI, between 29 March 2019 and 17 February 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Embryos from 298 women, aged 18-44 years, from cycles with or without preimplantation genetic testing (PGT) that did not meet criteria for biopsy and/or freeze on D6 were included in the study. Embryos were only included if there was a minimum of two embryos meeting the inclusion criteria in any cohort. Only the first cycle undertaken by each woman in the study period from which embryos were randomized was included. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1254 embryos were randomized from 312 cycles (209 non-PGT and 103 PGT) including 200 women undergoing IVF without PGT and 98 women who underwent PGT. The proportion of usable blastocysts on D7 did not differ between groups: 10.1% (61/603) in fresh versus 9.7% (60/620) in continuous medium (relative risk (RR) 1.05, 95% CI 0.74-1.47)). Embryos from women ≥40 years old had a significantly decreased likelihood of achieving a usable blastocyst on D7 after culture in fresh versus continuous medium: 3.5% versus 12.2%; RR 0.29, 95% CI 0.08-0.98. In total, 9.9% of embryos otherwise discarded on D6 met the criteria for biopsy and/or freeze on D7. LIMITATIONS, REASONS FOR CAUTION: Future work investigating implantation, clinical pregnancy and miscarriage rates with D7 embryos is still needed. WIDER IMPLICATIONS OF THE FINDINGS: Refreshment of medium on D6 did not increase the proportion of usable embryos on D7 overall. Younger women were more likely to develop D7 embryos after refreshment of medium on D6, while an adverse effect was seen in women ≥40 years old. However, by extending the culture of embryos to D7, additional blastocysts become available for clinical use. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided through the Department of Obstetrics and Gynecology at Brigham and Women's Hospital. I.G.I. works with Teladoc Health. A.L. has no disclosures. E.S.G. works as a consultant for Teladoc Health, and a writer and editor for UpToDate and BioMed Central. C.R. is a board member of the American Society for Reproductive Medicine and works with UpToDate. TRIAL REGISTRATION NUMBER: N/A.

Fertility preservation outcomes in women with gliomas: a retrospective case-control study.

PURPOSE: With advances in cancer therapy, reproductive-aged women can look forward to a life post-malignancy. Fortunately, fertility preservation (FP) may provide relief from potential infertility caused by cancer or associated caustic treatments. Outcomes of FP in pre-treatment reproductive-aged women with gliomas have not been previously characterized. METHODS: Between 2007 and 2018, 10 patients undergoing FP prior to chemotherapy and/or radiation treatment for gliomas were identified at Brigham and Women's Hospital. They were matched 3:1 to male-factor infertility patients by age ± 1 year. RESULTS: Patients with gliomas had significantly lower baseline anti-Müllerian hormone levels than male-factor infertility controls (2.37 vs 5.16 ng/mL, p = 0.002, log transformed). Despite higher starting (350 vs. 240 IU, p = 0.004) and total gonadotropin doses (4270 vs. 2270 IU, p < 0.001) over a similar stimulation duration (12.1 vs. 11.1 days, p = 0.219), cancer patients had lower peak estradiol levels (1420 vs. 2245 pg/mL, p = 0.003). The total number of follicles on the day of trigger (14.1 vs. 15.6, p = 0.284), the number of oocytes retrieved (18.4 vs. 20.5, p = 0.618), and the percentage of mature oocytes (69.9 vs. 73.8%, p = 0.076) were similar between cases and controls. One patient returned for a cryopreserved embryo transfer and delivered a healthy child. CONCLUSIONS: Patients undergoing FP prior to chemotherapy and/or radiation for a glioma achieve satisfactory FP outcomes and should be appropriately counseled regarding the opportunity to family-build after treatment.

Cancer Treatment-Related Infertility: A Critical Review of the Evidence.

Cancer treatments may compromise the fertility of children, adolescents, and young adults, and treatment-related infertility represents an important survivorship issue that should be addressed at diagnosis and in follow-up to ensure optimal decision-making, including consideration of pursuing fertility preservation. Risk of infertility varies substantially with patient and treatment factors. The ability to accurately assess fertility risk for many patients is hampered by limitations of the current literature, including heterogeneity in patient populations, treatments, and outcome measures. In this article, we review and synthesize the available data to estimate fertility risks from modern cancer treatments for both children and adult cancer survivors to enable clinicians to counsel patients about future fertility.

Effect of class III and class IV obesity on oocyte retrieval complications and outcomes.

OBJECTIVE: To assess the effect of class III (body mass index [BMI] 40-49.9 kg/m2) and class IV obesity (BMI ≥ 50 kg/m2) on oocyte retrieval complications and outcomes. DESIGN: Cohort study. SETTING: Academic center. PATIENT(S): Women who underwent an oocyte retrieval from January 1, 2012 to May 31, 2017. Women with BMI ≥ 40 kg/m2 (n = 144) were age-matched to women with BMI <25, 25-29.9, 30-34.9, and 35-39.9 kg/m2 (n = 1,016). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Anesthetic and procedural outcomes during oocyte retrieval. RESULT(S): Overall, 1,924 of 1,947 oocyte retrievals (98.8%) were performed under total intravenous anesthesia. No patients with BMI ≥ 40 kg/m2 required intraoperative conversion to endotracheal intubation or hospital admission. Two patients (0.8%) with BMI ≥ 40 kg/m2 required a laryngeal mask airway intraoperatively owing to oxygen desaturation. An oral/nasal airway was used to resolve oxygen desaturation in 16 patients (6.25%) with BMI ≥ 40 kg/m2, compared with in 17 patients (1.0%) with BMI < 40 kg/m2. As BMI increased, a statistically significant increase in propofol dose, fentanyl dose, and procedure time was observed. Eighteen patients (7.0%) with BMI ≥ 40 kg/m2 underwent a transabdominal retrieval, compared with 15 (0.9%) with BMI < 40 kg/m2. CONCLUSION(S): Serious intraoperative and postoperative complications were uncommon across all BMI groups, though minor complications were more common with class III and class IV obesity. These patients were also more likely to require higher doses of propofol and fentanyl, have longer oocyte retrievals, and require a transabdominal retrieval. Overall, oocyte retrieval can be safely performed as an outpatient procedure in women with class III and class IV obesity.

Patient experience in a randomized trial of a weekly progesterone vaginal ring versus a daily progesterone gel for luteal support after in vitro fertilization.

OBJECTIVE: To assess patient experience and convenience of using progesterone vaginal ring (VR) versus vaginal gel for women requiring luteal phase support during in vitro fertilization (IVF). DESIGN: Post hoc analysis of a prospective, randomized, single-blind, multicenter, phase 3 clinical trial. SETTING: Twenty-two U.S. IVF centers. PATIENT(S): Women undergoing IVF (N = 1,297). INTERVENTION(S): Randomization to weekly VR or daily gel the day after egg retrieval for up to 10 weeks, with fresh embryo transfer IVF per site-specific procedures. MAIN OUTCOME MEASURE(S): Patient satisfaction questionnaire completed at final study visit. RESULT(S): In the women who were taking ≥1 dose of either VR (n = 647) or gel (n = 650), >97% reported that learning to use the formulation, remembering to take it at the correct time, and using it as prescribed was "easy" or "somewhat easy." More VR than gel users reported noninterference with daily activity (93.3% vs. 74.7%, P<.001), sexual comfort (80.3% vs. 67.8%, P<.001), and sexual desire (73.8% vs. 61.8%, P<.001), as well as not being bothered during sexual intercourse (66.9% vs. 39.2%, P<.001). More gel than VR users reported no difficulty with application (97.4% vs. 80.9%, P<.001). Among women who had previously used progesterone during IVF, more VR users than gel users preferred their currently assigned treatment to their previous treatment (91.4% vs. 83.0%, P=.03). CONCLUSION(S): Weekly progesterone VR and daily progesterone gel were easy to use, with limited impact on quality of life. Overall, the VR appeared to interfere less with daily life, social activities, and sexual activity although the gel was less difficult or stressful to apply. CLINICAL TRIAL REGISTRATION NUMBER: NCT00615251.

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

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

First-trimester emergencies: a radiologist's perspective.

The purpose of this article is to help the practitioner ensure early diagnosis and response to emergencies in the first trimester by reviewing anatomy of the developing embryo, highlighting the sonographic appearance of common first-trimester emergencies, and discussing key management pathways for treating emergent cases. First-trimester fetal development is a stepwise process that can be challenging to evaluate in the emergency department (ED) setting. This is due, in part, to the complex anatomy of early pregnancy, subtlety of the sonographic findings, and the fact that fewer than half of patients with ectopic pregnancy present with the classic clinical findings of a positive pregnancy test, vaginal bleeding, pelvic pain, and tender adnexa. Ultrasound (US) has been the primary approach to diagnostic imaging of first-trimester emergencies, with magnetic resonance imaging (MRI) and computed tomography (CT) playing a supportive role in a small minority of cases. Familiarity with the sonographic findings diagnostic of and suspicious for early pregnancy failure, ectopic pregnancy, retained products of conception, gestational trophoblastic disease, failed intrauterine devices, and complications associated with assisted reproductive technology (ART) is critical for any emergency radiologist. Evaluation of first-trimester emergencies is challenging, and knowledge of key imaging findings and familiarity with management pathways are needed to ensure early diagnosis and response.

Ovarian Aging in Women With BRCA Germline Mutations.

Context: Recent clinical and laboratory studies suggested that women with BRCA mutations have lower ovarian reserve and their primordial follicle oocytes may be more prone to DNA damage; however, direct proof is lacking. Objective: To determine whether women with germline BRCA mutations have reduced primordial follicle reserve and increased oocyte DNA damage. Design: A comparative laboratory study of ovarian tissue obtained from unaffected BRCA mutation carriers (BMCs) vs age-matched organ donor cadavers. Setting: Two academic centers. Patients or Other Participants: Of the 230 ovarian specimens from BMCs, 18 met the study inclusion criteria. Healthy ovaries from 12 organ donor cadavers served as controls. Intervention: Histology and immunohistochemical analysis on paraffin-embedded ovarian sections. Main Outcome Measure(s): Primordial follicle density and the percentage of DNA double-strand break (DSB)-positive primordial follicle oocytes. Results: Ovaries from BMCs had significantly lower primordial follicle densities than those of controls (11.2 ± 2.0 vs 44.2 ± 6.2 follicles/mm3; P = 0.0002). BRCA mutations were associated with increased DNA DSBs in primordial follicle oocytes (62% ± 5.2% vs 36% ± 3.4%; P = 0.0005). In subgroup analyses, both BRCA1 and BRCA2 mutations were associated with lower primordial follicle density (P = 0.0001 and 0.0030, respectively), and BRCA1 mutations were associated with higher DNA DSBs (P = 0.0003) than controls. The rates of follicle decline (R2 = 0.74; P = 0.0001) and DNA DSB accumulation (R2 = 0.70; P = 0.0001) appeared to be accelerated, particularly in primordial follicle oocytes of BMCs over age 30 years. Conclusions: We provide direct evidence of diminished ovarian reserve as well as accelerated primordial follicle loss and oocyte DNA damage in women with BRCA mutations. These findings may further our understanding of ovarian aging, and be useful when counseling BMCs.

Preconception consultations with Maternal Fetal Medicine for obese women: a retrospective chart review.

BACKGROUND: Obesity is associated with impaired fertility and pregnancy complications, and preconception weight loss may improve some of these outcomes. The purpose of this study was to evaluate the quality and effectiveness of Maternal Fetal Medicine (MFM) preconception consults for obese women. METHODS: We performed a retrospective chart review examining 162 consults at an academic medical center from 2008 to 2014. The main outcome measures included consultation content - e.g. discussion of obesity-related pregnancy complications, screening for comorbidities, and referrals for weight loss interventions - and weight loss. RESULTS: Screening for diabetes and hypertension occurred in 48% and 51% of consults, respectively. Discussion of obesity-related pregnancy complications was documented in 96% of consults. During follow-up (median 11 months), 27% of patients saw a nutritionist, 6% saw a provider for a medically supervised weight loss program, and 6% underwent bariatric surgery. The median weight change was a loss of 0.6% body weight. CONCLUSIONS: In this discovery cohort, a large proportion of MFM preconception consultations lacked appropriate screening for obesity-related comorbidities. While the vast majority of consultations included a discussion of potential pregnancy complications, relatively few patients achieved significant weight loss. More emphasis is needed on weight loss resources and delaying pregnancy to achieve weight loss goals.

Outpatient endometrial aspiration: an alternative to methotrexate for pregnancy of unknown location.

BACKGROUND: Pregnancies of unknown location with abnormal beta-human chorionic gonadotropin trends are frequently treated as presumed ectopic pregnancies with methotrexate. Preliminary data suggest that outpatient endometrial aspiration may be an effective tool to diagnose pregnancy location, while also sparing women exposure to methotrexate. OBJECTIVE: The purpose of this study was to evaluate the utility of an endometrial sampling protocol for the diagnosis of pregnancies of unknown location after in vitro fertilization. STUDY DESIGN: A retrospective cohort study of 14,505 autologous fresh and frozen in vitro fertilization cycles from October 2007 to September 2015 was performed; 110 patients were diagnosed with pregnancy of unknown location, defined as a positive beta-human chorionic gonadotropin without ultrasound evidence of intrauterine or ectopic pregnancy and an abnormal beta-human chorionic gonadotropin trend (<53% rise or <15% fall in 2 days). These patients underwent outpatient endometrial sampling with Karman cannula aspiration. Patients with a beta-human chorionic gonadotropin decline ≥15% within 24 hours of sampling and/or villi detected on pathologic analysis were diagnosed with failing intrauterine pregnancy and had weekly beta-human chorionic gonadotropin measurements thereafter. Those patients with beta-human chorionic gonadotropin declines <15% and no villi identified were diagnosed with ectopic pregnancy and treated with intramuscular methotrexate (50 mg/m2) or laparoscopy. RESULTS: Across 8 years of follow up, among women with pregnancy of unknown location, failed intrauterine pregnancy was diagnosed in 46 patients (42%), and ectopic pregnancy was diagnosed in 64 patients (58%). Clinical variables that included fresh or frozen embryo transfer, day of embryo transfer, serum beta-human chorionic gonadotropin at the time of sampling, endometrial thickness, and presence of an adnexal mass were not significantly different between patients with failed intrauterine pregnancy or ectopic pregnancy. In patients with failed intrauterine pregnancy, 100% demonstrated adequate postsampling beta-human chorionic gonadotropin declines; villi were identified in just 46% (n=21 patients). Patients with failed intrauterine pregnancy had significantly shorter time to resolution (negative serum beta-human chorionic gonadotropin) after sampling compared with patients with ectopic pregnancy (12.6 vs 26.3 days; P<.001). CONCLUSION: With the use of this safe and effective protocol of endometrial aspiration with Karman cannula, a large proportion of women with pregnancy of unknown location are spared methotrexate, with a shorter time to pregnancy resolution than those who receive methotrexate.

Oncofertility: Fertile Ground for Conflict Between Patient Autonomy and Medical Values.

Oncofertility is a unique, multidisciplinary field that serves to bridge the gap between available fertility resources and the special reproductive needs of cancer patients. Oncofertility is a growing field due to the increasing number of survivors, development of new oncologic therapies, extension of duration of therapies, and development and refinement of reproductive therapies. While the technologies and demand for services expand, clinicians need to be appropriately prepared for dealing with various clinical scenarios that may require ethical deliberation. Three real cases are presented in which the patient wishes to pursue reproductive assistance, but her decision is met with hesitance or uncertainty by her care team. Discussion of these clinical scenarios highlights ethical implications of oncofertility practice and serves to highlight the need for the establishment of multidisciplinary care teams and guidelines to support both clinicians and patients. IMPLICATIONS FOR PRACTICE: The growing field of oncofertility is ripe for conflict between patient autonomy and medical values due to the nature of cancer and associated threat on an individual's health and survival, as well as the personal significance of childbearing. Cases are presented and ethical implications are discussed to further explore the inherent difficulties in oncofertility practice and guide clinicians in similar situations. Developing guidelines and establishing multidisciplinary teams to facilitate oncofertility discussions and care, as well as training of clinical team members, may improve patient safety, well-being, and satisfaction within the context of fertility decision making, care, and outcomes.