Effect of breast cancer prognostic factors on ovarian reserve and response in fertility preservation.

RESEARCH QUESTION: Do breast cancer prognostic factors influence ovarian reserve and response to ovarian stimulation in the context of fertility preservation? DESIGN: Observational, bicentric retrospective study of 352 women with breast cancer who underwent ovarian stimulation using a random start gonadotrophin releasing hormone antagonist protocol and vitrified oocytes between November 2015 and August 2022. Serum anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) were measured. The number of oocytes recovered, maturation rate and follicular output rate (FORT) were analysed according to patients' characteristics and breast cancer prognostic factors. RESULTS: Median age was 34 years (31.1-37.1). Median AFC and serum AMH level were 17 (12-26) follicles and 2 (1.2-3.4) ng/ml, respectively. After ovarian stimulation, 10.5 (6.0-16.0) oocytes were recovered, with eight (4-13) being mature. Mean oocyte maturation rate was 79% (62-92). Antral follicle count (>12) significantly affected the risk of recovering fewer than eight mature oocytes (P < 0.0001, multivariate analysis). Follicular responsiveness to FSH, assessed by the follicular output rate (FORT index) and number of oocytes recovered, were 31% (21-50) and 10.5% (6.0-16.0), respectively. FORT index and ovarian stimulation outcomes were not influenced by breast cancer prognostic factors. CONCLUSION: Breast cancer prognostic factors do not influence ovarian reserve markers or response to ovarian stimulation in fertility preservation. Therefore, tumour grade, triple-negative status, HER2 overexpression and high Ki67 should not alter the fertility-preservation strategy when considering ovarian stimulation for oocyte vitrification.

Effect of various contraceptives on oocyte yield and maturation in patients undergoing planned oocyte cryopreservation.

RESEARCH QUESTION: Do the various forms of hormonal and non-hormonal contraceptives have any association with ovarian stimulation outcomes, such as oocyte yield and maturation, in patients undergoing planned oocyte cryopreservation (POC)? DESIGN: This retrospective cohort study included all patients who underwent POC cycles between 2011 and 2023. The use of types of contraception before a POC cycle was recorded. The study evaluated the median number of cumulus-oocyte complexes obtained after vaginal oocyte retrieval and the proportion of metaphase II oocytes that underwent vitrification among all the cohorts. RESULTS: A total of 4059 oocyte freezing cycles were included in the analysis. Eight types of contraceptive method were recognized in patients undergoing ovarian stimulation: intrauterine device (IUD), copper (n = 84); IUD, levonorgestrel low dose (<52 mg) (n = 37); IUD, levonorgestrel (n = 192); subdermal etonogestrel implant (n = 14); injectable medroxyprogesterone acetate (n = 11); etonogestrel vaginal ring (n = 142); combined oral contraceptive pills (n = 2349); and norelgestromin transdermal patch (n = 10). The control group included patients not using contraceptives or using barrier or calendar methods (n = 1220). Among all the cohorts the median number of cumulus-oocyte complexes retrieved during oocyte retrieval was comparable (P = 0.054), and a significant difference in oocyte maturity rate with median number of vitrified oocytes was found (P = 0.03, P < 0.001, respectively). After adjusting for confounders a multivariate analysis found no association between the type of contraceptive and proportion of metaphase II oocytes available for cryopreservation. CONCLUSIONS: Among the various forms of contraception, none was shown to have an adverse association with oocyte yield or maturation rate in patients undergoing POC.

The Effect of Open and Closed Oocyte Vitrification Systems on Embryo Development: A Systematic Review and Network Meta-Analysis.

Background/Objectives: Open and closed vitrification systems are commonly employed in oocyte cryopreservation; however, there is limited evidence regarding a comparison of their separate impact on oocyte competence. This study uniquely brings to the literature, data on the effect of open versus closed vitrification systems on laboratory and clinical outcomes, and the effect of cooling and warming rates. Methods: A systematic search of the literature was performed using the databases PubMed/MEDLINE and the Cochrane Central Library, limited to articles published in English up to January 2023. A network meta-analysis was conducted comparing each vitrification system versus fresh oocytes. Results: Twenty-three studies were included. When compared to fresh oocytes, both vitrification devices resulted in lower fertilization rates per MII oocyte retrieved. When comparing the two systems in terms of survival rates, no statistically significant difference was observed. However, interestingly open systems resulted in lower cleavage and blastocyst formation rates per 2 pronuclear (2PN) oocyte compared to fresh controls, while at the same time no statistically significant difference was detected when comparing closed devices with fresh oocytes. Conclusions: In conclusion, closed vitrification systems appear to exert a less detrimental impact on the oocytes' competence, which is reflected in the blastocyst formation rates. Proof of superiority of one system versus the other may lead to standardization, helping to ultimately determine optimal practice in oocyte vitrification.

Embryos from vitrified vs. fresh oocytes in an oocyte donation program: a comparative morphokinetic analysis.

OBJECTIVE: To compare the morphokinetic patterns of human embryos originating from vitrified oocytes (VITRI group) with those derived from freshly collected oocytes (CONTROL group) in oocyte donation cycles. DESIGN: This is a retrospective observational study. SETTING: Embryolab Fertility Clinic, Embryology Lab, Thessaloniki, Greece. PATIENT(S): The study included embryos from 421 vitrified oocytes from 58 oocyte donation cycles and 196 fresh oocytes from 23 oocyte donation cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Key time parameters, dynamic events, fertilization rates, degeneration rates, cleavage rates, blastocyst rates, pregnancy rates, clinical pregnancy rates, implantation rates, and live birth rates were estimated. RESULTS: The mean survival rate of vitrified oocytes was 92.58% (±7.42%). Fertilization rates were significantly different between the 2 groups (VITRI group: 71.92% ± 20.29% and CONTROL group: 80.65% ± 15.22%) whereas the degeneration, cleavage, blastocyst, pregnancy, clinical pregnancy, ongoing pregnancy, implantation, and live birth rates were not significantly different between embryos derived from fresh or vitrified oocytes. Time-lapse analysis showed no significant difference in any key time parameter. However, when examining dynamic parameters, first cell cycle (CC1) (t2 - tPB2: from the second polar body extrusion (tPB2) up to 2 cells (t2)) showed a significant difference whereas CC1a (t2 - tPNf: from fading of the pronuclei (tPNf) up to 2 cells (t2)) was at the threshold of significance. CONCLUSION(S): CC1 in vitrified oocytes exhibited a comparatively slower progression in contrast to fresh oocytes. Conversely, CC1a in vitrified oocytes demonstrated faster progression compared with fresh oocytes. It is worth noting that these temporary deviations had minimal impact on the subsequent development. Despite the clinical outcomes showing a decrease in the vitrified group, none of them reached statistical significance. This lack of significance could be attributed to the limited sample size of the study.

Advanced Maternal Age Affects the Cryosusceptibility of Ovulated but not In Vitro Matured Mouse Oocytes.

Oocyte cryopreservation is offered to women of various age groups for both health and social reasons. Oocytes derived from either controlled ovarian stimulation or in vitro maturation (IVM) are cryopreserved via vitrification. As maternal age is a significant determinant of oocyte quality, there is limited data on the age-related susceptibility of oocytes to the vitrification-warming procedure alone or in conjunction with IVM. In the present study, metaphase II oocytes obtained from 2, 6, 9, and 12 month old Swiss albino mice either by superovulation or IVM were used. To understand the association between maternal age and oocyte cryotolerance, oocytes were subjected to vitrification-warming and compared to non vitrified sibling oocytes. Survived oocytes were evaluated for mitochondrial potential, spindle integrity, relative expression of spindle checkpoint protein transcripts, and DNA double-strand breaks. Maturation potential and vitrification-warming survival were significantly affected (p < 0.001 and p < 0.05, respectively) in ovulated oocytes from the advanced age group but not in IVM oocytes. Although vitrification-warming significantly increased spindle abnormalities in ovulated oocytes from advanced maternal age (p < 0.01), no significant changes were observed in IVM oocytes. Furthermore, Bub1 and Mad2 transcript levels were significantly higher in vitrified-warmed IVM oocytes (p < 0.05). In conclusion, advanced maternal age can have a negative impact on the cryosusceptibility of ovulated oocytes but not IVM oocytes in mice.

Oocyte vitrification for fertility preservation is an evolving practice requiring a new mindset: societal, technical, clinical, and basic science-driven evolutions.

Infertility is a condition with profound social implications. Indeed, it is not surprising that evolutions in both medicine and society affect the way in vitro fertilization is practiced. The keywords in modern medicine are the four principles, which implicitly involve a constant update of our knowledge and our technologies to fulfill the "prediction" and "personalization" tasks, and a continuous reshaping of our mindset in view of all relevant societal changes to fulfill the "prevention" and "participation" tasks. A worldwide aging population whose life priorities are changing requires that we invest in fertility education, spreading actionable information to allow women and men to make meaningful reproductive choices. Fertility preservation for both medical and nonmedical reasons is still very much overlooked in many countries worldwide, demanding a comprehensive update of our approach, starting from academia and in vitro fertilization laboratories, passing through medical offices, and reaching out to social media. Reproduction medicine should evolve from being a clinical practice to treat a condition to being a holistic approach to guarantee patients' reproductive health and well-being. Oocyte vitrification for fertility preservation is the perfect use case for this transition. This tool is acquiring a new identity to comply with novel indications and social needs, persisting technical challenges, brand-new clinical technologies, and novel revolutions coming from academia. This "views and reviews" piece aims at outlining the advancement of oocyte vitrification from all these tightly connected perspectives.

Views and reviews: fertility preservation from different perspectives.

Fertility preservation for different conditions provides women the chance to buy time that can be invested in improving their well-being, by curing their condition from a holistic perspective, in line with the precepts of modern medicine.

Current status of fertility preservation in a Spanish tertiary public hospital: multidisciplinary approach and experience in over 1500 patients.

PURPOSE: Currently, 15% of gynaecological and 9% of haematological malignancies are diagnosed before the age of 40. The increased survival rates of cancer patients who are candidates for gonadotoxic treatments, the delay in childbearing to older ages, and the optimization of in vitro fertilisation techniques have all contributed to an increased interest in fertility preservation (FP) treatments. This study reviews the experience of the Fertility Preservation Programme (FPP) of a tertiary public hospital with a multidisciplinary approach. METHODS: This retrospective study included all the available (FP) treatments, performed in patients of childbearing age between 2006 and 2022. RESULTS: 1556 patients were referred to the FPP: 332 oocyte vitrification cycles, 115 ovarian cortex cryopreservation with 11 orthotopic autotransplantations, 175 gonadotropin-releasing hormone (GnRH) agonist treatments, 109 fertility-sparing treatments for gynaecological cancer, and 576 sperm cryopreservation were performed. Malignancy was the main indication for FP (the main indications being breast cancer in women and haematological malignancies in men), although non-oncological pathologies, such as endometriosis and autoimmune diseases, have increased in recent years. Currently, the most widely used FP technique is oocyte vitrification, the increase of which has been associated with a decrease in the use of cortex CP and GnRH agonists. CONCLUSIONS: The increase in FP treatment reflects the implementation of reproductive counselling in oncology programmes. A multidisciplinary approach in a tertiary public hospital allows individualised FP treatment for each patient. In recent years, there has been a change in trend with the introduction of new indications for FP and a change in techniques due to their optimisation.

Oocyte Vitrification Reduces its Capability to Repair Sperm DNA Fragmentation and Impairs Embryonic Development.

Oocytes play a crucial role in repairing sperm DNA damage, which can affect the next generation; however, certain factors can impair this ability. This study examined whether oocyte vitrification, a widely used method for fertility preservation, negatively affects repair ability. Male DBA/2 mice (n = 28) were injected with 101.60 µmol/100 g body weight of tert-Butyl hydroperoxide (tBHP) for 14 days to induce sperm DNA damage. Histological changes, sperm functions, and DNA fragmentation were assessed using the TUNEL assay. Cumulus-oocyte-complexes (COCs) of superovulated female DBA/2 mice (n = 28) were vitrified using the Cryotop method. Fresh and vitrified oocytes were then fertilized by tBHP-treated and untreated sperms, and subsequent embryonic development was monitored. Additionally, the expression of Mre11a, Rad51, Brca1, and Xrcc4 was assessed in resulting zygotes and blastocysts using real-time PCR. The sperm tBHP treatment reduced differentiated spermatogenic cells in the testicular tissue, sperm concentration, and motility, while increasing DNA fragmentation (P < 0.05). The fertilization rate was decreased in the tBHP-treated sperm-vitrified oocyte group (P < 0.05), and the two-cell rate diminished in tBHP-treated sperm-fresh and vitrified oocyte groups (P < 0.05). The four-cell to blastocyst rate decreased in the untreated sperm-vitrified oocyte and the tBHP-treated sperm-fresh and vitrified oocyte groups (P < 0.05), and the tBHP-treated sperm-vitrified oocyte groups had the lowest blastocyst rate. In zygotes, Brca1 was upregulated in the tBHP-treated sperm-vitrified oocyte group (P < 0.05). Also, in blastocysts, Rad51, Brca1, and Xrcc4 were significantly upregulated in the untreated sperm-vitrified oocytes group (P < 0.05). Damages to the oocyte due to vitrification can disrupt the repair of sperm DNA fragmentation and consequently impair the embryo development.

Effects of multi-gradient equilibration during vitrification on oocyte survival and embryo development in mice.

Vitrification has been widely used for oocyte cryopreservation, but there is still a need for optimization to improve clinical outcomes. In this study, we compared the routine droplet merge protocol with modified multi-gradient equilibration vitrification for cryopreservation of mouse oocytes at metaphase II. Subsequently, the oocytes were thawed and subjected to intracytoplasmic sperm injection (ICSI). Oocyte survival and spindle status were evaluated by morphology and immunofluorescence staining. Moreover, the fertilization rates and blastocyst development were examined in vitro. The results showed that multi-gradient equilibration vitrification outperformed droplet merge vitrification in terms of oocyte survival, spindle morphology, blastocyst formation, and embryo quality. In contrast, droplet merge vitrification exhibited decreasing survival rates, a reduced proportion of oocytes with normal spindle morphology, and lower blastocyst rates as the number of loaded oocytes increased. Notably, when more than six oocytes were loaded, reduced oocyte survival rates, abnormal oocyte spindle morphology, and poor embryo quality were observed. These findings highlight that the vitrification of mouse metaphase II oocytes by the modified multi-gradient equilibration vitrification has the advantage of maintaining oocyte survival, spindle morphology, and subsequent embryonic development.

Oocyte Cryopreservation in Women with Ovarian Endometriosis.

Ovarian endometriosis is a gynecological condition that is closely associated with infertility-from its pathogenesis to treatment modalities, this condition presents a challenge both for patients and clinicians alike when seeking conception, due to low AMH levels, peritoneal inflammation, and the inadvertent removal of healthy ovarian parenchyma at surgery. In fact, around half of endometriosis patients seeking fertility require tertiary-level assisted reproduction techniques to achieve a live birth. Oocyte cryopreservation, a procedure initially designed for oncology patients, has emerged over recent years as a very promising treatment strategy for patients who have been diagnosed with ovarian endometriosis in order to preserve their fertility and obtain a live birth at a later stage in their lives. Counseling patients about oocyte preservation techniques at an early stage in the diagnosis, ideally before the age of 35 and especially prior to any surgical treatment, provides an excellent opportunity to discuss future fertility and the benefits associated with oocyte cryopreservation.

Efficiency and safety of vitrification of surplus oocytes following superovulation: a comparison of different clinical indications of oocyte cryopreservation in IVF/ICSI cycles.

Objective: To evaluate the effectiveness and safety of utilizing the small number of remaining vitrified oocytes after the failure of adequate fresh sibling oocytes. The outcome of present study would provide more comprehensive information about possible benefits or disadvantage to cryopreserve supernumerary oocytes for patients who have plenty oocytes retrieved. Methods: This retrospective cohort study included 791 IVF/ICSI cycles using 6344 oocytes that had been vitrified in the Reproductive Hospital affiliated to Shandong University between January 2013 and December 2019.They were divided into three groups: SOC group (supernumerary oocytes cryopreservation), relative-MOC group (relative male factor-oocyte cryopreservation), and absolute-MOC group (absolute male factor-oocyte cryopreservation). Laboratory and clinical outcomes were analysed, and multivariate regression analysis was used to study the effect of different indications of vitrification on CLBR. Results: The CLBR was highest in absolute-MOC, and lowest in SOC (39.0% vs 28.9%, P=0.006); however, after adjusting for confounding factors, the difference was not statistically significant. Multivariable regression analysis showed no impact of indications of vitrified oocytes on CLBR according to controlled age, BMI, preservation duration, use of donor sperm or not, use of PESA/TESA or not, number of oocytes retrieved, number of oocytes thawed, and oocyte survival rate. The preliminary data of safety showed no significant differences in the perinatal and neonatal outcoms after ET and FET between the SOC and MOC groups. Conclusion: Different indications of vitrification did not affect CLBR. The CLBR of vitrified oocytes for different indications was correlated with age and number of warmed oocytes. For women who have plenty oocytes retrieved, the strategy of cryopreserving a small number of oocytes is a valuable option and might benefit them in the future. Additional data from autologous oocyte vitrification research employing a large-scale and variable-controlled methodology with extending follow-up will complement and clarify the current results.

Reproductive Outcomes of Women with Turner Syndrome Undergoing Oocyte Vitrification: A Retrospective Multicenter Cohort Study.

BACKGROUND: Turner syndrome (TS) is accompanied with premature ovarian insufficiency. Oocyte vitrification is an established method to preserve fertility. However, data on the oocyte yield in women with TS who vitrify their oocytes and the return rate to utilize the oocytes are scarce. METHODS: Retrospective multicenter cohort study. Data was collected from medical records of women with TS who started oocyte vitrification between 2010 and 2021. RESULTS: Thirty-three women were included. The median cumulative number of vitrified oocytes was 20 per woman. Complications occurred in 4% of the cycles. Significant correlations were found between the cumulative number of vitrified oocytes and AMH (r = 0.54 and p < 0.01), AFC (r = 0.49 and p < 0.01), percentage of 46,XX cells (r = 0.49 and p < 0.01), and FSH (r = -0.65 and p < 0.01). Spontaneous (n = 8) and IVF (n = 2) pregnancies occurred in 10 women ± three years after vitrification. So far, none of the women have returned to utilize their vitrified oocytes. CONCLUSIONS: Oocyte vitrification is a feasible fertility preservation option for women with TS, particularly in those with 46,XX cell lines or sufficient ovarian reserve. Multiple stimulation cycles are recommended to reach an adequate number of vitrified oocytes for pregnancy. It is too early to draw conclusions about the utilization of vitrified oocytes in women with TS.

The study of the efficiency of in vitro maturation of ovarian tissue oocytes in pediatric patients.

PURPOSE: Although recent in vitro maturation (IVM) studies in pediatric patients have demonstrated successful retrieval and maturation of oocytes, the studies included only a small number of premenarchal patients. In the present study, we examined the potential use of oocyte retrieval and maturation for pediatric patients who undergo ovarian tissue cryopreservation (OTC). METHODS: We retrospectively examined the clinical records of pediatric patients who underwent OTC at our institution between October 2015 and December 2022. Data on the age, primary disease, menstrual history, pre-procedure chemotherapy, anti-Müllerian hormone (AMH) level, number of oocytes collected ex vivo from ovarian tissue, and number of mature oocytes from IVM were examined. RESULTS: Data of 60 pediatric patients (aged 1 to 17 years) were included for analysis. Oocytes were retrieved from 36 patients; the oocytes of 18 of these patients could be cryopreserved. The IVM rate was significantly lower in the premenarchal patients than in the postmenarchal patients. The number of mature oocytes retrieved from IVM was higher in the no-chemotherapy group than in the chemotherapy group. A significant positive correlation was observed between the AMH level and the IVM outcomes. CONCLUSION: Oocyte retrieval and maturation in pediatric patients undergoing OTC is particularly useful in those not receiving chemotherapy. In patients receiving chemotherapy, the AMH level may be useful for predicting the IVM outcome. Activation of the oocyte maturation process in vivo in pediatric patients and better understanding of the major regulators of oocyte maturation are necessary to improve the utility of the IVM procedure.

Vitrification induces a focused spindle pole in mouse MI oocytes.

Immature oocyte (germinal vesicle stage, GV) vitrification can avoid a cycle of ovarian stimulation, which is friendly to patients with hormone-sensitive tumors. However, the in vitro maturation of vitrification-thawed GV oocyte usually results in aneuploidy, and the underlying mechanism remains unclear. Stable spindle poles are important for accurate chromosome segregation. Acentriolar microtubule-organizing centers (aMTOCs) undergo fragmentation and reaggregation to form spindle poles. Microtubule nucleation is facilitated via the perichromosome Ran after GVBD, which plays an important role in aMTOCs fragmentation. This study showed that vitrification may reduce microtubule density by decreasing perichromosomal Ran levels, which reduced the localization of pKIF11, thereby decreased the fragmentation of aMTOCs and formed a more focused spindle pole, ultimately resulted in aneuploidy. This study revealed the mechanism of abnormal spindle pole formation in vitrified oocytes and offered a theoretical support to further improve the quality of vitrified oocytes.

Embryo ploidy in vitrified versus fresh oocytes: Is there a difference?

PURPOSE: To evaluate embryo ploidy in a cohort of patients who underwent preimplantation genetic testing for aneuploidy (PGT-A) with vitrified oocytes compared to fresh oocytes. METHODS: Patients who underwent their first autologous oocyte vitrification and warming followed by in vitro fertilization (IVF) and trophectoderm biopsy for PGT-A between 1/1/2017 and 12/31/2021 at a single academic institution were included. Patients were compared 1:3 to age-matched controls who underwent their first IVF cycle with fresh oocytes and subsequent trophectoderm biopsy for PGT-A. The primary outcome was the proportions of euploid, mosaic, and aneuploid embryos between those using vitrified versus fresh oocytes. RESULTS: 117 patients who cryopreserved a total of 1,272 mature oocytes were included in the study and were matched with 351 controls using fresh oocytes. The average age was 36.9 ± 2.6 years, and the median interval between oocyte vitrification and warming was 38 months. There were similar numbers of mature oocytes (10.9 ± 4.9 vs. 11.1 ± 6.3, P = .67), fertilized oocytes (7.8 ± 4.0 vs. 8.7 ± 5.5, P = .10), and blastocysts per patient (5.1 ± 3.1 vs. 5.8 ± 4.3, P = .10) between those using vitrified versus fresh oocytes. In terms of embryo ploidy results, there were no statistically significant differences in rates of euploidy (40.1% vs. 41.6%), mosaicism (15.7% vs. 12.0%), or aneuploidy (44.3% vs. 46.4%) (P = .06) between the two groups. CONCLUSIONS: Oocyte vitrification with subsequent warming, fertilization, and trophectoderm biopsy for PGT-A was not associated with adverse chromosomal competence when compared to age-matched controls utilizing fresh oocytes.

Effects of meiotic stage-specific oocyte vitrification on mouse oocyte quality and developmental competence.

Introduction: Acquisition of germinal vesicle (GV) stage oocytes for fertility preservation (FP) offers several benefits over in vivo matured oocyte cryopreservation following ovarian stimulation, particularly for cancer patients necessitating immediate treatment. Two FP approaches for GV oocytes are available: vitrification before in vitro maturation (IVM) at the GV stage (GV-VI) or post-IVM at the metaphase II (MII) stage (MII-VI). The optimal method remains to be determined. Methods: In this study, mouse oocytes were collected without hormonal stimulation and vitrified either at the GV stage or the MII stage following IVM; non-vitrified in vitro matured MII oocytes served as the control (CON). The oocyte quality and developmental competence were assessed to obtain a better method for immediate FP. Results: No significant differences in IVM and survival rates were observed among the three groups. Nevertheless, GV-VI oocytes exhibited inferior quality, including abnormal spindle arrangement, mitochondrial dysfunction, and early apoptosis, compared to MII-VI and CON oocytes. Oocyte vitrification at the GV stage impacted maternal mRNA degradation during IVM. In addition, the GV-VI group demonstrated significantly lower embryonic developmental competence relative to the MII-VI group. RNA sequencing of 2-cell stage embryos revealed abnormal minor zygotic genome activation in the GV-VI group. Conclusion: Vitrification at the GV stage compromised oocyte quality and reduced developmental competence. Consequently, compared to the GV stage, oocyte vitrification at the MII stage after IVM is more suitable for patients who require immediate FP.

Should we perform oocyte accumulation to preserve fertility in women with Turner syndrome? A multicenter study and systematic review of the literature.

STUDY QUESTION: Should we perform oocyte accumulation to preserve fertility in women with Turner syndrome (TS)? SUMMARY ANSWER: The oocyte cryopreservation strategy is not well adapted for all TS women as their combination of high basal FSH with low basal AMH and low percentage of 46,XX cells in the karyotype significantly reduces the chances of freezing sufficient mature oocytes for fertility preservation. WHAT IS KNOWN ALREADY: An oocyte cryopreservation strategy requiring numerous stimulation cycles is needed to preserve fertility in TS women, to compensate for the low ovarian response, the possible oocyte genetic alterations, the reduced endometrial receptivity, and the increased rate of miscarriage, observed in this specific population. The validation of reliable predictive biomarkers of ovarian response to hormonal stimulation in TS patients is necessary to help practitioners and patients choose the best-personalized fertility preservation strategy. STUDY DESIGN, SIZE, DURATION: A retrospective bicentric study was performed from 1 January 2011 to 1 January 2023. Clinical and biological data from all TS women who have received from ovarian stimulation for fertility preservation were collected. A systematic review of the current literature on oocyte retrieval outcomes after ovarian stimulation in TS women was also performed (PROSPERO registration number: CRD42022362352). PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 14 TS women who had undergone ovarian stimulation for fertility preservation were included, representing the largest cohort of TS patients published to date (n = 14 patients, 24 cycles). The systematic review of the literature identified 34 additional TS patients with 47 oocyte retrieval outcomes after ovarian stimulation in 14 publications (n = 48 patients, n = 71 cycles in total). MAIN RESULTS AND THE ROLE OF CHANCE: The number of cryopreserved mature oocytes on the first cycle for TS patients was low (4.0 ± 3.7). Oocyte accumulation was systematically proposed to increase fertility potential and was accepted by 50% (7/14) of patients (2.4 ± 0.5 cycles), leading to an improved total number of 10.9 ± 7.2 cryopreserved mature oocytes per patient. In the group who refused the oocyte accumulation strategy, only one patient exceeded the threshold of 10 mature cryopreserved oocytes. In contrast, 57.1% (4/7) and 42.9% (3/7) of patients who have underwent the oocyte accumulation strategy reached the threshold of 10 and 15 mature cryopreserved oocytes, respectively (OR = 8 (0.6; 107.0), P = 0.12; OR= 11 (0.5; 282.1), P = 0.13). By analyzing all the data published to date and combining it with our data (n = 48 patients, n = 71 cycles), low basal FSH and high AMH concentrations as well as a higher percentage of 46,XX cells in the karyotype were significantly associated with a higher number of cryopreserved oocytes after the first cycle. Moreover, the combination of low basal FSH concentration (<5.9 IU/l), high AMH concentration (>1.13 ng/ml), and the presence of 46,XX cells (>1%) was significantly predictive of obtaining at least six cryopreserved oocytes in the first cycle, representing objective criteria for identifying patients with real chances of preserving an adequate fertility potential by oocyte cryopreservation. LIMITATIONS, REASONS FOR CAUTION: Our results should be analyzed with caution, as the optimal oocyte number needed for successful live birth in TS patients is still unknown due to the low number of reports their oocyte use in the literature to date. WIDER IMPLICATIONS OF THE FINDINGS: TS patients should benefit from relevant clinical evaluation, genetic counseling and psychological support to make an informed choice regarding their fertility preservation technique, as numerous stimulation cycles would be necessary to preserve a high number of oocytes. STUDY FUNDING/COMPETING INTEREST(S): This research received no external funding. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

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

RESEARCH QUESTION: Can 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? DESIGN: A 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. RESULTS: In 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). CONCLUSIONS: Administration 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.