Ovarian Stimulation For Fertility Preservation Research Articles

P-409 Oocyte cryopreservation following ovarian stimulation for fertility preservation in transgender men: a French case series

Abstract Study question To evaluate the feasibility and results of a fertility preservation program for transgender men. Summary answer Ovarian stimulation outcomes are similar between transgender men and oocyte donation candidates, leading to a satisfactory mean number of cryopreserved oocytes. What is known already The reproductive potential of transgender people may be impaired by gender-affirming hormone treatment (GAHT) and is obviously suppressed in case of gender-affirming surgery involving bilateral ovariectomy and/or hysterectomy. The evolution of medical support for transgender people has made fertility preservation strategies possible. Fertility preservation in transgender men mainly relies on oocyte cryopreservation following controlled ovarian stimulation. However, few data are available to date on the subject, concerning small sample sizes, so no reliable conclusions can be drawn about the feasibility and efficiency of fertility preservation procedures in trans men. Study design, size, duration This retrospective study reports the results of fertility preservation counselling in 118 transgender men referred to our fertility centre from September 2018 to December 2022. Among them, 16 benefited from oocyte cryopreservation. Ovarian stimulation outcomes were compared with those of cisgender oocyte donors. Participants/materials, setting, methods Sixteen transgender men benefited from oocyte cryopreservation following ovarian stimulation and were matched 1:1 to cisgender oocyte donors according to age and body mass index. Antral follicle count and serum AMH levels were systematically measured. Primary outcomes included duration of the stimulation, total FSH dose, peak serum estradiol, oocyte yield, number of mature oocytes, and maturity rate (mature oocytes/total oocytes collected). Results were compared using Fisher’s exact or Wilcoxon’s rank sum tests. Main results and the role of chance One hundred and eighteen transgender men were referred in our centre for fertility preservation counselling. Among them, 95 asked for a medical consultation, and 86 came to the appointment. Following the consultation, only 16 (18.6%) finally decided to benefit from oocyte cryopreservation following ovarian stimulation, including 2 that had already started testosterone therapy. Sixteen presumably fertile oocyte donors were matched based on age and BMI. Mean age of trans’ men was 23.9 ± 5.0. Basal ovarian reserve tests showed satisfactory results in trans’ men and oocyte donors, with similar AMH (4.5 ± 2.3 vs. 4.4 ± 3.2, respectively, NS) but lower AFC in trans’men than in oocyte donors (13.8 ± 11.0 vs. 26.7 ± 10.1, p = 0.033). This result may be explained by a more frequent use of the abdominal approach to assess AFC in the transgender group. Ovarian stimulation outcomes were comparable, with no differences in the duration of stimulation, total FSH dose and peak estradiol levels, leading to a comparable mean number of mature oocyte (15.4 ± 9.9 vs. 17.2 ± 10.6, respectively, NS). Thirteen out 16 transgender men had 10 or more cryopreserved mature oocyte following a single procedure. Limitations, reasons for caution Only a low percentage of trans men that were referred to our centre finally chose to perform oocyte cryopreservation, leading to a small sample size. The majority of them had not started any GAHT, preventing us to evaluate the potential consequences of these treatments on ovarian stimulation outcomes. Wider implications of the findings While parenthood strategies for transgender people have long been ignored, fertility preservation is an important issue to consider, especially because medical treatments and surgeries may be undertaken in very young adults. Oocyte cryopreservation seems to represent a feasible way for trans men to preserve their fertility for future biological parenting. Trial registration number N/A

Impact of Breast Cancer and Germline BRCA Pathogenic Variants on Fertility Preservation in Young Women.

Several studies have suggested that breast cancer (BC) and germline BRCA pathogenic variants (gBRCA PVs) could have a deleterious impact on ovarian reserve. Nevertheless, data are limited and mixed. Our objective was to evaluate the performance of fertility preservation (FP) in terms of the number of collected mature oocytes after ovarian stimulation (OS) in young women carrying a gBRCA PV, associated or not with BC. We conducted a retrospective monocentric study at HUB-Hôpital Erasme in Brussels. All women aged between 18 and 41 years diagnosed with invasive non-metastatic BC and/or gBRCA PV carriers who underwent OS for FP or preimplantation genetic testing for monogenic disorder (PGT-M) between November 2012 and October 2021 were included. Three groups were compared: BC patients without a gBRCA PV, BC patients with a gBRCA PV, and healthy gBRCA PV carriers. Ovarian reserve was evaluated based on the efficacy of OS and AMH levels. A total of 85 patients underwent 100 cycles. The mean age (32.2 ± 3.9 years; p = 0.61) and median AMH level (1.9 [0.2-13] μg/L; p = 0.22) were similar between groups. Correlations between the number of mature oocytes and AMH level (p < 0.001) and between AMH and age (p < 0.001) were observed. No differences in the number of retrieved mature oocytes were observed between groups (p = 0.41), or for other OS parameters. Neither BC nor a gBRCA PV significantly affects ovarian reserve and FP efficacy in terms of the number of mature oocytes retrieved.

Progestin-primed ovarian stimulation for fertility preservation in women with cancer: A comparative study.

In women scheduled for cancer treatment, oocytes cryopreservation is a well-established procedure. Random start protocols have been a substantial improvement in this setting, allowing to prevent delay in the initiation of cancer treatments. However, there is still the need to optimize the regimen of ovarian stimulation, to make treatments more patient-friendly and to reduce costs. This retrospective study compares two periods (2019 and 2020), corresponding to two different ovarian stimulation regimens. In 2019, women were treated with corifollitropin, recombinant FSH and GnRH antagonists. Ovulation was triggered with GnRH agonists. In 2020, the policy changed, and women were treated with a progestin-primed ovarian stimulation (PPOS) protocol with human menopausal gonadotropin (hMG) and dual trigger (GnRH agonist and low dose hCG) Continuous data are reported as median [Interquartile Range]. To overcome expected changes in baseline characteristics of the women, the primary outcome was the ratio between the number of mature oocytes retrieved and serum anti-mullerian hormone (AMH) in ng/ml. Overall, 124 women were selected, 46 in 2019 and 78 in 2020. The ratio between the number of mature oocytes retrieved and serum AMH in the first and second period was 4.0 [2.3-7.1] and 4.0 [2.7-6.8], respectively (p = 0.80). The number of scans was 3 [3-4] and 3 [2-3], respectively (p<0.001). The total costs of the drugs used for ovarian stimulation were 940 € [774-1,096 €] and 520 € [434-564 €], respectively (p<0.001). Random start PPOS with hMG and dual trigger represents an easy and affordable ovarian stimulation protocol for fertility preservation in women with cancer, showing similar efficacy and being more friendly and economical.

Abstract P4-11-08: Impact of ovarian stimulation for fertility preservation in young women with breast cancer: Updated survival and pregnancy outcomes

Abstract Background: Chemotherapy (CTx) and hormone therapy may impair fertility in women with breast cancer (BC) by direct gonadotoxicity or delayed childbearing. Inconsistent data regarding the safety and efficacy of ovarian stimulation for fertility preservation (FP) in BC may limit clinician referral and patient uptake of FP. We previously examined the effect of FP on BC recurrence and herein present updated survival and pregnancy outcomes in relation to FP from an expanded BC cohort. Methods: Women aged ≤ 40 years diagnosed with stage I-III BC between 2007-2018 referred to one of six cancer centres and to a reproductive endocrinologist in British Columbia, Canada were identified from a central database. Clinicopathologic, treatment and outcome characteristics were compared using uni/multivariate Cox and logistic regression analyses for survival and pregnancy outcomes, respectively, for patients who did and did not undergo FP prior to systemic cancer treatment. Results: 158 patients were identified. Sixty-four (41%) had lymph node involvement, 119 (75%) had ER-positive and 39 (25%) had HER2-positive BC. The 72 (46%) patients who underwent FP were more likely to be younger (mean age 33 vs 34 y, p=0.030), ECOG 0 (p=0.013), have CTx (p&amp;lt;0.001) and GnRH agonist during CTx (p=0.010) compared to patients with no FP. Tumor stage, ER/HER2/BRCA-positivity, BMI, radiation and number of existing children were not associated with decision to pursue FP (p&amp;gt;0.05). After a median follow-up of 4.7 years, BC recurrence occurred in 15 (17%) non-FP patients and 9 (13%) FP patients (Table 1). FP did not affect overall survival by univariate (HR 0.9; 95% CI 0.7-1.3) or multivariate analysis controlling for age, BMI, ECOG/ER/HER2 status, tumor stage and receipt of CTx or radiation (HR 1.0, 95% CI 0.7-1.4). Post-diagnosis, 22 (31%) FP patients and 11 (13%) non-FP patients had ≥ 1 pregnancy (Table 2). The use of assisted reproductive technology (ART) was similar in both groups. Patients who had FP were 2.8 times more likely (p=0.013) to conceive at least once. The results remained significant on multivariate analysis controlling for age, BMI, ECOG status and baseline parity (p=0.030). Non-FP patients had a 31% higher miscarriage rate than those who did (p=0.26). Conclusions: FP was not associated with an increased risk of locoregional recurrence, distant recurrence or death over a follow-up period of 3-11 years, supporting its safety in young women with BC. Despite more often receiving CTx, patients who underwent FP were significantly more likely to conceive after BC than those who did not, even when accounting for differences in patient profiles. This may relate to greater use of GnRH agonists during CTx, known to protect ovarian function, and stronger desires for future childbearing in patients who pursued FP. Although there was similar use of ART in both groups, the higher pregnancy rate and more successful reproductive outcomes in FP patients support the value and promotion of pre-oncologic treatment FP in young BC patients early in their disease trajectory, to enhance survivorship family planning. Table 1.Survival outcomes of patients.CharacteristicNo FP (n=86)FP (n=72)p-valueRecurred [n (%)]0.85Locoregional6 (7)4 (6)Distant9 (10)5 (7)Deceased [n (%)]8 (9)4 (6)0.38 Table 2.Characteristics of first pregnancies in patients conceiving after diagnosis.CharacteristicNo FP (n=11)FP (n=21)p-valuePregnancy outcome [n (%)]0.26Completed3 (27)11 (52)Miscarriage7 (64)7 (33)Ongoing1 (9)3 (14)Pregnancy interval from diagnosis [n (%)]0.29≤ 2 y04 (19)2-5 y8 (73)13 (62)&amp;gt; 5 y3 (27)4 (19)Type of conception [n (%)]0.52Natural9 (82)15 (71)Assisted2 (18)6 (29) Citation Format: Megan E Tesch, Ying Wang, Chloe Lim, Ying Hui Xu, Shaina Lee, Kirstin Perdrizet, Dan Yokom, Ellen Warner, Jeffrey Roberts, Caroline Lohrisch. Impact of ovarian stimulation for fertility preservation in young women with breast cancer: Updated survival and pregnancy outcomes [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-08.

Abstract PD5-06: Safety of assisted reproductive technologies (ART) following treatment completion in young women with germline BRCA pathogenic variants having a pregnancy after breast cancer

Abstract BACKGROUND: Young breast cancer (BC) survivors are at risk of infertility. Ovarian stimulation for fertility preservation before (neo)adjuvant chemotherapy is standard of care. Research efforts have shown no negative prognostic effect of pregnancy following BC therapy, also among BRCA carriers. Currently, poor evidence is available on the safety to undergo ART following BC treatment, with no data in carriers of germline BRCA pathogenic variants. To provide evidence on the safety of fertility treatments in this specific population, we assessed the outcomes of a cohort of BRCA-mutated BC survivors who had a pregnancy after prior BC history by comparing the group of patients who underwent ART to achieve pregnancy to the group with spontaneous pregnancy. METHODS: We conducted a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤ 40 years with stage I-III BC, between January 2000 and December 2012, bearing germline BRCA1/2 pathogenic variants. Survivors with a pregnancy (any outcome) after BC, with no disease-free survival (DFS) event before pregnancy, were assigned to the ART and non-ART group if their pregnancy was achieved through ART or spontaneously, respectively. ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), and embryo transfer under hormonal replacement therapy (HRT). RESULTS: Of 1,424 patients registered in the study, 168 with a pregnancy after BC were included in the present analysis. A total of 22 patients were included in the ART group and 146 in the non-ART group. Before BC diagnosis, 18.2% patients in the ART group had at least one child, compared to 38.4% in the non-ART group (P=0.030). Patients had a median age at BC diagnosis of 33.0 vs 30.2 years old in the ART group and in the non-ART group, respectively (P=0.004); 45.4% and 17.1% had grade 1-2 tumors, respectively (P=0.008), and 59.1% vs 31.5% had hormone receptor-positive tumors, respectively (P=0.016). Both cohorts had similar tumor size and nodal stage characteristics. Type and duration of endocrine therapy were comparable between groups. The type of ART was not specified in 5 survivors (22.7%). Ovulation induction was used in 1 patient (4.5%), ovarian stimulation in 7 patients (31.8%), embryo transfer under HRT following oocyte donation in 5 patients (22.7%), and embryo transfer under HRT following oocyte and/or embryo cryopreservation for fertility preservation in 4 patients (18.2%). Median age at conception among survivors was 39.7 years in the ART group versus 35.4 years in the non-ART group (P&amp;lt;0.001). Overall, no differences in obstetrical outcomes were observed between groups, although there were more delivery complications in the ART group vs the non-ART group (22.1% vs 4.1%, respectively, P=0.011). Median follow-up from pregnancy was 3.4 years (range: 0.8-8.6) for patients in the ART group vs 5.0 years (range: 0.8-17.6) in the non-ART group (P=0.009). In the ART group, 2 patients (9.1%) experienced a DFS event (both were loco-regional recurrences) as compared to 40 patients (27.4%) in the non-ART group (P=0.182). No patients died in the ART group compared to 10 patients (6.9%) in the non-ART group. CONCLUSIONS: To our knowledge, this is the first study assessing the safety of ART in BC survivors bearing germline BRCA pathogenic variants. Even though the exposed cohort was small, results showed that the use of ART does not appear to increase the relapse risk at short-term follow-up. Further reproductive studies in BRCA-mutated BC patients are warranted. Citation Format: Margherita Condorelli, Marco Bruzzone, Marcello Ceppi, Alberta Ferrari, Albert Grinshpun, Anne-Sophie Hamy, Evandro de Azambuja, Estela Carrasco, Fedro A. Peccatori, Antonio Di Meglio, Shani Paluch-Shimon, Philip D. Poorvu, Marta Venturelli, Christine Rousset-Jablonski, Claire Senechal, Luca Livraghi, Riccardo Ponzone, Laura De Marchis, Katarzyna Pogoda, Amir Sonnenblick, Cynthia Villarreal-Garza, Octavi Córdoba, Luis Teixeira, Florian Clatot, Kevin Punie, Rossella Graffeo Galbiati, Maria Vittoria Dieci, Alejandro Pérez-Fidalgo, Francois P. Duhoux, Fabio Puglisi, Arlindo R. Ferreira, Eva Blondeaux, Tamar Peretz-Yablonski, Olivier Caron, Claire Saule, Lieveke Ameye, Judith Balmaña, Ann H. Partridge, Hatem A. Azim, Jr, Isabelle Demeestere, Matteo Lambertini. Safety of assisted reproductive technologies (ART) following treatment completion in young women with germline BRCA pathogenic variants having a pregnancy after breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD5-06.

A retrospective study evaluating the impact of scattering radiation from imaging procedures on oocyte quality during ovarian stimulation for fertility preservation in young breast cancer patients.

Ovarian stimulation for oocyte and embryo cryopreservation is the standard of care for fertility preservation in young breast cancer patients before gonadotoxic chemotherapy. The procedure should be started as soon as possible to avoid delay of treatment; thus, it is often performed concomitantly with tumor staging assessments. However, questions remain regarding the potential negative impact on oocyte quality that may occur due to exposure to scattered ionizing radiation from imaging techniques when staging assessment is conducted at the same time as ovarian stimulation. We conducted a retrospective study on all breast cancer patients who performed ovarian stimulation for fertility preservation at our center between November 2012 and May 2020. Gynecologic and oncological characteristics were similar between patients exposed (n = 14) or not (n = 60) to ionizing radiation. Exposed patients started the ovarian stimulation sooner after diagnosis than non-exposed patients (11.5 vs 28days, respectively, P < 0.01). Cycle parameters, including the median number of oocytes collected (10.5 vs 7, P = 0.16), maturation rates (92.5% vs 85.7%, P = 0.54), and fertilization rates (62.2% vs 65.4%, P = 0.70), were similar between groups. This study shows that scattered ionizing radiation due to staging assessment appears to be safe without compromising follicular growth and maturation. Larger studies on fertility and obstetrical outcomes are needed to confirm these preliminary data.

Patients undergoing elective and oncofertility preservation respond similarly to controlled ovarian stimulation for fertility preservation.

ObjectiveOutcome data for oocyte vitrification for fertility preservation are still scarce despite the scientific and technological advances. Studies suggest that patients with cancer have worse outcomes regarding mature vitrified oocytes when compared to healthy patients. Thus, the objective of this study was to evaluate and compare the oocyte vitrification response in patients undergoing elective and oncofertility preservation.MethodsThe ovarian stimulation response was verified by a cross-sectional and observational study, analyzing data from 367 patients between 2009 and 2018, which were divided into elective group (EG; n=327) and oncofertility group (OFG; n=40). The number of follicles, oocytes, mature oocytes, and duration of the cycle was evaluated, which were compared with clinical and ovarian stimulus data between groups.ResultsA significant difference in women's age (31.3±5.8 vs. 37.0±2.9 years; p<0.01) and basal values of Follicle Stimulating Hormone (FSH), (4.0 [3.3 - 6.2] vs. 9.0 [5.4 - 9.9] mIU/mL; p<0.01) were observed. When adjusting data for age, FSH and Gonadotropin-releasing Hormone protocols, no significant difference in the number of vitrified mature oocytes between the two groups were observed (6.0 [3.0-11.0] vs. 7.0 [3.0-12.0]; p=0.11).ConclusionsThus, patients undergoing elective and oncofertility preservation seem to respond similarly to controlled ovarian stimulation for fertility preservation. Breast cancer was the most frequent in the OFG (67%).

Comparison of embryo quality between standard controlled ovarian stimulation and random-start controlled ovarian stimulation for fertility preservation

Comparison of embryo quality between standard controlled ovarian stimulation and random-start controlled ovarian stimulation for fertility preservation

Do stage and grade of malignancy impact fertility preservation in breast cancer patients?

IntroductionThe impact of cancer on basal fertility and ovarian response to stimulation has not yet been clarified. Evidence on this topic is scarce and conflicting. Aim of this study was to assess the impact of breast cancer stage and grade on the number of retrieved mature oocytes during controlled ovarian stimulation for fertility preservation. MethodsRetrospective cohort study evaluating data on 101 stimulation cycles of women with breast cancer undergoing oocyte cryopreservation categorized according to breast cancer stage (low-stage: I; high-stage:II-III) and grade (low-grade: G1–2; high-grade: G3) using the American Joint Committee on Cancer staging system (VIII edition). ResultsHigh-stage disease was not associated with worse oocyte retrieval outcomes (median 7 vs 7, p = 0.75). High-grade disease patients showed a significantly lower antral follicle count (AFC) compared to low-grade disease patients (10 vs 13, p = 0.03), and required higher doses of FSH (2612 IU vs 2250 IU; p = 0.03) during stimulation. Median number of vitrified oocytes was 6 in low-grade disease patients and 7 in high-grade disease patients (p = 0.35). ConclusionsStage and grade of breast cancer do not impact the number of retrieved mature oocytes. However, higher grade of breast cancer is associated with lower AFC at baseline and need for higher doses of gonadotropin during ovarian stimulation.

P–463 Patients undergoing elective and onco-fertility preservation respond similarly to controlled ovarian stimulation for fertility preservation

Abstract Study question Is the oocyte vitrification response different in patients undergoing elective and onco-fertility preservation? Summary answer Patients undergoing elective and onco-fertility preservation seem to respond similarly to controlled ovarian stimulation for fertility preservation. What is known already Age persists as the factor with the most significant impact on the prognosis of female fertility. The ovarian reserve can also be threatened by surgical, radiotherapy or chemotherapy procedures. Thus, maternity delay and the increased incidence of malignant diseases are the most jeopardizing conditions for reproductive potential in women. Studies are still conflicting about oocyte freezing results in patients with and without cancer. Some studies suggest worse outcomes in patients with cancer regarding the number of mature vitrified oocytes when compared to healthy patients whether others show similar response to the ovarian stimulation for fertility preservation in both groups. Study design, size, duration Observational, cross-sectional, and historical study using data from 367 who underwent oocyte vitrification from a Reproductive Medicine Center, between 2009 and 2018. Participants/materials, setting, methods Patients were divided into an elective group (EG; n = 327) and an onco-fertility group (OFG; n = 40). Data were presented as mean ± standard deviation or median and interquartile range (IQR) and absolute and relative frequencies. Chi-square test, Student’s t-test, or Mann-Whitney test were applied. Generalized linear models were used to control confounding factors. Data were adjusted by women age, FSH, and GnRH protocol. The null hypothesis was rejected when p &amp;lt; 0.05. Main results and the role of chance: Patients age in OFG was significantly lower compared to EG (31.3±5.8 vs. 37.0 ±2.9 years; p &amp;lt; 0.01) and also FSH measurement (4.0 [3.3 – 6.2] vs. 9.0 (5.4 – 9.9) mIU/mL; p &amp;lt; 0.01). The presence of a partner was significantly higher in OFG (25 [62.5%] vs. [19.9%]; p &amp;lt; 0.001). GnRH antagonist protocol was used in 80.1% of cycles, and FSH-r was used in 80.4% of cycles. Letrozole was added for 20 breast cancer patients (74%). When adjusting data for age, FSH and Gonadotropin-releasing Hormone (GnRH) protocols, no significant difference in the number of vitrified mature oocytes between the two groups were observed (6.0 [3.0–11.0] vs. 7.0 [3.0–12.0]; p = 0.11). Limitations, reasons for caution: The number of women in the OFG was lower than the EG group. The OFG was composed of different types of tumors in different locations and stages. Thus, it can be questioned whether any patient with a more aggressive tumor might have had a negative impact on the results. Wider implications of the findings: Healthy patients and patients with cancer seem to respond similarly to ovarian stimulation for fertility preservation. The extensive number of cycles performed for EG in contrast to OFG leads to a reflection on patients who are still not referred for reproductive counseling after a cancer diagnosis. Trial registration number Not applicable

P–455 Breast cancer recurrence in women with and without controlled ovarian stimulation for fertility preservation. Cohort study

Abstract Study question Do patients diagnosed with breast cancer who undergo ovarian stimulation for fertility preservation prior to chemotherapy have a higher risk of recurrence of the disease? Summary answer There was no statistically significant difference in the hazard ratio for breast cancer recurrence in fertility preservation-stimulated women compared to non-stimulated ones What is known already While many women with early breast cancer benefit from chemotherapy treatments in increasing disease-free survival, they are also at risk of permanent chemotherapy induced ovarian failure. Oocyte cryopreservation with an adapted protocol with letrozole may reduce the possible deleterious effect of the hyper estrogenic state during the controlled ovarian hyperstimulation (COH). Although fertility preservation in women diagnosed with breast cancer seems safe, the follow-up periods of most studies are short in time. In addition, follow-up data of COH before neoadjuvant chemotherapy in women with hormone negative tumor receptors is still scarce and briefly reported. Study design, size, duration It was a retrospective cohort study, where 208 women with non-metastatic breast cancer were included. The recruitment period was from 01/01/2009 to 01/12/2019. The minimum follow-up period was 6 months, and the maximum, 130 months. Participants were divided into two cohorts, those who received controlled ovarian hyperstimulation prior to their cancer treatment and those who did not. Patients were followed until disease recurrence, death, loss to follow-up, or end of the study Participants/materials, setting, methods Setting: university hospital in Buenos Aires, Argentina. We included women aged 18 to 45 years with a recent histological diagnosis of non-metastatic breast cancer who had to receive chemotherapy with gonadal toxicity. We excluded patients with a history of previous chemotherapy or radiotherapy for another cancer disease, or menopause. Follow-up was at least an annual clinical check-up and breast imaging. Cohorts were analysed using a Cox-proportional hazards model, adjusted for propensity score for receiving stimulation. Main results and the role of chance We included 208 women, 39 in the COH group and 169 in the non-stimulated group (NSG). The only statistically significant difference was in age: median years 33.7 (interquartile range -IQR- 30.9 to 36.9) and 40.0 years (IQR 36.8 to 44.0), respectively. The median size of cancer nodules was 19.0 millimetres (IQR 10.0–30.0) and 17.0 (IQR 11.0–25.0), p 0.547; percentage of positive lymph nodes: 41.0% vs 39.3%, p 0.841; positive hormonal receptors: 84.6% vs 85.2%, p 0.925; percentage of neoadjuvant chemotherapy: 20.5% vs 11.4%, p 0.128. There were also no statistically significant differences regarding tumour stage, high Ki–67 labelling index, positive breast cancer genes (BRCA 1 or 2), and radiotherapy. Overall, 18.0% of patients had cancer recurrence in the COH group and 20.7% in the NSG (p 0.699). Crude cancer recurrence rates were similar: 5.96 per 100 patients/year (95%CI 2.84–12.50), and 4.65 per 100 patients/year (95%CI 3.34–6.47), respectively. The crude hazard ratio (HR), comparing the COH group vs the NSG was 1.32 (95%CI 0.58–2.97; p 0.507). The adjusted HR using a propensity score for receiving ovarian stimulation treatment was 1.08 (95%CI 0.39–2.98; p 0.887). Results were similar if adjusted for age, neoadjuvant chemotherapy, and other confounders. Limitations, reasons for caution This was a single-center retrospective cohort study. There might be unknown or residual confounders that could influence results. Nevertheless, we accounted for treatment bias using a propensity score for ovarian stimulation. Results should be extrapolated with caution, especially in other non-university institutions and populations. Wider implications of the findings: This study provides new evidence on the safety of controlled ovarian stimulation in breast cancer patients prior to chemotherapy treatment, in a Latin American population. Letrozole continues to show safety and efficacy as an adapted protocol in breast cancer. Trial registration number Not applicable

P–432 Do stage and grade of malignancy impact fertility preservation in breast cancer patients?

Abstract Study question Do stage and grade of breast cancer impact the number of retrieved mature oocytes during controlled ovarian stimulation for fertility preservation? Summary answer Stage and grade of breast cancer do not impact the number of retrieved mature oocytes. Higher grade breast cancer requires higher gonadotropin doses during stimulation. What is known already Cancer can impair ovarian response by unknown mechanisms. Some authors suggest that it could be detrimental on fertility because it elicits a catabolic state, increasing stress hormone levels. Some studies have also shown that ovarian response to controlled ovarian stimulation (COS) is, in some way, compromised in oncological patients. Little is known about the impact of different types of cancer on ovarian reserve, and specifically whether higher stage and grade could compromise egg retrieval during fertility preservation (FP) techniques. Study design, size, duration: Retrospective cohort study evaluating data of FP treatment cycles among women with breast cancer at the Oncofertility Unit of San Raffaele Hospital, Milan in the period from 2011 to 2019. Participants/materials, setting, methods Inclusion criteria were: breast cancer diagnosis; age 22–41; oocyte cryopreservation after stimulation with a random start GnRH-antagonist protocol. Patients receiving chemotherapy before FP were excluded. We compared outcomes between low-stage (stage I) and high-stage (stage II-III) patients and low-grade (G1-G2) and high-grade (G3) patients. Main study outcome was the total number of retrieved mature oocytes. Univariate analysis was performed by Mann-Whitney test, Kruskal-Wallis test and Fisher’s exact test. Multivariate analysis was performed by logistic regression. Main results and the role of chance 101 stimulation cycles were included. High-stage disease patients were significantly younger than low-stage. Median antral follicle count (AFC) was 12 in low-stage and 10 in high-stage (age-adjusted p = 0.92) and median anti-mullerian hormone (AMH) levels were 1.9 ug/L in low-stage and 1.8 ug/L in high-stage (age-adjusted p = 0.22). No significant difference in stimulation protocols and follicle-stimulating hormone (FSH) start and total dose could be detected between the 2 groups. Median number of vitrified oocytes was 7 in both groups (p = 0.75). No significant difference could be observed in median AFC (13 vs 10, p = 0.14) and AMH levels (2.1 vs 1.5, p = 0.88) between low-grade and high-grade disease patients. When adjusting for age, AFC was found to be significantly lower in high-grade disease patients (p = 0.03). Patients with high-grade tumors were stimulated with higher doses of FSH (age-adjusted p-value=0.03). Median number of vitrified oocytes was 6 in low-grade patients and 7 in high-grade (p = 0.35). In a multivariate model including age, cancer stage, cancer grade and molecular classification, the only significant factor found to be inversely associated with AFC was cancer grade (OR 3.6; 95% CI 0.7 – 6.5, p = 0.01), while only age was significantly associated with oocyte retrieval (OR 0.4; 95% CI 0.01 – 0.9, p = 0.04). Limitations, reasons for caution The main limitations of our study are its retrospective design and the small sample size. Wider implications of the findings: Fertility preservation counselling and ovarian stimulation protocols of breast cancer patients could be implemented with cancer grade. Trial registration number Not applicable

Circulating Tumor DNA to Interrogate the Safety of Letrozole-Associated Controlled Ovarian Stimulation for Fertility Preservation in Breast Cancer Patients.

BackgroundCurrent fertility preservation strategies for young breast cancer patients planning a future motherhood include the association of controlled ovarian stimulation with the aromatase inhibitor letrozole (let-COS) to harvest mature oocytes while maintaining low estradiol levels. Despite this is a widely adopted protocol, the safety of let-COS on breast cancer outcomes has been poorly investigated and its use remains off-label. We assessed the safety of let-COS in breast cancer patients using circulating tumor DNA (ctDNA) as a surrogate biomarker of disease recurrence.MethodsBROVALE is an interventional non-randomized prospective study designed to evaluate the efficacy and safety of let-COS for fertility preservation in early breast cancer patients before starting (neo)adjuvant chemotherapy. Letrozole was administered throughout the COS cycle, until ovulation triggering. Safety was a secondary endpoint. Data on oncological outcomes were collected during the follow-up as well as plasma and whole blood for evaluation of ctDNA levels at the time of enrollment (i.e. before starting let-COS) and oocyte retrieval (i.e. 48 hours after the last administration of letrozole). Targeted gene sequencing on the primary tumor samples was performed to identify specific mutations used for ctDNA analysis by digital PCR. DNA extracted from whole blood samples was used to discriminate between somatic and germline mutations.ResultsFrom April 2014 to May 2017, 29 young early breast cancer patients enrolled in the BROVALE study who had available tissue samples participated to the ctDNA substudy. Among them, 15 had at least one validated somatic mutation. ctDNA was undetectable neither before nor after let-COS in 9 of them. Six patients had detectable ctDNA in the plasma samples collected before Let-COS. No change in ctDNA level after let-COS was observed in 3 patients and the level decreased (fold-change ≤ 0.5) in two women. One patient experienced an increased (fold-change ≥ 2) in ctDNA level but without disease relapse 34 months after diagnosis.ConclusionsNo increase in ctDNA level was observed in 93% (14/15) of the patients receiving let-COS supporting its use as a safe strategy for young women with early breast cancer interested in fertility preservation before chemotherapy.

Ovarian stimulation for fertility preservation in an oncology patient with etonogestrel implant in place.

To describe a case of a young woman who presented for fertility preservation and underwent ovarian stimulation with an etonogestrel implant in place. A 24-year old, gravida 0, with an etonogestrel implant and newly diagnosed lower extremity sarcoma and DVT desiring oocyte cryopreservation prior to adjuvant chemotherapy and radiation. To avoid delay in her oncologic care and allow for continued use of contraception post-retrieval, the patient underwent controlled ovarian hyperstimulation (COH) without removal of the etonogestrel implant. Baseline labs included follicle-stimulating hormone 9 mIU/mL, luteinizing hormone 4.9 mIU/mL, estradiol 42 pg/mL, anti-Müllerian hormone 5.1 ng/mL, and antral follicle count greater than 40. The patient was placed on an antagonist protocol and stimulated with 125 IU Gonal-F and 75 IU Menopur. She received a total of 12 days of gonadotropin stimulation. On the day of trigger, her estradiol was 1472 pg/mL, lead follicle 21.5 mm with a total of 25 follicles measured > 12 mm. She was triggered with 5000 U hCG. She had a total of 23 oocytes retrieved, 17 of which were metaphase II and vitrified. COH and successful oocyte cryopreservation can be achieved in patients with an etonogestrel implant in situ without apparent detrimental effects to oocyte yield or maturity. Due to the etonogestrel implant's inhibitory effects on LH, it is recommended to use an hCG trigger for final oocyte maturation.

Predictors and outcomes in breast cancer patients who did or did not pursue fertility preservation.

Breast cancer is the most common cancer in reproductive age women, and treatment can affect fertility; however, there is often concern regarding the safety of increased estradiol (E2) levels and potential delays in treatment with ovarian stimulation for fertility preservation (FP). The aim of this study was to compare recurrence and survival in breast cancer patients who pursued FP without concurrent letrozole to those who did not (non-FP). We reviewed charts of women with breast cancer who contacted the FP patient navigator (PN) at Northwestern University from 01/2005-01/2018. Oncology and fertility outcome data were collected. Data were analyzed by Chi-square test or regression, as appropriate. Kaplan-Meier curves were used to examine breast cancer recurrence and survival. Statistical analyses were performed with SPSS IBM Statistics 26.0 for Windows. 332 patients were included, of which 157 (47.3%) underwent FP. Median days to treatment after consulting the PN was 35 in the FP group and 21 in non-FP (p < 0.05). Cancer recurrence was noted in 7 (4.7%) FP patients and 13 (7.9%) non-FP patients (NS), and mortality in 5 (3.2%) FP patients and 7 (4.2%) non-FP patients (NS). Within the FP group, no significant differences were found in recurrence or mortality based on ER status, age, BMI, peak E2 level or total gonadotropin dose. Likelihood of pursuing FP was primarily a function of age and parity, and was not affected by breast cancer stage. To date, 21 have used cryopreserved specimens, and 13 (62%) had a live birth. FP is safe and effective in breast cancer patients, regardless of receptor status; E2 elevations and the 2-week delay in treatment start are unlikely to be clinically significant. These findings are unique in that our institution does not use concomitant letrozole during stimulation to minimize E2 elevations in breast cancer patients.

Ovarian stimulation for fertility preservation in a woman with borderline serous ovarian tumor causing a large fluctuating subcutaneous fluid collection: a case report

Ovarian stimulation for fertility preservation in a woman with borderline serous ovarian tumor causing a large fluctuating subcutaneous fluid collection: a case report

THE USE OF DYDROGESTERONE TO PREVENT LH PEAK IN RANDOM-START OVARIAN STIMULATION FOR FERTILITY PRESERVATION

Compare the efficacy of oral dydrogesterone to prevent LH peak during ovarian stimulation versus usual antagonist protocol in fertility preservation cases with oocyte vitrification. Randomized prospective study from August 2019 to March 2020 at the Gynecology, Obstetric and Reproductive Medicine department of the Aziza Othmana University Hospital. Inclusion criteria: All patients underwent controlled ovarian stimulation for fertility preservation via oocyte vitrification. Exclusion criteria: Patients with hormone-dependent diseases (breast cancer, systemic lupus). Random-start ovarian stimulation was conducted with 300 IU of recombinant FSH for all patients. Patients were randomized into 2 groups on the day of the onset of ovarian stimulation: Group 1: prevention of LH peak using Dydrogesterone orally: 10 mg three times a day; beginning the first day of ovarian stimulation. Group 2: Prevention of LH peak by subcutaneous injection of Cetrotelix 0.25 mg per day from the first day of ovarian stimulation. Ovulation was triggered with 0.2 mg triptoreline. Oocyte pickup took place 37 hours later, either vaginally or per urethral transvesical route (for virgin patients). χ2 test was used to compare qualitative variables. Student’s t-test was used to compare quantitative variables. P-value < 0.05 was considered as statistically significant. Forty-seven patients were included in our study: 22 in Group 1 and 25 in Group 2. There was no significant difference regarding the clinical characteristics of the 2 groups (Group 1 vs Group 2) in terms of age (23.14 ± 5.07 vs 23.8 ± 5.7 , p: 0.7), BMI (21.63 ± 3.6 vs 22.48 ± 4.03 , p: 0.5), AMH levels (2.04 ± 1.24 vs 3.3 ± 1.93, p: 0.06), the duration of ovarian stimulation ( 9.14 ± 1.55 vs 9.33 ± 1.79 , p: 0.5), the number of follicles with a diameter > 15 mm on the day of triggering ( 7.62 ± 4.1 vs 7.5 ± 3.3, p: 0.6) and plasma oestrogen levels on the day of triggering ovulation (2587 ± 1601 vs 2083 ± 1163, p: 0.1) Moreover, pickup results were similar (goupe 1 vs group 2) for the number of CCOS( 12.71 ± 7.7 vs 12.29 ± 7.6 , p: 0.3) and the number of mature oocytes ( 9.85 ± 5.9 vs 9 ± 6.7 , p: 0.9). It should be noted that LH monitoring was performed in all patients and the difference was not significant either. Prevention of premature LH peak during COS is possible using dydrogesterone in Random-start protocols for fertility preservation, excluding cases of hormone-dependant diseases.

Oocyte vitrification for fertility preservation in women with endometriosis: an observational study

To describe the outcome of fertility preservation (FP) using vitrified oocytes in patients with endometriosis and to determine the impact of ovarian surgery. Retrospective observational study. University-affiliated private invitro fertilization (IVF) center. Four hundred and eighty-five women with endometriosis who underwent FP from January 2007 to July2018. Vitrification of metaphase II (MII) oocytes for future use. Oocyte survival rate and cumulative live-birth rate (CLBR). Mean age at vitrification was 35.7 ± 3.7 years. The women undergoing operations were younger than the nonsurgical patients (33.4 ± 3.6 years vs. 36.7 ± 3.7 years). The survival rate and CLBR were 83.2% and 46.4%, respectively. The number of vitrifiedoocytes per cycle (6.2 ± 5.8) was higher for the nonsurgical patients compared with the unilateral (5.0 ± 4.5) or bilateral (4.5 ± 4.4) surgery groups, but was comparable among the surgical patients. The effect of age (adjusted odds ratio [OR] 0.904; 95%CI, 0.858-0.952), number of oocytes (adjusted OR 1.050; 95% CI, 1.025-1.091), and survival (adjusted OR 1.011; 95% CI, 1.001-1.020) on the CLBR was confirmed. However, the effect of surgery was not observed (adjusted OR 1.142; 95% CI, 0.778-1.677). Nonetheless, the ovarian response (vitrified oocytes = 8.6 ± 6.9 vs. 5.1 ± 4.8) and CLBR (72.5% vs. 52.8%) were higher in young (≤35 years) nonsurgical patient versus the surgical patients; older women showed similar outcomes. Fertility preservation gives patients with endometriosis a valid treatment option to help them increase their reproductive chances. We suggest performing surgery after ovarian stimulation for FP in young women. In older women, an individualized treatment should be considered.

Impact of extent and biochemical parameters of lymphoma on fertility preservation outcome

To evaluate the impact of lymphoma aggressiveness on ovarian response during fertility preservation treatment. Retrospective cohort study. University-affiliated tertiary hospital. Women with lymphoma who underwent ovarian stimulation for fertility preservation in the period from 2009 to2018. None. Primary outcome: the number of mature oocytes; secondary outcomes: the number of retrieved oocytes, estradiol level, and number of follicles >14 mm on the day of oocyte maturation trigger. Patients with stage I-II lymphoid neoplasms (localized disease) were compared with those with stage III-IV lymphomas (advanced disease). Women with favorable levels of biochemical prognostic markers were also compared with those with unfavorable levels. Women with favorable levels of biochemical prognostic markers (n = 74) had a higher number of mature oocytes compared with patients with unfavorable serum levels (n = 67): 11 (7.8-16) versus 9 (5-11), respectively. The number of mature oocytes was similar between patients with localized (n = 75) and advanced (n = 66) lymphomas. Women with unfavorable combination of stage and biochemical factors had lower number of mature oocytes compared to patients with favorable combination: 8 (5-10) versus 11 (7-16), respectively. Multivariate logistic regression showed that favorable levels of biochemical markers as well as a combination of extent and biochemical parameters were statistically significantly associated with the result of over 10 mature oocytes. Highly-aggressive lymphoid neoplasms have a negative impact on ovarian function and response during fertility preservation treatment.

Ovarian stimulation for fertility preservation or family building in a cohort of transgender men.

The purpose of this study was to compare ovarian stimulation and pregnancy outcomes between transgender men (1) with and without a history of testosterone use (HRT) and (2) to cisgender women. Retrospective chart review between January 1st 2015 and March 1st, 2019 of transgender men and cisgender women seeking ovarian stimulation (OS) matched by BMI and age. Outcomes were compared using Fisher's exact or Wilcoxon's rank sum tests. Thirteen transgender men presented for OS, 7 who used HRT. When comparing transgender men with and without a history of HRT, there were no differences in the baseline follicle count, cycle length, or FSH and hmG used (p= 0.193, 0.306, 0.200, and 0.197, respectively). Transgender men who used HRT had lower peak estradiol and oocytes retrieved compared to transgender men with no HRT use; peak estradiol levels of 1175pg/mL IQR [559.5-2684]) vs 2713.5pg/mL IQR [2335-3105]; oocytes retrieved 12 IQR [4-26]) vs. 25.5 [18-28] (p= 0.046. and 0.038, respectively). There were no differences in the estradiol level per oocyte, meiosis II oocyte yield, or maturity rate (MII/oocytes) between the two groups (p= 1.000, 0.148, and 0.147, respectively). Peak estradiol levels were lower among transgender men compared to cisgender women (p= 0.016), but the remaining cycle characteristics were similar between the two groups. Three successful pregnancies were conceived using the oocytes of transgender men who used HRT. HRT use may not negatively impact ovarian stimulation outcomes. Clinical pregnancies are possible from the oocytes of transgender men with a history of HRT.