Reproductive Outcomes After Hysteroscopic Resection of Retained Products of Conception.

STUDY OBJECTIVE: To characterize pregnancy outcomes after hysteroscopic resection of retained products of conception (RPOCs), especially as it relates to abnormal placentation. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Academic medical center. PATIENTS: All women who underwent hysteroscopic resection of RPOCs at Northwestern Prentice Women's Hospital between January 2004 and December 2014. INTERVENTIONS: Hysteroscopic resection of RPOCs. MEASUREMENTS AND MAIN RESULTS: The medical records of all cases of hysteroscopic resection of RPOCs between January 2004 and December 2014 were reviewed. Demographic characteristics, operative findings, surgical procedure, surgical pathology, and pregnancy outcomes for preceding and subsequent pregnancies were obtained. Our primary outcome was abnormal placentation in the pregnancy after the procedure. There were a total of 55 subsequent pregnancies and 38 live births. Among these pregnancies, 54.5% (30/55) were vaginal deliveries, 34.5% (19/55) were cesarean deliveries, and 7.3% (4/55) were early pregnancy losses. Abnormal placentation was present in 18.1% of subsequent pregnancies (10/55). This consisted of 3 patients with placenta previa, 2 with placenta accreta, and 5 with retained placenta. CONCLUSION: Women who undergo hysteroscopic resection of RPOCs have a higher rate of abnormal placentation in subsequent pregnancies when compared with the general population. Although the etiology is likely multifactorial, the underlying pathology leading to the initial diagnosis of RPOCs is believed to play a major role.

Decreased expression of microRNA-29 family in leiomyoma contributes to increased major fibrillar collagen production.

OBJECTIVE: To determine the expression and function of the microRNA-29 family (miRNA-29a, miRNA-29b, miRNA-29c) in human leiomyoma and myometrium. DESIGN: Basic science experimental design. SETTING: Academic medical center. PATIENT(S): Women undergoing surgery for symptomatic uterine fibroids. INTERVENTION(S): Overexpression and knockdown of miRNA-29a, miRNA-29b, and miRNA-29c in primary leiomyoma and myometrial cells. MAIN OUTCOME MEASURE(S): [1] Expression of the miRNA-29 family members in vivo in leiomyoma versus myometrium; [2] Major fibrillar collagen (I, II, III) expression in leiomyoma and myometrial cells with manipulation of miRNA-29 species. RESULT(S): Members of the miRNA-29 family (29a, 29b, 29c) are all down-regulated in leiomyoma versus myometrium in vivo. The expression of the miRNA-29 family can be successfully modulated in primary leiomyoma and myometrial cells. Overexpression of the miRNA-29 family in leiomyoma cells results in down-regulation of the major fibrillar collagens. Down-regulation of the miRNA-29 species in myometrium results in an increase in collagen type III deposition. CONCLUSION(S): The miRNA-29 family is consistently down-regulated in leiomyoma compared to matched myometrial tissue. This down-regulation contributes to the increased collagen seen in leiomyomas versus myometrium. When miRNA-29 members are overexpressed in leiomyoma cells, protein levels of all of the major fibrillar collagens decrease. The miRNA-29 members are potential therapeutic targets in this highly prevalent condition.

Novel correlates between antimüllerian hormone and menstrual cycle characteristics in African-American women (23-35 years-old).

OBJECTIVE: To characterize normative antimüllerian hormone (AMH) levels and ascertain which factors are associated with AMH in a large cohort of reproductive-age women. DESIGN: Cross-sectional study. SETTING: Not applicable. PATIENT(S): A total of 1,654 African-American women (AAW) ages 23-34 at recruitment. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Serum AMH measured using an ultrasensitive ELISA. RESULT(S): The median AMH was 3.18 ng/mL, and there was a significant, but nonlinear, relationship between age and AMH, with levels peaking at age 25. As AMH was not normally distributed, log transformation was performed and used for all analyses. In a multivariable age-adjusted model, body mass index, current use of hormonal contraception, and history of a thyroid condition were inversely associated with AMH, while history of abnormal menstrual bleeding and menstrual cycles longer than 35 days were positively associated with AMH. CONCLUSION(S): While age is correlated with AMH, it accounts for only a portion of the variation seen. This study adds valuable information to the existing literature on normative AMH levels in young reproductive-age women. While our findings fill a critical data gap for ovarian reserve in AAW, the insights gained will be of benefit for all women.

Cellular Models of Trophoblast Differentiation.

Orchestrated trophoblast differentiation is necessary to establish and maintain a normal pregnancy, however the molecular mechanisms that guide this process remain largely unknown. Although early studies of cytotrophoblast differentiation relied on animal models, more recent trophoblast research has involved in vitro models of human tissue. These in vitro models have utilized cultured trophoblast cell lines, primary cell culture, and villous explant cultures-each with its advantages and disadvantages. Traditionally, attempts to develop in vitro models of human placental differentiation have relied on two-dimensional cell culture. Though monolayer culture methods have been refined over time this technique has several limitations, including the inability to study cell-to-cell interactions. Recently, several studies have employed three-dimensional culture methods to overcome many of the limitations of traditional two-dimensional trophoblast culture. These three-dimensional culture systems have an important role in both the study of cytotrophoblast differentiation and development of new therapeutics targeting placenta associated diseases.

Elective single embryo transfer trends and predictors of a good perinatal outcome--United States, 1999 to 2010.

OBJECTIVE: To assess trends in elective single ET and identify factors associated with a good perinatal outcome. DESIGN: Retrospective cohort study. SETTING: Clinic-based data. PATIENT(S): A total of 886,686 fresh, nondonor cycles reported to the National Assisted Reproductive Technology Surveillance System during 1999-2010, of which 17,166 met criteria for elective single ET. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rates of elective single ET and good perinatal outcome (term, singleton infant with normal birth weight). RESULT(S): In 2010, elective single ET comprised 5.6% of all fresh transfers, representing an eightfold increase since publication of first guidelines in 2004 recommending elective single ET. Compared with other ETs, elective single ETs were nearly twice as likely to result in a good perinatal outcome (37.1% vs. 18.9%, respectively). Among women using elective single ET, those aged <35 and 35-37 years had a good perinatal outcome (40.2% and 32.5%, respectively). In multivariable, log-binomial analyses, factors positively associated with a good perinatal outcome included male factor infertility, day 5 ET, and having ≥3 supernumerary embryos for cryopreservation. CONCLUSION(S): Between 1999 and 2010, national rates of elective single ET increased. Given the frequency of good perinatal outcomes among women aged 35-37 years, guidelines for elective single ET could be expanded to include patients in this age group with favorable prognoses.

Sepsis-induced inflammation is exacerbated in an animal model of type 2 diabetes.

Hyperglycemia is common in critically ill patients and pronounced hyperglycemia may lead to complications which include severe infections, polyneuropathy, multiple organ failure and death in such patients. Sustained hyperglycemia is generally observed in patients with Type 2 diabetes. To explore sepsis-induced inflammation in Type 2 diabetes, polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in the Goto-Kakizaki (GK) rat, a spontaneous animal model of Type 2 diabetes. The Wistar-Kyoto (WKY) rats, non-diabetic inbred rats, were used as controls for the experiment. Blood glucose levels were measured at basal, 2 hr and 20 hr after CLP. At 20 hr after CLP, blood and tissue samples were collected. Plasma levels of lactate, IL-6, IL-10 and endotoxins were measured. Total RNA from liver tissues were extracted and subjected to reverse transcription-polymerase chain reaction using rat specific IL-6 primers. GK rats exhibited significantly elevated basal glucose levels compared to WKY rats. Glucose levels in septic GK rats were significantly elevated compared to WKY rats at all time points studied. While both WKY and GK rats showed significant increases in IL-6 at 20 hr after CLP, the GK rats exhibited an average 2.68-fold increase than that of WKY rats. At 20 hr after CLP, hepatic IL-6 gene expression in GK rats was 1.77-fold greater than that of WKY rats. Although, both WKY and GK rats showed significant increases in plasma lactate levels at 20 hr after CLP, the GK rats exhibited an average increase of 1.69-fold, from the already elevated basal levels, than that of WKY rats. Since the lactate levels in GK sham groups were slightly higher than that of WKY sham, the relative changes in the fold induction by CLP between strains were similar. Both WKY and GK rats showed significantly elevated endotoxin levels at 20 hr after CLP, but no statistical differences were observed between the two groups. These studies suggest that sepsis-induced inflammation is exacerbated in an animal model of Type 2 diabetes.