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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.

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.

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]

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: 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]

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

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.

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]

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]

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 .

Background: Universal screening, including thyroid dysfunction, gestational diabetes, and performing morphology and growth scans, was introduced in the healthcare system to improve perinatal care and pregnancy outcomes. Pregnancy-related complications are usually higher in grand multiparous women and their advanced maternal age. This study aimed to compare the impact of implementing a universal screening strategy protocol versus the selective screening for grand multiparous pregnant women aged ≥35 years on the incidence of adverse pregnancy outcomes and the associated risk factors. Methods: A retrospective cohort study of two groups (n = 89/group) of healthy grand multiparous women aged ≥35 years and who either delivered between 2011–2012 and underwent selective screening, or between 2016–2017 and were universally screened, was conducted at the Department of Obstetrics and Gynecology, Jordan University Hospital. Results: The universal screening protocol detected more cases of women with gestational diabetes, gestational hypertension, and polyhydramnios 7, 4, and 9 more times, respectively, than the selective screening procedure. However, the results of universal screening tests for thyroid function and glucose tolerance were abnormal in only a small number of women. Furthermore, the cesarean section rate was reduced from 45% in the selective screening group to 1% in the universal screening group. No other significant differences in pregnancy or neonatal complications between the two groups were noted. Conclusions: Implementing new perinatal care protocols, including universal screening for thyroid disease and gestational diabetes, morphological and growth scans significantly decreased the rate of cesarean section in grand multiparous women with advanced maternal age, but did not affect pregnancy or neonatal complications. However, larger studies are needed to obtain more representative results among women in high-risk group for gestational diabetes mellitus (GDM) and thyroid dysfunction.

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 FROM AUTHOR]

Background: Age-related fertility decay is a great challenge for clinicians. Growth hormone (GH) supplementation has been studied as an adjuvant since late 1980s. However, it has not come to a consensus on the GH administration due to the ambiguous efficacy among studies with different enrolled population and dosage regime. Methods: A self-controlled retrospective study was conducted on women with advanced maternal age who underwent at least a previous cycle without GH (GH-) and a subsequent cycle with GH co-treatment (GH+). The ovarian stimulation parameters and outcomes were compared between the two cycles and logistical analysis was applied to further explore the association between GH administration protocol as well as other clinical parameters and cumulative live birth in GH+cycle. Results: A total of 150 women aged 35-43 were included. The number of oocytes retrieved, MII oocytes, 2PNs, transferrable embryos and good-quality embryos in GH+ significantly increased (p < 0.001). The proportion of cycles with no transferrable embryos was significantly reduced in GH+ cycle compared with previous GH- cycle (3 vs. 32; p < 0.001). GH co-treatment cycles showed significantly higher clinical pregnancy rates (43.75% vs. 6.06%; 38.35% vs. 12.04%, p < 0.001), live birth rates (29.17% vs. 0; 27.07% vs. 0, p < 0.001) in both fresh and frozen-thawed embryo transfer cycle. Cumulative live birth rate of the GH+ cycle reached 33.33%. Use of GH prior to Gn stimulation and lasting until the hCG day seemed to achieve a higher successful live birth rate (OR 2.312, 95%CI 1.074-5.163, p=0.032). Conclusion: GH supplementation could ameliorate pregnancy outcome in women with advanced maternal age. Dosage regimen of long-term pretreatment prior to Gn stimulation (4 IU every other day) and 4 IU per day until hCG day may of greater efficacy compared with concurrent administration with Gn. Additionally, it's worthy of exploring whether an individualized dosage regimen based on the IGF or IGFBP level of patient would be more reasonable and effective. More well-designed prospective trials with large sample size and fundamental experiments on the mechanism are required to testify findings above. [ABSTRACT FROM AUTHOR]

Endocrine disrupting chemicals (EDCs) are exogenous substances widely disseminated both in the environment and in daily-life products which can interfere with the regulation and function of the endocrine system. These substances have gradually entered the food chain, being frequently found in human blood and urine samples. This becomes a particularly serious issue when they reach vulnerable populations such as pregnant women, whose hormones are more unstable and vulnerable to EDCs. The proper formation and activity of the placenta, and therefore embryonic development, may get seriously affected by the presence of these chemicals, augmenting the risk of several pregnancy complications, including intrauterine growth restriction, preterm birth, preeclampsia, and gestational diabetes mellitus, among others. Additionally, some of them also exert a detrimental impact on fertility, thus hindering the reproductive process from the beginning. In several cases, EDCs even induce cross-generational effects, inherited by future generations through epigenetic mechanisms. These are the reasons why a proper understanding of the reproductive and gestational alterations derived from these substances is needed, along with efforts to establish regulations and preventive measures in order to avoid exposition (especially during this particular stage of life). [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This retrospective cohort study aimed to explore the association between advanced maternal age and the clinical manifestations as well as laboratory parameters of preeclampsia with severe features. This study included 452 patients who were diagnosed with preeclampsia with severe features. The clinical and laboratorial characteristics of patients with preeclampsia with severe features aged ≥40 years old (study group) were compared to those of patients aged <40 years old (control group). Multivariant analysis was applied to assess the association between advanced maternal age and the manifestations of preeclampsia with severe features, adjusting for the variables that exhibited significant differences between the study and control groups. The multivariate analysis revealed that a maternal age of ≥40 years old was an independent risk factor for acute kidney injury (OR = 2.5, CI = 1.2–4.9, p = 0.011) and for new-onset postpartum preeclampsia (OR = 2.4, CI = 1.0–5.6, p = 0.046). Conversely, a maternal age ≥ 40 years old was associated with a reduced risk of HELLP syndrome (OR = 0.4, CI = 0.2–0.9, p = 0.018) and thrombocytopenia (OR = 0.5, CI = 0.3–0.9, p = 0.016) compared to that of the patients < 40 years of age. In conclusion, this study demonstrates that maternal age is significantly associated with the clinical manifestations and laboratory parameters of preeclampsia with severe features, highlighting the importance of age-specific management. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the existing empirical literature on the psychosocial health and wellbeing of the parents and offspring born at an advanced parental age (APA), defined as 40 years onwards? SUMMARY ANSWER Although the studies show discrepancies in defining who is an APA parent and an imbalance in the empirical evidence for offspring, mothers, and fathers, there is a drive towards finding psychotic disorders and (neuro-)developmental disorders among the offspring; overall, the observed advantages and disadvantages are difficult to compare. WHAT IS KNOWN ALREADY In many societies, children are born to parents at advanced ages and there is rising attention in the literature towards the consequences of this trend. STUDY DESIGN, SIZE, DURATION The systematic search was conducted in six electronic databases (PubMed including Medline, Embase, Scopus, PsycInfo, CINAHL, and SocINDEX) and was limited to papers published between 2000 and 2021 and to English-language articles. Search terms used across all six electronic databases were: ('advanced parental age' OR 'advanced maternal age' OR 'advanced paternal age' OR 'advanced reproductive age' OR 'late parent*' OR 'late motherhood' OR 'late fatherhood') AND ('IVF' OR 'in vitro fertilization' OR 'in-vitro-fertilization' OR 'fertilization in vitro' OR 'ICSI' OR 'intracytoplasmic sperm injection' OR 'reproductive techn*' OR 'assisted reproductive technolog*' OR 'assisted reproduction' OR 'assisted conception' OR 'reproduction' OR 'conception' OR 'birth*' OR 'pregnan*') AND ('wellbeing' OR 'well-being' OR 'psycho-social' OR 'social' OR 'ethical' OR 'right to reproduce' OR 'justice' OR 'family functioning' OR 'parental competenc*' OR 'ageism' OR 'reproductive autonomy' OR 'outcome' OR 'risk*' OR 'benefit*'). PARTICIPANTS/MATERIALS, SETTING, METHODS The included papers were empirical studies in English published between 2000 and 2021, where the study either examined the wellbeing and psychosocial health of parents and/or their children, or focused on parental competences of APA parents or on the functioning of families with APA parents. A quality assessment of the identified studies was performed with the QATSDD tool. Additionally, 20% of studies were double-checked at the data extraction and quality assessment stage to avoid bias. The variables sought were: the geographical location, the year of publication, the methodological approach, the definitions of APA used, what study group was at the centre of the research, what research topic was studied, and what advantages and disadvantages of APA were found. MAIN RESULTS AND THE ROLE OF CHANCE A total number of 5403 articles were identified, leading to 2543 articles being included for title and abstract screening after removal of duplicates. This resulted in 98 articles included for a full-text reading by four researchers. Ultimately, 69 studies were included in the final sample. The key results concerned four aspects relevant to the research goals. (i) The studies showed discrepancies in defining who is an APA parent. (ii) There was an imbalance in the empirical evidence produced for different participant groups (mothers, fathers, and offspring), with offspring being the most studied study subjects. (iii) The research topics studied underlined the increased risks of neuro-developmental and psychotic disorders among offspring. (iv) The observed advantages and disadvantages were varied and could not be compared, especially for the offspring of APA parents. LIMITATIONS, REASONS FOR CAUTION Only English-language studies, published between 2000 and 2021, found in the above-mentioned databases were considered for this review. WIDER IMPLICATIONS OF THE FINDINGS More research is necessary to understand the risks and benefits of building a family at an APA for the offspring when they reach adulthood. Furthermore, studies that explore the perspective of older fathers and older parents from non-Western societies would be highly informative. STUDY FUNDING/COMPETING INTEREST(S) The writing of this manuscript was permitted by financial support provided by the Swiss National Science Foundation (Weave/Lead Agency funding program, grant number 10001AL_197415/1, project title 'Family Building at Advanced Parental Age: An Interdisciplinary Approach'). The funder had no role in the drafting of this manuscript and the views expressed therein are those of the authors. The authors have no conflicts of interest. REGISTRATION NUMBER This systematic review is registered in Prospero: CRD42022304564. [ABSTRACT FROM AUTHOR]

Abstract 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

Background Common maternal medical comorbidities such as hypertensive disorders, diabetes, tobacco use, and extremes of maternal age, body mass index, and gestational weight gain are known individually to influence the rate of cesarean delivery. Numerous studies have estimated the risk of individual conditions on cesarean delivery.

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.

Objective: To investigate if next-generation sequencing-based preimplantation genetic testing for aneuploidies could improve pregnancy outcomes in women of advanced maternal age. Materials and methods: A retrospective analysis. The clinical data of 1099 couples treated in the First Medical Center of the Chinese PLA General Hospital from January 2019 to December 2021 were analyzed. They were divided into two groups based on whether they underwent a Next-generation sequencing-based preimplantation genetic test for aneuploidies. We analyzed and compared the biochemical pregnancy rate, clinical pregnancy rate, abortion rate, and live birth rate between the two groups. Results: The Preimplantation genetic testing for aneuploidies (PGT-A) group was associated with higher rate of biochemical pregnancy and clinical pregnancy than the non-PGT-A group, which were 63.9% vs. 56.4% (P = 0.009) and 54.4% vs. 45.6% (P

Objective Objective To investigate the changes in hippocampal astrocytes and neuronal primary cilia, and neuronal apoptosis in the offspring brain of advanced maternal age and the role of LKB1/AMPK pathway. Methods The 12-month-old SD female rats were mated with 3-month-old SD male rats to produce offspring as the advanced maternal age (AMA) group, and the 3-month-old SD female rats were mated with 3-month-old SD males to produce offspring as the appropriate age (Control, Ctl) group. The following studies were conducted on postnatal days 14, 28 and 60 (P14, P28 and P60) in the 2 groups (14 rats per group at each time point, half males and half females). HE staining and Nissl staining were used to observe the changes in the morphology and the number of hippocampal neurons and their internal Nissl bodies. Immunofluorescence assay was employed to detect the expression of hippocampal primary cilia marker, anti-ADP ribosylation factor-like protein-13B (ARL13B), and Western blotting was applied to measure the expression of hippocampal intraflagellar transport protein 88 (IFT88) to assess functional changes in primary ciliogenesis. TUNEL staining and Western blotting were performed to detect the expression levels of pro-apoptotic BAX, and anti-apoptotic protein, BCL-2 to observe the changes of apoptosis in the hippocampus. Western blotting was also used to detect the expression levels of liver kinase B1 (LKB1), adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and the levels of their corresponding phosphorylated proteins to assess LKB1/AMPK pathway changes. Results Compared with the Ctl group: HE staining and Nissl staining showed that the number of hippocampal neurons was significantly reduced in the AMA group at P14 (P < 0.05), and there were abnormal changes in hippocampal neuron morphology and Nissl body number and morphology in the AMA group at all time points; the incidence of ARL13B primary cilia was significantly decreased in the AMA group at both P14 (P < 0.05) and P28 (P < 0.001), and the length of ARL13B was obviously shortened in the AMA group at both P14 (P < 0.05) and P28 (P < 0.05); the hippocampal expression level of IFT88 was notably lower in the AMA group at the P14 (P < 0.01). TUNEL staining showed that the apoptotic rate of hippocampal neurons at P14 was remarkably higher in the AMA group (P < 0.05), while Western blotting indicated that the expression of BAX was significantly higher (P < 0.001) and that of BCL-2 was lower (P < 0.01). In the AMA group, the expression of p-LKB1 was significantly decreased at P14 (P < 0.05), that of p-AMPK was statistically elevated at P28 (P < 0.01) and P60 (P < 0.01), and that of p-mTOR was notably decreased at P60 (P < 0.05). Conclusion Neuronal damage, defective primary ciliogenesis and growth inhibition, and abnormal activation of apoptosis are present in the hippocampus of juvenile offspring brain of advanced maternal age. Meanwhile, the LKB1/AMPK pathway, which is regulated by primary cilia in hippocampal astrocytes and neurons of advanced maternal age offspring brain, is abnormally activated at all ages.

Abstract Background Owing to the changes in childbirth policy in China, this work aimed to update the trimester-specific reference intervals (RIs) for Chinese pregnant women with diverse demographics and obstetric history. This study also investigated how advanced maternal age (AMA) (> 35 years old), gravity, and parity influence gestational coagulation parameters. Methods In this prospective cross-sectional study, five coagulation parameters were measured using assays provided by Roche diagnostics on Cobas t 711: prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib), and D-dimer, and the trimester-specific 2.5th -97.5th and 95th (D-dimer only) percentiles RIs were established accordingly. Linear regressions were undertaken to analyze the association with demographic characteristics and obstetric history for each parameter. Results 893 eligible pregnant women in different trimesters and at AMA/non-AMA and 275 non-pregnant healthy women were enrolled. For the first, second, and third trimester, respectively, RIs were as follows: APTT (s): 24.8–35.7, 24.6–34.1, and 23.5–34.7; TT (s): 14.4–17.3, 14.1–16.7, and 14.2–17.5; PT (s): 8.30–10.20, 8.00-9.77, and 7.92–9.57; PT-INR: 0.86–1.06, 0.83–1.02, and 0.82–0.98; Fib (g/L): 2.76–4.97, 3.14–5.31, and 3.44–5.93; D-dimer (µg/ml): 0-0.969, 0-2.14, and 0-3.28. No statistically significant differences were observed in TT, D-dimer, and APTT between the AMA and non-AMA women, while PT and PT-INR were shorter and Fib was higher in the AMA group. The association of gravidity and parity with each coagulation parameter is statistically significant (p

Purpose: To compare perinatal outcomes in in-vitro fertilization (IVF) pregnancies versus spontaneous conceptions in woman of advanced maternal age (AMA), and to evaluate the effect of increasing age on IVF pregnancies' outcomes. Methods: A retrospective population-based cohort study including pregnant women who delivered between 2008–2014 in the US. First, we included women aged 38–43 years and compared those with IVF conceptions (cases) to women with spontaneous conceptions (controls). Thereafter, we compared IVF pregnancies in women aged 38–43 years to IVF pregnancies at < 38 years of age. Multivariate logistic regression was performed to compare both groups regarding pregnancy,delivery, and neonatal outcomes after adjusting for plausible confounders. Results: Three hundred nine thousand five hundred sixty-seven pregnant women aged 38–43 years were identified, with 2,762 composing the IVF group, and 306,805 composing the control group. After adjusting for confounders, the IVF group had a higher risk of several adverse obstetrical outcomes, including hypertensive disorders of pregnancy (aOR 1.31,95%CI 1.06–1.62), gestational diabetes (aOR 1.26,95%CI 1.13–1.41),preterm delivery (aOR 1.45,95%CI 1.16–1.81), cesarean section (CS) (aOR 1.84,95%CI 1.55- 2.19),postpartum hemorrhage (aOR 1.68,95%CI 1.27- 2.24), and maternal infection (aOR 1.90,95%CI 1.31–2.77), with comparable neonatal outcomes. For the second analysis, 9712 IVF pregnancies were included (n = 6950 < 38 years, and n = 2762 ≥ 38 years). Women ≥ 38 years who underwent IVF were more likely to experience hypertensive disorders of pregnancy, CS, hysterectomy and blood transfusion, with comparable neonatal outcomes. Conclusion: IVF AMA pregnancies have a significant increase in myriad perinatal complications compared to spontaneous AMA pregnancies. Younger women undergoing IVF have mildly less complications than their older counterparts. [ABSTRACT FROM AUTHOR]

BACKGROUND A normal chromosomal constitution defined through PGT-A assessing all chromosomes on trophectoderm (TE) biopsies represents the strongest predictor of embryo implantation. Yet, its positive predictive value is not higher than 50–60%. This gap of knowledge on the causes of euploid blastocysts' reproductive failure is known as 'the black box of implantation'. OBJECTIVE AND RATIONALE Several embryonic, maternal, paternal, clinical, and IVF laboratory features were scrutinized for their putative association with reproductive success or implantation failure of euploid blastocysts. SEARCH METHODS A systematic bibliographical search was conducted without temporal limits up to August 2021. The keywords were '(blastocyst OR day5 embryo OR day6 embryo OR day7 embryo) AND (euploid OR chromosomally normal OR preimplantation genetic testing) AND (implantation OR implantation failure OR miscarriage OR abortion OR live birth OR biochemical pregnancy OR recurrent implantation failure)'. Overall, 1608 items were identified and screened. We included all prospective or retrospective clinical studies and randomized-controlled-trials (RCTs) that assessed any feature associated with live-birth rates (LBR) and/or miscarriage rates (MR) among non-mosaic euploid blastocyst transfer after TE biopsy and PGT-A. In total, 41 reviews and 372 papers were selected, clustered according to a common focus, and thoroughly reviewed. The PRISMA guideline was followed, the PICO model was adopted, and ROBINS-I and ROB 2.0 scoring were used to assess putative bias. Bias across studies regarding the LBR was also assessed using visual inspection of funnel plots and the trim and fill method. Categorical data were combined with a pooled-OR. The random-effect model was used to conduct the meta-analysis. Between-study heterogeneity was addressed using I 2. Whenever not suitable for the meta-analysis, the included studies were simply described for their results. The study protocol was registered at http://www.crd.york.ac.uk/PROSPERO/ (registration number CRD42021275329). OUTCOMES We included 372 original papers (335 retrospective studies, 30 prospective studies and 7 RCTs) and 41 reviews. However, most of the studies were retrospective, or characterized by small sample sizes, thus prone to bias, which reduces the quality of the evidence to low or very low. Reduced inner cell mass (7 studies, OR: 0.37, 95% CI: 0.27–0.52, I 2 = 53%), or TE quality (9 studies, OR: 0.53, 95% CI: 0.43–0.67, I 2 = 70%), overall blastocyst quality worse than Gardner's BB-grade (8 studies, OR: 0.40, 95% CI: 0.24–0.67, I 2 = 83%), developmental delay (18 studies, OR: 0.56, 95% CI: 0.49–0.63, I 2 = 47%), and (by qualitative analysis) some morphodynamic abnormalities pinpointed through time-lapse microscopy (abnormal cleavage patterns, spontaneous blastocyst collapse, longer time of morula formation I, time of blastulation (tB), and duration of blastulation) were all associated with poorer reproductive outcomes. Slightly lower LBR, even in the context of PGT-A, was reported among women ≥38 years (7 studies, OR: 0.87, 95% CI: 0.75–1.00, I 2 = 31%), while obesity was associated with both lower LBR (2 studies, OR: 0.66, 95% CI: 0.55–0.79, I 2 = 0%) and higher MR (2 studies, OR: 1.8, 95% CI: 1.08–2.99, I 2 = 52%). The experience of previous repeated implantation failures (RIF) was also associated with lower LBR (3 studies, OR: 0.72, 95% CI: 0.55–0.93, I 2 = 0%). By qualitative analysis, among hormonal assessments, only abnormal progesterone levels prior to transfer were associated with LBR and MR after PGT-A. Among the clinical protocols used, vitrified-warmed embryo transfer was more effective than fresh transfer (2 studies, OR: 1.56, 95% CI: 1.05–2.33, I 2 = 23%) after PGT-A. Lastly, multiple vitrification-warming cycles (2 studies, OR: 0.41, 95% CI: 0.22–0.77, I 2 = 50%) or (by qualitative analysis) a high number of cells biopsied may slightly reduce the LBR, while simultaneous zona-pellucida opening and TE biopsy allowed better results than the Day 3 hatching-based protocol (3 studies, OR: 1.41, 95% CI: 1.18–1.69, I 2 = 0%). WIDER IMPLICATIONS Embryo selection aims at shortening the time-to-pregnancy, while minimizing the reproductive risks. Knowing which features are associated with the reproductive competence of euploid blastocysts is therefore critical to define, implement, and validate safer and more efficient clinical workflows. Future research should be directed towards: (i) systematic investigations of the mechanisms involved in reproductive aging beyond de novo chromosomal abnormalities, and how lifestyle and nutrition may accelerate or exacerbate their consequences; (ii) improved evaluation of the uterine and blastocyst-endometrial dialogue, both of which represent black boxes themselves; (iii) standardization/automation of embryo assessment and IVF protocols; (iv) additional invasive or preferably non-invasive tools for embryo selection. Only by filling these gaps we may finally crack the riddle behind 'the black box of implantation'. [ABSTRACT FROM AUTHOR]

The aim of this multicenter retrospective cohort study was to examine the impact of maternal age on perinatal outcomes in multiparas, stratified according to maternal age in one- and two-year increments. The analysis involved 302,484 multiparas who delivered between the years 2003 and 2021 in four university-affiliated obstetrics departments. Maternal age was considered both as a continuous variable and in two-year intervals, as compared with a comparison group of parturients aged 25–30 years. The study focused on cesarean delivery and neonatal intensive care unit (NICU) admission as primary outcomes. The findings revealed that cesarean delivery rates increased as maternal age advanced, with rates ranging from 6.7% among 25–30 year olds, rising continuously from 13.5% to 19.9% between the age strata of 31 and 42, to exceeding 20% among those aged ≥ 43 years (p < 0.01 for each stratum when compared to 25–30 year old group). Similarly, NICU admission rates rose from 2.7% in the comparison group to 6% in parturients aged 45–46 years (p < 0.01 for each stratum when compared to 25–30 year old group). The study highlights the association between incrementally advanced maternal age and increased rates of maternal and neonatal complications, necessitating global awareness of these implications for family planning decisions and maternal care. [ABSTRACT FROM AUTHOR]

Introduction: Elderly women are believed to experience many risks associated with pregnancy. Literature fails to provide a clear consensus on the age group in which there is a rise in risk and pathophysiology contributing. 'Pregnancies over forty' are increasing in society, owing to changing lifestyles and sensibilities of youth and the advent of assisted reproductive techniques. In India, studies on elderly pregnant women above 40 years of age are lacking. The aim of this study is to assess these pregnancies, their course, obstetric and perinatal outcomes in women delivering above 40 years. Methods: The study group (Group A) comprised of pregnancies in 50 women at age ≥ 40 years on the date of delivery. The control group (Group B) had 50 women who delivered subsequent to the study group and age < 40. Various parameters and outcomes including parity, gestational age, number of gestations, co-existing medical illnesses, the incidence of hypertensive diseases of pregnancy (HDP), gestational diabetes mellitus (GDM), pre-term labor, mode of delivery, birth weight and obstetric and neonatal outcomes were compared. Chi-square test and independent T test were used for statistical analysis. Results: While a good number of patients conceived spontaneously and with basic infertility management, i.e., 84% in the elderly gravid group (Group A) and 96% in the control group (Group B), the number of patients who required ART in Group A were statistically significant (Group A 16% and Group B 4%). Incidence of pre-existing medical diseases like hypertension, diabetes mellitus, thyroid dysfunction, other auto-immune diseases and chronic diseases were noted to be high (26%) in Group A (statistically significant difference). Incidence of HDP, GDM and fetal growth restriction were high in Group A. Tendency to have the presence of fibroid uterus was high in patients in Group A, i.e., 24%, compared to only 8% in the control group; difference was statistically significant. Proportion of pre-term deliveries were high in Group A. Cesarean section rate was high in Group A, though it was not statistically significant. Other perinatal observations and neonatal outcomes were comparable in both groups; differences were not statistically significant. Conclusion: The study reveals an association of a high-risk course of pregnancies in women above the age of 40 years. Proportions of IVF pregnancies are higher in elderly women. Interestingly, the proportion of women in elderly group who conceived spontaneously and with basic infertility management including IUI was 84% in the present study. Medical comorbidities and incidence of fibroids were high in elderly women. Obstetric and neonatal outcomes of these pregnancies when managed efficiently are favorable. [ABSTRACT FROM AUTHOR]

The decision to postpone parenting has gained momentum in recent years, a shift driven by evolving social dynamics and improved access to fertility treatments. Despite their increasing prevalence, pregnancies at advanced maternal ages are associated with increased risks of adverse maternal and neonatal outcomes. This article addresses the association between advanced maternal age and hypertensive disorders of pregnancies (HDPs), which are more prevalent and a significant cause of maternal morbidity and mortality in this population. This review explores the biological mechanisms and age-related risk factors that underpin this increased susceptibility and offers practical management strategies that can be implemented prior to, as well as during, each stage of pregnancy to mitigate the incidence and severity of HDPs in this group. Lastly, this review acknowledges both the short-term and long-term postpartum implications of HDPs in women of advanced maternal age. [ABSTRACT FROM AUTHOR]

Abstract Background Advanced maternal age (AMA) has increased in many high-income countries in recent decades. AMA is generally associated with a higher risk of various pregnancy complications, and the underlying molecular mechanisms are largely unknown. In the current study, we profiled the DNA methylome of 24 human chorionic villi samples (CVSs) from early pregnancies in AMA and young maternal age (YMA), 11 CVSs from early spontaneous abortion (SA) cases using reduced representation bisulfite sequencing (RRBS), and the transcriptome of 10 CVSs from AMA and YMA pregnancies with mRNA sequencing(mRNA-seq). Single-cell villous transcriptional atlas presented expression patterns of targeted AMA-/SA-related genes. Trophoblast cellular impairment was investigated through the knockdown of GNE expression in HTR8-S/Vneo cells. Results AMA-induced local DNA methylation changes, defined as AMA-related differentially methylated regions (DMRs), may be derived from the abnormal expression of genes involved in DNA demethylation, such as GADD45B. These DNA methylation changes were significantly enriched in the processes involved in NOTCH signaling and extracellular matrix organization and were reflected in the transcriptional alterations in the corresponding biological processes and specific genes. Furthermore, the DNA methylation level of special AMA-related DMRs not only significantly changed in AMA but also showed more excessive defects in CVS from spontaneous abortion (SA), including four AMA-related DMRs whose nearby genes overlapped with AMA-related differentially expressed genes (DEGs) (CDK11A, C19orf71, COL5A1, and GNE). The decreased DNA methylation level of DMR near GNE was positively correlated with the downregulated expression of GNE in AMA. Single-cell atlas further revealed comparatively high expression of GNE in the trophoblast lineage, and knockdown of GNE in HTR8-S/Vneo cells significantly impaired cellular proliferation and migration. Conclusion Our study provides valuable resources for investigating AMA-induced epigenetic abnormalities and provides new insights for explaining the increased risks of pregnancy complications in AMA pregnancies. Graphical Abstract

Treatment of sub-fertile women aged ≥ 40 years old (advanced maternal age (AMA)) is challenging. Co-treatment with growth hormone (GH) is suggested to improve reproductive outcomes in poor responders. However, few studies, and with conflicting results, focused on women of AMA. A systematic review and meta-analysis of randomized controlled trials (RCTs) and comparative retrospective trials (CRTs) of GH cotreatment in AMA women undergoing in vitro fertilization or intracytoplasmic injection treatment using their autologous oocytes was performed. The search included studies published in English up to the end of 2021. The primary outcome was the clinical pregnancy rate per embryo transfer. Secondary outcomes were the number of mature and retrieved oocytes and the rate of live birth. A total of 406 studies were found. The final analysis included 3 RCTs and 4 CRTs with 481 patients who used GH and 400 patients who did not. Clinical pregnancy and live birth rates were significantly higher in the GH cotreatment group compared to the placebo as well as the group without GH co-treatment, (odds ratio (OR): 2.2; 95% CI: 1.34–3.61 and OR: 4.12; 95% CI: 1.82–9.32, respectively). Intriguingly, the subgroup analysis showed that poor-responder patients did not benefit from co-treatment with GH. There were no statistically significant differences in the number of mature or retrieved oocytes. GH cotreatment in a subgroup of women of AMA improves clinical pregnancy and live birth per fresh embryo transfer. However, this conclusion must be taken with caution and further research is needed. The review is registered in the PROSPERO database (www.crd.york.ac.uk/prospero/; CRD42021252618).

Abstract Background Advanced maternal age (AMA; ≥35 years) is considered to be a major risk factor for adverse pregnancy outcomes. Along with the global trend of delayed childbearing, and in particular, the implementation of China’s second and third-child policy leading to a dramatic increase of AMA in recent years, the association between maternal age and pregnancy outcomes requires more investigation. Methods A population-based retrospective study was performed. Data were derived from the Medical Birth Registry of Xiamen from 2011 to 2018. Univariate and multivariate logistic regression was used to evaluate the effects of maternal age on pregnancy outcomes. Results A total of 63,137 women categorized into different age groups (

Plain language summary In many countries, women’s age at the birth of their first child has risen markedly, and an increasing number of women do not establish a family until their late-twenties to mid-thirties. This causes risk of couples experiencing fertility problems, as fertility declines with increasing age. Although fertility problems can be caused by various reasons, advanced maternal age is the most frequent cause for women having difficulties achieving pregnancy. In this study, we investigated reflections on timing of motherhood in women who have not yet had children. Through a systematic literature search we identified eight qualitative studies published between 2011 and 2018 that focused on women’s reflections on timing of motherhood. The included studies were synthesized using a meta-ethnographic approach. We identified an overall theme ‘Timing of motherhood’ and four overlapping subthemes: Making a life-changing decision, The right time, Fear of regret, and Plan B. The dilemmas associated with timing of motherhood leave women of reproductive age balancing their priorities and values against a biological deadline for having children naturally or through assisted reproductive technology. Women of reproductive age are aware that they must make a life-changing decision as to if or when to have children, but they consider having children at ‘the right time’ to be important. Simultaneously, while some women are reluctant to have children for various reasons, they express fear that waiting too long could result in their regretting not having children later in life. Although women of reproductive age express concern about their ability to achieve pregnancy, they have limited focus on the medical risks associated with postponing motherhood, which emphasizes the need for establishing preventive health initiatives to support women of reproductive age in their considerations regarding timing of motherhood.

Abstract Background Gestational weight gain (GWG) criteria recommended by the Institute of Medicine may not be appropriate for Asians. Our aims are to investigate the association between GWG and adverse pregnancy outcomes, and to propose optimal total GWG and rates of GWG for Chinese women. Methods Prospective data of 51,125 mother-child pairs from 27 hospitals and community health care centers from Guizhou, Yunnan and Sichuan provinces in China between 2014 and 2018 were analyzed. Generalized Additive Models were performed to determine the associations of GWG with the risk of aggregated adverse outcomes (gestational diabetes mellitus, preeclampsia, cesarean delivery, stillbirth, preterm birth, macrosomia, large for gestational age, and small for gestational age). The range that did not exceed a 2.5% increase from the lowest risk of aggregated adverse outcomes was defined as the optimal GWG range. Results Among all participants, U-shaped prospective association was found between GWG and the risk of aggregated adverse pregnancy outcomes. The optimal GWG range of 8.2–13.0 kg was proposed for underweight, 7.3–12.5 kg for normal weight, and 2.0–9.4 kg for overweight/obese women. Meanwhile, a higher GWG rate in the first two trimesters than that in the last trimester was suggested, except for overweight/obese women. After stratified by maternal age, mothers ≥35 years were suggested to gain less weight compared to younger mothers. Conclusions To keep a balance between maternal health and neonatal growth, optimal GWG ranges based on Asia-specific BMI categories was suggested for Chinese women with different pre-gravid BMIs and maternal ages.

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.

Glick I, Kadish E, Rottenstreich M. Int J Womens Health. 2021;13:751-759. Page 756, Autism Spectrum Disorder section, second paragraph, first sentence, the text “A large meta-analysis, including 16 epidemiological papers with 5687 autism spectrum disorder (ASD) cases and 8,655,576 control subjects, was conducted” should read “A large meta-analysis, including 16 epidemiological papers with 25,687 autism spectrum disorder (ASD) cases and 8,655,576 control subjects, was conducted”. The authors apologize for this error.

Objective: Adverse pregnancy outcomes are closely related to advanced maternal age (AMA; age at pregnancy =35 years). Little research has been reported on aneuploid abnormalities and pathogenic copy number variations (CNVs) affecting pregnancy outcomes in women with AMA. The purpose of this study was to assess CNVs associated with AMA in prenatal diagnosis to determine the characteristics of pathogenic CNVs and assist with genetic counseling of women with AMA. Methods: Among 277 fetuses of women with AMA, 218 (78.7%) were isolated AMA fetuses and 59 (21.3%) were non-isolated AMA fetuses and showed ultrasound anomalies from January 2021 to October 2022. Isolated AMA was defined as AMA cases without sonographic abnormalities. Non-isolated AMA was defined as AMA cases with sonographic abnormalities such as sonographic soft markers, widening of the lateral ventricles, or extracardiac structural anomalies. The amniotic fluid cells underwent routine karyotyping followed by single nucleotide polymorphism array (SNP-array) analysis. Results: Of the 277 AMA cases, karyotype analysis identified 20 chromosomal abnormalities. As well as 12 cases of chromosomal abnormalities corresponded to routine karyotyping, the SNP array identified an additional 14 cases of CNVs with normal karyotyping results. There were five pathogenetic CNVs, seven variations of uncertain clinical significance (VOUS), and two benign CNVs. The detection rate of abnormal CNVs in non-isolated AMA cases was increasing (13/59; 22%) than in isolated AMA cases (13/218; 5.96%) (p < 0.001). We also determined that pathogenic CNVs affected the rate of pregnancy termination in women with AMA. Conclusion: Aneuploid abnormalities and pathogenic CNVs affect pregnancy outcomes in women with AMA. SNP array had a higher detection rate of genetic variation than did karyotyping and is an important supplement to karyotype analysis, which enables better informed clinical consultation and clinical decision-making. [ABSTRACT FROM AUTHOR]