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Abnormal uterine bleeding (AUB) is a common presentation that can occur in all age groups. AUB is an umbrella term for any uterine bleeding that occurs outside a woman’s normal pattern in volume, regularity, and/or timing. AUB is described by using frequency, regularity, duration, and volume or by using PALM-COEIN (Polyp, Adenomyosis, Leiomyoma, Malignancy and premalignant conditions; Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not yet classified). Workup for AUB comprises a history (with a detailed menstrual history), physical examination (including a pelvic and bimanual examination), lab tests, and imaging (primarily transvaginal ultrasonography). For treatment, medical therapies should be considered before surgical therapies, especially when fertility is desired. The decisions for treatment are based on etiology, fertility concerns, contraindications, or patient preference. Of the medical therapies, there are hormonal and nonhormonal therapies. The most common treatments for AUB are levonorgestrel intrauterine device, tranexamic acid, oral contraceptives, and nonsteroidal anti-inflammatory drugs. The most common surgical treatments are myomectomy, endometrial ablation, uterine artery embolization, and hysterectomy. This review contains 7 figures, 10 tables and 45 references Key words: abnormal uterine bleeding, adenomyosis, contraceptives, endometrial, fibroids, hysterectomy, menorrhagia

BACKGROUND Obesity has been associated with attenuated vaccine responses and an increased risk of contracting pneumococcal pneumonia, but no study to our knowledge has assessed the impact of obesity and genetics on 23-valent pneumococcal vaccine (PPSV23) efficacy. We assessed the relationship of obesity (primary analysis) and stimulator of interferon genes (STING1) genotype (secondary analysis) on PPSV23 efficacy. METHODS Nonobese (BMI 22–25 kg/m2) and obese participants (BMI ≥30 kg/m2) were given a single dose of PPSV23. Blood was drawn immediately prior to and 4–6 weeks after vaccination. Serum samples were used to assess PPSV23-specific antibodies. STING1 genotypes were identified using PCR on DNA extracted from peripheral blood samples. RESULTS Forty-six participants were categorized as nonobese (n = 23; 56.5% women; mean BMI 23.3 kg/m2) or obese (n = 23; 65.2% women; mean BMI 36.3 kg/m2). Obese participants had an elevated fold change in vaccine-specific responses compared with nonobese participants (P < 0.0001). The WT STING1 group (R232/R232) had a significantly higher PPSV23 response than individuals with a single copy of HAQ-STING1 regardless of BMI (P = 0.0025). When WT was assessed alone, obese participants had a higher fold serotype-specific response compared with nonobese participants (P < 0.0001), but no difference was observed between obese and nonobese individuals with 1 HAQ allele (P = 0.693). CONCLUSIONS These observations demonstrate a positive association between obesity and PPSV23 efficacy specifically in participants with the WT STING1 genotype. TRIAL REGISTRATION ClinicalTrials.gov NCT02471014. FUNDING This research was supported by the NIH and the University of Florida MD-PhD Training Program., Obesity and a WT STING1 genotype are positively associated with efficacy of the 23-valent pneumococcal vaccine in a small cohort of subjects.

Background: Cesarean sections (CS) are among the most commonly performed surgical procedures in the world. Epidemiologic data has associated delivery by CS with an increased risk of certain adverse health outcomes in children, such as asthma and obesity. Objective: To explore what is known about the effect of mode of delivery on the development of the infant microbiome and discuss the potentially mediating role of CS-related microbial dysbiosis in the development of adverse pediatric health outcomes. Recommendations for future inquiry are also provided. Methods: This study provides a narrative overview of the literature synthesizing the findings of literature retrieved from searches of PubMed and other computerized databases and authoritative texts. Results: Emerging evidence suggests that mode of delivery is involved in the development of the neonatal microbiome and may partially explain pediatric health outcomes associated with birth by CS. Specifically, the gut microbiome of vaginally delivered infants more closely resembles their mothers’ vaginal microbiome and thus more commonly consists of potentially beneficial microbiota such as Lactobacillus, Bifidobacterium, and Bacteroides. Conversely, the microbiome of infants born via CS shows an increased prevalence of either skin flora or potentially pathogenic microbial communities such as Klebsiella, Enterococcus, and Clostridium. Conclusions: Mode of delivery plays an important role in the development of the postnatal microbiome but likely tells only part of the story. More comprehensive investigations into all the pre- and perinatal factors that have the potential to contribute to the neonatal microbiome are warranted.

Cesarean sections (CSs) are the most commonly performed surgical procedures in the world today. Global epidemiological studies from the last decade suggest that the optimal CS rates in developed countries exist somewhere between 15% and 19%. Despite these findings, CS rates in the United States have remained stable at slightly over 32% over the past 10 years. Using primary and secondary literature published from 2010 to 2015, this review discusses how optimal CS rates were developed. In addition, we define a category of potentially avoidable CS (i.e., those conducted on nulliparous low-risk women who present with vertex infants at term) and explore how CS in this population appear to be one of the main drivers of high CS rates overall. The institutional, provider, and patient-related factors, which may be related to higher-than-recommended rates of CS, particularly those conducted in low-risk women, will be discussed. This review will then delve into clinician and patient-oriented interventions that have been shown to effectively reduce the rate of potentially avoidable CS. Our analysis showed that large-scale, multifaceted interventions that include audit and feedback cycles as well as peer review strategies were the most effective in decreasing rates of potentially avoidable CS. This review concludes with an agenda for future research into interventions that aim to achieve optimal CS rates.

The risk of cervical cancer (CC) among women immunosuppressed for a variety of reasons is well documented in the literature. Although there is improved organ function, quality of life and life expectancy gained through use of immunosuppressant therapy, there may be increased long-term risk of cervical neoplasia and cancer and the need for more intense screening, surveillance, and management. Although guidance for CC screening among HIV-infected women (see Table 1) has been supported by evidence from retrospective and prospective studies, recommendations for CC screening among non-HIV immunosuppressed women remains limited because quality evidence is lacking. Moreover, CC screening guidelines for HIV-infected women have changed because better treatments evolved and resulted in longer life expectancy.The objective of this report was to summarize current knowledge of CC, squamous intraepithelial lesions, and human papillomavirus (HPV) infection in non-HIV immunocompromised women to determine best practices for CC surveillance in this population and provide recommendations for screening. We evaluated those with solid organ transplant, hematopoietic stem cell transplant, and a number of autoimmune diseases.A panel of health care professionals involved in CC research and care was assembled to review and discuss existing literature on the subject and come to conclusions about screening based on available evidence and expert opinion. Literature searches were performed using key words such as CC, cervical dysplasia/squamous intraepithelial lesion, HPV, and type of immunosuppression resulting in an initial group of 346 articles. Additional publications were identified from review of citations in these articles. All generated abstracts were reviewed to identify relevant articles. Articles published within 10 years were considered priority for review. Reviews of the literature were summarized with relevant statistical comparisons. Recommendations for screening generated from each group were largely based on expert opinion. Adherence to screening, health benefits and risks, and available clinical expertise were all considered in formulating the recommendations to the degree that information was available.Solid Organ Transplant: Evidence specific for renal, heart/lung, liver, and pancreas transplants show a consistent increase in risk of cervical neoplasia and invasive CC, demonstrating the importance of long-term surveillance and treatment. Reports demonstrate continued risk long after transplantation, emphasizing the need for screening throughout a woman's lifetime.Hematopoietic Stem Cell Transplant: Although there is some evidence for an increase in CC in large cohort studies of these patients, conflicting results may reflect that many patients did not survive long enough to evaluate the incidence of slow-growing or delayed-onset cancers. Furthermore, history of cervical screening or previous hysterectomy was not included in registry study analysis, possibly leading to underestimation of CC incidence rates.Genital or chronic graft versus host disease is associated with an increase in high-grade cervical neoplasia and posttransplant HPV positivity.Inflammatory Bowel Disease: There is no strong evidence to support that inflammatory bowel disease alone increases cervical neoplasia or cancer risk. In contrast, immunosuppressant therapy does seem to increase the risk, although results of observational studies are conflicting regarding which type of immunosuppressant medication increases risk. Moreover, misclassification of cases may underestimate CC risk in this population. Recently published preventive care guidelines for women with inflammatory bowel disease taking immunosuppressive therapy recommend a need for continued long-term CC screening.Systemic Lupus Erythematosus and Rheumatoid Arthritis: The risk of cervical high-grade neoplasia and cancer was higher among women with systemic lupus erythematosus than those with rheumatoid arthritis (RA), although studies were limited by size, inclusion of women with low-grade neoplasia in main outcomes, and variability of disease severity or exposure to immunosuppressants. In studies designed to look specifically at immunosuppressant use, however, there did seem to be an increase in risk, identified mostly in women with RA. Although the strength of the evidence is limited, the increase in risk is consistent across studies.Type 1 DM: There is a paucity of evidence-based reports associating type 1 DM with an increased risk of cervical neoplasia and cancer.The panel proposed that CC screening guidelines for non-HIV immunocompromised women follow either the (1) guidelines for the general population or (2) current center for disease control guidelines for HIV-infected women. The following are the summaries for each group reviewed, and more details are noted in accompanying table:Solid Organ Transplant: The transplant population reflects a greater risk of CC than the general population and guidelines for HIV-infected women are a reasonable approach for screening and surveillance.Hematopoietic Stem Cell Transplant: These women have a greater risk of CC than the general population and guidelines for HIV-infected women are a reasonable approach for screening. A new diagnosis of genital or chronic graft versus host disease in a woman post-stem cell transplant results in a greater risk of CC than in the general population and should result in more intensive screening and surveillance.Inflammatory Bowel Disease: Women with inflammatory bowel disease being treated with immunosuppressive drugs are at greater risk of cervical neoplasia and cancer than the general population and guidelines for HIV-infected women are a reasonable approach for screening and surveillance. Those women with inflammatory bowel disease not on immunosuppressive therapy are not at an increased risk and should follow screening guidelines for the general population.Systemic Lupus Erythematosus and Rheumatoid Arthritis: All women with systemic lupus erythematosus, whether on immunosuppressant therapy or not and those women with RA on immunosuppressant therapy have a greater risk of cervical neoplasia and cancer than the general population and should follow CC screening guidelines for HIV-infected women. Women with RA not on immunosuppressant therapy should follow CC screening guidelines for the general population.Type 1 Diabetes Mellitus: Because of a lack of evidence of increased risk of cervical neoplasia and cancer among women with type 1 DM, these women should follow the screening guidelines for the general population.

A 33-year-old women with 3 children who has completed child bearing presents to your office for permanent sterilization via a laparoscopic approach. She has recently heard through the internet that removal of the fallopian tubes completely may decrease her ovarian cancer risk more than a tubal ligation with placement of clips or cauterization. She has no family history of gynecologic malignancies but is now curious about preventative measures for ovarian cancer that can decrease her risk. How do you counsel this patient?

1Clinical Lecturer, Department of Obstetrics and Gynecology, University of Florida, Gainesville, FL 32610, USA 2Associate Professor, Department of Obstetrics and Gynecology, College of Medicine, University of Florida, Gainesville, FL 32610, USA *Corresponding author Lisa Beth Spiryda, MD, PhD Associate Professor Department of Obstetrics and Gynecology College of Medicine University of Florida PO BOX 100294 Gainesville FL 32610, USA Tel. (352)-273-7660 E-mail: spirlb@ufl.edu

OBJECTIVE Although human papillomavirus (HPV) infection is necessary for cervical squamous intraepithelial lesion (SIL/CIN) and cancer to develop, exposure to HPV is not predictive of which women will develop SIL/CIN and cancer. This study examines mRNA expression of several potential biomarkers in exfoliated cervical cells collected from college-aged women. MATERIALS AND METHODS Freshman female students were recruited into the Carolina Women's Care Study, which was designed to prospectively evaluate factors that contribute to persistent HPV infections. One component of this study was to extract mRNA from exfoliated cervical cells. In this study, mRNA expression of Frizzled (FZD), growth differentiating factor 15, interleukin 1 beta (IL1β), and N-cadherin was assessed through real-time polymerase chain reaction. Statistical analysis was performed with a Student t test; all results were standardized with glyceraldehyde 3-phosphate dehydrogenase. RESULTS Fifty samples were selected that reflected the demographics of the Carolina Women's Care Study participants. IL1β mRNA expression was 9.4-fold higher in cervical cells from women with abnormal Pap tests (p = .0018); low-grade squamous intraepithelial lesion had 12.7-fold higher expression than negatives (p = .0011). The FZD mRNA expression was 5.7-fold higher in CIN 2 as compared with CIN 1 (p = .0041) and 8.5-fold higher compared with cytology/pathology negative (p = .0014). Other differences in mRNA expression showed trends but not reaching statistical significance for each condition. CONCLUSIONS It seems that several biomarkers involved in the cytokine/inflammatory pathway (IL1β), cell adhesion pathway (N-cadherin), growth factor (growth differentiating factor 15), and Wingless (WNT) signaling pathway (FZD) may be potential biomarkers in conjunction with the Pap test and HPV that help predict which women are at highest risk for developing CIN 3 and cervical cancer.

Over the past 30 years, the growing prevalence of obesity has become a major problem in the USA. The most recent National Health and Nutrition Examination Survey data from the year 2009–2010 states...

We describe a series of women after allogeneic stem cell transplantation with vaginal graft-versus-host disease (GVHD) who were treated with topical cyclosporine, surgery, or both. We reviewed the medical charts of 11 women who presented with vaginal pain, discomfort, and vaginal scarring (inability to perform a Papanicolaou test or have vaginal intercourse because of pain). Vaginal symptoms develop an average of 10 months from bone marrow transplantation. Symptoms and physical findings include excoriated and ulcerated mucosa, thickened mucosa, narrowed introitus, and obliterated introitus from dense scar tissue that does not resolve with systemic or topical estrogens. The severity of symptoms and the physical findings in our study population did not correlate with age, type of leukemia, type of transplant, or severity or acute or chronic GVHD. Excoriated mucosa and moderately thickened mucosa were successfully treated with topical cyclosporine. Extensive synechiae and complete obliteration of the vaginal canal required surgical lysis with postoperative topical cyclosporine. Vaginal GVHD can successfully be treated with topical cyclosporine when mild to moderate disease is present. Surgical lysis with topical cyclosporine is required when more severe disease ensues.

Background. Cervical cancer incidence and mortality rates are higher in African Americans than in European Americans (white, non-Hispanic of European ancestry). The reasons for this disparity are not known. Methods. We recruited a population-based longitudinal cohort of 326 European American and 113 African American female college freshmen in Columbia, South Carolina, to compare clearance of high-risk human papillomavirus (HR-HPV) infection between ethnicities. HPV testing and typing from samples obtained for Papanicolaou testing occurred every 6 months. Results. African American participants had an increased risk of testing positive for HR-HPV, compared with European American participants, but the frequency of incident HPV infection was the same in African American and European American women. Thus, exposure to HPV could not explain the higher rate of HPV positivity among African American women. The time required for 50% of participants to clear HR-HPV infection was 601 days for African American women (n = 63) and 316 days for European American women (n = 178; odds ratio [OR], 1.61; 95% confidence interval [CI], 1.08–2.53). African American women were more likely than European American women to have an abnormal result of a Papanicolaou test (OR, 1.58; 95% CI, 1.05–2.39). Conclusions. We propose that the longer time to clearance of HR-HPV among African American women leads to increased rates of abnormal results of Papanicolaou tests and contributes to the increased rates of cervical cancer observed in African American women.

Awareness of the contributions of thrombophilia to thrombosis-related morbidity and mortality has been growing in the last few decades. Thrombophilia is especially concerning in females seeking contraception because some types of hormonal contraception have been associated with venous thromboembolism (VTE). Clinicians face a growing need for awareness of evidence-based contraception selection for this population.PubMed literature searches were conducted to provide a review of the literature describing contraceptive use in patients with thrombophilia. This review also describes contraceptive selection and counseling for this population.Studies of combined hormonal contraceptive (CHC) use demonstrate a 2- to 50-fold increase in VTE in individuals with thrombophilia, depending on the type of thrombophilia and the reference group identified. Two small studies describing VTE incidence in progesterone-only contraceptive (POC) users with thrombophilia were identified but they did not provide conclusive information regarding VTE risk in this population.POC may be recommended for contraception in patients with most thrombophilias, but studies should be undertaken to further define the safety of POC use in this population.

Factors Influencing the Decision to Breastfeed by Mothers in a Southern Women’s Health Clinic The benefits of breastfeeding infants up to six months post-partum are well documented in literature, yet current data estimates that many populations in the United States fail to meet the recommended guidelines, in particular in the African American/Black communities.

Cervical cancer screening guidelines have evolved significantly over the past ten years in the adolescent population. The objective of this article is to review the cervical screening guidelines in the adolescent population as well as examine the evidence and studies that support delaying screening until 21 years old. Delaying HPV and Papanicolaou testing until 21 years old is safe and will not increase cervical cancer rates in the adolescent population.

This chapter illustrates assisted reproductive technologies in great detail. Over the years, thousands of births have been achieved successfully through these techniques which are now well recognized. In vitro fertilization (IVF) technique initially was used in women with tubal damage but now it has been expanded to help women with other causes of infertility including endometriosis, failed tuboplasty, poor prognosis pelvic disease, male infertility, or unexplained infertility. IVF involves several steps — namely, superovulation, follicle aspiration, fertilization, and embryo transfer. The standard use of IVF assists infertile couples to conceive and has enabled easy creation of human embryos in vitro. The role of these embryos in creating stem cells is well known. The potential utility of these stem cells to treat and cure a wide array of diseases through cell transplantation therapies is well established. Stem cells are cells with the capacity for prolonged or unlimited self-renewal in an undifferentiated state and having the capacity to develop into at least one type of highly differentiated descendent.

Carolyn E Banister,1,* Amy R Messersmith,2,* Hrishikesh Chakraborty,3 Yinding Wang,3 Lisa B Spiryda,4 Saundra H Glover,5 Lucia Pirisi,6 Kim E Creek1 1Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, 2Department of Pharmaceutical Sciences, Presbyterian College School of Pharmacy, Clinton, 3Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, 4Department of Obstetrics and Gynecology, University of South Carolina School of Medicine Columbia, 5Department of Health Services Policy and Management, and Institute for Partnerships to Eliminate Health Disparities, Arnold School of Public Health, University of South Carolina, Columbia, 6Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA*These authors contributed equally to this workBackground: Cervical cancer, a rare outcome of high-risk human papillomavirus (HPV) infection, disproportionately affects African American women, who are about twice more likely than European American women to die of the disease. Most cervical HPV infections clear in about one year. However, in some women HPV persists, posing a greater risk for cervical dysplasia and cancer. The Carolina Women’s Care Study (CWCS) was conducted to explore the biological, genetic, and lifestyle determinants of persistent HPV infection in college-aged European American and African American women. This paper presents the initial results of the CWCS, based upon data obtained at enrollment.Methods: Freshman female students attending the University of South Carolina were enrolled in the CWCS and followed until graduation with biannual visits, including two Papanicolaou tests, cervical mucus collection, and a questionnaire assessing lifestyle factors. We recruited 467 women, 293 of whom completed four or more visits for a total of 2274 visits.Results and conclusion: CWCS participants were 70% European American, 24% African American, 3% Latina/Hispanic, and 3% Asian. At enrollment, 32% tested positive for any HPV. HPV16 infection was the most common (18% of infections). Together, HPV16, 66, 51, 52, and 18 accounted for 58% of all HPV infections. Sixty-four percent of all HPV-positive samples contained more than one HPV type, with an average of 2.2 HPV types per HPV-positive participant. We found differences between African American and European American women in the prevalence of HPV infection (38.1% African American, 30.7% European American) and abnormal Papanicolaou test results (9.8% African-American, 5.8% European American). While these differences did not reach statistical significance at enrollment, as the longitudinal data of this cohort are analyzed, the sample size will allow us to confirm these results and compare the natural history of HPV infection in college-aged African American and European American women.Keywords: human papillomavirus, Carolina Women’s Care Study, papillomavirus persistence, race/ethnicity, health disparities

Human papillomavirus (HPV) is the causative agent of genital warts, cervical dysplasia and cervical cancer and is also associated with oropharyngeal and ano-rectal cancers. While HPV is necessary for these malignancies to develop, infection with HPV is not predictive of which women will develop cervical dysplasia or cancer. Most high-risk HPV (HR-HPV) infections resolve within 12-24 months. Persistence of HR-HPV infection is a risk factor for the development of pre-cancerous cervical lesions and cervical cancer. A disparity exists in the incidence and mortality rates for cervical cancer, with African American (AA) women being more likely to develop cervical cancer and about twice as likely to die of the disease, as compared to European American (EA) women. The Carolina Women's Care Study (CWCS) was initiated in 2004 to assess HPV infection and persistence in a college-age cohort from the University of South Carolina. In this longitudinal study, 467 study participants (70% EA and 24% AA) underwent biannual pelvic exams during the duration of their college experience. Exfoliated cervical cells were collected at each visit and screened for HPV using PCR and the Inno-LiPA assay was subsequently used to determine HPV types. The AA and EA participants in the CWCS were similar upon comparison of several demographic characteristics, including those often associated with increased risk of cervical lesions, such as age at sexual debut and average number of sexual partners. While the incidence of new HR-HPV infections in AA and EA participants was similar, at any visit AA participants were about 1.5-fold more likely to test HR-HPV positive than EA participants (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 550. doi:1538-7445.AM2012-550