Undergoing Fertility Preservation Research Articles

Fertility treatment outcomes in transgender men with a history of testosterone therapy

To evaluate fertility treatment outcomes among transgender (TG) men with a history of gender-affirming hormone therapy with exogenous testosterone. Descriptive, retrospective cohort study. Transgender men with a history of gender-affirming hormone therapy with exogenous testosterone underwent fertility treatments, including embryo cryopreservation, invitro fertilization (IVF), co-IVF, oocyte cryopreservation, and intrauterine insemination (IUI), between 2013 and 2021. Gender-affirming hormone therapy with testosterone. Live births (LBs), number of frozen embryos, and number of frozen oocytes. Other outcome measures included total gonadotropin used, peak estradiol levels, oocytes retrieved, oocyte maturity rate, fertilization rate, and embryo grade. A total of 77 TG men self-presented or were referred to care at a single academic fertility center, of which 46 (59.7%) TG men underwent fertility preservation and/or family-building counseling, with 16 (20.8%) patients proceeding to fertility treatment. Of those patients who underwent treatment, 11 (68.8%) had a history of gender-affirming hormone therapy with exogenous testosterone use. Cohort 1 included IVF (n = 1), co-IVF (n = 1), embryo cryopreservation (n = 2), cohort 2 included oocyte cryopreservation (n = 4), and cohort 3 included IUI (n = 3). In cohort 1, both the patients who underwent IVF and the patients who underwent co-IVF achieved LBs. All embryo cryopreservation cycles froze three or more embryos. In cohort 2, the average number of frozen mature oocytes was 19.3 ± 16.2 (range 6-43). All patients who underwent IUI cycles achieved LB. In this study, no correlation existed between patient age, time on or off gender-affirming hormone therapy with exogenous testosterone, total gonadotropin used, and number of oocytes retrieved. All patients who completed IVF or embryo cryopreservation produced high-quality blastocytes, and this is the first study to show successful IUI cycles in patients with a history of gender-affirming hormone therapy with exogenous testosterone. This study demonstrates that TG men who have used gender-affirming hormone therapy previously can successfully undergo fertility treatments to attain oocyte and embryo cryopreservation, pregnancy, and LBs.

Fallo ovárico prematuro en supervivientes a un tumor sólido: puntos clave de manejo

IntroductionPrimary ovarian insufficiency (POI) carries significant morbidity, causing infertility, sexual disfunction, decreased bone density, cardiovascular risk, emotional distress and early mortality. ObjectiveTo know the incidence and current management of POI in childhood/adolescent solid tumour survivors. Material and methodsWe conducted a multicentre observational study. It included female patients aged 12 to 18 years with a diagnosis of solid tumour and meeting clinical or biochemical criteria for POI. The risk was estimated based on the criteria of the Pediatric Initiative Network of the Oncofertility Consortium. ResultsWe found an incidence of 1.5 (30 cases of POI): The median age at the time of the event was 14 years (standard deviation, 2.09). The solid tumours associated most frequently with POI were Ewing sarcoma and brain and germ cell tumours. Eighty-three percent of patients did not undergo fertility preservation. Sixty-three percent reported not having undergone menarche at the time of ovarian failure. Ninety-seven percent were at high risk of gonadal toxicity, yet 47% were not monitored before the diagnosis. The median time elapsed to the occurrence of the event was 43.5 months after diagnosis and 29.5 months after completing treatment. The Kaplan-Meier curves showed that approximately 30% of POI cases developed within 2 years of diagnosis and that women at Tanner stage 1 developed insufficiency later than women at Tanner stage 5. ConclusionsThere is room for improvement in the followup of women at risk of POI in Spain. The tools currently available facilitate risk assessment at the time of treatment planning and allow the implementation of monitoring, education, early diagnosis, fertility preservation, and replacement therapy as needed. All of this would achieve significant improvement in health outcomes.

Serum Anti-Mullerian Hormone Levels Might Indicate Premenopausal Endometrial Lesions.

Endometrial proliferative lesions (EPL) usually refer to endometrial hyperplasia (EH) and endometrial cancer (EC). Among patients with premenopausal EPL who wish to preserve their fertility, only those with EH and early-stage EC have the possibility to undergo fertility preservation therapy. However, there is currently a lack of specific and reliable screening criteria and models for identifying these patients. This study utilized a retrospective diagnostic study design. The training set included medical record information that met the criteria between August 2017 and October 2022, while the validation set consisted of medical record information that met the criteria from November 2022 to May 2023. The endometrial pathological test served as the gold standard. The serum anti-Mullerian hormone (AMH) level before endometrial sampling and a regression model were employed to predict EPL. The study included a total of 1209 patients with PCOS (1119 in the control group and 90 in the endometrial proliferative lesion group) and 5366 women without PCOS (5249 in the control group and 117 in the proliferative lesion group). In the case of PCOS patients aged 20-39 years, the most effective screening threshold for AMH was found to be a serum AMH level of ≤5.39 ng/mL. The model used for this group was logit(p) = -2.562 - 0.430 × AMH + 0.127 × BMI + 1.512 × hypertension + 0.956 × diabetes -1.145 × regular menstruation. On the other hand, for non-PCOS women aged 20-39 years, the optimal screening threshold for AMH was determined to be a serum AMH value of ≤2.18 ng/mL. The model used for this group was logit(p) = -3.778 - 0.823 × AMH + 0.176 × BMI + 2.660 × diabetes -1.527 × regular menstruation -1.117 × dysmenorrhea. It is important to note that all of these findings have successfully passed internal verification. For PCOS and non-PCOS women aged 20-39 years, the serum AMH test and related multiple regression models were obtained for the warning of EPL.

Oocyte cryopreservation with in vitro maturation for fertility preservation in girls at risk for ovarian insufficiency.

To assess the feasibility and outcomes of oocyte cryopreservation with in vitro maturation (IVM) in post-pubertal girls undergoing fertility preservation (FP) for primary ovarian insufficiency (POI) risk. Ovarian stimulation was performed with an antagonist protocol or progesterone priming. Ultrasound monitoring was performed transabdominally. Oocytes were retrieved transvaginally under IV sedation. Immature oocytes were subjected to IVM for up to 36h. All MII oocytes were vitrified. The main outcome measure was the total number of mature oocytes cryopreserved. The secondary outcome was the increase in the mature oocyte yield after IVM. Indications for FP included mosaic Turner syndrome (mTS; n = 10), malignancy (n = 3), and POI risk (n = 2). The mean ± SD age, antral follicle count (AFC), and AMH levels were 14.2 ± 1.4years, 8 ± 5.2 and 1.3 ± 1.3ng/mL. In girls with mTS, the ovarian reserve was low for age (AFC 7.4 ± 4.7 and AMH 1.4 ± 1.6ng/mL). Oocyte cryopreservation was possible in all girls with a range of 1-27 mature oocytes obtained, even in those who were previously exposed to chemotherapy or with low ovarian reserve, and no surgical complications were encountered. After IVM, the median mature oocyte yield increased significantly from 7.5 to 10.5 (p = 0.001). Oocyte cryopreservation appears to be feasible and safe in girls as young as 12years of age at risk for POI The utility of IVM increases the yield of cryopreserved mature oocytes. Prior exposure to chemotherapy or low ovarian reserve should not be an automatic reason to exclude these girls from FP consideration.

Identifying barriers individuals face in accessing fertility care after a gynecologic cancer diagnosis

ObjectiveTo (1) identify the major barriers premenopausal individuals face in accessing fertility care at the time of gynecologic cancer diagnosis and (2) to assess patient experiences pertaining to fertility. MethodsWe distributed an online survey about cancer diagnosis and fertility goals to patients ages 18–40 who had been treated for ovarian, endometrial, or cervical cancer at a single, large academic hospital. Descriptive statistics were used to analyze survey results. Patients who completed the survey were given the option to participate in a follow-up virtual interview. We conducted semi-structured interviews to discuss their fertility goals and barriers to these. Grounded theory was used to qualitatively analyze the interviews. ResultsFifty-five patients completed the survey, and 20 patients participated in the interview. The median age at diagnosis was 32 years old. Seventy-three percent of patients recalled that at the time of their diagnosis they were considering future childbearing, and 32% underwent fertility preservation. Patients reported the emotional response to their diagnosis as a barrier to receiving fertility care, with patients reporting lack of control (80%), shock (55%), and confusion (45%). Patients also identified inadequate counseling (60.0%), lack of time (60.0%), economic constraints (55.0%) and prioritization of cancer treatment (55.0%) as barriers. Nearly all patients had a positive interview experience and expressed desire to help patients in similar situations. ConclusionMany premenopausal patients diagnosed with gynecologic malignancies are considering future childbearing at the time of diagnosis. Both logistical and emotional barriers prevent them from undergoing fertility preservation before initiating oncologic treatment.

Outcomes of random-start letrozole protocol with PGT-A in women with breast cancer undergoing fertility preservation.

One hundred and seventeen who underwent SSCOS and 39 who underwent RSCOS for oocyte and/or embryo cryopreservation before breast cancer chemotherapy were retrospectively evaluated. Mean number of embryos and blastocyst euploidy rates were the main outcome measures. A majority of RSCOS cycles were initiated in the luteal phase (66.6% luteal vs. 33.3% follicular). While the total dose of gonadotropins was significantly higher in the RSCOS (3720.8 ± 1230.0 vs. 2345.1 ± 803.6IU; P < 0.001), the mean number of mature oocytes and embryos was similar to SSCOS. However, there was a trend for a higher number of mean embryos with luteal start RSCOS (6.9 ± 2.7 in late follicular start vs. 9.4 ± 4.2 in luteal start, P = 0.08). PGT-A was performed in 48% of the cases that underwent embryo cryopreservation in RSCOS (12 women, mean age = 35.3 ± 4.1; 87 blastocysts), revealing a euploidy rate of 36.2 ± 22.3% per patient. This rate was comparable to a 45% aneuploidy rate from similarly aged published data. Of the 7 RSCOS patients who returned for frozen embryo transfer, 5 delivered and one has an ongoing pregnancy, while in SSCOS, 18 out of 40 cycles resulted in live birth. Our data suggests that RSCOS fertility preservation cycle outcomes are similar to those with SSCOS and result in age-appropriate euploidy rates.

A Review of Hodgkin Lymphoma in the Era of Checkpoint Inhibitors.

Hodgkin lymphoma (HL) is a hematopoietic malignancy of B-cells that has a bimodal distribution with respect to age and incidence. With the introduction of doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) and radiation combined, the prognosis of HL has significantly improved, with five-year survival rates approaching 95%. While HL has become highly curable, the side effect profiles of ABVD are dire and warrant continuous review. Because HL is often diagnosed in populations in their 20s-30s, patients are forced to undergo fertility preservation procedures as well as deal with other long-term side effects of chemotherapy (including doxorubicin dose-dependent cardiotoxicity and bleomycin-induced lung toxicity). The opportunity cost of the treatment in the short term and vulnerability to treatment-induced malignancies decades later dramatically affect the quality of life of HL patients. New therapies have developed over the past several decades with respect to immunotherapies, particularly programmed death protein 1 inhibitors (e.g., nivolumab and pembrolizumab). Studies have shown checkpoint inhibitors to be effective in treating HL with an objective response rate of 69% for relapsed/refractory classical HL for nivolumab use. Checkpoint inhibitors will continue to help maintain the high five-year survival rate for HL and hopefully have a more favorable side effect profile in the short term, as well as later in the patient's life. This article seeks to summarize treatment options for HL while comparing outcomes and side effect profiles with the addition of checkpoint inhibitors.

P-411 Cumulative live-birth rate after oocyte vitrification for fertility preservation (FP) in oncologic or benign conditions: a retrospective comparative monocentric study

Abstract Study question Does cumulative livebirth-rate (CLBR) after reutilization of vitrified oocytes differ between patients having undergone fertility preservation (FP) for oncologic (onco-FP) reason or benign conditions (benign-FP)? Summary answer Although CLBR per woman was lower in the onco-FP group, there was no statistically significant association in multivariate analysis between onco-FP and CLBR. What is known already Recent ESHRE guidelines reported oocyte vitrification after controlled ovarian hyperstimulation (COH) as an established option for FP. Although age at the time of oocyte vitrification remains the main predictive factor of success, several lines of evidence suggest that the use of COH or in vitro maturation (IVM), as well as the indication of FP, in particular the type of disease, may influence outcomes after devitrification. The present investigation aimed at clarifying this issue. Study design, size, duration Observational comparative, monocentric retrospective study including all patients having reused, between January 2014 and December 2021, their oocytes vitrified for oncologic or benign conditions between 2013 and 2021. Women having undergone FP for non-medical indication were excluded. Participants/materials, setting, methods Among the 2201 patients having vitrified their oocytes, 94 (4.7%) returned for reutilization. The primary objective was the comparison of CLBR between onco-FP (n = 48) and benign-FP (n = 46) groups. A logistic model was performed. Factors associated with the CLBR in univariate analysis were included in a multivariate model. A secondary analysis was performed, comparing the benign-FP group and 2 groups of onco-FP according to the use of COH (Onco-COH, n = 25) or in-vitro maturation (Onco-IVM, n = 23). Main results and the role of chance Overall, in comparison with benign FP, women with malignant diseases were younger (median [IQR]: 34.0 y [31.0;37.0] vs. 36.5 y [33.2;38.0], p = 0.04) and had fewer oocytes vitrified (median [IQR]: 6.0 [3.0;9.2] vs.15.5 [6.2;18.0]), p &amp;lt; 0.001). The CLBR in onco-FP and benign-FP groups were 14.6% (7/48), and 32.6% (15/46), respectively. In univariate analysis, the CLBR was significantly lower in the onco-FP group when compared with the benign-FP group: (OR [95%CI]: 0.35 [0.12;0.94], p = 0.04). However, this difference in the CLBR did not reach significance after multivariate analysis (OR [95%CI]: 0.38 [0.09;1.51], p = 0.18). As expected, age at the time of oocyte vitrification was negatively associated with CLBR (OR [95%CI]: 0.80 [0.67;0.92], p = 0.005), while the number of oocytes inseminated was positively related to CLBR (OR [95%CI]: 1.22 [1.08;1.40], p = 0.002). Unlike onco-COH, onco-IVM was associated with a significant decrease in CLBR when compared to benign-FP (only COH), in univariate analysis: 8.7% (OR [95%CI]: 0.20 [0.03;0.80], p = 0.04), without significance after multivariate analysis (OR [95%CI]: 0.37 [0.04;2.16], p = 0.29).The livebirth rate (LBR) per oocyte was 2.1% in the onco-IVM subgroup (3 babies for 141 oocytes thawed), 2.7% in the onco-COH subgroup (7 babies for 260 oocytes thawed) and 3.7% (18 babies for 479 oocytes thawed) in the benign-FP group. Limitations, reasons for caution The small size of our population was probably responsible for a lack of statistical power. The retrospective and monocentric nature of our study may also be a weakness. Furthermore, LBR per oocyte was analyzed without age-adjustment. Wider implications of the findings This study provides actual data on chances of achieving a livebirth after oocyte vitrification, according to the use of a COH or IVM and the context of FP, oncologic or benign conditions. Trial registration number not applicable

O-276 Fertility preservation and sperm quality in adolescent transgender patients prior to hormonal treatment

Abstract Study question This study investigated the take-up, hormonal profile and sperm quality in adolescents undergoing fertility preservation via different methods, prior to medical intervention for gender dysphoria. Summary answer Fertility preservation via surgical sperm retrieval (SSR) or masturbation, is possible in this group, however long-term data is required to check gamete health. What is known already As increasing numbers of adolescents with gender dysphoria (GD) start gonadotrophin-releasing hormone agonists (GnRHa) to delay puberty to minimise psychological distress. However, the uncertainty of the long-term effects of these medications highlights the importance of undergoing fertility preservation (FP) prior to starting any hormone treatment. Study design, size, duration Data for adolescents wanting to FP was prospectively maintained. A total of 122 patients were referred for FP, of which 23 declined (19%). Participants/materials, setting, methods Young people were counselled for FP and serum testosterone, FSH, and LH were recorded prior to providing semen samples. Semen samples were classified by concentration; normal &amp;gt;15mil/ml, oligospermia &amp;lt;15mil/ml, poor &amp;lt;1sperm/slide, azoospermia. Insufficient samples, or unwillingness to masturbate, meant SSR was offered in a stepwise manner using electroejaculation (EE), TESE and mTESE. Main results and the role of chance Most patients (n = 78, 64% - median age 16.7) were able to produce semen by masturbation, cryopreserving an average of 6.6 straws. Sperm concentration was normal in 44% of samples produced, 36% were oligozoospermic, 9% were poor sperm concentration, and 12% were azoospermic. Mean blood results showed: testosterone 12.32nmol/l, FSH 3.83 IU/L, LH 4.39 IU/L. 21 patients required SSR - median age of 14.9. EE was successful in 4 patients, 9 underwent TESE, and 8 underwent mTESE. 4 mTESE patients were azoospermic. Success rate was 77%, with an average of 5.5 vials stored. Semen parameters in this cohort were poor - however possibly adequate for ICSI. Hormone levels were similar to the masturbation cohort: mean testosterone 11.7nmol/l, FSH 3.4 IU/L, LH 3.5 IU/L. 3 patients used GnRHa pre-SSR. Following a washout period, 1 patient remained azoospermic despite a testosterone of 21 nmol/l. The other 2 patients had sperm found with abnormal morphology and motility. This is the largest UK cohort of transgender girls referred for FP. The results showed that semen parameters were abnormal in 67% of the masturbation samples produced, and within the SSR group, all patient’s testosterone levels were &amp;gt;8nmol/l, with an average of 5.5 vials saved. Limitations, reasons for caution The quantity of long-term data on whether adolescents end up using their gametes post FP is a factor to consider with this study, as more evidence is needed in order to display the actual long-term usage of gamete cryopreservation. Wider implications of the findings Masturbation is often possible in this group, but alternatively, SSR provides patients with a safe opportunity to potentially have their own biological children in the future. Trial registration number not applicable

P-581 Family of origin cohesion and intention to pursue fertility preservation in transgender and non-binary people

Abstract Study question Is the relationship with the family of origins associated with parenthood plans and fertility preservation of transgender and non-binary people? Summary answer Family of origin characteristics, namely family cohesion, is associated with the transgender and non-binary people intention to undergo fertility preservation. What is known already Few studies have explored parenting intentions and decision to undergo fertility preservation (FP) in transgender and non-binary people. Most studies have focused on the barriers and facilitators of this decision, focusing on the procedures involved in FP, but no studies have assessed the role or psychological (namely relational) variables in the decision making regarding FP. Previous research indicates that family closeness is an important factor in the psychological adjustment of transgender people. Similarly, research indicates that more favorable family relationships were associated with parenting intentions. No studies have examined how relationship with family of origin may affect fertility preservation intentions. Study design, size, duration This is a cross-sectional study. Participants were surveyed online from January to April 2022. Dissemination of the study was performed through the social networks of LGBTQIA+ associations. Participants/materials, setting, methods Participants were 69 transgender and non-binary people, aged 18-39. The assessment protocol included a questionnaire assessing childbearing intentions, importance of genetic and non-genetic parental connectedness and intention to pursue FP. A validated measure assessing family relationships (Fertility Environment scale, Moos &amp; Moos, 1976) was used, evaluating family cohesion (degree of commitment and support family members provide for one another) and family expression (the extent to which family members are encouraged to express their feelings directly). Main results and the role of chance Participants were 40 transgender men (58%), 8 transgender women (11,6%) and 21 non binary (30.4). About 55,1% participants had already initiated hormonal therapy. Almost half of the sample (47,8%) considered having children in the future, while 13 (18.8%) were sure about not wanting children. Genetic connection was not very important (M = 19.51, from 0 -100). A total of 48,1% indicated that that would envision undergo FP in the future. A mediational model examining indirect effects were tested to examine whether family of origin relationship (cohesion and expression) would be associated with fertility preservation intention. A significant indirect effect was found, suggesting that family cohesion is associated with the intention to undergo fertility preservation through the effect on the importance of genetic parenting (estimate: 0.56, bootstrap bias-corrected 95% confidence interval 0.052; 1.199) That is, participants with high family cohesion in their family of origin highly valued genetic parenting and this was positively associated with the intention to undergo fertility preservation. The same indirect effects was tested regarding family expression, but no significant effects were found, that is, the expression of the family of origin is not associated with the intention to undergo PF (estimate: 0.604, bootstrap bias-corrected 95% confidence interval -0.077; 1.366). Limitations, reasons for caution The dissemination of the study and participants recruitment was throughout LGBT+ associations, so it is possible that some transgender people that are less prone to be involved in these associations were not reached. Wider implications of the findings The importance of the relationships with the family of origin may be an important factor to consider when counselling transgender and non-binary people regarding fertility preservation This may be markedly important when lower family cohesion may be limiting patients’ future options. Trial registration number Not applicable

P-404 Sexual function, psychological distress, and remaining fertility in female cancer survivors

Abstract Study question How many women after fertility preservation and gonadotoxic treatment suffer from sexual dysfunction und psychological distress? Summary answer Sexual dysfunction was detected in 60.4% of 53 patients with no increased presence of psychological distress compared to the general population. What is known already Gonadotoxic treatment in female cancer patients can lead to reversible or permanent impaired fertility. The risk depends on the agent, number of cycles and age of the women. Different methods of fertility preservation are offered, including cryopreservation of (non-) fertilized oocytes, cryopreservation of ovarian tissue, and GnRH analogues. Improved survivorship leads to new challenging issues such as comorbidities resulting from the cancer treatment itself, secondary malignancy, and potential impairment of quality of life, sexual function, and fertility. Study design, size, duration This prospective single center study was conducted at the Department of Gynecological Endocrinology and Reproductive Medicine, Medical University of Innsbruck, Innsbruck, Austria between June 2021 and November 2021. The department holds the biggest cryobank of ovarian tissue in Austria, offering the procedure since 2007. Participants/materials, setting, methods In this prospective study, 202 female cancer survivors who underwent fertility preservation methods at time of cancer diagnosis between 2010 and 2020 were invited to a gynecological exam, laboratory assessment and two questionnaires (Female Sexual Function Index (FSFI) and Hospital anxiety and depression scale (HADS)) in 2022. FSFI and HADS scores were compared depending on Anti-Mullerian-hormone (AMH) levels, current desire to have a child, and age. Main results and the role of chance At time of cancer diagnosis, these patients underwent at least one of the following fertility preservation methods: cryopreservation of (non-) fertilized oocytes (n = 27 [48%]), cryopreservation of ovarian tissue (n = 38 [68%]), GnRH analogues (n = 53 [95%]). After a mean follow up time of 70 +/-50 months, sexual dysfunction was detected in 60.4% of the 53 patients. Normal results regarding HADS-D/Anxiety and HADS-D/Depression were found in 88.7% and 94.3% of patients, respectively. At time of follow up, 69.9% of patients regained regular menstrual cycles, 53% of patients &amp;lt;40 years showed a diminished ovarian reserve with AMH levels &amp;lt; 1.1ng/ml. and 15 patients (28.3 %) suffered from infertility. 14 (25%) women already fulfilled their desire to have children, whereas 16 (30%) women expressed the desire to have children at time of follow up. Out of 9 women, who conceived after gonadotoxic treatment, four used cryopreserved oocytes and one underwent ovarian tissue transplantation. Limitations, reasons for caution A possible limitation is the small sample size and varying follow up intervals. Wider implications of the findings Female cancer survivors are at highly increased risk for SD. Cancer patient should be informed about possible sexual dysfunction already at the start of cancer treatment and during follow up. Trial registration number 1471/2020

P-399 Oocyte vitrification does not impair clinical outcomes in women of advanced maternal age. An analysis of 1268 cycles using fresh and vitrified oocytes

Abstract Study question Does oocyte vitrification impair clinical outcomes in women of advanced maternal age (AMA, &amp;gt;35 years old)? Summary answer Up to the age of 39 years, clinical outcomes were comparable amongst cycles using fresh and vitrified oocytes. What is known already Primarily recommended for young women, oocyte vitrification is the most efficient method for elective fertility preservation. Nevertheless, various social and economic circumstances often compel women to undergo fertility preservation when already at an AMA. Recent studies in mouse suggest that AMA increases the vulnerability of oocytes to molecular and subcellular damage during vitrification, ultimately compromising embryo viability and implantation potential. However, the effects of oocyte vitrification on human preimplantation development and clinical outcomes in women of AMA currently remain unknown. Study design, size, duration This is a retrospective cohort single-center study. We compared outcomes of 1268 patients undergoing their first fresh ICSI cycle using autologous fresh (n = 1087) or vitrified oocytes (n = 181), performed between January 2019 and October 2022. All vitrified oocytes were obtained following elective fertility preservation for age-related fertility decline. Outcomes were stratified according to maternal age at oocyte pick-up: control group (≤35) and AMA groups (36-37, 38-39 and ≥40 years). Participants/materials, setting, methods We compared outcomes between fresh and vitrified oocytes across matching maternal age groups. These included fertilization rates, proportion of viable embryos on day 3, clinical pregnancy and live birth rates. Univariate and multivariate analyses (2-contrast linear and logistic regression) were used to establish correlations. Analyses were adjusting for sperm origin (partner or donor), day of transfer (3 or 5), number of embryos transferred and endometrial age. All p values &amp;lt;0.05 were considered significant. Main results and the role of chance Sperm donation and homologous cycles were equally distributed among the study groups (45% sperm donor and 55% male partner across the entire cohort). In our cohort, blastocyst transfer was performed less frequently in older women, 23.8% for women ≥40 years compared to 45.6% for women ≤35 years (p &amp;lt; 0.0001). When comparing oocyte status across matching maternal age groups, fertilization rates were ∼10% lower when vitrified oocytes were used (p &amp;lt; 0.05). Our adjusted analysis confirmed this negative impact of oocyte vitrification on fertilization rates. Oocyte vitrification also affected ongoing cleavage, as the proportion of viable embryos on day 3 was significantly lower across all groups when vitrified oocytes were used (p &amp;lt; 0.05). Nevertheless, this effect did not translate to clinical pregnancy rates, which were comparable across all maternal age groups regardless of oocyte status. As expected, live birth rate decreased steadily with advancing maternal age (from 38.5% in women ≤35 to 15.0% in women ≥40). While our adjusted analysis showed a negative effect of oocyte vitrification on live birth rates for patients ≥40 (OR: 0.60, 95%CI: 0.18-2.06), we observed no such effect in AMA patients ≤39 years. Limitations, reasons for caution The main limitation of this study is its retrospective design. The low number of women ≥40 undergoing fertility presentation (n = 39) warrants careful interpretation. Our results cannot be generalized to all patient populations and indications for fertility preservation. Wider implications of the findings Clinical outcomes were comparable between fresh and vitrified oocytes up to the age of 39 years. While oocyte vitrification before 35 years old remains the most established and effective method for preventing age-related fertility decline, our findings offer a valuable clinical resource for counselling AMA patients considering elective fertility preservation. Trial registration number Not applicable

P-413 Lessons learnt from a long-term fertility cryopreservation program regarding usage-rate of vitrified oocytes and embryos

Abstract Study question Does woman's age during cryopreservation affect usage-rate of the vitrified oocytes and embryos from fertility preservation cycles? Summary answer The usage-rate of vitrified oocytes and embryos from cryopreservation cycles is low. Sub-analysis shows a higher usage-rate with advanced age and increased storage time. What is known already previous studies show a 3-9% usage-rate in social oocyte freezing fertility preservation cycles. Studies show that social preservation of oocytes before the age of 39 is not cost effective. To the best of our knowledge, data is scarce regarding the vitrified oocyte and embryo usage-rate according to the woman's age during both social and medical fertility preservation cycles. Study design, size, duration A retrospective case series study including all fertility preservation cycles at our IVF unit between Dec 2010 and Jan 2023. During a period of 12 years, 558 cycles in 358 women without a known fertility problem were performed. Vitrification was performed in 535 cycles. A total of 3605 oocytes and 382 embryos were cryopreserved for social and medical reasons (272 and 286 cycles respectively). Participants/materials, setting, methods The treatment cycles were divided into 3 groups according to the time-period of cryopreservation, reflecting the length of storage. Group 1: 2010-2016 (54 cycles), Group 2: 2017-2020 (132 cycles), and Group 3: 2021-2023 (349 cycles). We analyzed usage-rate in each time group according to their age at freezing, 17-35 (334 cycles) or 36-44 (201 cycles) Main results and the role of chance Average age was 34±5 years (17-44). Overall, 30 women (30/358=8%) thawed their oocytes or embryos cryopreserved in 37 cycles (37/535=7%) of them 16 for social and 21 for medical reasons. In all three time-period groups there was a clear trend of increased usage among older women at cryopreservation (36-44y) compared to younger women (17-35y) : Group 1 [43%(9/21) vs 24%(8/33)], Group 2 [9%(6/64) vs 3%(2/68)] and Group 3 [8%(9/120) vs 1%(3/229)]; respectively. As shown, usage-rates also increased in accordance to length of storage. For thawed embryos positive β-hCG rate was higher for the 17-35 age group compared with 36-44 age groups [53% (10/19) vs 19% (3/16)] and Clinical pregnancy were [37% (7/19) vs 19% (3/16); respectively. For oocyte thawing usage-rates were extremely low; only one woman thawed her oocytes in the young age group and was pregnant and 6 women in the older age group thawed their oocytes and 2 were pregnant. Seven women transferred their frozen oocytes to another fertility center and the outcome is unknown. Overall usage-rate of vitrified oocytes and embryos from fertility preservation cycles is low. Sub analysis shows a higher usage-rate in correlation with women's age at time of cryopreservation and length of storage. Limitations, reasons for caution This is a single center retrospective study. Wider implications of the findings Cost effectiveness and success rates should be discussed with women undergoing fertility preservation cycles. Cost benefit should take into account the low usage rate, length of storage and the clinical pregnancy rates reported from oocyte and embryo thawing according to women's age. Trial registration number 0029-23-CMC

P-417 Biovular follicles are commonly found in prepubertal but not adult ovaries

Abstract Study question Is the morphology of ovarian tissue from paediatric and adolescent girls similar to that from adults? Summary answer The presence of biovular follicles was more frequently observed in paediatric ovary than in the adult ovary. What is known already At birth there are approximately 1 million ovarian follicles that reduce to around 380,000 by puberty. Limited information is available on the morphology of paediatric and adolescent ovary but it is thought that, before the age of 6 years, the prepubertal ovary contains around 20% abnormal primordial follicles - more than in the adult ovary. Polyovular follicles are common in some animal species but rarely observed in the human adult ovary. They are thought to contribute to dizygotic twinning but the low frequency suggests they are not the sole origin. Study design, size, duration Haematoxylin and eosin stained sections of ovarian tissue were examined by 2 operators blinded to patient age. Follicles were classified according to modified Gougeon criteria. The proportions were compared with Fisher’s exact test and the frequency by one- way ANOVA. Participants/materials, setting, methods Ovarian cortex tissue was collected from a total of 71 children and adolescents and 85 adults undergoing fertility preservation. Those who had had previous chemotherapy and or pelvic irradiation were excluded. The population was divided into 30 children (&amp;lt;8 years, range 1 - 7.6 years), 25 peripubertal (8 - 14.1 years), 16 with confirmed pubertal status (13.7 - 16.6 years) and compared to 85 adults (18-36 years). Main results and the role of chance Biovular follicles were observed in 36.7% (11/30) of the ovarian tissue from children &amp;lt;8 years with, where present, an average frequency of 1/10.6 x103 follicles, in 28% (7/25) of the peripubertal girls with an average frequency of 1/11.9x103 follicles, and 18.7% (3/16) of the post pubertal girls with an average frequency of 1/7.7x103 follicles. In contrast, biovular follicles were rarely seen in the adult ovarian tissue examined (3.5%, 3/85) with an average frequency of 1/25x103 follicles. The observed frequency in all of the younger samples was significantly different to the adult (p &amp;lt; 0.001 &amp;lt;8 years, p &amp;lt; 0.001 peripubertal, p &amp;lt; 0.05 post pubertal) but not between the young age groups. In those samples with biovular follicles the frequency was not significantly different between any of the groups. An antral follicle was observed in only one case &amp;lt;8 years of age (1.4 years) - 3.3%, in 2 in the peripubertal (8%), in 4 of the post pubertal (25%) and in 9 of the adult ovarian cases (10.6%). The higher observed frequency in the post pubertal ovary compared to the &amp;lt;8 year was significantly different (p &amp;lt; 0.05). Limitations, reasons for caution Only a small sample of the ovary cortex was examined for each individual, which may be more representative of the young ovary than the adult. It is not possible to predict potential function from this analysis. Wider implications of the findings Although follicle numbers in the paediatric ovary are high, follicles with structural anomalies such as biovular follicles are also more frequently observed in the paediatric ovary than in the adult. It appears that the changes at puberty may cause the loss of these abnormal follicles. Trial registration number Not Applicable

O-057 Prevalence of T-shaped uterus among women undergoing fertility treatments based on ESHRE/ESGE and Congenital Uterine Malformation by Experts (CUME) criteria.

Abstract Study question What is the prevalence of a T-shaped uterus among women undergoing fertility treatments based on ESHRE/ESGE (Grimbizis et al.,2013) and CUME (Ludwin et al.,2020)? Summary answer The prevalence of T-shaped uterus was 4.1% according to the ESHRE/ESGE, and according to the CUME, 1.1% T-shaped uterus and 0.9% borderline T-shaped uterus. What is known already The definition of a T-shaped uterus by the ESHRE/ESGE consensus (Grimbizis et al., 2013) was based on three-dimensional ultrasound (3D-US) images, defining it as a narrow uterine cavity caused by thickened lateral walls with a ratio of two-thirds uterine body and one-third cervix. This definition is subjective and therefore makes giving an objective diagnosis difficult. The CUME group (Ludwin et al., 2020) described practical diagnostic criteria for a T-shaped uterus according to 3D-US images. As there is no consensus regarding the definition, the overall prevalence according to different studies varied from 0.2 to 10.0%. Study design, size, duration A retrospective cohort study with prospective analysis of 3D-US images was conducted. All women who were admitted to our unit for fertility treatments and underwent 3D-US between 12/2017-12/2021 were included. Women were grouped according to infertility type. All 3D-US images of uteri suspected to be T-shaped according to ESHRE/ESGE were assessed according to the CUME criteria, based on the following three measurements: lateral indentation angle ≤130°, lateral indentation depth ≥7 mm, and T-angle ≤40°. Participants/materials, setting, methods The study was conducted in a single university-affiliated hospital. Women who underwent fertility treatments due to various indications were included. The exclusion criteria were women undergoing fertility preservation, egg donation and oocyte recipients. All 3D-US were performed by well-trained ultrasound technicians. We first screened all images and calculated the prevalence of T-shaped uteri in our population based on the ESHRE/ESGE consensus. Next, we performed the three measurements according to the CUME criteria. Main results and the role of chance Altogether 451 women were admitted to our fertility unit. Nine cases were excluded due to unsatisfactory 3D-US images because of technical difficulties. Finally, 442 women were included in the study and divided into in the following groups: anovulation 10.6% (n = 47), mechanical factor 11.1% (n = 49), male factor 38.7% (n = 171), and unexplained infertility 39.6% (n = 175). The prevalence of T-shaped uterus according to the ESHRE/ESGE was 4.1% (n = 18). Among them, 3.2% (n = 3) were from the female factor groups (anovulation + mechanical), 4.1% (n = 7) from the male factor group, and 4.6% (n = 8) from the unexplained infertility group. Afterwards, the 3D-US images were analyzed according to the CUME criteria. T-shaped uterus was defined when all three criteria were met, and borderline T-shaped uterus was defined when two out of three criteria were met. According to CUME criteria, the prevalence of T-shaped uterus was only 1.1% (n = 5), three being from the male factor group and two from the unexplained infertility group. No T-shaped uteri were found in the female factor groups. Additionally, 0.9% (n = 4) were considered borderline T-shaped. Limitations, reasons for caution The ESHRE/ESGE consensus is subjective and may lead to either under- or over-diagnosis. On the other hand, the CUME criteria are objective and well-defined, but due to their strictness, dysmorphic uteri with very narrow uterine cavities and thickened lateral walls may not be diagnosed as T-shaped uteri. Wider implications of the findings Diagnosis and management of women with T-shaped uteri are very controversial topics. Therefore, making the diagnosis more precise and objective can help us to screen for the most significant cases and tailor the management accordingly. The similar prevalence among different infertility groups reflects the incidental nature of this diagnosis. Trial registration number Not applicable.

P-670 Altered immunological conditions in women with PCOS and its correlation with the development and progression in infertile women with severe polycystic ovaries

Abstract Study question What is the impact of the dysfunctional lymphoid cells on the development and progression in infertile women with severe polycystic ovaries syndrome (SPCOS). Summary answer The dysfunctional lymphoid cells in immune system was deeply correlated with follicular remodeling, which prompting the progression of SPCOS. What is known already PCOS has been confirmed as a low-level chronic inflammation impacting on ovulation and luteinization regulated by a cytokine-mediated inflammatory response orchestrated by lymphocytes, granulocytes, and macrophages. However, the exact relationship between immunologic dysfunction and the pathogenesis of PCOS is still not clarified. Study design, size, duration A prospective cohort study including a total of 129 women aged 18 to 35 years were enrolled. PCOS patients with polycystic ovaries (ultrasound measurement of the number of ≥ 80 follicles ≥3 mm in diameter) were referred to SPCOS in this study. Peripheral Blood (PB) were collected to detect the immunological changes by using flow cytometry: CD8+ T cell (CD3+,CD8+); CD4+ T cell (CD3+,CD4+); NK cell (CD45+,CD3-,CD56+); NKT cell (CD45+,CD3+,CD56+); Treg cell (CD4+CD25hi); B cell (CD3-CD19+). Participants/materials, setting, methods PB from SPCOS cohort (n = 64) and healthy controls (n = 115) were collected to detect the immunological conditions. Furthermore, the discarded tissues from SPCOS patients (n = 5) who needed to avoid OHSS by surgical ovarian wedge resection and women undergoing fertility preservation procedures (n = 3) were digested to single cell suspension, which were used to outline the ovarian homeostasis changes by using scRNA-seq. Main results and the role of chance Peripheral blood NK cells from SPCOS patients were significantly decreased than those from healthy group (10.7% vs. 14.9 ± 6.2%, p = 0.04). Conversely, NKT cells in the PB of the SPCOS women were 11.2% vs. 6.9 ± 3.5% (P = 0.02), while B lymphocytes were 15.6% vs. 12.6 ± 4.2% (P = 0.04), compared to healthy controls. Furthermore, the immune cells and distinct cellular clusters of SPCO were disturbed in severe polycystic ovaries. The CD8+ T cell populations in ovarian of SPCOS group were strongly decreased (32.49% vs.22.35%, p &amp;lt; 0.001) and T cell activation signaling was downregulated by lowly expressed PTPRC, APBB1IP, LCP11 and MX12. Besides, the cytotoxicity-associated genes IFNG and TNF were highly expressed, especially in CD4+ T cells. The chemokines released by activated CD4+ T cells may increase the production and recruitment of CD8+ T cell and induce the compositional and functional alteration of ovarian, thereby prompting the progression of PCOS. Limitations, reasons for caution The study group is limited and transcriptome analysis covers much, but not enough. Although suggestive associations between immunological conditions and the severity of PCOS have concluded, additional animal models studies should be conducted to confirm our findings further. Wider implications of the findings The expression profiles of lymphoid cells provide deep insight into the molecular mechanisms of PCOS. Signaling receptors and gene data set will aid in future studies on the interorgan communication. It also facilitated discovery of novel biomarker for PCOS diagnosis and new immunological treatment. Trial registration number Not applicable

P-738 Attitude of BRCA1/2 mutation carriers towards fertility preservation, family planning and preimplantation genetic testing (PGT) for the next-generation primary prevention of breast and ovarian cancer

Abstract Study question What is BRCA1/2 mutation carriers' attitude toward preimplantation genetic testing (PGT) in attempt to prevent their offspring burden that comes with a known mutation status? Summary answer Less than ten percent of BRCA1/2 mutation carriers chose to perform PGT to avoid the birth of a child who is also a carrier. What is known already BRCA1/2 mutation carriers encounter many dilemmas during their life such as whether to undergo fertility preservation, when and how to plan their family, when to undergo risk reduction surgeries and whether to perform PGT for the selection of non-carrier embryos. Awareness and attitudes toward PGT are different across countries and has been shown to be associated with the degree of suffering from the knowledge of being a carrier, from personal or familial BRCA1/2 associated breast and ovarian cancer. Study design, size, duration This cross-sectional study was conducted by the distribution of an anonymous questionnaire in BRCA1/2 carriers social media platforms and clinics from August 2022 to January 2023. Participants/materials, setting, methods Female respondents of the questionnaire with a positive germline BRCA1/2 mutation at any age or marital status. Main results and the role of chance The questionnaire was completed by 494 BRCA1/2 mutation carriers. The median age of responders was 43 years old (range 22-79), 90% of them Ashkenazi (full or partial) Jewish ethnicy. 63% of patients were carriers of the BRCA1 mutation, while 37% were carriers of the BRCA2 mutation. 76% of patients became aware of their mutation status following a family history of malignancy. 35% of responders did not have children at the time of mutation discovery. 15% of patients had a fertility issue regardless of their BRCA mutation status. Following mutation discovery, 38% of responders changed their family planning, mostly choosing to have children earlier in life or to have less children than planned. 28% of BRCA carriers have been discussed about their option for fertility preservation and 11% underwent the oocyte or embryo vitrification. 45% of BRCA carriers admitted they have discussed the option of PGT and only 8% underwent the in vitro fertilization and preimplantation genetic testing to select non- carrier embryos. 14% of responders were firmly against the option of PGT. The need for fertility treatment regardless of the mutation status did not significantly change the PGT performance rates (p = 0.09). Limitations, reasons for caution This study’s limitations mostly stem from online distribution of the questionnaire. Responders' bias may cause an overestimation of treatment rates as responders may be those who encounter their physicians more frequently and maintain their follow-up as recommended. Nevertheless, the study represents 494 BRCA1/2 carriers and portrays an important healthcare view. Wider implications of the findings Physicians should discuss PGT, family planning and fertility preservation options with BRCA1/2 carriers enabling a personal based decision. It seems that among BRCA carriers, known mutation status largely affects family planning and to a much lesser degree affects fertility preservation and performance of PGT to select non carrier offsprings. Trial registration number Not applicable

O-130 Initiation of ovarian stimulation in the late follicular phase, a randomized controlled trial

Abstract Study question Does late follicular phase stimulation yield similar outcomes compared with conventional early follicular phase stimulation in a GnRH antagonist protocol in oocyte donors? Summary answer Late follicular phase stimulation is not inferior in terms of number of oocytes compared to early follicular phase stimulation in a GnRH antagonist protocol. What is known already In patients undergoing fertility preservation for medical reasons, late follicular phase stimulation has been effectively used, resulting in similar numbers of total and mature oocytes obtained, oocyte maturation rate, mature oocyte yield, and fertilization rates compared to conventional early follicular phase ovarian stimulation. Because of LH suppression by endogenous progesterone in the luteal phase, there is less need for the use of a GnRH antagonist. Study design, size, duration This is an open label, phase 3, non-inferiority, randomized controlled trial using a two-arm design with 1:1 allocation ratio. The study included 71 oocyte donors between 18 and 36 years, with a regular menstrual cycle length and BMI 19-35 kg/m2, who underwent ovarian stimulation between November 2018 and May 2022. Patients were allocated to either early follicular start (Group A, n = 36), or to late follicular start (Group B, n = 35). Participants/materials, setting, methods In Group A, patients followed a fixed GnRH antagonist protocol with r-FSH 225IU daily. In Group B, r-FSH 225IU daily was initiated when a dominant follicle and late follicular hormonal values were observed, a GnRH antagonist was added if serum LH-levels were &amp;gt;10IU/L. The primary outcome was number of cumulus-oocyte-complexes (COCs). Secondary endpoints included number of mature oocytes, consumption of gonadotropins, duration of ovarian stimulation, days of GnRH antagonist used, and cost of the stimulation. Main results and the role of chance Using an intention-to-treat analysis, the total number of oocytes did not differ between Group A and Group B (17.7±10.0 vs 17.2±9.1, p = 0.82, difference 0.49 ,95% CI (-4.04 to 5.03)). In the per protocol analysis, after excluding 4 patients, there was no difference between Group A and Group B (18.2±9.7 vs 18.8±7.8, p = 0.62, difference -0.6, 95% CI (-4.9 to 3.7)).The number of mature oocytes did not differ between Group A and Group B (14.1±8.1 vs 12.7±8.5, p = 0.48). In none of the treatment arms OHSS was observed. The duration of stimulation was shorter in Group A than in Group B (10.0±1.6 vs 10.9±1.5 days, p = 0.01). The total amount of r-FSH used was lower in group A than in Group B (2240.7±313.9 IU vs 2453.9±330.1 IU p = 0.008). A GnRH antagonist was used for approximately 6 days in Group A, while in group B, only in one patient a GnRH antagonist was prescribed for 4 days (6.0±1.4 days vs 0.13±0.7 days p &amp;lt; 0.001). There was a significant difference in total medication cost per cycle between both protocols (1147.9±182.8 € in Group A, vs 979.9±129.0 € in group B, p &amp;lt; 0.001), i.e. a cost reduction of 15% for Group B as compared with Group A. Limitations, reasons for caution A limitation of the study is the lack of embryology data. Because of adaptations in the oocyte donation program in our center over the years, this study contains a mix of fresh and frozen donation cycles, leading to a very heterogenous group, making correct interpretation of the embryology data difficult. Wider implications of the findings Late follicular phase stimulation is as efficient as early follicular phase stimulation in terms of number of oocytes. It is patient-friendly, with reduced cost and reduced number of injections. Trial registration number NCT03767218

Profils cliniques et prise en charge des enfants et adolescents transgenres dans une consultation spécialisée d’Île-de-France

ContextFrench clinical data on the medical management of transgender children and adolescents are scarce. Yet, the topic regularly comes to the forefront of the media. MethodIn this article, we propose to retrospectively describe all the children and adolescents received since 2012 in the largest specialized gender identity consultation for children and adolescents in Île-de-France. In addition to their sociodemographic characteristics, we study the presence or not of gender incongruence according to the ICD 11 criteria, the psychiatric and social vulnerabilities, and describe the main management modalities proposed: social transition, puberty blockage, hormonal transitions and/or rare surgical transitions. These last three proposals were discussed in multidisciplinary concertation meetings. ResultsWe collected 239 youths aged 3 to 20 years. The mean age at which youth and their families were seen at the first appointment was 14.5 years (±3.16). In all, 91% of the sample had gender incongruence, with 32% expressing gender incongruence before puberty. Two-thirds were youth assigned female at birth (P<0.05). In terms of psychopathology, depressive and anxiety disorders, as well as suicidality, came well ahead of other psychiatric co-occurrences. School ostracism and rejection were common. Compared to the general adolescent population, the young people in the specialized consultation are much more exposed to discrimination and insults, and even sexual aggression in the public space, than their peers, and the internalization of transphobia by these young people is particularly important. In all, 40% of the young people made a social transition before the first consultation and 74% and 61% of them did so within the family and at school (the average age of social transition at school=15.13 years). In all, 35% of the young people made the name change official at the town hall (the average age=16.26 years). Puberty blockers were used by 11% of the youths who had reached puberty (mean age=13.9 years, mean time to initiation=10 months). In total, fewer than half of the youths (44%) received masculinizing or feminizing sex hormone treatment (mean age=16.9 years, mean time to initiation=14 months). In all, 8.7% of the young people who received sex hormone treatment underwent fertility preservation. Requests for surgery before the age of 18 remain very rare. The most frequent are torsoplasties (20%) performed at a mean age of 18.44 years and never before 16 years. ConclusionThe results of this cohort are close to those reported by other European centers in terms of the higher proportion of young people assigned female at birth. However, they differ with a lower proportion of hormonal treatment. Social transition is the most frequent request in our center, but it is not systematic. We wonder whether the place of narration while in our care may explain these differences.

Controlled ovarian hyperstimulation in breast cancer patients: Does oestrogen receptor status make a difference?

The presence of different breast cancer receptor status may impact ovarian stimulation outcomes. To study the association between oestrogen receptor (ER) status in breast cancer patients and fertility preservation outcomes in a major tertiary referral centre. Women who underwent fertility preservation following the diagnosis of breast cancer from 2008 to 2018 were included in the study. Patient age, ovarian stimulation parameters and laboratory outcomes were recorded and compared between the ER positive and negative groups. The primary outcome was total number of oocytes frozen. Secondary outcomes included total number of oocytes collected, mature oocytes, and embryos frozen. The women included in the study (n = 214) were analysed in the following groups based on their fertility preservation method: oocyte freezing (n = 131), embryo freezing (n = 70), and both embryo and oocyte freezing (n = 13). There was an increase in the mean (but not mature) number of oocytes frozen (12.4 and 9.2, P-value = 0.03) favouring the ER positive group, even though the women in this group were older (35.0 and 33.4, P-value of 0.03). There is no difference in the starting follicle-stimulating hormone dose, duration of stimulation, mature oocytes collected, and embryos frozen in both groups. Patients with ER positive breast cancer may have more positive ovarian stimulation outcomes.