Advanced Maternal Age Patients Research Articles

IVF and perinatal outcomes of advanced maternal age patients after single frozen euploid embryo transfer: a propensity-matched analysis of autologous and donor cycles

ObjectiveTo evaluate in vitro fertilization (IVF) and perinatal outcomes of donor egg and autologous cycles in advanced reproductive-aged patients after undergoing single, frozen euploid embryo transfer (SET/FET). DesignA retrospective, multicenter cohort study. SettingUniversity-affiliated and private IVF centers. Patient(s)Patients between 39-46 years old undergoing IVF with intracytoplasmic sperm injection (ICSI) and preimplantation genetic testing for aneuploidy (PGT-A) using whole-chromosome sequencing with donor (n=278) or autologous (n=278) oocytes between October 2017 and October 2021. Intervention(s)SET/FET with donor or autologous euploid embryo Main outcome measure(s)The live birth rate after the first embryo transfer, calculated per embryo transfer. Secondary outcomes included implantation rate, ectopic pregnancy rate, miscarriage rate, and gestational age and birthweight at the time of delivery. Result(s)Patients using donor or autologous oocytes had a similar likelihood of implantation57.91% (51.87-63.78) versus 57.19% (51.15-63.09), p=0.93 and live birth rate 41.01% (95% CI:35.17-47.04) versus 42.45% (95% CI:36.56-48.49), p=0.86. Furthermore, there were no significant differences in ectopic pregnancy rate [0.72% (0.09-2.57) versus 0.36% (0.01-1.99), p=1] or miscarriage rate [16.19% (12.06-21.05) versus 14.39% (95% CI:10.48-19.08), p=0.98], gestational age [38.50 weeks (38.08-38.92) versus 39.16 weeks (38.25-40.07), p=0.19], or birthweight of infants [2982.25 kg (2606.69-3357.81) versus 3128.24 kg (2962.30-3294.17), p=0.95]. The univariate analysis showed no association of advanced maternal age on the live birth rate [risk relative (RR) 1.03 (IC95%: 0.84-1.25); p=0.79]. Multivariate analysis using putative confounders for embryo competency found no associations with live birth rate [adjusted risk relative (aRR) 1.22 (IC95%: 0.75-1.98); p=0.42] Conclusion(s)Patients with euploid blastocysts derived from donor or autologous oocytes did not reveal statistically significant differences in live birth rate, implantation rate, ectopic pregnancy rate, miscarriage rate, duration of gestation, or infant birthweight. These findings suggest that age-related reproductive decline and/or poor IVF outcomes associated with advanced reproductive-aged women undergoing IVF are heavily driven by embryonic aneuploidy.

Intrinsic and Extrinsic Apoptotic Pathways May Dictate In Vitro Fertilization Outcomes in Women of Advanced Maternal Age [ID 2683425

INTRODUCTION: Women of advanced maternal age (AMA) (≥35 years) are at an increased risk for a decline in ovarian reserve and have a decreased rate of live birth after one cycle of in vitro fertilization (IVF). Current practice recommends preimplantation genetic testing for aneuploidy (PGT-A) to women of AMA to increase live birth outcomes. However, recent studies have found that conventional IVF was non-inferior to PGT-A. Identifying additional biomarkers may provide another metric for selecting the most viable embryo. METHODS: Blastocoel fluid-conditioned media was collected from day 5 IVF embryos that underwent PGT-A. RNA was purified from pooled blastocoel fluid samples from four groups based on implantation status and maternal age, and then cDNA was synthesized. RT-qPCR was used to assess expression of CASP3, CASP7, CASP8, and BCL2L12 levels in a total of 64 embryos. RESULTS: CASP3 and CASP7 expression were higher in the media from IVF embryos with positive implantation outcomes from patients aged less than 35 years. There was increased CASP8 expression in media from IVF embryos from AMA patients regardless of implantation status. CONCLUSION: Preliminary analysis suggests increased CASP8 expression is associated with successful implantation outcomes in AMA patients. This suggests that CASP8 could be activated in preimplantation embryos as an aging response as found in AMA media samples. One explanation is that CASP8 is associated with aneuploidy in the AMA samples. Further research will determine whether expression and activation of CASP8 are required for positive implantation outcomes and be used as an additional embryo selection tool for other AMA patients utilizing IVF.

Maternal and Fetal Outcomes in Pregnancy in the Fifth Decade of Life and Beyond

ObjectivesThe objective is to evaluate maternal and fetal outcomes at an extremely advanced maternal age (AMA) (over age 50 years) in Calgary. The secondary objective is to determine if there is a role in protocolizing complex care plans for patients at extreme AMAs. MethodsA retrospective chart review was conducted of all pregnancies ≥20 weeks gestation in patients over the age of 50 years that delivered in Calgary between January 2007 and December 2021. Pregnancy data were collected, including maternal age, pre-existing medical conditions, mode and timing of delivery, neonatal outcomes, neonatal intensive care unit (NICU) and adult intensive care unit (ICU) admissions, postpartum complications, and maternal or neonatal death. Data were extracted for maternity patients as well as neonatal ICU databases. Maternal and neonatal outcomes were assessed until discharge from hospital. ResultsAll 23 pregnancies identified were achieved through assisted reproductive technologies. Comorbidities varied, but the most common comorbidities included hypertension and gestational diabetes. Cesarean delivery was the most common form of delivery. Three cases involved postpartum maternal ICU admission. Neonatal outcomes included gestational ages of 22–39 weeks and birth weights of 486–3593 g, with 8 confirmed NICU admissions. The most common neonatal complications were jaundice and small for gestational age. ConclusionsExtremely AMA patients are more likely to have pre-existing comorbidities and develop comorbidities during pregnancy. The potential for adverse maternal and fetal outcomes is greater for these pregnancies; however, the complications are diverse and developing a universal complex care plan is difficult.

Growth hormone supplementation during ovarian stimulation in women with advanced maternal age undergoing preimplantation genetic testing for Aneuploidy

BackgroundStudies have shown that supplementation with recombinant human GH (rh-GH) during ovarian stimulation (OS) may improve the ovarian response and clinical outcomes of IVF. However, it remains unclear whether GH is associated with the ploidy status of embryos, and therefore, is unable to explain the underlying reason for the effect of GH on IVF outcomes. This study aimed to investigate whether GH supplementation in women with advanced maternal age (AMA) during OS is related to an increased probability of obtaining euploid blastocysts.MethodsThis was a single center retrospective cohort study. The data of all women aged 38–46 years who underwent their first preimplantation genetic testing for aneuploidy (PGT-A) cycle between January 2021 and June 2022 were reviewed. Patients in the GH group received 4 IU/day subcutaneous GH supplementation from the beginning of OS to the trigger day, and patients in the control group did not. A total of 140 patients in the GH group and 272 patients in the control group were included after 1:2 propensity score matching.ResultsThe baseline and cycle characteristics between the two groups were similar. The proportion of cycles which obtained euploid blastocysts was significantly higher in the GH group than that in the control group (41.43% vs. 27.21%, P = 0.00). The GH group had a significantly higher euploid blastocyst rate per cohort (32.47% vs. 21.34%, P = 0.00) and mean euploid blastocyst rate per cycle (per biopsy cycle 0.35 ± 0.40 vs. 0.21 ± 0.33, P = 0.00; per OS cycle 0.27 ± 0.38 vs. 0.16 ± 0.30, P = 0.02). However, the benefit of GH was more significant in patients aged 38–40 years, but not significant in patients aged 41–46 years. Pregnancy outcomes were similar between the two groups after embryo transfer.ConclusionsGH supplementation during OS is associated with a significantly increased probability of obtaining euploid blastocysts in women aged 38–40 years, but this benefit is not significant in women aged 41–46 years. Our results explained the underlying reason for the effect of GH on IVF outcomes in existing studies, and might be helpful for AMA patients undergoing PGT-A cycles to obtain a better outcome meanwhile to avoid over-treatment.Trial registrationNCT05574894, www.clinicaltrials.gov.

Aneuploidy in oocytes from women of advanced maternal age: analysis of the causal meiotic errors and impact on embryo development.

In oocytes of advanced maternal age (AMA) women, what are the mechanisms leading to aneuploidy and what is the association of aneuploidy with embryo development? Known chromosome segregation errors such as precocious separation of sister chromatids explained 90.4% of abnormal chromosome copy numbers in polar bodies (PBs), underlying impaired embryo development. Meiotic chromosomal aneuploidies in oocytes correlate with AMA (>35 years) and can affect over half of oocytes in this age group. This underlies the rationale for PB biopsy as a form of early preimplantation genetic testing for aneuploidy (PGT-A), as performed in the 'ESHRE STudy into the Evaluation of oocyte Euploidy by Microarray analysis' (ESTEEM) randomized controlled trial (RCT). So far, chromosome analysis of oocytes and PBs has shown that precocious separation of sister chromatids (PSSC), Meiosis II (MII) non-disjunction (ND), and reverse segregation (RS) are the main mechanisms leading to aneuploidy in oocytes. Data were sourced from the ESTEEM study, a multicentre RCT from seven European centres to assess the clinical utility of PGT-A on PBs using array comparative genomic hybridization (aCGH) in patients of AMA (36-40 years). This included data on the chromosome complement in PB pairs (PGT-A group), and on embryo morphology in a subset of embryos, up to Day 6 post-insemination, from both the intervention (PB biopsy and PGT-A) and control groups. ESTEEM recruited 396 AMA patients: 205 in the intervention group and 191 in the control group. Complete genetic data from 693 PB pairs were analysed. Additionally, the morphology from 1034 embryos generated from fertilized oocytes (two pronuclei) in the PB biopsy group and 1082 in the control group were used for statistical analysis. Overall, 461/693 PB pairs showed abnormal segregation in 1162/10 810 chromosomes. The main observed abnormal segregations were compatible with PSSC in Meiosis I (MI) (n = 568/1162; 48.9%), ND of chromatids in MII or RS (n = 417/1162; 35.9%), and less frequently ND in MI (n = 65/1162; 5.6%). For 112 chromosomes (112/1162; 9.6%), we observed a chromosome copy number in the first PB (PB1) and second PB (PB2) that is not explained by any of the known mechanisms causing aneuploidy in oocytes. We observed that embryos in the PGT-A arm of the RCT did not have a significantly different morphology between 2 and 6 days post-insemination compared to the control group, indicating that PB biopsy did not affect embryo quality. Following age-adjusted multilevel mixed-effect ordinal logistic regression models performed for each embryo evaluation day, aneuploidy was associated with a decrease in embryo quality on Day 3 (adjusted odds ratio (aOR) 0.62, 95% CI 0.43-0.90), Day 4 (aOR 0.15, 95% CI 0.06-0.39), and Day 5 (aOR 0.28, 95% CI 0.14-0.58). RS cannot be distinguished from normal segregation or MII ND using aCGH. The observed segregations were based on the detected copy number of PB1 and PB2 only and were not confirmed by the analysis of embryos. The embryo morphology assessment was static and single observer. Our finding of frequent unexplained chromosome copy numbers in PBs indicates that our knowledge of the mechanisms causing aneuploidy in oocytes is incomplete. It challenges the dogma that aneuploidy in oocytes is exclusively caused by mis-segregation of chromosomes during MI and MII. Data were mined from a study funded by ESHRE. Illumina provided microarrays and other consumables necessary for aCGH testing of PBs. None of the authors have competing interests. Data were mined from the ESTEEM study (ClinicalTrials.gov Identifier NCT01532284).

P-240 High mitochondrial DNA content in Day6 blastocyst may impair ongoing pregnancy rate

Abstract Study question Is there an association between mitochondrial DNA (mtDNA) content and Ongoing Pregnancy Rate (OPR) in D5 or D6 euploid blastocyst? Summary answer Day6 OPR is decreased in high mtDNA content blastocyst. Day5 and Day6 mtDNA levels are independent of maternal age or standard morphology. What is known already Preimplantation development is an energy-demanding process and mitochondrial ATP production is crucial for cellular activity in fast replicating cells. Mitochondrial content in preimplantation embryo has been proposed as a marker of embryo potential in term of viability and implantation success though the dynamics and distribution of mitochondria in human embryo is still debated. In recent years, it has been suggested that low mtDNA levels were associated with euploid chromosomal complement and higher implantation rate while other studies failed to find a correlation between mtDNA content and reproductive outcome. Study design, size, duration This study is a retrospective cohort analysis from 2020 to 2022 including 343 Day5 and 187 D6 single euploid blastocyst transfer. Primary endpoint was OPR beyond pregnancy week 16. Day5 and Day6 frozen-thawed transfer were divided based on blastocyst mtDNA content in four groups: Day5-high, Day5-low, D6-high, D6-low. Secondary endpoints were relationship between mtDNA content, maternal age and standard morphology in all obtained blastocysts. Statistical differences were compared by Chi-Square test. Participants/materials, setting, methods 771 couples performed IVF cycles with next-generation sequencing (NGS)-preimplantation genetic testing of aneuploidy (PGT-A) (age 19-47yrs; Mean age 37.8yrs). Following culture in sequential media 700 euploid blastocyst were obtained and mitochondrial and chromosomal DNA copy number variation were examined simultaneously with next generation sequencing (NGS) methodology. mtDNA copy numbers was based on the observed ratios of sequence coverages between mtDNA and nuclear DNA. Main results and the role of chance In our clinical setting OPR is similar in Day5 vs. Day6 transfers (55% vs. 49% n.s.). However when mtDNA content is considered D6-low OPR is comparable to D5-high or low (57.3%; 53.3%; 57,3% respectively n.s.) while D6-high transfers yield significantly decreased OPR (31,2% p < 0.05). When stratified by age only Advanced Maternal Age (AMA) patients ( > = 38yrs) showed this decrease at a significant level (Day6 high OPR 20% p < 0,05).This result in transferred blastocyst is obtained despite high:low ratio of all biopsied blastocyst is constant in Day5 (1:1) (47%-53%) and markedly decreased in Day6 (1:4) (25%-75%) either overall or in younger (n.s.) and AMA patients (n.s.). Moreover when standard morphology distribution is evaluated according to Gardner classification criteria top, fair and poor quality blastocysts display the same 1:1 high:low blastocysts mtDNA ratio in Day5 and 1:4 in Day 6 overall and in younger and AMA patients. Hence, the mtDNA blastocyst content is independent of patients’ age and blastocyst quality. The origin of Day6 OPR decrease could therefore depend on the number of Day6-high blastocyst transferred in AMA patients and ultimately in the number of blastocyst available to transfer for each patient. Limitations, reasons for caution Due to the small numbers of Day6-high mtDNA blastocyst, a larger sample size is required to confirm these preliminary findings. Moreover, the retrospective nature of the study may introduce some bias mainly in patients’ characteristics and the strategy of embryo selected for transfer. Wider implications of the findings While Day5-high blastocyst yield higher OPR the persistence of higher mtDNA levels in Day6 blastocyst may hamper their implantation potential. Our findings may help to select the embryo to transfer to maximize transfer success. D6 blastocysts with low mtDNA content should be preferred whenever a choice is possible. Trial registration number Not Applicable

O-307 Aneuploidy in oocytes of women of advanced maternal age: impact on embryo development and evidence for a novel mechanism of meiotic error

Abstract Study question In oocytes of advanced maternal age (AMA) women, what is the association of aneuploidy with embryo development and what are the mechanisms leading to aneuploidy? Summary answer We confirmed precocious separation of sister chromatids as the main cause of aneuploidy. Known chromosome segregation errors explained 90.4% of the observed abnormal chromosome copy numbers in polar bodies. What is known already Meiotic chromosomal aneuploidies in oocytes correlate with AMA (>35 years), and can affect over half of oocytes in this age group. This underlies the rationale for polar body (PB) biopsy as a form of early PGT-A, as performed in the ‘ESHRE STudy into the Evaluation of oocyte Euploidy by Microarray analysis’ (ESTEEM) randomised controlled trial (RCT). So far, chromosome analysis of oocytes and PBs has shown that precocious separation of sister chromatids (PSSC), meiosis II (MII) nondisjunction (ND) and reverse segregation (RS) are the main mechanisms leading to aneuploidy in oocytes. Study design, size, duration Data was sourced from the ESTEEM study, a multicentre RCT from seven European centres to assess the clinical utility of PGT-A on PBs using array comparative genomic hybridisation (aCGH) in patients of AMA (36-40 years). This included data on the chromosome complement in PB pairs, and on embryo morphology in a subset of embryos, up to day 6 post insemination (dpi), from both the intervention (PB biopsy for PGT-A) and from control (no biopsy) arms. Participants/materials, setting, methods ESTEEM recruited 396 AMA patients: 205 in the intervention group and 191 in the control group. Complete genetic data from 693 PB pairs were analysed. Additionally, the morphology from 1034 embryos generated from fertilized oocytes (2 pronuclei) in the PB biopsy group and 1082 in the control group were compared using age-adjusted multilevel mixed-effect ordinal logistic regression for each day of embryo scoring and summarized with adjusted odds ratios (aOR) and 95% confidence intervals (CI). Main results and the role of chance Overall, 461/693 PB pairs showed abnormal segregation in 1162/10810 chromosomes. The main observed abnormal segregations were compatible with PSSC in meiosis I (MI) (n = 568/1162; 48,9%), ND of chromatids in MII or RS (n = 417/1162; 35.9%) and less frequently ND in MI (n = 65/1162; 5.6%). For 112 chromosomes (112/1162; 9,6%), we observed a chromosome copy number in PB1 and PB2 that is not explained by any of the known mechanisms causing aneuploidy in oocytes. We observed that embryos in the PGT-A arm of the RCT did not have a significantly different morphology between 2 and 6 dpi compared to the control group, indicating that polar body biopsy did not affect embryo quality. Following age-adjusted multilevel mixed-effect ordinal logistic regression models performed for each embryo evaluation day (using the before-mentioned embryo scoring subcategories), aneuploidy was associated with a decrease in embryo quality on day 3 (aOR 0.62, 95% CI 0.43-0.90), day 4 (aOR 0.15, 95% CI 0.06-0.39) and day 5 (aOR 0.28, 95% CI 0.14-0.58). Limitations, reason for caution RS cannot be distinguished from normal segregation or MII ND using aCGH. The observed segregations were based on the detected copy number of PB1 and PB2 only and were not confirmed by the analysis of embryos. The embryo morphology assessment was static and single observer. Wider implications of the findings Our finding of frequent unexplained chromosome copy numbers in polar bodies indicates that our knowledge of the mechanisms causing aneuploidy in oocytes is incomplete. It challenges the dogma that aneuploidy in oocytes is exclusively caused by missegregation of chromosomes during meiosis I and II. Study funding/competing interest(s) Data was mined from a study funded by ESHRE. Illumina provided microarrays and other consumables necessary for aCGH testing of polar bodies. None of the authors have competing interests. This work is dedicated to the memory of Professor Joep Geraedts. Trial registration number NCT01532284 Study funding Yes Funding source Funding by national/international organization(s)

P-303 Outcomes of day 5 versus day 6 blastocysts: correlation of euploidy, implantation and embryo quality

Abstract Study question Are outcomes of day 5 (D5) blastocysts better than day 6 (D6) blastocysts in a PGT-A program? Summary answer Outcomes of day 5 embryos show more blastocysts, better quality, more euploidy due to better quality and higher implantation on same quality than day 6. What is known already Human embryos optimally reach the blastocyst stage after five days of culture, but some have a slower development. The superiority of day 5 blastocysts compared to day 6 blastocysts in fresh cycle transfers was previously demonstrated and attributed mainly to endometrial asynchrony. Data from frozen blastocysts transfers showed conflicting results, some studies have announced higher pregnancy rates after day 5 transfer compared with day 6 transfer, while others have shown equivalent outcomes. However, none of these studies have compared outcomes between same quality and euploid day 5 (D5) frozen blastocysts versus those frozen on day 6 (D6). Study design, size, duration Retrospective observational study performed in a private centre between May 2017 and December 2022. The study includes the data analysis of 5599 D5 and D6 blastocysts undergoing PGT-A obtained from 819 patients following 1295 PGS cycles. 948 euploid blastocysts with known implantation outcome were transferred in 789 frozen embryo transfers. Blastocyst morphology was scored in 3 groups: A: excellent (AA, AB, BA), B: good (BB), C: average and poor-quality embryos (BC, CB, CC). (Gardner-Schoolcraft classification) Participants/materials, setting, methods PGT-A with NGS technology was offered to patients of advanced maternal age and/or with repeated IVF failures. Trophectoderm biopsies were performed on D5 and/or D6 embryos, with laser assistance. (Navilase, OCTAX) We compared both populations (D5 and D6) in terms of number of blastocysts achieved and distribution of embryo quality of each population. As primary outcome, same-quality group results of euploid rate and implantation were compared according to the day of blastocyst development (D5 and D6). Main results and the role of chance Vast majority of the blastocysts were biopsied on D5 (71.8%, n = 4017) versus (28.2%, n = 1582) biopsied on D6. The proportion of three quality-categories of blastocysts according to D5/D6 is uneven. Quality A = 18.6% vs 3,5%. Quality B = 72,4% vs 59,6%. Quality C = 9,0% vs 36,9%, respectively, showing significative differences between D5/D6 (Chi^2 p-values of 3 groups< 0.001), concluding that overall D5 quality is better than D6. Overall euploidy rate on D5 population versus D6 was 31,3% vs 23,3% (p value <0.001), showing significant difference in favour of D5. But layering on 3 quality categories on D5/D6, the euploidy rate was 44,7% vs 51,8% for quality A, 29,6% vs 26,6% for quality B and 17,6% vs 14,9% for quality C, respectively, showing no significative differences D5/D6 (Chi^2 p-values: A = 0,331; B = 0,067; C = 0,280). Euploidy is not D5/D6 dependant but quality dependant. Overall implantation on D5 (65,9%) is higher than D6 (40,4%) (p value <0.001). Layering again, on D5 the implantation was 75,0% vs 66,7% for quality A, 63,8% vs 46,4% for quality B and 35,3% vs 26,3% for quality C, respectively. Despite implantation being higher on D5 on all three groups only group B shows D5/D6 significative differences. (Chi^2 p-values: A = 0,651; B < 0.001; C = 0,360). Implantation is embryo quality and D5/D6 dependant. Limitations, reasons for caution The study is limited by its retrospective nature and the low number of grade A D6-euploid blastocysts available to transfer. Additionally, it is common to transfer more than one grade C quality embryo to increase the chances of pregnancy, losing implantation track of these type. Wider implications of the findings It was uncontested that D5 blastocysts had better reproductive potential, but we managed to quantify this potential according to euploidy and implantation rates based on embryo quality, which remains the most important predictive biomarker for selecting the best embryo to transfer and reducing the time to achieve a pregnancy. Trial registration number not applicable

P-639 Are our advanced maternal age population being affected by the shortage of HP-hMG?

Abstract Study question Could we stimulate patients of advanced maternal age in the face of a shortage of HP-hMG without impacting outcomes? Summary answer Given the current low availability of HP-hMG, it is safe to stimulate only with recombinant FSH in women of advanced maternal age without affecting results. What is known already . Studies on the role of luteinizing hormone (LH) supplementation in patients undergoing assisted reproductive treatments use different sources of LH bioactivity. It is well known that the addition of LH supplementation was associated with a tendency towards improved IVF outcome in specific profiles of patients undergoing Assisted Reproductive treatment. However, during the last quarter of 2022, we are facing a temporary fall in the global supply of HP-hMG, which has hCG-driven LH activity, and may impact ovarian stimulation outcomes in women of advanced maternal age undergoing a preimplantation genetic testing treatment (PGT). Study design, size, duration Retrospective and observational study during November-December 2022 in any of the 11 clinics belonging to the IVIRMA group in Spain. Study population included women ≥38 years undergoing PGT treatment who received monotherapy with recombinant FSH (n = 73), a combination of FSH + HMG containing an FSH: LH activity in a ratio 1:1 (n = 103), or a fertility drug with recombinant FSH + recombinant LH in a 2:1 ratio (n = 112). The study was approved by an IRB (2003-MAD-020-AR) Participants/materials, setting, methods All women underwent short GnRH antagonist protocol. Initial doses were adjusted based on weight and body mass index according to the clinician’s experience. Daily doses of 0.25 mg GnRH antagonist were started on day 6 of stimulation. Finally, a single dose of 0.2 mg GnRH agonist was administered to trigger final oocyte maturation. Embryo biopsy was performed on day 5 with a subsequent freeze-all. A frozen single embryo transfer was accomplished in a subsequent cycle. Main results and the role of chance Assuming the limitations of the study design, we observed significant differences in gonadotropin doses but not in retrieved oocytes, metaphase II oocytes or euploidy rate: the results were as follows for recombinant FSH, FHS + hMG and FSH + LH respectively: gonadotropin doses [2254 (692) vs. 2033 (680) vs. 2000 (660), p = 0.0035]; retrieved oocytes [10.1 (5.4) vs. 11.1 (8.0) vs. 9.2 (6.0), p = 0.131], metaphase II oocytes [8.7 (4.7) vs. 9.8 (7.1) vs. 8.3 (5.1), p = 0.147]; and euploidy rate (38.7% vs. 36.3% vs. 31.5%, p = 0.182). Moreover, recombinant FSH in monotherapy in this specific population could guarantee the efficiency of the cycle since there are no significant differences in the usable blastocyst rate. Finally, clinical results were analyzed in those cases in which a frozen single embryo had been performed in a subsequent artificial cycle, in which the effect of LH on the endometrium is obviated; once again, no significant differences were observed between the study groups neither for the implantation rate (50% vs. 56% vs. 45%, p = 0.780) or the clinical pregnancy rate (50% vs. 56% vs. 45%, p = 0.772). Limitations, reasons for caution This is a retrospective and observational study and thus possible confounders cannot be completely excluded. More data are needed to draw firm conclusions and it will be critical to increase the sample size to check if the results observed in this work remains in the general population. Wider implications of the findings In view of tailoring assisted reproductive protocols to meet patient needs and improve the likelihood of positive outcomes, these data suggest that it is optimal to perform an ovarian stimulation protocol only with recombinant FSH in a frozen embryo program in advanced maternal age context without clinical outcomes being affected. Trial registration number Not applicable

P-253 Clinical efficacy of PGT-A according to maternal age and embryo quality in blastocyst stage

Abstract Study question To establish the usefulness of PGT-A as an embryo selection tool based on the quality of the blastocyst and the age of the patient. Summary answer The euploidy rate of good quality blastocysts decreases dramatically with increasing maternal age. What is known already One of the fundamental objectives to achieve an optimal gestation rate is the selection of the embryo with the highest implantation potential. For this purpose, morphokinetics and aneuploidy detection are used. Most aneuploidies arise in maternal meiosis, and increase exponentially in women over the age of 35 years, coinciding with the rapid decline in IVF success and live birth rates in patients of advanced maternal age. Study design, size, duration In the present retrospective study, embryo quality of 321 blastocysts was evaluated from June 2020 to January 2023. They were analyzed according to the ASEBIR (2015) classification and using preimplantation genetic testing for aneuploidy (PGT-A) with next-generation sequencing (NGS). Participants/materials, setting, methods A total of 321 blastocysts were analyzed using PGT-A from which 101 were euploid. This 101 blastocysts were classified according to the morphokinetic (A or B (good quality) and C (medium quality)) and the maternal age (<35, 35-36, 37-38, 39-40, 41-42, 43-44 and 45 -46 years). Out of the 101 euploid blastocysts, 78 embryos were classified as A or B (good quality) and 23 as C (medium quality) according to the ASEBIR classification. Main results and the role of chance The euploidy rate of the embryos decreases as the age of the patient increases, being 73% for good quality embryos in patients under 35, 54% in patients between 35-36, 37% in patients between 37- 38, 31% in patients between 39-40, 23% in patients between 41-42, 5% in patients between 43- 44 and 0 % in patients between 45-46 years. For medium quality embryos, the euploidy rate is 58% in patients under 35, 38% in patients between 35-36, 30% in patients between 37-38, 26% in patients between 39-40, 0% in patients between 41-42, 0% in patients between 43-44 and 0% in patients between 45- 46 years. In patients under 35 years, PGT-A will improve pregnancy rates considering that it is an invasive and costly technique. In patients between 35-36 years, PGT-A is a very useful tool when embryos have C quality as well as, in patients between 37- 40, regardless of embryo quality. Furthermore, patients between 41-42 years with good quality embryos, PGT-A will decrease the abortion rates and increase the pregnancy rates. In contrast, patients with C-quality embryos should not start new cycles, as well as patients with over than 43 years due to the low probability of euploidy. Limitations, reasons for caution Studies of larger sample size and study period are required to validate our current findings. Furthermore, more information about fertilization, pregnancy, birth rate and perinatal outcomes could improve the current results. Wider implications of the findings Making the decision whether or not to use PGT-A on the day of blastocyst formation helps to choose the best strategy by individualizing each case according to the maternal age and the quality of the blastocysts. Decreasing cycle times will always be beneficial to patients and their outcomes. Trial registration number Does not apply

O-146 Oocyte donation does not increase live birth rates in young women suffering from recurrent pregnancy loss

Abstract Study question Does oocyte donation improve reproductive outcomes in recurrent pregnancy loss (RPL) patients? Summary answer Oocyte donation increases live birth and reduces miscarriage rates in RPL women older than 35, but it does not improve reproductive outcomes in younger patients. What is known already Recurrent pregnancy loss (RPL) is defined as 2 or more pregnancy losses prior to 20-24 weeks of gestation and has an incidence of approximately 1 to 2% in couples trying to conceive. Known risk factors for RPL are embryo aneuploidy, advanced maternal age (AMA), previous miscarriages, uterine abnormalities, parental chromosomal abnormalities, antiphospholipid syndrome, endocrine factors, such as thyroid function or obesity, and thrombophilia. However, 50-70% of patients suffering from RPL do not present any known risk factor, making the management of idiopathic RPL patients particularly challenging for ART clinicians. Study design, size, duration This is a cohort retrospective study involving 2 centers. Charts from 18,273 women undergoing IVF treatment between 2011 and 2020 were reviewed. A total of 912 patients (5%) met the definition of RPL and were classified into study groups based on their age and oocyte origin: ≤35 years old receiving oocyte donation (n = 39) or using their own oocytes (n = 35), and AMA women using donor eggs (n = 716) or their own (n = 122). Participants/materials, setting, methods Demographic variables analysed included known risk factors, number of transferred embryos, day of embryo transfer (3 vs 5) and sperm origin (partner/donor). Differences in biochemical, clinical, ongoing pregnancy, miscarriage and live birth rates were assessed by Pearson’s Chi-squared or Fisher’s exact test. P-values <0.05 were considered significant. Main results and the role of chance RPL patients had 2.77±1.27 pregnancy losses overall (2.76±1.37 in women ≤35 and 2.77±1.26 in patients >35). Most RPL patients (91.9%) were of AMA. Other RPL-associated risk factors, including uterine malformations, previous pregnancy losses, chromosomal abnormalities and thrombophilia were identified in 207/912 patients (22.7%). Interestingly, these were more frequent in patients <35 (37.8% vs 21%, p = 0.001). Young RPL women presented higher rates of karyotype abnormalities than older patients (17.6% vs 3.8%, p < 1x10-04), while showing a similar incidence of uterine abnormalities (14.9% vs 12.9%, p > 0.63) and thrombophilia (4.1% vs 4.7%, p > 0.81). RPL patients >35 preferentially underwent oocyte donation (85.4% vs 52.7%, p < 1x10-04), which led to significantly higher biochemical (52.5% vs 17.1%, p < 1x10-04), clinical (42.4% vs. 8.5% p < 1x10-04), ongoing pregnancy (37.9% vs 5.1%, p < 1x10-04), live birth (32% vs 4%, p < 1x10-04) and lower miscarriage rates (10.5% vs 40%, p = 0.0186) than in autologous cycles. In contrast, RPL patients <35 had similar reproductive outcomes: biochemical (41% vs. 52.9), clinical (28.2% vs. 37.1%), ongoing pregnancy (25.6% vs 29.4%), live birth (25.6% vs 26.4%) and miscarriage rates (9% vs 23%), regardless of oocyte origin (donated vs own, p > 0.05 for all cases). Importantly, this was also true for a small subgroup of idiopathic young RPL patients (n = 13). Limitations, reasons for caution The main limitation of this study is its retrospective nature, which does not allow for full elucidation of all potential confounders. The number of young RPL patients undergoing oocyte donation may be too low to draw significant conclusions. Wider implications of the findings RPL can be resolved in AMA patients by using donor oocytes, which points to key roles of oocyte quality and aneuploidy underlying RPL aetiology. However, RPL is not ameliorated by oocyte donation in young women, suggesting an endometrial/systemic origin and highlighting the need to further study mechanisms driving this disorder. Trial registration number Not applicable

P-710 Single-cell proteomic analysis of human oocytes reveals a decreased abundance of meiosis and proteostasis regulators with advanced maternal age

Abstract Study question How does maternal age affect the proteomic content of her oocytes during their final meiotic progression? Summary answer Compared to young oocytes, oocytes obtained from women of advanced maternal age (AMA) show a decreased abundance of meiosis and proteostasis regulators. What is known already It is well established that AMA leads to a decline in oocyte number and quality, key limiting factors of female reproductive success. Poor oocyte quality is tied to aneuploidies and alterations in cytoplasmic fitness, however the precise mechanisms that underlie oocyte aging remain unknown. Currently knowledge has been largely restricted to transcriptomic studies with no information on the proteome of oocytes obtained from women of AMA. Single-cell proteomic studies may shed light on these mechanisms, as proteins and (post)-translational modifications regulate events unfolding at the oocyte-to-embryo transition in transcriptionally silent oocytes. Study design, size, duration A total of 67 oocytes, obtained from 52 women undergoing controlled ovarian stimulation cycles between May 2021 and May 2022, were included in the study. We obtained 18 fresh germinal vesicle oocytes (GVs) and 17 vitrified in vivo matured metaphase II oocytes (MIIs) from young women (oocyte donors), and 18 GVs and 14 MIIs from AMA. Participants/materials, setting, methods The oocytes were obtained from oocyte donors (n = 27) and AMA patients (n = 25) with a mean age of 24 ± 3.9 years and 39 ± 1.8 years respectively. Single denuded oocytes were snap frozen and their proteomic profiles were generated using the mass spectometry based method plexDIA . Mann-Whitney U test (fold change >|1.5|, adjusted p-value <0.05), Spearman correlation (rs ≥|0.4|, p-value <0.05) and ggplot were used in R to compare the different groups. Main results and the role of chance A total of 2105 proteins were quantified across oocytes stages and age groups. Most of proteins were present in oocytes independently of their maturation state and related to vital processes, such as cellular respiration and energy metabolism. Fifty-four proteins varied in abundance between immature and mature oocytes, including RS14, YBOX2 and RL10A (translational regulation), CLUS and AHSA1 (post-translational modifications) and proteins involved in meiosis progression (WEE2, AURKA, BUB1B, SPDLY). Notably, we observed a negative correlation between protein levels and maternal age for meiosis regulators (e.g.1433E, CDK1; rs: -0.7 and -0.5), meiotic spindle proteins (e.g. DYL2, CAPZB, ARP3, GCP3; rs: -0.6, -0.6, -0.5, -0.5 respectively) and for 5 proteasome subunits (PRS8, PRS6A, PRS10, PSA6, PSMF1; rs: -0.4 to -0.7). The proteasome is a degradation machinery with multiple roles, including meiosis regulation and proteostasis maintenance. Additional proteins of the proteostasis network were found to decline with age (e.g., TCPH, TCPA; rs: -0.5, -0.5). Loss of proteostasis is a common feature of aging and diseases. We also observed a positive correlation between mitochondrial and stress response proteins and maternal age (e.g. ATP5L, TMX1; rs: 0.6, 0.5). Limitations, reasons for caution Unlike GVs that were collected fresh, MII oocytes underwent vitrification and warming before being included in the study due to clinical protocols. These procedures may have unknown effects on the proteome. Wider implications of the findings We show that a woman’s age correlates with changes in her oocyte proteome, which may contribute to the deterioration of oocyte quality through dysregulation of meiosis and disturbance of proteostasis. Proteins showing differential expression in oocytes from women of AMA, such as proteasome, may become targets for improving oocyte quality. Trial registration number Not applicable

O-205 Poor mitochondrial metabolism impairs meiosis and contributes to reduced oocyte maturation rates in patients with advanced maternal age

Abstract Study question Is there a relationship between poor mitochondrial metabolism and impaired meiotic progression of germinal vesicle (GVs) oocytes in women of advanced maternal age (AMA)? Summary answer Poor mitochondrial metabolism impairs meiotic progression in human oocytes, contributing to a lower oocyte maturation capacity in women of AMA. What is known already High aneuploidy rates and impaired metabolism are characteristic features of AMA oocytes. Studies in mouse suggest that successful meiotic maturation and metabolic competency may be functionally linked, however this relationship has not been clearly established in human. Metabolic dynamics can be visualized by indirect measurements through mitochondrial staining and quantified more directly using Fluorescence Lifetime Imaging Microscopy (FLIM). This live-imaging approach can generate metabolic timelapse profiles of oocytes throughout meiosis. We performed an extensive characterization of oocyte metabolism in maturing GVs, obtained from both young and AMA patients, to establish the importance of mitochondrial metabolism during meiosis. Study design, size, duration A total of 401 GVs from young (≤30 years, n = 264) and AMA (>37 years, n = 137) women were included in the study. GVs were matured in vitro in G2-plus medium for 30 hours. Maturation was determined by the presence of an extruded polar body. Oocytes were used for FLIM (n = 175) and immunofluorescence (IF) analysis (n = 226). Further, mitochondrial metabolism loss of function studies (n = 64) were performed by treating young GVs with 1μM Trifluoromethoxy-carbonylcyanide-phenylhydrazone (FCCP) for 30 minutes. Participants/materials, setting, methods The proteins Dihydrolipoamide-S-Acetyltransferase (D-LAT) and Translocase-of-outer mitochondrial-membrane (TOMM20) were analysed in young and AMA oocytes by IF (Arbitrary-Unit, AU) to assess mitochondrial activity and localization, respectively. Fluorescence mean intensities were quantified with ImageJ and compared by t-test; maturation rates were compared by Chi-squared test. FLIM comprehensive metabolism (NADH; FAD+) were taken at GV stage. Different FLIM parameters (fluorescence intensity, fraction bound, short/long lifetime) were evaluated individually and combined into the Redox ratio (NADH intensity/FAD+ intensity). Main results and the role of chance Mitochondrial staining showed a common pattern in young and AMA GV oocytes, with a uniform localization of mitochondria in the ooplasm (TOMM20) and a subcortical localization of active organelles (D-LAT). These patterns were confirmed by in-live FLIM analysis. The total mitochondria abundance was comparable between AMA and young GV oocytes (intensity of 61674±24322 AU in young, 32186±33414 AU in AMA, p = 0.195), however, active mitochondria were diminished in AMA compared to young GVs both by IF and FLIM (intensity of 78614±58534 AU in young, 12517±10187 AU in AMA, p = 0.003; Redox ratio in young 2e+00±0.15, in AMA 1e+00 ± 0.16, p = 2.969e-05). Notably, young oocytes matured at a significantly higher rate (86.3%; 63/73) than AMA oocytes (62.3%; 38/61; p = 0.002). Moreover, FLIM imaging revealed that GVs with a higher metabolism were more likely to complete meiosis to MII (Redox ratio 2e+00±0.17 in GVs matured to MII, 1e+00±0.18 in non-matured, p = 1.054e-06). Following treatment with FCCP, young GVs showed a similar phenotype to AMA oocytes, with a significant decrease in mitochondrial activity (intensity of 78614±58534 IU in untreated and 11554±16131 IU in treated GVs, p = 0.019), and an associated drop-in maturation rate. Ultimately, only 39.5% (17/43) of the young treated GVs were able to accomplish meiotic maturation. Limitations, reasons for caution Maturation rates were assessed by the presence of an extruded PB and variations in spindle assembly timings may have been overlooked. The quantification of mitochondrial activity in loss of function studies was assessed only by IF staining. Wider implications of the findings Our findings demonstrate the presence of a functional link between oocyte metabolism and impaired meiosis, which may contribute to the decline of oocyte quality with age. Given that live-metabolic imaging is able to discern GVs that progress through meiosis, this approach may represent a valuable non-invasive tool in oocyte selection. Trial registration number not applicable

P-636 Euploid blastocysts obtained in advanced maternal age women either in donor or autologous egg cycles showed similar live birth rates: a retrospective cohort study

Abstract Study question Do euploid blastocysts have the same implantation and live birth rate in autologous and donor egg cycles in patients with advanced maternal age (AMA)? Summary answer Euploid blastocysts transferred in AMA patients showed that implantation and live birth rates (LBR) were not significantly different between reproductively younger and older women. What is known already Aneuploidy rates increase steadily with age, reaching >80% in women >42 years old. The high prevalence of aneuploidies may provide an explanation for the low LBR achieved by assisted reproductive treatments, especially for women with AMA. Similarly, among oocyte donors, age is critical to achieving reproductive success independently of the recipients’ age. In donor cycles, recipients using oocytes from older donors had a statistically significantly lower LBR than younger donors. Currently, it still remains unclear whether the LBR differs between young donors versus old infertile patients in the context of euploid blastocyst transfers. Study design, size, duration Multicenter retrospective study with the preimplantation genetic test for aneuploidies (PGT-A) in both autologous and donor oocytes cycles between January 2018 and January 2021 was conducted at three different institutions (IVI-RMA, GeneraLife and Humanitas Fertility Center). 556 patients were included and matched 1:1 for the age of recipients, euploid blastocyst morphological quality, and day of development. In the frozen embryo transfers, endometrial preparation was done using hormonal replacement therapy (HRT) or natural cycles (NC). Participants/materials, setting, methods AMA patients older than 39 years underwent IVF. 556 patients who underwent autologous or donor oocyte cycles with at least one euploid blastocyst transferred were matched for oocyte age, blastocyst morphological quality and day of development. Blastocyst ploidy was assessed by aCGH or NGS analysis. Patients with uterine pathologies reported in the dataset were excluded. The primary outcome was LBR per first euploid blastocyst transfer. Outcomes were adjusted for confounders via logistic regression analyses. Main results and the role of chance 278 single euploid blastocysts tested by PGT-A were transferred in both autologous and donor oocyte cycles. No statistical differences were reported in the maternal age at transfer in the two groups (41.91 ± 2.03 and 41.75 ± 1.98, p = 0.55), endometrial thickness [(8.67, 95%CI: 8.45-8.88) and (8.36, 95%CI: 8.05-8.67)] and type of endometrial preparation (HRT or NC). Implantation rate and pregnancy rate were similar without statical difference in autologous or donor cycles, respectively [57.91%, (95%CI: 51.87-63.78) versus 56.83%, (95%CI: 50.79-62.74); p = 0.99)] and N = 158/278 (56.83%, 95%CI: 50.79-62.74) versus N = 161/278 (57.91%, 95%CI: 51.87-63.78), p = 0.86. The rate of ectopic pregnancy was not statistically different in both arms. Even the miscarriage rate was comparable in autologous N = 46/158, 16.55% (95%CI:12.38-21.45) versus donor group N = 45/161, 16.19%, (95%CI:12.06-21.05); p = 0.98. The LBR was not statistically different in autologous N = 111/278 (39.93%, 95%CI:34.13-45.95) and donor group 114/278 (41.01%, 95%CI:35.17-47.04), p = 0.86. No statistical difference was reported for gestational age and birthweight at delivery. The logistic regression analyzed as putative confounders: oocyte age, number of inseminated MII-oocytes, zygotes and euploid blastocysts, sperm parameters, endometrial preparation and endometrial thickness showed no statistical differences. Limitations, reasons for caution Despite the matched design, the retrospective nature is the major limitation of this study. Also, patients received PGT-A using NGS and CGH arrays technology. The aCGH analysis is less sensitive than more recent NGS technology. Lastly, the prevalence of adenomyosis could be underestimated due to retrospective data collection. Wider implications of the findings The dramatic decline in IVF treatment success is primarily caused by aneuploidies. Euploid blastocysts show LBR largely independent of oocyte age. Our study suggests no uterine effect of aging. The reproductive decline in women is mainly related to meiotic failure, therefore future insights should develop strategies to overcome chromosomal aneuploidies. Trial registration number NA

Rates of Vaginal Delivery With Increasing Cervical Dilation After Cervical Ripening and Advanced Maternal Age [ID: 1372406

INTRODUCTION: Pregnant patients of advanced maternal age (AMA) are at an increased risk for cesarean delivery. Our primary objective was to determine the association between cervical dilation after cervical ripening and vaginal delivery rates for AMA versus non-AMA patients. METHODS: This was an IRB-approved, retrospective cohort study conducted at a single tertiary care center, which included nulliparous, term deliveries that required cervical ripening from January 2020 to January 2022. We excluded patients with multifetal gestation, pregestational diabetes, lethal fetal anomalies, prior cesarean delivery, and prisoner status. RESULTS: Altogether, 964 patients met inclusion/exclusion criteria, of whom 17.7% were AMA. Increasing cervical dilation at the end of cervical ripening was associated with higher rates of vaginal delivery, with a mean of 3.7 cm for patients who underwent vaginal delivery and 3.2 cm for those who delivered via cesarean (P<.001). A logistic regression examined the interaction between AMA status with cervical dilation after ripening and vaginal delivery rates, which was not significant (P=.38). After adjusting for AMA status, the odds of having a vaginal delivery increased by 22% for every 1-unit increase in end cervical dilation after ripening (CI 1.12–1.33, P<.001). Compared to non-AMA, after adjusting for end dilation after ripening, AMA patients were 35% less likely to have a vaginal delivery (CI 0.46–0.91, P=.013). CONCLUSION: Advancing cervical dilation after ripening was associated with a higher rate of vaginal delivery overall. However, AMA patients had significantly fewer vaginal deliveries even when controlling for this end cervical dilation.

The Effect of Advanced Maternal Age on Adverse Outcomes Among Forceps-Assisted Vaginal Deliveries [ID: 1355950

INTRODUCTION: Delivery rates among patients of advanced maternal age (AMA) are increasing. Prior studies have shown that AMA is associated with increased pregnancy risks and adverse outcomes. This study’s objective was to evaluate whether AMA is associated with an increase in obstetric anal sphincter injury (OASIS) rates among patients who undergo forceps-assisted vaginal deliveries (FAVDs). METHODS: This was an IRB-approved, retrospective cohort study of singleton gestations with FAVD at a single institution between 2017 and 2021. Primary outcome was rate of OASIS among patients with and without AMA. Secondary outcomes included quantitative blood loss (QBL), neonatal composite of subgaleal and cephalohematoma (adverse neonatal composite), and neonatal intensive care unit (NICU) admission. Quantitative blood loss was assessed using Mann-Whitney U test. Remaining outcomes were assessed using multivariate logistic regression models while adjusting for provider clustering and confounding patient characteristics including episiotomy and birth weight. RESULTS: Nine hundred eighty-three records were included, 704 non-AMA and 279 AMA. Patients of AMA were more likely to be Caucasian and were less likely to be Hispanic, nulliparous, experience spontaneous labor, and undergo episiotomy. Patients of AMA did not demonstrate increased odds of OASIS compared to non-AMA patients (odds ratio [OR] 1.21 [0.78, 1.89]). When age was assessed continuously, there was no association between increasing age and rates of OASIS (OR 1.02 [0.98, 1.06]). There was no statistically significant difference in QBL among the two groups (357.0 versus 350.0 cc, P=.20), NICU admission or adverse neonatal composite. CONCLUSION: Advanced maternal age does not appear to be a risk factor for OASIS or other adverse outcomes in patients undergoing FAVD.

Advanced Maternal Age Associated With Significantly Increased Cervical Ripening Times and Decreased Vaginal Delivery Rates [ID: 1367634

INTRODUCTION: With increasing numbers of advanced maternal age (AMA) gravidas, labor characteristics specific to this population are important to understand. The objective of this study was to examine patterns in cervical ripening times and vaginal delivery rates for patients with AMA. METHODS: This was an IRB-approved retrospective cohort study conducted at a single academic center. Data were collected by retrospective chart review of deliveries from 2020 to 2021. We included nulliparous patients aged 18 or older with singleton pregnancies, pre-pregnancy body mass index of 18.5 or greater, and gestational age of 37.0 or greater. Patients with pregestational diabetes and lethal fetal anomalies were excluded. RESULTS: One thousand twenty-two patients met inclusion and exclusion criteria, 17.7% of whom were AMA. Lower gestational age and less Hispanic ethnicity were noted in the AMA group. Among AMA patients, there was an increase in cervical ripening time as compared to patients aged older than 35 with an average difference of 3.14 hours (CI 1.26–5.01, P=.001). Compared to participants younger than 35, those that are AMA were 36% less likely to have a vaginal delivery (CI 0.46–0.89, P=.008). Median cervical ripening time to vaginal delivery was 15.0 hours for non-AMA and 19.9 hours for AMA patients. At any point of cervical dilation, AMA patients had a 28% less chance to have a vaginal delivery than non-AMA (P<.001). CONCLUSION: Patients who were AMA experienced increased cervical ripening times and decreased rates of vaginal deliveries compared to patients younger than 35. Knowing labor characteristics specific to the AMA population is important for counseling and clinical decision-making.

Advanced Maternal Age Among Nulliparous at Term and Risk of Unscheduled Cesarean Delivery

With the rise in the number of women giving birth at an advanced age, the association between advanced maternal age and adverse obstetrical outcomes is a growing concern in developed countries. Despite the well-established link between advanced maternal age and pregnancy-related complications, there has been limited research examining the specific risks related to unscheduled cesarean delivery in nulliparas at term. This study aimed to evaluate the risks associated with unscheduled cesarean delivery in nulliparas at ≥37 weeks of gestation, comparing the outcomes of younger patients with those aged ≥40 years. This retrospective cohort study was conducted in a tertiary maternity hospital in Switzerland (high-income country). The study included nulliparas who delivered a live-born infant at ≥37 weeks between January 2015 and December 2019. We excluded pregnant women who had a planned cesarean delivery, were aged <18 years, multiparous, delivered before 37 weeks of gestation, or had pregnancies that ended in stillbirth. Participants were divided into 2 age groups: (1) ≥40 years and (2) <40 years. The primary outcome was the incidence of unscheduled cesarean delivery. Its association with advanced maternal age was evaluated after adjusting for confounding factors by multivariate logistic regression, expressed as an adjusted odds ratio. Secondary outcomes included pregnancy outcomes and neonatal outcomes. A total of 5211 patients were included: 173 in the ≥40-years (advanced maternal age) group and 5038 in the <40-years (non-advanced maternal age) group; 26.01% (95% confidence interval, 19.65-33.22; n=45) of women in the advanced maternal age group had an unscheduled cesarean delivery, whereas 15.26% (95% confidence interval, 14.28-16.29; n=769) of women in the non-advanced maternal age group underwent the procedure. Advanced maternal age was associated with unscheduled cesarean delivery, with an adjusted odds ratio of 1.51 (95% confidence interval, 1.06-2.17; P=.024). Among vaginal deliveries, assisted procedures were performed on 29.7% (95% confidence interval, 21.9-38.4; n=38) of advanced maternal age patients vs 20.1% (95% confidence interval, 18.9-21.3; n=856) of non-advanced maternal age patients. Postpartum blood loss >1000 mL occurred in 5.8% (95% confidence interval, 2.8-10.4; n=10) of advanced maternal age patients and 3.1% (95% confidence interval, 2.6-3.6; n=156) of non-advanced maternal age patients. Advanced maternal age is associated with increased risk of unscheduled cesarean delivery among nulliparas. This provides healthcare professionals with confirmation that advanced age may represent an individual risk factor, suggesting that nulliparous patients aged over 40 years may benefit from improved information regarding the factors contributing to this pregnancy outcome.

Increased peripartum bleeding complications in very advanced maternal age patients who conceive via in-vitro fertilization

Peripartum bleeding is a cause of severe maternal morbidity (SMM). In-vitro fertilization (IVF) is associated with hemorrhage risk factors, but is included in risk stratification. Very advanced maternal age patients (≥45 years at delivery) are more likely to require IVF. Our aim was to determine if vAMA patients who conceive with IVF are at increased risk of postpartum hemorrhage, blood transfusion, or unplanned hysterectomy compared to patients with non-IVF pregnancies.

Preimplantation genetic testing for aneuploidy and chromosomal structural rearrangement: A summary of a nationwide study by the Japan Society of Obstetrics and Gynecology.

The Japan Society of Obstetrics and Gynecology conducted a nationwide clinical study to evaluate the pregnancy outcomes of preimplantation genetic testing for aneuploidy or chromosomal structural rearrangement (PGT-A/SR). Patients that had experienced recurrent implantation failure, recurrent pregnancy loss, or chromosomal structural rearrangement were recruited from 200 fertility centers in Japan. For patients in whom one or more blastocysts were classified as euploid or euploid with suspected mosaicism, a frozen-thawed single embryo transfer (ET) was performed. A total of 10 602 cycles, maternal age 28-50 years, were enrolled in this study. 42 529 blastocysts were biopsied, and 25.5%, 11.7%, and 61.7% of embryos exhibited euploidy, mosaicism, and aneuploidy, respectively. At least one euploid blastocyst was obtained in 38.3% of egg retrieval cycles with embryo biopsy. A total of 6080 ETs were carried out, and the clinical pregnancy rate per ET, ongoing pregnancy rate per ET, and miscarriage rate per pregnancy were 68.8%, 56.3%, and 10.4%, respectively. The rates of clinical pregnancy and miscarriage remained relatively constant across all maternal ages. Preimplantation genetic testing for aneuploidy or chromosomal structural rearrangement may improve the pregnancy rate per ET and reduce the miscarriage rate per pregnancy, especially in patients of advanced maternal age.