Pregnancy After 40: Recommendations for Counseling, Evaluation, and Management From Preconception to Delivery.

IMPORTANCE: Pregnant patients over age 40 often have unique risk factors and potential complications before and during pregnancy that play a role in their counseling and management. OBJECTIVE: To provide practitioners an overview on how to approach preconception evaluation and counseling, prenatal care, and management of associated comorbidities, as well as potential complications, in pregnant patients over age 40. EVIDENCE ACQUISITION: Literature review was performed using OVID and PubMed, with further relevant information queried from guidelines of professional organizations. RESULTS: Pregnant patients over age 40 should receive preconception evaluations by their obstetrician-gynecologist and other appropriate specialty care providers as they pertain to preexisting medical comorbidities. In the preconception period, attention should be given to managing and optimizing preexisting medical conditions and associated pharmacotherapeutics. Referral to specialists in assisted reproductive technologies or maternal-fetal medicine should be considered if indicated for appropriate evaluation and counseling. During pregnancy, accurate dating and counseling on aneuploidy screening, with consideration for early diabetes screening, should be performed in the first trimester. A detailed anatomy scan and fetal echocardiogram should be completed by 22 weeks' gestation, along with routine and high-risk (if indicated) prenatal care. Close attention should be given to the development of pregnancy-related complications associated with advancing age. Third-trimester fetal surveillance can be considered. Given that no contraindications exist, these patients should be encouraged to pursue a vaginal delivery with consideration for induction at 39 to 40 weeks' gestation. CONCLUSIONS AND RELEVANCE: Pregnancy rates are increasing in persons over age 40. As a result, preconception evaluation and counseling tailored to that demographic are essential. In addition to standard prenatal care, they should have early screening and diligent monitoring for pregnancy-related comorbidities associated with advancing age. RELEVANCE STATEMENT: With the increased pregnancy-associated comorbidities in patients over age 40, providers should be familiar with how to evaluate, counsel, and manage them during the preconception and pregnancy periods.

Is a Surrogate Pregnancy a High-Risk Pregnancy?

IMPORTANCE: As assisted reproductive technology has advanced, there has been an increase in gestational carriers/surrogate pregnancies. Information is needed to determine if these pregnancies are high-risk pregnancies and should be managed by maternal fetal medicine or if they are not high risk and should be cared for by residency-trained obstetricians and gynecologists. OBJECTIVE: In this review of the literature, we explore whether surrogate pregnancies should be classified as high-risk pregnancies and managed by subspecialists. EVIDENCE ACQUISITION, RESULTS: Our literature search discovered 28 relevant studies that evaluated surrogate pregnancy and pregnancy complications/outcomes. We learned that the overall risk by using artificial reproductive technology and risks for hypertension, preterm delivery, cesarean delivery, low birth weight neonate, fetal anomalies, and stillbirth did not seem to increase maternal/perinatal risk to the level where a subspecialist was required for the inclusive management of a gestational surrogate. Given that the ideal gestational carrier is healthy, has previously had a term pregnancy, has a single embryo implanted, and has had no more than 3 prior cesarean deliveries, these pregnancies should be lower-risk pregnancies. CONCLUSIONS: We recommend that close monitoring and high index of suspicion should be maintained for complications, but care for the surrogate pregnancy can be accomplished by a residency-trained obstetrician-gynecologist. RELEVANCE: An uncomplicated surrogate pregnancy can be managed by a residency-trained obstetrician-gynecologist and does not need to be managed by high-risk obstetric subspecialists.

Obesity leads to distinct metabolomic signatures in follicular fluid of women undergoing in vitro fertilization.

Although obesity negatively influences the metabolic homeostasis of cells within a broad range of tissues, its impact on oocyte metabolism is not fully understood. Prior evidence suggests that obesity increases expression of oocyte genes associated with inflammation, oxidative stress, and lipid metabolism; however, the metabolic impact of these genetic differences is not known. To address this gap, we conducted an exploratory assessment of the follicular fluid (FF) metabolome in eight overweight/obese (OW) and nine normal-weight (NW) women undergoing in vitro fertilization. FF and serum were collected and analyzed by untargeted metabolomics using gas chromatography-quadrupole time-of-flight mass spectrometry and charged-surface hybrid column-electrospray ionization quadrupole time-of-flight tandem mass spectrometry. Untargeted metabolomics identified obesity-associated changes in FF metabolites related to oxidative stress/antioxidant capacity, xenometabolism/amino acid biosynthesis, and lipid metabolism. Discriminant FF metabolites included elevated uric acid, isothreonic acid, one unknown primary metabolite, and six unknown complex lipids in OW compared with NW women. Conversely, 2-ketoglucose dimethylacetal, aminomalonate, two unknown primary metabolites, and two unknown complex lipids were decreased in FF of OW relative to NW women. Indole-3-propionic acid (IPA), a bacteria-derived metabolite, was also decreased in both FF and serum of OW women ( P < 0.05). The significant correlation between antioxidant IPA in serum and FF ( R = 0.95, P < 0.0001) suggests a potential serum biomarker of FF antioxidant status or reflection of the gut metabolism interaction with the follicle. These results suggest that obesity has important consequences for the follicular environment during the preconception period, a window of time that may be important for lifestyle interventions to ameliorate obesity-associated risk factors.

Obesity Modulates Inflammation and Lipid Metabolism Oocyte Gene Expression: A Single-Cell Transcriptome Perspective.

Context: It is hypothesized that obesity adversely affects the ovarian environment, which can disrupt oocyte maturation and embryonic development. Objective: This study aimed to compare oocyte gene expression profiles and follicular fluid (FF) content from overweight/obese (OW) women and normal-weight (NW) women who were undergoing fertility treatments. Design: Using single-cell transcriptomic analyses, we investigated oocyte gene expression using RNA sequencing. Patients or Other Participants: Eleven OW women and 13 NW women undergoing fertility treatments were enrolled. Main Outcome Measures: Oocyte messenger RNA profiles as well as serum and FF hormone and lipid levels were assessed. Results: OW women had significantly higher body mass index, body fat percentage, and serum homeostatic model assessment-insulin resistance index compared with NW women (P < 0.01). Serum leptin and C-reactive protein (CRP) levels as well as FF leptin, CRP, and triglyceride levels were increased (P < 0.05) in OW compared with NW women. Oocytes from OW women had increased expression of proinflammatory (CXCL2; P = 0.071) and oxidative stress-related (DUSP1; P = 0.051) genes but had decreased expression of GAS7 (fat metabolism; P = 0.065), TXNIP (oxidative stress; P = 0.055), and transcription factors ID3 (P = 0.075) and TWIST1 (P = 0.099) compared with NW women. Conclusions: These findings provide evidence for the significant influence of body composition on oocyte transcript abundance in women undergoing hormonal induction to retrieve oocytes. They further identify the potential for maternal diet to influence oocyte gene expression. The preconception period is, therefore, an important window of opportunity to consider for lifestyle interventions.