Abstract
Context
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of reproductive-aged women. In pregnancy, women with PCOS experience increased risk of miscarriage, gestational ...diabetes, preeclampsia, and extremes of fetal birth weight, and their offspring are predisposed to reproductive and cardiometabolic dysfunction in adulthood. Pregnancy complications, adverse fetal outcomes, and developmental programming of long-term health risks are known to have placental origins. These findings highlight the plausibility of placental compromise in pregnancies of women with PCOS.
Evidence Synthesis
A comprehensive PubMed search was performed using terms “polycystic ovary syndrome,” “placenta,” “developmental programming,” “hyperandrogenism,” “androgen excess,” “insulin resistance,” “hyperinsulinemia,” “pregnancy,” and “pregnancy complications” in both human and animal experimental models.
Conclusions
There is limited human placental research specific to pregnancy of women with PCOS. Gestational androgen excess and insulin resistance are two clinical hallmarks of PCOS that may contribute to placental dysfunction and underlie the higher rates of maternal–fetal complications observed in pregnancies of women with PCOS. Additional research is needed to prevent adverse maternal and developmental outcomes in women with PCOS and their offspring.
In this review, we summarize current knowledge of placental dysfunction in human and animal models of PCOS and propose future directions for placental research in the population with PCOS.
To investigate infertility rates and access to infertility care among women in the United States.
Retrospective cross-sectional.
Not applicable.
Women between 20 and 44 years-old who participated in ...the National Health and Nutrition Examination Survey between 2013 and 2016 and answered questions RHQ074 (“have you ever attempted to become pregnant over a period of at least a year without becoming pregnant?”) and RHQ076 (“have you ever been to a doctor or other medical provider because you were unable to become pregnant?”).
None.
Rates of infertility and accessing infertility care.
Women reported infertility at a rate of 12.5% (95% confidence interval, 10.8–14.4). Higher infertility rates were noted with increasing age and body mass index. There were no differences in infertility rates by race/ethnicity, education, income, U.S. citizenship, insurance, or primary location of health care. However, women with less than a high school diploma accessed infertility care less than women with a college degree (5.0% vs. 11.6%). Women with incomes less than $25,000 sought infertility care less than those with incomes above $100,000 (5.4% vs. 11.6%). Non-U.S. citizens accessed infertility care less than U.S. citizens (6.9% vs. 9.4%), and uninsured women reported fewer visits for infertility than insured women (5.9% vs. 9.9%). Women who used the emergency department as their primary medical location reported accessing infertility care less than those who relied on a hospital outpatient unit (1.4% vs. 14.9%).
These nationally representative findings highlight the need to address disparities in access to infertility care.
Disparidad en el acceso al tratamiento de la infertilidad en estados unidos: resultados del national health and nutritiona examination survey, 2013-16
Investigar las tasas de infertilidad y el acceso al tratamiento de la infertilidad entre las mujeres de Estados Unidos.
Estudio retrospectivo de corte transversal.
No aplica.
Mujeres entre 20 y 44 años de edad que participaron en el National Health and Nutrition Examination Survey entre 2013 y 2016 y que respondieron a las preguntas RHQ074 (“¿Ha intentado alguna vez quedar embarazada durante un periodo de al menos un año sin conseguirlo?”) y RHQ076 (“¿Ha consultado usted a algún doctor u otro personal sanitario porque no conseguía quedar embarazada?”).
Ninguna.
Tasas de infertilidad y acceso a los tratamientos de infertilidad.
Las mujeres refirieron tasas de infertilidad del 12.5% (intervalo de confianza del 95%: 10.8-14.4). Se observaron mayores tasas de infertilidad con el aumento de la edad e índice de masa corporal. No se encontraron diferencias entre en las tasas de infertilidad según la raza/etnia, educación, poder adquisitivo, ciudadanía estadounidense, cobertura de seguro o localización del centro sanitario. Sin embargo, las mujeres sin estudios secundarios accedieron menos a los tratamientos de infertilidad que las mujeres con estudios universitarios (5.0% vs. 11.6%). Las mujeres con ingresos inferiores a 25,000 $ solicitaron menos tratamientos de infertilidad que aquellas con ingresos superiores a 100,000$ (5.4%vs.11.6%). Las que no tenían ciudadanía estadounidense utilizaron menos los servicios de infertilidad que las ciudadanas estadounidenses (6.9%vs.9.4%) y las mujeres sin cobertura de seguro informaron menos visitas por infertilidad que las mujeres con seguro médico (5.9% vs. 9.9%). Aquellas mujeres que utilizaron el servicio de urgencias como principal lugar de acceso médico informaron menos acceso a los tratamientos de infertilidad que aquellas que consultaron en los servicios ambulatorios (1.4% vs. 14.9%).
Estos resultados nacionales representativos subrayan la necesidad de abordar las desigualdades en el acceso a los tratamientos de infertilidad.
The article discusses the personal experiences of the author, an obstetrician/gynecologist with regards to pregnancy loss. The depression, grief faced and ways in which one can overcome it to move ...forward in life are highlighted.
Endocrine disrupting chemicals (EDCs) are ubiquitous, and pregnancy is a sensitive window for toxicant exposure. EDCs may disrupt the maternal immune system, which may lead to poor pregnancy ...outcomes. Most studies investigate single EDCs, even though "real life" exposures do not occur in isolation. We tested the hypothesis that uniquely weighted mixtures of early pregnancy exposures are associated with distinct changes in the maternal and neonatal inflammasome. First trimester urine samples were tested for 12 phthalates, 12 phenols, and 17 metals in 56 women. Twelve cytokines were measured in first trimester and term maternal plasma, and in cord blood after delivery. Spearman correlations and linear regression were used to relate individual exposures with inflammatory cytokines. Linear regression was used to relate cytokine levels with gestational age and birth weight. Principal component analysis was used to assess the effect of weighted EDC mixtures on maternal and neonatal inflammation. Our results demonstrated that maternal and cord blood cytokines were differentially associated with (1) individual EDCs and (2) EDC mixtures. Several individual cytokines were positively associated with gestational age and birth weight. These observed associations between EDC mixtures and the pregnancy inflammasome may have clinical and public health implications for women of childbearing age.
Polycystic ovary syndrome (PCOS) is a common condition of reproductive-aged women. In a well-validated sheep model of PCOS, testosterone (T) treatment of pregnant ewes culminated in placental ...insufficiency and intrauterine growth restriction of offspring. The purpose of this study was to explore specific mechanisms by which T excess compromises placental function in early, mid, and late gestation. Pregnant Suffolk sheep received T propionate 100 mg intramuscularly or control vehicle twice weekly from gestational days (GD) 30 to 90 (term = 147 days). Placental harvest occurred at GD 65, 90, and 140. Real-time RT-PCR was used to assess transcript levels of proinflammatory (TNF, IL1B, IL6, IL8, monocyte chemoattractant protein-1/chemokine ligand 2, cluster of differentiation 68), antioxidant (glutathione reductase and superoxide dismutase 1 and 2), and angiogenic vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF1A) genes. Lipid accumulation was assessed using triglyceride assays and Oil Red O staining. Placental measures of oxidative and nitrative stress included the thiobarbituric acid reactive substance assay and high-pressure liquid chromatography. Tissue fibrosis was assessed with Picrosirius Red staining. Student t tests and Cohen effect-size analyses were used for statistical analysis. At GD 65, T-treated placentomes showed increased lipid accumulation and collagen deposition. Notable findings at GD 90 were a significant increase in HIF1A expression and a large effect increase in VEGF expression. At GD 140, T-treated placentomes displayed large effect increases in expression of hypoxia and inflammatory markers. In summary, T treatment during early pregnancy induces distinct gestational age-specific effects on the placental milieu, which may underlie the previously observed phenotype of placental insufficiency.
Abstract
Context
Steroids play an important role in fetal development and parturition. Gestational exposures to endocrine-disrupting chemicals (EDCs) affect steroidal milieu and pregnancy outcomes, ...raising the possibility of steroids serving as biomarkers. Most studies have not addressed the impact of EDC mixtures, which are reflective of real life scenarios.
Objective
Assess the association of maternal and neonatal steroids with pregnancy outcomes and early pregnancy EDC levels.
Design
Prospective analysis of mother-infant dyads.
Setting
University hospital.
Participants
121 mother-infant dyads.
Main Outcome Measures
The associations of maternal and neonatal steroidal hormones from 121 dyads with pregnancy outcomes, the associations of first trimester EDCs individually and as mixtures with maternal and neonatal steroids in a subset of 56 dyads and the influence of body mass index (BMI), age, and offspring sex in modulating the EDC associations with steroids were determined.
Results
Steroid-specific positive or negative associations with pregnancy measures were evident; many maternal first trimester EDCs were negatively associated with estrogens and positively with androgen/estrogen ratios; EDC-steroid associations were influenced by maternal age, pre-pregnancy BMI, and fetal sex; and EDCs individually and as mixtures showed direct and inverse fetal sex-dependent associations with maternal and neonatal steroids.
Conclusions
This proof-of-concept study indicates association of steroids with pregnancy outcomes depending on maternal age, prepregnancy BMI, and fetal sex, with the effects of EDCs differing when considered individually or as mixtures. These findings suggest that steroidal hormonal measures have potential to serve as biomarkers of impact of EDC exposures and pregnancy outcome.
Enhanced inflammation and reduced apoptosis sustain the growth of endometriotic lesions. Alterations in the expression of estrogen receptor-alpha (ERα) and estrogen receptor-beta (ERβ) accompany the ...conversion of resident endometrial cells within the normal uterine environment to ectopic lesions located in extrauterine sites. Recent studies highlighted in this focused review linked ERβ to dysregulation of apoptotic and inflammatory networks involving novel interacting partners in endometriosis. The elucidation of these nongenomic actions of ERβ using human cells and mouse models is an important step in understanding key regulatory pathways that are disrupted leading to disease establishment and progression.
Ovarian hyperstimulation syndrome (OHSS) is a rare, but serious, risk of assisted reproductive technologies. In severe cases, patients may present to the emergency department (ED) for assessment, ...treatment of related complications, and even in-patient admission. Significant effort has been made to reduce the incidence and complications of OHSS; however, it is unknown if these strategies have decreased patient presentation for treatment in the ED.
To assess ED utilization for OHSS over time and to examine admission rates, patient demographics, and charges.
Retrospective longitudinal study utilizing data from the Nationwide Emergency Department Sample Database and the National ART Surveillance System. All ED visits between 2006 and 2016 with an ICD-9 or −10 diagnosis of OHSS were included. Demographics including age, geographic location, and income quartile and alternative diagnoses, admission rates, overall charges, and number of stimulation cycles annually were assessed.
The number of ovarian stimulation cycles steadily increased from 2006 (n = 110,183) to 2016 (n = 157,721), while the number of OHSS-related ED visits remained relatively stable (APC 2.08, p = 0.14). Admission rates for OHSS decreased from 52.7% in 2006 to 33.1% in 2016 (APC −4.43%, p < 0.01). The average charge for OHSS-related ED visits almost doubled from 2006 to 2016 (APC 8.53, p < 0.01) and was significantly higher than charges for non-OHSS-related visits for age-matched controls (p < 0.01).
Despite an increase in total stimulation cycles, there was no significant change in the estimated number of patients presenting to the ED; however, admission rates significantly declined. These observations suggest a possible shift in the severity and/or management of OHSS during the study period.
This study investigates changes in in vitro fertilization (IVF) rates among health plan enrollees between 2012 and 2017 after a large US empoloyer (University of Michigan) began providing coverage ...for IVF in 2015.
Health care claims have an inherent limitation in that noncovered services are unreported. This limitation is particularly problematic when researchers wish to study the effects of changes in the ...insurance coverage of a service. In prior work, we studied the change in the use of in vitro fertilization (IVF) after an employer added coverage. To estimate IVF use before coverage began, we developed and tested an Adjunct Services Approach that identified patterns of covered services cooccurring with IVF.
Based on clinical expertise and guidelines, we developed a list of candidate adjunct services and used claims data after IVF coverage began to assess associations of those codes with known IVF cycles and whether any additional codes were also strongly associated with IVF. The algorithm was validated by primary chart review and was then used to infer IVF in the precoverage period.
The selected algorithm included pelvic ultrasounds and either menotropin or ganirelix, yielding a sensitivity of 93.0% and specificity of >99.9%.
The Adjunct Services Approach effectively assessed the change in IVF use postinsurance coverage. Our approach can be adapted to study IVF in other settings or to study other medical services experiencing coverage changes (eg, fertility preservation, bariatric surgery, and sex confirmation surgery). Overall, we find that an Adjunct Services Approach can be useful when (1) clinical pathways exist to define services delivered adjunct to the noncovered service, (2) those pathways are followed for most patients receiving the service, and (3) similar patterns of adjunct services occur infrequently with other procedures.
PDF
