Fertility Preservation Cycles Research Articles

P-677 Letrozole inhibits ovulation via reducing responsiveness to luteinizing hormone in in vitro-grown mouse follicles

Abstract Study question Does letrozole reduce responsiveness to luteinizing hormone (LH) in in vitro-grown mouse follicles? Summary answer We found that letrozole reduced responsiveness to LH via reducing of luteinizing hormone/chorionic gonadotropin receptor (Lhcgr) transcription in in vitro. What is known already The continuous dosing of letrozole, the third-generation aromatase inhibitor, is used for the controlled ovarian stimulation (COS) of fertility preservation cycles in women with hormone-sensitive breast cancer to prevent the transient rise of serum estrogen levels. Recently, lower oocyte maturation rates and higher abnormal fertilization rates in COS with letrozole compared to standard COS have been reported. The studies using aromatase knockout mice and estrogen receptor beta knockout mice showed that intra-follicular estrogen is essential for responsiveness to LH of granulosa cells. However, whether letrozole reduces responsiveness to LH of follicles remains unknown. Study design, size, duration We evaluated the effect of letrozole on responsiveness to LH using in vitro mouse follicle culture system. Preantral follicles (150-200 µm) with a small number of stromal cells were isolated from 3 weeks old C57BL/6jjcl mouse ovaries and cultured in the presence of letrozole. We analyzed in vitro ovulation ability, and expression levels of ovulation-related genes to clarify the effect of letrozole on responsiveness to LH of follicles. Participants/materials, setting, methods The follicles were cultured with letrozole (0.01µM, 0.1µM, or 1µM) or vehicle (0.1% DMSO) for 5 days followed by 5 IU/ml hCG and 5 ng/ml hEGF stimulation as ovulation induction. The diameter and survival rate of follicles were assessed. After16 hours after ovulation induction, we assessed the ovulation and measured the transcription of Lhcgr, Ptgs2, Runx1 and Actb (internal control) in the follicles by RT-qPCR. We conducted a collateral experiment in the presence of estradiol. Main results and the role of chance The follicle growth and survival rate did not change by letrozole in vitro. However, in vitro ovulation was reduced by the addition of letrozole in a dose-dependent manner (Cochran-Armitage trend test, P < 0.0001): 41.2% in the 0.01µM letrozole treated group (n = 23), 10.5% in the 0.1µM letrozole treated-group (n = 17), and no ovulation in the 1µM letrozole treated-group (n = 19) compared with 69.6% in the vehicle-group (n = 18). Exogenous estrogen addition restored the ovulation ability of 1µM letrozole-treated follicle to the same levels as the vehicle group. RT-qPCR revealed that 0.1 µM letrozole significantly reduce the transcription levels of Lhcgr (P = 0.0027), Runx1 (P = 0.0124), and Ptgs2 (P = 0.0067) compared with vehicle-treated follicles. Exogenous estrogen addition restored the transcription of these genes to levels observed in vehicle-treated follicles. We also observed a positive correlation between the transcription of Lhcgr and Ptgs2 (R = 0.55, P = 0.0003), Lhcgr and Runx1 (R = 0.71, P < 0.0001), and Ptgs2 and Runx1 (R = 0.77, P < 0.0001). Our results suggested that letrozole-treated follicles impaired ovulation due to dysregulation of Lhcgr transcription and its downstream cascade caused by estrogen deficiency. Limitations, reasons for caution This is an in vitro experiment using a mouse model. Further research is needed to determine whether our findings are applicable to humans. Wider implications of the findings Our findings imply that letrozole may have disadvantages in not only ovulation, but also subsequent reproductive processes affected by the effectiveness of the LH surge, such as oocyte maturation, fertilization, and preimplantation embryo development. When evaluating oocyte cryopreservation for fertility preservation, it may be necessary to consider the COS protocol. Trial registration number Not applicable

P-598 Analysis of the oocyte yield and Ovarian Sensitivity Index with the use of two gonadotropins (FSHr/FSHu) and two pituitary suppression protocols (PPOS/GnRH-ant)

Abstract Study question Is there a difference, in terms of ovarian yield and sensitivity, comparing a progestin-primed protocols (PPOS) to a GnRH antagonist (GnRH-ant) and using different follitropin? Summary answer PPOS is an effective choice, with both follitropis. Nevertheless, could improve ovarian sensitivity to FSHu increasing the number of oocyte yield without compromising oocyte quality. What is known already The use of new ovarian stimulation protocols, starting during the luteal phase or randomly shows that endogenous progesterone alone is sufficient to block the LH surge and does not compromises oocyte competence and pregnancy outcomes. For these reasons, exogenous progesterone was utilized as an innovative model of pituitary suppression. Most studies have shown the effectiveness of the use of PPOS compared to the GnRH (antagonist or agonist) in IVF cycles. For oocyte donation only three studies were carried out analyzing the effect of PPOS with a recombinant FSH (FSHr) Study design, size, duration It is a retrospective, cohort, paired study. We analyzed egg donation cycles carried out in Next Fertility Valencia from January 2020 to May 2021. In total 93 donors were selected as eligible, each one undergoing both the PPOS and GnRH antagonist cycles for a total of 186 cycles, 54 received FSHr and 39 HP-FSHu. To attempt to eliminate possible bias due to interpersonal differences, every patient was her own control. Participants/materials, setting, methods All donors underwent two controlled ovarian stimulation cycles within 6 months, one using flexible GnRH antagonist (Ganirelix) and the other using medroxyprogesterone acetate (MPA), with FSHr or FSHu monotherapy and a GnRH-agonist triggering. The oocyte yield was analyzed focusing on: the number of oocytes retrieved, mature (MII) oocytes and useful oocytes (mature oocytes without morphological alterations). We also evaluated the Ovarian sensitivity index (OSI) calculating the oocyte number for each 1000 IU of gonadotropin used Main results and the role of chance Total gonadotropin consumption and duration of ovarian stimulation were similar in both models of pituitary suppression regardless the type of FSH. One less control is required with MPA than the GnRH-ant in both FSH groups. There were no premature ovulations in MPA or GnRH antagonist cycles regardless of the gonadotropin used. In the FSHr group no difference was observed in the oocyte yield and OSI between MPA and GnRHa. On the other hand, in the FSHu group a statistically significant improvement in the number of total oocytes retrieved (20,2 ± 8,5 vs 23,8 ± 10,9), total MII (18,0 ± 7,2 vs 21,2 ± 10,4) and OSI (6,4 ± 3,5 vs 7,7 ± 4,6) was observed in favor of the use of MPA. Also, the number of useful MII was higher with MPA (15,7 ± 6,5 vs 18,6 ± 10,4). No significant differences were detected in fertilization and blastocyst rate regardless the type of pituitary suppression and FSH used Limitations, reasons for caution The main limitation lies in the retrospective nature of the study. However, since each patient is her own control (Paired study), it gives an added value Wider implications of the findings The efficacy and efficiency of the MPA does not seem to be affected by the type of gonadotropin used, this further reassures about the possibility of using it with patients in case of fertility preservation cycles, PGT-A/M, "DuoStim" cycles Trial registration number Not applicable

Medroxyprogesterone acetate: an alternative to GnRH-antagonist in oocyte vitrification for social fertility preservation and preimplantation genetic testing for aneuploidy

Research questionCan medroxyprogesterone acetate (MPA) be used as a pituitary suppressor instead of a gonadotrophin releasing hormone (GnRH) antagonist during ovarian stimulation in elective fertility preservation and preimplantation genetic testing for aneuploidy (PGT-A) cycles? DesignA multicentre, retrospective, observational, cohort study conducted in 11 IVIRMA centres affiliated to private universities. Of a total of 1652 cycles of social fertility preservation, 267 patients were stimulated using a progestin-primed ovarian stimulation protocol (PPOS), and 1385 patients received a GnRH antagonist. In the PGT-A cycles, 5661 treatments were analysed: 635 patients received MPA and 5026 patients received GnRH antagonist. A further 66 fertility preservation and 1299 PGT-A cycles were cancelled. All cycles took place between June 2019 and December 2021. ResultsIn the social fertility preservation cycles, the number of mature oocytes vitrified in MPA was similar to the number of those treated with an antagonist, a trend that was seen regardless of age (≤35 or >35 years). In the PGT-A cycles, no differences were found in number of metaphase II, two pronuclei, number of biopsied embryos (4.4 ± 3.1 versus 4.5 ± 3.1), rate of euploidy (57.9% versus 56.4%) or ongoing pregnancy rate (50.4% versus 47.1%, P = 0.119) between the group receiving MPA versus a GnRH antagonist, whereas the clinical miscarriage rate was higher in the antagonist group (10.4% versus 14.8%, P = 0.019). ConclusionsAdministration of PPOS yields similar results to GnRH antagonists in oocytes retrieved, rate of euploid embryos and clinical outcome. Hence, PPOS can be recommended for ovarian stimulation in social fertility preservation and PGT-A cycles, as it allows greater patient comfort.

Fertility Preservation in Endometriosis: Does Patient Symptomatology Affect the Extent of the Ovarian Response?

This study is to identify factors and patient symptomatology affecting ovarian response in women with endometriosis who seek fertility preservation. An observational cross-sectional study was conducted from July 2017 to May 2020 at a tertiary university-affiliated medical center. We included patients who were treated in the endometriosis clinic and underwent fertility preservation. Patients completed an online questionnaire that was cross-referenced with electronic charts. An analysis related to patient data and fertility preservation cycles and a mediation analysis were performed. The mean patient age at time of fertility preservation was 35.2 (± 4.9) years. The mean accumulated number of oocytes vitrified per patient was 16.7 (± 12.1) oocytes. The correlation coefficient assessed between the number of oocytes vitrified per cycle and AMH was significantly positive at +0.472, p = 0.006. The examined reported symptoms were lethargy, chronic pelvic pain, dyschezia, dyspareunia, bowel-associated symptoms, and urinary tract symptoms. The number of oocytes vitrified correlated with the number of reported symptoms and clinical characteristics at - 0.497, p = 0.0001, and - 0.442, p = 0.0001, respectively. In a mediation analysis, the potential causality of surgical intervention in the relationship between the number of symptoms and ovarian response was - 0.300 (95% CI [0.15, 1.905], p = 0.05), and the calculated proportion of mediation was estimated to be 17%. We observed a significant negative association between the number of clinical symptoms and the quantity of vitrified oocytes. This relationship was only partly associated with prior surgical intervention. AMH was found to have the highest correlation with treatment success in patients with endometriosis undergoing fertility preservation.

Why are they not coming back? A single-center follow-up study on oncological women oocyte's storing for fertility preservation.

Oocyte cryopreservation is a valid option for female cancer patients to preserve fertility. The number of patients undergoing fertility preservation (FP) cycles has increased over the past years. Nevertheless, the rates of patients returning to use their cryopreserved material have shown to be considerably low, ranging from 5-8%, but significant data regarding the reasons of such low return rates are scarce. This study is a single-center follow-up retrospective study evaluating the return rate of oncological women who underwent FP at a tertiary care Fertility Center and assessing the reasons influencing the patients who did not return. Data about patients who returned to attempt pregnancy were retrieved from internal registries. Non-returned patients were assessed with a standardized phone survey investigating health condition, marital status and family projects, spontaneous conceptions, and the reasons why they had not returned to use their gametes. A univariate analysis between returned and non-returned patients was performed. Of the 397 patients who received counseling about FP, 171 (43.1%) underwent oocyte cryopreservation between 2001 and 2017. Nine (5%) died, and 17 (10%) were lost at follow-up. A total of 20 patients (11.7%) returned and 125 did not. In the non-returned group, 37 (29.6%) did not have a partner, 10 (8%) had a previous spontaneous conception, and 15 (12%) had recurrent malignancy at the time of follow-up. In the univariate analysis, younger age at freezing (31.8±6.2 vs. 35.2±4.7; p 0.018), lack of a partner (p 0.002), type of cancer (other than breast cancer; p 0.024) were the significant factors in the non-returned group. As for the personal reason for not coming back, patients mainly answered as follows: lack of a partner (29, 23.2%), the desire for spontaneous motherhood (24, 19.2%), previous spontaneous pregnancies after FP procedures (16, 12.8%), and still ongoing hormonal therapy for breast cancer (13, 10.4%). All patients confirmed their will to keep the storage of their oocytes. The impact of a cancer diagnosis on a woman's maternal desire, sentimental status and life priorities should be studied more thoroughly. Studies investigating hormonal therapy suppression in breast cancer patients seeking pregnancy should be encouraged. https://clinicaltrials.gov, identifier NCT05223764.

Use of gonadotropin-releasing hormone (GnRH) agonist trigger in fertility preservation for patients with inherited genetic disorders.

In patients with varying hematologic disorders (thalassemia, sickle cell anemia, aplastic anemia, etc.), inherited bone marrow failure syndromes, and immune deficiencies due to a single gene disorder, the advent of stem cell transplantation (SCT) as a treatment option has allowed for significant disease improvement, and possibly cure. This specific treatment option often requires exposure to chemotherapeutic agents and sometimes whole body radiation; therefore, primary ovarian insufficiency is often sequelae of the therapy. The optimization of fertility preservation protocols within this patient population is of extreme importance. This review aims to detail the use of GnRH agonist use within this patient population, within the context of fertility preservation cycles.

P-601 Is Medroxiprogesterone acetate (MPA) an adequate alternative to GnRH antagonist in oocyte vitrification for non oncological fertility preservation (FP) and preimplantation genetic test (PGT-A) cycles?

Abstract Study question Can we use MPA as a pituitary inhibitor instead of the GnRH antagonist in ovarian stimulation protocols in non-oncological fertility preservation and PGT-A cycles? Summary answer MPA can act as a substitute of GnRH antagonist for pituitary suppression in FP and PGT-A cycles, since the results are similar between both groups. What is known already Progestin-primed ovarian stimulation (PPOS) protocols using exogenous progesterone to replace GnRH analogs during the follicular phase of OS have emerged as an efficient alternative to prevent LH from peaking and have been used successfully in different types of patients. Fertility preservation (FP) and preimplantation genetic testing (PGT-A) have become new emerging areas of assisted reproduction. FP gives women the ability to have children using their own gametes after age-related fertility decline, while PGT-A appears to improve reproductive outcomes in advanced maternal age at increased risk of aneuploid embryos. However, few data are available for both indications regarding PPOS cycle outcomes. Study design, size, duration Multicenter, retrospective, observational, cohort study conducted in eleven IVIRMA centers attached to private universities. We included a total of 4,961 cycles of non-oncological fertility preservation that were distributed as follows: n = 494 were stimulated under a PPOS protocol while n = 4,467 received a GnRH antagonist. Regarding PGT-A cycles, we analyzed 12,461 treatments, of which n = 686 and n = 11,775 received MPA and GnRH antagonist, respectively. Cycles were performed from January 2017 to December 2021. Participants/materials, setting, methods Patients were divided according to the protocol used for preventing premature luteinization during follicular phase of OS. In the MPA group, participants received 10 mg daily administered orally, while in the control group, women received an antagonist once the main follicle reached 13 mm. In FP cycles, ovarian response specific parameters were evaluated, such as endocrine profile and mature oocytes; in PGT-A treatments, main variables were number of biopsied and aneuploid embryos and reproductive outcomes. Main results and the role of chance Regarding FP's baseline characteristics, age was statistically but not clinically significant between the two groups. Length of ovarian stimulation and total dose of hMG administered were similar in both groups, despite the significantly higher total dose of FSH administered in MPA compared to the GnRH antagonist group (p = 0.008) . Number of mature oocytes retrieved (10.2 [95% CI 9.6-10.8] vs 9 [95% CI 8.8-9.2]) was significantly higher in MPA compared to antagonist group; this trend continued regardless of age (≤ 35 or > 35 years). PGT-A cycles followed the same tendency in terms of demographic characteristics. Length of OS was comparable between groups, whilst the total dose of rFSH and hp-HMG administered in the MPA were significantly higher than that in the GnRH antagonist group. Although the number of MII was comparable and despite the lower number of embryos biopsied in the MPA group (4.5±0.2 vs 4.7±0.06, p = 0.031) the number of aneuploid embryos was similar between the two groups (2.3±0.1 vs 2.4±0.04, p = 0.474), as well as implantation (56% vs. 54% p = 0.359) and clinical pregnancy rate (64.1% vs. 62.1, p = 0.316). The miscarriage rate was significantly lower in the group treated with MPA compared to GnRH antagonists (4.7% vs. 8.2%, p = 0.001). Limitations, reasons for caution The retrospective nature of this study may be a reason for caution and only association, not causation, can be inferred from the results. Despite being the largest sample size ever reported with PPOS in no oncological FP and PGT-A, the number of patients included is still low. Wider implications of the findings The administration of PPOS yielded similar or even better results than those observed with GnRH antagonists in terms of oocytes retrieved, rate of aneuploid embryos or clinical results. Therefore, PPOS could be recommended for ovarian stimulation in non-oncological FP and PGT-A cycles as it allows for a more patient-friendly approach. Trial registration number Not applicable

P-673 GnRH Agonist Early Follicular Challenge Test as a Predictor of Ovarian Response in Short Antagonist Cycles for Fertility Preservation

Abstract Study question Does the response to GnRH agonist can be used to predict ovarian function in short GnRH antagonist cycles in women undergoing oocyte cryopreservation IVF cycles? Summary answer Response to a single GnRH agonist dose at the beginning of stimulation during short antagonist cycle can predict the outcome of the fertility preservation cycle What is known already There is a need for a reliable test for ovarian reserve. Gonadotrophin agonist stimulation test (GAST) is considered a valid marker for ovarian reserve but the test was never validated for short antagonist protocol. The reported dose for this test was 0.1 mg, however, from the vast experience with GnRH agonist triggering, it is now agreed that the optimal dose for GnRH agonist flare effect is 0.2 mg. Study design, size, duration A prospective observational study of fertility preservation cycles patient in an academic hospital setting. Seventy-four Short GnRH antagonist cycles that underwent an oocyte retrieval between 1 December 2020 and 1 January 2022. Participants/materials, setting, methods On day 2, blood was sampled for basal FSH, LH, and E2 measurements, followed by a subcutaneous injection of 0.2mg GnRH agonist as part of the initial ovarian stimulation. Twelve hours later blood sampling was repeated. E2 response was used as test parameter. The major outcome was the number of cryopreserved oocytes. Main results and the role of chance Participants were divided to groups according to Day 3 E2 to Day 2 E2 response (E3/E2 ratio) to lower and upper third percentiles (<3.32, n = 24 and >5.41, n = 25). Age (32.68 vs. 32.79, p = 0.965), total gonadotropin dose injected 3216.67 vs. 2773.42 IU p = 0.16) and day 3 FSH levels (7.39 vs. 7.16, p = 0.768) were not significantly different between groups. Ovarian response as measured by E2 levels on ovulation trigger (7879.72 vs. 17572.54 pmol/ml, p = 0.001) and number of M2 oocytes retrieved were significantly different (17.92 vs. 6.24, p < 0.001). Linear correlation between E3/E2 ratio and number of M2 oocytes was calculated (R = 0.48, p < 0.001). ROC curve analysis of E3/E2 ratio for more than fifteen M2 oocytes indicate AUC value of 0.82 (cutoff value of 4.22, p < 0.001, 84.6% sensitivity, 70.8% specificity) and for less than five M2 oocytes AUC value of 0.84 (cutoff value of 3.34, p < 0.001, 76.3% sensitivity, 73.3% specificity). The results suggest that the testing response to 0.2mg GnRH agonist positively correlates with treatment outcome of the current cycle. Limitations, reasons for caution Although all patients were tested for FSH levels for ovarian reserve, they were not tested for AMH levels. Wider implications of the findings The response to single GnRH agonist dose during short antagonist cycle can be used as another biomarker of ovarian reserve. This simple, widely available marker, which reflect the estradiol response of small follicles, might predict accurately the outcome of the specific cycle, and potentially used to adjust the treatment dose. Trial registration number NCT04973969

P-459 Timing of testosterone discontinuation and assisted reproductive technology in transgender patients

Abstract Study question What is the relationship between the duration of testosterone cessation and assisted reproductive technology outcomes in transgender patients? Summary answer There is no association between the timing of testosterone cessation &number of mature oocytes and the number of total oocytes in transgender patients undergoing ART What is known already Many transgender patients do not undergo fertility treatment, citing the delay or discontinuation of testosterone as the main reason. There has been an increase in the number of referrals to specialist clinics for hormone replacement for gender affirmation. There are variable reported durations in the literature on when to discontinue testosterone before starting the fertility preservation cycle. Presently, no guidelines specify the duration or necessity of testosterone discontinuation. Study design, size, duration This study is a retrospective cohort study of consecutive transgender patients seeking fertility preservation at single academic fertility clinic between October 2019 to June 2021. Patients that identify as transgender that started taking androgens for at least one month were included in the study. Transgender patients that did not start hormone replacement therapy were not included. Participants/materials, setting, methods Primary analyses evaluated whether an association between testosterone discontinuation duration & number of mature oocytes and total #of oocytes, adjusted for AMH & AFC. Secondary analyses included unadjusted analyses to evaluate whether an association between patient age, AMH, AFC, duration on HRT prior to ART, and duration off HRT prior to ART. The primary analysis was a multiple linear regression. Simple regression model was used for secondary analyses. Main results and the role of chance Nineteen patients (mean age 27.9 years [range 19-37], mean BMI 27.1 [20-34], mean AMH 24.8 [6.5-49], mean AFC 23.6 [11-50]) were included in the analysis. No patient underwent gender-affirming (eg: oophorectomy, hysterectomy) surgery. None of the patients were previously pregnant. Mean time on testosterone was 44.4 [1-96] months. Mean time off testosterone was 3.5 [0.6-13] months. All patients underwent egg freezing, except one who had embryo cryopreservation. Simple linear regression showed that maternal age (p = 0.044), AMH (0.028), and AFC (p = 0.0008) were associated with the number of mature oocytes. Duration of time on testosterone (p = 0.319) and duration off testosterone prior to ART (p = 0.628) were not associated with the number of mature oocytes. For the outcome of total oocytes, age (p = 0.047), AMH (p = 0.042), and AFC (p < 0.00001) were significant; duration of time on testosterone (p = 0.414) and duration off testosterone prior to ART (p = 0.471) were not significant. Multiple regression models evaluating duration of time off testosterone prior to ART, adjusted for AFC and AMH, demonstrated no significant association with the outcome of mature oocytes (p = 0.712) and total oocytes (p = 0.564). Limitations, reasons for caution Thistudy is limited by including only 19 patients. The lack of effect of testosterone discontinuation duration and number of mature oocytes and total oocytes may be due to a lack of power. In addition, our study is single-centre, and may only include a small sample of transgender patients. Wider implications of the findings The majority of publications have documented successful ART outcomes in patients who have stopped testosterone for 3-6 months. Our study is critical as it is the first to evaluate whether an association exists between the timing of testosterone duration and ART outcomes. Trial registration number not applicable

P-477 Ovarian stimulation and PGT-A outcomes with random start letrozole protocol for fertility preservation in breast cancer patients

Abstract Study question Data on random start letrozole ovarian stimulation (RSL) in breast cancer patients is scant. We studied RSL outcomes from a single-center with fertility preservation expertise. Summary answer RSL appears to result in high oocyte and embryo/blastocyst yield, with an age-appropriate aneuploidy rate. What is known already With increasing utility of neoadjuvant chemotherapy regimens in breast cancer, young women have limited time to undergo fertility preservation (FP) by oocyte or embryo cryopreservation. Random start stimulation protocols were developed to complete an ovarian stimulation cycle in the shortest time possible before cancer patients started chemotherapy. In addition, letrozole protocols were developed to mitigate the potential risks of high estrogen levels during ovarian stimulation in breast cancer patients. Even though both random start and letrozole supplemented ovarian stimulation have been studied individually, there is limited data on combining both strategies in random start letrozole (RSL) protocols. Study design, size, duration We reviewed our records from 2014 to 2021. We included the first FP cycle of all breast cancer patients undergoing RSL ovarian stimulation for oocyte or embryo cryopreservation. Cancer stages were grouped as 0-4, 0 being ductal carcinoma in situ (DCIS). Twenty-eight cycles met the criteria. Main outcome measures were number of oocytes retrieved and embryos cryopreserved. Secondary outcome measures were fertilization, blastocyst, and euploidy rates for the embryo cryopreservation group. Participants/materials, setting, methods Ovarian stimulation began on cycle days 3-26 with letrozole 5 mg/day initiated simultaneously with rFSH. The rFSH dose was based on age and antral follicle counts (AFC). Oocyte maturation was triggered with leuprolide acetate, rhCG or both 35h prior to retrieval. Main results and the role of chance The mean age was 33.5±4.9 years (range 26-40) and BMI 22.3±2.9(18.4-30.3). The mean breast cancer stage at FP was 1.7±0.9 (0-4), with 42.3% being stage-I disease. 77% of cases were estrogen receptor positive. AMH was 2.7±2.4 (0.16-7.9) and AFC 18.5±8.9(4-42). Ovarian stimulation began on cycle-day 13.7±7.3(2-26). 15(54%) cycles were started in the follicular and 13(46%) in the luteal-phase. The mean total rFSH dose was 3880±1615.4 IU(1275-8325) with a stimulation length of 11.8±2.4 days(8-19). Mean oocytes retrieved were 16.4±6.9(1-36) with a maturity rate of 71.4±17.9%(35.7-94.4). From 13 patients, 10.4±4.7(1-22) oocytes were cryopreserved. Among the 15 patients proceeding to embryo cryopreservation, the fertilization rate was 96.9±6.8%(80-100), resulting in 7.1±4.4(1-15) embryos. 24 embryos were cryopreserved on day-3 and 82 as blastocysts. PGT-A was performed in 72% of the cases, with euploidy rate of 37.7±24.4%(0-63.6). There was no difference in oocyte or embryo yield between follicular and luteal start patients. Likewise, fertilization rates and euploidy rates were similar. The comparative results are summarized in Table 1. To date, two patients conceived utilizing cryopreserved embryos. Both pregnancies resulted in healthy term babies. Limitations, reasons for caution Though our report is one of the largest series of RSL, it can be strengthened with longer follow up that includes pregnancy outcomes in a greater proportion of patients. Wider implications of the findings This is the first detailed report of the RSL protocol utility with PGT-A results in a breast-cancer population. RSL appears to result in high oocyte-yield, fertilization, and blastocyst formation rates, with age-appropriate euploidy. Additionally, the outcomes appear to be similar between patients undergoing follicular and luteal phase start RSL. Trial registration number not applicable

P-476 Why are they not coming back? A single-center follow-up study on oncological women oocyte's storing for fertility preservation

Abstract Study question Which is the return rate and which factors are responsible for the non-return in cancer patients who underwent oocyte cryopreservation for fertility preservation? Summary answer Return rate was 11.7%. Young age at freezing, lack of a partner and type of cancer were the main factors responsible for the non-return. What is known already Improvements in oncological early diagnoses and therapies have significantly increased the survival rates of patients, allowing clinicians to focus on long-term quality-of-life issues, such as access to motherhood. An extensive literature on the importance of fertility preservation (FP) has been produced thanks to the growing number of patients undergoing FP cycles over the years. Nevertheless, the rates of patients returning to use their cryopreserved material have shown to be considerably low, ranging from 5 to 8%. Significant data regarding the reasons that might explain such low return rates are still scarce. Study design, size, duration This is a single-center follow-up retrospective study that includes all women who underwent oocyte cryopreservation cycles for oncological purposes at referral University affiliated center, from January 2001 to December 2017. Participants/materials, setting, methods The database consists of 171 patients, among those 110 (64%) were diagnosed with breast cancer, 45 (26%) hematological cancer, 5 (3%) gynecologic cancer and 11 (7%) other cancers. Data about returned patients were retrieved from internal registries. Non-returned patients were assessed by standardized phone survey on health and marital status, family projects, spontaneous conceptions, and reasons why they had not returned to use their gametes. A univariate analysis between returned and non-returned patients was performed. Main results and the role of chance Among the 171 women who underwent oocyte cryopreservation, 9 (5%) died and 17 (10%) were lost at follow up. In the remaining 145-patient group, the mean age at freezing was 32.2±6.1 and at follow-up 38.2±6.7 years. A total of 20 patients (11.7%) returned to use their frozen material and 125 did not. In the non-returned group, 37 (29.6%) did not have a partner, 10 (8%) had a previous spontaneous conception and 15 (12%) had recurrent malignancy at the time of follow-up. In the univariate analysis, younger age at freezing (31.8±6.2 vs 35.2±4.7; p 0.018), lack of a partner (p 0.002), type of cancer (other than breast cancer; p 0.024) were the significant factors in the non-returned group. As for the personal reason for not coming back, patients mainly answered as follows: lack of a partner (29, 23.2%), desire of spontaneous motherhood (24, 19.2%), previous spontaneous pregnancies after FP procedures (16, 12.8%), and still ongoing hormonal therapy for breast cancer (13, 10.4%). Nonetheless all of them confirmed their will to keep the storage of their oocytes. Limitations, reasons for caution The study population consists of a limited number of patients from a single Italian Fertility Center. Since the Italian law limits ART access to heterosexual couples, this setting may limit any possible adaptation of the study to other countries, with different legislations. Wider implications of the findings The impact of a cancer diagnosis on a woman’s maternal desire, sentimental status and life priorities should be studied more thoroughly. Moreover, it is important to encourage studies investigating so long hormonal therapy suppression in breast cancer patients seeking pregnancy in order to reduce their time to pregnancy. Trial registration number na

Fertility Preservation During the COVID-19 Pandemic: Modified But Uncompromised.

Purpose: Throughout COVID-19, our clinic remained operational for patients requiring urgent fertility preservation (FP). This study aimed to characterize changes to clinical protocols during the first wave of COVID-19 and compare outcomes to historical controls.Methods: We performed a retrospective cohort study at a university fertility center examining all patients who underwent medically indicated FP cycles during the American Society for Reproductive Medicine (ASRM) COVID-19 Task Force-recommended suspension of fertility treatment (March 17–May 11, 2020) and patients from the same time period in 2019. FP care was modified for safety during the first wave of COVID-19 with fewer monitoring visits and infection control measures. FP cycle characteristics and outcomes were compared across years.Results: The volume of cycles was nearly 30% higher in 2020 versus 2019 (27 vs. 19). Diagnoses, age, and anti-Mullerian hormone were similar between cohorts. More patients elected to pursue embryo cryopreservation over oocyte cryopreservation in 2020 versus 2019 (45.8% vs. 5.2%, p < 0.005). Patients managed during COVID-19 had fewer monitoring visits (5 ± 1 vs. 6 ± 1, p = 0.02), and 37.5% of cycles utilized a blind trigger injection. There was no difference in total days of ovarian stimulation (11 ± 1 vs. 11 ± 2, p > 0.05), but 2020 cycles utilized more gonadotropin (4770 ± 1480 vs. 3846 ± 1438, p = 0.04). There was no difference in total oocytes retrieved (19 ± 14 vs. 22 ± 12, p > 0.05) or mature oocytes vitrified (15 ± 12 vs. 17 ± 9, p > 0.05) per cycle.Conclusions: FP continued during COVID-19, and more cycles were completed in 2020 versus 2019. Despite minimized monitoring, outcomes were optimal and equivalent to historical controls, suggesting FP care can be adapted without compromising outcomes.

The effect of follicle flushing during oocyte retrieval on fertility preservation cycle outcomes, retrospective study

Amaç: Kanser hastalarının kemoterapi sonrası yumurtalık rezervlerini kaybetme riski altında olduğu göz önüne alındığında, fertilite prezervasyonu (FP) döngülerinde oosit kalitesini en üst düzeye çıkarmak çok önemlidir. Amacımız, FP için letrozol ve gonadotropinler ile oositleri veya embriyoları korumak için kontrollü yumurtalık stimülasyonu uygulanan kadınlarda elde edilen oosit ve embriyo sayısını maksimize etmede foliküler yıkamanın yararlılığını belirlemekti.&#x0D; Gereç ve Yöntem: Fertilite prezervasonu planlanan meme kanserli olgular retrospektif olarak tarandı. Çift lümenli yıkama yaklaşımı (ÇLY) kullanılarak oositlerin aspire edildiği 11 döngü, oositlerin tek lümenli aspirasyon (TLA) yoluyla alındığı yaş uyumlu 31 döngü ile karşılaştırıldı. 10 mm ve üzerinde ölçüm yapılan tüm foliküller aspire edildi. ÇLY grubunda, foliküller 6 defaya veya oosit elde edilene kadar yıkandı.&#x0D; Bulgular: Ortalama yaş ve anti-müllerian hormon (AMH) değerleri ÇLY ve TLA grupları arasında benzerdi (sırasıyla, yaş:39,8 ± 0,48 / 37,9 ± 0,74; p=0,162; AMH: 1,69 ± 0,37 / 1,47 ± 0,25 ng/mL p=0,635). Pik estradiol seviyeleri ÇLY grubunda anlamlı olarak daha yüksekti (ÇLY / TLA: 1022,66 ± 205,45 / 715,5 ± 33,69 pg/mL, p= 0,026). Toplam gonadotropin dozu ( ÇLY / TLA: 5345 ± 344 / 5017 ± 108 IU, p= 0,236) ve toplam letrozol dozu (ÇLY / TLA: 59,0 ± 2,84 / 57,9 ± 1,08 mg, p=0,633) her iki grupta benzerdi. Tetikleme öncesi ultrasonografide 10 mm üzerindeki folikül sayısı temel alındığında benzer sayıda folikül saptandı (16,2 ± 1,2 / 12,5 ± 1,3; p=0,16). Çift lümenli yıkama yaklaşımı ile daha yüksek toplam oosit sayısı (17,4 ± 2,3 / 10,9 ± 1,2; p=0,015) ve daha yüksek sayıda olgunlaşmamış oosit elde edildi (8,36 ± 1,12 / 3,53± 0,45; p &lt; 0,001). Ancak dondurularak saklanan embriyoların sayısındaki fark istatistiksel anlamlılığa ulaşmadı (7,2 ± 1,94 / 5,2 ± 0,79; p = 0,279).&#x0D; Sonuçlar: Fertilite prezervasyonu döngülerinde ÇLY kullanımı, küçük foliküllerden elde edilen immatür oosit sayısını arttırabilir. Çift lümenli yıkama yaklaşımının nihai embriyo verimini artırmadaki değeri, FP uygulanan kadınlar arasında daha geniş prospektif çalışmalarda araştırılmalıdır.

MORE COVERAGE, MORE CARE: INCREASED FERTILITY PRESERVATION VOLUME BEFORE AND AFTER STATEWIDE INSURANCE MANDATES

As of January 1, 2019, Illinois state law mandates that insurers cover fertility preservation (FP) for patients facing iatrogenic infertility. As of April 2021, 10 states have enacted similar mandates, but only Illinois extended coverage to Medicaid recipients. Few studies have examined the impact of these laws on FP care. Our study aimed to examine FP care at a single large academic medical center in Illinois before and after the enactment of law mandating FP coverage. DESIGN: Retrospective cross-sectional study We analyzed all medically indicated FP consultations and completed cycles performed at our fertility center between January 1, 2017 and December 31, 2020, representing the two years before and after enactment of the insurance mandate. Data were analyzed using Mann-Whitney-U, student’s T test and Fisher’s exact test where indicated (p<0.05). 436 FP consultations were performed, and 282 patients completed 319 cycles at our center over the study period. Minimal change in patient and cycle volume was seen in the first year after the insurance mandate took effect, but there was a sharp increase in consult, patient, and cycle volume in 2020 (Table). More patients with Medicaid insurance were seen after enactment of the mandate (11 vs 28), and more of these completed FP cycles (3 vs 16, p=0.003). Among patients who completed cycles pre- and post-mandate, there was no difference in race or ethnicity (9.3% vs 12.0% identified as Black, and 8.5% vs 9.2% identified as Hispanic or Latinx). Clinical characteristics pre- and post-mandate were similar when comparing age (29.6 vs 29.1, p>0.05) and medical diagnosis, with the most common diagnoses being breast cancer (32% vs 30%, p>0.05) and hematologic malignancies (19% vs 18%, p>0.05). AMH was higher (2.70 vs 3.54, p=0.02) and more oocytes were retrieved per cycle (16±10 vs 20±12, p=0.02) in patients completing FP post-mandate. There was no difference in rates of oocyte cryopreservation and embryo cryopreservation pre- (65%, 36%) and post- mandate (69%, 31%) (p>0.05). Our data from a large academic medical center suggest Illinois legislation may lead to increased FP consultation and cycle volumes and expanded access to FP for publicly insured patients. Further research is needed to examine the how implementation of insurance mandates can maximize access and affordability for patients.

P-479 Are FET and IUI cycles less emotionally difficult for patients than IVF? Evidence from smartphone app based emotional tracking data

Abstract Study question Is the emotional experience different in FET and stimulated IUI cycles compared to IVF cycles? Summary answer Emotional tracking data demonstrated cautious optimism and lower harm emotions in IUI, but FET cycles are associated with higher harm emotions than fresh IVF. What is known already It is sometimes claimed on clinic websites and by advocates for elective freeze all that FET cycles are inherently less stressful. However, little research evaluates the emotional difference between fresh and frozen cycles and the assumed emotional ease of FET may reflect clinician interpretation/bias rather than patient’s lived experiences. Many undertaking FET will have experienced disappointment in a fresh cycle and with increasing cycles comes increased cost. IUI treatment is perceived as less physically and emotionally intense, but studies have shown increased depression levels after a failed IUI cycle and high drop-out. Study design, size, duration Retrospective single-centre analysis of anonymised emotional tracking data entered by 707 patients using MediEmo app alongside IVF, 104 during stimulated IUI and 65 during medicated FET from May 2017-September 2020. MediEmo includes medication timeline/ notifications, coping tools and emotional tracking. Patients rate 2 questions daily in each emotion domain (challenge, threat, harm, e.g. ‘I am feeling tense’) on a 0-3 scale and indicate coping ability (‘I am unable to cope with the stress I’m experiencing’). Participants/materials, setting, methods Egg donor, recipient and fertility preservation cycles were excluded. Mean and standard deviation of scores in each mood domain entered per cycle day were calculated, centred on luteal day 0/ egg collection, from cycle day +/-14. Between group analysis performed using one-way analysis of variance (ANOVA) is presented here. Time series analysis, graphical presentation of emotions by cycle day and analysis of cycles resulting in live birth or return for further treatment will be presented. Main results and the role of chance Analysis of emotional tracking data demonstrated patients experience higher levels of positive challenge emotions (confident/encouraged/hopeful/positive) during FET and IUI cycles than fresh IVF: mean(s.d) score FET 1.64(1.1), IUI 1.74(0.89), IVF 1.48(1.06) (ANOVA p &amp;lt; 0.00001). The difference between FET and IUI challenge levels was not significant (p = 0.07). Threat emotions (worried/nervous/anxious/tense) are significantly lower in FET compared to IVF and IUI cycles: FET mean 0.67(0.91), IUI 0.97(0.90), IVF 0.87(0.91), (ANOVA p &amp;lt; 0.00001). The difference between IVF and IUI threat levels was not significant (p = 0.06). However, the harm emotions (sad/discouraged/disappointed) experienced by patients are significantly higher in FET, mean 0.62(0.89) compared to IVF 0.50(0.81), which are higher than IUI cycles, 0.36(0.68), (ANOVA p &amp;lt; 0.00001). There were no significant differences in numbers recording intolerable stress between the three groups (FET mean scores 0.24(0.66), IUI 0.21(0.58), IVF 0.21(0.59), (ANOVA p = 0.67). As this is retrospective observational data, there are differences between groups in addition to treatment modality, e.g. mean patient ages in the FET and IUI groups were older than those entering data during IVF; FET 34.2(4.09), IUI 33.9(5.2), IVF 32.6(4.47). However, age was not correlated with levels of challenge emotions, suggesting assumptions that patient emotions, e.g. hopefulness, are closely linked to objective prognosis may be flawed. Limitations, reasons for caution Emotional data was only available for those who chose to use MediEmo, entered emotional tracking data and who gave consent for use of data in research. As such, this analysis may not fully reflect all patients’ experiences. However, these limitations apply to all groups and should not prevent useful comparison. Wider implications of the findings Patients have less contact with clinic staff during FET or IUI than fresh IVF cycles. Fertility staff need to ensure availability of support during all treatment cycles and be empathic, particularly for those embarking on FET, who may still be coming to terms with a failed fresh transfer cycle. Trial registration number Not applicable

P–479 Are FET and IUI cycles less emotionally difficult for patients than IVF? Evidence from smartphone app based emotional tracking data

Abstract Study question Is the emotional experience different in FET and stimulated IUI cycles compared to IVF cycles? Summary answer Emotional tracking data demonstrated cautious optimism and lower harm emotions in IUI, but FET cycles are associated with higher harm emotions than fresh IVF. What is known already It is sometimes claimed on clinic websites and by advocates for elective freeze all that FET cycles are inherently less stressful. However, little research evaluates the emotional difference between fresh and frozen cycles and the assumed emotional ease of FET may reflect clinician interpretation/bias rather than patient’s lived experiences. Many undertaking FET will have experienced disappointment in a fresh cycle and with increasing cycles comes increased cost. IUI treatment is perceived as less physically and emotionally intense, but studies have shown increased depression levels after a failed IUI cycle and high drop-out. Study design, size, duration Retrospective single-centre analysis of anonymised emotional tracking data entered by 707 patients using MediEmo app alongside IVF, 104 during stimulated IUI and 65 during medicated FET from May 2017-September 2020. MediEmo includes medication timeline/ notifications, coping tools and emotional tracking. Patients rate 2 questions daily in each emotion domain (challenge, threat, harm, e.g. ‘I am feeling tense’) on a 0–3 scale and indicate coping ability (‘I am unable to cope with the stress I’m experiencing’). Participants/materials, setting, methods Egg donor, recipient and fertility preservation cycles were excluded. Mean and standard deviation of scores in each mood domain entered per cycle day were calculated, centred on luteal day 0/ egg collection, from cycle day +/–14. Between group analysis performed using one-way analysis of variance (ANOVA) is presented here. Time series analysis, graphical presentation of emotions by cycle day and analysis of cycles resulting in live birth or return for further treatment will be presented. Main results and the role of chance Analysis of emotional tracking data demonstrated patients experience higher levels of positive challenge emotions (confident/encouraged/hopeful/positive) during FET and IUI cycles than fresh IVF: mean(s.d) score FET 1.64(1.1), IUI 1.74(0.89), IVF 1.48(1.06) (ANOVA p &amp;lt; 0.00001). The difference between FET and IUI challenge levels was not significant (p = 0.07). Threat emotions (worried/nervous/anxious/tense) are significantly lower in FET compared to IVF and IUI cycles: FET mean 0.67(0.91), IUI 0.97(0.90), IVF 0.87(0.91), (ANOVA p &amp;lt; 0.00001). The difference between IVF and IUI threat levels was not significant (p = 0.06). However, the harm emotions (sad/discouraged/disappointed) experienced by patients are significantly higher in FET, mean 0.62(0.89) compared to IVF 0.50(0.81), which are higher than IUI cycles, 0.36(0.68), (ANOVA p &amp;lt; 0.00001). There were no significant differences in numbers recording intolerable stress between the three groups (FET mean scores 0.24(0.66), IUI 0.21(0.58), IVF 0.21(0.59), (ANOVA p = 0.67). As this is retrospective observational data, there are differences between groups in addition to treatment modality, e.g. mean patient ages in the FET and IUI groups were older than those entering data during IVF; FET 34.2(4.09), IUI 33.9(5.2), IVF 32.6(4.47). However, age was not correlated with levels of challenge emotions, suggesting assumptions that patient emotions, e.g. hopefulness, are closely linked to objective prognosis may be flawed. Limitations, reasons for caution Emotional data was only available for those who chose to use MediEmo, entered emotional tracking data and who gave consent for use of data in research. As such, this analysis may not fully reflect all patients’ experiences. However, these limitations apply to all groups and should not prevent useful comparison. Wider implications of the findings: Patients have less contact with clinic staff during FET or IUI than fresh IVF cycles. Fertility staff need to ensure availability of support during all treatment cycles and be empathic, particularly for those embarking on FET, who may still be coming to terms with a failed fresh transfer cycle. Trial registration number Not applicable

P–308 Fertility preservation in endometriosis: Appraising the factors affecting the ovarian response

Abstract Study question To estimate the factors affecting the ovarian response in women with endometriosis who seek fertility preservation. Summary answer AMH was the most important predictor of ovarian response. What is known already Endometriosis is a chronic disease characterised by the presence of endometrial tissue outside the uterine mucosa. This condition affects up to 10% of reproductive-aged women and up to 50% of women with infertility. Infertility in patients affected with endometriosis has been thought to stem mainly from the inherent effect of implants on the ovarian reserve or by the distortion of the female upper reproductive tract organs in the late stages of the disease. Women diagnosed with endometriosis should be counselled about family planning however, the data available to guide these patients regarding fertility preservation or oocyte freezing is scarce. Study design, size, duration A Retrospective cross-sectional study was conducted from July 2017 to May 2020 at a university-affiliated medical center. Patients who had been treated in the endometriosis clinic and underwent controlled ovarian stimulation and oocyte retrieval for fertility preservation, filled an online questionnaire crossed reference with electronic chart analysis related to patient data and fertility preservation cycles. Participants/materials, setting, methods Eighty-one patients were included and categorized into two groups according to the number of oocytes retrieved: 0–5 (Group A, n = 26) low ovarian response and 6 or more oocytes (Group B, n = 55). Main results and the role of chance The severity and duration of the disease so as the symptoms indicative of deep infiltrating endometriosis, were not associated with reduced numbers of vitrified oocytes. The presence of deep infiltrating implants was not associated with numbers of vitrified oocytes (44.4% vs 70.6%, p = 0.08). More Patients who underwent surgical interventions, had significantly lower ovarian responses compared to women who had no intervention (95.2% vs 61.5%, respectively, p = 0.005). A multivariate logistic regression adjusted for the number of oocyte vitrified revealed that anti-Müllerian hormone (AMH) level below 0.8 ng/ml was the only factor significantly associated with low ovarian response, with an adjusted odds ratio of 13.40 (2.02–157.27, p = 0.015). Limitations, reasons for caution: The size of our cohort is relatively small for the number of covariates, reducing the impact of our results when put on an international scope and the lack of information regarding the return rate of patients who had their oocytes vitrified in the attempt of achieving a pregnancy. Wider implications of the findings: We believe that since the practice of FP for endometriosis is relatively new and there is a substantial lack of data, this cohort represents an important contribution to existing literature by extracting data from medical files and cross-referencing them with existing data for fertility specialists, patient encounters, and hospital registries. Trial registration number Not applicable

O-194 Insights from smartphone app based emotional tracking data on the impact of the Covid-19 pandemic on IVF patients

Study questionIs the emotional experience of patients during IVF different since the start of the global Covid-19 pandemic?Summary answerTracking data since re-opening demonstrated patients lower positive challenge emotions but no significant change in harm, threat, or stress.What is known alreadyCovid-19 caused widespread shutdown of fertility centres, including in the UK, when the HFEA mandated closure from March until May 2020. Research shows clinic closure and an uncertain future were a significant psychological burden for patients anticipating treatment. However, emotional experiences before, during and after closure have not yet been compared, which is the aim of the study.Study design, size, durationRetrospective single-centre analysis of anonymised emotional tracking data entered by 707 patients using the MediEmo smartphone app alongside their IVF cycle, from May 2017-September 2020.MediEmo includes medication timeline/ notifications, coping tools and emotional tracking. Patients rate 2 questions daily in each emotion domain (challenge, threat, harm, e.g. ‘I am feeling tense’) on a 0-3 scale and indicate coping ability (‘I am unable to cope with the stress I am experiencing’) on a binary scale.Participants/materials, setting, methodsEgg donor, recipient and fertility preservation cycles were excluded. First, mood scores were analysed by 2020 month of entry to capture the emotional impact of closure. Second, “Pre-Covid” (May 2017-Feb 2020) and “After Re-opening” (May 2020–Sept 2020) emotional experiences were compared, using student t-tests. Mean and standard deviation of scores in each mood domain entered on each cycle day were calculated, centred on luteal day 0/ egg collection, from cycle day -14 to + 14.Main results and the role of chanceGraphical presentation of emotional data by month clearly demonstrates the significant increase in threat, harm and stress emotions and reduced positive emotions experienced immediately prior to and during mandatory clinic closure. Of patients entering emotional data during closure in March/April 2020, 40% (14/35) stated they felt unable to cope with the stress they were currently experiencing.From May 2020 after the clinic reopened, analysis of in-cycle emotional tracking data showed there are no significant differences in harm or threat emotion levels or numbers reporting intolerable stress during IVF, compared to cycles pre-pandemic (May17-Feb 2020). Patients undertaking IVF cycles since closure are logging lower challenge scores (confident, encouraged, positive, hopeful), demonstrating less optimism, particularly in the ‘two-week wait’ phase of the cycle. The mean (s.d) of challenge scores pre-Covid was 1.50 (1.07), compared to 1.38 (1.04) after re-opening, p = 0.00085.The women who had treatment cycles post re-opening from May 2020 onwards were older (33.4(5.2) vs 32.6(4.4)), which may reflect clinical treatment prioritisation decisions. There was no significant differences in number of eggs collected (mean(s.d) Pre-Covid 12.08 (8.0) vs After re-opening 11.83 (9.4), p = 0.84) or live birth/ ongoing pregnancy rates for undelivered pregnancies (p = 0.69) between the groups.Limitations, reasons for cautionEmotional data was only available for those who chose to use MediEmo, entered emotional tracking data and who gave consent for use of their clinical data in research. As such, this analysis may not fully reflect all patients’ experiences. Most of the available data were entered prior to the pandemic.Wider implications of the findingsFor Covid-19 safety reasons, patients currently have less in-person staff contact when undertaking IVF. The findings reassuringly suggest emotional wellbeing was not markedly different in most domains. However, daily ratings did show the emotional fall-out of clinic closures which for most threatened attainability of parenthood goals (e.g., less hope).Trial registration numberNot applicable

Effects of letrozole or tamoxifen coadministered with a standard stimulation protocol on fertility preservation among breast cancer patients.

To assess the effects of letrozole or tamoxifen coadministration on fertility preservation treatment outcomes. Retrospective cohort study of 118 breast cancer patients undergoing fertility preservation treatment between 2008 and 2018. Patients who received letrozole (n = 36) or tamoxifen (n = 30) were compared to controls (n = 52) who underwent standard ovarian stimulation protocols. The primary outcome measures included the number of retrieved oocytes, mature oocytes (MII), fertilization, and top-quality embryo rates. The secondary outcome measures included duration of stimulation, gonadotropin dose and peak estradiol level. The number of oocytes retrieved, MII oocytes, fertilization rate, duration of stimulation, or gonadotropin dose were similar inthe letrozole and tamoxifen groups, compared to controls. Top-quality embryo rate was lower in the tamoxifen group compared to controls (25% vs 39.4%, respectively, P = 0.034). The abnormal fertilization rate was higher in the letrozole group compared to controls (7.8% vs 3.60%, respectively, P = 0.015). A stepwise logistic regression analysis revealed that letrozole and peak estradiol were significantly associated with abnormal fertilization (OR 11.94; 95% CI 2.35-60.4, P = 0.003 for letrozole and OR 1.075; 95% CI 1.024-1.12, P = 0.004 per 100 unit change in estradiol). There may be a negative effect of letrozole or tamoxifen on fertilization and embryo quality, in fertility preservation cycles. Further studies are needed to confirm these findings.

Is Fertility Preservation Feasible and Safe With Neoadjuvant Therapy for Breast Cancer?

Many women of reproductive age who are newly diagnosed with cancer have not yet started their families, whereas others have not completed their families.1 Previously, the majority of these women would remain childless.2 Although spontaneous pregnancy is sometimes possible after treatment, fertility potential in the majority of these women will decline as a result of the gonadotoxic nature of some of the most effective chemotherapeutic agents, first and foremost alkylating agents.3 The immediate, long-term effect is, almost uniformly, diminished ovarian reserve, and in many cases, premature ovarian insufficiency (characterized by amenorrhea or oligomenorrhea in combination with low estradiol levels and high gonadotropin levels).3-7 With recent advances in assisted reproductive technology (ART), women newly diagnosed with cancer increasingly are pursuing fertility preservation (FP) before chemotherapy or radiation. These patients pursue controlled ovarian stimulation with gonadotropins to produce mature oocytes, which are surgically removed. Subsequently, oocytes can be frozen (through vitrification) if the patient does not have a partner. Alternatively, oocytes may be fertilized with a partner’s sperm and the resulting embryos (usually day 5 or day 6 blastocysts) vitrified. These frozen oocytes or embryos can be thawed and used to affect a pregnancy in cancer survivors after clearance by their oncologists to conceive. Breast cancer is the most common diagnosis among women referred to oncofertility programs8,9 for two reasons. First, breast cancer is the most common cancer in reproductive-age women,10 and second, the gold standard treatment has been surgery followed by chemotherapy, which provides oncofertility specialists a window of opportunity (approximately 6 weeks) between surgery and adjuvant therapy. This interval allows ample time for preparation of the patient, including the scheduling of ovarian stimulation according to the patient’s cycle and, in some instances, even in managing to complete two FP cycles.11,12 Neoadjuvant therapy (NAT) flips the order of treatment, where the oncologist recommends chemotherapy before surgery. Breast cancer treatment is one example of a growing shift from surgery first to NAT.13,14 The National Comprehensive Cancer Network has outlined clinical scenarios in which NAT is the preferred approach.15 Previous studies indicated that NAT candidates referred for FP are more reluctant to undergo FP, and many of them will have a consultation with a fertility specialist but never return.9 Among reasons that have influenced patients’ decisions not to pursue FP are concerns with the cost of the procedure (medications usually are donated) and the fear that FP will delay their cancer treatment. For women diagnosed with breast cancer where NAT is preferred, under what circumstances is a referral for FP appropriate and indicated? Does NAT obligate a shift in priorities? How can we manage to allow as many women as possible to undergo FP without compromising cancer care? We address the medical as well as the emotional aspects of these dilemmas. Although these issues are considered in the context of breast cancer, the most common type of cancer presenting to oncofertility centers, NAT treatment increasingly is used across a wide spectrum of cancer types. As a result, the discussion is relevant to any reproductive-age female diagnosed with cancer when the treatment plan includes NAT.