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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. [ABSTRACT FROM AUTHOR]

Objectives: To assess the age‐specific cumulative live birth rates (CLBRs) in intrauterine insemination (IUI) cycles using either donor or husband sperm, and to investigate the impact of sperm sources on IUI success among women within the same age group. Methods: This retrospective cohort study comprised women who underwent IUI with donor sperm (IUI‐D) or husband sperm (IUI‐H) from 2017 to 2021. The women were stratified based on their age at the initiation of insemination into four categories: <35, 35–37, 38–39 and ≥40 years. Results: A total of 5253 women undergoing 10 415 insemination cycles (3354 with IUI‐D and 7061 with IUI‐H) were included. The CLBRs decreased significantly with increasing maternal age within donor and husband insemination groups (P < 0.001). In the IUI‐D group, the crude CLBRs were 61.50% in women aged <35, 48.91% in 35–37, 24.14% in 38–39 and 11.76% in the ≥40‐year age category, respectively. The corresponding rates in the IUI‐H group were 27.62%, 22.96%, 13.73% and 6.90%, respectively. Within the <35 and 35–37‐year age categories, the CLBRs were significantly higher following IUI‐D cycles compared to IUI‐H cycles, with hazard ratios (HR) of 1.85 (1.68–2.04) and 1.69 (1.16–2.47), respectively. However, within the 38–39 and ≥40‐year age categories, both IUI‐D and IUI‐H resulted in comparable low CLBRs, with HRs of 1.91 (0.77–4.76) and 1.80 (0.33–9.86), respectively. Conclusion: Advanced maternal age affects the whole process of fertility. Therefore, it could be reasonable to limit the number of IUI performed in women aged 40 years and older, even in couple using donor sperm for reproduction. Synopsis: In women of advanced maternal age, intrauterine insemination (IUI) using donor sperm resulted in comparably low cumulative live birth rates as well as using husband sperm. [ABSTRACT FROM AUTHOR]

Aims/Background Pregnancy may cause physiological and pathological changes in multiple organs in a woman's body, including the heart, liver, and eyes. With rapid advances in societies and economies, the proportion of advanced maternal age (AMA) women has significantly increased. Here, we aimed to investigate the changes in arteriole retinal diameter, venule diameter, macular layer thickness, and arteriole to venule ratio (AVR) in this population. Methods This retrospective case-control study included 523 pregnant women (1046 eyes) and was performed on both eyes. In total, 318 subjects were included in the AMA group, and 205 subjects were included in the non-AMA group. Nonmydriatic fundus photography and optical coherence tomography (OCT) were performed on the same day, and the results were analyzed for the central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), AVR, and macular thickness (9 subfields) by integrative vessel analysis and automatic OCT software. Results In both eyes, the CRAE was significantly lower in the AMA group than that in the non-AMA group (p < 0.05; respectively). The CRVE in the AMA group was higher than that in the non-AMA group (p < 0.001; respectively). Compared to the non-AMA group, the AMA group exhibited a significant reduction in macular thickness within the inner nasal, outer nasal, and inner temporal subfields of both eyes (p < 0.05; respectively). Age was significantly correlated with CRVE and AVR in both eyes of pregnant women (CRVE: p < 0.0001; AVR: p < 0.01). Conclusion This study reports variations in the diameter of the retinal vasculature and the thickness of the macula in women of AMA. It is important to consider these changes when interpreting the adverse eye outcomes experienced by women of AMA. [ABSTRACT FROM AUTHOR]

This article discusses the introduction of advanced maternal age based on mortality-specific severe morbidity. The study examines the association between maternal age at delivery and severe maternal morbidity and mortality. The results suggest that maternal age thresholds of 33 and 45 years may represent inflection points where an increased risk of severe maternal morbidity is present. The study provides valuable information for triaging and counseling pregnant individuals with potentially increased risks of serious complications at delivery. However, there are limitations to the study, such as the lack of information on cause of death and the reliance on administrative codes for measuring morbidity. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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.

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.

Abstract 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 = 2 (aOR > 1, P = 3 (aOR = 1.95, 95%CI: 1.50–2.55), prenatal examinations = 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.

Objective Among patients ≥45 years, the birth rate in the United States continues to increase. As fertility declines with age, this cohort often utilizes assisted reproductive technology, specifically in vitro fertilization (IVF). While both advancing maternal age and IVF are independently associated with adverse maternal outcomes, data regarding their additive effect are scant. This article aims to determine if patients who conceive via IVF are at increased risk for preterm birth (PTB) compared to patients with non-IVF pregnancies in a very advanced maternal age (vAMA) cohort (≥45 years). Study Design Retrospective cohort study of all pregnant patients ≥45 years old who delivered at a single institution (2014–2021). Those with incomplete delivery/neonatal records or multiples beyond twins were excluded. We compared individuals who conceived via IVF to those who conceived without IVF. The primary outcome was preterm delivery <37 weeks gestation. Secondary outcomes included other adverse perinatal outcomes. Using multivariable logistic regression, we adjusted for multiple gestation as well as confounders found to be significantly different in the univariable analysis and other known risk factors for PTB. Results In our study cohort of 420 vAMA patients, individuals who underwent IVF were more likely to be older, privately insured, nulliparous, and with a twin gestation. The PTB rate in vAMA patients who underwent IVF was 24.4 compared to 8.4% in patients who did not use IVF (p < 0.001). After adjusting for confounders, IVF was an independent risk factor for PTB <37 weeks in vAMA patients (adjusted odds ratio {aOR] = 4.3, 95% confidence interval [CI]: 1.7–10.4, p = 0.001). In vitro fertilization was also associated with a composite of adverse maternal outcomes (hypertensive disorder of pregnancy, postpartum hemorrhage, blood transfusion, and unplanned hysterectomy) (aOR = 1.7, 95% CI: [1.1–2.9], p = 0.03). Conclusion In the vAMA population, conception via IVF is associated with an increased risk of PTB <37 weeks. Key Points This study examines IVF as an independent risk factor for PTB in patients ≥45 years at delivery, which has not been specifically addressed in prior studies. In vAMA patients, use of IVF is associated with an increased risk of PTB <37 weeks. These patients also have higher rates of cesarean delivery. Neonates from IVF pregnancies are more likely to be very low birth weight or low birth weight. Bodies of research exist for both advanced maternal age and assisted reproductive technology, there is a paucity of data specifically in parturients of vAMA who conceive via IVF. [ABSTRACT FROM AUTHOR]

A study published in Human Reproduction explores the role of oxidative stress and mitochondrial dysfunction in ovarian aging and its impact on female fertility. The study found evidence of oxidative damage in oocytes of advanced maternal age, suggesting that oxidative stress may play an early role in the decline of oocyte quality and fertility. The authors also examined cellular and molecular pathways affected by oxidative stress and aging, as well as potential therapeutic strategies to mitigate mitochondrial dysfunction and oxidative stress in oocytes of advanced maternal age. However, further research is needed to develop effective treatments for mitochondrial dysfunctions and infertility related to oxidative stress in oocytes. [Extracted from the article]

Objective Methods Results Conclusions To evaluate whether extending embryo culture to day 5 (D5) affects pregnancy rates in women older than 38 years undergoing in vitro fertilization (IVF).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).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.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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Zygotes with 2.1 pronuclei (2.1PN) present with two normal-sized pronuclei, and an additional smaller pronucleus, that is approximately smaller than two thirds the size of a normal pronucleus. It remains unclear whether the additional pronucleus causes embryonic chromosome abnormalities. In the majority of cases, in vitro fertilization (IVF) clinics discarded 2.1PN zygotes. Thus, the present study aimed to evaluate the developmental potential and value of 2.1PN zygotes. Methods: 2.1PN-derived embryos from 164 patients who underwent IVF or intracytoplasmic sperm injection (ICSI) treatment between January 2021 and December 2022 were included in the present study. All embryos were monitored using a time-lapse system, and blastocyst formation was used to assess 2.1PN-derived embryo developmental potential. The blastocyst formation was quantified using generalized estimating equations, and chromosome euploidy was analyzed using next-generation sequencing (NGS). In addition, the potential association between age and occurrence of 2.1PN zygotes was determined. Results: The present study demonstrated that numerous 2.1PN zygotes developed into blastocysts. Early cleavage patterns and embryo quality on Day 3 were the independent predictors for the blastocyst formation of 2.1PN-derived embryos. The 2.1PN zygotes displayed a comparable developmental potential compared to 2PN zygotes in advanced age patients (≥ 38). Moreover, there was a tendency that 2.1PN-derived blastocysts showed a similar euploidy rate compared to 2PN-derived blastocysts. Conclusion: Clinicians should consider using 2.1PN-derived euploid embryos for transfer after preimplantation genetic testing in the absence of available 2PN embryo cycles. 2.1PN-derived embryos could be a candidate, particularly beneficial for patients at advanced age. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Advancing maternal age is increasingly prevalent and is associated with severe maternal morbidity often requiring intensive care unit (ICU) admission. Objectives: To describe maternal ICU admissions at a quaternary care hospital in Montreal, Canada, and evaluate the association between maternal age and composite of: need for invasive interventions, ICU stay > 48 h, or maternal death. Methods: Chart review of ICU admissions during pregnancy/postpartum (2006–2016); logistic regressions to evaluate the impact of age on outcomes. Results: With 5.1 ICU admissions per 1000 deliveries, we included 187 women (mean age 32 ± 6.3 years; 20 (10.7%) ≥ 40 years). The composite outcome occurred in 105 (56.2%) patients; there were two maternal deaths. Age ≥ 40 years increased the odds of invasive interventions (OR 4.03; 95% confidence interval [CI] 1.15–14.1) but not of the composite outcome (OR 2.30; 95% CI 0.66–8.02). Conclusion: Peripartum women aged ≥ 40 years had worse outcomes in ICU, with an increased need for invasive interventions. [ABSTRACT FROM AUTHOR]

BackgroundBirth weights have continued to decline in Japan in recent years. However, secular trend changes such as the birth weight relative to the week of gestation remain to be explored. This study aimed to determine the trends over time in mean birth weight and small for gestational age (SGA) rate for each gestational week.MethodsWe used a large dataset of 27,015,792 births obtained from birth certificates between 1997 and 2021. Births from 22 to 41 weeks of gestation were evaluated in six groups (22–24, 25–27, 28–31, 32–33, 34–36, and 37–41 weeks of gestational age). For each group, secular trend changes in the z-scores calculated from standard birth weight values were assessed. Time trends in the proportion of SGA and mean birth weight z-scores were evaluated using the Cochran–Armitage trend test and linear regression analysis. Binomial logistic regression was performed to ascertain the effects of gestational age, sex, primiparity, number of births, and maternal age on the likelihood of SGA.ResultsThe mean birth weight of preterm infants continued to decrease, and the z-score for mean birth weight decreased linearly, falling to −0.7 at 25–27 weeks of gestation from 1997–2001 (first period) to 2017–2021 (final period). Maternal age continued to increase from the first period to the last period for all weeks of gestation. There was a linear increase in the SGA rate in preterm infants born at

Abstract 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.

Abstract Background Pregnancy-related cancers are mostly breast cancers, and their incidence is likely to increase as a result of the modern trend of delaying childbearing. In particular, advanced maternal age increases breast cancer risk, and younger breast cancer patients are more likely to die and metastasize. This study compared a population with a high incidence of delayed childbearing with another population with a lower mean age at childbirth in order to determine whether breast cancer diagnosis and childbearing age overlap. Methods We retrospectively analyzed multiple data sources. The Surveillance, Epidemiology, and End Results (SEER) program, the United States National Center for Health Statistics as part of the National Vital Statistics System, the United Nations Population Division, the GLOBOCAN Cancer Observatory, the CLIO-INFRA project database, the Human Fertility Database, and anonymized local data were used. Results As women’s age at delivery increased, the convergence between their age distribution at breast cancer diagnosis and childbearing increased. In addition, the overlap between the two age distributions increased by more than 200% as the average age at delivery increased from 27 to 35 years. Conclusions As women’s average childbearing age has progressively risen, pregnancy and breast cancer age distributions have significantly overlapped. This finding emphasizes the need for increased awareness and educational efforts to inform women about the potential consequences of delayed childbearing. By providing comprehensive information and support, women can make more informed decisions about their reproductive health and cancer prevention strategies.

Abstract Background Mothers of advanced age, defined as pregnant women aged ≥ 35 years at the time of giving birth, are traditionally known to be associated with increased risks of adverse maternal outcomes. We determined the prevalence of adverse maternal outcomes and associated factors among mothers of advanced age who delivered at Kabale Regional Referral Hospital (KRRH), in Southwestern Uganda. Methods We conducted a cross-sectional study at the Maternity Ward of KRRH from April to September 2023. We consecutively enrolled pregnant women aged ≥ 35 years during their immediate post-delivery period and before discharge. We obtained data on their socio-demographic, obstetric, medical characteristics and their maternal outcomes using interviewer-administered questionnaires. We defined adverse maternal outcome as any complication sustained by the mother that was related to pregnancy, delivery and immediate post-partum events (obstructed labour, antepartum haemorrhage, mode of delivery [cesarean or vacuum extraction], postpartum haemorrhage, hypertensive disorders of pregnancy, preterm or postdate pregnancy, anemia, premature rupture of membranes, multiple pregnancy, and maternal death). A participant was considered to have an adverse outcome if they experienced any one of these complications. We identified factors associated with adverse outcomes using modified Poisson regression. Results Out of 417 participants, most were aged 35–37 years (n = 206; 49.4%), and had parity ≥ 5 (65.5%). The prevalence of adverse maternal outcomes was 37.6% (n = 157, 95%CI: 33.1–42.4%). Common adverse maternal outcomes included caesarian delivery (23%), and obstructed labour (14.4%). Other complications included anemia in pregnancy (4.5%), chorioamnionitis (4.1%), preterm prelabour rupture of membranes (3.9%), and chronic hypertension and preeclampsia (both 2.4%). Factors associated with adverse maternal outcomes were precipitate labour (adjusted prevalence ratio [aPR] = 1.95, 95%CI: 1.44–2.65), prolonged labour, lasting > 12 h (aPR = 2.86, 95%CI: 1.48–3.16), and chronic hypertension (aPR = 2.01, 95%CI: 1.34–3.9). Conclusion Approximately two-fifth of the advanced-aged mothers surveyed had adverse outcomes. Mothers with prolonged labour, precipitate labour and chronic hypertension were more likely to experience adverse outcomes. We recommend implementation of targeted interventions, emphasizing proper management of labor as well as close monitoring of hypertensive mothers, and those with precipitate or prolonged labor, to mitigate risks of adverse outcomes within this study population.

Purpose: Does preimplantation genetic testing for aneuploidy (PGT-A) in embryos help women of advanced maternal age (AMA) of Indian origin to achieve better reproductive outcomes? Methods: In this retrospective study, a total of 267 patients were recruited, of which 53 patients (PGT-A group) consented to PGT-A, followed by euploid embryo transfer, whereas the remaining 214 patients (non-PGT-A group) underwent frozen embryo transfer (FET) of unscreened morphologically graded blastocysts. Results: A significant increase in the clinical pregnancy rate was observed in the PGT-A group when compared to the non-PGT-A group (71.6% vs. 51%, [Formula: see text]), while the miscarriage rate was found to be lower in the PGT-A group compared to the non-PGT-A group (11% vs. 25%, [Formula: see text]). The live birth rates were also significantly better in PGT-A group (60.3% vs. 25.6%, [Formula: see text]). In the PGT-A group, similarly, the implantation rate was found to be significantly higher than in the non-PGT-A group (53% vs. 33%, [Formula: see text]). Conclusions: The data suggest that PGT-A testing in women of AMA can improve their reproductive outcomes. Role of PGT-A seemed equally efficient in women of Indian origin and showed no difference based on ethnicity.

The fecundity of women decreases significantly beginning approximately at age 35 and decreases more rapidly after age 40. Age affects not only the size of the oocyte pool but also the quality of germ cells. Despite the continuous advancement of assisted reproductive technology, infertility remains a challenge for women of advanced maternal age. Here, we present a case of a woman in her forties who had two successful live births after treatment with Traditional Chinese Medicine. At her initial visit (at age 43), the patient presented with a short menstrual cycle and signs of a diminished ovarian reserve (FSH: 26.2 mIU/mL; AMH: 0.23 ng/mL). Three years after her first delivery (at age 47), the patient showed signs of further diminished ovarian reserve (FSH: 27.1 mIU/mL; AMH: 0.07 ng/mL). Notably, after five months of Chinese herbal medicine treatment, she achieved another successful pregnancy, and resulted in a live birth. This case demonstrates that Chinese herbal medicine can have a positive clinical impact on improving hormonal balance and fecundity. Further research is needed to investigate the pharmacokinetics of Chinese herbal medicine in improving fecundity for women of advanced maternal age.

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. [ABSTRACT FROM AUTHOR]

Background: Pregnancy-related cancers are mostly breast cancers, and their incidence is likely to increase as a result of the modern trend of delaying childbearing. In particular, advanced maternal age increases breast cancer risk, and younger breast cancer patients are more likely to die and metastasize. This study compared a population with a high incidence of delayed childbearing with another population with a lower mean age at childbirth in order to determine whether breast cancer diagnosis and childbearing age overlap. Methods: We retrospectively analyzed multiple data sources. The Surveillance, Epidemiology, and End Results (SEER) program, the United States National Center for Health Statistics as part of the National Vital Statistics System, the United Nations Population Division, the GLOBOCAN Cancer Observatory, the CLIO-INFRA project database, the Human Fertility Database, and anonymized local data were used. Results: As women's age at delivery increased, the convergence between their age distribution at breast cancer diagnosis and childbearing increased. In addition, the overlap between the two age distributions increased by more than 200% as the average age at delivery increased from 27 to 35 years. Conclusions: As women's average childbearing age has progressively risen, pregnancy and breast cancer age distributions have significantly overlapped. This finding emphasizes the need for increased awareness and educational efforts to inform women about the potential consequences of delayed childbearing. By providing comprehensive information and support, women can make more informed decisions about their reproductive health and cancer prevention strategies. Highlights: • As the age of women at childbirth increased, the convergence of their age distribution at breast cancer diagnosis grew. • When the average age at delivery increases from 27 to 35 years, the overlap between age distribution at delivery and that at breast cancer diagnosis increases by more than 200%. • These results highlights the need for more education and awareness about the risks of delayed childbearing. Women can make better reproductive health and cancer prevention decisions with comprehensive information and support. [ABSTRACT FROM AUTHOR]

Background: Mothers of advanced age, defined as pregnant women aged ≥ 35 years at the time of giving birth, are traditionally known to be associated with increased risks of adverse maternal outcomes. We determined the prevalence of adverse maternal outcomes and associated factors among mothers of advanced age who delivered at Kabale Regional Referral Hospital (KRRH), in Southwestern Uganda. Methods: We conducted a cross-sectional study at the Maternity Ward of KRRH from April to September 2023. We consecutively enrolled pregnant women aged ≥ 35 years during their immediate post-delivery period and before discharge. We obtained data on their socio-demographic, obstetric, medical characteristics and their maternal outcomes using interviewer-administered questionnaires. We defined adverse maternal outcome as any complication sustained by the mother that was related to pregnancy, delivery and immediate post-partum events (obstructed labour, antepartum haemorrhage, mode of delivery [cesarean or vacuum extraction], postpartum haemorrhage, hypertensive disorders of pregnancy, preterm or postdate pregnancy, anemia, premature rupture of membranes, multiple pregnancy, and maternal death). A participant was considered to have an adverse outcome if they experienced any one of these complications. We identified factors associated with adverse outcomes using modified Poisson regression. Results: Out of 417 participants, most were aged 35–37 years (n = 206; 49.4%), and had parity ≥ 5 (65.5%). The prevalence of adverse maternal outcomes was 37.6% (n = 157, 95%CI: 33.1–42.4%). Common adverse maternal outcomes included caesarian delivery (23%), and obstructed labour (14.4%). Other complications included anemia in pregnancy (4.5%), chorioamnionitis (4.1%), preterm prelabour rupture of membranes (3.9%), and chronic hypertension and preeclampsia (both 2.4%). Factors associated with adverse maternal outcomes were precipitate labour (adjusted prevalence ratio [aPR] = 1.95, 95%CI: 1.44–2.65), prolonged labour, lasting > 12 h (aPR = 2.86, 95%CI: 1.48–3.16), and chronic hypertension (aPR = 2.01, 95%CI: 1.34–3.9). Conclusion: Approximately two-fifth of the advanced-aged mothers surveyed had adverse outcomes. Mothers with prolonged labour, precipitate labour and chronic hypertension were more likely to experience adverse outcomes. We recommend implementation of targeted interventions, emphasizing proper management of labor as well as close monitoring of hypertensive mothers, and those with precipitate or prolonged labor, to mitigate risks of adverse outcomes within this study population. [ABSTRACT FROM AUTHOR]

Introduction: As maternal age during pregnancy is rising all over the world, there is a growing need for prognostic factors that determine maternal and perinatal outcomes in older women. Material and methods: This study is a retrospective cohort study of women aged 40 years or older at the time of delivery in four Santeon hospitals across the Netherlands between January 2016 and December 2019. Outcomes were compared between women of 40–44 years (advanced maternal age) and 45 years and older (very advanced maternal age). Primary outcome was unplanned cesarean section, secondary outcomes included postpartum hemorrhage and neonatal outcomes. Multivariate regression analysis was performed to analyze predictive factors for unplanned cesarean sections in women who attempted vaginal delivery. Subsequently, a predictive model and risk scores were constructed to predict unplanned cesarean section. Results: A cohort of 1660 women was analyzed; mean maternal age was 41.4 years, 4.8% of the women were 45 years and older. In both groups, more than half of the women had not delivered vaginally before. Unplanned cesarean sections were performed in 21.1% of the deliveries in advanced maternal age and in 29.1% in very advanced maternal age. Four predictive factors were significantly correlated with unplanned cesarean sections: higher body mass index (BMI), no previous vaginal delivery, spontaneous start of delivery and number of days needed for cervical priming. A predictive model was constructed from these factors with an area under the curve of 0.75 (95% confidence interval 0.72–0.78). A sensitivity analysis in nulliparous women proved that BMI, days of cervical priming, age, and gestational age were risk factors, whereas spontaneous start of delivery and induction were protective factors. There was one occurrence of neonatal death. Conclusions: Women of advanced maternal age and those of very advanced maternal age have a higher chance of having an unplanned cesarean section compared to the general obstetric population in the Netherlands. Unplanned cesarean sections can be predicted through use of our predictive model. Risk increases with higher BMI, no previous vaginal delivery, and increasing number of days needed for cervical priming, whereas spontaneous start of labor lowers the risk. In nulliparous women, age and gestational age also increase risk, but induction lowers the risk of having an unplanned cesarean section. [ABSTRACT FROM AUTHOR]

A significant number of pregnancies occur at advanced maternal age (>35 yr), which is a risk factor for pregnancy complications. Healthy pregnancies require massive hemodynamic adaptations, including an increased blood volume and cardiac output. There is growing evidence that these cardiovascular adaptations are impaired with age, however, little is known about maternal cardiac function with advanced age. We hypothesized that cardiac adaptations to pregnancy are impaired with advanced maternal age. Younger (4 mo; ~early reproductive maturity in humans) and aged (9 mo; ~35 yr in humans) pregnant Sprague-Dawley rats were assessed and compared with age-matched nonpregnant controls. Two-dimensional echocardiographic images were obtained (ultrasound biomicroscopy; under anesthesia) on gestational day 19 (term = 22 days) and compared with age-matched nonpregnant rats (n = 7-9/group). Left ventricular structure and function were assessed using short-axis images and transmitral Doppler signals. During systole, left ventricular anterior wall thickness increased with age in the nonpregnant rats, but there was no age-related difference between the pregnant groups. There were no significant pregnancy-associated differences in left ventricular wall thickness. Calculated left ventricular mass increased with age in nonpregnant rats and increased with pregnancy only in young rats. Compared with young pregnant rats, the aortic ejection time of aged pregnant rats was greater and Tei index was lower. Overall, the greater aortic ejection time and lower Tei index with age in pregnant rats suggest mildly altered cardiac adaptations to pregnancy with advanced maternal age, which may contribute to adverse outcomes in advanced maternal age pregnancies. NEW & NOTEWORTHY We demonstrated that even before the age of reproductive senescence, rats show signs of age-related alterations in cardiac structure that suggests increased cardiac work. Our data also demonstrate, using an in vivo echocardiographic approach, that advanced maternal age in a rat model is associated with altered cardiac function and structure relative to younger pregnant controls. [ABSTRACT FROM AUTHOR]

Objective Evidence is inconsistent regarding grand multiparity and its association with adverse obstetric outcomes. Few large American cohorts of grand multiparas have been studied. We assessed if increasing parity among grand multiparas is associated with increased odds of adverse perinatal outcomes. Study Design Multicenter retrospective cohort of patients with parity ≥ 5 who delivered a singleton gestation in New York City from 2011 to 2019. Outcomes included postpartum hemorrhage, preterm delivery, hypertensive disorders of pregnancy, shoulder dystocia, birth weight > 4,000 and <2,500 g, and neonatal intensive care unit (NICU) admission. Parity was analyzed continuously, and multivariate analysis determined if increasing parity and other obstetric variables were associated with each adverse outcome. Results There were 2,496 patients who met inclusion criteria. Increasing parity among grand multiparas was not associated with any of the prespecified adverse outcomes. Odds of postpartum hemorrhage increased with history (adjusted odds ratio [aOR]: 2.65, 95% confidence interval [1.83, 3.84]) and current cesarean delivery (aOR: 4.59 [3.40, 6.18]). Preterm delivery was associated with history (aOR: 12.36 [8.70–17.58]) and non-White race (aOR: 1.90 [1.27, 2.84]). Odds of shoulder dystocia increased with history (aOR: 5.89 [3.22, 10.79]) and birth weight > 4,000 g (aOR: 9.94 [6.32, 15.65]). Birth weight > 4,000 g was associated with maternal obesity (aOR: 2.92 [2.22, 3.84]). Birth weight < 2,500 g was associated with advanced maternal age (aOR: 1.69 [1.15, 2.48]), chronic hypertension (aOR: 2.45 [1.32, 4.53]), and non-White race (aOR: 2.47 [1.66, 3.68]). Odds of hypertensive disorders of pregnancy increased with advanced maternal age (aOR: 1.79 [1.25, 2.56]), history (aOR: 10.09 [6.77–15.04]), and non-White race (aOR: 2.79 [1.95, 4.00]). NICU admission was associated with advanced maternal age (aOR: 1.47 [1.06, 2.02]) and non-White race (aOR: 2.57 [1.84, 3.58]). Conclusion Among grand multiparous patients, the risk factor for adverse maternal, obstetric, and neonatal outcomes appears to be occurrence of those adverse events in a prior pregnancy and not increasing parity itself. Key Points Increasing parity is not associated with adverse obstetric outcomes among grand multiparas. Prior adverse pregnancy outcome is a risk factor for the outcome among grand multiparas. Advanced maternal age is associated with adverse obstetric outcomes among grand multiparas. [ABSTRACT FROM AUTHOR]

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Urbanization remains an important factor affecting the mental health of people. Currently, there is insufficient research on depression among the offspring of women who have children at an advanced maternal age (AMA). The objective of this study is to investigate the urban and rural disparities in depressive symptoms among the offspring of AMA and related influencing factors. In this study, a total of 1273 offspring born to AMA were selected from the fourth wave of the China Health and Retirement Longitudinal Study (CHARLS) database. The questionnaire used in the study included demographic information and the Center for Epidemiologic Studies Depression Scale (CES D). Chi-square tests and logistic regression analysis were employed to examine the urban-rural differences. The likelihood of developing depressive symptoms of the offspring of AMA in rural areas was 1.633 times higher (AOR = 1.633; 95%CI: 1.211–2.202) compared to their urban counterparts. Several factors including gender, education, marital status, disability, chronic diseases, and sleep duration showed a linkage with depression among rural based offspring of AMA. For the urban offspring of AMA, only disability and sleep duration exhibited a significant association with depressive symptoms. This study cannot establish a causal relationship between depressive symptoms and the influencing factors for the offspring of AMA. Age range and variables of the respondents needs further consideration. This study has brought to light the elevated risk of depressive symptoms among rural-based offspring of AMA. Thus, emphasizing the urgent need for targeted interventions and measures to address the negative impact. • The prevalence of depressive symptoms among offspring of AMA was found to be high; • The prevalence of depressive symptoms was significantly higher among offspring of AMA in rural areas than in urban areas; • There are more influencing factors for depressive symptoms among offspring of AMA in rural areas than in urban areas. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated age-related maternal outcomes of vacuum-assisted vaginal deliveries (VAD). Methods: This retrospective cohort study included all nulliparous women with singleton VAD in one academic institution. Study group parturients were maternal age ≥ 35 years and controls < 35. Power analysis revealed that 225 women/group would be sufficient to detect a difference in the rate of third- and fourth-degree perineal tears (primary maternal outcome) and umbilical cord pH < 7.15 (primary neonatal outcome). Secondary outcomes were maternal blood loss, Apgar scores, cup detachment, and subgaleal hematoma. Outcomes were compared between groups. Results: From 2014 to 2019, 13,967 nulliparas delivered at our institution. Overall, 8810 (63.1%) underwent normal vaginal delivery, 2432 (17.4%) instrumental, and 2725 (19.5%) cesarean. Among 11,242 vaginal deliveries, 10,116 (90%) involved women < 35, including 2067 (20.5%) successful VAD vs. 1126 (10%) women ≥ 35 years with 348 (30.9%) successful VAD (p < 0.001). Rates of third- and fourth-degree perineal lacerations were 6 (1.7%) with advanced maternal age and 57 (2.8%) among controls (p = 0.259). Cord pH < 7.15 was similar: 23 (6.6%) study group and 156 (7.5%) controls (p = 0.739). Conclusion: Advanced maternal age and VAD are not associated with higher risk for adverse outcomes. Older, nulliparous women are more likely to undergo vacuum delivery than younger parturients. [ABSTRACT FROM AUTHOR]

Objective: To describe maternal and fetal outcomes of pregnancies after 42 years and to compare maternal and fetal morbidities according to the conception mode; comparing pregnancies obtained spontaneously and those resulting from assisted reproductive technology (ART). Methods: This retrospective cohort study was conducted in a level 3 maternity hospital. This study covered all women, aged 42 years or older, who gave birth between January 1, 2014 and December 31, 2019. Univariate and multivariate analyses with logistic regression models were used to compare maternal and perinatal outcomes depending on conception mode: spontaneous or using ART. Results: A sample of 532 women, including 335 spontaneous pregnancies (63%) and 147 pregnancies after ART (27.6%) were studied. Conception mode was missing for 50 (9.4%). We found increased rates not only of maternal complications such as maternal overweight and obesity, pre‐eclampsia, and gestational diabetes, but also of interventions such as hospitalization during pregnancy, cesarean section, postpartum hemorrhage, and perinatal outcome like preterm birth. There were also more maternal and perinatal negative outcomes among the ART group. After multivariate analysis, pre‐eclampsia was predominant in the ART group (odds ratio 0.25, 95% confidence interval 0.07–0.85, P = 0.02). Conclusion: While maternal and fetal risks increase for late pregnancies, there also appears to be a difference depending on the conception mode, with pregnancies resulting from ART having more pregnancy‐related complications than those obtained spontaneously. Synopsis: Women aged 42 years or older have more maternal and fetal morbidities, and especially those from assisted reproductive technology group. [ABSTRACT FROM AUTHOR]

Purpose: The trend of delaying childbirth has resulted in a growing number of advanced-aged women who are opting for preimplantation genetic testing (PGT) to screen for monogenic diseases or structural chromosomal rearrangements (PGT-M and PGT-SR). This increase in demand necessitates the development of a clinical predictive model for live birth outcomes in these women. Therefore, the objective of this study is to construct a comprehensive predictive model that assesses the likelihood of achieving a successful live birth in advanced-aged women undergoing PGT-M and PGT-SR treatments. Methods: A retrospective cohort study of 37–45-year-old women undergoing preimplantation genetic testing for monogenic disease or structural chromosomal rearrangement cycles from 2010 to 2021 was conducted at a university hospital reproductive centre. The purpose was to develop a clinical predictive model for live birth in these women. The main outcome studied was the cumulative live birth rate in the first or subsequent cycles. Developing a decision tree enabled a comprehensive study of clinical parameters and expected outcomes. Results: The analysis included 158 women undergoing 753 preimplantation genetic testing cycles. The cumulative live birth rate was 37.342% (59/158). Decision tree analysis revealed that women aged ≤ 40.1 or women > 40.1 with one or more top-quality transferable embryos in their first cycle had the best chance for a live baby (56% and 41%, respectively). Those older than 40.1 without top-quality embryos and seven or fewer dominant follicles had no live births. A Kaplan–Meier curve showed that for autosomal dominant diseases, there was a negligible increase in live birth rate after three cycles, compared to six cycles in autosomal recessive inheritance. Conclusion: In older women, the chance of delivering after repeated cycles is higher in those with at least one top-quality unaffected embryo in their first preimplantation genetic testing cycle. Additional preimplantation genetic testing cycles after three in carriers of an autosomal dominant disorder and six in those with an autosomal recessive disorder should be considered prudently. [ABSTRACT FROM AUTHOR]

The mean age at childbirth in Europe has gradually increased, and it is now around 29 years of age. It has been shown that older maternal age is associated with problems of fertility; in fact, with increasing age, the chance of conceiving diminishes, and fetal and obstetric complications grow. Research has focused particularly on the biological risks associated with late pregnancy, both for the child and the woman. Less space has been dedicated to the potential psychological and relational benefits of motherhood at an advanced age. The aim of this review was to summarize the existing literature on this issue. Qualitative and quantitative studies were sourced from Pubmed, Science Direct, PsycINFO, and SciELO. The selected works highlight that advanced maternal age can be associated with some advantages for both mothers and their offspring in terms of physical healthcare, parenting styles, and child developmental outcomes. Specifically, the review suggests that older mothers have greater emotional maturity and feel more prepared for motherhood; also, advanced maternal age appears to exert a protective influence on children's behavioral, social, and emotional functioning, compensating for the biological risks. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on clinical outcomes among high-risk patients. Methods: This retrospective study involved 1,368 patients and the same number of cycles, including 520 cycles with PGT-A and 848 cycles without PGT-A. The study participants comprised women of advanced maternal age (AMA) and those affected by recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or severe male factor infertility (SMF). Results: PGT-A was associated with significant improvements in the implantation rate (IR) and the ongoing pregnancy rate/live birth rate (OPR/LBR) per embryo transfer cycle in the AMA (39.3% vs. 16.2% [p<0.001] and 42.0% vs. 21.8% [p<0.001], respectively), RIF (41.7% vs. 22.0% [p<0.001] and 47.0% vs. 28.6% [p<0.001], respectively), and RPL (45.6% vs. 19.5% [p<0.001] and 49.1% vs. 24.2% [p<0.001], respectively) groups, as well as the IR in the SMF group (43.3% vs. 26.5%, p=0.011). Additionally, PGT-A was associated with lower overall incidence rates of early pregnancy loss in the AMA (16.7% vs. 34.3%, p=0.001) and RPL (16.7% vs. 50.0%, p<0.001) groups. However, the OPR/LBR per total cycle across all PGT-A groups did not significantly exceed that for the non-PGT-A groups. Conclusion: PGT-A demonstrated beneficial effects in high-risk patients. However, our findings indicate that these benefits are more pronounced in carefully selected candidates than in the entire high-risk patient population. [ABSTRACT FROM AUTHOR]

Objectives: The association between pregestational diabetes mellitus (PDM) and risk of congenital heart disease (CHD) is well recognized; however, the importance of glycemic control and other coexisting risk factors during pregnancy is less clear. We sought to determine the relative risk (RR) of major CHD (mCHD) among offspring from pregnancies complicated by PDM and the effect of first‐trimester glycemic control on mCHD risk. Methods: We determined the incidence of mCHD (requiring surgery within 1 year of birth or resulting in pregnancy termination or fetal demise) among registered births in Alberta, Canada. Linkage of diabetes status, maximum hemoglobin A1c (HbA1c) at < 16 weeks' gestation and other covariates was performed using data from the Alberta Perinatal Health Program registry. Risk of mCHD according to HbA1c was estimated as an adjusted RR (aRR), calculated using log‐binomial modeling. Results: Of 1412 cases of mCHD in 594 773 (2.37/1000) births in the study period, mCHD was present in 48/7497 with PDM (6.4/1000; RR, 2.8 (95% CI, 2.1–3.7); P < 0.0001). In the entire cohort, increased maternal age (aRR, 1.03 (95% CI, 1.02–1.04); P < 0.0001) and multiple gestation (aRR, 1.37 (95% CI, 1.1–1.8); P = 0.02) were also associated with mCHD risk, whereas maternal prepregnancy weight > 91 kg was not. The stratified risk for mCHD associated with HbA1c ≤ 6.1%, > 6.1–8.0% and > 8.0% was 4.2/1000, 6.8/1000 and 17.1/1000 PDM/gestational diabetes mellitus births, respectively; the aRR of mCHD associated with PDM and HbA1c > 8.0% was 8.5 (95% CI, 5.0–14.4) compared to those without diabetes and 5.5 (95% CI, 1.6–19.4) compared to PDM with normal HbA1c (≤ 6.1%). Conclusions: PDM is associated with a RR of 2.8 for mCHD, increasing to 8.5 in those with HbA1c > 8%. These data should facilitate refinement of referral indications for high‐risk pregnancy screening. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. Linked article: There is a comment on this article by Jiang and Li. Click here to view the Correspondence. [ABSTRACT FROM AUTHOR]

ObjectiveThis 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.MethodsA 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.ResultsThe 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

Background: Several studies have compared the effects of fixed and flexible gonadotropin releasing hormone antagonist (GnRH-ant) protocols during in vitro fertilization and embryo transfer (IVF-ET). However, which GnRH-ant initiation strategy is better remains controversial. Moreover, no studies have assessed the optimal timing of GnRH-ant initiation in women of advanced maternal age (AMA). Methods: In this retrospective cohort study, a total of 472 infertile women aged = 35 years old undergoing their first IVF cycle from August 2015 to September 2021 at a tertiary academic medical center were recruited, of whom 136 followed fixed GnRH-ant protocol and 336 followed flexible GnRH-ant protocol. The primary outcomes measured were the cumulative live birth rate (CLBR) per IVF cycle and the time to live birth (TTLB) from the date of oocyte retrieval. Cox proportional models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of CLBR regarding GnRH-ant timing. Results: No significant difference in CLBR was found between the fixed and flexible GnRH-ant groups (27.9% vs 20.5%, p=0.105). The TTLB was also comparable between groups (10.56 vs 10.30 months, p=0.782). The Kaplan-Meier analysis for CLBR also showed comparable results between groups (P=0.351, HR=0.83; 95%CI: 0.56-1.23). After establishing a multiple Cox proportional hazard model, the fixed GnRH-ant group still had comparable CLBR with the flexible GnRH-ant group (HR=0.85; 95%CI: 0.53-1.38; P=0.518). Subgroup and sensitivity analyses also demonstrated similar results. Conclusion: GnRH-ant protocols can be tailored to the needs of AMA women, and timing of GnRH-ant initiation can be adjusted flexibly. [ABSTRACT FROM AUTHOR]

Background and Aims: The prevalence of gestational diabetes mellitus (GDM) continues to increase, and the phenomenon of women giving birth at an older age is becoming more common worldwide. Less is known abouts the impact of GDM combined with advanced maternal age (AMA) on pregnancy outcomes. To explore the impact of AMA complicated with GDM on pregnancy outcomes. Methods: This study included 34,602 pregnancies between 2018 and 2020 in Hangzhou, China. The pregnant women were divided into four groups according to advanced age (≥35 years) and GDM as follows: AMA women without GDM (non‐AGDM) group (n = 2614), young pregnant women with GDM (YGDM) group (n = 4016), AMA women with GDM (AGDM) group (n = 850), and young pregnant women without GDM (non‐YGDM) group (n = 27,122). Univariate analysis was carried out by Mann–Whitney U test or Pearson's χ2 test. Multivariate logistic regression analysis was used to investigate the effect of AMA and GDM on pregnancy outcomes. Results: Multivariate logistic regression analysis showed that in the comparison against non‐YGDM garoup, the ORs of fetal chromosome abnormality, parity, urgent cesarean section, gravidity, scheduled cesarean section, body mass index (BMI) ≥30 kg/m2, pre‐eclampsia, thrombocytopenia, hyperlipidemia, BMI 25–29.9 kg/m2, blood urea nitrogen, fasting blood glucose, and creatinine in AGDM group were 16.044, 4.284, 3.530, 3.284, 3.257, 2.049, 1.935, 1.898, 1.690, 1.471, 1.304, 1.216, and 1.026 (all p < 0.05). Conclusions: The prevalence of pregnant women with AGDM was 2.46% in Hang Zhou, China. The increasing gravidity of AMA women was related to a greater risk of GDM. The AGDM group associated with a greater risks of chromosomal abnormality in offspring and cesarean section, especially urgent cesarean section. [ABSTRACT FROM AUTHOR]

During recent decades, the application of intracytoplasmic sperm injection has increased considerably worldwide, especially in couples with non‐male factor infertility. However, several studies analyzing the broad use of intracytoplasmic sperm injection, even in cases with a normal semen analysis, have collectively demonstrated no benefits compared to conventional in‐vitro fertilization. Currently, there is insufficient evidence to support the intracytoplasmic sperm injection technique vs. in‐vitro fertilization in cases of poor ovarian response or a low number of oocytes collected, or in patients with advanced maternal age. Since the intracytoplasmic sperm injection technique is more operator‐dependent and invasive, its use should only be recommended in cases of male‐factor infertility. There is some evidence showing that intracytoplasmic sperm injection is linked with an increased risk of birth defects. Albeit this evidence is limited, and currently it is not possible to draw a firm conclusion on these concerns, we do believe that these risks should be rigorously investigated. Thus, this review aims to clarify the debate on the application of the intracytoplasmic sperm injection procedure, as compared to standard in‐vitro fertilization, in those assisted reproductive technology cycles without a clear male factor infertility. Furthermore, we try to clarify whether intracytoplasmic sperm injection would result in a higher live birth rate than in‐vitro fertilization, in couples with non‐male factor infertility. [ABSTRACT FROM AUTHOR]

Advanced maternal age (AMA, >35 years at delivery) confers maternal and foetal risks, particularly with age >45 years and nulliparity, but longitudinal comparative data on age- and parity-specific AMA fertility is lacking. We used the Human Fertility Database (HFD), a publicly available, international database, to analyse fertility in US and Swedish women aged 35–54 from 1935 to 2018. Age-specific fertility rates (ASFR), total birth counts, and proportion of AMA births were evaluated across maternal age, parity, and time, and compared to maternal mortality rates during the same time. In the US, total AMA births nadired in the 1970s, and have risen since. Until 1980, most AMA births were to women completing parity 5 or higher; since then, most have been to low parity women. While ASFR in 35 to 39 year olds was highest in 2015, ASFR in women 40–44 and 45–49 were highest in 1935, though they have been rising recently, especially in low-parity women. While the same AMA fertility trends were seen in the US and Sweden from 1970–2018, maternal mortality rates have risen in the US despite remaining low in Sweden. Although AMA is known to contribute to maternal mortality, this discrepancy merits further consideration. [ABSTRACT FROM AUTHOR]

This document examines the relationship between advanced maternal age (AMA) and pregnancy complications. The study compares the cardiovascular control of pregnant women aged 35 and older with those aged 30 and younger. The researchers hypothesized that AMA would result in reduced heart rate variability, higher blood pressure variability, and higher left ventricular contractility. The study analyzed various measures of cardiovascular control and found that resting systolic blood pressure was lower in the AMA group. There were no significant differences in heart rate variability, but diastolic and mean blood pressure variability were lower in the AMA group, as was left ventricular contractility. This suggests that older pregnant women may have reduced blood pressure variability and left ventricular contractility compared to younger pregnant women. [Extracted from the article]

This article explores the use of machine learning (ML) models in predicting the ploidy status of embryos in in vitro fertilization (IVF). The study compares different ML models using morphokinetic and clinical data to predict the ploidy status of blastocysts. The authors find that a traditional logistic regression model performs better than more complex ML algorithms when predicting aneuploidy, but its performance decreases when predicting euploidy. The article also discusses the impact of dataset characteristics, the relevance of clinical variables, potential bias in ML models based on oocyte age, and the influence of outcome imbalance on model predictions. The authors caution that ML models should be used cautiously and in conjunction with other clinical factors, and emphasize the importance of interdisciplinary collaboration and ethical considerations in their use. [Extracted from the article]

STUDY QUESTION 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? SUMMARY ANSWER 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. 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 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. STUDY DESIGN, SIZE, DURATION 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. 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 (two pronuclei) in the PB biopsy group and 1082 in the control group were used for statistical analysis. MAIN RESULTS AND THE ROLE OF CHANCE 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). 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 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. STUDY FUNDING/COMPETING INTEREST(S) 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. TRIAL REGISTRATION NUMBER Data were mined from the ESTEEM study (ClinicalTrials.gov Identifier NCT01532284). [ABSTRACT FROM AUTHOR]

Abstract Background Early prediction of gestational diabetes mellitus(GDM) can be beneficial for lifestyle modifications to prevent GDM. The aim of this study was to investigate the predictive values of Homeostasis of Model Assessment -Insulin Resistance (HOMA-IR) in early pregnancy to predict GDM development in different body mass index (BMI) and age risk categories. Materials and methods This study is part of the Qazvin Maternal and Neonatal Metabolic Study (QMNMS) in Iran (2018–2021). In this prospective longitudinal study, pregnant women with a gestational age ≤ 14 weeks were enrolled in the study using convenience sampling method and were followed up until delivery to investigate risk factors for maternal and neonatal complications. Data collection was done using questionnaires. Serum sampling was done at a gestational age ≤ 14 weeks and sera were frozen until the end of study. GDM was diagnosed at 24–28 weeks of pregnancy using 75gr oral glucose tolerance test. Fasting blood glucose and insulin were measured in sera taken during early pregnancy in 583 participants. The Mann-Whitney U test, independent t-test, and Chi-square test were used for comparing variables between groups. The logistic regression analysis was used to examine the independent association of HOMA-IR with GDM development and receiver operating characteristic analysis was used for finding the best cut-off of HOMA-IR for predicting GDM. Results GDM was developed in 90 (15.4%) of the participants. The third HOMA-IR tertile was independently associated with 3.2 times higher GDM occurrence (95% CI:1.6–6.2, P = 0.001). Despite the high prevalence of GDM in advanced maternal age (GDM rate = 28.4%), HOMA-IR had no association with GDM occurrence in this high-risk group. In both normal BMI and overweight/obese groups, HOMA-IR was a moderate predictor of GDM development (AUC = 0.638, P = 0.005 and AUC = 0.622, P = 0.008, respectively). However, the best cut-off for predicting GDM was 2.06 (sensitivity 67.5%, specificity 61.1%) in normal BMI and 3.13 (sensitivity 64.6%, specificity61.8%) in overweight/obese BMI. Conclusion The present study revealed the necessity of considering the BMI and age risk groups when using the HOMA-IR index to predict GDM. Using lower cut-offs is more accurate for women with a normal BMI. In the advanced maternal age, there is no yield of HOMA-IR for predicting GDM.

Abstract Background Childbearing in women with advanced maternal age (AMA) has increased the need for artificial reproductive technology (ART). ART and oxidative stress are associated with many pregnancy complications. Paraoxonase (PON) 1 is one of the key components responsible for antioxidative activity in high-density lipoprotein (HDL). This study aimed to investigate the longitudinal changes of oxidative stress and PON1 lactonase activity and status in older women undergoing ART. Methods This prospective nested case-control study included 129 control and 64 ART women. Blood samples were obtained respectively at different stages of pregnancy. PON1 level and lactonase activity were assessed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL) as a substrate, respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA), homocysteine (HCY), PON1 C-108T and Q192R genetic polymorphisms, and metabolic parameters were analyzed. Results Lactonase activity and level of PON1 gradually decreased with pregnancy progression, while glycolipid metabolism parameters and TAC levels increased with pregnancy progression or significantly raised during the 2nd and 3rd trimesters, and NLA of PON1, TOS, OSI, MDA, and HCY significantly increased before delivery in the ART and control groups. Compared with the control women, the ART women had substantially higher or relatively high lactonase activity and NLA of PON1 and TAC during pregnancy; higher triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, atherogenic index, apolipoprotein (apo) B, and apoB/apoA1 ratio in the 1st trimester; and higher fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, and TG levels before delivery. No significant differences were found in the frequencies of PON1 C-108T and Q192R genotypes and alleles between the ART and control groups. Conclusions Women with AMA undergoing ART had higher TAC, PON1 lactonase activity, and PON1 NLA than control women, suggesting increased compensatory antioxidant capacity in ART women, thus showing higher sensitivity to oxidative stress-related injury and diseases.

Abstract Background Studies 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. Methods This 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. Results The 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. Conclusions GH 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 registration NCT05574894, www.clinicaltrials.gov .

Objective: To assess the pregnancy outcomes, including live birth rate and pregnancy loss for women aged 45–49 years at the time of oocyte retrieval, who underwent frozen autologous transfer of embryos. Methods: Among frozen-thawed embryo transfers (ET) performed at our clinic from September 2013 to March 2021, 1,114 cycles of women aged 45–49 years at the time of oocyte retrieval were examined retrospectively. Positive pregnancy test, clinical pregnancy, pregnancy loss, and live birth rates per transfer among each age group were analyzed using one-way analysis of variance or the Fisher’s exact test. Results: The mean age at the time of oocyte retrieval and ET was 45.8 and 46.5 years, respectively. Positive pregnancy test rate was 7.6%, of which 72.9% resulted in pregnancy loss. The clinical pregnancy and live birth rates were 5.1% and 2.0%, respectively, with a live birth rate of 3.0% for women with oocytes retrieved at 45 years of age. Multivariate analysis revealed that younger oocyte retrieval age was associated with biochemical and clinical pregnancy; however, no such association was observed for cases with live birth. The oocyte retrieval age of patients with live births was 45 years in 16 cases, 46 years in six cases, and 47 years in one case. In one case of live birth (46 years old), 21 trisomy was observed in the child; however, congenital abnormalities were not observed in other cases. Chorionic tests were performed on the fetuses in 12 of the 33 clinical abortions, of which 11 showed chromosomal abnormalities. Conclusions: Fertility treatment with autologous oocytes in advanced-age women has a low success rate. Although prognosis is poor above 45 years of age, these results can help in providing information to aid patients in their decisions regarding whether or not to pursue treatment.