To determine whether there are differences in adverse pregnancy outcomes in very advanced maternal age (vAMA) women who conceived with assisted reproductive technologies (ART) compared with ...spontaneous conceptions.
Retrospective cohort study.
Academic tertiary care medical center.
A total of 472 women aged ≥45 years who delivered at one institution.
Mode of conception.
Maternal and neonatal outcomes.
For singleton pregnancies, vAMA women who conceived with ART were significantly older (47.0 ± 2.3 vs. 45.6 ± 0.1 years), more likely to be white (88.1% vs. 75.6%), and less parous (0.4 ± 0.9 vs. 1.2 ± 1.8) than vAMA women who conceived spontaneously. They were at significantly increased risk for cesarean delivery (CD) (75.1% vs. 49.7%) and were more likely to undergo elective primary CD without labor (25.4% vs. 9.4%). Risk of retained placenta was also significantly higher (2.7% vs. 0%). Rates of other maternal complications and neonatal outcomes were similar. Subgroup analysis of ART singleton pregnancies did not demonstrate differences in women using autologous oocytes versus donor oocytes.
Very advanced maternal age women who conceive after ART are more likely to be white, older, primiparous, and are more likely to proceed with an elective CD compared with vAMA women who conceive spontaneously. The increased risk of retained placenta in women who conceive with ART may indicate an underlying risk for placentation defects.
To examine the relation of menstrual cyclicity abnormalities to hyperandrogenism (HA) and dynamic state insulin resistance (IR) in oligo-ovulatory women with polycystic ovary syndrome (PCOS).
...Prospective cross-sectional study.
Tertiary-care academic center.
Fifty-seven women with PCOS (1990 National Institutes of Health criteria) and 57 healthy control women matched by body mass index (BMI).
Short insulin tolerance test (ITT).
Menstrual cyclicity, sex hormone-binding globulin (SHBG), measures of HA (i.e., modified Ferriman-Gallwey score, total and free testosterone, dehydroepiandrosterone sulfate), and the rate constant for plasma glucose disappearance (kITT) derived from the short ITT.
Adjusting for age, BMI, and ethnicity, the mean androgen measures were higher and SHBG trended lower, kITT was lower, and the prevalence of IR was higher in PCOS than in controls, independent of menstrual cyclicity. The optimal cutoff point for IR was set at kITT value of 3.57%/minute or lower. Overall, 79% of the women with PCOS had IR. To control further for the effect of ethnicity, a subgroup of 46 non-Hispanic white PCOS participants were studied; those who exhibited amenorrhea (n = 15) or oligomenorrhea (n = 19) had or tended toward having a lower kITT and a higher prevalence of IR than the women with PCOS and oligo-ovulatory eumenorrhea (n = 12). The kITT trended lower and the prevalence of IR trended higher in women with PCOS and amenorrhea than those with oligomenorrhea. The measures of SHBG and HA were similar across the three menstrual groups.
Oligo-ovulatory women with PCOS and overt oligo/amenorrhea have greater degrees of IR but not HA when compared with oligo-ovulatory eumenorrheic women with PCOS, suggesting that IR and hyperinsulinemia but not HA play a role in determining the degree of menstrual dysfunction, which can be used as a clinical marker for the degree of IR in oligo-ovulatory PCOS.
Normal placentation during the first trimester sets the stage for the rest of pregnancy and involves a finely orchestrated cellular and molecular interplay of maternal and fetal tissues. The ...resulting intrauterine environment plays an important role in fetal programming and the future health of the fetus, and is impacted by multiple genetic and epigenetic factors. Abnormalities in placentation and spiral artery invasion can lead to ischemia, placental disease, and adverse obstetrical outcomes including preeclampsia, intrauterine growth restriction, and placental abruption. Although first trimester placentation is affected by multiple factors, preconception environmental influences such as mode of conception, including assisted reproductive technologies which result in fertilization in vitro and intrauterine influences due to sex differences, are emerging as potential significant factors impacting first trimester placentation.
Abstract
Context
Infertility affects 10% of the reproductive-age population. Even the most successful treatments such as assisted reproductive technologies still result in failed implantation. In ...addition, adverse pregnancy outcomes associated with infertility have been attributed to these fertility treatments owing to the presumed epigenetic modifications of in vitro fertilization and in vitro embryo development. However, the diagnosis of infertility has been associated with adverse outcomes, and the etiologies leading to infertility have been associated with adverse pregnancy and long-term outcomes.
Evidence Acquisition
We have comprehensively summarized the data available through observational, experimental, cohort, and randomized studies to better define the effect of the underlying infertility diagnosis vs the epigenetics of infertility treatments on treatment success and overall outcomes.
Evidence Synthesis
Most female infertility results from polycystic ovary syndrome, endometriosis, and unexplained infertility, with some cases resulting from a polycystic ovary syndrome phenotype or underlying endometriosis. In addition to failed implantation, defective implantation can lead to problems with placentation that leads to adverse pregnancy outcomes, affecting both mother and fetus.
Conclusion
Current research, although limited, has suggested that genetics and epigenetics of infertility diagnosis affects disease and overall outcomes. In addition, other fertility treatments, which also lead to adverse outcomes, are aiding in the identification of factors, including the supraphysiologic hormonal environment, that might affect the overall success and healthy outcomes for mother and child. Further studies, including genome-wide association studies, epigenomics studies, and experimental studies, are needed to better identify the factors leading to these outcomes.
Genetics and epigenetics of infertility etiologies and epigenetics of fertility treatment affect implantation and placentation, which affect short- and long-term maternal and fetal/childhood outcomes.
Abstract
Context
Crosstalk through receptor ligand interactions at the maternal-fetal interface is impacted by fetal sex. This affects placentation in the first trimester and differences in outcomes. ...Sexually dimorphic signaling at early stages of placentation are not defined.
Objective
Investigate the impact of fetal sex on maternal-fetal crosstalk.
Design
Receptors/ligands at the maternal-fetal surface were identified from sexually dimorphic genes between fetal sexes in the first trimester placenta and defined in each cell type using single-cell RNA-Sequencing (scRNA-Seq).
Setting
Academic institution.
Samples
Late first trimester (~10-13 weeks) placenta (fetal) and decidua (maternal) from uncomplicated ongoing pregnancies.
Main outcome measures
Transcriptomic profiling at tissue and single-cell level; immunohistochemistry of select proteins.
Results
We identified 91 sexually dimorphic receptor-ligand pairs across the maternal-fetal interface. We examined fetal sex differences in 5 major cell types (trophoblasts, stromal cells, Hofbauer cells, antigen-presenting cells, and endothelial cells). Ligands from the CC family chemokine ligand (CCL) family were most highly representative in females, with their receptors present on the maternal surface. Sexually dimorphic trophoblast transcripts, Mucin-15 (MUC15) and notum, palmitoleoyl-protein carboxylesterase (NOTUM) were also most highly expressed in syncytiotrophoblasts and extra-villous trophoblasts respectively. Gene Ontology (GO) analysis using sexually dimorphic genes in individual cell types identified cytokine mediated signaling pathways to be most representative in female trophoblasts. Upstream analysis demonstrated TGFB1 and estradiol to affect all cell types, but dihydrotestosterone, produced by the male fetus, was an upstream regulator most significant for the trophoblast population.
Conclusions
Maternal-fetal crosstalk exhibits sexual dimorphism during placentation early in gestation.
OBJECTIVE: To study the expression and function of adiponectin and its receptors in mouse and human follicle cells and in early embryo development. DESIGN: Whole ovaries, granulosa cells, and ...cumulus-oocyte complexes isolated from immature mice before and during hormone-induced ovulation were used to analyze the expression of adiponectin, its receptors, and ovulation-related genes; human cumulus cells and granulosa cells were isolated from patients undergoing in vitro fertilization (IVF) procedures. SETTING: Multicenter. PATIENT(S): Women in IVF programs in Japan and the United States. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Expression of adiponectin receptors and fertility. RESULT(S): Adiponectin expression is absent/low in mouse and human granulosa cells and cumulus cells. Adiponectin receptors are hormonally regulated in mouse granulosa and cumulus cells in vivo and in culture. Adiponectin differentially alters the expression of Adipor1/Adipor2 as well as genes related to steroidogenesis, ovulation, and apoptosis in cumulus cells versus granulosa cells. Adiponectin enhances oocyte maturation and early embryo development in mouse and human IVF procedures. CONCLUSION(S): Adiponectin can modulate not only follicle growth but also embryo development in mice and humans.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that impacts women worldwide. There are several racial and ethnic differences in PCOS phenotypes and in PCOS- associated metabolic ...dysfunction. In this review, we summarize the current literature on disparities in the diagnosis and outcomes associated with PCOS in the United States. Future studies are needed to address gaps in knowledge for racial and ethnic-specific differences in PCOS, and include a large number of non-White and/or Hispanic participants in PCOS studies.
Abstract
Context
Epidemiologic studies of polycystic ovary syndrome (PCOS) are limited, especially in populations where diagnostic resources are less available. In these settings, an accurate, ...low-cost screening tool would be invaluable.
Objective
To test the use of a simple questionnaire to identify women at increased risk for PCOS and androgen excess (AE) disorders.
Study Design
Prospective cohort study from 2006–2010.
Setting
Community-based.
Participants
Women aged 14 to 45 years.
Intervention
A screening telephone questionnaire consisting of 3 questions was tested, where participants were asked to self-assess the presence/absence of male-like hair and menstrual irregularity. Participants were then invited to undergo a direct examination, including completing a medical history and undergoing a modified Ferriman-Gallwey (mFG) hirsutism score, ovarian ultrasound, and measurement of circulating total and free testosterone, DHEAS, TSH, prolactin and 17-hydroxyprogesterone levels.
Main Outcome Measure
Accuracy of questionnaire in predicting PCOS, AE, and irregular menses.
Results
Participants with self-assessed irregular menses and/or excess hair were labeled “Possible Androgen Excess (Poss-AE)” and those self-assessed with regular menses and no excess hair were labeled “Probable Non-Androgen Excess (Non-AE).” The study was completed in 206/298 (69%) of the Poss-AE and in 139/192 (73%) of the Non-AE. Of Poss-AE and Non-AE subjects, 82.5% and 15.8%, respextively, presented with PCOS. The calculated sensitivity, specificity, positive predictive value, and negative predictive value of the 3-question telephone survey to predict PCOS was 89%, 78%, 85%, and 83%, respectively.
Conclusions
A simple telephone questionnaire, based on self-assessment of body hair and menstrual status, can be used with a high predictive value to identify women at risk for AE disorders, including PCOS, and to detect healthy controls. This approach could be an important tool for needed epidemiologic studies.
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