Obstetrics and Gynecology

  • Recent Publications- July 2014

    Inflammation and inflammatory control in interstitial cystitis/bladder pain syndrome: Associations with painful symptoms

    Schrepf A, O'Donnell M, Luo Y, Bradley CS, Kreder K, Lutgendorf S; Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.
    Pain. 2014 Jun 5. pii: S0304-3959(14)00262-0. doi: 10.1016/j.pain.2014.05.029. [Epub ahead of print]

    Toll-like receptors (TLR) are known to play a role in chronic pain, from animal models and limited research in humans, but their role in interstitial cystitis/bladder pain syndrome (IC/BPS) is unknown. Similarly, alterations of the hypothalamic-pituitary-adrenal axis have been reported in some pain conditions. Our objectives were to identify inflammatory processes that might distinguish individuals with IC/BPS from healthy controls (HC) and to examine their associations with IC/BPS symptoms. Female participants (58IC/BPS patients and 28HCs) completed pain and urinary symptom questionnaires and collected saliva for cortisol as part of the Multidisciplinary Approach to Pelvic Pain study. Inflammatory cytokines were assayed in plasma, and in TLR-2- and TLR-4-stimulated peripheral blood mononuclear cells. Controlling for BMI and negative affect, between-group differences were analyzed by general linear models, and relationships between symptoms and inflammatory variables were analyzed by regression. Compared to HCs, IC/BPS patients had higher levels of plasma interleukin-6 (P=.040), greater interleukin-1β responsive to TLR-2 stimulation (P=.040), and flatter diurnal cortisol slopes (P=.010), indicating inflammatory dysregulation. In IC/BPS patients, inflammation after TLR-4 stimulation was associated with multiple symptoms, including genitourinary pain (P=.010), sexual pain (P=.002), and marginally with urinary symptoms (P=.068). Genitourinary pain severity (P=.008), frequency (P=.001), and pain with intercourse (P=.002) were strongly associated with TLR-4 inflammatory response. TLR-4 appears to play a central role in painful symptoms of IC/BPS patients, which may be linked to poor endogenous inflammatory control. These findings may help to identify new mechanisms in IC/BPS and lead to new therapeutic approaches.

    For a full text of the article, click here: http://www.sciencedirect.com/science/article/pii/S0304395914002620#

    MUC16 (CA125): tumor biomarker to cancer therapy, a work in progress

    Felder M, Kapur A, Gonzalez-Bosquet J, Horibata S, Heintz J, Albrecht R, Fass L, Kaur J, Hu K, Shojaei H, Whelan RJ, Patankar MS.
    Mol Cancer. 2014 May 29;13(1):129. doi: 10.1186/1476-4598-13-129.

    Over three decades have passed since the first report on the expression of CA125 by ovarian tumors. Since that time our understanding of ovarian cancer biology has changed significantly to the point that these tumors are now classified based on molecular phenotype and not purely on histological attributes. However, CA125 continues to be, with the recent exception of HE4, the only clinically reliable diagnostic marker for ovarian cancer. Many large-scale clinical trials have been conducted or are underway to determine potential use of serum CA125 levels as a screening modality or to distinguish between benign and malignant pelvic masses. CA125 is a peptide epitope of a 3-5 million Da mucin, MUC16. Here we provide an in-depth review of the literature to highlight the importance of CA125 as a prognostic and diagnostic marker for ovarian cancer. We focus on the increasing body of literature describing the biological role of MUC16 in the progression and metastasis of ovarian tumors. Finally, we consider previous and on-going efforts to develop therapeutic approaches to eradicate ovarian tumors by targeting MUC16. Even though CA125 is a crucial marker for ovarian cancer, the exact structural definition of this antigen continues to be elusive. The importance of MUC16/CA125 in the diagnosis, progression and therapy of ovarian cancer warrants the need for in-depth research on the biochemistry and biology of this mucin. A renewed focus on MUC16 is likely to culminate in novel and more efficient strategies for the detection and treatment of ovarian cancer.

    For a full text of the article, click here: http://www.molecular-cancer.com/content/13/1/129

    Collection of a lifetime: A practical approach to developing a longitudinal collection of women's healthcare biological samples

    Santillan MK, Leslie KK, Hamilton WS, Boese BJ, Ahuja M, Hunter SK, Santillan DA.
    Eur J Obstet Gynecol Reprod Biol. 2014 Jun 2;179C:94-99. doi: 10.1016/j.ejogrb.2014.05.023. [Epub ahead of print]

    OBJECTIVE: The objective is to develop a biorepository of samples that represent all stages of a women's life. Importantly, our goal is to collect longitudinal physical specimens as well as the associated short and long-term clinical information.

    STUDY DESIGN: The Women's Health Tissue Repository was established to encompass four tissue banks: Well Women Tissue Bank, Reproductive Endocrinology and Infertility Tissue Bank, Maternal Fetal Tissue Bank, and the long-established Gynecologic Malignancies Tissue Bank. Based on their health status, women being seen in Women's Health at the University of Iowa are recruited to contribute samples and grant access to their electronic medical record to the biorepository. Samples are coded, processed, and stored for use by investigators.

    RESULTS: The Maternal Fetal Tissue Bank was the first expansion of our department's biobanking efforts. Approximately 75% of the women approached consent to participate in the Maternal Fetal Tissue Bank. Enrollment has steadily increased. Samples have been used for over 20 projects in the first 3 years and are critical to 7 funded grants and 3 patent applications.

    CONCLUSION: Patient samples with corresponding clinical data are initially important to women's health research. Our model demonstrates that many research projects by faculty, fellows, and residents have benefited from the existence of the Women's Health Tissue Repository. While challenging to achieve, longitudinal sampling allows for the greatest opportunity to study normal and pathological changes throughout all phases of a women's life, including pregnancy. This bank facilitates and accelerates the development of novel research, technologies, and possible therapeutic options in women's health. The establishment of more longitudinal biorepositories based on our model would enhance women's health research.

    For a full text of the article, click here: http://www.sciencedirect.com/science/article/pii/S030121151400298X

    Voluntary and involuntary childlessness in female veterans: associations with sexual assault.

    Ryan GL, Mengeling MA, Booth BM3, Torner JC, Syrop CH, Sadler AG
    Fertil Steril. 2014 May 26. pii: S0015-0282(14)00402-6. doi: 10.1016/j.fertnstert.2014.04.042. [Epub ahead of print]

    OBJECTIVE: To assess associations between lifetime sexual assault and childlessness in female veterans.

    DESIGN: Cross-sectional, computer-assisted telephone interview study.

    SETTING: Two Midwestern Veterans Administration (VA) medical centers.

    PATIENT(S): A total of 1,004 women aged ≤52 years, VA-enrolled between 2000 and 2008.


    MAIN OUTCOME MEASURE(S): Sociodemographic variables, reproductive history and care utilization, and mental health.

    RESULT(S): A total of 620 veterans (62%) reported at least one attempted or completed sexual assault in their lifetime (LSA). Veterans with LSA more often self-reported a history of pregnancy termination (31% vs. 19%) and infertility (23% vs. 12%), as well as sexually transmitted infection (42% vs. 27%), posttraumatic stress disorder (32% vs. 10%), and postpartum dysphoria (62% vs. 44%). Lifetime sexual assault was independently associated with termination and infertility in multivariate models; sexually transmitted infection, posttraumatic stress disorder, and postpartum dysphoria were not. The LSA by period of life was as follows: 41% of participants in childhood, 15% in adulthood before the military, 33% in military, and 13% after the military (not mutually exclusive). Among the 511 who experienced a completed LSA, 23% self-reported delaying or foregoing pregnancy because of their assault.

    CONCLUSION(S): This study demonstrated associations between sexual assault history and pregnancy termination, delay or avoidance (voluntary childlessness), and infertility (involuntary childlessness) among female veterans. Improved gender-specific veteran medical care must attend to these reproductive complexities.

    For a full text of the article, click here: http://www.sciencedirect.com/science/article/pii/S0015028214004026

    Alcohol and male reproductive health: a cross-sectional study of 8344 healthy men from Europe and the USA

    Jensen TK, Swan S, Jørgensen N, Toppari J, Redmon B, Punab M, Drobnis EZ, Haugen TB, Zilaitiene B, Sparks AE, Irvine DS, Wang C, Jouannet P, Brazil C, Paasch U, Salzbrunn A, Skakkebæk NE, Andersson AM
    Hum Reprod. 2014 Jun 3. pii: deu118. [Epub ahead of print]

    STUDY QUESTION: Is there an association between alcohol intake and semen quality and serum reproductive hormones among healthy men from the USA and Europe?

    SUMMARY ANSWER: Moderate alcohol intake is not adversely associated with semen quality in healthy men, whereas it was associated with higher serum testosterone levels.

    WHAT IS KNOWN ALREADY: High alcohol intake has been associated with a wide range of diseases. However, few studies have examined the correlation between alcohol and reproductive function and most have been conducted in selected populations of infertile men or have a small sample size and the results have been contradictory.

    STUDY DESIGN, SIZE, DURATION: A coordinated international cross-sectional study among 8344 healthy men. A total of 1872 fertile men aged 18-45 years (with pregnant partners) from four European cities and four US states, and 6472 young men (most with unknown fertility) aged 18-28 years from the general population in six European countries were recruited.

    PARTICIPANTS/MATERIALS, SETTING, METHODS: The men were recruited using standardized protocols. A semen analysis was performed and men completed a questionnaire on health and lifestyle, including their intake of beer, wine and liquor during the week prior to their visit. Semen quality (semen volume, sperm concentration, percentage motile and morphologically normal sperm) and serum reproductive hormones (FSH, LH, testosterone, sex hormone-binding globulin, and inhibin B and free testosterone) were examined.

    MAIN RESULTS AND THE ROLE OF CHANCE: The participation rate for our populations was 20-30%. We found no consistent association between any semen variable and alcohol consumption, which was low/moderate in this group (median weekly intake 8 units), either for total consumption or consumption by type of alcohol. However, we found a linear association between total alcohol consumption and total or free testosterone in both groups of men. Young and fertile men who consumed >20 units of alcohol per week had, respectively, 24.6 pmol/l (95% confidence interval 16.3-32.9) and 19.7 pmol/l (7.1-32.2) higher free testosterone than men with a weekly intake between 1 and 10 units. Alcohol intake was not significantly associated with serum inhibin B, FSH or LH levels in either group of men. The study is the largest of its kind and has sufficient power to detect changes in semen quality and reproductive hormones.

    LIMITATIONS, REASONS FOR CAUTION: The participation rate was low, but higher than in most previous semen quality studies. In addition, the study was cross-sectional and the men were asked to recall their alcohol intake in the previous week, which was used as a marker of intake up to 3 months before. If consumption in that week differed from the typical weekly intake and the intake 3 months earlier, misclassification of exposure may have occurred. However, the men were unaware of their semen quality when they responded to the questions about alcohol intake. Furthermore, we cannot exclude that our findings are due to unmeasured confounders, including diet, exercise, stress, occupation and risk-taking behavior.

    WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that moderate alcohol intake is not adversely associated with semen quality in healthy men, whereas it was associated with higher serum testosterone levels which may be due to a changed metabolism of testosterone in the liver. Healthy men may therefore be advised that occasional moderate alcohol intake may not harm their reproductive health; we cannot address the risk of high alcohol consumption of longer duration or binge drinking on semen quality and male reproductive hormones.

    STUDY FUNDING/COMPETING INTERESTS: All funding sources were non-profitable and sponsors of this study played no role in the study design, in data collection, analysis, or interpretation, or in the writing of the article. The authors have no conflicts of interest.

    For a full text of the article, click here: http://humrep.oxfordjournals.org/content/early/2014/06/03/humrep.deu118.long

    Physician pain and discomfort during minimally invasive gynecologic cancer surgery.

    McDonald ME, Ramirez PT, Munsell MF, Greer M, Burke WM, Naumann WT, Frumovitz M
    Gynecol Oncol. 2014 Jun 2. pii: S0090-8258(14)00979-2. doi: 10.1016/j.ygyno.2014.05.019. [Epub ahead of print]

    OBJECTIVE: Despite increasing awareness of physical strain to surgeons associated with minimally invasive surgery (MIS), its use continues to expand. We sought to gather information from gynecologic oncologists regarding physical discomfort due to MIS.

    METHODS: Anonymous surveys were e-mailed to 1279 Society of Gynecologic Oncology (SGO) members. Physical symptoms (numbness, pain, stiffness, and fatigue) and surgical and demographic factors were assessed. Univariate and multivariate analyses were performed to determine risk factors for physical symptoms.

    RESULTS: We analyzed responses of 350 SGO members who completed the survey and currently performed >50% of procedures robotically (n=122), laparoscopically (n=67), or abdominally (n=61). Sixty-one percent of members reported physical symptoms related to MIS. The rate of symptoms was higher in the robotic group (72%) than the laparoscopic (57%) or abdominal groups (49%) (p=0.0052). Stiffness (p=0.0373) and fatigue (p=0.0125) were more common in the robotic group. Female sex (p<0.0001), higher caseload (p=0.0007), and academic practice (p=0.0186) were associated with increased symptoms. On multivariate analysis, robotic surgery (odds ratio [OR] 2.38, 95% CI 1.20-4.69) and female sex (OR 4.20, 95% CI 2.13-8.29) were significant predictors of symptoms. There was no correlation between seeking treatment and surgical modality (laparotomy 11%, robotic 20%, laparoscopy 25%, p=0.12).

    CONCLUSIONS: Gynecologic oncologists report physical symptoms due to MIS at an alarming rate. Robotic surgery and female sex appear to be risk factors for physical discomfort. As we strive to improve patient outcomes and decrease patient morbidity with MIS, we must also work to improve the ergonomics of MIS for surgeons.

    For a full text of the article, click here: http://www.sciencedirect.com/science/article/pii/S0090825814009792