Changing the Perspective on Fertility Preservation for Women with Metastatic or Advanced Stage Cancer.

PURPOSE OF REVIEW: In this Perspective we share the personal story of a 33-year-old patient diagnosed with metastatic breast cancer and her journey through fertility preservation, surrogacy, and eventually motherhood, highlighting misconceptions about fertility preservation in this population. RECENT FINDINGS: There are nearly 1 million women under the age of 50 diagnosed and living with cancer in the USA. These patients are met with life-altering decisions, including those that may limit their reproductive ability. While there have been tremendous advances and advocacy in the field of oncofertility, there has been limited focus on patients with advanced stage or metastatic cancer. We describe five key misconceptions surrounding fertility preservation in patients with advanced stage cancer, offering a review of the literature and our approach to challenging topics like desiring fertility preservation in the face of Stage 4 disease, the safety and timing of ovarian stimulation during cancer treatment, and passing away following fertility preservation. We review the importance of assessing perceptions of fertility preservation in patients with metastatic cancer and highlight the lack of research in this area as a call to action.

Presence of Fibroids on Transvaginal Ultrasonography in a Community-Based, Diverse Cohort of 996 Reproductive-Age Female Participants.

Importance: Fibroids are benign uterine tumors that can cause significant morbidity. Knowledge on fibroid prevalence, especially in the asymptomatic population and in Asian and Hispanic or Latina individuals, is limited, and a better understanding of affected groups will improve timely diagnosis and motivate appropriate recruitment in clinical trials to reduce health disparities. Objective: To estimate the prevalence of fibroids in a diverse cohort of female individuals. Design, Setting, and Participants: This cross-sectional study included female individuals not seeking treatment for fertility or other conditions who were prospectively recruited in an academic medical center in San Francisco, California. Effort was made to recruit an equal proportion of participants from 4 large racial and ethnic groups in the United States (Asian-Chinese, Black or African American, Hispanic or Latina, and White) and across 4 equal age groups between 25 and 45 years. All participants reported regular menses (21-35 days), had not used estrogen- or progestin-containing medications in the 3 months prior to enrollment, and denied history of pelvic surgery. The assessment of ultrasonography results was part of an ongoing longitudinal cohort, with initial recruitment from October 2006 to September 2012. Data analysis was performed in April to September 2022. Main Outcomes and Measures: Fibroid presence and burden as assessed by transvaginal ultrasonography. Results: A total of 996 female participants were included in the analysis, including 229 (23.0%) Asian-Chinese, 249 (25.0%) Black or African American, 237 (23.8%) Hispanic or Latina, and 281 (28.2%) White individuals. Mean (SD) age was 34.8 (5.7) years in Asian-Chinese participants, 35.4 (6.1) years in Black or African American participants, 34.8 (5.3) years in Hispanic or Latina participants, and 35.3 (5.0) years in White participants. Fibroids were present in 21.8% (95% CI, 16.7%-27.8%) of Asian-Chinese participants, 35.7% (95% CI, 29.8%-42.0%) of Black or African American participants, 12.7% (95% CI, 8.7%-17.6%) of Hispanic or Latina participants, and 10.7% (95% CI, 7.3%-14.9%) of White participants. Black or African American and Asian-Chinese participants were more likely to have fibroids than White participants (Black or African American: adjusted odds ratio [OR], 4.72 [95% CI, 2.72-8.18]; P < .001; Asian-Chinese: adjusted OR, 3.35 [95% CI, 1.95-5.76]; P < .001). In those with fibroids, the proportion with multiple fibroids were 48.3% in Black or African American participants, 33.3% in White participants, 33.3% in Hispanic or Latina participants, and 26.0% in Asian-Chinese participants (P = .06). The largest mean (SD) fibroid diameter was 3.9 (1.9) cm in Black or African American participants, 3.2 (1.6) cm in Asian-Chinese participants, 3.2 (1.6) cm in White participants, and 3.0 (1.4) cm in Hispanic or Latina participants (P = .03). Conclusions and Relevance: In this study of female participants in a nonclinical setting, Black or African American and Asian-Chinese participants were disproportionately affected by uterine fibroids. Hispanic or Latina participants had similar fibroid burden to White participants.

A deep dive into the morphokinetics and ploidy of low-quality blastocysts.

Objective: To describe morphokinetic parameters and ploidy among low-quality blastocysts not meeting the criteria for clinical use. Design: Prospective cohort study. Setting: Academic medical center. Patients: Two hundred patients undergoing in vitro fertilization between February 2018 and November 2019. Interventions: All embryos were cultured in a time-lapse incubator. All expanded blastocysts underwent preimplantation genetic testing for aneuploidy using next-generation sequencing. Main Outcome Measures: Static blastocyst morphology grading; morphokinetic parameters, including time to each cell division (2-cell formation to 8-cell formation); time to morula formation; time to the start of blastulation; time to blastocyst formation; and preimplantation genetic testing for aneuploidy results. Results: A total of 1,306 embryos progressed to the expanded blastocyst stage; of these, 935 embryos met the criteria for clinical use and were designated as high quality, whereas 371 embryos were graded as low quality and did not meet the criteria for use. In morphokinetic evaluation, low-quality embryos developed more quickly to 5-cell formation (t5) 48.4 [42.4-48.7) vs 50.2 [46.3-50.1] hours, but progressed more slowly thereafter with tM 91.5 [85.9-92.3] vs 88.3 [82.1-88.3] and tB 114.0 [106.4-113.9] vs 106.9 [101.3-107.4] hours. Among the low-quality embryos, 75.5% were aneuploid, 22.4% were euploid, and 2.2% had undetermined chromosome copy number results. Morphokinetic parameters did not differ between the euploid and aneuploid low-quality embryos. Conclusions: Morphokinetic analysis did not distinguish between euploid and aneuploid low-quality embryos.

Hormone concentrations of dominant follicles in the TALES randomized controlled trial comparing letrozole with tamoxifen.

BACKGROUND: In this secondary analysis of the TAmoxifen or Letrozole in Estrogen Sensitive tumors (TALES) trial, we aimed to investigate if concurrent administration of letrozole vs. tamoxifen vs. no added treatment affects hormonal composition and size of stimulated ovarian follicles. METHODS: TALES is a randomized controlled trial of IVF stimulation for estrogen receptor (ER)-positive breast cancer patients stimulated with gonadotropins and administered concurrent tamoxifen 20 mg or letrozole 5 mg. We analyzed estradiol (E2), testosterone (T), progesterone (P4), follicle stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH). We used ANOVA/Kruskal-Wallis, logistic, and linear regression models to examine differences in follicular hormone levels, size, and mature oocyte yield between trial arm. RESULTS: We included data from total 246 follicles (94 letrozole, 82 tamoxifen, and 70 control) from 123 unique participants. E2 was lower (letrozole 187.4, tamoxifen 1026.0, control 821.5 ng/mL, p < 0.01) and T was higher (letrozole 2489, tamoxifen 571, and control 504 ng/mL, p < 0.03) in the letrozole group compared to tamoxifen and control groups, while other hormone levels and follicle size were similar across groups. There were no significant differences in hormone concentrations within the follicle between tamoxifen and control arms. On multivariate logistic regression, there was no significant association of mature oocyte yield by follicle size, hormone levels, or trial arm. CONCLUSIONS: Concurrent administration of letrozole with gonadotropins affects follicular E2 and T concentrations compared to tamoxifen/control. Tamoxifen was not associated with any differences in hormone concentrations within the follicle. Mature oocyte yield was similar across groups.

Fertility preservation practices for female oncofertility differ significantly across the USA: results of a survey of SREI members.

PURPOSE: The field of oncofertility has maintained an important focus on improving access, yet standardized practices are lacking. To assess how female cancer patients are provided oncofertility care, we sought to determine provider-level differences and whether there are physician or practice characteristics that predict these variations. METHODS: A cross-sectional survey was sent to SREI members. The survey included fifteen questions about physician practice characteristics and oncofertility cryopreservation protocols. Topics included ovarian stimulation protocols, fertilization techniques, stage of embryo cryopreservation, routine use of pre-implantation genetic testing for aneuploidy (PGT-A), and ovarian tissue cryopreservation (OTC). Statistical analyses assessed whether practice setting, geographic region, time in practice, and mandatory state insurance coverage had effects on cryopreservation protocols. RESULTS: A total of 141 (17%) from diverse REI practice backgrounds completed the survey. The median number of new female oncofertility consults per year was 30 (range 1 to 300). Providers in academic settings treated more patients (median 40 vs. 15, p < 0.001). Providers in academic settings more often use gonadotropin-releasing hormone agonists (85% vs. 52%, p < 0.001) and perform OTC (41% vs. 4%, p < 0.001). Providers in academic practices were less likely to perform intracytoplasmic sperm injection in every cycle (37% vs. 55%, p = 0.032) and less likely to usually advise PGT-A (21% vs. 36%, p = 0.001). Mandated state insurance coverage had no effect on oncofertility practices. CONCLUSION: Oncofertility practices vary among providers. Factors such as practice setting and region may affect the services provided. We do not yet know the best practices in oncofertility patients, and future research is needed.

Triggering with 1,500 IU of human chorionic gonadotropin plus follicle-stimulating hormone compared to a standard human chorionic gonadotropin trigger dose for oocyte competence in in vitro fertilization cycles: a randomized, double-blinded, controlled noninferiority trial.

OBJECTIVE: To assess if triggering with 1,500 IU of human chorionic gonadotropin (hCG) with 450 IU of follicle-stimulating hormone (FSH) induces noninferior oocyte competence to a standard dose of hCG trigger used in in vitro fertilization (IVF). The alternative trigger will be considered noninferior if it is at least 80% effective in promoting oocyte competence. DESIGN: Randomized, double-blinded, controlled noninferiority trial. SETTING: Academic infertility practice. PATIENTS: Women aged 18-41 undergoing IVF with antral follicle count ≥8, body mass index ≤30 kg/m2, and no history of ≥2 IVF cycles canceled for poor response were enrolled. Participants with a serum estradiol >5,000 pg/mL on the day of trigger were excluded because of high risk of ovarian hyperstimulation syndrome. INTERVENTIONS: Participants were randomized to receive an alternative trigger of 1,500 IU of hCG plus 450 IU of FSH or a standard trigger dose of hCG (5,000 or 10,000 IU) for final oocyte maturation. MAIN OUTCOME MEASURES: The primary outcome was total competent proportion, defined as the probability of 2 pronuclei from an oocyte retrieved. The alternative trigger will be considered noninferior to the standard trigger if a 1-sided 95% confidence interval (CI) of the relative risk (RR) is not <0.8. Secondary outcomes included oocyte recovery and maturity, intracytoplasmic sperm injection fertilization, embryo quality, pregnancy rates, as well as serum and follicular hormones. Secondary outcomes were compared using a 2-sided superiority test. Outcomes were analyzed by intention-to-treat and per-protocol. RESULTS: A total of 105 women undergoing IVF were randomized from May 2015 to June 2018. The probability of the primary outcome was 0.59 with the alternative trigger and 0.65 with the standard trigger, with a RR of 0.91 and a 1-sided 95% CI of 0.83. Noninferiority of the alternative trigger was demonstrated. Live birthrate from all fresh transfers in the alternative trigger group vs. standard trigger was 46.9 vs. 46.4% (RR, 1.01; 95% CI, 0.62-1.62), respectively. Live birthrate per randomized participant was 48.1% in the alternative trigger group vs. 62.7% with the standard trigger (RR, 0.73; 95% CI, 0.48-1.11). No participants had a failed retrieval. CONCLUSION: Triggering with 1,500 IU of hCG plus 450 IU of FSH promoted noninferior oocyte competence compared to a standard hCG trigger dose. TRIAL REGISTRATION: NCT02310919.

Microfluidic preparation of spermatozoa for ICSI produces similar embryo quality to density-gradient centrifugation: a pragmatic, randomized controlled trial.

STUDY QUESTION: Does processing of spermatozoa for IVF with ICSI by a microfluidic sperm separation device improve embryo quality compared with density-gradient centrifugation? SUMMARY ANSWER: Patients randomized to microfluidic sperm preparation had similar cleavage- and blastocyst-stage embryo quality and clinical and ongoing pregnancy rates to those who underwent standard sperm processing for IVF with ICSI. WHAT IS KNOWN ALREADY: Microfluidic sperm preparation can isolate spermatozoa for clinical use with minimal DNA fragmentation but with unclear impact on clinical outcomes. STUDY DESIGN, SIZE, DURATION: A prospective randomized controlled trial of 386 patients planning IVF from June 2017 through September 2021 was carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS: One hundred and ninety-two patients were allocated to sperm processing with a microfluidic sperm separation device for ICSI, while 194 patients were allocated to clinical standard density-gradient centrifugation (control) at an academic medical centre. MAIN RESULTS AND THE ROLE OF CHANCE: In an intention to treat analysis, there were no differences in high-quality cleavage-stage embryo fraction [66.0 (25.8)% control versus 68.0 (30.3) microfluidic sperm preparation, P = 0.541, absolute difference -2.0, 95% CI (-8.5, 4.5)], or high-quality blastocyst fraction [37.4 (25.4) control versus 37.4 (26.2) microfluidic sperm preparation, P = 0.985, absolute difference -0.6 95% CI (-6, 5.9)] between groups. There were no differences in the clinical pregnancy or ongoing pregnancy rates between groups. LIMITATIONS, REASONS FOR CAUTION: The population studied was inclusive and did not attempt to isolate male factor infertility cases or patients with a history of elevated sperm DNA fragmentation. WIDER IMPLICATIONS OF THE FINDINGS: Microfluidic sperm separation performs similarly to density-gradient centrifugation in sperm preparation for IVF in an unselected population. STUDY FUNDING/COMPETING INTEREST(S): No external funding to declare. M.P.R. is a member of the Clinical Advisory Board for ZyMot® Fertility, Inc. TRIAL REGISTRATION NUMBER: NCT03085433. TRIAL REGISTRATION DATE: 21 March 2017. DATE OF FIRST PATIENT'S ENROLLMENT: 16 June 2017.

Breast cancer grade and stage do not affect fertility preservation outcomes.

PURPOSE: To investigate if breast cancer stage and grade affect fertility preservation outcomes. METHODS: We performed a retrospective cohort study that included premenopausal women with breast cancer undergoing fertility preservation diagnosed between January 2011 and January 2019. The primary outcome measure was the number of mature oocytes (MII) per antral follicle count (AFC). Secondary outcome measures included total oocytes retrieved, total mature oocytes retrieved, and greater than 10 mature oocytes preserved. Univariate and multivariate models were used to assess the association of low vs. high stage (low stage I-II and high stage III-IV) and grade I vs. grade II/III with each outcome, with adjustment for confounders. RESULTS: A total of 267 premenopausal breast cancer patients undergoing fertility preservation were included in our study, with the majority presenting with low stage (N = 215, 80.5%), grade II/III (N = 235, 88.1%) disease. Baseline AFC, total gonadotropin dose, days of stimulation, and follicles [Formula: see text] 13 mm on the day of trigger did not differ by stage or grade. After adjusting for age, BMI, and baseline AFC, we found that the mean MII per AFC did not differ by stage (1.0 vs. 1.1, P = 0.3) or grade (1.0 vs. 1.0, P = 0.92). Similarly, total oocytes retrieved, total MII retrieved, and percentage of patients who were able to preserve greater than 10 MII did not differ by breast cancer stage or grade (all P > 0.2). CONCLUSION: Breast cancer grade and stage do not impact ovarian stimulation or fertility preservation outcome.

Aneuploidy rates and morphokinetic parameters of embryos cultured in distinct culture media: a sibling oocyte study.

STUDY QUESTION: Do embryos from sibling oocytes assigned to distinct single-step media culture systems demonstrate differences in early embryo development, morphokinectics or aneuploidy rates? SUMMARY ANSWER: Embryo quality, morphokinetic parameters and aneuploidy rates from trophectoderm biopsy were similar between sibling embryos cultured in distinct media systems from the time of gamete isolation. WHAT IS KNOWN ALREADY: Studies on the effect of commercially available embryo culture media systems have demonstrated inconsistent impact on human embryonic development, morphokinetics, aneuploidy rates and clinical outcomes. In addition, these studies have been primarily randomized at the level of the embryo or the patient to culture media. STUDY DESIGN, SIZE, DURATION: Prospective sibling oocyte cohort derived from 200 subjects undergoing IVF at a tertiary academic medical center between February 2018 and November 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sibling oocytes were allocated to Global® or SAGE® media system based upon laterality of ovary from which they were retrieved. All embryos were cultured in a time-lapse incubator. Blastocysts underwent trophectoderm biopsy for preimplantation genetic testing for aneuploidy using next-generation sequencing. MAIN RESULTS AND THE ROLE OF CHANCE: One hundred twenty-seven subjects (n = 127) had paired blastocysts for biopsy in each culture media system. There was no difference in top quality blastocyst formation (47.1 ± 31.0 vs 48.1 ± 27.2%; P = 0.87) nor aneuploidy rate (62.3 ± 34.0 vs 56.1 ± 34.4%; P = 0.07) for sibling embryos cultured in Global versus SAGE media system. Embryo morphokinetic parameters including time to each cell division from two cells (t2) to eight cells (t8), time to morula stage (tM), time to blastocele formation (tSB), time to fully formed blastocyst (tB) and time to expansion of the blastocyst (tEB) were similar between paired blastocysts from each culture media system. LIMITATIONS, REASONS FOR CAUTION: Pregnancy outcomes and offspring health data were not available for analysis. WIDER IMPLICATIONS OF THE FINDINGS: Commercially available culture media may not have a differential impact on embryo development and blastocyst aneuploidy rate when patient and stimulation-related factors are held constant. STUDY FUNDING/COMPETING INTEREST(S): There was no external funding for this study. C.H. is owner of a consultancy company, IVF Professionals, Chief Scientific Officer at Apricity, Executive Director at TMRW and co-owner and shareholder of Aria Fertility. She has received speaker fees, consulting fees and travel support from Cooper Surgical and Vitrolife. J.B. is an employee and shareholder of vitrolife. TRIAL REGISTRATION NUMBER: N/A.

Effect of an Active vs Expectant Management Strategy on Successful Resolution of Pregnancy Among Patients With a Persisting Pregnancy of Unknown Location: The ACT or NOT Randomized Clinical Trial.

Importance: Women with an early nonviable pregnancy of unknown location are at high risk of ectopic pregnancy and its inherent morbidity and mortality. Successful and timely resolution of the gestation, while minimizing unscheduled interventions, are important priorities. Objective: To determine if active management is more effective in achieving pregnancy resolution than expectant management and whether the use of empirical methotrexate is noninferior to uterine evacuation followed by methotrexate if needed. Design, Setting, and Participants: This multicenter randomized clinical trial recruited 255 hemodynamically stable women with a diagnosed persisting pregnancy of unknown location between July 25, 2014, and June 4, 2019, in 12 medical centers in the United States (final follow up, August 19, 2019). Interventions: Eligible patients were randomized in a 1:1:1 ratio to expectant management (n = 86), active management with uterine evacuation followed by methotrexate if needed (n = 87), or active management with empirical methotrexate using a 2-dose protocol (n = 82). Main Outcomes and Measures: The primary outcome was successful resolution of the pregnancy without change from initial strategy. The primary hypothesis tested for superiority of the active groups combined vs expectant management, and a secondary hypothesis tested for noninferiority of empirical methotrexate compared with uterine evacuation with methotrexate as needed using a noninferiority margin of -12%. Results: Among 255 patients who were randomized (median age, 31 years; interquartile range, 27-36 years), 253 (99.2%) completed the trial. Ninety-nine patients (39%) declined their randomized allocation (26.7% declined expectant management, 48.3% declined uterine evacuation, and 41.5% declined empirical methotrexate) and crossed over to a different group. Compared with patients randomized to receive expectant management (n = 86), women randomized to receive active management (n = 169) were significantly more likely to experience successful pregnancy resolution without change in their initial management strategy (51.5% vs 36.0%; difference, 15.4% [95% CI, 2.8% to 28.1%]; rate ratio, 1.43 [95% CI, 1.04 to 1.96]). Among active management strategies, empirical methotrexate was noninferior to uterine evacuation followed by methotrexate if needed with regard to successful pregnancy resolution without change in management strategy (54.9% vs 48.3%; difference, 6.6% [1-sided 97.5% CI, -8.4% to ∞]). The most common adverse event was vaginal bleeding for all of the 3 management groups (44.2%-52.9%). Conclusions and Relevance: Among patients with a persisting pregnancy of unknown location, patients randomized to receive active management, compared with those randomized to receive expectant management, more frequently achieved successful pregnancy resolution without change from the initial management strategy. The substantial crossover between groups should be considered when interpreting the results. Trial Registration: ClinicalTrials.gov Identifier: NCT02152696.

A machine learning algorithm can optimize the day of trigger to improve in vitro fertilization outcomes.

OBJECTIVE: To determine whether a machine learning causal inference model can optimize trigger injection timing to maximize the yield of fertilized oocytes (2PNs) and total usable blastocysts for a given cohort of stimulated follicles. DESIGN: Descriptive and comparative study of new technology. SETTING: Tertiary academic medical center. PATIENT(S): Patients undergoing IVF with intracytoplasmic sperm injection from 2008 to 2019 (n = 7,866). INTERVENTION(S): Causal inference was performed with the use of a T-learner. Bagged decision trees were used to perform inference. The decision was framed as either triggering on that day or waiting another day. All patient characteristics and stimulation parameters on a given day were used to determine the recommendation. MAIN OUTCOME MEASURE(S): Average outcome improvement in total 2PNs and usable blastocysts compared with the physician's decision. RESULT(S): For evaluation of average outcome improvement on 2PNs, the benefit of following the model's recommendation was 3.015 (95% CI 2.626, 3.371) more 2PNs. For total usable blastocysts, the benefit was 1.515 (95% CI 1.134, 1.871) more usable blastocysts. Given that the physicians-model agreement was 52.57% and 61.89%, respectively, algorithm-assisted trigger decisions yield, on average, 1.430 more 2PNs and 0.577 more total usable blastocysts per stimulation. The most important features weighted in the model's decision were the number of follicles 16-20 mm in diameter, the number of follicles 11-15 mm in diameter, and estradiol level, in that order. CONCLUSION(S): The use of this machine learning algorithm to optimize trigger injection timing may lead to a significant increase in the number of 2PNs and total usable blastocysts obtained from an IVF stimulation cycle when compared with physician decisions. Future research is required to confirm these findings prospectively.

Concomitant tamoxifen or letrozole for optimal oocyte yield during fertility preservation for breast cancer: the TAmoxifen or Letrozole in Estrogen Sensitive tumors (TALES) randomized clinical trial.

PURPOSE: To determine whether concomitant tamoxifen 20 mg with gonadotropins (tamoxifen-gonadotropin) versus letrozole 5 mg with gonadotropins (letrozole-gonadotropin) affects mature oocyte yield. METHODS: Open-label, single-institution, randomized trial. Inclusion criteria included the following: females, ages 18-44 years old, with new diagnosis of non-metastatic breast cancer, who were undergoing fertility preservation with either oocyte or embryo cryopreservation. Those with estrogen-receptor-positive (ER+) breast cancer were randomized to tamoxifen-gonadotropin or letrozole-gonadotropin. Another group with estrogen-receptor-negative (ER-) breast cancer was recruited, as a prospectively collected comparison arm who took neither letrozole nor tamoxifen (gonadotropin only). The primary outcome was the number of mature oocytes obtained from the cycle. The randomized groups were powered to detect a difference of three or more mature oocytes. RESULTS: Forty-five patients were randomized to tamoxifen-gonadotropin and fifty-one to letrozole-gonadotropin. Thirty-eight patients completed gonadotropin only. Age, antral follicle count, and body mass index were similar between the randomized groups. Our primary outcome of mature oocyte yield was similar between the tamoxifen-gonadotropin and letrozole-gonadotropin groups (12±8.6 vs. 11.6±7.5, p=0.81, 95%CI of difference =-2.9 to 3.7). In a pre-specified secondary comparison, mature oocyte yield was also similar with tamoxifen-gonadotropin or letrozole-gonadotropin versus gonadotropin only (12±8.6 vs. 11.6±7.5 vs. 12.4±7.2). There were no serious adverse events in any of the groups. CONCLUSIONS: Tamoxifen-gonadotropin and letrozole-gonadotropin produced a similar number of mature oocytes. Women who received either tamoxifen-gonadotropin or letrozole-gonadotropin had a similar number of oocytes to the gonadotropin-only group. TRIAL REGISTRATION: NCT03011684 (retrospectively registered 1/5/2017, after 9% enrolled).

Regional air transportation of ovarian tissue for cryopreservation in a prepubertal female with cancer.

Ovarian tissue cryopreservation is the only fertility preservation (FP) option available to prepubescent females receiving gonadotoxic therapy, but it has limited availability. A 6-year-old female was diagnosed with high-risk rhabdomyosarcoma, and the planned treatment carried an 80% risk of ovarian failure. Her parents desired FP, but the nearest center was 500 miles away. The patient underwent oophorectomy at the cancer center with air transport of the tissue to the oncofertility center, where it was successfully cryopreserved. Formation of networks between full-service and limited oncofertility centers in a hub-and-spoke model would increase access to FP services, particularly in children.

Changing stimulation protocol on repeat conventional ovarian stimulation cycles does not lead to improved laboratory outcomes.

OBJECTIVE: To evaluate whether physicians' choice of ovarian stimulation protocol is associated with laboratory outcomes. DESIGN: Retrospective cohort study. SETTING: Single academic center. PATIENT(S): The subjects were 4,458 patients who completed more than one in vitro fertilization ovarian stimulation cycle within 1 year. On second stimulation, 49% repeated the same protocol and 51% underwent a different one. INTERVENTION(S): Estradiol priming antagonist, antagonist +/- oral contraceptive pill priming, long luteal protocol, Lupron (Lupron [AbbVie Inc, North Chicago, IL]) stop protocol, and flare were compared. Logistic or linear regression with cluster robust standard errors to account for covariates and paired data was used. MAIN OUTCOME MEASURE(S): Oocytes collected (OC), fertilization rate, blastocyst progression (BP), usable embryos (UE), and euploid rate (ER). RESULT(S): First stimulation outcomes were comparable across all protocols for FR, BP, UE, and ER but were different for OC, after adjustment for covariates. For OC, the effect of switching protocols differed according to the type of the second stimulation. There was improvement in OC if the same stimulation was repeated, except for flare. In addition, there were slight, significant improvements in fertilization rate (difference in values or coefficient of 0.02; 95% confidence interval [CI], 0.004, 0.4) and UE (coefficient 1.25; 95% CI, 0.79, 1.72) when the same stimulation was repeated. There were no changes in BP (coefficient 0.03; 95% CI, -0.01, 0.08) or ER (coefficient 0.01; 95% CI, -0.04, 0.06) when protocols were changed. In a low-BP subgroup, greater improvement was seen when the same protocol was repeated (coefficient 0.03; 95% CI 0.01, 0.04). CONCLUSION(S): There was a slight but significant improvement in laboratory outcomes when the same stimulation protocol was repeated, so careful consideration should be made before switching stimulation protocols for the purpose of improving laboratory outcomes.

Conception after chemotherapy: post-chemotherapy method of conception and pregnancy outcomes in breast cancer patients.

PURPOSE: As the paradigm shifts towards improving cancer survivorship, an important concern for reproductive-aged women diagnosed with cancer is how their disease and its treatment will affect their future fertility. We sought to characterize pregnancy attempts and outcomes in breast cancer patients following chemotherapy. METHODS: We conducted a prospective cohort study of women diagnosed with breast cancer seen between 2010 and 2019. A questionnaire was administered following cancer treatment with questions regarding oncologic and reproductive history and attempts and method of conception. RESULTS: Of 181 participants, 46 (25.4%) attempted to conceive following chemotherapy. Thirty-five patients (76.1%) had return of ovarian function. Of those, 34 patients (mean age 32.8 years) first attempted to conceive by intercourse, and 22 (64.7%) became pregnant, resulting in 17 live births. Of the remaining 12 who did not successfully conceive through intercourse, eight went on to try other methods, resulting in five additional pregnancies and one live birth. Twelve patients (mean age 34.6 years) proceeded directly to ART; of those, eight (66.7%) became pregnant, resulting in six live births. CONCLUSION: In breast cancer patients with return of ovarian function after chemotherapy, half were able to conceive by intercourse alone. In order to maximize reproductive potential in patients who have return of ovarian function, providers should offer natural conception as a reasonable option prior to the use of cryopreserved tissue. For those who did not attempt to conceive on their own, the use of pre-treatment cryopreserved eggs or embryos had a high likelihood of success.

Diminished ovarian reserve is associated with reduced euploid rates via preimplantation genetic testing for aneuploidy independently from age: evidence for concomitant reduction in oocyte quality with quantity.

OBJECTIVE(S): To determine whether women with diminished ovarian reserve (DOR) (quantitatively) had lower rates of euploid blastocysts, as a proxy for oocyte quality. DESIGN: Retrospective cohort study. SETTING: University reproductive health clinic. PATIENT(S): A total of 1,152 women aged 19-42 years underwent 1,675 IVF cycles yielding 8,073 blastocysts for biopsy from 2010 to 2019. INTERVENTIONS(S): Preimplantation genetic testing for aneuploidy. MAIN OUTCOME MEASURE(S): Euploid rates, defined as the number of euploid blastocysts divided by the number of biopsied blastocysts per cycle. RESULT(S): A total of 225 women (20%) had DOR as infertility diagnosis per the Bologna criteria. Age was higher among the women with DOR (39.5 y vs. 37.0 y). Euploid rates were lower among women with vs. without DOR (29.0% vs. 44.9%). In generalized linear models controlling for age, women with DOR had 24% reduced odds of a biopsied blastocyst being euploid versus women without DOR. In a secondary analysis assigning DOR status to women producing the lowest quartile of age-adjusted mature oocyte yield, this relationship remained. No differences were identified in live birth rates between women with and without DOR after euploid single-embryo transfer independently from age (n = 944 transfers; 56.8% vs. 54.8%, respectively). CONCLUSION(S): Blastocysts from women with DOR are less likely to be euploid than those from women without DOR after adjustment for age. Given the concomitant reduction in euploid rates with quantity of oocytes observed in this study, quantitative ovarian reserve assessments (i.e., follicular machinery) may yield insight into relative ovarian aging.

Perceptions, motivations and decision regret surrounding preimplantation genetic testing for aneuploidy.

STUDY QUESTION: Is there a difference in level of decision regret following IVF treatment between those who choose to complete or not complete preimplantation genetic testing for aneuploidy [PGT-A]? SUMMARY ANSWER: Approximately one-third of the participants expressed moderate to severe regret (MSR) following their decision to either complete or not complete PGT-A; notably, decision regret was higher in those who chose not to complete PGT-A, primarily driven by significantly higher regret scores in those that experienced a miscarriage after not testing. WHAT IS KNOWN ALREADY: Previous research has found that 39% of participants who completed PGT-A expressed some degree of decision regret and that negative clinical outcomes, such as lack of euploid embryos, negative pregnancy test or miscarriage, were associated with a higher level of decision regret. To date, there are no published studies assessing the possible disparity in decision regret surrounding PGT-A in a population of IVF patients that either chose to pursue PGT-A or not. STUDY DESIGN, SIZE, DURATION: An anonymous online survey was distributed to 1583 patients who underwent IVF with or without PGT-A at a single university institution between January 2016 and December 2017. In total, 335 women accessed the survey, 220 met eligibility criteria and 130 completed the full study survey. Six participants were excluded due to refusal of medical record review, and nine participants were excluded after record review due to not meeting eligibility based on cycle start date or completing only embryo banking without attempting transfer. One hundred and fifteen participants were included in the final analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of the 115 participants included, 55 (48%) completed PGT-A and 60 (52%) did not complete PGT-A. The online survey included four sections: Demographics; Perceptions about PGT-A risks and benefits [scale from 0 (absolutely not true) to 100 (absolutely true)]; Decision-making factors [scale from 0 (not important) to 100 (very important)]; and Brehaut Decision Regret Scale [DRS] [range 0-100, with >25 indicating MSR]. A retrospective chart review was conducted to confirm study eligibility and collect cumulative clinical outcomes of consenting participants who completed the survey. MAIN RESULTS AND THE ROLE OF CHANCE: Demographics of the PGT-A and no PGT-A cohorts were similar, with the majority of respondents being Caucasian or Asian, unaffiliated with any religion and with a graduate or professional degree. The two groups differed significantly in mean age, with the PGT-A group being slightly older (mean ± SD: 37 ± 3.7 versus 36 ± 3.4; P = 0.048), and in rate of miscarriages, with fewer participants in the PGT-A cohort experiencing a miscarriage (5% versus 22%; P = 0.012). The majority of participants in both PGT-A and no PGT-A cohorts strongly believed in the purported benefits of PGT-A, including that it decreases the risk of birth defects (median 82 versus 77; P = 0.046), improves the chances of having a healthy baby (median 89 versus 74; P = 0.002) and selects the best embryo for transfer (median 85 versus 80; P = 0.049). When asked to report their motivating factors for decision-making, both groups cited physician counseling as important (median 70 versus 71; P = 0.671); however, the PGT-A cohort was more strongly motivated by a desire to not transfer abnormal embryos (median 84 versus 53; P = 0.0001). Comparison of DRS score between those who did or did not undergo PGT-A showed significantly higher median DRS score after not completing PGT-A (median 15 versus 0; P = 0.013). There was a significantly higher proportion of participants who did not complete PGT-A that expressed mild (36% versus 16%) and MSR (32% versus 24%) compared to those who completed PGT-A (χ2 = 9.03, df = 2; P = 0.011). Sub-group analyses of DRS scores by outcomes of clinical pregnancy, miscarriage and live birth revealed that the higher DRS score in those not completing PGT-A was driven by a large increase in regret noted by those with history of a miscarriage (median 45 versus 0; P = 0.018). Multivariate logistic regression modeling found no evidence that any specific demographic factor, clinical outcome or perception/motivation surrounding PGT-A was independently predictive of increased risk for MSR. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of data collection incurs the possibility of sampling and recall bias. As only 59% of eligible respondents completed the full survey, it is possible that mainly those with very positive or negative sentiments following treatment felt compelled to complete their response. This bias, however, would apply to the whole of the population, and not simply to those who did or did not complete PGT-A. WIDER IMPLICATIONS OF THE FINDINGS: The proportion of participants expressing any degree of decision regret in this PGT-A cohort was 40%, which is comparable to that shown in prior research. This study adds to prior data by also assessing decision regret experienced by those who went through IVF without PGT-A, and showed that 68% expressed some level of regret with their decision-making. These results should not be interpreted to mean that all patients should opt for PGT-A to pre-emptively mitigate their risk of regret. Instead, it suggests that drivers of decision regret are likely multifactorial and unique to the experience of one's personal expectations regarding PGT-A, motivations for pursuing or not pursuing it and resultant clinical outcome. Highlighting the complex nature of regret, these data should encourage physicians to more carefully consider individual patient values toward risk-taking or risk-averse behavior, as well as their own positions regarding PGT-A. Until there are clear recommendations regarding utilization of PGT-A, a strong collaboration between physicians and genetic counselors is recommended to educate patients on the risks and potential benefits of PGT-A in a balanced and individualized manner. STUDY FUNDING/COMPETING INTEREST(S): No funding was utilized for study completion and the authors have no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Fertility preservation before breast cancer treatment appears unlikely to affect disease-free survival at a median follow-up of 43 months after fertility-preservation consultation.

BACKGROUND: The objective of this study was to determine whether fertility preservation (FP) with oocyte/embryo cryopreservation is associated with differences in disease-free survival (DFS). METHODS: This retrospective study included patients aged 18 to 45 who were diagnosed with invasive breast cancer between 2007 and 2017 and were seen for FP consultation at a university fertility center before cancer treatment. The primary endpoint, DFS, was defined as the time from FP consultation until patients developed a locoregional recurrence, distant metastasis, a contralateral breast tumor, or a new primary malignancy. DFS was compared for FP versus no FP using Kaplan-Meier survival estimates and Cox proportional-hazard regression analysis. RESULTS: The study included 329 women, with 207 (63%) in the FP group and 122 (37%) in the no FP group. Patients who underwent FP had more aggressive initial disease profiles than those in the no FP group. In addition, they were younger (35 vs 37 years; P = .009), more often had stage II or III disease (67% vs 55%; P = .03), and had higher rates of requiring chemotherapy (77% vs 65%; P = .01). Over a median follow-up of 43 months, the rates of DFS were similar among patients in the FP group and the no FP group (93% vs 94%, respectively; hazard ratio [HR] 0.7; 95% CI, 0.3-1.7). Positive ER status (79% vs 83%; P = .38), neoadjuvant chemotherapy (41% vs 48%; P = .32), ER-positive DFS (HR, 0.4; 95% CI, 0.1-1.6), and neoadjuvant chemotherapy DFS (HR, 1.4; 95% CI, 0.2-9.1) were similar in the FP and no FP groups, respectively. CONCLUSIONS: At a median follow-up of 43 months, FP appears unlikely to affect DFS, even in the setting of tumors with positive ER status or treatment with neoadjuvant chemotherapy (in which the tumor remains in situ during FP).

Attitudes toward fertility and fertility preservation in women with glioma.

BACKGROUND: No studies have examined the fertility priorities of women undergoing treatment for their glioma. Glioma patients frequently undergo chemotherapy as part of their treatment; however, it is unknown whether patients truly are aware of its possible effects on their fertility. Our objective was to assess the fertility priorities of glioma patients and ascertain whether female glioma patients are being effectively counseled on the effects of chemotherapy on their fertility prior to beginning treatment. METHODS: The sample was composed of female patients from the Neuro-oncology clinic of the University of California, San Francisco. Participants completed a cross-sectional survey between October 2010 and December 2013 exploring their attitudes toward fertility and their experience with fertility counseling prior to chemotherapy initiation. RESULTS: Seventy-two women completed the survey. Analysis of the survey results showed that 30% of women receiving chemotherapy reported having a discussion regarding fertility preservation prior to beginning treatment. Of those who reported having this discussion, 80% were aware that chemotherapy could negatively affect their fertility. Many women reported that while fertility preservation was not important to them at the time of diagnosis, it was a priority for them at the time of survey completion. Although interest in having children tended to decrease after cancer treatment, the majority of respondents reported wanting a child after treatment. CONCLUSIONS: The data obtained in this study suggest a lack of understanding of reproductive priorities, which may be addressed with a more comprehensive fertility discussion prior to beginning treatment.