Aleksandar K. Stanic

Uterine fibroids and subfertility: an update on the role of myomectomy.

Purpose of review Uterine fibroids, the most common neoplasm of reproductive-aged women, can have a significant impact on quality of life, and may affect fertility and pregnancy outcomes. Although it is generally accepted that submucosal fibroids are of clinical significance, the effect of intramural and subserosal fibroids, and the benefit of surgical removal remains an area of active debate. Because of this controversy, this article will review current evidence for an association of fibroids and subfertility, and assess the impact of surgical management on fertility outcomes. Recent findings Recent analyses of patients with intramural fibroids have reported an increase in pregnancy loss and reduction in pregnancy and live birth rates. However, when analyzing studies with high quality diagnostic methods for assessing the endometrial cavity, no significant impact on reproductive outcomes was observed, and no benefit of myomectomy was consistently demonstrated. Myomectomy for submucosal fibroids greater than 2 cm and for intramural fibroids distorting the endometrial contour likely confers improvement of fertility outcome. Summary Submucosal fibroid location and distortion of the endometrial cavity (either submucosal or deeply infiltrating intramural fibroids) are most predictive of impaired fertility and probable benefit of surgical removal, and warrant consideration of myomectomy in the subfertile patient.

Dendritic cells in the circulation of women with preeclampsia demonstrate a pro-inflammatory bias secondary to dysregulation of TLR receptors

Toll-like receptors (TLRs) are central components of the innate immune system that recognize both microbial ligands and host products released during tissue damage. Data from epidemiologic studies and animal models suggest that inappropriate activation of the immune system plays a critical role in the development of preeclampsia. This study evaluates in a systematic fashion the expression and function of TLRs in the circulation of patients with preeclampsia compared to healthy pregnant controls. We evaluated TLR expression and function in primary dendritic cells (DCs) of 30 patients with preeclampsia and 30 gestational age-matched healthy pregnant controls. DCs were stimulated with the different TLR ligands engaging TLR1/2, TLR2/6, TLR3, TLR4, TLR5, TLR7, TLR8 and TLR9. The expression of TLR-induced production of TNF-α, IFN-α, IL-6, and IL-12 were measured by multicolor flow cytometry. Basal expression of TLR3, TLR4 and TLR9 was significantly increased in DCs isolated from women with preeclampsia. Preeclamptic DCs also expressed significantly higher basal levels of cytokines. In contrast, preeclamptic DCs demonstrated a less robust response to stimulation with various TLR ligands as compared with healthy pregnant controls. Under basal conditions, DCs from preeclamptic individuals express higher levels of select TLRs and produce more pro-inflammatory cytokines as compared with healthy controls. As such, the ability of these cells to mount an inflammatory reaction in response to a TLR ligand is limited. These data demonstrate a dysregulated pattern of TLR expression and cytokine production in DCs from PE patients that may limit further activation by TLR engagement.

Dendritic Cells Attenuate the Early Establishment of Endometriosis-Like Lesions in a Murine Model

Complex interplay of innate and adaptive immune cells has been implicated in the establishment, maintenance, and progression of endometriosis. Defining the identity, activation state, and functional role of immune cells during lesion establishment will provide invaluable insight into the underlying mechanisms of disease. This study utilized a transgenic mouse model with conditional dendritic cell (DC) depletion (diphtheria toxin-treated B6.FVB-Itgax-hDTR-EGFPtg) and multiparametric flow cytometry to examine immune cell composition and activation state and to assess the functional role of DCs in endometriosis-like lesions. T cells and DCs were increased in lesions compared to native uteri and control splenocytes and demonstrated an activated phenotype (P < .05). Lesions in DC-depleted hosts demonstrated greater size (P < .001) and reduced expression of T-cell activation marker CD69 compared to controls (P < .05). Collectively, these results suggest that activated DCs within lesions activate T cells and result in the impairment of early lesion establishment.

Longitudinal expression of Toll-like receptors on dendritic cells in uncomplicated pregnancy and postpartum

OBJECTIVE Toll-like receptors (TLRs) are integral parts of the innate immune system and have been implicated in complications of pregnancy. The longitudinal expression of TLRs on dendritic cells in the maternal circulation during uncomplicated pregnancies is unknown. The objective of this study was to prospectively evaluate TLRs 1-9 as expressed on dendritic cells in the maternal circulation at defined intervals throughout pregnancy and postpartum. STUDY DESIGN This was a prospective cohort of 30 pregnant women with uncomplicated pregnancies and 30 nonpregnant controls. TLRs and cytokine expression was measured in unstimulated dendritic cells at 4 defined intervals during pregnancy and postpartum. Basal expression of TLRs and cytokines was measured by multicolor flow cytometry. The percent-positive dendritic cells for each TLRs were compared with both nonpregnant and postpartum levels with multivariate linear regression. RESULTS TLRs 1, 7, and 9 were elevated compared with nonpregnant controls with persistent elevation of TLR 1 and interleukin-12 (IL-12) into the postpartum period. Concordantly, levels of IL-6, IL-12, interferon alpha, and tumor necrosis factor alpha increased during pregnancy and returned to levels similar to nonpregnant controls during the postpartum period. The elevated levels of TLR 1 and IL-12 were persistent postpartum, challenging notions that immunologic changes during pregnancy resolve after the prototypical postpartum period. CONCLUSION Normal pregnancy is associated with time-dependent changes in TLR expression compared with nonpregnant controls; these findings may help elucidate immunologic dysfunction in complicated pregnancies.

The Anti-Inflammatory Impact of Omega-3 Polyunsaturated Fatty Acids During the Establishment of Endometriosis-Like Lesions

The anti‐inflammatory impact of three polyunsaturated fatty acids (3‐PUFA) in endometriosis is incompletely understood. The effect of 3‐PUFA on endometriosis‐like lesions is evaluated as a potential anti‐inflammatory treatment target.

Sleep Deprivation and Pregnancy

Pregnancy is anecdotally equated with sleep disturbance, most commonly resulting in sleep deprivation, with the possible exception of the first trimester when hypersomnia may be present. The relationship between sleep and pregnancy is likely bidirectional. The dynamic hormonal and physiological changes of pregnancy affect a large variety of sleep parameters, ranging from homeostatic sleep drive to sleep latency, maintenance, duration, fragmentation, and perceived quality to sleep stages. Conversely, sleep disturbance, in any form, including decreased total sleep duration versus increased number of awakenings with or without respiratory disturbance, may affect pregnancy outcomes such as gestational hypertensive disease, labor type and duration, prematurity, and gestational weight. We will review the various aspects of sleep disturbance during pregnancy and the existing evidence that sleep deprivation and disturbance affect pregnancy outcomes.