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.

Decision regret, and other mental health outcomes, following fertility preservation in the transgender individual compared to the cisgender woman.

PURPOSE: This study aimed to (1) determine differences in depression, anxiety, body image, quality-of-life (QOL), and decision regret scale (DRS) scores in transgender individuals undergoing fertility preservation (FP) compared to those who decline and (2) determine if DRS score following FP varies between transgender individuals and cisgender women. METHODS: Sixteen transgender birth-assigned (BA) females and 13 BA males, undergoing FP consultation at an academic center between January 2016 and November 2019, were compared to each other and cisgender cohorts with pre-existing data: 201 women undergoing elective oocyte cryopreservation (EOC) between 2012 and 2016 and 44 women with cancer undergoing FP between 1993 and 2007. Outcomes included demographics; validated scales for depression, anxiety, body image, QOL (see below) in the trans cohort; DRS score in all three cohorts. RESULTS: Of 29 transgender individuals participating, 10 BA females (62%) and 12 BA males (92%) underwent FP. Beck Depression Inventory II, Hospital Anxiety and Depression Scale, Body Image Scale for Transsexuals, Satisfaction with Life Scale, Short Form Health Survey-36, and DRS scores were not significantly different between trans individuals who underwent FP and those who declined. On univariate modeling, regret was significantly lower in transpeople undergoing FP compared to those who did not (OR 0.118, p = 0.03). BA female and BA male transpatients undergoing FP reported DRS median scores 5 (mean 9) and 7.5 (mean 15), respectively, both were not significantly different from cisgender women (p = 0.97, p = 0.25) nor from each other (p = 0.43). CONCLUSIONS: Depression, anxiety, body image, and QOL, in a group of individuals presenting for FP consultation, appear similar between transpeople undergoing FP and not, while regret is significantly lower in those choosing FP. FP is an option for transgender individuals without significant differences in regret compared to cisgender women.

Lower female partner live birth rate in male cancer survivors: An age-matched cohort analysis of the Utah Population Database.

We determine the time to first live birth for female partners of males after a cancer diagnosis. Our group performed a retrospective, population-based, age-matched cohort study of Utah male residents diagnosed with cancer at age 18 years or later between 1956 and 2013 (exposed) matched to male Utah residents without cancer diagnosis (unexposed). Using stratified Cox proportional hazard models, we adjusted for race, ethnicity and number of live births prior to cancer diagnosis, to estimate the effect of time to a partner live birth following cancer diagnosis. Our study cohort included 19,303 men diagnosed with cancer (exposed) and 93,608 age-matched men without cancer diagnoses (unexposed). Exposed men were less likely to have a live birth prior to first cancer diagnosis (60.7% vs. 65.4%, p < 0.001) and after first cancer diagnosis (10.9% vs. 12.2%, p < 0.001) compared to unexposed men. Exposed men had a fertility hazard rate that was 31% lower after cancer diagnosis date than unexposed men (HR: 0.69; 95% CI: 0.65-0.72). This was most profound for men aged 18-30 years (HR: 0.59, 95% CI: 0.55-0.63). Male cancer survivors have a 31% lower female partner live birth rate after cancer diagnosis. These findings are important for patient counselling regarding fertility preservation at the time of cancer diagnosis.

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.

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.

Association of multifetal gestation with obstetric and neonatal outcomes in gestational carrier pregnancies.

OBJECTIVE: Multifetal gestation is more frequent among gestational carrier pregnancies than non-surrogacy IVF pregnancies. We aimed to evaluate the association between multifetal gestation and obstetric and neonatal morbidity among gestational carrier pregnancies. METHODS: Pooled cross-sectional study of birth certificate data from gestational carrier pregnancies in Utah from 2009 to 2018. Our primary outcome was a composite of severe obstetric morbidity; secondary outcomes included cesarean delivery (CD), hypertensive disorders of pregnancy, preterm birth (PTB), and a neonatal morbidity composite. Logistic regression was utilized to compare odds of these outcomes between gestational carrier pregnancies with and without multifetal gestation. RESULTS: A total of 361 gestational carrier pregnancies resulted in the delivery of 435 neonates during the study period. Of these, 284 were singleton pregnancies, and 77 were multifetal, a multifetal gestation rate of 21.3%. Baseline demographic characteristics did not differ between singleton and multifetal gestations. Multifetal gestation was not associated with higher rates of severe obstetric morbidity (odds ratio [OR] 1.87, 95% confidence interval [CI] 0.34-10.39). Multifetal gestation was associated with increased odds of neonatal morbidity (OR 9.49, 95% CI 5.35-15.83); PTB < 37, 34, and 32 weeks (OR 21.88, 95% CI 11.64-41.12; OR 11.67, 95% CI 5.25-25.91; OR 8.79, 95% CI 3.41-22.68); and CD (OR 4.82, 95% CI 2.81-8.27). CONCLUSION: Severe obstetric morbidity did not differ between singleton and multifetal gestations among gestational carrier pregnancies. However, multifetal gestation was associated with increased odds of neonatal morbidity, CD, and PTB. This information may be useful when counseling prospective gestational carriers and intended parents.

Obstetric morbidity in gestational carrier pregnancies: a population-based study.

PURPOSE: We sought to characterize severe obstetric morbidity among women who are gestational carriers compared to other patients. METHODS: This was a population-based study comparing gestational carrier pregnancies to non-surrogate pregnancies (non-surrogate IVF pregnancies, all non-gestational carrier pregnancies, and a cohort of matched controls) delivering in Utah between 2009 and 2018, using birth certificate data. Our primary outcome was a composite of severe morbidity, including death, ICU admission, eclampsia, HELLP syndrome, transfusion, and unplanned hysterectomy. Our secondary outcomes were cesarean delivery (CD) and hypertensive disorders of pregnancy. RESULTS: During the study period, 361 gestational carrier pregnancies and 509,015 other pregnancies resulted in live births. Severe morbidity was less common among gestational carrier pregnancies than IVF pregnancies (1.7% versus 5.5%, odds ratio [OR] 0.29, 95% confidence interval [CI] 0.12-0.70), but was not different when compared to all other pregnancies (1.0%, OR 1.61, 95% CI 0.72-3.60), or a cohort of matched controls (1.0%, OR 1.37, 95% CI 0.55-3.40). CD was less common among gestational carrier pregnancies than IVF pregnancies, but not different than all other pregnancies or matched controls. While frequency of hypertensive disorders of pregnancy was lower among gestational carrier pregnancies than IVF pregnancies, it was higher than all other women who delivered and comparable to matched controls. CONCLUSION: Severe obstetric morbidity is uncommon among gestational carrier pregnancies. Women who are gestational carriers are at lower risk of morbidity and CD than others who conceive through IVF and do not appear to be at increased risk compared to matched controls.

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.

Autologous platelet-rich plasma treatment for moderate-severe Asherman syndrome: the first experience.

PURPOSE: Treatment of Asherman syndrome (AS) presents a significant clinical challenge. Based on our in vitro data showing that PRP could activate endometrial cell proliferation and migration, we hypothesized that intrauterine infusion of autologous platelet-rich plasma (PRP) may improve endometrial regeneration and fertility outcomes in patients with moderate-severe AS. MATERIALS AND METHODS: Subjects with moderate-severe AS were randomized to PRP or saline control administered following hysteroscopic adhesiolysis. Due to relative inability to randomize patients to the control group, after initial randomization of 10 subjects (6 in PRP and 4 in control groups), the remainder were prospectively enrolled in PRP group (n = 9), with 11 historic controls added to control group, for a total of 30 subjects (PRP n = 15; saline control n = 15). Right after hysteroscopy, 0.5-1 mL of PRP or saline was infused into the uterus via a Wallace catheter, followed by estrogen therapy. The primary outcomes were changes in endometrial thickness (EMT, checked in 3 weeks) and in menstrual flow; secondary outcomes were pregnancy and live birth rates. EMT and menstrual bleeding pattern were assessed before and after the intervention. Pregnancy was assessed over a 6-month period. RESULTS: There were no statistically significant differences in age, gravidity/parity, cause of AS, preoperative menses assessment, AS hysteroscopy score, and intrauterine balloon placement between the groups. There was no statistically significant difference (p = 0.79) in EMT pre-PRP infusion for control (5.7 mm, 4.0-6.0) and study arm (5.3 mm, 4.9-6.0). There was no statistically significant change (p = 0.78) in EMT after PRP infusion (1.4 mm, - 0.5-2.4) vs saline (1.0 mm, 0.0-2.5). Patients tolerated the procedure well, with no adverse effects. There was no difference in the predicted likelihood of pregnancy (p = 0.45) between the control (0.67, 0.41-0.85) and study arm (0.53, 0.29-0.76). CONCLUSIONS: PRP was well accepted and tolerated in AS patients. However, we did not observe any significant EMT increase or improved pregnancy rates after adding PRP infusion, compared to standard treatment only. The use of intrauterine PRP infusion may be a feasible option, and its potential use must be tested on a larger sample size of AS patients.

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).

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).

Current Approaches to Fertility Preservation.

The 5 principal reasons a patient may consider fertility preservation are: treatment for cancer that may affect fertility, treatment for nonmalignant medical conditions that may affect fertility, planned indications, planned gender-affirming hormone therapy or surgery, or in the setting of genetic conditions that may increase the risks of premature ovarian insufficiency or early menopause. This paper will focus on describing who may consider preserving their fertility, how to provide the best clinical evaluation of those seeking fertility preservation, and current and future fertility preservation techniques. Last, we will highlight a need to continue to expand access to fertility preservation technologies.

Back-to-back random-start ovarian stimulation prior to chemotherapy to maximize oocyte yield.

PURPOSE: To evaluate the feasibility of utilizing back-to-back random-start ovarian stimulation to increase oocyte yield for fertility preservation prior to cancer treatment. METHODS: A case series of 15 patients who underwent back-to-back random-start stimulation cycles prior to chemotherapy. RESULTS: Of the 15 back-to-back random-start stimulation cases, 13 had breast cancer and 2 had other cancers. The average age was 38 years (range 30-43) and average AFC was 8 (range 3-14). Fourteen of the 15 women (93%) who underwent two ovarian stimulation cycles completed both of them. The average time to complete back-to-back random-start ovarian stimulation was 33 days (range 13-43 days). The average time between the first cycle completion and the second cycle start in our back-to-back random-start stimulations was 9 days (range 0-14 days). Two of the women underwent back-to-back random-start ovarian stimulation prior to starting neoadjuvant chemotherapy for breast cancer. Eleven of our 15 women at least doubled their oocyte or embryo yield relative to their first cycle. Only 1 of the 15 second cycles was canceled. The mature oocyte rate, fertilization rate, and embryo yield were similar among the first and second cycles. CONCLUSIONS: Back-to-back random-start ovarian stimulation may be an effective way to maximize fertility preservation, even in time-limited settings.

Author Correction: A novel oocyte maturation trigger using 1500 IU of human chorionic gonadotropin plus 450 IU of follicle-stimulating hormone may decrease ovarian hyperstimulation syndrome across all in vitro fertilization stimulation protocols.

The original version of this article unfortunately contained a mistake. The middle initial of Douglas A. Mata was omitted. The original article has been corrected.

A novel oocyte maturation trigger using 1500 IU of human chorionic gonadotropin plus 450 IU of follicle-stimulating hormone may decrease ovarian hyperstimulation syndrome across all in vitro fertilization stimulation protocols.

PURPOSE: Modification of the trigger used to induce final oocyte maturation in in vitro fertilization (IVF) is a major strategy used to reduce the risk of ovarian hyperstimulation syndrome (OHSS). A novel trigger composed of 1500 IU of human chorionic gonadotropin (hCG) plus 450 IU of follicle-stimulating hormone (FSH) has been developed to reduce OHSS risk. This study compares outcomes of the novel trigger to conventional triggers used in high-risk OHSS patients undergoing IVF. METHODS: In this retrospective cohort study, IVF cycles at high risk for OHSS based on a serum estradiol > 5000 pg/ml on trigger day conducted between January 2008 and February 2016 were evaluated. Oocyte maturation was induced with the novel trigger (1500 IU hCG plus 450 IU FSH) or a conventional trigger [3300 IU hCG, gonadotropin-releasing hormone agonist (GnRHa) alone, or GnRHa plus 1500 IU hCG]. IVF cycle outcomes were compared. Trigger strategies were examined for associations with OHSS development using logistic regression. RESULTS: Among 298 eligible IVF cycles identified, there were no differences in oocyte maturation, fertilization, embryo quality, or pregnancy outcomes among all triggers. After adjusting for serum estradiol level and number of follicles, the novel trigger was associated with lower odds of OHSS symptom development compared to the 3300 IU hCG and GnRHa plus hCG 1500 IU triggers (p = 0.007 and 0.04, respectively). CONCLUSIONS: This study suggests that 1500 IU hCG plus 450 IU FSH may be associated with decreased OHSS symptoms compared to conventional triggers, while producing similar IVF and pregnancy outcomes. More important, this novel trigger may provide a superior alternative in down-regulated cycles and in patients with hypothalamic dysfunction where GnRHa triggers cannot be utilized.

Fertility preservation with ovarian stimulation and time to treatment in women with stage II-III breast cancer receiving neoadjuvant therapy.

PURPOSE: To determine whether fertility preservation with ovarian stimulation (OS) results in treatment delay in breast cancer (BC) patients receiving neoadjuvant therapy (NAT). METHODS: This is a retrospective study of women screened for the prospective neoadjuvant ISPY2 trial at the University of California San Francisco. All patients were <43, had stage II-III BC, and received neoadjuvant therapy. Time to initiation of NAT was compared between women who underwent OS (STIM) and women who did not (control). Patient and tumor characteristics, as well as oncologic outcomes, were compared between STIM and control groups. RESULTS: 82 patients were included (34 STIM and 48 control). STIM patients were overall younger (mean = 35 vs. 36.9 years old, p = 0.06), and more likely to be childless (79.4 vs 31.2%, p < 0.0001) than controls. Mean time from diagnosis to initiation of NAT was 40 days, with no significant difference between STIM and control groups (mean 39.8 days vs 40.9 days, p = 0.75). Mean time from diagnosis to fertility consultation was 16.3 days. With median follow-up of 79 months, 16 (19.5%) patients have recurred or died from BC. Rates of pCR, recurrence, and death were similar in both groups. Six of 34 STIM patients have undergone embryo transfer, resulting in one patient with two live births. CONCLUSION: Fertility preservation with OS can be performed in the neoadjuvant setting without delay in initiation of systemic therapy and should be discussed with all early-stage BC patients of reproductive age.

Response to ovarian stimulation is not impacted by a breast cancer diagnosis.

STUDY QUESTION: Does a breast cancer diagnosis impact ovarian function in the setting of fertility preservation? SUMMARY ANSWER: Ovarian reserve and ovarian stimulation outcomes are similar in patients with a new diagnosis of breast cancer and patients undergoing elective fertility preservation. WHAT IS KNOWN ALREADY: Prior studies, with small study populations, lack of controlling for individual differences in ovarian reserve and infertile controls, have reported conflicting outcomes for cancer patients undergoing ovarian stimulation for fertility preservation. STUDY DESIGN, SIZE, DURATION: This retrospective cohort analysis included 589 patients undergoing ovarian stimulation for fertility preservation between 2009 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with a recent breast cancer diagnosis (n = 191) and women desiring elective fertility preservation (n = 398) underwent ovarian stimulation with an antagonist protocol at an academic medical center. The aromatase inhibitor letrozole was administered to breast cancer patients with estrogen-sensitive disease. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline antral follicle count (AFC) was not different between the breast cancer patients and controls (15.4 ± 10.4 [mean ± SD] vs 15.4 ± 10.0, P = NS), even after categorization by age. Total (19.4 ± 0.9 [mean ± SEM] vs 17.0 ± 0.5, P = NS) and mature (MII) oocytes retrieved (13.7 ± 0.7 vs 13.2 ± 0.4, P = NS), adjusted for age, BMI and total gonadotropin dose, were also similar between the two groups. Letrozole use was associated with a decreased maturity rate (MII/total oocytes retrieved) compared to elective cryopreservation (0.71 ± 0.01 vs 0.77 ± 0.01, P < 0.001), although the mature oocyte yield [MII/AFC] was comparable (1.01 ± 0.06 vs 0.93 ± 0.03, P = NS). LIMITATIONS, REASONS FOR CAUTION: The single center design may impact generalizability. Additionally, the lack of subsequent embryo and pregnancy data is an inherent weakness. WIDER IMPLICATIONS OF THE FINDINGS: In females, a breast cancer diagnosis does not impact gonadal function as measured by AFC or ovarian stimulation outcomes. Breast cancer patients should be counseled that their response to ovarian stimulation for fertility preservation is similar to that of patients undergoing elective oocyte cryopreservation. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Random start ovarian stimulation for fertility preservation appears unlikely to delay initiation of neoadjuvant chemotherapy for breast cancer.

STUDY QUESTION: Is random start ovarian stimulation associated with delays in initiation of neoadjuvant chemotherapy for breast cancer? SUMMARY ANSWER: Among women who complete fertility preservation (FP) consultation, random start ovarian stimulation is unlikely to delay time to initiation of neoadjuvant chemotherapy start. WHAT IS KNOWN ALREADY: Neoadjuvant chemotherapy is now a widely accepted treatment modality for operable breast cancer and random start ovarian stimulation is an increasingly-utilized modality for FP. While conventional ovarian stimulation does not appear to delay starting adjuvant chemotherapy, the relationship between random start ovarian stimulation and neoadjuvant chemotherapy start is not well-understood. STUDY DESIGN, SIZE, DURATION: Cross-sectional study of all women seen between from January 2011 to April 2017 for FP consultation prior to starting neoadjuvant chemotherapy for breast cancer. PARTICIPANTS/MATERIALS, SETTING, METHODS: A chart-review was performed. Study inclusion criteria were female sex; age 18-45; non-metastatic breast cancer diagnosis; underwent FP consultation; underwent neoadjuvant chemotherapy. Referrals for FP evaluation came from a regional referral base of oncology clinics. Various time-points related to cancer diagnosis, FP or chemotherapy were obtained from medical record review. We compared time-points between those who underwent ovarian stimulation for FP versus those who did not using T-tests and linear modeling. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 89 women who had FP consultation prior to neoadjuvant chemotherapy were identified. Sixty-seven percent underwent ovarian stimulation prior to cancer treatment and 33% did not. Women who underwent ovarian stimulation were similar in parity and clinical cancer stage to those who did not. Overall, the average time from cancer diagnosis to chemotherapy start was similar between the group that did undergo ovarian stimulation and those who did not (38.1 ± 11.3 versus 39.4 ± 18.5 days, P = 0.672). Those that underwent ovarian stimulation were referred 9.4 ± 6.8 days after diagnosis versus 17.9 ± 15.3 days for those who did not undergo ovarian stimulation (P < 0.001). LIMITATIONS REASONS FOR CAUTION: Retrospective study with potential for selection bias among those who underwent ovarian stimulation versus those who did not. Reasons for caution include the possibility of unmeasured differences among those who did and did not undergo ovarian stimulation, including: patients' and providers' perceptions of the urgency to start chemotherapy, ongoing oncology work-up and treatment planning, FP decision-making, and the pursuit of second and third opinions. The difference in time from referral to FP consultation may have also influenced patients' decisions about whether to undergo ovarian stimulation. WIDER IMPLICATIONS OF THE FINDINGS: In this study, FP with random start ovarian stimulation was not associated with a delay cancer treatment in the neoadjuvant setting, so long as there was a prompt FP referral. Patients undergoing neoadjuvant chemotherapy should be informed of these findings to avoid unnecessary anxiety due to concern for delays. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by departmental research funding within the University of California, San Francisco Department of Obstetrics, Gynecology and Reproductive Sciences. There are no conflicts of interest to declare.

Long-term hormonal contraceptive use is associated with a reversible suppression of antral follicle count and a break from hormonal contraception may improve oocyte yield.

PURPOSE: Unlike infertility, patients presenting for fertility preservation (FP) are often using combined hormonal contraceptives (CHC). We studied whether long-term (≥6 months) CHC use is associated with reversible suppression of antral follicle count (AFC). METHODS: This is a longitudinal study of FP cycles from 2012 to 2016. We studied three groups: those without CHC exposure (NO CHC), those with CHC usage with a CHC break (BREAK), and without a break (NO BREAK) prior to ovarian stimulation. We assessed ovarian reserve by AFC at initial consultation and discussed the possibility of CHC suppression of AFC. Patients chose between ovarian stimulation with no CHC break versus ovarian stimulation after a CHC break. AFC was measured serially in the BREAK group. We assessed whether AFC suppression was reversed in the BREAK group. Total oocyte yield was compared among the NO CHC, BREAK, and NO BREAK groups. T tests, ANOVA, and linear/logistic regressions were used. RESULTS: Seven hundred forty-three women underwent FP. Twenty-one percent (n = 154) were taking long-term CHC (≥6 months). AFC suppression was more likely with CHC use (OR 1.6, 95% CI 1.1-2.4, P = 0.011). The BREAK group (n = 79) stopped CHC for an average of 4 months. AFC improvement started at 1 month and plateaued at approximately 6- to 7-month break. The BREAK group had approximately twice as many oocytes per initial AFC as NO BREAK (2.8 ± 3.8 vs. 1.4 ± 0.9, P < 0.001). CONCLUSIONS: When women present for FP on CHC, AFC may be suppressed. A CHC break of several months is associated with an increase in AFC and a potential improvement in overall egg yield.