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Research question In women at advanced age of 43–45 years undergoing repeated IVF cycles with autologous oocytes, who has the highest chance for birth and who should be referred early to receive donor oocytes? Design A retrospective cohort study was conducted at a university hospital reproductive center. The computerized database of 394 women aged 43–45 undergoing 1528 non-donor IVF or ICSI cycles between 2010 and 2019 was analyzed. a decision tree was developed, enabling a comprehensive study of a set of clinical parameters and the expected outcomes. Results The analysis included the outcomes of 394 women undergoing a total of 1528 cycles. The cumulative clinical pregnancy rate was 15% (59/394) and the cumulative live birth rate was 8.4% (33/394). The decision tree developed to predict women that should be offered egg donation included age, poor ovarian response to stimulation, the number of top-quality embryos, dominant follicles, previous pregnancy or live birth, fertilized oocytes and BMI. The model showed that a good ovarian response in the first cycle was the best predictor for live birth (13.3% gave birth). However, among women with poor responses, 7.1% of those who were younger than 43.5 years gave birth, and none of the women who were older than 43.5 years did. Conclusion Women over 43.5 years old with less than four oocytes collected in their first IVF cycle should be offered ovum donation, since their live birth rate in subsequent cycles is negligible.

Maternal morbidity and mortality are rising due in part to the rising prevalence of chronic illness, socioeconomic and racial disparities, and advanced maternal age. Prevention of maternal adverse outcomes requires prompt escalation of care to facilities with appropriate capabilities including intensive care services. The development of obstetrical-specific risk assessment tools and protocolized care for the most common causes of maternal intensive care unit (ICU) admission has helped to reduce preventable complications. However, significant work remains to address barriers to the escalation of maternal care and minimize delays in appropriate management.

Worldwide, there has been a trend toward later motherhood. Concurrently, the incidence of subfertility has been on the rise, necessitating conception using assisted reproductive technologies (ARTs). These pregnancies are considered high risk due to fetal complications such as antepartum stillbirth and growth restriction and maternal complications such as increase in maternal morbidity and mortality. Early induction of labor can help to mitigate these risks. However, this has to be balanced against the iatrogenic harms of earlier delivery to both the baby, including respiratory distress and NICU stay, and the mother who might experience longer labor and other complications such as uterine hyperstimulation. Induction of labor at 39 weeks is the optimal timing for preventing antepartum stillbirth and avoiding iatrogenic harm. Delivery by elective cesarean section is not advocated as its benefits in these patients are unclear compared with the short- and long-term complications of a major abdominal surgery.

Objective It is recognised that advanced maternal age is associated with adverse pregnancy outcomes. It is less known what the psychological impact of having a pregnancy in later maternal age is. This study aimed to establish whether women having children over 50 experience challenges with regards to their mental well-being during the pregnancy and thereafter. Study design 17 women delivered aged ≥ 50 at our maternity unit in a central London hospital between 2014 and 2020. Of these, one had died of metastatic ampullary carcinoma two years following delivery, one declined taking part, and two we were unable to get hold of, leaving 13 women in the study. Two validated questionnaires were used to survey the women: (i) Warwick-Edinburgh Mental Well-being Scale (WEMWBS), (ii) Parenting Daily Hassles Scale (PDHS). We analysed the questionnaire data using their individual scoring systems. Results The WEMWBS showed a median score of 60 out of a possible 70 (range: 45–70), indicating a high level of mental well-being among these women. The PDHS results indicated that reported hassles were overall low in both frequency and intensity for the mothers. Conclusion Women giving birth over 50 have often experienced long, emotional and financially-burdensome journeys in order to fall pregnant, usually involving assisted reproductive techniques (ART), with multiple antenatal and delivery complications thereafter. As a result, they are extremely happy and grateful to have the child, and are often in better socioeconomic positions that can help with the stress that comes with child-caring.

OBJECTIVES Pregnancies and births following assisted reproductive treatment (ART) are related to an increased risk for adverse perinatal outcomes. The aim of this retrospective cohort study at a University Hospital with a tertiary perinatal center was the combined risk analysis of singleton and twin pregnancies after ART in comparison to spontaneously conceived pregnancies. STUDY DESIGN Maternal and fetal risks were analyzed in subgroups after spontaneous conception (N = 14,233) and ART (N = 785) during the 6-year study period from 2014 to 2019. Odds ratios for perinatal risks between the groups were calculated and adjusted for maternal age and gestational week at birth using a matched control analysis. Subgroups of preterm delivery were compared. RESULTS The overall maternofetal risks after ART are higher than after spontaneous conception. Maternal risks after ART are mainly related to higher maternal age (p

Objective To determine the cost-effectiveness of different fertility options in men who have undergone vasectomy in couples with a female of advanced maternal age (AMA). The options include vasectomy reversal (VR), sperm retrieval (SR) with in vitro fertilization (IVF), and the combination of VR and SR with IVF, which is a treatment pathway that has been understudied. Materials and Methods Using TreeAge software, a model-based cost-utility analysis was performed estimating the cost per quality-adjusted life years (QALY) in couples with infertility due to vasectomy and advanced female age over a period of one year. The model stratified for female age (35-37, 38-40, >40) and evaluated four strategies: VR followed by natural conception (NC), SR with IVF, VR and SR followed by failed NC and then IVF, and VR and SR followed by failed IVF and then NC. QALY estimates and outcome probabilities were obtained from the literature and average patient charges were calculated from high-volume centers. Results The most cost-effective fertility strategy was to undergo VR and try for NC (cost-per-QALY: $7,150 (35-37 y), $7,203 (38-40 y), and $7,367 (>40 y)). The second most cost-effective strategy was the “back-up vasectomy reversal”: undergo VR and SR, attempt IVF and switch to NC if IVF fails. Conclusion In couples with a history of vasectomy and female of AMA, it is most cost-effective to undergo a VR. If the couple opts for SR for IVF, it is more cost-effective to undergo a concomitant VR than SR alone.

Do women of racial minorities aged 40 years or older have similar reproductive and obstetric outcomes as white women undergoing IVF?A retrospective cohort study conducted at a single academic university-affiliated centre. The study population included women aged 40 years or older undergoing their first IVF cycle with fresh cleavage-stage embryo transfer stratified by racial minority status: minority (black or Asian) versus white. Clinical intrauterine pregnancy and live birth rate were the primary outcomes. Preterm delivery (37 weeks) and small for gestational age were the secondary outcomes. Odds ratios with 95% confidence intervals were estimated. P0.05 was considered to be statistically significant.A total of 2050 cycles in women over the age of 40 years were analysed, 561 (27.4%) of which were undertaken by minority women and 1489 (72.6%) by white women. Minority women were 30% less likely to achieve a pregnancy compared with their white (non-Hispanic) counterparts (adjusted OR 0.68, CI 0.54 to 0.87). Once pregnant, however, the odds of live birth were similar (adjusted OR 1.23, CI 0.91 to 1.67). Minority women were significantly more likely to have lower gestational ages at time of delivery (38.5 versus 39.2 weeks, P = 0.009) and were more likely to have extreme preterm birth delivery 24-28 weeks (5.5 versus 1.0%, P = 0.021).Minority women of advanced reproductive age are less likely to achieve a pregnancy compared with white (non-Hispanic) women. Once pregnancy is achieved, however, live birth rates are similar albeit with minority women experiencing higher rates of preterm delivery.

Objective The present study aimed to determine the diagnostic value of prenatal chromosomal microarray analysis (CMA) for fetuses with several indications of being at high risk for various conditions. Materials and methods This retrospective analysis included 1256 pregnancies that were prenatally evaluated due to high-risk indications using invasive CMA. The indications for invasive prenatal diagnosis mainly included ultrasound anomalies, high-risk for maternal serum screening (MSS), high-risk for non-invasive prenatal tests (NIPT), family history of genetic disorders or birth defects, and advanced maternal age (AMA). The rate of clinically significant genomic imbalances between the different groups was compared. Results The overall prenatal diagnostic yield was 98 (7.8%) of 1256 pregnancies. Clinically significant genomic aberrations were identified in 2 (1.5%) of 132 patients with non-structural ultrasound anomalies, 36 (12.7%) of 283 with structural ultrasound anomalies, 2 (4.5%) of 44 at high-risk for MSS, 38 (26.6%) of 143 at high-risk for NIPT, 11 (3.8%) of 288 with a family history, and 7 (2.1%) of 328 with AMA. Submicroscopic findings were identified in 29 fetuses, 19 of whom showed structural ultrasound anomalies. Conclusion The diagnostic yields of CMA for pregnancies with different indications greatly varied. CMA could serve as a first-tier test for structural anomalies, especially multiple anomalies, craniofacial dysplasia, urinary defects, and cardiac dysplasia. Our results have important implications for genetic counseling.

Made available in DSpace on 2021-06-26T04:30:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-03-01 Objective: To assess the relationship of early developmental kinetics with competence to provide a live birth and the impact of maternal age in this context. Design: Retrospective cohort study including 4,915 embryos, of which 1,390 were transferred and provided a clinical outcome paired with morphokinetic data; 168 of them resulted in a live birth (LB), and 1,222 did not (NLB). Early morphokinetic parameters were compared between LB and NLB embryos from patients stratified into two age groups (= 37 years), and between embryos at the same competence group from patients aged = 37 years. The association of morphokinetic parameters with live birth was tested by univariate and multivariate analyses. Setting: Fertility clinic. Patient(s): The study population included 1,066 patients undergoing autologous intracytoplasmic sperm injection cycles with fresh single (SET), double (DET) or triple (TET) embryo transfers on day 2 or 3. Of them, 669 patients produced NLB embryos and 134 produced LB embryos. Intervention(s): None. Main Outcome Measure(s): Fertilization and cleavage morphokinetic parameters and live birth. Result(s): In the total patient population, all morphokinetic parameters were achieved earlier in LB compared with NLB embryos. The same was observed in patients aged = 37 years. Except for the t8 (time at which an 8-blastomere embryo was identified), all morphokinetic parameters were reached earlier in LB embryos from patients aged = 37 years. Univariate analysis revealed that earlier occurrence of all morphokinetic parameters was associated with live birth, although only earlier t2 (time at which two separate and distinct cells were identified) was associated with live birth independently from maternal age in the multivariate analysis. Conclusion(s): Despite its retrospective nature and performance in a single IVF center, this study presents novel data indicating that embryos competent to provide a live birth display overall faster early developmental kinetics compared with embryos that do not achieve a live birth after transfer, a difference that, however, narrows as maternal age advances. The findings suggest that fertilization and cleavage morphokinetic parameters may constitute valuable references for embryo selection strategies aiming to improve live birth rates, specifically before advanced maternal age while holding limited usefulness in advanced maternal age. (C) 2020 by American Society for Reproductive Medicine. Reprod Med Ctr, Biogenesi, Monza, Italy Azienda Socio Sanit Territ Monza, Dept Med Phys, Monza, Italy Sao Paulo State Univ, Inst Biosci, Dept Struct & Funct Biol, Botucatu, SP, Brazil Sao Paulo State Univ, Inst Biosci, Dept Struct & Funct Biol, Botucatu, SP, Brazil

Objective The delay of childbearing in women has become a worldwide issue in recent decades. The application of assisted reproductive technology in women of advanced maternal age (AMA) is increasing. Evidence on the safety and outcomes of frozen embryo transfer (FET) compared with fresh embryo transfer (ET) in AMA women is still lacking. Therefore, the objective of the present study was to compare perinatal and maternal outcomes after autologous FET and fresh ET cycles in women of AMA. Study design A retrospective study of 1663 FET and 3964 fresh ET cycles in reproductive medical centers from 2009 to 2014. Women who aged ≥35 years and had clinical pregnancies after autologous frozen or fresh ET were included. The main perinatal outcomes included birth weight, gestational age, rates of preterm birth, macrosomia, low birth weight (LBW), and very low birth weight. The main maternal outcomes included rates of hypertensive disorders of pregnancy, gestational diabetes mellitus, and preterm premature rupture of the membranes. Results Women who underwent FET had an increased risk of hypertensive disorders of pregnancy [1.1 % vs. 0.4 %, adjusted OR (95 % CI): 2.76 (1.39−5.51); p = 0.004]. Singletons born after FET had significantly higher mean birth weight (3388.78 ± 538.47 vs. 3316.19 ± 549.08; p = 0.001). Furthermore, increased risk of macrosomia [13.5 % vs. 10.4 %, adjusted OR (95 % CI): 1.35 (1.07−1.71); p = 0.013] and decreased risk of LBW [3.6 % vs. 5.3 %, adjusted OR (95 % CI): 0.67 (0.45−1.00); p = 0.048] were found in singletons born after FET. Conclusions Perinatal risks of AMA patients are higher in FET than in fresh ET, including higher birth weight, risks of macrosomia in singleton births, and hypertensive disorders of pregnancy.

Background Advanced maternal age (AMA) has been linked to both higher risk of adverse birth outcomes and higher levels of comorbidities. It is unclear if adverse outcomes are higher for older healthy women. This study examined the association between AMA and adverse birth outcomes among women with and without preexisting and pregnancy-related health conditions. Methods Analysis of data for 14,933 singleton births between 2004 and 2015 from the population-based Maryland Pregnancy Risk Assessment Monitoring System was conducted, comparing women aged 20–34 years and 35 years and older. Multivariable logistic regression estimated the difference in odds of preterm birth (PTB) and low birthweight (LBW) by age group among women with and without health conditions. The analysis of women without health conditions was stratified by parity. Results Among women without health conditions, AMA was associated with higher odds of PTB regardless of birthweight, LBW regardless of term, LBW term births, and LBW PTBs; stratified analysis showed higher risk of these outcomes among both older primiparas and multiparas. Compared with younger women with hypertensive disorders, older women with similar health conditions had higher odds of PTB regardless of birthweight. Older women with asthma had higher odds of LBW term births. Conclusions AMA is associated with adverse birth outcomes among women with and without health conditions compared with younger women with similar health status. Improved screening and management of health conditions during pregnancy is needed for older women, regardless of parity.

In this review, we evaluate the different modalities of embryo genetic testing including preimplantation genetic testing for aneuploidy (PGT-A), for monogenic/single-gene abnormalities (PGT-M), and for chromosomal structural rearrangements (PGT-SR), with a clinical focus on indications, strengths, limitations, and testing parameters of each technique. Articles were obtained from PubMed and American College Obstetricians and Gynecologists and American Society Reproductive Medicine committee opinions. While some studies have suggested that PGT-A increases live births in women of advanced maternal age, a recent large randomized controlled trial has shown no benefit to PGT-A compared with morphology grading alone, including in the subgroup of women >35 years of age. Aneuploidy screening shortens the time to live birth in women with advanced maternal age. However, PGT-A is not without risk (false positive and false negative and “no read” results and embryonic damage), has significant financial cost, and should only be used in conjunction with genetic counseling and under the supervision of a qualified infertility subspecialist. PGT-A is most cost-effective among women ≥38 years of age. PGT-M and PGT-SR offer useful low-risk screening modalities for debilitating inherited disorders. Significant advances have been made in the ability to analyze human embryos for genetic abnormalities. Screening for monogenic and chromosomal structural abnormalities potentially eliminates disease transmission to subsequent generations. Optimization of these molecular techniques remains necessary to decrease the false positive rates. Additional study of embryo mosaicism is needed to clarify which embryos are appropriate for transfer.

A delay in childbearing to later in life has increased the number of women of advanced maternal age (AMA) opting for assisted reproduction. Women should be made aware that there are age-related changes to fertility, including a decline in oocyte reserve and quality, in addition to an increase in the number of oocyte chromosomal aberrations. Success rates of assisted reproductive technology (ART) cycles decrease with advanced maternal age. There are different fertility options for women of AMA, including fertility preservation (oocyte or embryo freezing), in vitro fertilisation (IVF treatment) with or without preimplantation genetic screening and oocyte or embryo donation. Detailed counselling needs to be offered to these women with regard to the risks, success rates, ethical and legal implications of these fertility treatment options. Women of AMA should be screened for underlying medical conditions that could have an impact on maternal and neonatal morbidity and mortality.

Objective We present mosaic Xq duplication, or 46,X,der(X)dup(X)(q22.1q22.2)dup(X)(q25q22.3)/46,XX at amniocentesis in a pregnancy with a favorable outcome. Case Report A 40-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a result of 46,X,der(X)dup(X)(q22.1q22.2)dup(X)(q25q22.3)[7]/46,XX[20]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1–22, X) × 2. Cytogenetic analysis on maternal blood revealed a karyotype of 46,XX. At 22 weeks of gestation, she underwent repeat amniocentesis which revealed a karyotype of 46,XX in 22/22 colonies of cultured amniocytes and an aCGH result of (1–22, X) × 2 in the uncultured amniocytes. Prenatal ultrasound findings were unremarkable. The parents decided to continue the pregnancy, and a healthy female baby was delivered at 39 weeks of gestation with a body weight of 3510 g and a body length of 49 cm. The cord blood had a karyotype of 46,X,der(X)dup(X)(q22.1q22.2)dup(X)(q25q22.3)[3]/46,XX[37]. At age two months, interphase fluorescence in situ hybridization (FISH) analysis on buccal mucosal cells showed Xq duplication signals in 1.25% (1/80 cells), compared with 0% (0/90 cells) in the normal control. At age nine months, the neonate had normal physical and psychomotor development. Her body weight was 9.6 Kg (85th - 97th centile), and body length was 72 cm (50th - 85th centile). Cytogenetic analysis of peripheral blood revealed a karyotype of 46,X,der(X)dup(X) (q22.1q22.2)dup(X)(q25q22.3)[1]/46,XX[39]. Interphase FISH analysis on 100 buccal mucosal cells revealed no abnormal signal. Conclusion In case of mosaicism for an Xq duplication with a normal euploid cell line at amniocentesis, the in-vitro culture process of amniocytes may cause over-estimation of the mosaic level for the aberrant chromosome because of culture artifacts, and the abnormal cell line can decline after birth.

Background: To evaluate the effects of prepregnancy body mass index (BMI) on pregnancy outcomes, prevalence of urinary incontinence, and quality of life. Methods: The observational cohort included 2210 pregnant women who were divided into 4 groups according to their prepregnancy BMI: underweight (

A total of 551 pregnancies with positive results for noninvasive prenatal testing (NIPT) using traditional karyotyping and chromosomal microarray analysis were analyzed. Confirmatory results, positive predictive values, etiology exploration of false-positive results, and pregnancy outcomes were recorded. The study demonstrated that NIPT performed better in predicting trisomy 21 and trisomy 18 for pregnancies with advanced maternal age than for pregnancies with young maternal age; as for trisomy 13 and sex chromosomal aneuploidy (SCA) prediction, there was no significant difference between the two groups. The positive predictive values for trisomy 21, trisomy 18, trisomy 13, and SCA showed no significant upward trend when compared based on specific age categories (an interval of 5 years), which suggested that NIPT-positive result deserves equal attention from both providers and patients regardless of maternal age. In addition, the termination rates of 45,X, 47,XXY, 47,XXX, and 47,XYY were 100% (2/2), 92.9% (26/28), 33.3% (5/15), and 9.5% (2/21), respectively, which demonstrated that the decision-making regarding pregnancies varied greatly according to the types of SCAs, and further reinforce the importance of confirmatory prenatal diagnosis. The current study also supported the viewpoint that confined placental mosaicism and maternal mosaicism were the important etiology of false-positive results.

Advanced maternal age is an emerging health problem which involves many functional and structural alterations in oocytes, and its study is relevant to design better approaches to improve the reproductive function in women of advanced age. A constraint to this type of studies is the limited amount of samples and the ethical problems of working with human gametes. This study aims to characterize the in vitro-induced age-related modifications in a bovine model, as well as to determine if this model is a reliable approach to study human aging. For this purpose, we have focused on aging-related alterations related to oocyte mitochondrial dysfunction, a key hallmark in aging. Morphological and bioenergetic in vitro-induced alterations in bovine oocytes were compared to an in vivo aged group and to the already reported information regarding humans and other animal models. Parameters monitored included ooplasmic volume; mitochondrial mass, distribution and aggregation, assessed by MitoTracker Green; mitochondrial activity, monitored by JC-1; and the mitochondrial levels of hydrogen peroxide (H2O2), quantified using MitoPY. Results show a significant decrease in oocyte cytoplasmic volume after both in vitro and in vivo aging (p

Objective: To analyze and compare the expression profile of TAC3, TACR3, KISS1, and KISS1R in mural granulosa and cumulus cells from healthy oocyte donors and patients with different infertility etiologies, including advanced maternal age, endometriosis, and low ovarian response. Design: Genetic association study. Setting: Private fertility clinic and public research laboratory. Patient(s): Healthy oocyte donors and infertile women undergoing in vitro fertilization (IVF) treatment. Intervention(s): IVF. Main Outcome Measure(s): Gene expression levels of KISS1, KISS1R, TAC3, and TACR3 in human mural granulosa and cumulus cells. Result(s): Infertile women showed statistically significantly altered expression levels of KISS1 (-2.57 +/- 2.30 vs. -1.37 +/- 2.11), TAC3 (-1.21 +/- 1.40 vs. -1.49 +/- 1.98), and TACR3 (-0.77 +/- 1.36 vs. -0.03 +/- 0.56) when compared with healthy oocyte donors. Advanced maternal age patients, endometriosis patients, and low responders showed specific and altered expression profiles in comparison with oocyte donors. Conclusion(s): Abnormal expression levels of KISS1/KISS1R and TAC3/TACR3 systems in granulosa cells might be involved in the decreased fertility associated to advanced maternal age, endometriosis, and low ovarian response. ((C) 2020 by American Society for Reproductive Medicine.)

Objective To determine whether intracytoplasmic sperm injection (ICSI) is associated with improved outcomes compared with conventional in vitro fertilization (IVF) for patients with nonsevere male factor infertility. Design Retrospective cohort. Setting University-affiliated reproductive endocrinology unit. Patient(s) Couples who received their first-cycle embryo transfer without severe oligoasthenozoospermia (OA) between January 2012 and December 2016 were included in this study. Intervention(s) Six subgroup analyses were performed according to the proposed indications for the use of ICSI as follows: non−male factor infertility, advanced maternal age (≥38 years), unexplained infertility, low oocyte yield (≤6), mild OA, and moderate OA. Main Outcome Measure(s) Live birth rates and selected perinatal outcomes. Result(s) ICSI resulted in live birth rates similar to those achieved with IVF (41.68% vs. 44.31%). There were no significant differences in the incidences of gestational diabetes mellitus, hypertension disorder of pregnancy, placental previa, postpartum hemorrhage, cesarean delivery, fetal macrosomia, small for gestational age, large for gestational age, neonatal intensive care unit (NICU) admission, and congenital anomalies between the two groups. Subgroup analyses showed that ICSI resulted in a lower rate of NICU admission in couples with moderate OA. Conclusion(s) Our results suggested that routine use of ICSI for all causes of infertility did not result in better pregnancy and perinatal outcomes compared with conventional IVF in the first cycle. ICSI might be associated with a lower risk of NICU admission when used in couples with moderate OA. Large prospective studies are required to validate our current findings.

This study aimed to examine impacts of gestational diabetes mellitus (GDM) on quality of life (QoL) domains in Chinese pregnant women.We recruited 13,358 pregnant women in Tianjin, China. GDM was diagnosed using the criteria of International Association of Diabetes and Pregnancy Study Group. QoL was measured using the 36-Item Short-Form Health Survey. General linear model was used to obtain β-coefficient and 95% confidence intervals (CI) of GDM for QoL domain and summary scores.7.25% of the pregnant women developed GDM. Among the QoL domain and summary scores, only general health (GH) score was lower in the GDM group than in the non-GDM group. GDM and advanced maternal age (i.e., ≥ versus30 years) were negatively associated with GH in multivariable analyses (β-coefficient: -1.17, 95%CI: -2.17 to -0.17-0.79, -1.40 to -0.18, respectively). In subgroup analyses, the β-coefficient of GDM for GH among women with maternal age ≥30 years was enhanced to -2.17 (-3.94 to -0.40) in multivariable analysis while the β-coefficient of GDM for GH among women aged30 years was attenuated to non-significance.GDM and advanced maternal age were associated with reducing GH, and presence of advanced maternal age markedly increased the effect of GDM on GH.

Normal physiologic changes in pregnancy include mild hyponatremia. In some cases of preeclampsia, more significant hyponatremia has been associated with syndrome of inappropriate antidiuretic hormone secretion and hypervolemic hyponatremia. A 45-year-old gravida 2, para 0010 with a dichorionic twin gestation was diagnosed with preeclampsia at 30 weeks 6 days and noted to have concomitant hyponatremia of 125 mEq/L at our institution. Her hyponatremia was initially managed with furosemide and water restriction. She was delivered at 33 weeks 5 days due to worsening preeclampsia and continued significant hyponatremia despite treatment. Her hyponatremia resolved within 48 h after delivery. Our objectives were to discuss trends, treatment, and outcomes of cases with hyponatremia in preeclampsia. We performed a systematic review of the literature using Ovid Medline (1963-2017), Scopus (1962-2017), and PubMed (1963-2017, including Cochrane database). Relevant articles describing any case report of hyponatremia in preeclampsia were identified from the above databases without any time, language, or study limitations. Studies were deemed eligible for inclusion if they described a case of hyponatremia in the setting of preeclampsia. 18 manuscripts detailing 55 cases were identified. Pertinent demographic data and laboratory values were extracted. Maternal management strategy, diagnosis, delivery, and neonatal outcome data were also collected. Mean, range, standard deviation, and percentage calculations were used as applicable. Advanced maternal age (46 %), nulliparity (79 %), and multifetal gestation (34 %) were noted in patients with preeclampsia and low sodium. Hyponatremia was detected on average at 34 weeks gestation. 64 % were diagnosed with preeclampsia with severe features. When reported, diagnoses related to hyponatremia were syndrome of inappropriate antidiuretic hormone secretion (41 %) or hypervolemic hyponatremia (59 %). Indications for delivery included severe hyponatremia unresponsive to conservative measures in addition to other known obstetric or preeclamptic indications. Hyponatremia resolved within 48 h on average in cases where postpartum resolution was reported. It may be prudent to screen women with preeclampsia for electrolyte disturbances as part of their evaluation, especially in the setting of severe features. Initially, hyponatremia may be treated with medical management. In addition to established obstetric or preeclamptic indications, delivery may be considered if severe hyponatremia no longer responds to conservative measures.

The aim of the present study is to investigate the correlation between pregnancies complicated by morphological or chromosomal fetal anomalies and an obstetric history of two or more pregnancy losses, analyzing the association with any maternal risk factor.Retrospective analysis of women who had access to the Day Hospital Clinic of Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome from 2012 to 2018 for a pregnancy complicated by fetal malformation and/or abnormal karyotype, and who had an obstetric history of at least one pregnancy loss. Patients were divided into four groups depending on the number of miscarriages and the presence of a genetic anomaly: Group 0 included women with2 miscarriages and fetal malformations, Group 1 included women with ≥2 miscarriages and fetal malformations, Group 2 included women with2 abortion, fetal malformations and the presence of genetic anomalies; Group 3 included women with 2 ≥ abortions, fetal malformations and genetic anomalies. Statistical analysis was performed using the SAS v. 9.4 (SAS Institute Inc., Cary, NC, USA).A total of 466 patients were included in the present analysis. Out of these, 379 patients belonged to Group 0; 40 patients entered in Group 1; Group 2 included 42 patients, and 5 patients were part of Group 3. Pregnancies complicated by fetal congenital malformations in patients with two or more pregnancy losses were significantly associated with maternal trombophilic disease and previous birth defects. Recurrent miscarriage and fetal structural anomalies were also significantly correlated with advanced maternal age.An adequate periconceptional counseling regarding the risk of fetal congenital anomalies may be indicated in patients affected by thrombophilic disease, as well as in those of advanced maternal age and with a pregnancy history of fetal malformations. The screening for thrombophilia may be advisable in patients with an obstetric history of congenital birth defects.

Stillbirth is one of the most common adverse pregnancy outcomes, occurring in 1 in 160 deliveries in the United States. In developed countries, the most prevalent risk factors associated with stillbirth are non-Hispanic black race, nulliparity, advanced maternal age, obesity, preexisting diabetes, chronic hypertension, smoking, alcohol use, having a pregnancy using assisted reproductive technology, multiple gestation, male fetal sex, unmarried status, and past obstetric history. Although some of these factors may be modifiable (such as smoking), many are not. The study of specific causes of stillbirth has been hampered by the lack of uniform protocols to evaluate and classify stillbirths and by decreasing autopsy rates. In any specific case, it may be difficult to assign a definite cause to a stillbirth. A significant proportion of stillbirths remains unexplained, even after a thorough evaluation. Evaluation of a stillbirth should include fetal autopsy; gross and histologic examination of the placenta, umbilical cord, and membranes; and genetic evaluation. The method and timing of delivery after a stillbirth depend on the gestational age at which the death occurred, maternal obstetric history (eg, previous hysterotomy), and maternal preference. Health care providers should weigh the risks and benefits of each strategy in a given clinical scenario and consider available institutional expertise. Patient support should include emotional support and clear communication of test results. Referral to a bereavement counselor, peer support group, or mental health professional may be advisable for management of grief and depression.

Background: The objective of this study was to evaluate the course of pregnancy and delivery of obstetric patients admitted for intensive care, and determine the health status of their infants. Methods: This was a retrospective register-based study. Four university hospitals in Finland participated. Obstetric patients admitted to the intensive care unit in any trimester of pregnancy, during delivery or up to 42 days post partum were identified from clinical information systems over a five-year study period. Parturient and infant data were collected from the Medical Birth Register. Results: During the study period (2007-2011), 283 obstetric patients were identified from the clinical information system. The most common reason for admission was hypertensive complications (58%), followed by obstetric haemorrhage (25.1 %). Advanced maternal age, nulliparity and multiple pregnancies were associated with obstetric intensive care unit admissions. Of patients admitted to intensive care, 68.9% delivered by unscheduled caesarean section. Nearly 60% of neonates were born preterm, 56.1% needed treatment in a neonatal intensive care unit or an observation unit and 4.6 % died within one week. Conclusion: Advanced maternal age, nulliparity and multiple pregnancy were more common among intensive care unit-admitted women than in the general obstetric population. The main causes for admission were hypertensive complications and obstetric haemorrhage. Compared with the general obstetric population, neonates of intensive care unit-admitted mothers were eight times more likely to require treatment on a neonatal ward and their risk of neonatal death was also eight times greater. (C) 2019 Elsevier Ltd. All rights reserved.

Objectives The increasing prevalence of advanced maternal age (AMA) coupled with poor sleep quality among pregnant women makes it important to study their association with perinatal outcomes. However, little is known about the interaction of AMA and maternal antenatal sleep on perinatal outcomes. Here, we examined whether associations between AMA and perinatal outcomes are modified by antenatal sleep quality. Participants Data were collected from 446 women, with a singleton pregnancy and no pregnancy complications, who participated in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study. Measurements Participants completed the Pittsburgh Sleep Quality Index (PSQI) at 26-28 weeks gestation and had perinatal outcome data collected upon delivery. Interactions between AMA and maternal sleep quality on perinatal outcomes were investigated and where significant, analyses were further stratified by maternal age. All analyses were adjusted for maternal BMI at 26-28 weeks gestation, ethnicity, and maternal education. Results Neonates of mothers of AMA and poor sleep quality (PSQI score >5) had increased odds of stay in the neonatal intensive care unit (adjusted odds ratio = 3.53, 95% CI: −1.21 to 10.27) and shorter birth length (adjusted mean difference = −1.05 cm, 95% CI: −1.82 to −0.20), as compared with women of AMA and good sleep quality (PSQI score ≤5). In women Conclusion Poor sleep quality in women of AMA was associated with neonatal health outcomes. Improving maternal antenatal sleep may potentially improve perinatal outcomes in offspring of women of AMA.

Among live births, Down syndrome (DS) due to trisomy 21 is the most commonly occurring autosomal trisomy, typically resulting from meiotic nondisjunction. Currently, advanced maternal age and altered recombination patterns are the only well-known risk factors for nondisjunction. Maternal occupation has not been investigated as a risk factor for maternally-derived cases of trisomy 21.This study explored the association between maternal occupation and chromosome 21 nondisjunction, stratified by the stage of maternal error - either Meiosis I (MI) or Meiosis II (MII). Additionally, we investigated specific toxic agents associated with occupation classes.Using narrative job descriptions from the National Down Syndrome Project (NDSP), a population-based case-control study, occupation was coded using the 2010 Standard Occupational Classification (SOC). Odds ratios were calculated for the association between occupation class and having a child with DS, stratified by meiotic stage. An exposure analysis was performed within occupational classes that were statistically significant predictors of having a child with DS. Odds ratios were calculated to analyze associations between individual exposures and having a child with DS.The odds of MII nondisjunction were increased among Production Workers (OR = 3.15; 95%CI = 1.52,6.55). Women who worked as Life, Physical and Social Scientists or in Food Preparation and Serving-Related Occupations experienced greater likelihood of MI errors (OR = 5.72(1.80,18.20), and OR = 1.87(1.08,3.24), respectively). Exposure to solvents within the Production Worker group was a significant predictor (p 0.05) for MI nondisjunction. No other environmental agents had a significant association with nondisjunction.Specific maternal occupation classes were associated with MI and MII chromosome 21 nondisjunction. These occupation classes were selected for an exposure analysis, which determined solvents as highly predictive of MI nondisjunction among Production Workers. Findings from this analysis will serve to further explore the relationship between maternal occupation and chromosome 21 nondisjunction.

Age is a known risk factor for both maternal cardiovascular disease and adverse outcomes in pregnancy. We aimed to characterize the hemodynamic profiles in pregnancies of advanced maternal age (AMA) and correlate these with fetal outcomes.This was a prospective observational study of pregnancies undergoing antenatal testing. Maternal hemodynamics were measured non-invasively using an imaging probe at the descending aorta and the Uscom BP + arm cuff utilizing pulse pressure wave analysis. The Wilcoxon rank-sum test, Fisher's exact test, and Spearman rank correlation test were used for statistical analysis in R.Hemodynamic measurements, neonatal birthweight.Twenty-one AMA and twenty-four control patients were enrolled. Mean age ± SD was 39 ± 3.22 in the AMA cohort and 28 ± 4.32 in the control cohort (p 0.001). AMA patients were evaluated at a later gestational age (36 4/7 weeks) compared to control (34 1/7 weeks, p = 0.02). Between groups, there was no difference in BMI, race, hypertensive disease, diabetes, asthma, drug use, or indication for antenatal testing. 38% (AMA) and 37% (control) had hypertensive disorders of pregnancy. In AMA patients but not control patients, cardiac output (r = 0.52, p = 0.01), systemic vascular resistance (r = -0.53, p = 0.01), and systemic vascular resistance index (r = -0.62, p = 0.002) were significantly correlated with neonatal birthweight percentile.Hemodynamic alterations consistent with a low output, high resistance cardiovascular circuit were associated with lower birthweight in AMA, but not in control pregnancies.

Research question Does fresh embryo transfer after IVF with or without intracytoplasmic sperm injection (ICSI) increase the small for gestational age (SGA) rate, and frozen embryo transfer (FET) after IVF with or without ICSI increase the large for gestational age (LGA) rate versus natural conception? Design Retrospective comparison of an exposed historical group/cohort involving singletons conceived after fresh embryo transfer and after FET with an unexposed group/cohort involving singletons conceived after a natural conception. Results A total of 1961 fresh embryo transfer babies and 366 FET babies were compared with 6981 natural conception babies. The SGA rate in fresh embryo transfer babies was not significantly different to natural conception babies (6.9% versus 6.8%, P = 0.856). This outcome was not influenced by the fresh embryo transfer (adjusted odds ratio [aOR] 1.0; 95% confidence interval [CI] 0.8–1.3), but rather by a low rate of multiparity (aOR 0.5; 95% CI 0.3–0.7), advanced maternal age (aOR 1.1; 95% CI 1.0–1.2), maternal underweight (aOR 1.5; 95% CI 1.1–2.1), maternal smoking or cessation during pregnancy (aOR 1.8; 95% CI 1.4–2.3), pre-existing hypertension (aOR 2.3; 95% CI 1.3–4.1) and pregnancy-induced hypertension (aOR 2.5; 95% CI 1.7–3.7). The LGA rate in FET babies was significantly different from natural conception babies (6.6% versus 3.2%, P = 0.012). This outcome was influenced by the transfer of frozen embryos (aOR 2.2; 95% CI 1.3–3.8) and by a high maternal weight (aOR 1.9; 95% CI 1.1–3.6). Conclusions Maternal background and obstetric parameters are more likely to influence the SGA rate than fresh embryo transfer conception. FET conception could be associated with an increase in LGA rate.

Objective The number of births among women of higher age has been rapidly increasing in many countries for several decades. While recent epidemiological studies on the impact of maternal age on infant outcomes in developed countries have evaluated the outcomes of singleton infants, few population-based studies have investigated all deliveries including multiple births. Thus, we aimed to assess the impact of maternal age on adverse infant outcomes using data from all birth certificates, including multiple births, in Shiga prefecture, Japan. Study design The data from all birth certificates in Shiga Prefecture from 2013 to 2014 (23,294 births from 23,048 mothers) were obtained. We evaluated the impact of maternal age on adverse infant outcomes, including small for gestational age (SGA), low birth weight (LBW), and preterm birth (PTB). A multivariable logistic regression analysis was performed to determine adjusted odds ratios (aORs) for infant outcomes with various maternal factors, including multiple pregnancies. Statistical analysis for trend was performed using the Jonckheere-Terpstra test. Results The incidence rates of adverse infant outcomes began to increase at a maternal age of 30 years. A maternal age of ≥35 years was associated with significantly increased risks of adverse infant outcomes, including SGA (adjusted odds ratio [aOR]: 1.15, 95% confidence interval [95% CI]: 1.03–1.29), LBW (aOR: 1.29, 95% CI: 1.16–1.43), and PTB (aOR: 1.17, 95%CI: 1.04–1.33). Conclusions The risk of adverse infant outcomes was significantly increased in women older than 35 years of age. These data would be useful for younger women to decide family-planning in advance.

Objective To determine some of the unresolved questions related to chromosome anomalies in early human embryos, such are the detection of any advanced maternal age effect; the complete assessment of mosaicism, which requires analysis of all cells; and the relationship with embryonic dysmorphism. Fluorescence in situ hybridization has been used in this study to answer these issues. Design Fluorescence in situ hybridization analysis of human embryos using simultaneously probes for three or five chromosomes. Five hundred twenty-four cleavage-stage human embryos obtained by IVF were analyzed by fluorescence in situ hybridization. Embryos were allocated into three groups according to morphological and developmental characteristics (arrested; slow and/or fragmented; morphologically and developmentally normal). The embryos also were analyzed according to maternal age. Results Dysmorphic embryos had higher rates of polyploidy and diploid mosaicism. Aneuploidy increased with maternal age in nonarrested embryos. Preimplantation genetic diagnosis successfully detected these abnormalities. Conclusion This study demonstrates that, in morphologically and developmentally normal human embryos, cleavage-stage aneuploidy significantly increases with maternal age. The results suggest that implantation failure in older women largely could be due to aneuploidy.

Transgender men are assigned female at birth, but self-identify as male. Although some transgender men undergo gender-affirming hormonal treatment and/or surgery that preclude pregnancy, many (if not most) retain their female reproductive organs and, as a result, their capacity to become pregnant. Although the visibility of the transgender community has increased, the exposure of healthcare providers to transgender individuals, especially transgender men during pregnancy, as well as research that addresses evidence-based practice remain limited. In this review, we discuss obstetrical issues for transgender men who are ≥35 years old, termed the "new" advanced paternal age. We review preconception care and focus on fertility issues, the impact of stopping gender-affirming hormonal treatment, and age-appropriate health maintenance. We review antepartum and postpartum care, including labor and delivery, monitoring for perinatal depression, contraception, and chest feeding. Finally, we conclude with suggestions for areas for further research and study.

Objective We present prenatal diagnosis and management of monozygotic (MZ) twins discordant for severe fetal abnormalities. Case report A 36-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age, and hydrops fetalis, a giant cystic hygroma of 5 × 3.5 cm and left hydronephrosis in a co-twin. The other co-twin was structurally normal. Amniocentesis revealed a karyotype of 46,XY in both co-twins. Simultaneous polymorphic DNA marker analysis using the DNAs extracted from maternal blood and uncultured amniocytes confirmed MZ twinning. The woman underwent a successful selective fetal reduction by radiofrequency ablation at 22 weeks of gestation. At 28 weeks of gestation, premature rupture of membranes occurred, and a 1280-g normal male baby and a 275-g dead malformed co-twin were delivered. The normal co-twin was phenotypically normal and was doing well at age seven weeks. Conclusions Prenatal diagnosis of MZ twins discordant for structural abnormalities should include a differential diagnosis of MZ twinning, and a zygosity test is necessary under such a circumstance.

Objective Acute pulmonary edema is a rare complication in women with preeclampsia especially at advanced maternal age. We aimed to determine the cardiovascular hemodynamics in advanced maternal age women who developed acute pulmonary edema and preeclampsia. Study design Retrospective cohort study of women aged over 45 years giving birth at single university affiliated tertiary medical center which developed acute pulmonary edema due to severe preeclampsia. Clinical features were identified in order to predict and potentially prevent this severe complication of pregnancy. Main outcome measures Advanced maternal age women who developed acute pulmonary edema due to preeclampsia. Results Overall, during the study period 90,540 women delivered in our hospital, of them, 540 women (0.6%) above the age of 45 years gave birth. Of those, 67 women (12.4%) had preeclampsia in which 4 women (6%) were complicated with acute pulmonary edema. The common clinical relevant characteristics for all four women were: preterm delivery by cesarean section for preeclampsia with severe features, non-restrictive fluid management around the time of delivery, post-partum pain control medication with non-steroidal anti-inflammatory drug, blood pressure stabilization with oral labetalol and a sudden hemodynamic deterioration to hypertensive crisis and pulmonary edema between post-operative days 4–9. Conclusion Although the precise trigger for the sudden presentation of acute pulmonary edema remains unknown, we suggest that there is a multi-factorial combination of etiologies that are common to women of advanced maternal age and women with preeclampsia that could have contributed to the development of pulmonary edema.

Objective To study whether embryonic cell-free DNA (cfDNA) in spent blastocyst media is representative of the chromosomal constitution of a blastocyst. Design Pilot prospective blinded study. Setting In vitro fertilization center and genetics laboratory. Patient(s) A total of 115 trophectoderm (TE) biopsies and spent blastocyst media (SBM) from 46 patients with ages ranging from 32 to 46 years, whose indications for preimplantation genetic testing of aneuploidy (PGT-A) were advanced maternal age, recurrent miscarriage, or recurrent implantation failure. Interventions(s) Spent blastocyst media collection and TE biopsy. Main Outcome Measure(s) Concordance rates, sensitivity, and specificity between TE biopsies and SBM. Clinical outcomes in cases with euploid TE biopsies and euploid SBM compared with cases with euploid TE and aneuploid SBM. Result(s) In general, the total concordance rate for ploidy and sex was 78.7%, and sensitivity and specificity were 94.5% and 71.7%, respectively. A significant increase for all parameters was observed for day 6/7 samples compared with day 5 samples, with day 6/7 samples showing total concordance for ploidy and sex of 84%, and sensitivity and specificity of 95.2% and 82.1%, respectively. Ongoing implantation rates in euploid TE/euploid SBM showed a threefold increase compared with euploid TE/aneuploid SBM (52.9% vs. 16.7%, respectively), without reaching significant differences. Interestingly, no miscarriages were observed when TE and SBM were euploidy concordant. Conclusion(s) These results offer a better understanding of the dynamics of cfDNA during embryo development and despite more basic research being needed, they are reassuring to consider in the future this noninvasive approach as an alternative to TE biopsy for PGT-A.

Objective: Recommendations for venous thromboembolism (VTE) prophylaxis from authoritative guidelines for women undergoing caesarean delivery differed significantly and may not be applicable to Chinese populations. We aim to formulate a local risk model for VTE prophylaxis for caesarean section women. Material and methods: A local risk score model based on demographic, obstetric and medical parameters was used to assess the risk of VTE in women undergoing caesarean delivery from May 2017 to April 2018 in a regional obstetric unit. Women with increased risk (VTE Score ≥ 2) are given mechanical prophylaxis with pneumatic cuff and those with high risk (VTE Score ≥ 3) are additionally prescribed low molecular weight heparin (LMWH) as pharmacological prophylaxis in the early postpartum period. The risk scores obtained by applying other major guidelines were then compared. Results: Of 859 patients were included for analysis, overweight (15.3%), advanced maternal age (9.7%), multiple pregnancy (5.1%), obesity (4.7%), and primary postpartum haemorrhage (4.1%) were the most common risk factors. Overall, 109 (12.7%) patients required mechanical prophylaxis and 28 (3.3%) patients required additional pharmacological prophylaxis. No patient had postpartum VTE events nor serious haemorrhage after receiving LMWH prophylaxis. In contrast, applying the Royal College of Obstetricians and Gynaecologists guidelines to our cohort, 649 (75.6%) patients would receive LMWH after caesarean section, compared with no patients under the American College of Obstetrics and Gynaecology guidelines. Conclusions: Our local risk score model avoided the need for large proportions of women to be subjected to pharmacological prophylaxis, and appeared safe and practical. Keywords: Thromboembolism, Prophylaxis, Caesarean section, Chinese

Background Peripartum cardiomyopathy (PPCM) and preeclampsia are strongly associated, yet a description of risk factors for PPCM among women with preeclampsia is currently lacking. Additionally, the effect of preeclampsia on PPCM-related outcomes is not well known. Methods We constructed a cohort of delivery admissions from 2011 to 2014 using a large US administrative database (Marketscan). We assessed risk factors for the development of PPCM among women with preeclampsia. We compared the risks of major adverse cardiovascular events (MACE) at 6 months between PPCM with co-incident preeclampsia (pePPCM) and PPCM without preeclampsia (npePPCM). Results We included 1,024,035 pregnancies, of which 64,503 (6.3%) had preeclampsia. A total of 874 had PPCM (283 with preeclampsia and 591 without preeclampsia). Among women with preeclampsia, clinical risk factors for PPCM consisted in chronic kidney disease (OR 3.18, 95% CI [1.51, 6.69]), multiple pregnancy (OR 2.11, 95% CI [1.49, 2.98]), chronic hypertension (OR 1.88, 95% CI [1.43, 2.47]), advanced maternal age (OR 1.82, 95% CI [1.42, 2.33]), and type 2 diabetes (OR 1.58, 95% CI [1.00, 2.48]). Women with pePPCM had a higher risk of MACE than women with npePPCM (adjusted RR 1.29, 95% CI [1.06, 1.57]) due to increased rates of clinical heart failure and pulmonary embolism in the pePPCM group. Mortality did not differ between groups. Conclusion Preeclamptic women with risk factors for PPCM and women with pePPCM at increased risk of MACE should be followed closely. Further studies are required to determine whether preeclampsia affects the long-term prognosis of women with PPCM.

Background The advanced maternal age rate increases in developed countries. Older women have more pre-existing condition than youngest women and develop more frequently obstetrical pathologies responsible for a higher rate of caesarean delivery before labour and labour induction. For aged nulliparous without pathology who experience spontaneous labour, there is few data on the mode of delivery and on physiological labour according to maternal age. Objective To compare the intrapartum caesarean delivery rate according to maternal age, for nulliparous with planned vaginal delivery and spontaneous labour at term. Methods Retrospective cohort in a single academic institution between January 2000 and June 2017. All nulliparous women with planned vaginal delivery with live singleton in cephalic presentation at and after 37 weeks of gestation with spontaneous labour were included (n = 10,611). Two groups were compared: nulliparous women aged 20–34 and nulliparous women aged 35 and over. The main outcome was the intrapartum caesarean delivery rate. A subgroup analysis was performed for nulliparous with more advanced maternal age defined as women over 40. Results Among the 10,611 women included in this analysis, 8,993 (84.8%) were aged 20–34 and 1,618 (15.2%) were aged over 35. From the latter 367 (22.7%) were over 40 years old. The intrapartum caesarean delivery rate was similar between women aged between 20 and 34 and women aged over 35 (10.8% compared to 8.8%; cOR 0.91, 95% CI 0.76–1.08; aOR 0.91, 95% CI 0.76–1.09). The indications of caesarean were similar in both groups. No differences were found between both groups for mean labour duration (430.9 min for the [20–34] years group compared to 428.0 min for the over 35 years group, p = 0.654). The subgroup analysis performed on nulliparous with more advanced maternal age yielded similar results. Conclusion For nulliparous at term in spontaneous labour, an advanced maternal age was not associated with an increased intrapartum caesarean delivery rate.

Advanced maternal age, historically defined as ages 35 years and older, is used to describe the later years in the female reproductive life span when rates of adverse pregnancy outcomes increase. The preconception period represents an opportunity to ensure the use of safe medications and optimize care for medical comorbidities. Routine prenatal care should be augmented with counseling on fetal aneuploidy with a detailed anatomic survey. Surveillance for preterm labor and preeclampsia is recommended. Growth assessment and antepartum testing for specific women are advised, particularly those ages 40 years and older and those with select medical problems. Despite an increased incidence of complications, most women of advanced maternal age will have normal pregnancies and will benefit from the compassionate care provided by midwives, advanced practice registered nurses (including nurse practitioners and clinical nurse specialists), and perinatal nurses.

Objective: The aim of this study was to investigate cumulative live birth rate (CLBR) per oocyte retrieval cycle and per patient in women over 40 years old undergoing IVF/ICSI treatments, stratified for age, ovarian response and oocyte retrieval cycle number. Materials and methods: 244 patients with poor ovarian response (POR) and 372 patients with normal ovarian response (NOR) were retrospectively investigated. Results: Of the patients aged 40 to 43 years, CLBR per oocyte retrieval cycle and per patient (4.3%; 8.8%) in POR group were both lower than those in NOR group (15.8%; 24.8%) (P

Cardiovascular disease complicating pregnancy is rising in prevalence secondary to advanced maternal age, cardiovascular risk factors, and the successful management of congenital heart disease conditions. The physiological changes of pregnancy may alter drug properties affecting both mother and fetus. Familiarity with both physiological and pharmacological attributes is key for the successful management of pregnant women with cardiac disease. This review summarizes the published data, available guidelines, and recommendations for use of cardiovascular medications during pregnancy. Care of the pregnant woman with cardiovascular disease requires a multidisciplinary team approach with members from cardiology, maternal fetal medicine, anesthesia, and nursing.

Background Delayed pregnancy is increasingly common in many countries including the UK. There has been international interest in providing maternity care which aims to improve outcomes for mothers and babies when pregnancy occurs after the age of 35. Despite this, there is a lack of understanding of the experience of pregnancy at advanced maternal age from the woman's perspective. Objectives To explore the experience of uncomplicated pregnancy for nulliparous women aged 35 and over and determine key processes involved in their pregnancy journey. Design A two phase constructivist grounded theory study. Setting South West of England, United Kingdom. Participants 15 nulliparous women aged 35 and over, in their third trimester of pregnancy. Methods Data were collected through semi-structured, in depth interviews which were transcribed and analysed using coding, constant comparison and memo-writing. Results The core category ‘It's now or never’ reflects how women may experience their pregnancy. This appears to influence feelings of readiness to become a mother, anxieties about the pregnancy and their care choices. This was felt more acutely as maternal age advances towards 40 years and beyond. Conclusions Women's understanding that their future chances to have a baby may be limited can impact upon the way pregnancy is experienced. Despite having an uncomplicated pregnancy, older pregnant women may experience considerable worry throughout their pregnancy. Further research is required on how health care providers can better support women in early pregnancy and in making decisions regarding childbirth choices which are related to age.

BACKGROUND Chromosomal microarray analysis detects a clinically significant amount of copy number variants in approximately 1% of low-risk pregnancies. As the constantly growing use of noninvasive prenatal screening has facilitated the detection of chromosomal aberrations, defining the rate of abnormal chromosomal microarray analysis findings following normal noninvasive prenatal screening is of importance for making informed decisions regarding prenatal testing and screening options. OBJECTIVE To calculate the residual risk for clinically significant copy number variants following theoretically normal noninvasive prenatal screening. STUDY DESIGN The chromosomal microarray results of all pregnancies undergoing amniocentesis between the years 2013 and 2021 in a large hospital-based laboratory were collected. Pregnancies with sonographic anomalies, abnormal maternal serum screening, or multiple fetuses were excluded. Clinically significant (pathogenic and likely pathogenic) copy number variants were divided into the following: 3-noninvasive prenatal screening-detectable (trisomies 13, 18, and 21), 5- noninvasive prenatal screening-detectable (including sex chromosome aberrations), 5-noninvasive prenatal screening and common microdeletion-detectable (including 1p36.3-1p36.2, 4p16.3-4p16.2, 5p15.3-5p15.1, 15q11.2-15q13.1, and 22q11.2 deletions), and genome-wide noninvasive prenatal screening-detectable (including variants >7 Mb). The theoretical residual risk for clinically significant copy number variants was calculated following the exclusion of noninvasive prenatal screening-detectable findings. RESULTS Of the 7235 pregnancies, clinically significant copy number variants were demonstrated in 87 cases (1.2%). The residual risk following theoretically normal noninvasive prenatal screening was 1.07% (1/94) for 3-noninvasive prenatal screening, 0.78% (1/129) for 5- noninvasive prenatal screening, 0.74% (1/136) for 5- noninvasive prenatal screening including common microdeletions, and 0.68% (1/147) for genome-wide noninvasive prenatal screening. In the subgroup of 4048 pregnancies with advanced maternal age, the residual risk for clinically significant copy number variants following theoretically normal noninvasive prenatal screening ranged from 1.36% (1/73) for 3- noninvasive prenatal screening to 0.82% (1/122) for genome-wide noninvasive prenatal screening. In 3187 pregnancies of women

Poor sleep quality is related to old age among the general population, but few studies have focused on postpartum women of advanced maternal age. The present study aimed to describe and compare sleep quality between women younger or older than 35 years of age at 3 months postpartum, and to examine the related factors.A cross-sectional survey was conducted with 160 postpartum women who had given birth at a teaching hospital in Taiwan. The participants were assigned to two groups according to age (≥35 years, n=80; and 20-34 years, n=80). Sleep quality was measured using the Pittsburgh Sleep Quality Index with a cut-off score of 5.The prevalence of poor sleep quality at 3 months postpartum was higher in older mothers (61.6%) than in younger mothers (38.4%, p0.01). Multiple logistic regression revealed that poor sleep quality was positively correlated with the severity of postpartum physical symptoms, lack of exercise, and room-sharing with infants. After adjustment for those variables, older mothers were three times more likely to have poor sleep quality than younger mothers (odds ratio=3.08; 95% confidence interval 1.52-6.23).Health care providers should pay attention to sleep problems among postpartum women, especially mothers of advanced maternal age. In particular, health care providers should evaluate sleep quality among postpartum women, instruct them not to share the bed with their infants at night, perform exercise, and manage their postpartum physical symptoms to improve the sleep quality.

What is the cumulative incidence of live birth (CILB) for high-order consecutive IVF cycles, and which factors are associated with live birth in women aged ≥41 years using autologous oocytes?A retrospective cohort study including 146 patients aged 41 years to44 years who started their first IVF cycle attempt using autologous oocytes, between January 2006 and December 2013.After 13 IVF cycles, CILB reached up to 33.6%. After six IVF cycles, 42 (28.8%) women delivered a live infant (85.7% of the total live birth). Mean live birth rate per cycle declined with age at the initial cycle (8% at 41 years; 5.8% at 42 years; and 4.1% at 43 years). Multivariable modified Poisson regression models identified patient's age (RR for 41 years versus 43 years: 0.47; 95% CI 0.25 to 0.87; P = 0.01), smoking status (RR 0.21; 95% CI 0.05 to 0.08; P = 0.02), and mean number of fertilized oocytes (RR 1.23; 95% CI 1.08 to 1.39; P0.01) as factors significantly associated with the probability of a live birth.Multiple repeat IVF cycles in women aged 41-44 years offers a reasonable long-term success rate. After six cycles of treatment, about 29% of women of advanced reproductive age using autologous oocytes expected to achieve a live birth. This information might assist in fertility counselling and managing patients' expectations by adjusting the appropriate treatment strategy and number of IVF cycle attempts, especially in countries in which egg donation is prohibited or when multiple repeated IVF cycles attempts are financially affordable.

Objective To discuss the detectability of NIPT for pregnant women at advanced maternal age (AMA), and mainly focused on how many fetal abnormalities will be missed by NIPT. Methods A total of 4194 women at AMA who accepted cytogenetic prenatal diagnosis were recruited in this study. All the AMA women received amniocentesis at 18–23 weeks. Combined with our detection level of NIPT and literature reports, we evaluated the detectability of NIPT. Results After cell karyotype analysis, a total of 233 (5.56%) fetuses were confirmed to have chromosomal abnormalities, including 91.0% were abnormal chromosome number and 9.0% were abnormal chromosome structure. According to the detectability of NIPT we calculated, 87.6% abnormal results could also be detected by NIPT. However, NIPT would miss 12.4% abnormal results which could be originally found by the karyotype analysis of amniotic fluid cells. The major types of missed fetal abnormalities include structural rearrangement, mosaic and triploidy. Meanwhile, there were no relationship between the detectability of NIPT and the age of AMA pregnant women. Conclusions About 12.4% of fetal chromosomal abnormalities will be missed if NIPT completely replaces invasive prenatal diagnosis in AMA women. Fortunately, these types of fetal abnormalities missed by NIPT did not increase with the age elevating of pregnant women.

To study case mix, risk factors, adverse outcomes and associations of hyperglycemia in pregnancy in a cohort of Sri Lankans.Prospective observational study, from April 2011-October 2015 at a tertiary care referral center, Colombo, Sri Lanka. Data from first trimester to delivery of HIP was analyzed. Three subgroups were defined: Diabetes in pregnancy (DIP), Hyperglycemia in early Pregnancy (HIEP) [24 weeks] and Gestational diabetes (GDM) [24 weeks].Of 782 patients 572 (73.1%) had complete data. Case-mix: 137(24.0%) DIP, 331(57.9%) GDM and 104 (18.2%) HIEP. Primigravidae commoner in GDM (0.05). DIP older - mean 33.3 ± 5.5 years (0.01). Previous GDM commoner and pharmacological interventions needed in DIP and HIEP. Majority GDM (66.8%) required Medical Nutrition Therapy (MNT) alone. There was no difference in pregnancy outcomes between the 3 subgroups. Macrosomia significantly greater in HIEP (33.7%); neonatal cardiac defects more in DIP and HIEP.Increasing maternal age is a significant risk for DIP, while previous GDM is a risk for DIP and HIEP and neonatal congenital cardiac defects in subsequent pregnancies of South Asian women. We recommend preconception screening for glucose intolerance and achieving normoglycaemia among South Asian women with advanced maternal age and previous GDM.

Due to socio-economic development, an increasing number of women delay childbirth to their late 30 s and older. However, this delay brings a series of health problems to pregnant women and their offspring. The few studies on the effects of advanced maternal age (AMA) on offspring development, especially regarding neurocognitive and emotional development, reported mixed results. We examined the relationship between AMA and the performance of immature offspring of 3- versus 12-month-old Sprague-Dawley rat females on neurocognitive development tests and the possible mechanism of this relationship; the rats were individually housed with a randomly selected 3-month-old male, and the cognitive development of the offspring was evaluated by behavior tests including the Morris water maze, elevated plus maze, forced swimming and 3-chambered social behavior tests. Moreover, hematoxylin-eosin (HE) staining and Nissl staining were conducted to detect differences in the hippocampal morphology of the offspring, and Western blot analysis was conducted to detect the protein expression of brain-derived neurotrophic factor (BDNF), cAMP response element binding protein (CREB) and phosphorylated CREB (pCREB). The behavior tests detected defects in the AMA rats compared with the control group. The HE and Nissl staining results showed no significant difference. However, the expression of BDNF, CREB and pCREB was reduced in the immature offspring of AMA rats compared with that in control rats. Based on our results, CREB-dependent expression of BDNF may be responsible for the damage to cognitive and emotional development in offspring caused by delayed motherhood.

Background The epidemiology of Hirschsprung's disease (HSCR) in Bangladesh has never been studied. The aim of this study was to determine the epidemiological characteristics of HSCR in Bangladesh. Methods Data from fifty patients were collected prospectively from two hospitals in Chittagong, Bangladesh. Results The rate of consanguinity (16%) among parents of HSCR patients was higher than that of the general population (10%). Maternal age at the time of birth of the affected child was ≤30years in all cases except one. No association was found between parents' occupation and HSCR. No patient was born preterm and only three patients (6%) had low birth weight. Nine patients (18%) had associated anomalies. We found coexistence of bilateral accessory tragi and ankyloglossia in one patient, and coexistence of rectal duplication cyst in another. Neither anomaly had been previously reported in HSCR patients. Conclusions Our study suggests that consanguinity might increase the risk of HSCR whereas advanced maternal age does not. HSCR patients were found more likely to born at term and with normal birth weight. The coexistence of HSCR with previously unreported anomalies highlights the diversity of conditions that can co-occur with HSCR. Levels of evidence IV

Background: Maternal near miss (MNM) is one of the most vital health indicators reflecting the quality of obstetric care. The aim of this study was to explore the causes and change patterns in the maternal near miss ratio (MNMR) during the era of the two-child policy in Jiangsu Province, China. Methods: A retrospective cross-sectional study of 247,261 women who were pregnant in 11 hospitals in Jiangsu Province between January 2012 and December 2018 was conducted. The study period was divided into 3 stages: baseline, from January 2012 to June 2014; stage 1, from July 2014 (time of selective two-child policy begins to take effect) to June 2016; and stage 2, from July 2016 (time of universal two-child policy begins to take effect) to December 2018. Findings: Over seven years, a total of 883 mothers were identified as maternal near miss (MNM), yielding an overall MNMR of 3·70/1000 live births (LBs) (95% CI, 3·52-4·01). The MNMR slightly fluctuated around a mean of 2·75/1000 LBs at baseline and stage 1, and leveled at an additional 2·67/1000 LBs (95% CI 1·08-4·25, P = 0·001) at stage 2. We further investigated what conventional factors were the main determinants of the increase in the MNMR. Multivariate logistic regression analysis was used to identify the MNM-related risk factors: advanced maternal age (OR=1·55 and 1·82 for aged 30~35 and aged ≥35), multipara (OR=1·24), cesarean section (OR=3·22), abortion (OR=4·42), no antenatal visits (OR=1·99) and multiple births (OR=7·05). Among the identified MNM-related risk factors, the monthly percentage of multiparity pregnancy, advanced maternal age (≥35) and multiple births accumulated over time were positively related to the increasing monthly MNMR (r=0·54, 0·61, 0·31, respectively). We further evaluated that the accumulation of multiparas and mothers with advanced maternal age accounted for 71·75% of the increase in the MNMR. We then revealed that haemorrhagic disorder was the leading cause of MNM (n = 613, 69·42%). The heamorrhage-caused MNMR increased over seven years (Ptrend < 0·001), and the accumulation of multiparas and mothers with advanced maternal age were also main determinants of the increase (75·62%). Interpretation: Overall, the MNMR considerably increased from 2012 to 2018, which was largely driven by the increase of multiparas and advanced age. More attention needs to be paid to the health of mothers with advanced age and multiple pregnancies, including improving the referral system for pregnant women and raising the quality and standard of obstetric care. Funding Statement: This work was supported by grants from the National Key Research and Development Program of China, the Natural Science Foundation of Jiangsu Province, the State Key Program of National Natural Science of China, the National Health and Family Planning Commission of the People’s Republic of China, the National Natural Science Foundation of China, the China Medical Board, WHO, UNICEF, and China Postdoctoral Science Foundation. Declaration of Interests: The authors have declared that no competing interests exist. Ethics Approval Statement: The study was approved by the ethics committee of the West China Second University Hospital (protocol ID, 2012008). Informed consent was obtained for each participant.

Down syndrome (DS) or trisomy of chromosome 21 is one of the most common cause of autosomal chromosomal disorder that occurs in about 1 in 700 live born children, and main cause of mental retardation and intellectual disability. Several studies in different countries have shown that advanced maternal age (˃30 years) at conception, impaired folate status and/folate metabolism, impaired maternal recombination, maternal weight gain during pregnancy, low socioeconomic conditions, radiation exposure, use of contraceptive pills, and taking tobacco/cigarette are major maternal risk factors for giving birth child with DS. However, the occurrence of those factors in pregnant women at advanced age has not yet been investigated in Bangladesh. Hence, first time in Bangladesh this study aimed to determine the serum folate and homocysteine status at second/third trimester pregnant women at advanced age. We used the Enzyme-Linked Immunosorbent Assay (ELISA) technique method to determine serum folate concentration. In this study, out of 70 pregnant women serum we found folate level low (