Identifying key predictive features for live birth rate in advanced maternal age patients undergoing single vitrified-warmed blastocyst transfer.

BACKGROUND: Infertility affects one in six couples worldwide, with advanced maternal age (AMA) posing unique challenges due to diminished ovarian reserve and reduced oocyte quality. Single vitrified-warmed blastocyst transfer (SVBT) has shown promise in assisted reproductive technology (ART), but success rates in AMA patients remain suboptimal. This study aimed to identify and refine predictive factors for live birth following SVBT in AMA patients, with the goal of enhancing clinical decision-making and enabling personalized treatment strategies. METHODS: This retrospective cohort study analyzed 1,168 SVBT cycles conducted between June 2016 and December 2022 at the First Affiliated Hospital of Guangxi Medical University and Nanning Maternity and Child Health Hospital. Nineteen machine-learning models were applied to identify key predictive factors for live birth. Feature selection and 10-fold cross-validation were employed to validate the models. RESULTS: The most significant predictors of live birth included inner cell mass quality, trophectoderm quality, number of oocytes retrieved, endometrial thickness, and the presence of 8-cell blastomeres on day 3. The stacking model demonstrated the best predictive performance (AUC: 0.791), followed by Extra Trees (AUC: 0.784) and Random Forest (AUC: 0.768). These models outperformed traditional methods, achieving superior accuracy, sensitivity, and specificity. CONCLUSION: Leveraging advanced machine-learning models and identifying critical predictive factors can improve the accuracy of live birth outcome predictions for AMA patients undergoing SVBT. These findings offer valuable insights for enhancing clinical decision-making and managing patient expectations. Further research is needed to validate these results in larger, multi-center cohorts and to explore additional factors, including fresh embryo transfers, to broaden the applicability of these models in clinical practice.

How two-child policy affects cesarean section in women with advanced maternal age (AMA): using the Robson classification system.

OBJECTIVES: To study the possible associations between advanced maternal age and cesarean section(CS) under the two child policy. METHODS: This study used a cohort study from Dongguan People's Hospital in Guangdong Province, China from 2017 to 2020. The cohort was restricted to women aged ≥ 20 who give birth to babies with a gestational age of > 28 weeks and a weight of > 1000 g. Divide the advanced maternal age (AMA) pregnant women into two age groups: 35-39 years old and 40 years old or older age. We analyzed CS rate and CS contribution using the modified Robson classification system. Frequency of cesarean was determined for each group and compared by using χ2 and prevalence ratio. RESULTS: Overall, 47654 women were included, of which 7924 (16.63%) were between the ages of 35 and 39, and 1529 (3.21%) were aged 40 or older. The total CS rate is 40.64%, with 36.10% for mothers aged 20 to 34, 57.90% for women aged 35 to 40, and 64.75% for women aged 40 or older age. In the AMA groups (n = 9453), Robson group 2' was the most common, followed by groups 5 and 10. Women at 40 years or older age were 3 times more likely to undergo a cesarean delivery in Robson group 1', and 1.76 times more likely in group 10. The CS rate in group 2' were statistically significantly higher in the very AMA group. CONCLUSIONS: The CS rates increased noticeably with maternal age under the two child policy. Based on the modified Robson classification system, AMA women should pay more attention to primiparous women with single pregnancy, uterine scars, and premature birth in multiple pregnancies.

Effect of advanced maternal age on ischemic stroke vulnerability in aged rats: Investigating on blood-brain barrier permeability and gene expression.

Background: Advanced maternal age (AMA), commonly defined as pregnancy at or above 35 years old. Based on the evidence, this trend has raised concerns about potential health consequences for mothers, particularly in relation to ischemic stroke. Studies suggest that AMA may be associated with a higher risk of ischemic stroke in women due to physiological changes that impact vascular health and increase cardiovascular risk factors. The aim of this study was to investigate the effect of AMA on the extent of damage after ischemic stroke in aged rats. Methods: Female rats that gave birth at an old age (10 months) and at a young age (4 months) were subjected to ischemic stroke in old age (20 months) and subsequently compared.We assessed neurological deficits, infarct volume, blood-brain barrier (BBB) permeability, TNF-alpha levels, total oxidant capacity, and gene expressions that play a role in BBB integrity (VEGF, Occludin, and MMP-9) following ischemic stroke. Results: There were significantly elevated levels of MMP-9 expression and reduced levels of occludin in AMA rats. Additionally, AMA rats had significantly higher levels of TNF-alpha and total oxidant capacity after experiencing an ischemic stroke. AMA rats showed significantly higher brain water content (BBB permeability), infarct volume, and neurological deficits compared to young-aged pregnancies. Discussion: Complex relationship between pregnancy-related physiological changes, aging, vascular gene expression, and inflammatory factors may play a role in the increased vulnerability observed in older pregnant rats. The similarities between pregnancy-related alterations and aging highlight the influence of advanced maternal age on susceptibility to ischemic stroke.

The effect of postpartum nursing guidance on early pelvic floor dysfunction recovery in women of advanced maternal age: a randomized controlled trial.

Objective: This study aimed to investigate the efficacy of postpartum nursing guidance in the treatment of early pelvic floor dysfunction (PFD) in women of advanced maternal age. Methods: A total of 146 patients of advanced maternal age admitted to our hospital between January and December 2021 were enrolled in this study and randomly divided into two groups: the control group and the experimental group, with 73 patients in each group. Parturients in the control group received routine pelvic floor rehabilitation treatment, whereas those in the experimental group were given individualized postpartum nursing guidance alongside routine pelvic floor rehabilitation treatment. The recovery of pelvic floor muscle (PFM) strength, the incidence of PFD diseases and nursing satisfaction were compared between the two groups after 3 months of treatment. Results: The enhancement of PFM strength in the experimental group significantly surpassed that in the control group. Furthermore, the experimental group exhibited a notably lower overall occurrence of PFD and significantly greater maternal satisfaction compared with the control group, and the difference was statistically significant (p < 0.05). Conclusion: Combining postpartum nursing guidance with pelvic floor rehabilitation for women of advanced maternal age represents a treatment regimen deserving of clinical endorsement, as it offers numerous advantages, including substantial improvement in PFM strength, decreased incidence of PFD and enhanced patient satisfaction.

Comparison of Clinical Outcomes in the Slow-Developing Blastocysts With or Without Preimplantation Genetic Testing-Aneuploidy on Day 6 in the Frozen-Thawed Cycle.

OBJECTIVES: This study investigated the potential of the slow-developing blastocysts using preimplantation genetic testing-aneuploidy (PGT-A) in patients undergoing frozen-thawed embryo transfer, stratified by age. METHODS: A retrospective analysis was performed including a total of 743 cycles, the first frozen embryo transfer (FET) cycle with single embryo transfer, who underwent treatment between January 2020 and July 2023 in a single fertility centre, Gangnam CHA Fertility Center. A total of 743 cycles, in which we performed intracellular sperm injection and freeze-all strategy, from 743 patients were included. The patient group was divided into 4 groups as follows: group 1 (G1), 208 FET on day 5; group 2 (G2), 177 FET with PGT-A on day 5; group 3 (G3), 220 FET on day 6; group 4 (G4), 138 FET with PGT-A on day 6. We also divided into 2 groups-under 35 years of age and over 35 years of age-and performed the analysis separately for each group. RESULTS: In the under 35 years of age group, there were no significant differences in clinical pregnancy and miscarriage rates in G1 and G2 (67.2% vs. 63.8%, not statistically significantly different). Also, G4 had a higher clinical pregnancy rate than G3, but it was not significant (51.8% vs. 54.7%, not statistically significantly different). In the 35 years or older group, G2 had higher pregnancy rates than G1 and lower miscarriage rates (clinical pregnancy rate: 43.3% vs. 67.7%, P = 0.001, miscarriage rate: 22.5% vs. 3.4%, P = 0.001). In addition, G4 had a higher pregnancy rate than G3 and a lower miscarriage rate (clinical pregnancy rate: 31.8% vs. 46.9%, P = 0.003, miscarriage rate: 22.9% vs. 2.2%, P = 0.023). CONCLUSIONS: In the under-35-year-old group, PGT-A on day 5 and day 6 showed a high pregnancy rate and a low miscarriage rate. Therefore, using PGT-A seems advantageous for patients of an advanced maternal age.

IVF and obstetric outcomes among women of advanced maternal age (≥45 years) using donor eggs.

RESEARCH QUESTION: Does very advanced maternal age (VAMA; age ≥45 years) influence obstetric outcomes among women using donor oocytes in IVF? DESIGN: This retrospective cohort study analysed data from a nationwide IVF registry in Taiwan, focusing on IVF cycles involving women aged 45 years and older using donated oocytes between 2007 and 2016. The study assessed cumulative live birth rates (CLBR) and secondary outcomes such as clinical pregnancy, miscarriage, live birth and twin pregnancy rates, alongside perinatal outcomes such as Caesarean section rates, pre-eclampsia, gestational diabetes and birthweight. RESULTS: The study included 1226 embryo transfer cycles from 745 women, with a stable live birth rate of about 40% across the study period. The CLBR was slightly lower in women aged 50 years and older (54.2%) compared with those aged 45-46 years (58.0%), but these differences were not statistically significant (P = 0.647). Secondary outcomes and perinatal outcomes did not significantly differ across age groups. Regression analysis suggested a non-significant trend towards a decrease in live birth rate and birthweight with increasing maternal age. The study also found that single-embryo transfer (SET) minimized the risk of twin pregnancies without significantly affecting live birth rates. CONCLUSIONS: IVF with donor oocytes remains a viable option for women of VAMA, with consistent live birth rates across age groups. However, the study underscores the importance of elective SET to reduce the risk of twin pregnancies and associated adverse outcomes. Further research is needed to explore the impact of other factors such as paternal age and embryo development stage on IVF success in this population.

Advanced maternal age (AMA) and pregnancy: a feasible but problematic event.

This narrative review aimed to summarize all adverse outcomes of pregnancy in advanced maternal age (AMA) to assess the age of the mother as a potentially crucial risk factor. AMA refers to women older than 35 years. While expectations and the role of women in society have undergone significant changes today, the biology of aging remains unchanged. Various pathologic changes occur in the human body with age, including chronic noncommunicable diseases, as well as notable changes in reproductive organs, that significantly affect fertility. Despite substantial advancements in technology and medicine, pregnancy in AMA remains a formidable challenge. Although there are some advantages to postponing childbirth, they primarily relate to maternal maturity and economic stability. However, regrettably, there are also many adverse aspects of pregnancy at advanced ages. These include complications affecting both the mother and the fetus. Pregnants in AMA were more prone to suffer from gestational diabetes mellitus, preeclampsia, and eclampsia during pregnancy compared to younger women. In addition, miscarriages and ectopic pregnancies were more prevalent. Delivery was more frequently completed via cesarean section, and postpartum complications and maternal mortality were also higher. Unfortunately, there were also complications concerning the fetus, such as chromosomal abnormalities, premature birth, low birth weight, admission to the neonatal intensive care unit, and stillbirth.

Establishing a risk score for prediction of intrapartum cesarean delivery among older women: A retrospective cohort study.

OBJECTIVE: To determine risk factors and to develop a risk prediction score for intrapartum cesarean delivery (CD) in women over 40 years old. STUDY DESIGN: A retrospective cohort study, in a single university-affiliated tertiary medical center. All women aged 40 years or more who planned a trial of labor between 2012 and 2022. Women who opted for an elective CD and those with non-viable fetuses were excluded. Maternal and neonatal characteristics of women who delivered vaginally were compared to those who underwent an intrapartum CD. Risk factors were examined using univariate and multivariate analysis. A score was developed to predict the need for intrapartum CD. We assessed a receiver operating characteristic curve to evaluate the performance of our model. MAIN OUTCOME MEASURE: An unplanned intrapartum cesarean section. RESULTS: During the study period, 122,583 women delivered at our center, of whom 6122 (4.9 %) aged 40 years or more attempted a trial of labor. Of them, 428 (7 %) underwent intrapartum CD. Several independent risk factors were identified, including nulliparity, regional anesthesia, induction of labor, use of antibiotics during labor, multiple gestation, previous cesarean delivery, and the presence of gestational diabetes or preeclampsia. A risk score model, employing a cut-off of 7, demonstrated successful prediction of intrapartum CD, with an area under the curve of 0.86. CONCLUSION: The score model for intrapartum CD can be used by caregivers to offer a more informed consultation to women aged 40 years or more deciding on the mode of delivery.

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Objective: To determine the humoral immunity in advanced maternal-age women with recurrent spontaneous abortion (RSA). Methods: A retrospective study was performed between January 2022 and October 2023 in the Department of Reproductive Immunity of Shanghai First Maternity and Infant Hospital. Women with RSA were recruited and multiple autoantibodies were tested. Multivariate logistic regression was performed to compare the associations between different age groups (20 to 34 years old in the low maternal-age group and 35 to 45 years in the advanced maternal-age group) and multiple autoantibodies, while controlling for three confounding factors, including body mass index (BMI), previous history of live birth, and the number of spontaneous abortions. Then, we investigated the differences in the humoral immunity of advanced maternal-age RSA women and low maternal-age RSA women. Result: A total of 4009 women with RSA were covered in the study. Among them, 1158 women were in the advanced maternal-age group and 2851 women were in the low maternal-age group. The prevalence of antiphospholipid syndrome, systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, and undifferentiated connective tissue disease was 15.6% and 14.1%, 0.0% and 0.1%, 0.9% and 0.9%, 0.3% and 0.0%, and 23.7% and 22.6% in the advanced maternal-age group and low maternal-age group, respectively, showing no statistical difference between the two groups. The positive rates of antiphospholipid antibodies (aPLs), antinuclear antibody (ANA), extractable nuclear antigen (ENA) antibody, anti-double stranded DNA (dsDNA) antibody, anti single-stranded DNA (ssDAN) antibody, antibodies against alpha-fodrin (AAA), and thyroid autoimmunity (TAI) were 19.1% and 19.5%, 6.6% and 6.6%, 9.2% and 10.5%, 2.0% and 2.0%, 2.2% and 1.2%, 5.1% and 4.9%, and 17.8% and 16.8%, respectively. No differences were observed between the two groups. 1.6% of the women in the advanced maternal-age group tested positive for lupus anticoagulant (LA), while 2.7% of the women in the low maternal-age group were LA positive, with the differences being statistically significant (odds ratio=0.36, 95% confidence interval: 0.17-0.78). In the 4008 RSA patients, the cumulative cases tested positive for the three antibodies of the aPLs spectrum were 778, of which 520 cases were positive for anti-ß2 glycoprotein Ⅰ antibodies (ß2GPⅠ Ab)-IgG/IgM, 58 were positive for aCL-IgG/IgM, 73 were positive for LA, 105 were positive for both ß2GPⅠ Ab-IgG/IgM and aCL-IgG/IgM, 17 were positive for both ß2GPⅠ Ab-IgG/IgM and LA, 2 were positive for both aCL-IgG/IgM and LA, and 3 were positive for all three antibodies. Conclusion: Our study did not find a difference in humoral immunity between RSA women of advanced maternal age and those of low maternal age.

Basal FSH values are positively associated with aneuploidy incidence in pre-advanced maternal age (AMA) but not in AMA patients.

PURPOSE: To assess the impact of maternal age on the association between maternal basal FSH and aneuploidy. METHODS: A retrospective study including data from 1749 blastocysts diagnosed as euploid or aneuploid by PGT-A (preimplantation genetic testing for aneuploidy). Aneuploidy incidence was compared between embryos from mothers with high vs. low basal FSH levels (above and below the group median, respectively) in total, pre-AMA (advanced maternal age; < 35 years, 198 embryos) and AMA (≥ 35 years, 1551 embryos) patient groups, separately. To control for the interference of potentially confounding variables, the association between aneuploidy and high basal FSH levels was assessed by multivariate logistic analysis in overall, pre-AMA and AMA patient groups. RESULTS: Overall, aneuploidy rate was 9% higher (p = 0.02) in embryos from patients with high basal FSH (63.7%) compared to those with low basal FSH (58.4%). In the pre-AMA subgroup, aneuploidy incidence was 35% higher (p = 0.04) in embryos from patients with high basal FSH (53.5%) compared to those with low basal FSH (39.4%). Differently, aneuploidy occurrence did not vary between embryos from AMA patients with low (61.0%) and high (64.8%) basal FSH (p = 0.12). The multivariate analysis revealed that, in pre-AMA embryos, the association between aneuploidy occurrence and high basal FSH is independent of potential confounding variables (p = 0.04). CONCLUSION: Maternal basal FSH values are associated with embryo aneuploidy in pre-AMA but not in AMA patients. The present findings suggest that basal FSH is a useful parameter to assess aneuploidy risk in pre-AMA patients and reinforce the hypothesis that excessive FSH signalling can predispose to oocyte meiotic errors.

Association between interpregnancy interval and the labor curve.

BACKGROUND: Both short and long interpregnancy intervals are associated with adverse pregnancy outcomes; however, the impact of interpregnancy intervals on labor progression is unknown. OBJECTIVE: We examined the impact of interpregnancy intervals on the labor curve, hypothesizing that those with a longer interpregnancy intervals would have slower labor progression. STUDY DESIGN: This is a retrospective cohort study of patients with a history of one prior vaginal delivery admitted for induction of labor or spontaneous labor with a singleton gestation ≥37 weeks at an academic medical center between 2004 and 2015. Repeated measures regression was used to construct labor curves, which were compared between patients with short interpregnancy intervals, defined as <3 years since the last delivery, and long interpregnancy intervals, defined as >3 years since the last delivery. We chose this interval as it approximates the median birth interval in the United States. Interval-censored regression was used to estimate the median duration of labor after 4 centimeters of dilation, stratified by type of labor (spontaneous vs induced). Multivariate analysis was used to adjust for potential confounders. RESULTS: Of the 1331 patients who were included in the analysis, 544 (41%) had a long interpregnancy interval. Among the entire cohort, there were no significant differences in first or second-stage progression between short and long interpregnancy interval groups. In the stratified analysis, first-stage progression varied between groups on the basis of labor type: long interpregnancy interval was associated with a slower active phase among those being induced and a quicker active phase among those in spontaneous labor. The second-stage duration was similar between cohorts regardless of labor type. CONCLUSION: Multiparas with an interpregnancy interval >3 years may have a slower active phase than those with a shorter interpregnancy interval when undergoing induction of labor. Interpregnancy interval does not demonstrate an effect on the length of the second stage.

Pretreatment with luteal estradiol for programming antagonist cycles compared to no pretreatment in advanced age women stimulated with corifollitropin alfa: a non-inferiority randomized controlled trial.

STUDY QUESTION: Does luteal estradiol (E2) pretreatment give a similar number of retrieved oocytes compared to no-pretreatment in advanced-aged women stimulated with corifollitropin alfa in an antagonist protocol? SUMMARY ANSWER: Programming antagonist cycles with luteal E2 gave similar number of retrieved oocytes compared to no-pretreatment in women aged 38-42 years. WHAT IS KNOWN ALREADY: Programming antagonist cycles with luteal E2 pretreatment is a valuable tool to organize the IVF procedure better and is safe without any known impact on cycle outcome. However, variable effects were observed on the number of retrieved oocytes depending on the treated population. In advanced-age women, recruitable follicles tend to decrease in number and to be more heterogeneous in size but it remains unclear if estradiol pretreatment could change the oocyte yield through its negative feed-back effect on FSH intercycle rise. STUDY DESIGN, SIZE, DURATION: This non-blinded randomized controlled non-inferiority trial was conducted between 2016 and 2022 with centrally computerized randomization and concealed allocation. Participants were 324 women aged 38-42 years undergoing IVF treatment. The primary endpoint was the total number of retrieved oocytes. Statistical analysis was performed with one-sided alpha risk of 2.5% and 95% confidence interval (CI) with the non-inferiority of E2 pretreatment proved by a P value <0.025 and a lower delta margin of the CI within two oocytes compared to no pretreatment. Secondary endpoints were duration and total dosage of recombinant FSH, cancellation rate, percentage of oocyte pick-up (OPU) on working days, total number of metaphase II oocytes and obtained embryos, fresh transfer live birth rate, and cumulative live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: This multicentric study enrolled women with regular cycles, weight >50 kg and body mass index <32, IVF cycle 1-2. According to randomization, micronized estradiol 2 mg twice a day was started on days 20-24 and continued until Wednesday beyond the onset of menses followed by administration of corifollitropin alfa on Friday, i.e. stimulation (S)1 or from D1-3 of a natural cycle in unpretreated patients. GnRH antagonist was started at S6 and additional FSH at S8. MAIN RESULTS AND THE ROLE OF CHANCE: Basal characteristics were similar in patients randomized in E2 pretreated (n = 164) and non-pretreated (n = 160) groups (intended to treat (ITT) population). A total of 291 patients started treatment (per protocol (PP) population), 147 in E2 pretreated group with a mean number [SD] of pre-treatment days 9.8 [2.6] and 144 in the non-pretreated group. Despite advanced age, oocyte yields ranged from 0 to 29 in both groups with a median number of 6 retrieved oocytes in accordance with a mean anti-Müllerian hormone (AMH) level above 1.2 ng/ml. We demonstrated the non-inferiority of E2 pretreatment with a mean difference of -0.1 oocyte 95% CI [-1.5; 1.3] P = 0.004 in the PP population and a mean difference of -0.44 oocyte [-1.84; 0.97] P = 0.014 in the ITT population. Oocyte retrieval was more often on working days in E2 pretreated patients (91.9 versus 74.2%, P < 0.001). In patients reaching OPU, the duration of stimulation was statistically significantly longer (11.7 [1.7] versus 10.8 [1.8] days, P < 0.001) and the extra FSH dosage in addition to corifollitropin alfa was statistically significantly higher (1040 [548] versus 778 [504] IU, P < 0.001) in E2 pretreated than non-pretreated patients. We did not observe any significant differences in the number of retrieved oocytes (8.4 [6.1] versus 9.1 [6.0]), in the number of Metaphase 2 oocytes (7 [5.5] versus 7.3 [5.2]) nor in the number of obtained embryos (5 [4.6] versus 5.2 [4.2]) in E2 pretreated patients compared to non-pretreated patients. The live birth rate after fresh transfer (16.2% versus 18.5%, respectively), and the cumulative live birth rate per patient (17.7% versus 22.9%, respectively) were similar in both groups. Among the PP population, 31.6% of patients fulfilled the criteria for group 4 of Poseïdon classification (AMH <1.2 ng/ml and/or antral follicle count <5). In this sub-group of patients, we observed in contrast a statistically higher number of retrieved oocytes in E2 pretreated patients compared to non-pretreated (5.1 [3.8] versus 3.4 [2.7], respectively, the mean difference of +1.7 oocyte [0.2; 3.2] P = 0.022) but without significant difference in the cumulative live birth rate per patient (15.7% versus 7.3%, respectively). LIMITATIONS, REASONS FOR CAUTION: Our stimulated women older than 38 years obtained a wide range of collected oocytes suggesting very different stages of ovarian aging in both groups. E2 pretreatment is more likely to increase oocyte yield at the stage of ovarian aging characterized by asynchrony of a reduced follicular cohort. Another limitation is the sample size in sub-group analysis of patients with AMH <1.2 ng/ml. Finally, the absence of placebo for pretreatment could also introduce possible bias. WIDER IMPLICATIONS OF THE FINDINGS: Programming antagonist cycles with luteal E2 pretreatment seems a useful tool in advanced age women to better schedule oocyte retrievals on working days. However, the potential benefit of the number of collected oocytes remains to be demonstrated in a larger population displaying the characteristics of decreased ovarian reserve encountered in Poseïdon classification. STUDY FUNDING/COMPETING INTEREST(S): Research grant from (MSD) Organon, France. I.C., S.D., B.B., X.M., S.G., and C.J. have no conflict of interest with this study. I.C.D. declares fees as speaker from Merck KGaA, Gedeon Richter, MSD (Organon, France), Ferring, Theramex, and IBSA and participation on advisory board from Merck KGaA. I.C.D. also declares consulting fees, and travel and meeting support from Merck KGaA. N.M. declares grants paid to their institution from MSD (Organon, France); consulting fees from MSD (Organon, France), Ferring, and Merck KGaA; honoraria from Merck KGaA, General Electrics, Genevrier (IBSA Pharma), and Theramex; support for travel and meetings from Theramex, Merck KGaG, and Gedeon Richter; and equipment paid to their institution from Goodlife Pharma. N.C. declares grants from IBSA Pharma, Merck KGaA, Ferring, and Gedeon Richter; support for travel and meetings from IBSA Pharma, Merck KGaG, MSD (Organon, France), Gedeon Richter, and Theramex; and participation on advisory board from Merck KGaA. A.G.L. declares fees as speaker from Merck KGaA, Gedeon Richter, MSD (Organon, France), Ferring, Theramex, and IBSA. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02884245. TRIAL REGISTRATION DATE: 29 August 2016. DATE OF FIRST PATIENT'S ENROLMENT: 4 November 2016.

In Vitro Fertilization/Intracytoplasmic Sperm Injection with Autologous Oocytes in Healthy Women of Advanced Maternal Age: A Comparative Study Investigating Obstetric and Perinatal Outcomes Through Single Versus Double Embryo Transfer.

Introduction: The aim of this study was to assess whether the choice between double embryo transfer (DET) and single embryo transfer (SET) in healthy women of advanced maternal age (AMA) was associated with an increased risk of adverse outcomes. Materials and Methods: Healthy women aged 39-40 years who achieved live birth after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment between 2009 and 2020 at Karolinska University Hospital, Stockholm in Sweden, were included in this prospective, single-center cohort study. Results: A total of 310 women, who underwent IVF/ICSI treatments and achieved live births, were included in our analysis. Within this cohort, 78% of the women received SET, while 22% received DET. Nulliparity was common in both the SET (62.7%) and DET (85.3%) groups. Fresh embryo transfers were more prevalent in the DET group (91.2%) than in the SET group (31.1%). The rate of pregnancy-induced hypertension was higher in the SET group (8.3%) compared to the DET group (1.5%, p = 0.048). Furthermore, the DET group had a significantly higher rate of twin pregnancies (13.2%) compared to the SET group (0.4%). No statistically significant differences were observed in composite obstetric and perinatal complications between the SET and DET groups across all model estimates following different adjustments.Clinical Trial Registration number: ClinicalTrials.gov NTC04602962. Conclusions: While DET was more common in nulliparous women and associated with a higher rate of twin pregnancies, our analysis did not reveal significant differences in adverse outcomes between the SET and DET groups after comprehensive adjustments. Our study suggests that in the absence of co-morbidities, meticulous patient selection coupled with comprehensive maternal care can potentially mitigate potential DET-associated risks in women of AMA.

Examining Cesarean Among Individuals of Advanced Maternal Age in Nurse-Midwifery Care.

INTRODUCTION: Cesarean rates are rising, especially for individuals of advanced maternal age (AMA), defined as aged 35 or older. The Robson 10-Group Classification System (TGCS) facilitates assessment and comparison of cesarean rates among individuals in different settings. In midwifery-led care, in which pregnant people are typically healthier and seek a vaginal birth, it is unknown whether individuals of AMA have different antecedents leading to cesarean compared with younger counterparts. This study aimed to examine antecedents contributing to cesarean using Robson TGCS for individuals across age groups in midwifery care. METHODS: This study was a secondary analysis of 2 cohort data sets from Oregon Health & Science University (OHSU) and University of Michigan Health Systems (UMHS) hospitals. The samples were individuals in midwifery-led care birthing at either OHSU from 2012 to 2019 or UMHS from 2007 to 2019. RESULTS: A total of 11,951 individuals were studied. Overall cesarean rates were low; however, the rate for individuals of AMA was higher than the rate of their younger counterparts (18.30% vs 15.10%). The Robson groups were similar; however, the primary contributor among AMA individuals was group 5 (multiparous with previous cesarean), followed by group 2 [nulliparous with labor induced or prelabor cesarean], and group 1 [nulliparous with spontaneous labor]. In contrast, the primary contributors for younger individuals were groups 1, 2, and 5, respectively. In addition, prelabor cesarean and induced labor partly mediated the relationship between AMA and cesarean among nulliparous individuals, whereas prelabor cesarean was the key contributor to cesarean among multiparous people. DISCUSSION: The cesarean rate in midwifery-led care was low. Using Robson TGCS provided additional insight into the antecedents to cesarean, rather than viewing cesarean as a single outcome. Future studies should continue to use Robson TGCS and investigate antecedents to cesarean, including factors influencing successful vaginal birth after cesarean in individuals of AMA.

Mosaicism for Autosomal Trisomies: A Comprehensive Analysis of 1266 Published Cases Focusing on Maternal Age and Reproductive History.

Mosaicism for autosomal trisomy is uncommon in clinical practice. However, despite its rarity among both prenatally and postnatally diagnoses, there are a large number of characterized and published cases. Surprisingly, in contrast to regular trisomies, no attempts at systematic analyses of mosaic carriers' demographics were undertaken. This is the first study aimed to address this gap. For that, we have screened more than eight hundred publications on mosaic trisomies, reviewing data including gender and clinical status of mosaic carriers, maternal age and reproductive history. In total, 596 publications were eligible for analysis, containing data on 948 prenatal diagnoses, including true fetal mosaicism (TFM) and confined placental mosaicism (CPM), and on 318 cases of postnatally detected mosaicism (PNM). No difference was found in maternal age between normal pregnancy outcomes with appropriate birth weight and those with intrauterine growth restriction. Unexpectedly, a higher proportion of advanced maternal ages (AMA) was found in normal outcomes compared to abnormal ones (abnormal fetus or newborn) and fetal losses, 73% vs. 56% and 50%, p = 0.0015 and p = 0.0011, correspondingly. Another intriguing finding was a higher AMA proportion in mosaic carriers with concomitant uniparental disomy (UPD) for chromosomes 7, 14, 15, and 16 compared to carriers with biparental disomy (BPD) (72% vs. 58%, 92% vs. 55%, 87% vs. 78%, and 65% vs. 24%, correspondingly); overall figures were 78% vs. 48%, p = 0.0026. Analysis of reproductive histories showed a very poor reporting but almost two-fold higher rate of mothers reporting a previous fetal loss from PNM cohort (in which almost all patients were clinically abnormal) compared to mothers from the TFM and CPM cohorts (with a large proportion of normal outcomes), 30% vs. 16%, p = 0.0072. The occurrence of a previous pregnancy with a chromosome abnormality was 1 in 13 in the prenatal cohort and 1 in 16 in the postnatal cohort, which are five-fold higher compared to published studies on non-mosaic trisomies. We consider the data obtained in this study to be preliminary despite the magnitude of the literature reviewed since reporting of detailed data was mostly poor, and therefore, the studied cohorts do not represent "big data". Nevertheless, the information obtained is useful both for clinical genetic counseling and for modeling further studies.

Does cleavage- versus blastocyst-stage embryo transfer improve fertility rates in women over 38 years of age undergoing assisted reproductive technology?

OBJECTIVE: To evaluate whether extending embryo culture to day 5 (D5) affects pregnancy rates in women older than 38 years undergoing in vitro fertilization (IVF). METHODS: This retrospective, observational cohort study included data from fresh IVF cycles of women over 38 years, during 2011-2021. The cohort was divided according to day 3 (D3) versus D5 embryo transfer (ET). RESULTS: A total of 346 patients (ages 38-45 years) who underwent 496 IVF cycles were included, each yielding one to six embryos. A total of 374 (75%) fresh D3 ETs were compared with 122 (25%) D5 ETs. Demographically, there were more nulliparas in the D3 group (189 [50.9%] vs 47 [38.8%], P = 0.021). Higher gonadotropin dosage was used (3512 ± 1346 vs 3233 ± 1212 IU, P = 0.045) and lower maximum estradiol levels were reached in the D3 group (1129 ± 685 vs 1432 ± 708 pg/mL, P = 0.002). Thirty-three (27%) of the D5 cycles resulted in transfer cancelation due to failure of blastocyst formation (P = 0.001). However, clinical pregnancy rates (P = 0.958), live birth rates (P = 0.988), and miscarriage rates (P = 0.710) did not differ between D3 and D5 ETs. Multivariable logistic regression for clinical pregnancy rate showed that day of transfer did not have a significant effect on the odds (P = 0.376), but maternal age (P = 0.001) and number of retrieved oocytes (P = 0.009) were significant variables. CONCLUSIONS: In older women, culturing embryos to blastocyst stage can decrease invalid ETs without reducing pregnancy rates. Cancelation rates are higher but it may avoid interventions and conserve valuable time.

Single-cell proteomics reveals decreased abundance of proteostasis and meiosis proteins in advanced maternal age oocytes.

Advanced maternal age is associated with a decline in oocyte quality, which often leads to reproductive failure in humans. However, the mechanisms behind this age-related decline remain unclear. To gain insights into this phenomenon, we applied plexDIA, a multiplexed data-independent acquisition, single-cell mass spectrometry method, to analyze the proteome of oocytes from both young women and women of advanced maternal age. Our findings primarily revealed distinct proteomic profiles between immature fully grown germinal vesicle and mature metaphase II oocytes. Importantly, we further show that a woman's age is associated with changes in her oocyte proteome. Specifically, when compared to oocytes obtained from young women, advanced maternal age oocytes exhibited lower levels of the proteasome and TRiC complex, as well as other key regulators of proteostasis and meiosis. This suggests that aging adversely affects the proteostasis and meiosis networks in human oocytes. The proteins identified in this study hold potential as targets for improving oocyte quality and may guide future studies into the molecular processes underlying oocyte aging.

Risk factors for maternal near-miss in an undeveloped province in south-central China, 2012-2022.

OBJECTIVE: To explore the risk factors for maternal near-miss (MNM) using the WHO near-miss approach. METHODS: Data were obtained from the Maternal Near-Miss Surveillance System in Hunan Province, China, 2012-2022. Multivariate logistic regression analysis (method: Forward, Wald, α = 0.05) and adjusted odds ratios (aORs) were used to identify risk factors for MNM. RESULTS: Our study included 780,359 women with 731,185 live births, a total of 2461 (0.32%) MNMs, 777,846 (99.68%) non-MNMs, and 52 (0.006%) maternal deaths were identified. The MNM ratio was 3.37‰ (95%CI: 3.23-3.50). Coagulation/hematological dysfunction was the most common cause of MNM (75.66%). Results of multivariate logistic regression analysis showed risk factors for MNM: maternal age > = 30 years old (aOR > 1, P < 0.05), unmarried women (aOR = 2.21, 95%CI: 1.71-2.85), number of pregnancies > = 2 (aOR > 1, P < 0.05), nulliparity (aOR = 1.51, 95%CI: 1.32-1.72) or parity > = 3 (aOR = 1.95, 95%CI: 1.50-2.55), prenatal examinations < 5 times (aOR = 1.13, 95%CI: 1.01-1.27), and number of cesarean sections was 1 (aOR = 1.83, 95%CI: 1.64-2.04) or > = 2 (aOR = 2.48, 95%CI: 1.99-3.09). CONCLUSION: The MNM ratio was relatively low in Hunan Province. Advanced maternal age, unmarried status, a high number of pregnancies, nulliparity or high parity, a low number of prenatal examinations, and cesarean sections were risk factors for MNM. Our study is essential for improving the quality of maternal health care and preventing MNM.

Development and validation of a prenatal predictive nomogram for the risk of NICU admission in infants born to Chinese mothers over 35 years of age: a retrospective cohort study.

BACKGROUND: The rising number of women giving birth at advanced maternal age has posed significant challenges in obstetric care in recent years, resulting in increased incidence of neonatal transfer to the Neonatal Intensive Care Unit (NICU). Therefore, identifying fetuses requiring NICU transfer before delivery is essential for guiding targeted preventive measures. OBJECTIVE: This study aims to construct and validate a nomogram for predicting the prenatal risk of NICU admission in neonates born to mothers over 35 years of age. STUDY DESIGN: Clinical data of 4218 mothers aged ≥ 35 years who gave birth at the Department of Obstetrics of the Second Hospital of Shandong University between January 1, 2017 and December 31, 2021 were reviewed. Independent predictors were identified by multivariable logistic regression, and a predictive nomogram was subsequently constructed for the risk of neonatal NICU admission. RESULTS: Multivariate logistic regression demonstrated that the method of prenatal screening, number of implanted embryos, preterm premature rupture of the membranes, preeclampsia, HELLP syndrome, fetal distress, premature birth, and cause of preterm birth are independent predictors of neonatal NICU admission. Analysis of the nomogram decision curve based on these 8 independent predictors showed that the prediction model has good net benefit and clinical utility. CONCLUSION: The nomogram demonstrates favorable performance in predicting the risk of neonatal NICU transfer after delivery by mothers older than 35 years. The model serves as an accurate and effective tool for clinicians to predict NICU admission in a timely manner.