Study question Is partial premature ovulation (PPO) detection during the oocyte pick-up (OPU) a sign of poor prognosis in in vitro fertilization (IVF) cycles with own oocytes? Summary answer PPO halves the number of metaphase II oocytes available for an IVF treatment without reducing their quality, demonstrated by unaltered fertilization and top-quality blastocyst rates. What is known already PPO detected during the OPU procedure has not been extensively studied in the literature. This phenomenon may result in a reduction in the number and/or competence of the oocytes retrieved, due to the potential loss of the already expelled oocytes, as well as the likely dominance exerted by the ruptured follicle/s in the rest of the cohort. Despite this, several authors have demonstrated that competent oocytes can be retrieved from these already ruptured follicles, suggesting that oocyte extrusion frequently does not occur after follicle rupture. The potential negative effect exerted in the rest of sibling oocytes remains unknown. Study design, size, duration Retrospective cohort analysis performed in IVIRMA Valencia (Spain), including 8994 cycles of controlled ovarian stimulation (COS) for an IVF treatment with fresh own oocytes, between January 2016 and May 2021. OPU procedures for oocyte cryopreservation, as well as mixed cycles with both fresh and frozen oocytes, were discarded. PPO diagnosis was based on ultrasound visualization of any already formed corpus luteum structure/s, a lower follicular count than expected, and/or free fluid. Participants/materials, setting, methods Female patients undergoing OPU after COS for a fresh IVF treatment. Cycles in which PPO has been detected will be compared with a random, and of the same size, sample without PPO. Mean number of oocytes, metaphase II, fertilized oocytes and top-quality embryos, as well as IVF success rates, will be compared between both groups. Patients’ basal characteristics and COS parameters will be analyzed in order to detect any potential early indicator of PPO. Main results and the role of chance PPO was detected in 123 of the 8994 cycles (1.37%) performed. A random control group of 123 cycles without PPO was selected. Patients’ mean age was 37.6±3.6, with a BMI of 23.3±4.1 kg/m2 and an anti-mullerian hormone of 1.62±1.3 ng/mL. Patient’s basal characteristics and COS parameters were statistically comparable among groups (p > 0.05), except for lower serum estradiol levels (2037.64 vs. 1582.24 pg/mL; p = 0.004) in the PPO group on the last ultrasound prior to OPU. Patients with PPO showed lower aspiration rates (88.95% vs. 55.78% in the PPO gr.), as well as a reduced mean number of oocytes (10.69 vs. 5.68 in the PPO gr.), metaphase II (8.41 vs. 4.33 in the PPO gr.), fertilized oocytes (6.23 vs. 3.26 in the PPO gr.) and top-quality blastocysts (2.77 vs. 1.35 in the PPO gr.) (p = 0.000). In contrast, maturation (80.72% vs. 76.57% in the PPO gr.), fertilization (73.52% vs. 75.18% in the PPO gr.) and top-quality blastocyst rates (44.03% vs. 38.68% in the PPO gr.) were statistically similar between both groups (p > 0.05). Limitations, reasons for caution The main limitations of the present study are its retrospective design and its small sample size, derived from the low frequency of the PPO phenomenon in our clinic. Larger prospective studies should be proposed in order to accurately define the negative impact of PPO in IVF success rates. Wider implications of the findings PPO clearly reduces the number of oocytes available for an IVF treatment, although it does not seem to impair the competence of the remaining cohort. Once PPO is detected, cycle cancellation may not be worth the associated loss of money, time and morale, especially given its low prevalence (around 1%). Trial registration number Not applicable

Study question Which is the minimum number of mature oocytes needed to obtain at least one euploid blastocyst regarding female age in In Vitro Fertilization (IVF) treatments? Summary answer The validated model estimates with a 74% accuracy the probability of having one euploid blastocyst regarding the number of mature oocytes and female age. What is known already Female age is significantly and directly related to embryo aneuploidy rates, thus lowering the chances of success in IVF treatments. The current delay in motherhood has led to a large proportion of women of advanced maternal age seeking infertility treatment. The aim of the present study is to determine the number of metaphase II (MII) oocytes needed to obtain at least one euploid blastocyst regarding female age. This information will help to decide the best strategy for each patient, taking also into account other variables such as ovarian reserve, semen quality and oocyte quality. Study design, size, duration Retrospective analysis of IVF cycles with pre-implantational genetic testing for aneuploidies (PGT-A) performed over the last 5 years in an infertility clinic in Spain, from January 2017 to March 2022. Participants/materials, setting, methods Patients undergoing an IVF cycle in an infertility clinic with own or donated oocytes, regardless semen origin. Only trophoectoderm biopsies performed on day 5 or 6 of development and analyzed using Next Generation Sequencing (NGS) were included. PGT-A was used for reasons such as advanced maternal age, implantation failure and recurrent miscarriage. PGT-A cycles due to a known abnormal karyotype were excluded. Endpoints were analized using binary logistic regression models. Main results and the role of chance A total of 3840 IVF-PGT-A cycles meeting the inclusion criteria were performed in the study period. Of them, 939 cycles were discarded due to the absence of any biopsied/analyzed embryo (final sample size=2901). A model for the probability of having at least one euploid blastocyst (pEB) regarding female age and the number of MII oocytes retrieved was created with 80% of the sample (n = 2320) and validated in the remaining 20% (n = 581). The validation of this model showed that it was capable of estimate with an accuracy of 73.88%. The pEB was directly related to the number of MII oocytes retrieved (odds ratio (OR) 1.130, confidence interval (IC) 95% (1.110-1.150); p < 0.001), but indirectly related to female age (OR 0.751, IC95% (0.725-0.778); p < 0.001). The ROC curve showed a significant predictive value of the number of MII oocytes (area under the curve (AUC):0.8041 (0.7882-0.82)) for this model. A mathematical formula was created for the calculation of pEB using this model. The number of MII oocytes needed for a pEB of 75% regarding female age (female age:number MII) was 35:6, 36:9, 37:12, 38:15, 39:18, 40:21, 41:24, 42:27, 43:30, 44:32, 45:35, 46:38, 47:41, 48:44, 49:47, 50:50. Limitations, reasons for caution The main limitation of this study is its retrospective design. In addition, it’s important to keep in mind that many other variables should be taken into consideration along with maternal age in the assessment of the number of oocytes needed to obtain at least one euploid blastocyst in IVF treatments. Wider implications of the findings Results from this study may constitute a useful tool for both clinical and patient. The clinician may be able to better decide the best strategy for each patient, while the patient will understand more easily this information, helping her morally with the treatment. Trial registration number 2204-VLC-040-CR